Female sexual stimulation during antidepressant treatment.

PubMed

Elmore, J L; Quattlebaum, J T

1997-01-01

Three women with several diagnoses, including depression and psychosis, personality disorder, attention deficit hyperactivity disorder, alcohol abuse, and physical disease, were treated with selective serotonin reuptake inhibitors (fluoxetine, paroxetine, fluvoxamine). One patient was prescribed paroxetine in addition to methylphenidate. While receiving these agents, two women experienced undesirable sexual arousal and the third had increased sexual desire, arousal, and hypersexuality.

Antidepressant pharmaceuticals in two U.S. effluent-impacted streams: Occurrence and fate in water and sediment and selective uptake in fish neural tissue

USGS Publications Warehouse

Schultz, M.M.; Furlong, E.T.; Kolpin, D.W.; Werner, S.L.; Schoenfuss, H.L.; Barber, L.B.; Blazer, V.S.; Norris, D.O.; Vajda, A.M.

2010-01-01

Antidepressant pharmaceuticals are widely prescribed in the United States; release of municipal wastewater effluent is a primary route introducing them to aquatic environments, where little is known about their distribution and fate. Water, bed sediment, and brain tissue from native white suckers (Catostomus commersoni)were collected upstream and atpoints progressively downstream from outfalls discharging to two effluentimpacted streams, Boulder Creek (Colorado) and Fourmile Creek (Iowa). A liquid chromatography/tandem mass spectrometry method was used to quantify antidepressants, including fluoxetine, norfluoxetine (degradate), sertraline, norsertraline (degradate), paroxetine, Citalopram, fluvoxamine, duloxetine, venlafaxine, and bupropion in all three sample matrices. Antidepressants were not present above the limit of quantitation in water samples upstream from the effluent outfalls but were present at points downstream at ng/L concentrations, even at the farthest downstream sampling site 8.4 km downstream from the outfall. The antidepressants with the highest measured concentrations in both streams were venlafaxine, bupropion, and Citalopram and typically were observed at concentrations of at least an order of magnitude greater than the more commonly investigated antidepressants fluoxetine and sertraline. Concentrations of antidepressants in bed sediment were measured at ng/g levels; venlafaxine and fluoxetine were the predominant chemicals observed. Fluoxetine, sertraline, and their degradates were the principal antidepressants observed in fish brain tissue, typically at low ng/g concentrations. Aqualitatively different antidepressant profile was observed in brain tissue compared to streamwater samples. This study documents that wastewater effluent can be a point source of antidepressants to stream ecosystems and that the qualitative composition of antidepressants in brain tissue from exposed fish differs substantially from the compositions observed in streamwater and sediment, suggesting selective uptake. ?? 2010 American Chemical Society.

Comparative efficacy and safety of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in older adults: a network meta-analysis.

PubMed

Thorlund, Kristian; Druyts, Eric; Wu, Ping; Balijepalli, Chakrapani; Keohane, Denis; Mills, Edward

2015-05-01

To establish the comparative efficacy and safety of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in older adults using the network meta-analysis approach. Systematic review and network meta-analysis. Individuals aged 60 and older. Data on partial response (defined as at least 50% reduction in depression score from baseline) and safety (dizziness, vertigo, syncope, falls, loss of consciousness) were extracted. A Bayesian network meta-analysis was performed on the efficacy and safety outcomes, and relative risks (RRs) with 95% credible intervals (CrIs) were produced. Fifteen randomized controlled trials were eligible for inclusion in the analysis. Citalopram, escitalopram, paroxetine, duloxetine, venlafaxine, fluoxetine, and sertraline were represented. Reporting on partial response and dizziness was sufficient to conduct a network meta-analysis. Reporting on other outcomes was sparse. For partial response, sertraline (RR=1.28), paroxetine (RR=1.48), and duloxetine (RR=1.62) were significantly better than placebo. The remaining interventions yielded RRs lower than 1.20. For dizziness, duloxetine (RR=3.18) and venlafaxine (RR=2.94) were statistically significantly worse than placebo. Compared with placebo, sertraline had the lowest RR for dizziness (1.14) and fluoxetine the second lowest (1.31). Citalopram, escitalopram, and paroxetine all had RRs between 1.4 and 1.7. There was clear evidence of the effectiveness of sertraline, paroxetine, and duloxetine. There also appears to be a hierarchy of safety associated with the different antidepressants, although there appears to be a dearth of reporting of safety outcomes. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Uptake of human pharmaceuticals in bull sharks (Carcharhinus leucas) inhabiting a wastewater-impacted river.

PubMed

Gelsleichter, James; Szabo, Nancy J

2013-07-01

The presence of human pharmaceuticals in sewage-impacted ecosystems is a growing concern that poses health risks to aquatic wildlife. Despite this, few studies have investigated the uptake of active pharmaceutical ingredients (APIs) in aquatic organisms. In this study, the uptake of 9 APIs from human drugs was examined and compared in neonate bull sharks (Carcharhinus leucas) residing in pristine (Myakka River) and wastewater-impacted (Caloosahatchee River) tributaries of Florida's Charlotte Harbor estuary. The synthetic estrogen used in human contraceptives (17α-ethynylestradiol) and 6 of the selective serotonin/norepinephrine reuptake inhibitors (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine) used in human antidepressants were observed at detectable and, in some cases, quantifiable levels in plasma of Caloosahatchee River sharks. Comparatively, only venlafaxine was detected in the plasma of a single Myakka River shark at a level below the limit of quantitation. These results suggest that sharks residing in wastewater-impacted habitats accumulate APIs, a factor that may pose special risks to C. leucas since it is one of few shark species to regularly occupy freshwater systems. Further research is needed to determine if the low levels of API uptake observed in Caloosahatchee River bull sharks pose health risks to these animals. Copyright © 2013 Elsevier B.V. All rights reserved.

Prediction of clinical response based on pharmacokinetic/pharmacodynamic models of 5-hydroxytryptamine reuptake inhibitors in mice

PubMed Central

Kreilgaard, M; Smith, D G; Brennum, L T; Sánchez, C

2008-01-01

Background and purpose: Bridging the gap between preclinical research and clinical trials is vital for drug development. Predicting clinically relevant steady-state drug concentrations (Css) in serum from preclinical animal models may facilitate this transition. Here we used a pharmacokinetic/pharmacodynamic (PK/PD) modelling approach to evaluate the predictive validity of 5-hydroxytryptamine (5-HT; serotonin) transporter (SERT) occupancy and 5-hydroxytryptophan (5-HTP)-potentiated behavioral syndrome induced by 5-HT reuptake inhibitor (SRI) antidepressants in mice. Experimental approach: Serum and whole brain drug concentrations, cortical SERT occupancy and 5-HTP-potentiated behavioral syndrome were measured over 6 h after a single subcutaneous injection of escitalopram, paroxetine or sertraline. [3H]2-(2-dimethylaminomethylphenylsulphanyl)-5-methyl-phenylamine ([3H]MADAM) was used to assess SERT occupancy. For PK/PD modelling, an effect-compartment model was applied to collapse the hysteresis and predict the steady-state relationship between drug exposure and PD response. Key results: The predicted Css for escitalopram, paroxetine and sertraline at 80% SERT occupancy in mice are 18 ng mL−1, 18 ng mL−1 and 24 ng mL−1, respectively, with corresponding responses in the 5-HTP behavioral model being between 20–40% of the maximum. Conclusions and implications: Therapeutically effective SERT occupancy for SRIs in depressed patients is approximately 80%, and the corresponding plasma Css are 6–21 ng mL−1, 21-95 ng mL−1 and 20–48 ng mL−1 for escitalopram, paroxetine and sertraline, respectively. Thus, PK/PD modelling using SERT occupancy and 5-HTP-potentiated behavioral syndrome as response markers in mice may be a useful tool to predict clinically relevant plasma Css values. PMID:18552871

High-Dose Citalopram and Escitalopram and the Risk of Out-of-Hospital Death.

PubMed

Ray, Wayne A; Chung, Cecilia P; Murray, Katherine T; Hall, Kathi; Stein, C Michael

2017-02-01

Studies demonstrating that higher doses of citalopram (> 40 mg) and escitalopram (> 20 mg) prolong the corrected QT interval prompted regulatory agency warnings, which are controversial, given the absence of confirmatory clinical outcome studies. We compared the risk of potential arrhythmia-related deaths for high doses of these selective serotonin reuptake inhibitors (SSRIs) to that for equivalent doses of fluoxetine, paroxetine, and sertraline. The Tennessee Medicaid retrospective cohort study included 54,220 persons 30-74 years of age without cancer or other life-threatening illness who were prescribed high-dose SSRIs from 1998 through 2011. The mean age was 47 years, and 76% were female. Demographic characteristics and comorbidity for individual SSRIs were comparable. Because arrhythmia-related deaths are typically sudden and occur outside the hospital, we analyzed out-of-hospital sudden unexpected death as well as sudden cardiac deaths, a more specific indicator of proarrhythmic effects. The adjusted risk of sudden unexpected death for citalopram did not differ significantly from that for the other SSRIs. The respective hazard ratios (HRs) for citalopram versus escitalopram, fluoxetine, paroxetine, and sertraline were 0.84 (95% CI, 0.40-1.75), 1.24 (95% CI, 0.75-2.05), 0.75 (95% CI, 0.45-1.24), and 1.53 (95% CI, 0.91-2.55). There were no significant differences for sudden cardiac death or all study deaths, nor were there significant differences among high-risk patients (≥ 60 years of age, upper quartile baseline cardiovascular risk). Escitalopram users had no significantly increased risk for any study end point. We found no evidence that risk of sudden unexpected death, sudden cardiac death, or total mortality for high-dose citalopram and escitalopram differed significantly from that for comparable doses of fluoxetine, paroxetine, and sertraline. © Copyright 2016 Physicians Postgraduate Press, Inc.

High-Dose Citalopram and Escitalopram and the Risk of Out-of-Hospital Death

PubMed Central

Ray, Wayne A.; Chung, Cecilia P.; Murray, Katherine T.; Hall, Kathi; Stein, C. Michael

2018-01-01

Objective Studies demonstrating higher doses of citalopram (>40mg) and escitalopram (>20mg) prolong the QTc interval prompted regulatory agency warnings, which are controversial, given the absence of confirmatory clinical outcome studies. We compared the risk of potential arrhythmia-related deaths for high doses of these SSRIs to that for equivalent doses of fluoxetine, paroxetine, and sertraline. Method The Tennessee Medicaid retrospective cohort study included 54,220 persons 30–74 years of age without cancer or other life-threatening illness prescribed high-dose SSRIs. The mean age was 47 years and 76% were female. Demographic characteristics and comorbidity for individual SSRIs were comparable. Because arrhythmia-related deaths are typically sudden and occur outside the hospital, we analyzed out-of-hospital sudden unexpected death as well as sudden cardiac deaths, a more specific indicator of pro-arrhythmic effects. Results The adjusted risk of sudden unexpected death for citalopram did not differ significantly from that for the other SSRIs. The respective hazard ratios (HRs) for citalopram versus escitalopram, fluoxetine, paroxetine, and sertraline were 0.84 (95% confidence interval [CI], 0.40–1.75), 1.24 (0.75–2.05), 0.75 (0.45–1.24), and 1.53 (0.91–2.55). There were no significant differences for sudden cardiac death or all study deaths, nor were there significant differences among high-risk patients (≥60 years of age, upper quartile baseline cardiovascular risk). Escitalopram users had no significantly increased risk for any study endpoint. Conclusions We found no evidence that risk of sudden unexpected death, sudden cardiac death, or total mortality for high-dose citalopram and escitalopram differed significantly from that for comparable doses of fluoxetine, paroxetine, and sertraline. PMID:27736049

Effects of antidepressant drugs on synaptic protein levels and dendritic outgrowth in hippocampal neuronal cultures.

PubMed

Seo, Mi Kyoung; Lee, Chan Hong; Cho, Hye Yeon; Lee, Jung Goo; Lee, Bong Ju; Kim, Ji Eun; Seol, Wongi; Kim, Young Hoon; Park, Sung Woo

2014-04-01

The alteration of hippocampal plasticity has been proposed to play a critical role in both the pathophysiology and treatment of depression. In this study, the ability of different classes of antidepressant drugs (escitalopram, fluoxetine, paroxetine, sertraline, imipramine, tranylcypromine, and tianeptine) to mediate the expression of synaptic proteins and dendritic outgrowth in rat hippocampal neurons was investigated under toxic conditions induced by B27 deprivation, which causes hippocampal cell death. Postsynaptic density protein-95 (PSD-95), brain-derived neurotrophic factor (BDNF), and synaptophysin (SYP) levels were evaluated using Western blot analyses. Additionally, dendritic outgrowth was examined to determine whether antidepressant drugs affect the dendritic morphology of hippocampal neurons in B27-deprived cultures. Escitalopram, fluoxetine, paroxetine, sertraline, imipramine, tranylcypromine, and tianeptine significantly prevented B27 deprivation-induced decreases in levels of PSD-95, BDNF, and SYP. Moreover, the independent application of fluoxetine, paroxetine, and sertraline significantly increased levels of BDNF under normal conditions. All antidepressant drugs significantly increased the total outgrowth of hippocampal dendrites under B27 deprivation. Specific inhibitors of calcium/calmodulin kinase II (CaMKII), KN-93, protein kinase A (PKA), H-89, or phosphatidylinositol 3-kinase (PI3K), LY294002, significantly decreased the effects of antidepressant drugs on dendritic outgrowth, whereas this effect was observed only with tianeptine for the PI3K inhibitor. Taken together, these results suggest that certain antidepressant drugs can enhance synaptic protein levels and encourage dendritic outgrowth in hippocampal neurons. Furthermore, effects on dendritic outgrowth likely require CaMKII, PKA, or PI3K signaling pathways. The observed effects may be may be due to chronic treatment with antidepressant drugs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

PubMed Central

Tiradentes, R.V.; Pires, J.G.P.; Silva, N.F.; Ramage, A.G.; Santuzzi, C.H.; Futuro, H.A.

2014-01-01

Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central. PMID:25003632

Atomoxetine Augmentation in a Case of Treatment Resistant Panic Disorder with Multiple Augments Failure: A Case Report

PubMed Central

Ram, Dushad; Patil, Shwetha; Gowdappa, Basavana; Rajalakshmi, Iyshwarya

2015-01-01

Atomoxetine, a selective norepinephrine inhibitor, is effective in comorbid anxiety and attention deficit hyperactivity disorder, however its role in panic disorder is unknown. We are presenting a case of panic disorder, who initially partially responded to clonazepam. When clonazepam was added with sertraline, escitalopram, desvenlafaxin, she did not improve significantly until paroxetine was added. When clonazepam-paroxetine combination was added with propranolol, etizolam, olanzepine, risperidone and amisulpride the symptom remission did not occur until a trial of Atomoxetine was done. PMID:26598594

Antidepressant-Induced Hyponatremia in Older Adults.

PubMed

Viramontes, Terry S; Truong, Havan; Linnebur, Sunny A

2016-03-01

To describe the prevalence of hyponatremia in older adults related to antidepressive agents and identify potential alternative options in older adults with a low-baseline serum sodium concentration and/or when a patient has experienced hyponatremia as a result of taking an antidepressant. A PubMed search was conducted on November 10, 2015. Search terms included: antidepressive agents, antidepressive agents second-generation, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, hyponatremia, milnacipran, mirtazapine, paroxetine, reboxetine, syndrome of inappropriate antidiuretic hormone, sertraline, trazodone, venlafaxine, and vilazodone. Filters included English language. A search of product labeling was also conducted. Out of 363 results, 124 publications were identified and reviewed along with 11 additional references. Publications were chosen based on relevance to the review: case reports of patients 60 years of age or older or clinical investigations of the association between hyponatremia and antidepressants in older adults. Hyponatremia was counted as an adverse effect if an antidepressant was the likely cause of hyponatremia, and hyponatremia was resolved after withdrawal. Antidepressant-induced hyponatremia in older adults is fairly common. Selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, and mirtazapine were implicated in the majority of the case reports and clinical studies evaluating older adults. Bupropion, trazodone, and tricyclic antidepressants were implicated less often in the same literature. Given its unique mechanism of action, bupropion may be the most appropriate antidepressant for older adults at risk for antidepressant-induced hyponatremia.

Serotonin uptake inhibitors: uses in clinical therapy and in laboratory research.

PubMed

Fuller, R W

1995-01-01

Fluoxetine, zimelidine, sertraline, paroxetine, fluvoxamine, indalpine and citalopram are the selective inhibitors of serotonin uptake that have been most widely studied. Some of these compounds are or have been used clinically in the treatment of mental depression, obsessive-compulsive disorder and bulimia, and therapeutic benefit has been claimed in additional diseases as well. By blocking the membrane uptake carrier which transports serotonin from the extracellular space to inside the serotonin nerve terminals, these compounds increase extracellular concentrations of serotonin and amplify signals sent by serotonin neurons. Because serotonin neurons are widespread in the central nervous system, the functional consequences of blocking serotonin uptake are diverse, but are generally subtle. Animals treated with serotonin uptake inhibitors look normal in gross appearance, but effects such as reduced aggressive behavior, decreased food intake and altered food selection, analgesia, anticonvulsant activity, endocrine changes and neurochemical changes have been demonstrated and characterized. Serotonin uptake inhibitors have helped in revealing some dynamics of serotonin neurons; for example, when uptake is inhibited and extracellular serotonin concentration increases, presynaptic as well as postsynaptic receptors for serotonin are activated to a greater degree. A consequence of increased activation of autoreceptors on serotonin cell bodies and nerve terminals is a reduction in firing of serotonin neurons and a decrease in serotonin synthesis and release. The result is a limit on the degree to which extracellular serotonin and serotonergic neurotransmission are increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Effectiveness and Cost-Effectiveness of Antidepressants in Primary Care: A Multiple Treatment Comparison Meta-Analysis and Cost-Effectiveness Model

PubMed Central

Ramsberg, Joakim; Asseburg, Christian; Henriksson, Martin

2012-01-01

Objective To determine effectiveness and cost-effectiveness over a one-year time horizon of pharmacological first line treatment in primary care for patients with moderate to severe depression. Design A multiple treatment comparison meta-analysis was employed to determine the relative efficacy in terms of remission of 10 antidepressants (citalopram, duloxetine escitalopram, fluoxetine, fluvoxamine mirtazapine, paroxetine, reboxetine, sertraline and venlafaxine). The estimated remission rates were then applied in a decision-analytic model in order to estimate costs and quality of life with different treatments at one year. Data Sources Meta-analyses of remission rates from randomised controlled trials, and cost and quality-of-life data from published sources. Results The most favourable pharmacological treatment in terms of remission was escitalopram with an 8- to 12-week probability of remission of 0.47. Despite a high acquisition cost, this clinical effectiveness translated into escitalopram being both more effective and having a lower total cost than all other comparators from a societal perspective. From a healthcare perspective, the cost per QALY of escitalopram was €3732 compared with venlafaxine. Conclusion Of the investigated antidepressants, escitalopram has the highest probability of remission and is the most effective and cost-effective pharmacological treatment in a primary care setting, when evaluated over a one year time-horizon. Small differences in remission rates may be important when assessing costs and cost-effectiveness of antidepressants. PMID:22876296

Aggravation by paroxetine, a selective serotonin reuptake inhibitor, of antral lesions generated by nonsteroidal anti-inflammatory drugs in rats.

PubMed

Takeuchi, Koji; Tanaka, Akiko; Nukui, Kazuo; Kojo, Azusa; Gyenge, Melinda; Amagase, Kikuko

2011-09-01

Recent clinical studies have suggested a risk of adverse gastric reactions from the concomitant use of selective serotonin (5-HT) reuptake inhibitors (SSRIs) with nonsteroidal anti-inflammatory drugs (NSAIDs). We examined the adverse effects of SSRIs on antral lesions produced by indomethacin in rats. Rats fasted for 24 h were refed for 1 h, then administered indomethacin (30 mg/kg s.c.) 1 h after the refeeding and killed 6 h later. Paroxetine (1-10 mg/kg) was given orally 30 min before indomethacin. Indomethacin caused antral lesions in refed rats. Paroxetine dose-dependently aggravated these lesions, despite provoking no damage by itself. Similar results were obtained when other NSAIDs such as diclofenac, flurbiprofen, and loxoprofen were coadministered with paroxetine or when indomethacin was coadministered with other antidepressants such as fluvoxamine and milnacipran, but not imipramine or maprotiline. Exogenous 5-HT also worsened the indomethacin-induced antral damage, whereas the aggravating effect of paroxetine was attenuated by ondansetron, a selective 5-HT(3) antagonist, but not antagonists for other 5-HT receptor subtypes. Indomethacin plus paroxetine had no effect on gastric secretion but significantly decreased mucosal superoxide dismutase (SOD) activity as well as GSH content. The antral damage induced by indomethacin plus paroxetine was significantly prevented by antisecretory (acid or pepsin) agents and mucosal protective agents as well as SOD and allopurinol. These results suggest that SSRIs aggravate NSAID-induced antral lesions, probably via the activation of 5HT(3) receptors, and the mechanism of aggravation may involve the corrosive action of acid/pepsin as well as an impaired antioxidative system.

Enhancement of the anti-immobility action of antidepressants by risperidone in the forced swimming test in mice.

PubMed

Rogóż, Zofia; Kabziński, Marcin

2011-01-01

The aim of the present study was to examine the effect of antidepressants (ADs) belonging to different pharmacological groups and risperidone (an atypical antipsychotic drug), given separately or jointly, on immobility time in the forced swimming test in male C57BL/6J mice. The antidepressants: citalopram, fluvoxamine, sertraline, reboxetine, milnacipran (5 and 10 mg/kg), or risperidone in low doses (0.05 and 0.1 mg/kg) given alone did not change the immobility time of mice in the forced swimming test. Co-treatment with reboxetine or milnacipran (10 mg/kg) and risperidone in a lower dose of 0.05 mg/kg or with sertraline, reboxetine (5 and 10 mg/kg), citalopram, fluvoxamine, milnacipran (10 mg/kg) and risperidone in a higher dose of 0.1 mg/kg produced antidepressant-like effect in the forced swimming test. WAY100635 (a 5-HT(1A) receptor antagonist) inhibited the effects induced by co-administration of ADs and risperidone. Active behavior in the forced swimming test was not a consequence of an increased general activity, since the combined treatment with ADs and risperidone failed to enhance the locomotor activity of mice. The obtained results indicate that a low dose of risperidone enhances the activity of ADs in an animal model of depression, and that, among other mechanisms, 5-HT(1A) receptors may play a role in these effects.

Comparative Safety of Antidepressant Agents for Children and Adolescents Regarding Suicidal Acts

PubMed Central

Schneeweiss, Sebastian; Patrick, Amanda R.; Solomon, Daniel H.; Dormuth, Colin R.; Miller, Matt; Mehta, Jyotsna; Lee, Jennifer C.; Wang, Philip S.

2010-01-01

OBJECTIVE The objective of this study was to assess the risk of suicide attempts and suicides after initiation of antidepressant medication use by children and adolescents, for individual agents. METHODS We conducted a 9-year cohort study by using population-wide data from British Columbia. We identified new users of antidepressants who were 10 to 18 years of age with a recorded diagnosis of depression. Study outcomes were hospitalization attributable to intentional self-harm and suicide death. RESULTS Of 20 906 children who initiated antidepressant therapy, 16 774 (80%) had no previous antidepressant use. During the first year of use, we observed 266 attempted and 3 completed suicides, which yielded an event rate of 27.04 suicidal acts per 1000 person-years (95% confidence interval [CI]: 23.9–30.5 suicidal acts per 1000 person-years). There were no meaningful differences in the rate ratios (RRs) comparing fluoxetine with citalopram (RR: 0.97 [95% CI: 0.54–1.76]), fluvoxamine (RR: 1.05 [95% CI: 0.46–2.43]), paroxetine (RR: 0.80 [95% CI: 0.47–1.37]), and sertraline (RR: 1.02 [95% CI: 0.56–1.84]). Tricyclic agents showed risks similar to those of selective serotonin reuptake inhibitors (RR: 0.92 [95% CI: 0.43–2.00]). CONCLUSION Our finding of equal event rates among antidepressant agents supports the decision of the Food and Drug Administration to include all antidepressants in the black box warning regarding potentially increased suicidality risk for children and adolescents beginning use of antidepressants. PMID:20385637

Differential effects of sertraline in a predator exposure animal model of post-traumatic stress disorder.

PubMed

Wilson, C Brad; McLaughlin, Leslie D; Ebenezer, Philip J; Nair, Anand R; Dange, Rahul; Harre, Joseph G; Shaak, Thomas L; Diamond, David M; Francis, Joseph

2014-01-01

Serotonin (5-HT), norepinephrine (NE), and other neurotransmitters are modulated in post-traumatic stress disorder (PTSD). In addition, pro-inflammatory cytokines (PIC) are elevated during the progression of the disorder. Currently, the only approved pharmacologic treatments for PTSD are the selective-serotonin reuptake inhibitors (SSRI) sertraline and paroxetine, but their efficacy in treating PTSD is marginal at best. In combat-related PTSD, SSRIs are of limited effectiveness. Thus, this study sought to analyze the effects of the SSRI sertraline on inflammation and neurotransmitter modulation via a predator exposure/psychosocial stress animal model of PTSD. We hypothesized that sertraline would diminish inflammatory components and increase 5-HT but might also affect levels of other neurotransmitters, particularly NE. PTSD-like effects were induced in male Sprague-Dawley rats (n = 6/group × 4 groups). The rats were secured in Plexiglas cylinders and placed in a cage with a cat for 1 h on days 1 and 11 of a 31-day stress regimen. PTSD rats were also subjected to psychosocial stress via daily cage cohort changes. At the conclusion of the stress regimen, treatment group animals were injected intraperitoneally (i.p.) with sertraline HCl at 10 mg/kg for 7 consecutive days, while controls received i.p. vehicle. The animals were subsequently sacrificed on day 8. Sertraline attenuated inflammatory markers and normalized 5-HT levels in the central nervous system (CNS). In contrast, sertraline produced elevations in NE in the CNS and systemic circulation of SSRI treated PTSD and control groups. This increase in NE suggests SSRIs produce a heightened noradrenergic response, which might elevate anxiety in a clinical setting.

Poor guideline adherence in the initiation of antidepressant treatment in children and adolescents in the Netherlands: choice of antidepressant and dose.

PubMed

de Vries, Ymkje Anna; de Jonge, Peter; Kalverdijk, Luuk; Bos, Jens H J; Schuiling-Veninga, Catharina C M; Hak, Eelko

2016-11-01

The Dutch guideline for the treatment of depression in young people recommends initiating antidepressant treatment with fluoxetine, as the evidence for its efficacy is strongest and the risk of suicidality may be lower than with other antidepressants. Furthermore, low starting doses are recommended. We aimed to determine whether antidepressant prescriptions are in accord with guidelines. A cohort of young people aged between 6 and 17 at the time of antidepressant initiation was selected from IABD, a Dutch pharmacy prescription database. The percentage of prescriptions for each antidepressant was determined. Starting and maintenance doses were determined and compared with recommendations for citalopram, fluoxetine, fluvoxamine, and sertraline. During the study period, 2942 patients initiated antidepressant treatment. The proportion of these young people who were prescribed fluoxetine increased from 10.1 % in 1994-2003 to 19.7 % in 2010-2014. However, the most commonly prescribed antidepressants were paroxetine in 1994-2003 and citalopram in 2004-2014. The median starting and maintenance doses were ≤0.5 DDD/day for tricyclic antidepressants and 0.5-1 DDD/day for SSRIs and other antidepressants. Starting doses were guideline-concordant 58 % of the time for children, 31 % for preteens, and 16 % for teens. Sixty percent of teens were prescribed an adult starting dose. In conclusion, guideline adherence was poor. Physicians preferred citalopram over fluoxetine, in contrast to the recommendations. Furthermore, although children were prescribed a low starting dose relatively frequently, teens were often prescribed an adult starting dose. These results suggest that dedicated effort may be necessary to improve guideline adherence.

Comparative risk of self-harm hospitalization amongst depressive disorder patients using different antidepressants: a population-based cohort study in Taiwan.

PubMed

Wu, C-S; Liao, S-C; Tsai, Y-T; Chang, S-S; Tsai, H-J

2017-01-01

The aim of the study was to evaluate the comparative risk of self-harm associated with the use of different antidepressants. A cohort study was conducted using data from Taiwan's National Health Insurance Research Database from 2001 to 2012. A total of 751 606 new antidepressant users with depressive disorders were included. The study outcome was hospitalization due to self-harm (International Classification of Diseases, Ninth Revision, Clinical Modification codes: E950-E958 and E980-E988). Cox proportional hazards models with stratification of the propensity score deciles were used to estimate the hazard ratios of self-harm hospitalization during the first year following the initiation of antidepressant treatment. There were 1038 hospitalization episodes due to self-harm that occurred during the follow-up of 149 796 person-years, with an overall incidence rate of 6.9 [95% confidence interval (CI) 6.5-7.4] per 1000. Compared with fluoxetine, the risk of self-harm hospitalization was higher for maprotiline [adjusted hazard ratio (aHR) = 3.00, 95% CI 1.40-6.45], milnacipran (aHR = 2.34, 95% CI 1.24-4.43) and mirtazapine (aHR = 1.40, 95% CI 1.06-1.86), lower for bupropion (aHR = 0.51, 95% CI 0.30-0.86), and similar level of risk was found for other selective serotonin reuptake inhibitors (citalopram, escitalopram, fluvoxamine, paroxetine and sertraline). The risk of self-harm may vary across different antidepressant drugs. It would be of importance to conduct further research to investigate the influence of antidepressant use on self-harm behaviors.

A rapid, Web-based method for obtaining patient views on effects and side-effects of antidepressants.

PubMed

Rizo, Carlos; Deshpande, Amol; Ing, Alton; Seeman, Neil

2011-04-01

This project was undertaken to develop a rapid method for obtaining a widespread sample of patient views on the efficacy and side-effects of antidepressants. A Web-based method is described for rapidly and objectively obtaining patient views on the effects and side-effects of treatment with antidepressants. The method entails a systematized search of many URLs (Uniform Resource Locators, or Web page addresses), using keywords and phrases to extract the named drug and symptom that are reliably relevant to the medication being taken by the individual reporting the experience online. Unwanted medical conditions (e.g., cancer) are excluded. Three successive searches of thousands of Web pages revealed a cumulative total of 835 "mentions" of patient experience on duloxetine, 756 for venlafaxine, 637 for citalopram, 636 for sertraline, 559 for paroxetine, 457 for fluoxetine, 318 for desvenlafaxine, 289 for fluvoxamine, and 210 for mirtazapine, in association with various symptoms. A comparison of the associated symptoms for each of the antidepressants found that the prevalence of the combined factor of fatigue, drowsiness, tiredness or lethargy ranged from 6.4±0.8% down to 2.9±0.15% of the mentions, where the S.E. was derived from three repeats of the Web-based analysis. The prevalence of dizziness or vertigo ranged from 7.6±0.8% down to 1.9±0.3% of the mentions. Given the increasing number of patient narratives about drug experiences on open-access Web forums, this rapid novel method will have increasing utility in post-marketing surveillance and in comparing the effects of psychiatric medications. Copyright © 2010 Elsevier B.V. All rights reserved.

Effect of sildenafil on the activity of some antidepressant drugs and electroconvulsive shock treatment in the forced swim test in mice.

PubMed

Socała, Katarzyna; Nieoczym, Dorota; Wyska, Elżbieta; Wlaź, Piotr

2017-04-01

Sildenafil, a potent and selective inhibitor of phosphodiesterase type 5, is used clinically to treat erectile dysfunction and pulmonary arterial hypertension. It is often taken by patients suffering from depression and receiving antidepressant drug treatment. However, its influence on the efficacy of antidepressant treatment was not sufficiently studied. Therefore, the aim of the present study was to investigate the influence of sildenafil on the anti-immobility action of several antidepressant drugs (i.e., sertraline, fluvoxamine, citalopram, maprotiline, trazodone, and agomelatine) as well as on antidepressant-like effect of electroconvulsive stimulations in the forced swim test in mice. The obtained results showed that acute sildenafil treatment enhanced the antidepressant-like activity of all of the studied drugs. The observed effects were not due to the increase in locomotor activity. The interactions between sildenafil and sertraline, maprotiline, and trazodone were pharmacodynamic in nature, as sildenafil did not affect concentrations of these drugs neither in serum nor in brain tissue. Increased concentrations of fluvoxamine, citalopram, and agomelatine in brain tissue evoked by sildenafil co-administration suggest that pharmacokinetic interactions between sildenafil and these drugs are very likely. Sildenafil injected acutely did not alter the antidepressant-like efficacy of electroconvulsive stimulations in mice, as assessed in the forced swim test. Interestingly, repeated (14 days) administration of sildenafil decreased the anti-immobility action of the electroconvulsive stimulations. In conclusion, the present study shows that sildenafil may alter the effectiveness of antidepressant treatment. Further studies are warranted to better characterize the influence of sildenafil on the activity of antidepressant drugs and electroconvulsive therapy.

[Exploring the clinical characters of Shugan Jieyu capsule through text mining].

PubMed

Pu, Zheng-Ping; Xia, Jiang-Ming; Xie, Wei; He, Jin-Cai

2017-09-01

The study was main to explore the clinical characters of Shugan Jieyu capsule through text mining. The data sets of Shugan Jieyu capsule were downloaded from CMCC database by the method of literature retrieved from May 2009 to Jan 2016. Rules of Chinese medical patterns, diseases, symptoms and combination treatment were mined out by data slicing algorithm, and they were demonstrated in frequency tables and two dimension based network. Then totally 190 literature were recruited. The outcomess suggested that SC was most frequently correlated with liver Qi stagnation. Primary depression, depression due to brain disease, concomitant depression followed by physical diseases, concomitant depression followed by schizophrenia and functional dyspepsia were main diseases treated by Shugan Jieyu capsule. Symptoms like low mood, psychic anxiety, somatic anxiety and dysfunction of automatic nerve were mainy relieved bv Shugan Jieyu capsule.For combination treatment. Shugan Jieyu capsule was most commonly used with paroxetine, sertraline and fluoxetine. The research suggested that syndrome types and mining results of Shugan Jieyu capsule were almost the same as its instructions. Syndrome of malnutrition of heart spirit was the potential Chinese medical pattern of Shugan Jieyu capsule. Primary comorbid anxiety and depression, concomitant comorbid anxiety and depression followed by physical diseases, and postpartum depression were potential diseases treated by Shugan Jieyu capsule.For combination treatment, Shugan Jieyu capsule was most commonly used with paroxetine, sertraline and fluoxetine. Copyright© by the Chinese Pharmaceutical Association.

In vitro anti-Candida activity of selective serotonin reuptake inhibitors against fluconazole-resistant strains and their activity against biofilm-forming isolates.

PubMed

Costa Silva, Rose Anny; da Silva, Cecília Rocha; de Andrade Neto, João Batista; da Silva, Anderson Ramos; Campos, Rosana Sousa; Sampaio, Letícia Serpa; do Nascimento, Francisca Bruna Stefany Aires; da Silva Gaspar, Brenda; da Cruz Fonseca, Said Gonçalves; Josino, Maria Aparecida Alexandre; Grangeiro, Thalles Barbosa; Gaspar, Danielle Macedo; de Lucena, David Freitas; de Moraes, Manoel Odorico; Cavalcanti, Bruno Coêlho; Nobre Júnior, Hélio Vitoriano

2017-06-01

Recent research has shown broad antifungal activity of the classic antidepressants selective serotonin reuptake inhibitors (SSRIs). This fact, combined with the increased cross-resistance frequency of the genre Candida regarding the main treatment today, fluconazole, requires the development of novel therapeutic strategies. In that context, this study aimed to assess the antifungal potential of fluoxetine, sertraline, and paroxetine against fluconazole-resistant Candida spp. planktonic cells, as well as to assess the mechanism of action and the viability of biofilms treated with fluoxetine. After 24 h, the fluconazole-resistant Candida spp. strains showed minimum inhibitory concentration (MIC) in the ranges of 20-160 μg/mL for fluoxetine, 10-20 μg/mL for sertraline, and 10-100.8 μg/mL for paroxetine by the broth microdilution method (M27-A3). According to our data by flow cytometry, each of the SSRIs cause fungal death after damaging the plasma and mitochondrial membrane, which activates apoptotic signaling pathways and leads to dose-dependant cell viability loss. Regarding biofilm-forming isolates, the fluoxetine reduce mature biofilm of all the species tested. Therefore, it is concluded that SSRIs are capable of inhibit the growth in vitro of Candida spp., both in planktonic form, as biofilm, inducing cellular death by apoptosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Psychopharmacologic interventions for repetitive behaviors in autism spectrum disorders.

PubMed

Soorya, Latha; Kiarashi, Jessica; Hollander, Eric

2008-10-01

This article provides an overview of psychopharmacological treatments for repetitive behaviors in autism spectrum disorders (ASDs) in the context of current conceptualizations of this understudied core symptom domain. The available literature on the widely used selective serotonin reuptake inhibitors (SSRIs), including fluvoxamine, fluoxetine, citalopram, escitalopram, and sertraline, are reviewed. In addition to SSRIs, research on effects of other pharmacologic interventions such as divalproex sodium, risperidone, and the neuropeptide oxytocin are presented. To date, data are mixed for interventions commonly prescribed in clinical practice and suggest several areas of investigation in advancing research on the medication management of repetitive behaviors.

Sertraline versus other antidepressive agents for depression.

PubMed

Cipriani, Andrea; La Ferla, Teresa; Furukawa, Toshi A; Signoretti, Alessandra; Nakagawa, Atsuo; Churchill, Rachel; McGuire, Hugh; Barbui, Corrado

2010-04-14

The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin reuptake inhibitors should be the first-line option when drug therapy is indicated for a depressive episode. Preliminary evidence suggested that sertraline might be slightly superior in terms of effectiveness. To assess the evidence for the efficacy, acceptability and tolerability of sertraline in comparison with tricyclics (TCAs), heterocyclics, other SSRIs and newer agents in the acute-phase treatment of major depression. MEDLINE (1966 to 2008), EMBASE (1974 to 2008), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to July 2008. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data. Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent. Two review authors independently extracted data. Discrepancies were resolved with another member of the team. A double-entry procedure was employed by two reviewers. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side-effects). A total of 59 studies, mostly of low quality, were included in the review, involving multiple treatment comparisons between sertraline and other antidepressant agents. Evidence favouring sertraline over some other antidepressants for the acute phase treatment of major depression was found, either in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine, paroxetine and mirtazapine). However, some differences favouring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion) were also found. In terms of individual side effects, sertraline was generally associated with a higher rate of participants experiencing diarrhoea. This systematic review and meta-analysis highlighted a trend in favour of sertraline over other antidepressive agents both in terms of efficacy and acceptability, using 95% confidence intervals and a conservative approach, with a random effects analysis. However, the included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear relevance to patients and clinicians were not reported in any of the included studies.

Sertraline versus other antidepressive agents for depression.

PubMed

Cipriani, Andrea; La Ferla, Teresa; Furukawa, Toshi A; Signoretti, Alessandra; Nakagawa, Atsuo; Churchill, Rachel; McGuire, Hugh; Barbui, Corrado

2010-01-20

The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin reuptake inhibitors should be the first-line option when drug therapy is indicated for a depressive episode. Preliminary evidence suggested that sertraline might be slightly superior in terms of effectiveness. To assess the evidence for the efficacy, acceptability and tolerability of sertraline in comparison with tricyclics (TCAs), heterocyclics, other SSRIs and newer agents in the acute-phase treatment of major depression. MEDLINE (1966 to 2008), EMBASE (1974 to 2008), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to July 2008. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data. Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent. Two review authors independently extracted data. Discrepancies were resolved with another member of the team. A double-entry procedure was employed by two reviewers. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side-effects). A total of 59 studies, mostly of low quality, were included in the review, involving multiple treatment comparisons between sertraline and other antidepressant agents. Evidence favouring sertraline over some other antidepressants for the acute phase treatment of major depression was found, either in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine, paroxetine and mirtazapine). However, some differences favouring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion) were also found. In terms of individual side effects, sertraline was generally associated with a higher rate of participants experiencing diarrhoea. This systematic review and meta-analysis highlighted a trend in favour of sertraline over other antidepressive agents both in terms of efficacy and acceptability, using 95% confidence intervals and a conservative approach, with a random effects analysis. However, the included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear relevance to patients and clinicians were not reported in any of the included studies.

Sertraline versus other antidepressive agents for depression

PubMed Central

Cipriani, Andrea; La Ferla, Teresa; Furukawa, Toshi A; Signoretti, Alessandra; Nakagawa, Atsuo; Churchill, Rachel; McGuire, Hugh; Barbui, Corrado

2014-01-01

Background The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin reuptake inhibitors should be the first-line option when drug therapy is indicated for a depressive episode. Preliminary evidence suggested that sertraline might be slightly superior in terms of effectiveness. Objectives To assess the evidence for the efficacy, acceptability and tolerability of sertraline in comparison with tricyclics (TCAs), heterocyclics, other SSRIs and newer agents in the acute-phase treatment of major depression. Search methods MEDLINE (1966 to 2008), EMBASE (1974 to 2008), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to July 2008. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data. Selection criteria Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent. Data collection and analysis Two review authors independently extracted data. Discrepancies were resolved with another member of the team. A double-entry procedure was employed by two reviewers. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side-effects). Main results A total of 59 studies, mostly of low quality, were included in the review, involving multiple treatment comparisons between sertraline and other antidepressant agents. Evidence favouring sertraline over some other antidepressants for the acute phase treatment of major depression was found, either in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine, paroxetine and mirtazapine). However, some differences favouring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion) were also found. In terms of individual side effects, sertraline was generally associated with a higher rate of participants experiencing diarrhoea. Authors’ conclusions This systematic review and meta-analysis highlighted a trend in favour of sertraline over other antidepressive agents both in terms of efficacy and acceptability, using 95% confidence intervals and a conservative approach, with a random effects analysis. However, the included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear relevance to patients and clinicians were not reported in any of the included studies. PMID:20393946

Health resource use and costs of vilazodone and other selective serotonin re-uptake inhibitors in treating major depressive disorder.

PubMed

Zhou, Zheng-Yi; Sun, Shawn; Chopra, Pooja; Zhong, Yichen; Totev, Todor; Signorovitch, James

2015-01-01

Selective serotonin re-uptake inhibitors (SSRIs) are widely prescribed antidepressants. This claims database study compared healthcare resource use and costs among patients with major depressive disorder (MDD) treated with vilazodone vs other SSRIs. Adults with an MDD diagnosis and ≥ 1 prescription fill for vilazodone, citalopram, escitalopram, fluoxetine, paroxetine, or sertraline were identified from administrative claims data (2010-2012). Patients who concomitantly used adjunctive medication, either a second-generation antidepressant or antipsychotic, were excluded. All-cause and MDD-related healthcare resource use and costs (in 2012 USD) were compared between patients treated with vilazodone vs other SSRIs over a 6-month follow-up period using unadjusted and multivariable analyses. The study cohort included 49 861 patients (mean age = 44.0 years; 70% female). Compared with the vilazodone cohort (n = 3527), patients in the citalopram (n = 12 187), escitalopram (n = 8275), fluoxetine (n = 10 142), paroxetine (n = 3146), and sertraline (n = 12 584) cohorts had significantly more all-cause inpatient hospital visits, longer hospital stays and more frequent emergency department visits, following the index date, after adjusting for baseline characteristics. All-cause medical service costs (inpatient + outpatient + emergency department visits) were significantly higher across all other SSRI cohorts vs vilazodone by $758-$1165 (p < 0.05). Similarly, all-cause total costs, were significantly or numerically (non-significantly) higher across all SSRI cohorts vs vilazodone by $351-$780. The was no clinical measurement of disease severity, partial coverage of the Medicare-eligible population, and short follow-up. MDD treatment with vilazodone was associated with significantly lower rates of inpatient and emergency services, and with significantly lower all-cause medical service costs and numerically (non-significantly) lower total costs to payers than with the other SSRIs included in this study.

Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants.

PubMed

Weissman, Alicia M; Levy, Barcey T; Hartz, Arthur J; Bentler, Suzanne; Donohue, Micca; Ellingrod, Vicki L; Wisner, Katherine L

2004-06-01

The available data on antidepressant levels in nursing infants were analyzed in order to calculate average infant drug levels and determine what factors influence plasma drug levels in breast-feeding infants of mothers treated with antidepressants. Electronic searches of MEDLINE, PreMEDLINE, Current Contents, Biological Abstracts, and PsycINFO from 1966 through July 2002 followed by bibliographic searches identified 67 relevant studies (two unpublished). By consensus the authors identified 57 studies of maternal plasma, breast milk, and/or infant plasma antidepressant levels from nursing mother-infant pairs, measured by liquid chromatography. Infants with recent prenatal exposure and symptomatic infants included in case reports were analyzed separately. Infant plasma levels were standardized against the average maternal level for each drug. The average infant-maternal plasma ratio was calculated for each drug, and correlations of infant plasma level to maternal dose, maternal plasma level, and breast milk level were calculated. Nortriptyline, paroxetine, and sertraline usually produce undetectable infant levels. Of drugs currently used, fluoxetine produces the highest proportion (22%) of infant levels that are elevated above 10% of the average maternal level. Based on smaller numbers, the data on citalopram indicate that it produces elevated levels in 17% of infants. The milk-to-plasma ratios for 11 antidepressants had a statistically significant negative association with the percentage of the drug bound to protein. Nortriptyline, paroxetine, and sertraline may be preferred choices in breast-feeding women. Minimizing the maternal dose may be helpful with citalopram. Current data do not support monitoring breast milk levels in individual patients. Future researchers should report maternal, breast milk, and infant antidepressant levels along with other appropriate variables.

Sertraline versus other antidepressive agents for depression.

PubMed

Cipriani, Andrea; La Ferla, Teresa; Furukawa, Toshi A; Signoretti, Alessandra; Nakagawa, Atsuo; Churchill, Rachel; McGuire, Hugh; Barbui, Corrado

2009-04-15

The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin reuptake inhibitors should be the first-line option when drug therapy is indicated for a depressive episode. Preliminary evidence suggested that sertraline might be slightly superior in terms of effectiveness. To assess the evidence for the efficacy, acceptability and tolerability of escitalopram in comparison with tricyclics (TCAs), heterocyclics, other SSRIs and newer agents in the acute-phase treatment of major depression. MEDLINE (1966 to 2008), EMBASE (1974 to 2008), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to July 2008. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data. Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent. Two review authors independently extracted data. Discrepancies were resolved with another member of the team. A double-entry procedure was employed by two reviewers. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side-effects). A total of 59 studies, mostly of low quality, were included in the review, involving multiple treatment comparisons between sertraline and other antidepressant agents. Evidence favouring sertraline over some other antidepressants for the acute phase treatment of major depression was found, either in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine, paroxetine and mirtazapine). However, some differences favouring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion) were also found. In terms of individual side effects, sertraline was generally associated with a higher rate of participants experiencing diarrhoea. This systematic review and meta-analysis highlighted a trend in favour of sertraline over other antidepressive agents both in terms of efficacy and acceptability, using 95% confidence intervals and a conservative approach, with a random effects analysis. However, the included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear relevance to patients and clinicians were not reported in any of the included studies.

The comparative evidence basis for the efficacy of second-generation antidepressants in the treatment of depression in the US: A Bayesian meta-analysis of Food and Drug Administration reviews.

PubMed

Monden, Rei; Roest, Annelieke M; van Ravenzwaaij, Don; Wagenmakers, Eric-Jan; Morey, Richard; Wardenaar, Klaas J; de Jonge, Peter

2018-08-01

Studies have shown similar efficacy of different antidepressants in the treatment of depression. Data of phase-2 and -3 clinical-trials for 16 antidepressants (levomilnacipran, desvenlafaxine, duloxetine, venlafaxine, paroxetine, escitalopram, vortioxetine, mirtazapine, venlafaxine XR, sertraline, fluoxetine, citalopram, paroxetine CR, nefazodone, bupropion, vilazodone), approved by the FDA for the treatment of depression between 1987 and 2016, were extracted from the FDA reviews that were used to evaluate efficacy prior to marketing approval, which are less liable to reporting biases. Meta-analytic Bayes factors, which quantify the strength of evidence for efficacy, were calculated. In addition, posterior pooled effect-sizes were calculated and compared with classical estimations. The resulted Bayes factors showed that the evidence load for efficacy varied strongly across antidepressants. However, all tested drugs except for bupropion and vilazodone showed strong evidence for their efficacy. The posterior effect-size distributions showed variation across antidepressants, with the highest pooled estimated effect size for venlafaxine followed by paroxetine, and the lowest for bupropion and vilazodone. Not all published trials were included in the study. The results illustrate the importance of considering both the effect size and the evidence-load when judging the efficacy of a treatment. In doing so, the currently employed Bayesian approach provided clear insights on top of those gained with traditional approaches. Copyright © 2018 Elsevier B.V. All rights reserved.

Pharmacotherapy for anxiety and comorbid alcohol use disorders.

PubMed

Ipser, Jonathan C; Wilson, Don; Akindipe, Taiwo O; Sager, Carli; Stein, Dan J

2015-01-20

Anxiety disorders are a potentially disabling group of disorders that frequently co-occur with alcohol use disorders. Comorbid anxiety and alcohol use disorders are associated with poorer outcomes, and are difficult to treat with standard psychosocial interventions. In addition, improved understanding of the biological basis of the conditions has contributed to a growing interest in the use of medications for the treatment of people with both diagnoses. To assess the effects of pharmacotherapy for treating anxiety in people with comorbid alcohol use disorders, specifically: to provide an estimate of the overall effects of medication in improving treatment response and reducing symptom severity in the treatment of anxiety disorders in people with comorbid alcohol use disorders; to determine whether specific medications are more effective and tolerable than other medications in the treatment of particular anxiety disorders; and to identify which factors (clinical, methodological) predict response to pharmacotherapy for anxiety disorders. Review authors searched the specialized registers of The Cochrane Collaboration Depression, Anxiety and Neurosis Review Group (CCDANCTR, to January 2014) and the Cochrane Drugs and Alcohol Group (CDAG, to March 2013) for eligible trials. These registers contain reports of relevant randomized controlled trials (RCT) from: the Cochrane Central Register of Controlled Trials (CENTRAL, all years), MEDLINE (1950 to date), EMBASE (1974 to date) and PsycINFO (1967 to date). Review authors ran complementary searches on EMBASE, PubMed, PsycINFO and the Alcohol and Alcohol Problems Science Database (ETOH) (to August 2013). We located unpublished trials through the National Institutes of Health (NIH) RePORTER service and the World Health Organization (WHO) International Clinical Trials Registry Platform (to August 2013). We screened reference lists of retrieved articles for additional studies. All true RCTs of pharmacotherapy for treating anxiety disorders with comorbid alcohol use disorders. Trials assessing drugs administered for the treatment of drinking behaviour, such as naltrexone, disulfiram and acomprosate were not eligible for inclusion in this systematic review. A systematic review is a standardised evaluation of all research studies that address a particular clinical issue.Two review authors independently assessed RCTs for inclusion in the review, collated trial data and assessed trial quality. We contacted investigators to obtain missing data. We calculated categorical and continuous treatment effect estimates and their 95% confidence intervals (CI) for treatment using a random-effects model with effect-size variability expressed using Chi(2) and I(2) heterogeneity statistics. We included five placebo-controlled pharmacotherapy RCTs (with 290 participants) in the review. Most of the trials provided little information on how randomization was performed or on whether both participants and study personnel were blinded to the intervention. Two of the three trials reporting superiority of medication compared with placebo on anxiety symptom outcomes were industry funded. We regarded one trial as being at high risk of bias due to selective reporting.Study participants had Diagnostic and Statistical Manual (DSM) III- and DSM IV-diagnosed alcohol use disorders and post-traumatic stress disorder (two studies), social anxiety disorder (SAD; two studies) or generalized anxiety disorder (GAD; one study). Four trials assessed the efficacy of the selective serotonin re-uptake inhibitors (SSRIs: sertraline, paroxetine); one RCT investigated the efficacy of buspirone, a 5-hydroxytryptamine (5-HT) partial agonist. Treatment duration lasted between eight and 24 weeks. Overall, 70% of participants included in the review were male.There was very low quality evidence for an effect of paroxetine on global clinical response to treatment, as assessed by the Clinical Global Impressions - Improvement scale (CGI-I). Global clinical response was observed in more than twice as many participants with paroxetine than with placebo (57.7% with paroxetine versus 25.8% with placebo; risk ratio (RR) 2.23, 95% CI 1.13 to 4.41; 2 trials, 57 participants). However, there was substantial uncertainty regarding the size of the effect of paroxetine due to the small number of studies providing data on clinically diverse patient samples. The second primary outcome measure was reduction of anxiety symptom severity. Although study investigators reported that buspirone (one trial) was superior to placebo in reducing the severity of anxiety symptoms over 12 weeks, no evidence of efficacy was observed for paroxetine (mean difference (MD) -14.70, 95% CI -33.00 to 3.60, 2 trials, 44 participants) and sertraline (one trial). Paroxetine appeared to be equally effective in reducing the severity of post-traumatic stress disorder (PTSD) symptoms as the tricyclic antidepressant desipramine in one RCT. The maximal reduction in anxiety disorder symptom severity was achieved after six weeks with paroxetine (two RCTs) and 12 weeks with buspirone (one RCT), with maintenance of medication efficacy extending to 16 with paroxetine and 24 weeks with buspirone. There was no evidence of an effect for any of the medications tested on abstinence from alcohol use or depression symptoms. There was very low quality evidence that paroxetine was well tolerated, based on drop-out due to treatment-emergent adverse effects. Nevertheless, levels of treatment discontinuation were high, with 43.1% of the participants in the studies withdrawing from medication treatment. Certain adverse effects, such as sexual problems, were commonly reported after treatment with paroxetine and sertraline. The evidence-base for the effectiveness of medication in treating anxiety disorders and comorbid alcohol use disorders is currently inconclusive. There was a small amount of evidence for the efficacy of medication, but this was limited and of very low quality. The majority of the data for the efficacy and tolerability of medication were for SSRIs; there were insufficient data to establish differences in treatment efficacy between medication classes or patient subgroups. There was a small amount of very low quality evidence that medication was well tolerated. There was no evidence that alcohol use was responsive to medication.Large, rigorously conducted RCTs would help supplement the small evidence-base for the efficacy and tolerability of pharmacotherapy for anxiety and comorbid alcohol use disorders. Further research on patient subgroups who may benefit from pharmacological treatment, as well as novel pharmacological interventions, is warranted.

Cost-effectiveness analysis of treatments for premenstrual dysphoric disorder.

PubMed

Rendas-Baum, Regina; Yang, Min; Gricar, Joseph; Wallenstein, Gene V

2010-01-01

Premenstrual syndrome (PMS) is reported to affect between 13% and 31% of women. Between 3% and 8% of women are reported to meet criteria for the more severe form of PMS, premenstrual dysphoric disorder (PMDD). Although PMDD has received increased attention in recent years, the cost effectiveness of treatments for PMDD remains unknown. To evaluate the cost effectiveness of the four medications with a US FDA-approved indication for PMDD: fluoxetine, sertraline, paroxetine and drospirenone plus ethinyl estradiol (DRSP/EE). A decision-analytic model was used to evaluate both direct costs (medication and physician visits) and clinical outcomes (treatment success, failure and discontinuation). Medication costs were based on average wholesale prices of branded products; physician visit costs were obtained from a claims database study of PMDD patients and the Agency for Healthcare Research and Quality. Clinical outcome probabilities were derived from published clinical trials in PMDD. The incremental cost-effectiveness ratio (ICER) was calculated using the difference in costs and percentage of successfully treated patients at 6 months. Deterministic and probabilistic sensitivity analyses were used to assess the impact of uncertainty in parameter estimates. Threshold values where a change in the cost-effective strategy occurred were identified using a net benefit framework. Starting therapy with DRSP/EE dominated both sertraline and paroxetine, but not fluoxetine. The estimated ICER of initiating treatment with fluoxetine relative to DRSP/EE was $US4385 per treatment success (year 2007 values). Cost-effectiveness acceptability curves revealed that for ceiling ratios>or=$US3450 per treatment success, fluoxetine had the highest probability (>or=0.37) of being the most cost-effective treatment, relative to the other options. The cost-effectiveness acceptability frontier further indicated that DRSP/EE remained the option with the highest expected net monetary benefit for ceiling values

Pharmacologic factors associated with transient neonatal symptoms following prenatal psychotropic medication exposure.

PubMed

Oberlander, Tim F; Misri, Shaila; Fitzgerald, Colleen E; Kostaras, Xanthoula; Rurak, Dan; Riggs, Wayne

2004-02-01

Selective serotonin reuptake inhibitor antidepressants (SSRIs) and benzodiazepines are frequently used to treat maternal depression and anxiety disorders during pregnancy. Recent reports suggest that prenatal SSRI exposure is associated with a neonatal discontinuation syndrome. It remains unclear whether these symptoms are directly related to SSRI exposure alone or are due to concurrent pharmacologic factors. Also, this study explores relationships between neonatal outcomes and medication levels during pregnancy, at delivery, and in the newborn period. This study sought to compare newborn behavior following second and third trimester exposure to either single-agent SSRIs (group 1) or SSRIs combined with clonazepam (group 2). A prospective cohort of mothers and their infants (N = 46) who had received SSRI medication alone or in combination with clonazepam were studied from June 1996 through June 2000 and compared with a nonexposed control group (N = 23). Infants were assessed in the newborn period for signs suggestive of a "discontinuation syndrome." Maternal drug levels were measured during the pregnancy and at delivery. Infant drug levels from cord blood and at day 2 of life were also obtained. Overall, 30% of the exposed infants (groups 1 and 2, N = 14) showed symptoms of transient poor neonatal adaptation compared with 9% (N = 2) of control infants. In group 1, 25% had symptoms (fluoxetine N = 3; paroxetine N = 3; sertraline N = 1) and in group 2, 39% of infants had symptoms (paroxetine with clonazepam, N = 7). Symptoms were typically mild respiratory distress and, less commonly, hypotonia. Symptoms were self limited and not associated with other neonatal conditions. When paroxetine was combined with clonazepam, infants with symptoms had significantly elevated paroxetine levels when compared with similarly exposed infants without symptoms (p <.05). Among single-agent paroxetine-exposed infants, drug levels did not differ significantly between those with and without symptoms. Maternal dose of clonazepam was significantly higher (p <.05) during pregnancy and at delivery among symptomatic infants compared with nonsymptomatic infants. Developmental outcomes at 2 and 8 months of age did not differ between symptomatic and nonsymptomatic infants. While transient neonatal symptoms were found in infants after single-agent prenatal exposure to SSRIs and when paroxetine was combined with clonazepam, the addition of clonazepam appeared to alter paroxetine metabolism, leading to increased drug levels and risk for transient neonatal symptoms. These data highlight the importance of accounting for a variety of pharmacologic factors beyond single-agent SSRI exposure that may lead to poor neonatal adaptation. Further studies are needed with a larger sample of infants to determine the role of clonazepam and whether similar outcomes occur when exposure includes other SSRIs in combination with clonazepam.

Maternal drug use and the risk of anorectal malformations: systematic review and meta-analysis.

PubMed

Zwink, Nadine; Jenetzky, Ekkehart

2018-05-10

Origin of anorectal malformations (ARM) are considered multifactorial. Several genetic and non-genetic risk factors are discussed in literature. Maternal periconceptional medical drug use as possible risk factor, however, has not been reviewed systematically. Studies published between 1977 and April 2017 were reviewed through systematic search in PubMed, ISI Web of Knowledge and Scopus databases. Furthermore, related and cross-referencing publications were reviewed. Pooled odds ratios (95% confidence intervals) were determined to quantify associations of maternal periconceptional use of folic acid, multivitamins, anti-asthma medication (separated in any anti-asthma medication, inhaled corticosteroids and salbutamol), thyroid hormone supplements, psychiatric drugs (separated in antidepressants, any selective serotonin reuptake inhibitors [SSRI], sertraline, citalopram, fluoxetine, paroxetine, hypnotics and benzodiazepine) and aspirin with ARM using meta-analyses. Thirty-seven studies that reported on the association between maternal periconceptional drug intake and infants born with ARM were included in this review. These were conducted in the United States of America (n = 14), Sweden (n = 6), Hungary (n = 5), Germany (n = 3), the Netherlands (n = 3), Denmark (n = 2), France (n = 2), Norway (n = 1) and the UK (n = 1). However, only few of these studies reported on the same risk factors. Studies were heterogeneous with respect to case numbers, period ingestion of medical drug use, control selection and adjustment for covariates. Consistently increased risks were observed for any anti-asthma medication, and hypnotics and benzodiazepine, but not for folic acid, multivitamins, inhaled corticosteroids, salbutamol, thyroid hormone supplements, antidepressants, any SSRI, sertraline, citalopram, fluoxetine, paroxetine and aspirin. In meta-analyses, pooled odds ratios (95% confidence intervals) for any anti-asthma medication, and hypnotics and benzodiazepine were 1.64 (1.22-2.21), and 2.43 (1.03-5.73), respectively. Evidence on maternal drug use before conception and during pregnancy as risk factor for ARM from epidemiological studies is still very limited. Nevertheless, the few available studies indicate any anti-asthma medication, and hypnotics and benzodiazepine to be associated with increased risks. Further, ideally large-scale multicenter and register-based studies are needed to clarify the role of maternal drug intake for the development of ARM.

The cost of antidepressant overdose.

PubMed

D'Mello, D A; Finkbeiner, D S; Kocher, K N

1995-11-01

Ninety percent of suicide attempts referred to a general hospital are by self-poisoning. Among women, drug overdose is the commonest means of suicide. In a retrospective naturalistic review of 200 patients who were treated in the Critical Care Unit of a general hospital following medication overdose, 12% were antidepressant overdoses. The mean duration of hospital stay for overdose with tricyclic antidepressants (TCA) was more than double that for overdose with selective serotonin reuptake inhibitors (SSRI) (7 vs 3 days; z = 2.20, p < 0.05). The dollar cost of hospital treatment for patients who overdosed on TCAs was four times greater than that for patients who overdosed on SSRIs ($22,923 vs $5,379; z = 2.30, p < 0.05). The tricyclic compounds clearly have a price advantage over more recently introduced antidepressant agents fluoxetine, sertraline, paroxetine, venlafaxine, and bupropion. The apparent cost advantage of prescribing a less expensive drug may be nullified by the cost associated with adverse consequences.

PSYCHOTHERAPY VERSUS PHARMACOTHERAPY FOR POSTTRAUMATIC STRESS DISORDER: SYSTEMIC REVIEW AND META-ANALYSES TO DETERMINE FIRST-LINE TREATMENTS.

PubMed

Lee, Daniel J; Schnitzlein, Carla W; Wolf, Jonathan P; Vythilingam, Meena; Rasmusson, Ann M; Hoge, Charles W

2016-09-01

Current clinical practice guidelines (CPGs) for posttraumatic stress disorder (PTSD) offer contradictory recommendations regarding use of medications or psychotherapy as first-line treatment. Direct head-to-head comparisons are lacking. Systemic review of Medline, EMBASE, PILOTS, Cochrane Central Register of Controlled Trials, PsycINFO, and Global Health Library was conducted without language restrictions. Randomized clinical trials ≥8 weeks in duration using structured clinical interview-based outcome measures, active-control conditions (e.g. supportive psychotherapy), and intent-to-treat analysis were selected for analyses. Independent review, data abstraction, and bias assessment were performed using standardized processes. Study outcomes were grouped around conventional follow-up time periods (3, 6, and 9 months). Combined effect sizes were computed using meta-analyses for medication versus control, medication pre-/posttreatment, psychotherapy versus control, and psychotherapy pre-/posttreatment. Effect sizes for trauma-focused psychotherapies (TFPs) versus active control conditions were greater than medications versus placebo and other psychotherapies versus active controls. TFPs resulted in greater sustained benefit over time than medications. Sertraline, venlafaxine, and nefazodone outperformed other medications, although potential for methodological biases were high. Improvement following paroxetine and fluoxetine treatment was small. Venlafaxine and stress inoculation training (SIT) demonstrated large initial effects that decreased over time. Bupropion, citalopram, divalproex, mirtazapine, tiagabine, and topiramate failed to differentiate from placebo. Aripiprazole, divalproex, guanfacine, and olanzapine failed to differentiate from placebo when combined with an antidepressant. Study findings support use of TFPs over nontrauma-focused psychotherapy or medication as first-line interventions. Second-line interventions include SIT, and potentially sertraline or venlafaxine, rather than entire classes of medication, such as SSRIs. Future revisions of CPGs should prioritize studies that utilize active controls over waitlist or treatment-as-usual conditions. Direct head-to-head trials of TFPs versus sertraline or venlafaxine are needed. © 2016 Wiley Periodicals, Inc.

May selective serotonin reuptake inhibitors (SSRIs) provide some benefit for the treatment of schizophrenia?

PubMed

Buoli, Massimiliano; Serati, Marta; Ciappolino, Valentina; Altamura, A Carlo

2016-07-01

The treatment of some psychopathological dimensions of schizophrenia (e.g. negative and depressive symptoms) is still challenging for the modest efficacy of atypical antipsychotics. Among pharmacological alternatives, augmentative Selective Serotonin Reuptake Inhibitors (SSRIs) to antipsychotics are frequently prescribed in clinical practice to improve negative/depressive symptoms of schizophrenia patients; however, the data about the efficacy of these molecules on negative, depressive and obsessive-compulsive symptoms of schizophrenia are contrasting. Research using the main database sources has been conducted to obtain an overview of the use and efficacy of SSRIs in schizophrenia. Data are too scanty to draw definitive recommendations. In a preliminary way, it can be said that available data do not show effectiveness of SSRIs on depressive symptoms of schizophrenia. Regarding negative symptoms, studies are contrasting, but paroxetine appears to be the most effective compound among SSRIs. Despite limited data, SSRIs appear to be useful for the treatment of obsessive-compulsive symptoms of schizophrenia, particularly fluvoxamine. Close clinical and pharmacological monitoring is needed in case of concomitant administration of antipsychotics and antidepressants for potential serious side effects and influence on plasma drug dosages.

Rapid screening of selective serotonin re-uptake inhibitors in urine samples using solid-phase microextraction gas chromatography-mass spectrometry.

PubMed

Salgado-Petinal, Carmen; Lamas, J Pablo; Garcia-Jares, Carmen; Llompart, Maria; Cela, Rafael

2005-07-01

In this paper a solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) method is proposed for a rapid analysis of some frequently prescribed selective serotonin re-uptake inhibitors (SSRI)-venlafaxine, fluvoxamine, mirtazapine, fluoxetine, citalopram, and sertraline-in urine samples. The SPME-based method enables simultaneous determination of the target SSRI after simple in-situ derivatization of some of the target compounds. Calibration curves in water and in urine were validated and statistically compared. This revealed the absence of matrix effect and, in consequence, the possibility of quantifying SSRI in urine samples by external water calibration. Intra-day and inter-day precision was satisfactory for all the target compounds (relative standard deviation, RSD, <14%) and the detection limits achieved were <0.4 ng mL(-1) urine. The time required for the SPME step and for GC analysis (30 min each) enables high throughput. The method was applied to real urine samples from different patients being treated with some of these pharmaceuticals. Some SSRI metabolites were also detected and tentatively identified.

Clonazepam as a therapeutic adjunct to improve the management of depression: a brief review.

PubMed

Morishita, Shigeru

2009-04-01

Clonazepam, first used for seizure disorders, is now increasingly used to treat affective disorders. We summarize the use of clonazepam to improve the management of depression. Clonazepam is useful for treatment-resistant and/or protracted depression, as well as for acceleration of response to conventional antidepressants. Clonazepam is at this time recommended for use in combination with SSRIs (fluoxetine, fluvoxamine, sertraline) as an antidepressant, and should be used at a dosage of 2.5-6.0 mg/day. If clonazepam is effective, a response should be observed within 2-4 weeks. It is significantly more effective for unipolar than for bipolar depression. Low-dose, long-term treatment with clonazepam exhibits a prophylactic effect against recurrence of depression. Although the mechanism of action of clonazepam has not yet been established, some investigators have been suggested that it involves enhancement of anti-anxiety effects, anticonvulsant effects on subclinical epilepsy, increase in 5-HT/monoamine synthesis or decrease in 5-HT receptor sensitivity mediated through the GABA system, and regulate in GABA activity.

Treatment of alcoholic organic brain syndrome with the serotonin reuptake inhibitor fluvoxamine: a preliminary study.

PubMed

Stapleton, J M; Eckardt, M J; Martin, P; Adinoff, B; Roehrich, L; Bone, G; Rubinow, D; Linnoila, M

1988-01-01

The chronic effects of fluvoxamine (200 mg per day for 4 weeks) were studied in ten alcoholic organic brain syndrome patients in a double-blind cross-over design. Complete neuropsychological evaluation was performed as well as measurement of neurochemical changes in CSF. Fluvoxamine produced a small but significant improvement in memory performance. An analysis of fluvoxamine minus placebo difference scores showed a significant correlation between memory functioning and CSF 5HIAA levels. Alcohol amnestic syndrome patients who had the highest blood levels of fluvoxamine demonstrated the largest changes in CSF 5HIAA and improvement in memory performance under fluvoxamine. These findings implicate a role of serotonergic mechanisms in alcoholic organic brain syndrome and suggest that with individual titration of the drug dose, fluvoxamine might be a clinically useful agent in the treatment of this syndrome.

Efficacy of antidepressants for dysthymia: a meta-analysis of placebo-controlled randomized trials.

PubMed

Levkovitz, Yeciel; Tedeschini, Enrico; Papakostas, George I

2011-04-01

The authors sought to determine the efficacy of antidepressants in dysthymic disorder and to compare antidepressant and placebo response rates between major depressive disorder (MDD) and dysthymic disorder. PubMed/MEDLINE databases were searched for double-blind, randomized, placebo-controlled trials of antidepressants used as monotherapy for treatment of MDD or dysthymic disorder. We defined antidepressants as those with a letter of approval by the US, Canadian, or European Union drug regulatory agencies for treatment of MDD or dysthymic disorder, which included the following: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, trimipramine, protriptyline, dothiepin, doxepin, lofepramine, amoxapine, maprotiline, amineptine, nomifensine, bupropion, phenelzine, tranylcypromine, isocarboxazid, moclobemide, brofaromine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, zimelidine, tianeptine, ritanserin, trazodone, nefazodone, agomelatine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, reboxetine, mirtazapine, and mianserin. Eligible studies were identified by cross-referencing the search term placebo with each of the above-mentioned agents. The search was limited to articles published between January 1, 1980, and November 20, 2009 (inclusive). To expand our database, we also reviewed the reference lists of the identified studies. We selected randomized, double-blind, placebo-controlled trials of antidepressants for either MDD or dysthymic disorder according to preset criteria relating to comorbidities, patient age, drug formulation, study duration, diagnostic criteria, choice of assessment scales, and whether or not the study reported original data. Final selection of articles was determined by consensus among the authors. A total of 194 studies were found that were eligible for inclusion in our analysis. Of these, 177 focused on the treatment of MDD and 17 on the treatment of dysthymic disorder. We found that antidepressant therapy was significantly more effective than placebo in dysthymic disorder (risk ratio = 1.75; 95% CI, 1.49-2.04; P < .0001), while placebo response rates in dysthymic disorder trials were significantly lower compared to MDD trials (29.9% vs 37.9%, respectively; P = .042). Meta-regression suggested a statistically significant difference in the risk ratio of responding to antidepressants versus placebo when comparing studies either on dysthymic disorder or on MDD, suggesting a greater risk ratio for response in favor of antidepressant therapy versus placebo in patients with dysthymic disorder versus MDD (coefficient of -0.113; P = .007). These results support the utility of antidepressants for dysthymic disorder. In fact, the margin of efficacy of antidepressants for dysthymic disorder was larger than for MDD. Future studies providing longer-term data on the treatment of dysthymic disorder with antidepressants are essential. © Copyright 2011 Physicians Postgraduate Press, Inc.

Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors

PubMed Central

Cryan, John F.; O'Leary, Olivia F.; Jin, Sung-Ha; Friedland, Julie C.; Ouyang, Ming; Hirsch, Bradford R.; Page, Michelle E.; Dalvi, Ashutosh; Thomas, Steven A.; Lucki, Irwin

2004-01-01

Mice unable to synthesize norepinephrine (NE) and epinephrine due to targeted disruption of the dopamine β-hydroxylase gene, Dbh, were used to critically test roles for NE in mediating acute behavioral changes elicited by different classes of antidepressants. To this end, we used the tail suspension test, one of the most widely used paradigms for assessing antidepressant activity and depression-related behaviors in normal and genetically modified mice. Dbh–/– mice failed to respond to the behavioral effects of various antidepressants, including the NE reuptake inhibitors desipramine and reboxetine, the monoamine oxidase inhibitor pargyline, and the atypical antidepressant bupropion, even though they did not differ in baseline immobility from Dbh+/– mice, which have normal levels of NE. Surprisingly, the effects of the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and paroxetine were also absent or severely attenuated in the Dbh–/– mice. In contrast, citalopram (the most selective SSRI) was equally effective at reducing immobility in mice with and without NE. Restoration of NE by using l-threo-3,4-dihydroxyphenylserine reinstated the behavioral effects of both desipramine and paroxetine in Dbh–/– mice, thus demonstrating that the reduced sensitivity to antidepressants is related to NE function, as opposed to developmental abnormalities resulting from chronic NE deficiency. Microdialysis studies demonstrated that the ability of fluoxetine to increase hippocampal serotonin was blocked in Dbh–/– mice, whereas citalopram's effect was only partially attenuated. These data show that NE plays an important role in mediating acute behavioral and neurochemical actions of many antidepressants, including most SSRIs. PMID:15148402

Fatigue: an overview.

PubMed

Rosenthal, Thomas C; Majeroni, Barbara A; Pretorius, Richard; Malik, Khalid

2008-11-15

Fatigue, a common presenting symptom in primary care, negatively impacts work performance, family life, and social relationships. The differential diagnosis of fatigue includes lifestyle issues, physical conditions, mental disorders, and treatment side effects. Fatigue can be classified as secondary to other medical conditions, physiologic, or chronic. The history and physical examination should focus on identifying common secondary causes (e.g., medications, anemia, pregnancy) and life-threatening problems, such as cancer. Results of laboratory studies affect management in only 5 percent of patients, and if initial results are normal, repeat testing is generally not indicated. Treatment of all types of fatigue should include a structured plan for regular physical activity that consists of stretching and aerobic exercise, such as walking. Caffeine and modafinil may be useful for episodic situations requiring alertness. Short naps are proven performance enhancers. Selective serotonin reuptake inhibitors, such as fluoxetine, paroxetine, or sertraline, may improve energy in patients with depression. Patients with chronic fatigue may respond to cognitive behavior therapy. Scheduling regular follow-up visits, rather than sporadic urgent appointments, is recommended for effective long-term management.

The Effects of Fluvoxamine on the Steady-State Plasma Concentrations of Escitalopram and Desmethylescitalopram in Depressed Japanese Patients.

PubMed

Yasui-Furukori, Norio; Tsuchimine, Shoko; Kubo, Kazutoshi; Ishioka, Masamichi; Nakamura, Kazuhiko; Inoue, Yoshimasa

2016-08-01

The aim of this study was to determine the impact of fluvoxamine, an inhibitor of Cytochrome P450 (CYP) 2C19 (CYP2C19), on the pharmacokinetics of escitalopram, a substrate of CYP2C19. Thirteen depressed patients initially received a 20-mg/d dose of escitalopram alone. Subsequently, a 50-mg/d dose of fluvoxamine was administered because of the insufficient efficacy of escitalopram. Plasma concentrations of escitalopram and desmethylescitalopram were quantified using high-performance liquid chromatography before and after fluvoxamine coadministration. The QT and corrected QT (QTc) intervals were measured before and after fluvoxamine coadministration. Fluvoxamine significantly increased the plasma concentrations of escitalopram (72.3 ± 36.9 ng/mL versus 135.2 ± 79.7 ng/mL, P < 0.01) but not those of desmethylescitalopram (21.5 ± 7.0 ng/mL versus 24.9 ± 12.0 ng/mL, no significance [ns]). The ratios of desmethylescitalopram to escitalopram were significantly decreased during fluvoxamine coadministration (0.37 ± 0.21 versus 0.21 ± 0.10, P < 0.01). The CYP2C19 genotype did not fully explain the degree of the change. Fluvoxamine coadministration did not change the QT or QTc intervals. The results of this study suggest that adjunctive treatment with fluvoxamine increases the concentration of escitalopram. The QTc interval did not change in this condition.

Adverse effects of long-term administration of fluvoxamine on haematology, blood biochemistry and fertility in male albino rats: a possible effect of cessation.

PubMed

Galal, A A A; Alam, R T M; Abd El-Aziz, R M

2016-11-01

Fluvoxamine is recommended as first-line treatment for a number of obsessive-compulsive disorders, anxiety disorders, social phobia, and post-traumatic stress disorder and panic disorder. The adverse effects of prolonged oral administration of fluvoxamine on haematology, biochemical parameters and fertility in male rats were evaluated in this study. Sixty adult male rats were allocated into 5 equal groups and orally treated with fluvoxamine 9 mg kg -1 b.wt. (low therapeutic dose, LTD) and 27 mg kg -1 b.wt. (high therapeutic dose, HTD), while the control rats received 0.5 ml distilled water for a period of 8 weeks. The 4 th and 5 th groups were gavaged with LTD and HTD of fluvoxamine for 8 weeks and then left untreated for another 8 weeks (recovery groups). HTD of fluvoxamine induced leukocytosis, lymphocytosis and monocytosis. LTD and HTD of fluvoxamine evoked hepatic, renal and cardiac dysfunction. Moreover, fluvoxamine treatment might lead to the risk of male infertility, which is indicated by its deleterious impacts on spermiogram and steroidogenesis hormones. They also induced oxidative stress, apoptosis in testicular tissue. Fortunately, the previous alterations were mostly reversed during the recovery period. © 2016 Blackwell Verlag GmbH.

Effects of chronic fluvoxamine on ethanol- and food-maintained behaviors

PubMed Central

Ginsburg, Brett C.; Lamb, R.J.

2011-01-01

Acute treatment with fluvoxamine reduces responding for ethanol more than responding for food. However, pharmacotherapy for alcoholism is likely to require chronic treatment. These experiments were performed to assess the effects of chronic fluvoxamine on ethanol- and food-maintained behaviors. Effects of chronic fluvoxamine (10 and 17.8 mg/kg/day × 30 days) on ethanol- and food-maintained responding were compared to responding during saline treatment in four Sprague-Dawley rats responding for ethanol and food under a multiple fixed-ratio 5, fixed-ratio 5 schedule. In two subjects, chronic fluvoxamine reduced ethanol-maintained responding more than food-maintained responding; however this effect was transient. In another subject, treatment persistently decreased food-maintained responding relative to ethanol-maintained responding. Finally, in one subject, fluvoxamine nonspecifically disrupted responding for food and ethanol. Similar to results in humans, outbred Sprague-Dawley rats had differential responses to chronic fluvoxamine. The effect was transient in rats that responded favorably (greater reduction of ethanol relative to food responding), while response reductions persisted throughout treatment in rats that responded unfavorably (greater reduction of food relative to ethanol or nonspecific reductions). PMID:16647721

The relationship between adverse events during selective serotonin reuptake inhibitor treatment for major depressive disorder and nonremission in the suicide assessment methodology study.

PubMed

Daly, Ella J; Trivedi, Madhukar H; Fava, Maurizio; Shelton, Richard; Wisniewski, Stephen R; Morris, David W; Stegman, Diane; Preskorn, Sheldon H; Rush, A John

2011-02-01

Little is known about the association between antidepressant treatment-emergent adverse events and symptom nonremission in major depressive disorder. The objective of the current analysis was to determine whether particular baseline symptoms or treatment-emergent symptoms (adverse events) during the first 2 weeks are associated with nonremission after 8 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI).Outpatients clinically diagnosed with nonpsychotic major depressive disorder were recruited from 6 primary and 9 psychiatric care sites. Participants (n = 206) were treated with an SSRI antidepressant (citalopram [20-40 mg/d], escitalopram [10-20 mg/d], fluoxetine [20-40 mg/d], paroxetine [20-40 mg/d], paroxetine CR [25-37.5 mg/d], or sertraline [50-150 mg/d]) for 8 weeks. Remission was defined as having a score of 5 or less on the 16-item Quick Inventory of Depressive Symptomatology-Clinician-Rated at week 8, or using last observation carried forward. Adverse events were identified using the 55-item Systematic Assessment for Treatment Emergent Events-Systematic Inquiry completed by participants at baseline and week 2.Findings indicated that the emergence of adverse events of weakness/fatigue, strange feeling, and trouble catching breath/hyperventilation at week 2 were independently associated with lack of remission even after controlling for the potential confounders of baseline depressive severity, anxious symptoms, antidepressant medication, chronic depression, race, burden of general medical comorbidity, and time in study. Hearing/seeing things appeared to have a protective effect. In conclusion, during SSRI treatment, the adverse events of weakness/fatigue, feeling strange, and trouble catching breath/hyperventilation are associated with nonremission, possibly due to lower adherence, early attrition, difficulty increasing the dose, and reduced efficacy.

Antiulcer activity of fluvoxamine in rats and its effect on oxidant and antioxidant parameters in stomach tissue

PubMed Central

2009-01-01

Background Although many drugs are available for the treatment of gastric ulcers, often these drugs are ineffective. Many antidepressant drugs have been shown to have antiulcer activity in various models of experimental ulcer. One such drug, the antidepressant mirtazapine, has been reported to have an antiulcer effect that involves an increase in antioxidant, and a decrease in oxidant, parameters. To date, however, there is no information available regarding the antiulcer activity for a similar antidepressant, fluvoxamine. This study aimed to investigate the antiulcer effects of fluvoxamine and to determine its relationship with antioxidants. Methods Groups of rats fasted for 24 h received fluvoxamine (25, 50, 100 and 200 mg/kg), ranitidine (50 mg/kg) or distilled water by oral gavage. Indomethacin (25 mg/kg) was orally administered to the rats as an ulcerative agent. Six hours after ulcer induction, the stomachs of the rats were excised and an ulcer index determined. Separate groups of rats were treated with the same doses of fluvoxamine and ranitidine, but not with indomethacin, to test effects of these drugs alone on biochemical parameters. The stomachs were evaluated biochemically to determine oxidant and antioxidant parameters. We used one-way ANOVA and least significant difference (LSD) options for data analysis. Results The 25, 50, 100 and 200 mg/kg doses of fluvoxamine exerted antiulcer effects of 48.5, 67.5, 82.1 and 96.1%, respectively, compared to the control rat group. Ranitidine showed an 86.5% antiulcer effect. No differences were observed in the absence of indomethacin treatment for any dose of fluvoxamine or for ranitidine. The levels of antioxidant parameters, total glutathione and nitric oxide, were increased in all fluvoxamine groups and in the ranitidine group when compared with the indomethacin-only group. In addition, fluvoxamine and ranitidine decreased the levels of the oxidant parameters, myeloperoxidase and malondialdeyhyde, in the stomach tissues of the rats when compared to indomethacin group. Conclusion We conclude that fluvoxamine has antiulcer effects, and that these occur by a mechanism that involves activation of antioxidant parameters and inhibition of some toxic oxidant parameters. PMID:19457229

Inhibitory effect of fluvoxamine on β-casein expression via a serotonin-independent mechanism in human mammary epithelial cells.

PubMed

Chiba, Takeshi; Maeda, Tomoji; Kimura, Soichiro; Morimoto, Yasunori; Sanbe, Atsushi; Ueda, Hideo; Kudo, Kenzo

2015-11-05

Selective serotonin reuptake inhibitors (SSRIs) are widely used as a first-line therapy in postpartum depression. The objective of this study was to determine the mechanism underlying the inhibitory effects of the SSRI, fluvoxamine, on β-casein expression, an indicator of lactation, in MCF-12A human mammary epithelial cells. Expression levels of serotonin (5-hydroxytryptamine; 5-HT) transporter, an SSRI target protein, and tryptophan hydroxylase 1, a rate-limiting enzyme in 5-HT biosynthesis, were increased in MCF-12A cells by prolactin treatment. Treatment with 1 μM fluvoxamine for 72 h significantly decreased protein levels of β-casein and phosphorylated signal transducer and activator transcription 5 (pSTAT5). Extracellular 5-HT levels were significantly increased after exposure to 1 μM fluvoxamine, in comparison with those of untreated and vehicle-treated cells; however, extracellular 5-HT had little effect on the decrease in β-casein expression. Expression of glucose-related protein 78/binding immunoglobulin protein, a regulator of endoplasmic reticulum (ER) stress, was significantly increased after treatment with 1 μM fluvoxamine for 48 h. Exposure to tunicamycin, an inducer of ER stress, also decreased expression of β-casein and pSTAT5 in a manner similar to fluvoxamine. Our results indicate that fluvoxamine suppresses β-casein expression in MCF-12A cells via inhibition of STAT5 phosphorylation caused by induction of ER stress. Further studies are required to confirm the effect of fluvoxamine on the function of mammary epithelial cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of Fluvoxamine on Amyloid-β Peptide Generation and Memory.

PubMed

Kim, Woojin Scott; Fu, Yuhong; Dobson-Stone, Carol; Hsiao, Jen-Hsiang T; Shang, Kani; Hallupp, Marianne; Schofield, Peter R; Garner, Brett; Karl, Tim; Kwok, John B J

2018-01-01

Alzheimer's disease is characterized by abnormal amyloid-β (Aβ) peptide accumulation beginning decades before symptom onset. An effective prophylactic treatment aimed at arresting the amyloidogenic pathway would therefore need to be initiated prior to the occurrence of Aβ pathology. The SIGMAR1 gene encodes a molecular chaperone that modulates processing of the amyloid-β protein precursor (AβPP). Fluvoxamine is a selective serotonin reuptake inhibitor and a potent SIGMAR1 agonist. We therefore hypothesized that fluvoxamine treatment would reduce Aβ production and improve cognition. We firstly investigated the impact of SIGMAR1 on AβPP processing, and found that overexpression and knockdown of SIGMAR1 significantly affected γ-secretase activity in SK-N-MC neuronal cells. We then tested the impact of fluvoxamine on Aβ production in an amyloidogenic cell model, and found that fluvoxamine significantly reduced Aβ production by inhibiting γ-secretase activity. Finally, we assessed the efficacy of long-term treatment (i.e., ∼8 months) of 10 mg/kg/day fluvoxamine in the J20 amyloidogenic mouse model; the treatment was initiated prior to the occurrence of predicted Aβ pathology. Physical examination of the animals revealed no overt pathology or change in weight. We conducted a series of behavioral tests to assess learning and memory, and found that the fluvoxamine treatment significantly improved memory function as measured by novel object recognition task. Two other tests revealed no significant change in memory function. In conclusion, fluvoxamine has a clear impact on γ-secretase activity and AβPP processing to generate Aβ, and may have a protective effect on cognition in the J20 mice.

Serotonin reuptake inhibitors in pregnancy and the risk of major malformations: a systematic review.

PubMed

Bellantuono, Cesario; Migliarese, Giovanni; Gentile, Salvatore

2007-04-01

To review studies conducted to establish the risk of major congenital malformations in women exposed to serotonin reuptake inhibitors (SRIs) during the first trimester of pregnancy. A literature search [corrected] was conducted within PsycINFO [corrected] EMBASE, MEDLINE and Cochrane databases from 1966 to October 2006, to identify studies assessing the risk of major malformations in infants whose mother was taking SRIs (SSRIs and SNRIs) during the first trimester of pregnancy. Fifteen studies were selected for the analysis: seven adopted a prospective cohort design and seven a retrospective design, of these one was a case-control study. The reviewed studies suggest that exposure to fluoxetine, sertraline, citalopram and venlafaxine in early pregnancy is not associated with an increased risk of major congenital malformations. For paroxetine, recent data call for caution in prescribing such a drug in early pregnancy. For the other SRIs, the risk remains substantially undetermined, as data are so far scanty. Given this background, large prospective cohort studies are urgently needed to better assess the risk/benefit ratio of SRIs-treatment during pregnancy. Copyright 2007 John Wiley & Sons, Ltd.

Fluoxetine (Prozac) Binding to Serotonin Transporter Is Modulated by Chloride and Conformational Changes

PubMed Central

Tavoulari, Sotiria; Forrest, Lucy R.; Rudnick, Gary

2010-01-01

Serotonin transporter (SERT) is the main target for widely used antidepressant agents. Several of these drugs, including imipramine, citalopram, sertraline, and fluoxetine (Prozac), bound more avidly to SERT in the presence of Cl–. In contrast, Cl– did not enhance cocaine or paroxetine binding. A Cl– binding site recently identified in SERT, and shown to be important for Cl– dependent transport, was also critical for the Cl– dependence of antidepressant affinity. Mutation of the residues contributing to this site eliminated the Cl–-mediated affinity increase for imipramine and fluoxetine. Analysis of ligand docking to a single state of SERT indicated only small differences in the energy of interaction between bound ligands and Cl–. These differences in interaction energy cannot account for the affinity differences observed for Cl– dependence. However, fluoxetine binding led to a conformational change, detected by cysteine accessibility experiments, that was qualitatively different from that induced by cocaine or other ligands. Given the known Cl– requirement for serotonin-induced conformational changes, we propose that Cl– binding facilitates conformational changes required for optimal binding of fluoxetine and other antidepressant drugs. PMID:19641126

A Stability Indicating HPLC Method for the Determination of Fluvoxamine in Pharmaceutical Dosage Forms.

PubMed

Souri, Effat; Donyayi, Hassan; Khaniha, Reza Ahmad; Barazandeh Tehrani, Maliheh

2015-01-01

Fluvoxamine maleate is a selective serotonin reuptake inhibitor, which is used for the treatment of different types of depressive disorders. In the present study, a stability indicating HPLC method was developed and validated for the determination of fluvoxamine maleate. The chromatographic separation was carried out using a Nova-Pak CN column and a mixture of K2HPO4 50 mM (pH 7.0) and acetonitrile (60: 40, v/v) as the mobile phase. Target compounds were detected using a UV detector set at 235 nm. The developed method was linear over the concentration range of 1-80 μg/ml with acceptable precision (CV values < 2.0%) and accuracy (error values < 1.6%). The degradation studies showed that fluvoxamine maleate is relatively unstable under acidic, basic and oxidative conditions and also when exposed to UV radiation. On the other hand, the bulk powder of fluvoxamine maleate was relatively stable when exposed to visible light or heat. The proposed method was successfully applied for the determination of active ingredient of fluvoxamine dosage form without any interference from tablet excipients.

Multiple-Dose Pharmacokinetics of Fluvoxamine in Children and Adolescents.

ERIC Educational Resources Information Center

Labellarte, Michael; Biederman, Joseph; Emslie, Graham; Ferguson, James; Khan, Arifulla; Ruckle, Jon; Sallee, Randy; Riddle, Mark

2004-01-01

Objective: To determine the pharmacokinetics of fluvoxamine in children and adolescents and to compare pharmacokinetic data from adolescents to adults from a previous study. Method: Fluvoxamine was titrated to a target dose of 100 mg b.i.d. in children (6-11 years) and 150 mg b.i.d. in adolescents (12-17 years) with obsessive-compulsive disorder…

The potency of fluvoxamine to reduce ethanol self-administration decreases with concurrent availability of food.

PubMed

Ginsburg, Brett C; Pinkston, Jonathan W; Lamb, Richard J

2012-04-01

The selective serotonin reuptake inhibitor fluvoxamine reduces responding for ethanol at lower doses than responding for food when each is available in separate components or separate groups of rats. However, when both are available concurrently and deliveries earned per session are equal, this apparent selectivity inverts and food-maintained behavior is more sensitive than ethanol-maintained behavior to rate-decreasing effects of fluvoxamine. Here, we investigated further the impact that concurrent access to both food and ethanol has on the potency of fluvoxamine. Fluvoxamine (5.6-17.8 mg/kg) potency was assessed under conditions in which food and ethanol were available concurrently and response rates were equal [average variable intervals (VIs) 405 and 14 s for food and ethanol, respectively], as well as when density of food delivery was increased (average VI 60 s for food and VI 14 s for ethanol). The potency of fluvoxamine was also determined when only ethanol was available (food extinction and average VI 14 s for ethanol) and under multiple VIs (VI 30 s for food and ethanol) wherein either food or ethanol was the only programmed reinforcement available during each component. Fluvoxamine was less potent at decreasing ethanol self-administration when food was available concurrently {ED50 [95% confidence limit (CL): 8.2 (6.5-10.3) and 10.7 (7.9-14.4)]} versus when ethanol was available in isolation [ED50: 4.0 (2.7-5.9) and 5.1 (4.3-6.0)]. Effects on food were similar under each condition in which food was available. The results demonstrate that the potency of fluvoxamine in reducing ethanol-maintained behavior depends on whether ethanol is available in isolation or in the context of concurrently scheduled food reinforcement.

A display of hypomania in a depressed male in response to fluvoxamine.

PubMed

Horiguchi, T; Sai, S

2001-10-01

The present report describes the behavioural and psychological changes in a 55-year-old depressed male who displayed hypomania after the use of fluvoxamine in addition to other antidepressant medications. The patient experienced his first major depressive episode after the bankruptcy of his company. When fluvoxamine was prescribed at a dose of 50 mg/day in addition to sulpiride at 150 mg/day and a 50 mg dose of trazodone before sleep seven months after admission, grinning and a violation of ward rules occurred repeatedly. The patient became verbally aggressive to the staff and addicted to gambling and alcohol. Six days after the cessation of fluvoxamine, his condition remitted. None of the neuromuscular abnormalities indicative of serotonin syndrome appeared during the episode. Upon review of previous reports on manic switches induced by SSRIs and other antidepressants, we speculate that the fluvoxamine accounted for his hypomania.

Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans.

PubMed Central

Skene, D J; Bojkowski, C J; Arendt, J

1994-01-01

1. Acute administration of the specific serotonin uptake inhibitor, fluvoxamine (100 mg at 16.00 h), markedly increased nocturnal plasma melatonin concentrations, with high levels extending into the morning hours. 2. Acute administration of the noradrenaline uptake inhibitor, desipramine (DMI) (100 mg at 16.00 h), increased evening plasma melatonin concentrations. 3. Both drug treatments increased the duration of melatonin secretion, fluvoxamine significantly delaying the offset time and DMI significantly advancing the onset time. 4. The stimulatory effect of DMI on plasma melatonin was mirrored by increased urinary 6-sulphatoxymelatonin (aMT6s) excretion. 5. On the contrary, there was no correlation between plasma melatonin and urinary aMT6s concentrations following fluvoxamine treatment, suggesting that fluvoxamine may inhibit the metabolism of melatonin. 6. Treatment with DMI increased plasma cortisol concentrations in the evening and early morning, treatment with fluvoxamine increased plasma cortisol at 03.00 h, 10.00 h and 11.00 h. 7. The drug treatments affected different aspects of the nocturnal plasma melatonin profile suggesting that the amplitude of the melatonin rhythm may depend upon serotonin availability and/or melatonin metabolism whilst the onset of melatonin production depends upon noradrenaline availability. PMID:8186063

Fluvoxamine in the treatment of compulsive buying.

PubMed

Black, D W; Monahan, P; Gabel, J

1997-04-01

The authors report the results of an open trial of fluvoxamine in the treatment of compulsive buying. Ten nondepressed subjects were recruited through word-of-mouth and rnet restrictive inclusion/exclusion criteria. Subjects were assessed with the Yale-Brown Obsessive-Compulsive Scale modified for compulsive buying, the Clinical Global Impression scale, and other measures. After a single-blind 1-week placebo run-in, subjects received fluvoxamine up to 300 mg daily for 9 weeks. Nine of 10 subjects improved and were less preoccupied with shopping, spent less time shopping, and reported spending less money. We conclude that compulsive buyers can be recruited for research and their symptoms measured and monitored and, finally, that fluvoxamine may be effective in its treatment.

Selective serotonin reuptake inhibitors for fibromyalgia syndrome

PubMed Central

Walitt, Brian; Urrútia, Gerard; Nishishinya, María Betina; Cantrell, Sarah E; Häuser, Winfried

2016-01-01

Background Fibromyalgia is a clinically well-defined chronic condition with a biopsychosocial aetiology. Fibromyalgia is characterized by chronic widespread musculoskeletal pain, sleep problems, cognitive dysfunction, and fatigue. Patients often report high disability levels and poor quality of life. Since there is no specific treatment that alters the pathogenesis of fibromyalgia, drug therapy focuses on pain reduction and improvement of other aversive symptoms. Objectives The objective was to assess the benefits and harms of selective serotonin reuptake inhibitors (SSRIs) in the treatment of fibromyalgia. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 5), MEDLINE (1966 to June 2014), EMBASE (1946 to June 2014), and the reference lists of reviewed articles. Selection criteria We selected all randomized, double-blind trials of SSRIs used for the treatment of fibromyalgia symptoms in adult participants. We considered the following SSRIs in this review: citalopram, fluoxetine, escitalopram, fluvoxamine, paroxetine, and sertraline. Data collection and analysis Three authors extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion. Main results The quality of evidence was very low for each outcome. We downgraded the quality of evidence to very low due to concerns about risk of bias and studies with few participants. We included seven placebo-controlled studies, two with citalopram, three with fluoxetine and two with paroxetine, with a median study duration of eight weeks (4 to 16 weeks) and 383 participants, who were pooled together. All studies had one or more sources of potential major bias. There was a small (10%) difference in patients who reported a 30% pain reduction between SSRIs (56/172 (32.6%)) and placebo (39/171 (22.8%)) risk difference (RD) 0.10, 95% confidence interval (CI) 0.01 to 0.20; number needed to treat for an additional beneficial outcome (NNTB) 10, 95% CI 5 to 100; and in global improvement (proportion of patients who reported to be much or very much improved: 50/168 (29.8%) of patients with SSRIs and 26/162 (16.0%) of patients with placebo) RD 0.14, 95% CI 0.06 to 0.23; NNTB 7, 95% CI 4 to 17. SSRIs did not statistically, or clinically, significantly reduce fatigue: standard mean difference (SMD) −0.26, 95% CI −0.55 to 0.03; 7.0% absolute improvement on a 0 to 10 scale, 95% CI 14.6% relative improvement to 0.8% relative deterioration; nor sleep problems: SMD 0.03, 95 % CI −0.26 to 0.31; 0.8 % absolute deterioration on a 0 to 100 scale, 95% CI 8.3% relative deterioration to 6.9% relative improvement. SSRIs were superior to placebo in the reduction of depression: SMD −0.39, 95% CI −0.65 to −0.14; 7.6% absolute improvement on a 0 to 10 scale, 95% CI 2.7% to 13.8% relative improvement; NNTB 13, 95% CI 7 to 37. The dropout rate due to adverse events was not higher with SSRI use than with placebo use (23/146 (15.8%) of patients with SSRIs and 14/138 (10.1%) of patients with placebo) RD 0.04, 95% CI −0.06 to 0.14. There was no statistically or clinically significant difference in serious adverse events with SSRI use and placebo use (3/84 (3.6%) in patients with SSRIs and 4/84 (4.8%) and patients with placebo) RD −0.01, 95% CI −0.07 to 0.05. Authors’ conclusions There is no unbiased evidence that SSRIs are superior to placebo in treating the key symptoms of fibromyalgia, namely pain, fatigue and sleep problems. SSRIs might be considered for treating depression in people with fibromyalgia. The black box warning for increased suicidal tendency in young adults aged 18 to 24, with major depressive disorder, who have taken SSRIs, should be considered when appropriate. PMID:26046493

Paroxetine (Paxil) and Pregnancy

MedlinePlus

... become pregnant? Some animal studies have suggested poor fertility with paroxetine exposure. Animal studies do not always ... of paroxetine before delivery. For other women, the effects from stopping paroxetine may be more harmful than ...

Fluvoxamine versus other anti-depressive agents for depression

PubMed Central

Omori, Ichiro M; Watanabe, Norio; Nakagawa, Atsuo; Cipriani, Andrea; Barbui, Corrado; McGuire, Hugh; Churchill, Rachel; Furukawa, Toshi A

2014-01-01

Background Fluvoxamine, one of the oldest selective serotonin reuptake inhibitors (SSRIs), is prescribed to patients with major depression in many countries. Several studies have previously reviewed the efficacy and tolerability of fluvoxamine for the treatment of major depression. However, these reviews are now outdated. Objectives Our objective is to evaluate the effectiveness, tolerability and side effect profile of fluvoxamine for major depression in comparison with other anti-depressive agents, including tricyclics (TCAs), heterocyclics, other SSRIs, SNRIs, other newer agents and other conventional psychotropic drugs. Search methods We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register. Trial databases and ongoing trial registers in North America, Europe, Japan and Australia, were handsearched for randomised controlled trials. We checked reference lists of the articles included in the review, previous systematic reviews and major textbooks of affective disorder for published reports and citations of unpublished research. The date of last search was 31 August 2008. Selection criteria We included all randomised controlled trials, published in any language, that compared fluvoxamine with any other active antidepressants in the acute phase treatment of major depression. Data collection and analysis Two independent review authors inspected citations and abstracts, obtained papers, extracted data and assessed the risk of bias of included studies. We analysed dichotomous data using odds ratios (ORs) and continuous data using the standardised mean difference (SMD). A random effects model was used to combine studies. Main results A total of 54 randomised controlled trials (n = 5122) were included. No strong evidence was found to indicate that fluvoxamine was either superior or inferior to other antidepressants regarding response, remission and tolerability. However, differing side effect profiles were evident, especially with regard to gastrointestinal side effects of fluvoxamine when compared to other antidepressants. For example, fluvoxamine was generally associated with a higher incidence of vomiting/nausea (versus imipramine, OR 2.23, CI 1.59 to 3.14; versus clomipramine, OR 2.13, CI 1.06 to 4.27; versus amitriptyline, OR 2.86, CI 1.31 to 2.63). Authors’ conclusions We found no strong evidence that fluvoxamine was either superior or inferior to any other antidepressants in terms of efficacy and tolerability in the acute phase treatment of depression. However, differing side effect profiles were evident. Based on these findings, we conclude that clinicians should focus on practical or clinically relevant considerations, including these differences in side effect profiles. PMID:20238342

A Clinician’s Guide to PTSD Treatments for Returning Veterans

PubMed Central

Sharpless, Brian A.; Barber, Jacques P.

2011-01-01

What options are available to mental health providers helping clients with posttraumatic stress disorder (PTSD)? In this paper we review many of the current pharmacological and psychological interventions available to help prevent and treat PTSD with an emphasis on combat-related traumas and Veteran populations. There is strong evidence supporting the use of several therapies including prolonged exposure (PE), eye movement desensitization and reprocessing (EMDR), and cognitive processing therapies (CPT), with PE possessing the most empirical evidence in favor of its efficacy. There have been relatively fewer studies of non-exposure based modalities (e.g., psychodynamic, interpersonal, and dialectical behavior therapy perspectives), but there is no evidence that these treatments are less effective. Pharmacotherapy is promising (especially paroxetine, sertraline, and venlafaxine), but more research comparing the relative merits of medication vs. psychotherapy and the efficacy of combined treatments is needed. Given the recent influx of combat-related traumas due to ongoing conflicts in Iraq and Afghanistan, there is clearly an urgent need to conduct more randomized clinical trials research and effectiveness studies in military and Department of Veterans Affairs PTSD samples. Finally, we provide references to a number of PTSD treatment manuals and propose several recommendations to help guide clinicians’ treatment selections. PMID:21475611

Plasma levels of catecholamine metabolites predict the response to sulpiride or fluvoxamine in major depression.

PubMed

Ueda, N; Yoshimura, R; Shinkai, K; Nakamura, J

2002-09-01

We investigated the relationships between the changes in plasma catecholamine metabolites obtained from depressed patients before and after administration of sulpiride, a benzamide compound, or fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), and between clinical responses to treatment with each of these drugs. Responders to sulpiride had significantly lower plasma homovanillic acid (pHVA) levels before administration of sulpiride than did non-responders or controls (responders: 4.5 +/- 3.1 ng/ml, non-responders: 11.1 +/- 5.9 ng/ml, controls: 10.9 +/- 5.3 ng/ml). Positive relationships were observed between changes in pHVA levels and improvement rates in the 17-item Hamilton Depression Rating Scale (Ham-D). In contrast, responders to fluvoxamine had significantly higher plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels before administration of fluvoxamine than did non-responders or controls (responders: 8.5 +/- 1.8 ng/ml, non-responders: 5.9 +/- 2.I ng/ml, controls: 5.2 +/- 2.9 ng/ml). Negative relationships were observed between changes in pMHPG levels and improvement rates in Ham-D. These results suggest that lower pretreatment pHVA levels and higher pretreatment levels of pMHPG might be predictors of response to sulpiride and fluvoxamine, respectively, and that sulpiride might produce a functional increase in the dopaminergic system, resulting in improvement in some depressive symptoms; fluvoxamine, on the other hand, might produce a functional decrease in the noradrenergic system via serotonergic neurons, resulting in improvement of those symptoms.

Initial results of the use of prescription order change forms to achieve dose form optimization (consolidation and tablet splitting) of SSRI antidepressants in a state Medicaid program.

PubMed

Hamer, Ann M; Hartung, Daniel M; Haxby, Dean G; Ketchum, Kathy L; Pollack, David A

2006-01-01

One method to reduce drug costs is to promote dose form optimization strategies that take advantage of the flat pricing of some drugs, i.e., the same or nearly the same price for a 100 mg tablet and a 50 mg tablet of the same drug. Dose form optimization includes tablet splitting; taking half of a higher-strength tablet; and dose form consolidation, using 1 higher-strength tablet instead of 2 lower-strength tablets. Dose form optimization can reduce the direct cost of therapy by up to 50% while continuing the same daily dose of the same drug molecule. To determine if voluntary prescription change forms for antidepressant drugs could induce dosing changes and reduce the cost of antidepressant therapy in a Medicaid population. Specific regimens of 4 selective serotonin reuptake inhibitors (SSRIs)- citalopram, escitalopram, paroxetine, and sertraline- were identified for conversion to half tablets or dose optimization. Change forms, which served as valid prescriptions, were faxed to Oregon prescribers in October 2004. The results from both the returned forms and subsequent drug claims data were evaluated using a segmented linear regression. Citalopram claims were excluded from the cost analysis because the drug became available in generic form in October 2004. A total of 1,582 change forms were sent to 556 unique prescribers; 9.2% of the change forms were for dose consolidation and 90.8% were for tablet splitting. Of the 1,118 change forms (70.7%) that were returned, 956 (60.4% of those sent and 85.5% of those returned) authorized a prescription change to a lower-cost dose regimen. The average drug cost per day declined by 14.2%, from Dollars 2.26 to Dollars 1.94 in the intervention group, versus a 1.6% increase, from Dollars 2.52 to Dollars 2.56, in the group without dose consolidation or tablet splitting of the 3 SSRIs (sertraline, escitalopram, and immediate-release paroxetine). Total drug cost for the 3 SSRIs declined by 35.6%, from Dollars 333,567 to Dollars 214,794, as a result of a 24.8% decline in the total days of SSRI drug therapy and the 14.2% decline in average SSRI drug cost per day. The estimated monthly cost avoidance from this intervention, based on pharmacy claims data, was approximately Dollars 35,285, about 2% of the entire spending on SSRI drugs each month, or about Dollars 0.09 per member per month. Program administration costs, excluding costs incurred by prescribers and pharmacy providers, were about 2% of SSRI drug cost savings. Voluntary prescription change forms appear to be an effective and well-accepted tool for obtaining dose form optimization through dose form consolidation and tablet splitting, resulting in reduction in the direct costs of SSRI antidepressant drug therapy with minimal additional program administration costs.

Three year naturalistic outcome study of panic disorder patients treated with paroxetine

PubMed Central

Dannon, Pinhas N; Iancu, Iulian; Cohen, Ami; Lowengrub, Katherine; Grunhaus, Leon; Kotler, Moshe

2004-01-01

Background This naturalistic open label follow-up study had three objectives: 1) To observe the course of illness in Panic Disorder patients receiving long-term versus intermediate-term paroxetine treatment 2) To compare the relapse rates and side-effect profile after long-term paroxetine treatment between patients with Panic Disorder and Panic Disorder with Agoraphobia. 3) To observe paroxetine's tolerability over a 24 month period. Methods 143 patients with panic disorder (PD), with or without agoraphobia, successfully finished a short-term (ie 12 week) trial of paroxetine treatment. All patients then continued to receive paroxetine maintenance therapy for a total of 12 months. At the end of this period, 72 of the patients chose to discontinue paroxetine pharmacotherapy and agreed to be monitored throughout a one year discontinuation follow-up phase. The remaining 71 patients continued on paroxetine for an additional 12 months and then were monitored, as in the first group, for another year while medication-free. The primary limitation of our study is that the subgroups of patients receiving 12 versus 24 months of maintenance paroxetine therapy were selected according to individual patient preference and therefore were not assigned in a randomized manner. Results Only 21 of 143 patients (14%) relapsed during the one year medication discontinuation follow-up phase. There were no significant differences in relapse rates between the patients who received intermediate-term (up to 12 months) paroxetine and those who chose the long-term course (24 month paroxetine treatment). 43 patients (30.1%) reported sexual dysfunction. The patients exhibited an average weight gain of 5.06 kg. All patients who eventually relapsed demonstrated significantly greater weight increase (7.3 kg) during the treatment phase. Conclusions The extension of paroxetine maintenance treatment from 12 to 24 months did not seem to further decrease the risk of relapse after medication discontinuation. Twenty-four month paroxetine treatment is accompanied by sexual side effects and weight gain similar to those observed in twelve month treatment. PMID:15191617

The antidepressant sertraline inhibits translation initiation by curtailing mammalian target of rapamycin signaling.

PubMed

Lin, Chen-Ju; Robert, Francis; Sukarieh, Rami; Michnick, Stephen; Pelletier, Jerry

2010-04-15

Sertraline, a selective serotonin reuptake inhibitor, is a widely used antidepressant agent. Here, we show that sertraline also exhibits antiproliferative activity. Exposure to sertraline leads to a concentration-dependent decrease in protein synthesis. Moreover, polysome profile analysis of sertraline-treated cells shows a reduction in polysome content and a concomitant increase in 80S ribosomes. The inhibition in translation caused by sertraline is associated with decreased levels of the eukaryotic initiation factor (eIF) 4F complex, altered localization of eIF4E, and increased eIF2alpha phosphorylation. The latter event leads to increased REDD1 expression, which in turn impinges on the mammalian target of rapamycin (mTOR) pathway by affecting TSC1/2 signaling. Sertraline also independently targets the mTOR signaling pathway downstream of Rheb. In the Emu-myc murine lymphoma model where carcinogenesis is driven by phosphatase and tensin homologue (PTEN) inactivation, sertraline is able to enhance chemosensitivity to doxorubicin. Our results indicate that sertraline exerts antiproliferative activity by targeting the mTOR signaling pathway in a REDD1-dependent manner. (c) 2010 AACR.

Solid-phase microextraction-gas chromatography-mass spectrometry for the analysis of selective serotonin reuptake inhibitors in environmental water.

PubMed

Lamas, J Pablo; Salgado-Petinal, Carmen; García-Jares, Carmen; Llompart, María; Cela, Rafael; Gómez, Mariano

2004-08-13

The continuous contamination of surface waters by pharmaceuticals is of most environmental concern. Selective serotonin reuptake inhibitors (SSRIs) are drugs currently prescribed for the treatment of depressions and other psychiatric disorders and then, they are among the pharmaceuticals that can occur in environmental waters. Solid-phase microextraction (SPME) coupled to gas chromatography-mass spectrometry has been applied to the extraction of five SSRIs--venlafaxine, fluvoxamine, fluoxetine, citalopram and sertraline--from water samples. Some of the analytes were not efficiently extracted as underivatized compounds and so, an in situ acetylation step was introduced in the sample preparation procedure. Different parameters affecting extraction efficiency such as extraction mode, fiber coating and temperature were studied. A mixed-level fractional factorial design was also performed to simultaneously study the influence of other five experimental factors. Finally, a method based on direct SPME at 100 degrees C using polydimethylsiloxane-divinylbenzene fibers is proposed. The performance of the method was evaluated, showing good linearity and precision. The detection limits were in the sub-ng/mL level. Practical applicability was demonstrated through the analysis of real samples. Recoveries obtained for river water and wastewater samples were satisfactory in all cases. An important aspect of the proposed method is that no matrix effects were observed. Two of the target compounds, venlafaxine and citalopram, were detected and quantified in a sewage water sample.

Effects of sertraline on brain current source of the high beta frequency band: analysis of electroencephalography during audiovisual erotic stimulation in males with premature ejaculation.

PubMed

Kwon, O Y; Kam, S C; Choi, J H; Do, J M; Hyun, J S

2011-01-01

To identify the effects of sertraline, a selective serotonin reuptake inhibitor, for the treatment of premature ejaculation (PE), changes in brain current-source density (CSD) of the high beta frequency band (22-30 Hz) induced by sertraline administration were investigated during audiovisual erotic stimulation. Eleven patients with PE (36.9±7.8 yrs) and 11 male volunteers (24.2±1.9 years) were enrolled. Scalp electroencephalography (EEG) was conducted twice: once before sertraline administration and then again 4 h after the administration of 50 mg sertraline. Statistical non-parametric maps were obtained using the EEG segments to detect the current-density differences in the high beta frequency bands (beta-3, 22-30 Hz) between the EEGs before and after sertraline administration in the patient group and between the patient group and controls after the administration of sertraline during the erotic video sessions. Comparing between before and after sertraline administration in the patients with PE, the CSD of the high beta frequency band at 4 h after sertraline administration increased significantly in both superior frontal gyri and the right medial frontal gyrus (P<0.01). The CSD of the beta-3 band of the patients with PE were less activated significantly in the middle and superior temporal gyrus, lingual and fusiform gyrus, inferior occipital gyrus and cuneus of the right cerebral hemisphere compared with the normal volunteers 4 h after sertraline administration (P<0.01). In conclusion, sertraline administration increased the CSD in both the superior frontal and right middle temporal gyrus in patients with PE. The results suggest that the increased neural activity in these particular cerebral regions after sertraline administration may be associated with inhibitory effects on ejaculation in patients with PE.

Autoradiographic localization of /sup 3/H-paroxetine-labeled serotonin uptake sites in rat brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Souza, E.B.; Kuyatt, B.L.

1987-01-01

Paroxetine is a potent and selective inhibitor of serotonin uptake into neurons. Serotonin uptake sites have been identified, localized, and quantified in rat brain by autoradiography with 3H-paroxetine; 3H-paroxetine binding in slide-mounted sections of rat forebrain was of high affinity (KD = 10 pM) and the inhibition affinity constant (Ki) values of various drugs in competing 3H-paroxetine binding significantly correlated with their reported potencies in inhibiting synaptosomal serotonin uptake. Serotonin uptake sites labeled by 3H-paroxetine were highly concentrated in the dorsal and median raphe nuclei, central gray, superficial layer of the superior colliculus, lateral septal nucleus, paraventricular nucleus of themore » thalamus, and the islands of Calleja. High concentrations of 3H-paroxetine binding sites were found in brainstem areas containing dopamine (substantia nigra and ventral tegmental area) and norepinephrine (locus coeruleus) cell bodies. Moderate concentrations of 3H-paroxetine binding sites were present in laminae I and IV of the frontal parietal cortex, primary olfactory cortex, olfactory tubercle, regions of the basal ganglia, septum, amygdala, thalamus, hypothalamus, hippocampus, and some brainstem areas including the interpeduncular, trigeminal, and parabrachial nuclei. Lower densities of 3H-paroxetine binding sites were found in other regions of the neocortex and very low to nonsignificant levels of binding were present in white matter tracts and in the cerebellum. Lesioning of serotonin neurons with 3,4-methylenedioxyamphetamine caused large decreases in 3H-paroxetine binding. The autoradiographic distribution of 3H-paroxetine binding sites in rat brain corresponds extremely well to the distribution of serotonin terminals and cell bodies as well as with the pharmacological sites of action of serotonin.« less

Sertraline Induces Toxicity and Behavioral Alterations in Planarians.

PubMed

Thumé, Isabela Salvador; Frizzo, Marcos Emílio

2017-01-01

Toxicity attributed to sertraline has been demonstrated recently in different cell types and also in some organisms. We investigated the effect of sertraline on planarians, which are considered suitable for investigations in neurotoxicology and currently are widely used as an animal model in neuropharmacological studies. Planarians treated with 10  µ M sertraline showed a rapid reduction in their spontaneous movement until they became completely motionless and then showed a series of asynchronous paroxysms (seizures) followed by progressive tissue damage, beginning 48 h after the sertraline treatment, and died approximately 72 h later. Our data showed that sertraline does not cause planarian death within the range of therapeutic concentrations; however, behavioral alterations were observed with concentrations that can be considered compatible with therapeutic ones, such as a significant reduction in planarian locomotory activity at 0.4  µ M. Treatment with 4  µ M sertraline had a significant effect, reducing planarian locomotory activity and increasing the number of asynchronous paroxysms; both effects were significantly maintained even 24 h after the sertraline was withdrawn. These behavioral changes observed at low micromolar concentrations suggest that sertraline might have residual biological consequences for planarians, even after it is withdrawn.

Fluvoxamine effects on concurrent ethanol- and food-maintained behaviors

PubMed Central

Ginsburg, Brett C.; Lamb, R.J.

2011-01-01

In previous studies, the selective serotonin reuptake inhibitor fluvoxamine preferentially reduced responding for ethanol compared with responding for food under conditions in which each was available alone in separate groups or in the same subjects under a multiple schedule in which baseline response rates were matched. The impact of providing concurrent access to food on pharmacological effects on ethanol self-administration remains largely unexplored. In this study, acute doses of fluvoxamine (3.0-17.8 mg/kg) were administered 30-min before the experimental session to Lewis rats responding under a concurrent fixed-ratio, fixed-ratio schedule of ethanol and food presentation. Ratios for food were adjusted for each subject to provide matched rates of food and ethanol reinforcement across the 30-min session. Although the number of ethanol and food deliveries did not significantly differ under baseline conditions, response rates did differ. Following fluvoxamine administration, responding for food was decreased more than responding for ethanol. This differential effect did not appear to be related to response rate or fixed-ratio size. Thus, the selectivity of fluvoxamine on ethanol- versus food-maintained responding depends upon the context in which the behavior occurs. Such results may help explain inconsistencies between preclinical results and those in humans, and could provide insight into the behavioral determinants of pharmacological effects on ethanol self-administration. PMID:17115876

Effects of acute or repeated paroxetine and fluoxetine treatment on affective behavior in male and female adolescent rats

PubMed Central

Amodeo, Leslie R.; Greenfield, Venuz Y.; Humphrey, Danielle E.; Varela, Veronica; Pipkin, Joseph A.; Eaton, Shannon E.; Johnson, Jelesa D.; Plant, Christopher P.; Harmony, Zachary R.; Wang, Li; Crawford, Cynthia A.

2015-01-01

Rationale The SSRI antidepressant fluoxetine is one of the few drugs that is effective at treating depression in adolescent humans. In contrast, the SSRI paroxetine has limited efficacy and is more at risk for inducing suicidal behavior. Objective The purpose of the present study was to more fully characterize the differential actions of paroxetine and fluoxetine. Methods In Experiment 1, male and female rats were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (10 mg/kg), or vehicle for 10 days starting on postnatal day (PD) 35, and affective behaviors were assessed using sucrose preference and elevated plus maze tasks. A separate set of rats were used to examine monoamine levels. In Experiment 2, rats were injected with paroxetine (2.5, 5 or 10 mg/kg), fluoxetine (5, 10 or 20 mg/kg), or vehicle during the same time frame as Experiment 1 and anxiety-like behaviors were measured using elevated plus maze, light/dark box, and acoustic startle. Results Repeated SSRI treatment failed to alter sucrose preference, although both paroxetine and fluoxetine reduced time spent in the open arms of the elevated plus maze and light compartment of the light/dark box. Paroxetine, but not fluoxetine, enhanced acoustic startle and interfered with habituation. Serotonin turnover was decreased by both acute and repeated fluoxetine treatment but unaltered by paroxetine administration. Discussion These results show that repeated treatment with paroxetine and fluoxetine has dissociable actions in adolescent rats. In particular, paroxetine, but not fluoxetine, increases acoustic startle at low doses and may increase sensitivity to environmental stressors. PMID:26141193

Effects of acute or repeated paroxetine and fluoxetine treatment on affective behavior in male and female adolescent rats.

PubMed

Amodeo, Leslie R; Greenfield, Venuz Y; Humphrey, Danielle E; Varela, Veronica; Pipkin, Joseph A; Eaton, Shannon E; Johnson, Jelesa D; Plant, Christopher P; Harmony, Zachary R; Wang, Li; Crawford, Cynthia A

2015-10-01

The SSRI antidepressant fluoxetine is one of the few drugs that is effective at treating depression in adolescent humans. In contrast, the SSRI paroxetine has limited efficacy and is more at risk for inducing suicidal behavior. The purpose of the present study was to more fully characterize the differential actions of paroxetine and fluoxetine. In experiment 1, male and female rats were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (10 mg/kg), or vehicle for 10 days starting on postnatal day (PD) 35, and affective behaviors were assessed using sucrose preference and elevated plus maze tasks. A separate set of rats were used to examine monoamine levels. In experiment 2, rats were injected with paroxetine (2.5, 5, or 10 mg/kg), fluoxetine (5, 10, or 20 mg/kg), or vehicle during the same time frame as experiment 1, and anxiety-like behaviors were measured using elevated plus maze, light/dark box, and acoustic startle. Repeated SSRI treatment failed to alter sucrose preference, although both paroxetine and fluoxetine reduced time spent in the open arms of the elevated plus maze and light compartment of the light/dark box. Paroxetine, but not fluoxetine, enhanced acoustic startle and interfered with habituation. Serotonin turnover was decreased by both acute and repeated fluoxetine treatment but unaltered by paroxetine administration. These results show that repeated treatment with paroxetine and fluoxetine has dissociable actions in adolescent rats. In particular, paroxetine, but not fluoxetine, increases acoustic startle at low doses and may increase sensitivity to environmental stressors.

Paroxetine decreased plasma exposure of glyburide partly via inhibiting intestinal absorption in rats.

PubMed

Jiang, Shuwen; Zhao, Weiman; Chen, Yang; Zhong, Zeyu; Zhang, Mian; Li, Feng; Xu, Ping; Zhao, Kaijing; Li, Ying; Liu, Li; Liu, Xiaodong

2015-06-01

Accumulating evidences have shown that diabetes is often accompanied with depression, thus it is possible that oral antidiabetic agent glyburide and antidepressive agent paroxetine are co-administered in diabetic patients. The aim of this study was to assess interactions between glyburide and paroxetine in rats. Effect of paroxetine on pharmacokinetics of orally administered glyburide was investigated. Effect of naringin (NAR), an inhibitor of rat intestinal organic anion transporting polypeptides 1a5 (Oatp1a5), on pharmacokinetics of glyburide was also studied. The results showed that co-administration of paroxetine markedly reduced plasma exposure and prolonged Tmax of glyburide, accompanied by significant increase in fecal excretion of glyburide. Co-administration of naringin also significantly decreased plasma exposure of glyburide. Data from intestinal perfusion experiments showed that both paroxetine and naringin significantly inhibited intestinal absorption of glyburide. Caco-2 cells were used to investigate whether paroxetine and naringin affected intestinal transport of glyburide and fexofenadine (a substrate of Oatp1a5). The results showed that both paroxetine and naringin greatly inhibited absorption of glyburide and fexofenadine. All results gave a conclusion that co-administration of paroxetine decreased plasma exposure of glyburide in rats via inhibiting intestinal absorption of glyburide, which may partly be attributed to the inhibition of intestinal Oatp1a5 activity. Copyright © 2015 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Did intense adverse media publicity impact on prescribing of paroxetine and the notification of suspected adverse drug reactions? Analysis of routine databases, 2001-2004.

PubMed

Martin, Richard M; May, Margaret; Gunnell, David

2006-02-01

To document the impact on clinical practice in England of media attention around possible adverse effects of paroxetine. Analysis of national selective serotonin reuptake inhibitor (SSRI) prescribing trends and yellow-card adverse drug reaction reports, 2001-2004. From a steady state in 2001, paroxetine prescribing declined sharply from April 2002, coinciding with a USA regulatory action; the subsequent decline in paroxetine prescribing was 1.87% per month (95% confidence interval - 2.06, -1.68). Other SSRI prescribing increased by 1% per month until a major UK review of SSRIs in children in December 2003, after which prescribing plateaued. Media publicity was associated with short-term peaks in yellow-card reports related to paroxetine. Falls in paroxetine and other SSRI prescribing in the UK coincided, respectively, with regulatory communications from the USA and the UK, but associations may have noncausal or other explanations. Reports of adverse reactions to paroxetine appeared to increase after adverse media publicity about the drug.

Paroxetine in the treatment of dysthymic disorder without co-morbidities: A double-blind, placebo-controlled, flexible-dose study.

PubMed

Ravindran, Arun V; Cameron, Colin; Bhatla, Raj; Ravindran, Lakshmi N; da Silva, Tricia L

2013-04-01

Few published studies have evaluated selective serotonin reuptake inhibitors in dysthymia without current co-morbid major depression. In this 12-week study, 40 dysthymic patients were randomly assigned to either placebo (n=19) or 20-40 mg/day of paroxetine (n=21). At endpoint, the paroxetine group showed significantly greater improvement on the Clinical Global Impression Scale, Beck Depression Inventory, and Quality of Life Enjoyment and Satisfaction Questionnaire (p<0.05), and a trend to superiority over placebo on the Hamilton Depression Rating Scale. Response and remission were significantly higher with paroxetine than placebo (p<0.05). There were no significant differences in drop out rates or frequency of adverse effects, except for excessive sweating (greater with paroxetine, p=0.04). Reporting of multiple side effects was also higher with paroxetine than with placebo (p=0.02). Paroxetine is more effective than placebo in improving symptoms and quality of life in dysthymia, and is generally tolerable. Copyright © 2012 Elsevier B.V. All rights reserved.

[Studies on the adverse effects of fluvoxamine treatment in children with autistic disorder: correlation with genetic polymorphism in serotonin related genes].

PubMed

Sugie, Yoko; Sugie, Hideo; Fukuda, Tokiko; Ito, Masataka; Ohzeki, Takehiko

2003-05-01

Selective serotonin re-uptake inhibitors (SSRIs) have recently been applied to the children with autistic disorder. To create better treatment, we studied here clinical adverse effects of fluvoxamine and correlated them with genetic polymorphism of two genes, the promoter region of serotonin transporter gene (5-HTTLPR) and serotonin 2A receptor gene (5-HT2AR). Twenty-eight subjects, consisting of 23 boys and 5 girls, aged from 3 to 18 years old diagnosed as having autistic disorder were analyzed during fluvoxamine administration. The dosages and duration of fluvoxamine treatment are 1.5 to 3 mg/kg/day and 2 weeks to 17 months (mean 7.9 months), respectively. There were several clinical adverse effects such as sleep disturbance in 9 cases, climb up to high places in 8, gastrointestinal symptoms in 6, hyperactivities in 5, excitement in 4, general fatigability in 2 and urticaria in 1. Medication was discontinued in 2 patients with fatigability and 1 with sleep disturbance, diarrhea and poor appetite. There was no significant correlation between genetic polymorphism in 5-HTTLPR and the occurrence of clinical adverse effects of fluvoxamine. However hyperactivity was significantly more frequent in the subjects with 102T/102T polymorphism of 5-HT2AR, and patients with sleep disturbance were significantly less frequent in the subjects with 102C/102C polymorphism. We conclude that the clinical adverse effects such as climb up to high places and hyperactivity during fluvoxamine treatment may be relatively specific in children, and that genetic polymorphism of 5-HT2AR may be related to the appearance of clinical adverse effects.

The burden and management of cytochrome P450 2D6 (CYP2D6)-mediated drug-drug interaction (DDI): co-medication of metoprolol and paroxetine or fluoxetine in the elderly.

PubMed

Bahar, Muh Akbar; Hak, Eelko; Bos, Jens H J; Borgsteede, Sander D; Wilffert, Bob

2017-07-01

Metoprolol and paroxetine/fluoxetine are inevitably co-prescribed because cardiovascular disorders and depression often coexist in the elderly. This leads to CYP2D6-mediated drug-drug interactions (DDI). Because systematic evaluations are lacking, we assessed the burden of metoprolol-paroxetine/fluoxetine interaction in the elderly and how these interactions are managed in Dutch community pharmacies. Dispensing data were collected from the University of Groningen pharmacy database (IADB.nl, 1999-2014) for elderly patients (≥60 years) starting beta-blockers and/or antidepressants. Based on the two main DDI alert systems (G-Standard and Pharmabase), incidences were divided between signalled (metoprolol-fluoxetine/paroxetine) and not-signalled (metoprolol-alternative antidepressants and alternative beta-blockers-paroxetine/fluoxetine) combinations. Incident users were defined as patients starting at least one signalled or a non-signalled combination. G-Standard signalled throughout the study period, whereas Pharmabase stopped after 2005. A total of 1763 patients had 2039 metoprolol-paroxetine/fluoxetine co-prescriptions, despite DDI alert systems, and about 57.3% were signalled. The number of metoprolol-alternative antidepressant combinations (incidences = 3150) was higher than alternative beta-blocker-paroxetine/fluoxetine combinations (incidences = 1872). Metoprolol users are more likely to be co-medicated with an alternative antidepressant (incidences = 2320) than paroxetine/fluoxetine users (incidences = 1232) are. The number of paroxetine/fluoxetine users co-prescribed with alternative beta-blockers was comparable to those co-medicated with metoprolol (about 50%). Less than 5% of patients received a substitute therapy after using metoprolol-paroxetine/fluoxetine. Most of the metoprolol users (90%) received a low dose (mean DDD = 0.47) regardless whether they were prescribed paroxetine/fluoxetine. Despite the signalling software, metoprolol-paroxetine/fluoxetine combinations are still observed in the elderly population. The clinical impact of these interactions needs further investigation. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Fluvoxamine for blonanserin-associated akathisia in patients with schizophrenia: report of five cases

PubMed Central

2010-01-01

Background Atypical antipsychotic drugs have been reported to cause fewer incidences of extrapyramidal side effects (EPS) than typical antipsychotic drugs, but adverse events such as akathisia have been observed even with atypical antipsychotic drugs. Although understanding of the pathophysiology of akathisia remains limited, it seems that a complex interaction of several neurotransmitter systems plays a role in its pathophysiology. The endoplasmic reticulum protein sigma-1 receptors have been shown to regulate a number of neurotransmitter systems in the brain. Methods We report on five cases in which monotherapy of the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the akathisia of patients with schizophrenia treated with the new atypical antipsychotic drug blonanserin. Results The global score on the Barnes Akathisia Scale in five patients with schizophrenia treated with blonanserin rapidly decreased after fluvoxamine treatment. Conclusion Doctors should consider that fluvoxamine may be an alternative approach in treating akathisia associated with atypical antipsychotic drugs. PMID:20416096

Fluvoxamine for blonanserin-associated akathisia in patients with schizophrenia: report of five cases.

PubMed

Furuse, Tsutomu; Hashimoto, Kenji

2010-04-24

Atypical antipsychotic drugs have been reported to cause fewer incidences of extrapyramidal side effects (EPS) than typical antipsychotic drugs, but adverse events such as akathisia have been observed even with atypical antipsychotic drugs. Although understanding of the pathophysiology of akathisia remains limited, it seems that a complex interaction of several neurotransmitter systems plays a role in its pathophysiology. The endoplasmic reticulum protein sigma-1 receptors have been shown to regulate a number of neurotransmitter systems in the brain. We report on five cases in which monotherapy of the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the akathisia of patients with schizophrenia treated with the new atypical antipsychotic drug blonanserin. The global score on the Barnes Akathisia Scale in five patients with schizophrenia treated with blonanserin rapidly decreased after fluvoxamine treatment. Doctors should consider that fluvoxamine may be an alternative approach in treating akathisia associated with atypical antipsychotic drugs.

From selective to highly selective SSRIs: a comparison of the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram.

PubMed

Schreiber, Shaul; Pick, Chaim G

2006-08-01

Most Serotonin Selective Reuptake Inhibitors (SSRIs) have been found to possess secondary binding properties, while citalopram and its S-enantiomer (escitalopram) have been reconfirmed "purest SSRIs". Using the mouse model of acute pain hotplate analgesia meter, we evaluated the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram, injected i.p. Fluvoxamine induced a dose-dependent clear antinociceptive effect (with an ED(50) value of 6.4 mg/kg). Both fluoxetine and citalopram induced (separately) only a weak antinociceptive effect with an inverse "U" shape curve. All three drug's effects were not abolished by naloxone. Escitalopram did not elicit any effect at quasi-equipotent doses. These findings show that fluoxetine, fluvoxamine and citalopram given i.p. are weak antinociceptors, (not mediated through opioid mechanisms), while escitalopram possesses no antinociceptive properties when injected i.p. This difference between citalopram and escitalopram calls for further studies in order to assess the various differences between the two enantiomers of citalopram, and between each enantiomer and the racemic mixture.

Yokukansan, a traditional Japanese herbal medicine, enhances the anxiolytic effect of fluvoxamine and reduces cortical 5-HT2A receptor expression in mice.

PubMed

Ohno, Rintaro; Miyagishi, Hiroko; Tsuji, Minoru; Saito, Atsumi; Miyagawa, Kazuya; Kurokawa, Kazuhiro; Takeda, Hiroshi

2018-04-24

Yokukansan is a traditional Japanese herbal medicine that has been approved in Japan as a remedy for neurosis, insomnia, and irritability in children. It has also been reported to improve behavioral and psychological symptoms in patients with various forms of dementia. To evaluate the usefulness of co-treatment with an antidepressant and an herbal medicine in the psychiatric field, the current study examined the effect of yokukansan on the anxiolytic-like effect of fluvoxamine in mice. The anxiolytic-like effect in mice was estimated by the contextual fear conditioning paradigm. Contextual fear conditioning consisted of two sessions, i.e., day 1 for the conditioning session and day 2 for the test session. The expression levels of 5-HT 1A and 5-HT 2A receptor in the mouse brain regions were quantified by western blot analysis. A single administration of fluvoxamine (5-20 mg/kg, i.p.) before the test session dose-dependently and significantly suppressed freezing behavior in mice. In the combination study, a sub-effective dose of fluvoxamine (5 mg/kg, i.p.) significantly suppressed freezing behavior in mice that had been repeatedly pretreated with yokukansan (0.3 and 1 g/kg, p.o.) once a day for 6 days after the conditioning session. Western blot analysis revealed that the expression level of 5-HT 2A receptor was specifically decreased in the prefrontal cortex of mice that had been administered yokukansan and fluvoxamine. Furthermore, microinjection of the 5-HT 2A receptor antagonist ketanserin (5 nmol/mouse) into the prefrontal cortex significantly suppressed freezing behavior. The present findings indicate that repeated treatment with yokukansan synergistically enhances the anxiolytic-like effect of fluvoxamine in the contextual fear conditioning paradigm in mice in conjunction with a decrease in 5-HT 2A receptor-mediated signaling in the prefrontal cortex. Therefore, combination therapy with fluvoxamine and yokukansan may be beneficial for the treatment of anxiety disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Investigation of a Potential Pharmacokinetic Interaction Between Nebivolol and Fluvoxamine in Healthy Volunteers.

PubMed

Gheldiu, Ana-Maria; Vlase, Laurian; Popa, Adina; Briciu, Corina; Muntean, Dana; Bocsan, Corina; Buzoianu, Anca; Achim, Marcela; Tomuta, Ioan; Todor, Ioana; Neag, Maria

2017-01-01

To investigate whether fluvoxamine coadministration can influence the pharmacokinetic properties of nebivolol and its active hydroxylated metabolite (4-OH-nebivolol) and to assess the consequences of this potential pharmacokinetic interaction upon nebivolol pharmacodynamics. This open-label, non-randomized, sequential clinical trial consisted of two periods: Period 1 (Reference), during which each volunteer received a single dose of 5 mg nebivolol and Period 2 (Test), when a combination of 5 mg nebivolol and 100 mg fluvoxamine was given to all subjects, after a 6-days pretreatment regimen with fluvoxamine (50-100 mg/day). Non-compartmental analysis was used to determine the pharmacokinetic parameters of nebivolol and its active metabolite. The pharmacodynamic parameters (blood pressure and heart rate) were assessed at rest after each nebivolol intake, during both study periods. Fluvoxamine pretreatment increased Cmax and AUC0-∞  of nebivolol (Cmax: 1.67 ± 0.690  vs 2.20 ± 0.970  ng/mL; AUC0-∞: 12.1 ± 11.0  vs 19.3 ± 19.5  ng*h/mL ) and of its active metabolite (Cmax: 0.680  ± 0.220  vs 0.960 ± 0.290  ng/mL; AUC0-∞: 17.6 ±20.1  vs 25.5 ± 29.9  ng*h/mL). Apart from Cmax,AUC0-t and AUC0-∞, the other pharmacokinetic parameters (tmax, kel and t½) were not significantly different between study periods. As for the pharmacodynamic analysis, decreases in blood pressure and heart rate after nebivolol administration were similar with and without fluvoxamine concomitant intake. Due to enzymatic inhibition, fluvoxamine increases the exposure to nebivolol and its active hydroxylated metabolite in healthy volunteers. This did not influence the blood pressure and heart-rate lowering effects of the beta-blocker administered as single-dose. However, more detail studies involving actual patients are required to further investigate the clinical relevance of this drug interaction. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.

PubMed

Cipriani, Andrea; Furukawa, Toshi A; Salanti, Georgia; Chaimani, Anna; Atkinson, Lauren Z; Ogawa, Yusuke; Leucht, Stefan; Ruhe, Henricus G; Turner, Erick H; Higgins, Julian P T; Egger, Matthias; Takeshima, Nozomi; Hayasaka, Yu; Imai, Hissei; Shinohara, Kiyomi; Tajika, Aran; Ioannidis, John P A; Geddes, John R

2018-04-07

Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder. We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291. We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89-2·41) for amitriptyline and 1·37 (1·16-1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72-0·97) and fluoxetine (0·88, 0·80-0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01-1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19-1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51-0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43-0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30-2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low. All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants. National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Agomelatine versus Sertraline: An Observational, Open-labeled and 12 Weeks Follow-up Study on Efficacy and Tolerability

PubMed Central

Akpınar, Esma; Cerit, Cem; Talas, Anıl; Tural, Ümit

2016-01-01

Objective In this open-labeled, 12 weeks follow-up study, we aimed to compare the efficacy and tolerability of agomelatine with sertraline Methods The outpatients of adult psychiatry clinic who have a new onset of depression and diagnosed as ‘major depressive episode’ by clinician according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition and prescribed agomelatine (25 mg/day) or sertraline (50 mg/day) were included in the study. Results The decline of mean Montgomery-Asberg Depression Rating Scale (MADRS) scores of agomelatine group was significantly higher than the sertraline group at the end of 2nd week; however, the difference was not significant at the end of 3 months. Mean Clinical Global Impression-Improvement scale (CGI-I) scores of agomelatine group was lower than sertraline group at first week. Mean CGI-Severity scale and CGI-I scores were favour to sertraline group at the end of the study. Remission rates were 46.7% for sertraline group and 33.3% for agomelatine group while response rates were 76.7% for both groups. Any patient from agomelatine group dropped-out due to adverse effects. The amount of side effects was also less with agomelatine. Conclusion Agomelatine has a rapid onset efficacy on depressive symptoms and this can be beneficial for some critical cases. Considering MADRS scores, agomelatine seems to have similar efficacy with sertraline but we also point the need for long term studies since CGI scores were favour to sertraline group at the end of the study. Agomelatine has a favourable tolerability profile both in terms of discontinuation and the amount of side effects compared to sertraline. PMID:27776387

Antidepressant-like Effect of Insulin in Streptozotocin-induced Type 2 Diabetes Mellitus Rats.

PubMed

Sestile, Caio C; Maraschin, Jhonatan C; Rangel, Marcel P; Cuman, Roberto K N; Audi, Elisabeth A

2016-09-01

This study evaluated the antidepressant-like effect of insulin compared to sertraline and a combination of insulin and sertraline in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats submitted to the forced swim test (FST). Male Wistar rats were daily treated for 21 days with insulin (1 or 2 IU/kg, i.p.), with the selective serotonin reuptake inhibitor (SSRI), sertraline (10 mg/kg, i.p.), or with a combination of insulin (1 or 2 IU/kg, i.p.) and sertraline (10 mg/kg, i.p.) and submitted to the FST. We also evaluated the water and food intake, urine volume and weight gain of the rats. Rats treated with STZ showed impaired glucose tolerance. Chronic treatment with sertraline showed an antidepressant-like effect in non-diabetic and diabetic rats. Furthermore, sertraline promoted lower weight gain in diabetic rats. Insulin reduced the immobility behaviour in T2DM rats with impaired glucose tolerance. In conclusion, our results showed that insulin has an antidepressant-like effect comparable to that of sertraline. Sertraline is effective as an antidepressant and reduces weight gain, which reinforces its superiority over other SSRIs in the treatment of major depression disorder in patients with T2DM. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Neuroprotective Effects of Psychotropic Drugs in Huntington’s Disease

PubMed Central

Lauterbach, Edward C.

2013-01-01

Psychotropics (antipsychotics, mood stabilizers, antidepressants, anxiolytics, etc.) are commonly prescribed to treat Huntington’s disease (HD). In HD preclinical models, while no psychotropic has convincingly affected huntingtin gene, HD modifying gene, or huntingtin protein expression, psychotropic neuroprotective effects include upregulated huntingtin autophagy (lithium), histone acetylation (lithium, valproate, lamotrigine), miR-222 (lithium-plus-valproate), mitochondrial protection (haloperidol, trifluoperazine, imipramine, desipramine, nortriptyline, maprotiline, trazodone, sertraline, venlafaxine, melatonin), neurogenesis (lithium, valproate, fluoxetine, sertraline), and BDNF (lithium, valproate, sertraline) and downregulated AP-1 DNA binding (lithium), p53 (lithium), huntingtin aggregation (antipsychotics, lithium), and apoptosis (trifluoperazine, loxapine, lithium, desipramine, nortriptyline, maprotiline, cyproheptadine, melatonin). In HD live mouse models, delayed disease onset (nortriptyline, melatonin), striatal preservation (haloperidol, tetrabenazine, lithium, sertraline), memory preservation (imipramine, trazodone, fluoxetine, sertraline, venlafaxine), motor improvement (tetrabenazine, lithium, valproate, imipramine, nortriptyline, trazodone, sertraline, venlafaxine), and extended survival (lithium, valproate, sertraline, melatonin) have been documented. Upregulated CREB binding protein (CBP; valproate, dextromethorphan) and downregulated histone deacetylase (HDAC; valproate) await demonstration in HD models. Most preclinical findings await replication and their limitations are reviewed. The most promising findings involve replicated striatal neuroprotection and phenotypic disease modification in transgenic mice for tetrabenazine and for sertraline. Clinical data consist of an uncontrolled lithium case series (n = 3) suggesting non-progression and a primarily negative double-blind, placebo-controlled clinical trial of lamotrigine. PMID:24248060

Studying the association complex formation of atomoxetine and fluvoxamine with eosin Y and its application in their fluorimetric determination

NASA Astrophysics Data System (ADS)

Derayea, Sayed M.; Omar, Mahmoud A.; Abu-hassan, Ahmed A.

2018-03-01

A simple, sensitive and non-extractive spectrofluorimetric method has been developed and validated for the determination of two psychoanaleptic drugs, atomoxetine and fluvoxamine, in pure forms and pharmaceutical dosage forms. The proposed method is based on the formation of binary complexes between eosin Y and the studied drugs in the presence of a Teorell-Stenhagen buffer. The quenching of the native fluorescence of eosin Y due to complex formation with the studied drugs was measured spectrofluorimetrically at 545 nm after excitation at 302 nm. At the optimum reaction conditions, the fluorescence quenching values (ΔF) and concentrations were rectilinear over the concentration ranges of 0.2-2.2 and 0.3-2.2 µg ml-1 for atomoxetine and fluvoxamine, respectively. The developed method was successfully applied for the determination of the studied drugs in their pharmaceutical formulations with average percentage recoveries of 100.13 ± 0.66 and 99.69 ± 0.44 for atomoxetine and fluvoxamine, respectively (n = 5), without interference from common excipients.

Studying the association complex formation of atomoxetine and fluvoxamine with eosin Y and its application in their fluorimetric determination

PubMed Central

Omar, Mahmoud A.; Abu-hassan, Ahmed A.

2018-01-01

A simple, sensitive and non-extractive spectrofluorimetric method has been developed and validated for the determination of two psychoanaleptic drugs, atomoxetine and fluvoxamine, in pure forms and pharmaceutical dosage forms. The proposed method is based on the formation of binary complexes between eosin Y and the studied drugs in the presence of a Teorell–Stenhagen buffer. The quenching of the native fluorescence of eosin Y due to complex formation with the studied drugs was measured spectrofluorimetrically at 545 nm after excitation at 302 nm. At the optimum reaction conditions, the fluorescence quenching values (ΔF) and concentrations were rectilinear over the concentration ranges of 0.2–2.2 and 0.3–2.2 µg ml−1 for atomoxetine and fluvoxamine, respectively. The developed method was successfully applied for the determination of the studied drugs in their pharmaceutical formulations with average percentage recoveries of 100.13 ± 0.66 and 99.69 ± 0.44 for atomoxetine and fluvoxamine, respectively (n = 5), without interference from common excipients. PMID:29657744

Effect of sertraline on proliferation and neurogenic differentiation of human adipose-derived stem cells

PubMed Central

Razavi, Shahnaz; Jahromi, Maliheh; Amirpour, Nushin; Khosravizadeh, Zahra

2014-01-01

Background: Antidepressant drugs are commonly employed for anxiety and mood disorders. Sertraline is extensively used as antidepressant in clinic. In addition, adipose tissue represents an abundant and accessible source of adult stem cells with the ability to differentiate in to multiple lineages. Therefore, human adipose-derived stem cells (hADSCs) may be useful for autologous transplantation. Materials and Methods: In the present study, we assessed the effect of antidepressant drug Sertraline on the proliferation and neurogenic differentiation of hADSCs using MTT assay and immunofluorescence technique respectively. Results: MTT assay analysis showed that 0.5 μM Sertraline significantly increased the proliferation rate of hADSCs induced cells (P < 0.05), while immunofluorescent staining indicated that Sertraline treatment during neurogenic differentiation could be decreased the percentage of glial fibrillary acidic protein and Nestin-positive cells, but did not significantly effect on the percentage of MAP2 positive cells. Conclusion: Overall, our data show that Sertraline can be promoting proliferation rate during neurogenic differentiation of hADSCs after 6 days post-induction, while Sertraline inhibits gliogenesis of induced hADSCs. PMID:24800186

Sertraline and/or interpersonal psychotherapy for patients with dysthymic disorder in primary care: 6-month comparison with longitudinal 2-year follow-up of effectiveness and costs.

PubMed

Browne, Gina; Steiner, Meir; Roberts, Jacqueline; Gafni, Amiram; Byrne, Carolyn; Dunn, Edward; Bell, Barbara; Mills, Michael; Chalklin, Lori; Wallik, David; Kraemer, James

2002-04-01

There is little information on the long-term effects and costs of a combination of Sertraline and interpersonal psychotherapy (IPT) for the treatment of dysthymia in primary care. In a single-blind, randomized clinical trial, 707 adults (18-74 years of age inclusive) with DSM-IV dysthymic disorder, with or without past and/or current major depression, as an acute or chronic episode, in a community-based primary care practice in Ontario, Canada, were randomized to treatment with either Sertraline alone (50-200 mg), or IPT alone (10 sessions), or Sertraline plus IPT combined. In the acute treatment phase (first 6 months) all groups received full active treatment. This was followed by an additional 18-month naturalistic follow-up phase. Subjects were assessed for effectiveness of treatment in reducing depressive symptoms using the Montgomery Asberg Depression Rating Scale (MADRS) at 6 months and twice again during the 18-month follow-up by blind independent observers. Treatment costs and subjects' use of other health and social services were also investigated. At 6 months, 586 subjects completed the MADRS questionnaire. There was a significant difference (P=0.025) in mean MADRS scores: 14.3 (Group I); 14.9 (Group II); 16.8 (Group III), using analysis of covariance. Response (40% improvement) rates were 60.2% for Sertraline alone, 46.6% for IPT alone, and 57.5% for Sertraline augmented by IPT (P=0.02). At 2 years, 525 subjects were retained for follow-up. There was no statistically significant difference between Sertraline alone and Sertraline plus IPT in symptom reduction. However, both were more effective than IPT alone in reducing depressive symptoms (P=0.03). There was a statistically significant difference between groups in costs for use of health and social services. The IPT treatment groups had the lower costs for use of health and social services. Sertraline or Sertraline plus IPT was more effective than IPT alone after 6 months. Over the long term (2 years), all three treatments provide reasonably effective treatment for reducing symptoms of dysthymia, but Sertraline or combining Sertraline with IPT is more effective than IPT alone. Of these two more effective treatments, subjects in the Sertraline plus IPT group had less health and social service costs by $480 per person over 2 years. These findings underscore the effects of combining pharmacotherapy and psychotherapy and the economic value of this more comprehensive treatment of dysthymia in primary care.

Effect of co-administration of memantine and sertraline on the antidepressant-like activity and brain-derived neurotrophic factor (BDNF) levels in the rat brain.

PubMed

Amidfar, Meysam; Réus, Gislaine Z; Quevedo, João; Kim, Yong-Ku; Arbabi, Mohammad

2017-01-01

A developing body of data has drawn attention to the N-methyl-d-aspartate (NMDA) receptor antagonists as potential drugs for the treatment of major depressive disorder (MDD). We investigated the possibility of synergistic interactions between the antidepressant sertraline with the uncompetitive NMDA receptor antagonist, memantine. The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with memantine and sertraline alone or in combination in rats. To this aim, rats were chronically treated with memantine (2.5 and 5mg/kg) and sertraline (5mg/kg) for 14days once a day, and then exposed to the forced swimming test. The brain-derived neurotrophic factor (BDNF) levels were assessed in the hippocampus and prefrontal cortex in all groups by ELISA sandwich assay. Sertraline and memantine (2.5mg/kg) alone did not have effect on the immobility time; however, the effect of sertraline was enhanced by both doses of memantine. Combined treatment with memantine and sertraline produced stronger increases in the BDNF protein levels in the hippocampus and prefrontal cortex. Our results indicate that co-administration of antidepressant memantine with sertraline may induce a more pronounced antidepressant activity than treatment with each antidepressant alone. Antidepressant properties using the combination of memantine and sertraline could be attributed to increased levels of BDNF. This finding may be of particular importance in the case of drug-resistant patients and could suggest a method of obtaining significant antidepressant actions whereas limiting side effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Paroxetine Can Enhance Neurogenesis during Neurogenic Differentiation of Human Adipose-derived Stem Cells

PubMed Central

Jahromi, Maliheh; Razavi, Shahnaz; Amirpour, Nushin; Khosravizadeh, Zahra

2016-01-01

Background: Some antidepressant drugs can promote neuronal cell proliferation in vitro as well as hippocampal neurogenesis in human and animal models. Furthermore, adipose tissue is an available source of adult stem cells with the ability to differentiate in to multiple lineages. Therefore, human Adipose-Derived Stem Cells (hAD-SCs) may be a suitable source for regenerative medical applications. Since there is no evidence for the effect of Paroxetine as the most commonly prescribed antidepressant drug for neurogenic potential of hADSCs, an attempt was made to determine the effect of Paroxetine on proliferation and neural differentiation of hADSCs. Methods: ADSCs were isolated from human abdominal fat. These cells differentiated to neuron-like cells and were treated with Paroxetine. 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay and immunofluorescence technique were used for assessment of cell proliferation and neurogenic differentiation potential of induced cells, respectively. Results: MTT assay analysis showed that Paroxetine significantly increased the proliferation rate of induced hADSCs (p<0.05), while immunofluorescent staining indicated that Paroxetine treatment during neurogenic differentiation could enhance the mean percentage of Nestin and MAP2 (Microtubule-associated protein-2) positive cells but the mean percentage of GFAP (Glial acidic fibrillary protein) positive cells significantly decreased relative to control group (p<0.05). Conclusion: Our results provide evidence that Paroxetine can promote proliferation and differentiation rate during neurogenic differentiation of hADSCs. Moreover, Paroxetine can reduce gliogenesis of induced hADSCs during neurogenic differentiation. PMID:27920882

Pilot Study: Fluvoxamine Treatment for Depression and Anxiety Disorders in Children and Adolescents with Cancer

ERIC Educational Resources Information Center

Gothelf, Doron; Rubinstein, Maly; Shemesh, Eyal; Miller, Orit; Farbstein, Ilana; Klein, Anat; Weizman, Abraham; Apter, Alan; Yaniv, Isaac

2005-01-01

Objective: To evaluate the safety, tolerability, and benefit of fluvoxamine for the treatment of major depressive disorder or anxiety disorders in children and adolescents with cancer. Method: The study was conducted from 2001 to 2004 at a pediatric hematology-oncology center. Fifteen children and adolescents with cancer were treated with…

Paroxetine reduces crying in young women watching emotional movies.

PubMed

van der Veen, Frederik M; Jorritsma, Joyce; Krijger, Carola; Vingerhoets, Ad J

2012-03-01

Crying is a unique human emotional reaction that has not received much attention from researchers. Little is known about its underlying neurobiological mechanisms, although there is some indirect evidence suggesting the involvement of central serotonin. We examined the acute effects of the administration of 20 mg paroxetine on the crying of young, healthy females in response to emotional movies. We applied a double-blind, crossover randomised design with 25 healthy young females as study participants. On separate days, they received either paroxetine or placebo and were exposed to one of two emotional movies: 'Once Were Warriors' and 'Brian's Song'. Crying was assessed by self-report. In addition, the reactions to emotional International Affective Picture System (IAPS) pictures and mood were measured. Paroxetine had a significant inhibitory effect on crying. During both films, the paroxetine group cried significantly less than the placebo group. In contrast, no effects on mood and only minor effects on the reaction to the IAPS pictures were observed. A single dose of paroxetine inhibits emotional crying significantly. It is not sure what the underlying mechanism is. However, since there was no effect on mood and only minor effects on the response to emotional pictures, we postulate that paroxetine mainly acts on the physiological processes involved in the crying response.

Unraveling the association between SSRI use and falls: an experimental study of risk factors for accidental falls in long-term paroxetine users.

PubMed

Hegeman, Judith; van den Bemt, Bart; Weerdesteyn, Vivian; Nienhuis, Bart; van Limbeek, Jacques; Duysens, Jacques

2011-01-01

Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat depression and are also associated with an increased falls risk. However, the biological mechanism underlying accidental falls with SSRI intake has yet to be elucidated. The present experimental study was designed to investigate whether obstacle avoidance skills in long-term (>90 days), senior paroxetine users (61 ± 5.8 years) are affected during gait, simple and challenging postural balance tasks, as well as during manual reaction time tasks. The performance of the paroxetine users was compared with healthy group-matched controls (60 ± 4.8 years). The results demonstrated impaired postural balance in the paroxetine users, especially during one-legged stance or under various dual-task conditions. Although the deficit in one-legged stance could indicate vestibular involvement, this was deemed unlikely because performance of standing on compliant surface with closed eyes remained unaffected. Paroxetine use also failed to affect manual reaction times or obstacle avoidance performance. It is suggested that paroxetine affects attentional capacities particularly in conjunction with balance control. Compared with healthy seniors, long-term senior users of paroxetine seem to be at an increased risk of falling due to impairments in balance control, especially when attention has to be divided between 2 concurrent activities.

Rhodiola rosea versus sertraline for major depressive disorder: A randomized placebo-controlled trial

PubMed Central

Mao, Jun J.; Xie, Sharon X.; Zee, Jarcy; Soeller, Irene; Li, Qing S.; Rockwell, Kenneth; Amsterdam, Jay D.

2015-01-01

Background We performed a proof of concept trial to evaluate relative safety and efficacy of Rhodiola rosea (R. rosea) versus sertraline for mild to moderate major depressive disorder. Hypothesis We hypothesize that R. rosea would have similar therapeutic effects as sertraline but with less adverse events. Study Design Phase II randomized placebo controlled clinical trial Methods 57 subjects were randomized to 12 weeks of standardized R. rosea extract, sertraline, or placebo. Changes over time in Hamilton Depression Rating (HAM-D), Beck Depression Inventory (BDI), and Clinical Global Impression Change (CGI/C) scores among groups were examined using mixed-effects models. Results Modest, albeit statistically non-significant, reductions were observed for HAM-D, BDI, and CGI/C scores for all treatment conditions with no significant difference between groups (p=0.79, p=0.28, and p=0.17, respectively). The decline in HAM-D scores was greater for sertraline (−8.2, 95% confidence interval [CI], −12.7 to −3.6) versus R. rosea (−5.1, 95% CI: −8.8 to −1.3) and placebo (−4.6, 95% CI: −8.6 to −0.6). While the odds of improving (versus placebo) were greater for sertraline (1.90 [0.44–8.20]; odds ratio [95% CI]) than R. rosea (1.39 [0.38–5.04]), more subjects on sertraline reported adverse events (63.2%) than R. rosea (30.0%) or placebo (16.7%) (p=0.012). Conclusions Although R. rosea produced less antidepressant effect versus sertraline, it also resulted in significantly fewer adverse events and was better tolerated. These findings suggest that R. rosea, although less effective than sertraline, may possess a more favorable risk to benefit ratio for individuals with mild to moderate depression. PMID:25837277

Acupuncture versus paroxetine for the treatment of premature ejaculation: a randomized, placebo-controlled clinical trial.

PubMed

Sunay, Didem; Sunay, Melih; Aydoğmuş, Yasin; Bağbancı, Sahin; Arslan, Hüseyin; Karabulut, Ayhan; Emir, Levent

2011-05-01

Acupuncture therapy has been used by many researchers in both male and female sexual dysfunction studies. To determine whether acupuncture is effective as a premature ejaculation (PE) treatment compared with paroxetine and placebo. The study was conducted with methodologic rigor based on Consolidated Standards of Reporting Trials (CONSORT) criteria. Ninety patients referred to the urology clinic at a tertiary training and research hospital with PE were included in this randomized controlled trial and randomly assigned into paroxetine, acupuncture, and placebo groups. Heterosexual, sexually active men aged between 28 and 50 yr were included. Men with other sexual disorders, including erectile dysfunction; with chronic psychiatric or systemic diseases; with alcohol or substance abuse; or who used any medications were excluded. The medicated group received paroxetine 20 mg/d; the acupuncture or sham-acupuncture (placebo) groups were treated twice a week for 4 wk. Intravaginal ejaculation latency times (IELTs) and the Premature Ejaculation Diagnostic Tool (PEDT) were used to assess PE. IELTs were calculated by using a partner-held stopwatch. Data were analyzed statistically. Median PEDT scores of paroxetine, acupuncture, and placebo groups were 17.0, 16.0, and 15.5 before treatment, and 10.5, 11.0, and 16.0 after treatment, respectively (p=0.001, p=0.001, and p=0.314, respectively). Subscores after treatment were significantly lower than subscores before treatment in the paroxetine and acupuncture groups but remained the same in the placebo group. Significant differences were found between mean-rank IELTs of the paroxetine and placebo groups (p=0.001) and the acupuncture and placebo groups (p=0.001) after treatment. Increases of IELTs with paroxetine, acupuncture, and placebo acupuncture were 82.7, 65.7, and 33.1 s, respectively. Extent of ejaculation delay induced by paroxetine was significantly higher than that of acupuncture (p=0.001). The most important limitation of the study was the lack of follow-up. Although less effective than daily paroxetine, acupuncture had a significant stronger ejaculation-delaying effect than placebo. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Fluorine magnetic resonance spectroscopy measurement of brain fluvoxamine and fluoxetine in pediatric patients treated for pervasive developmental disorders.

PubMed

Strauss, Wayne L; Unis, Alan S; Cowan, Charles; Dawson, Geraldine; Dager, Stephen R

2002-05-01

Pediatric populations, including those with autistic disorder or other pervasive developmental disorders, increasingly are being prescribed selective serotonin reuptake inhibitors (SSRIs). Little is known about the age-related brain pharmacokinetics of SSRIs; there is a lack of data regarding optimal dosing of medications for children. The authors used fluorine magnetic resonance spectroscopy ((19)F MRS) to evaluate age effects on whole-brain concentrations of fluvoxamine and fluoxetine in children taking SSRIs. Twenty-one pediatric subjects with diagnoses of autistic disorder or other pervasive developmental disorders, 6-15 years old and stabilized with a consistent dose of fluvoxamine or fluoxetine, were recruited for the study; 16 successfully completed the imaging protocol. Whole-brain drug levels in this group were compared to similarly acquired data from 28 adults. A significant relationship between dose and brain drug concentration was observed for both drugs across the age range studied. Brain fluvoxamine concentration in the children was lower, consistent with a lower dose/body mass drug prescription; when brain concentration was adjusted for dose/mass, age effects were no longer significant. Brain fluoxetine concentration was similar between age groups; no significant age effects on brain fluoxetine drug levels remained after adjustment for dose/mass. Observations of brain fluoxetine bioavailability and elimination half-life also were similar between age groups. These findings suggest that fluvoxamine or fluoxetine prescriptions adjusted for dose/mass are an acceptable treatment approach for medicating children with autistic disorder or other pervasive developmental disorders. It must be determined whether these findings can be generalized to other pediatric populations.

Post-marketing observational program of the effectiveness of fluvoxamine for the treatment of depression in patients with neurological disorders: the FRIENDS study.

PubMed

Yahno, Nikolay N; Fedotova, Anastasia V

2017-01-01

In a prospective, non-blinded, uncontrolled, multicenter, post-marketing, observational study (FRIENDS; NCT02043197), fluvoxamine (50-300 mg/day for 90 days) was effective for the treatment of depression in 299 adult patients (age ≥18 years) with neurological disorders at baseline. The therapeutic effect of fluvoxamine was measured by means of changes in the Hospital Anxiety and Depression Scale depression and anxiety scores (HADS-D and HADS-A, respectively), global severity of illness, and clinical condition (measured using the Clinical Global Improvement [CGI] scale). The mean HADS-D subscale score at baseline in the per-protocol cohort (n=296) was 11.7±3.1 points and the corresponding mean HADS-A score was 12.6±3.2. Significant ( P <0.0001) improvements in both scores were recorded during fluvoxamine treatment and later follow-up. Most patients (>85%) recorded reductions versus baseline in both indices. In the CGI-based assessment, most evaluated patients (>200) experienced moderate to very substantial clinical improvement, with no or limited side effects. Significant improvements were also recorded in the exploratory outcomes of sleep quality, assessed using the Insomnia Severity Index, and cognitive function, assessed using the Montreal Cognitive Assessment ( P <0.0001 vs baseline for both). No death or serious adverse drug reactions were reported during the study. The results of this observational study affirm that fluvoxamine is effective and well tolerated for the treatment of depression in the context of neurological disorders. The effects on the exploratory endpoints of this research merit evaluation in controlled trials.

Strain differences in paroxetine-induced reduction of immobility time in the forced swimming test in mice: role of serotonin.

PubMed

Guzzetti, Sara; Calcagno, Eleonora; Canetta, Alessandro; Sacchetti, Giuseppina; Fracasso, Claudia; Caccia, Silvio; Cervo, Luigi; Invernizzi, Roberto W

2008-10-10

We studied the antidepressant-like effect of paroxetine in strains of mice carrying different isoforms of tryptophan hydroxylase-2 (TPH-2), the enzyme responsible for the synthesis of brain serotonin (5-HT). The effect of paroxetine alone and in combination with pharmacological treatments enhancing or lowering 5-HT synthesis or melatonin was assessed in the forced swimming test in mice carrying allelic variants of TPH-2 (1473C in C57BL/6 and 1473G in DBA/2 and BALB/c). Changes in brain 5-hydroxytryptophan (5-HTP) accumulation and melatonin levels were measured by high-performance liquid chromatography. Paroxetine (2.5 and 5 mg/kg) reduced immobility time in C57BL/6J and C57BL/6N mice but had no such effect in DBA/2J, DBA/2N and BALB/c mice, even at 10 mg/kg. Enhancing 5-HT synthesis with tryptophan reinstated the antidepressant-like effect of paroxetine in DBA/2J, DBA/2N and BALB/c mice whereas inhibition of 5-HT synthesis prevented the effect of paroxetine in C57BL/6N mice. The response to paroxetine was not associated with changes in locomotor activity, brain melatonin or brain levels of the drug measured at the end of the behavioral test. These results support the importance of 5-HT synthesis in the response to SSRIs and suggest that melatonin does not contribute to the ability of tryptophan to rescue the antidepressant-like effect of paroxetine.

Treatment of depression with comorbid anxiety disorders: differential efficacy of paroxetine versus moclobemide.

PubMed

Pini, Stefano; Amador, Xavier F; Dell'Osso, Liliana; Baldini Rossi, Nicolò; Cassano, Paolo; Savino, Mario; Cassano, Giovanni B

2003-01-01

To compare the efficacy and tolerability of moclobemide versus paroxetine for the treatment of depression with comorbid anxiety disorders. Outpatients fulfilling DSM-III-R criteria for major depression or dysthymia and for a co-occurring comorbid anxiety disorder (panic disorder, generalized anxiety disorder or obsessive-compulsive disorder) after a 1-week run-in phase were randomly assigned to open-label moclobemide (300-600 mg/day) or paroxetine (20-40 mg/day) for 4 months. Primary criterion for response was a 50% score reduction from baseline on Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores. Mean changes in Clinical Global Impressions Severity of Illness and Improvement Scales (CGI-I) were also used to evaluate treatment response. Of the 123 patients included in the study, 65 were randomly assigned to moclobemide and 58 to paroxetine. At study end, the two treatment groups did not differ significantly in terms of proportion of responders. Treatment group differences emerged when comorbid anxiety diagnoses were considered. In patients with comorbid panic disorder, paroxetine was superior to moclobemide in improving both anxiety and depression (five patients out of 18 in the moclobemide group and nine out of 14 in the paroxetine group were rated as responders according to CGI-I, P = 0.04). Neither medication was superior in treating comorbid generalized anxiety disorder. These findings indicate that both moclobemide and paroxetine are effective for treatment of depression with comorbid anxiety disorders. However, in the subgroup with comorbid panic disorder, paroxetine is more effective than moclobemide in reducing both depressive and anxiety symptoms.

Treating Chronic Tension-type Headache Not Responding to Amitriptyline Hydrochloride With Paroxetine Hydrochloride: A Pilot Evaluation

PubMed Central

Holroyd, Kenneth A.; Labus, Jennifer S.; O'Donnell, Francis J.; Cordingley, Gary E.

2007-01-01

Context In some individuals, chronic tension-type headache fails to respond to tricyclic antidepressant medications that often serve as first-line therapy. Objective To evaluate the clinical efficacy of paroxetine hydrochloride for chronic tension-type headache not responding to amitriptyline hydrochloride. Design and Setting Open-label trial of paroxetine conducted at 2 outpatient sites in Ohio. Participants and Intervention Thirty-one adults (mean age, 37 years; 20 women) with chronic tension-type headache (mean, 25 headache days per month) who had failed to respond (less than 30% improvement) to treatment with either amitriptyline (n = 13) or matched placebo (n = 18). All participants were treated with paroxetine (up to 40 mg per day) in a 9-month protocol. Outcome Measures Monthly headache index calculated as the mean of pain ratings (0 to 10 scale) recorded by participants in a diary 4 times per day, number of days per month with at least moderate pain (pain rating of 5 or greater), and analgesic medication use. Results In patients who had not responded to amitriptyline, paroxetine failed to reduce chronic tension-type headaches or analgesic medication use. In patients who had not responded to placebo, paroxetine produced modest reductions in chronic tension-type headaches and analgesic use. Conclusions We found no evidence that chronic tension-type headaches that failed to respond to tricyclic antidepressant therapy with amitriptyline improved when subsequently treated with paroxetine. More support was found for the efficacy of paroxetine in patients with chronic tension-type headaches who had failed to respond to placebo. PMID:14511278

Established amyloid-β pathology is unaffected by chronic treatment with the selective serotonin reuptake inhibitor paroxetine.

PubMed

Severino, Maurizio; Sivasaravanaparan, Mithula; Olesen, Louise Ø; von Linstow, Christian U; Metaxas, Athanasios; Bouzinova, Elena V; Khan, Asif Manzoor; Lambertsen, Kate L; Babcock, Alicia A; Gramsbergen, Jan Bert; Wiborg, Ove; Finsen, Bente

2018-01-01

Treatment with selective serotonin reuptake inhibitors has been suggested to mitigate amyloid-β (Aβ) pathology in Alzheimer's disease, in addition to an antidepressant mechanism of action. We investigated whether chronic treatment with paroxetine, a selective serotonin reuptake inhibitor, mitigates Aβ pathology in plaque-bearing double-transgenic amyloid precursor protein (APP) swe /presenilin 1 (PS1) ΔE9 mutants. In addition, we addressed whether serotonin depletion affects Aβ pathology. Treatments were assessed by measurement of serotonin transporter occupancy and high-performance liquid chromatography. The effect of paroxetine on Aβ pathology was evaluated by stereological plaque load estimation and Aβ 42 /Aβ 40 ratio by enzyme-linked immunosorbent assay. Contrary to our hypothesis, paroxetine therapy did not mitigate Aβ pathology, and depletion of brain serotonin did not exacerbate Aβ pathology. However, chronic paroxetine therapy increased mortality in APP swe /PS1 ΔE9 transgenic mice. Our results question the ability of selective serotonin reuptake inhibitor therapy to ameliorate established Aβ pathology. The severe adverse effect of paroxetine may discourage its use for disease-modifying purposes in Alzheimer's disease.

Treating individuals with social anxiety disorder and at-risk drinking: Phasing in a brief alcohol intervention following paroxetine

PubMed Central

Book, Sarah W.; Thomas, Suzanne E.; Smith, Joshua P.; Randall, Patrick K.; Kushner, Matt G.; Bernstein, Gail A.; Specker, Sheila M.; Miller, Peter M.; Randall, Carrie L.

2013-01-01

Paroxetine alone is not sufficient to decrease alcohol use in socially anxious alcoholics seeking anxiety treatment. We tested the hypothesis that adding a brief-alcohol-intervention (BI) to paroxetine would decrease alcohol use. All subjects (N = 83) had a diagnosis of social anxiety disorder, endorsed drinking to cope with anxiety, were NIAAA-defined at-risk drinkers, and were randomized to either paroxetine alone, or paroxetine plus BI. Both groups showed significant improvement in both social anxiety severity (F(5,83) = 61.5, p < 0.0001) and drinking to cope (e.g. F(4,79) = 23, p < 0.0001) and these two constructs correlated with each other (B = 3.39, SE = 0.696, t(71) = 4.88, p < 0.001). BI was not effective at decreasing alcohol use (e.g. no main effect of group, all p values >0.3). Paroxetine decreased social anxiety severity in the face of heavy drinking and decreasing the anxiety was related to a concurrent decrease in coping related drinking. BI was not effective at decreasing drinking or drinking to cope. PMID:23523988

Paroxetine and fluoxetine in pregnancy: a prospective, multicentre, controlled, observational study

PubMed Central

Diav-Citrin, Orna; Shechtman, Svetlana; Weinbaum, Dafna; Wajnberg, Rebecka; Avgil, Meytal; Di Gianantonio, Elena; Clementi, Maurizio; Weber-Schoendorfer, Corinna; Schaefer, Christof; Ornoy, Asher

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT In recent years there has been concern regarding the possibility that selective serotonin reuptake inhibitors (SSRIs) cause an increased rate of congenital cardiovascular anomalies. As of today, there is still debate in the literature as to the possible effects of paroxetine and fluoxetine on the embryonic cardiovascular system. WHAT THIS STUDY ADDS Based on prospective data from three Teratogen Information Services, we have demonstrated an increased rate of congenital cardiovascular anomalies among the offspring of fluoxetine- and paroxetine-treated mothers. AIMS Recent studies have suggested a possible association between maternal use of selective serotonin reuptake inhibitors (SSRIs) in early pregnancy and cardiovascular anomalies. The aim of the present study was to evaluate the teratogenic risk of paroxetine and fluoxetine. METHODS This multicentre, prospective, controlled study evaluated the rate of major congenital anomalies after first-trimester gestational exposure to paroxetine, fluoxetine or nonteratogens. RESULTS We followed up 410 paroxetine, 314 fluoxetine first-trimester exposed pregnancies and 1467 controls. After exclusion of genetic and cytogenetic anomalies, there was a higher rate of major anomalies in the SSRI groups compared with the controls [paroxetine 18/348 (5.2%), fluoxetine 12/253 (4.7%) and controls 34/1359 (2.5%)]. The main risk applied to cardiovascular anomalies [paroxetine 7/348 (2.0%), crude odds ratio (OR) 3.47, 95% confidence interval (CI) 1.13, 10.58; fluoxetine 7/253 (2.8%), crude OR, 4.81 95% CI 1.56, 14.71; and controls 8/1359 (0.6%)]. On logistic regression analysis only cigarette smoking of ≥10 cigarettes day−1 and fluoxetine exposure were significant variables for cardiovascular anomalies. The adjusted ORs for paroxetine and fluoxetine were 2.66 (95% CI 0.80, 8.90) and 4.47 (95% CI 1.31, 15.27), respectively. CONCLUSION This study suggests a possible association between cardiovascular anomalies and first-trimester exposure to fluoxetine. PMID:18754846

Human-Health Pharmaceutical Compounds in Lake Mead, Nevada and Arizona, and Las Vegas Wash, Nevada, October 2000-August 2001

DTIC Science & Technology

2002-01-01

Miconazole Antifungal -- Paroxetine metabolite Metabolite of Paroxetine (antianxiety) 0.26 Ranitidine Antiulcerant; antacid 0.01 Salbutamol...LRL <LRL <LRL <LRL Lisinopril ND ND ND ND Metformin <LRL <LRL <LRL <LRL Miconazole ND ND ND ND Paroxetine metabolite <LRL <LRL <LRL <LRL Ranitidine... Miconazole ND ND ND ND Paroxetine metabolite <LRL <LRL <LRL <LRL Ranitidine <LRL <LRL <LRL <LRL Salbutamol (albuterol) <LRL <LRL <LRL <LRL Sulfamethoxazole

Pharmacokinetics of paroxetine, a selective serotonin reuptake inhibitor, in Grey parrots (Psittacus erithacus erithacus): influence of pharmaceutical formulation and length of dosing.

PubMed

van Zeeland, Y R A; Schoemaker, N J; Haritova, A; Smit, J W; van Maarseveen, E M; Lumeij, J T; Fink-Gremmels, J

2013-02-01

Paroxetine, a selective serotonin reuptake inhibitor, may be beneficial in the treatment of behavioural disorders in pet birds. The lack of pharmacokinetic data and clinical trials currently limits the use of this drug in clinical avian practice. This paper evaluates the pharmacokinetic properties and potential side effects of single and repeated dosing of paroxetine in Grey parrots (Psittacus erithacus erithacus). Paroxetine pharmacokinetics were studied after single i.v. and single oral dosing, and after repeated oral administration during 1 month. Plasma paroxetine concentrations were determined by liquid chromatography-tandem mass spectrometry. No undesirable side effects were observed during the study. Pharmacokinetic analysis revealed a quick distribution and rapid elimination after i.v. administration. Oral administration of paroxetine HCl dissolved in water resulted in a relatively slow absorption (T(max)=5.9±2.6 h) and a low bioavailability (31±15%). Repeated administration resulted in higher rate of absorption, most likely due to a saturation of the cytochrome P450-mediated first-pass metabolism. This study shows that oral administration of paroxetine HCl (4 mg/kg twice daily) in parrots results in plasma concentrations within the therapeutic range recommended for the treatment of depressions in humans. Further studies are needed to demonstrate the clinical efficacy of this dosage regimen in parrots with behavioural disorders. © 2012 Blackwell Publishing Ltd.

Paroxetine-induced apoptosis in human osteosarcoma cells: Activation of p38 MAP kinase and caspase-3 pathways without involvement of [Ca{sup 2+}]{sub i} elevation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chou, C.-T.; Department of Biological Sciences, National Sun Yat-sen University, 804, Taiwan; He Shiping

2007-02-01

Selective serotonin reuptake inhibitors (SSRIs), a group of antidepressants, are generally used for treatment of various mood and anxiety disorders. There has been much research showing the anti-tumor and cytotoxic activities of some antidepressants; but the detailed mechanisms were unclear. In cultured human osteosarcoma cells (MG63), paroxetine reduced cell viability in a concentration- and time-dependent manner. Paroxetine caused apoptosis as assessed by propidium iodide-stained cells and increased caspase-3 activation. Although immunoblotting data revealed that paroxetine could activate the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH{sub 2}-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK), only SB203580 (a p38more » MAPK inhibitor) partially prevented cells from apoptosis. Paroxetine also induced [Ca{sup 2+}]{sub i} increases which involved the mobilization of intracellular Ca{sup 2+} stored in the endoplasmic reticulum and Ca{sup 2+} influx from extracellular medium. However, pretreatment with BAPTA/AM, a Ca{sup 2+} chelator, to prevent paroxetine-induced [Ca{sup 2+}]{sub i} increases did not protect cells from death. The results suggest that in MG63 cells, paroxetine caused Ca{sup 2+}-independent apoptosis via inducing p38 MAPK-associated caspase-3 activation.« less

A comparison of paroxetine versus paroxetine plus amisulpride in the treatment of dysthymic disorder: efficacy and psychosocial outcomes.

PubMed

Rocca, Paola; Marchiaro, Livio; Rasetti, Roberta; Rivoira, Elisa; Bogetto, Filippo

2002-10-10

Dysthymic disorder is a chronic depressive condition with considerable psychosocial impairment. Even if DD patients respond to various antidepressant medications, there has been little systematic study on antidepressant-refractory DD. Only a few trials have evaluated the effects of treatment on psychosocial functioning of dysthymic patients. In this 3-month, open-label study, 60 outpatients with DSM-IV criteria for dysthymic disorder who failed to respond to 3-month treatment with paroxetine 20 mg/day were randomly assigned to treatment with paroxetine 40 mg/day or paroxetine 20 mg/day plus amisulpride 50 mg/day. The effects of the two treatments were assessed for both mood symptoms (21-item Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression, severity and improvement) and psychosocial outcomes (DSM-IV Global Assessment of Functioning, Social Adaptation Self-evaluation Scale). Analysis of variance on all rating scales showed that both treatments were effective over this observation period. Response and remission rates did not differ in the treatment groups. A significantly greater psychosocial improvement was observed in the group receiving combined treatment compared with patients receiving paroxetine alone. Both treatments appeared to be effective in our sample of dysthymic subjects. Combined treatment with paroxetine and amisulpride resulted in a better outcome in terms of social functioning.

Hyperforin plasma level as a marker of treatment adherence in the National Institutes of Health Hypericum Depression Trial.

PubMed

Vitiello, Benedetto; Shader, Richard I; Parker, Corette B; Ritz, Louise; Harlan, William; Greenblatt, David J; Gadde, Kishore M; Krishnan, K Ranga R; Davidson, Jonathan R T

2005-06-01

A previously reported clinical trial of Hypericum perforatum (St John's wort) in depression did not demonstrate efficacy. We assessed treatment adherence by measuring plasma hyperforin and evaluated the possible impact of adherence on study results. Outpatients with major depression (N = 340) were randomized to an 8-week trial of H. perforatum (900-1500 mg/d), sertraline (50-100 mg/d) as active comparator, or placebo. Plasma was available from 292 patients (86% of randomized). Samples from the placebo and H. perforatum groups were assayed for hyperforin, and samples from the sertraline group for sertraline/N-desmethyl-sertraline. Of the 104 patients randomized to placebo, 18 (17%) had detectable plasma hyperforin. Of the 97 patients randomized to H. perforatum, 17 (17%) had no detectable plasma hyperforin. All the assayed sertraline patients (N = 91) had plasma sertraline/N-desmethyl-sertraline. The clinical trial conclusions remained unchanged when only patients with plasma assay consistent with random assignment were included in the analyses. One of every 6 patients assigned to placebo had plasma hyperforin, and 1 of every 6 patients assigned to H. perforatum had no detectable plasma hyperforin. The finding underscores the difficulty of enforcing treatment adherence in clinical trials of preparations that are readily available in the community.

Paroxetine and its uses in psychiatry.

PubMed

Bell, C; Nutt, D

1999-05-01

Paroxetine is one of the specific serotonin-reuptake inhibitor antidepressants which is used in a variety of psychiatric disorders. It has recently gained considerable publicity because of its use in social anxiety disorder and its subsequent labelling by the media as a 'lifestyle drug'. This review summarizes current indications for paroxetine and outlines doses and duration of treatment for each condition.

Analysis of Electrocardiographic Data Following Use of Paroxetine in Pediatric Depression and Obsessive-Compulsive Disorder

ERIC Educational Resources Information Center

Krulewicz, Stan; Carpenter, David J.; Fong, Regan; Horrigan, Joseph P.; Lipschitz, Alan; Perera, Philip; Wagner, Karen Dineen

2006-01-01

Objective: This retrospective analysis of electrocardiographic (ECG) data investigated the cardiovascular effects of paroxetine 10-50 mg/day in pediatric patients (7-18 years of age). Data were collected from three 8- to 10-week, randomized, placebo-controlled, double-blind trials of paroxetine in pediatric patients with major depressive disorder…

Treatment of Comorbid Alcohol Dependence and Anxiety Disorder: Review of the Scientific Evidence and Recommendations for Treatment

PubMed Central

Gimeno, Carmen; Dorado, Marisa Luisa; Roncero, Carlos; Szerman, Nestor; Vega, Pablo; Balanzá-Martínez, Vicent; Alvarez, F. Javier

2017-01-01

Patients with alcohol-use disorders (AUDs) have a high prevalence of anxiety disorders (AnxDs). “Co-occurring disorders” refers to the coexistence of an AUD and/or drug related disorders with another non-addictive psychiatric disorder. The aim of this study was to assess the effectiveness of psychopharmacological treatments and psychotherapy in patients with AUD and AnxD and to propose recommendations for the treatment of patients with comorbid AnxDs and AUDs. Randomized clinical trials, meta-analyses, and clinical guidelines were retrieved from PubMed, Embase, and Cochrane databases. Paroxetine was found to be effective in social anxiety patients with alcohol dependence. Selective serotonin reuptake inhibitors (SSRIs), especially sertraline, showed effective results in posttraumatic stress disorder and in comorbid AnxD–AUD. However, SSRIs should be used with caution when patients are actively drinking because they may increase alcohol consumption. Buspirone, gabapentin, and pregabalin were found to be effective in comorbid AnxD–AUD. The treatment of dual AnxDs should start as early as possible. Since AUDs and AnxDs can reinforce each other, treatments targeting both pathologies can be effective. Women suffer from higher levels of stress and AnxDs than men, and they are also more vulnerable to maintaining alcohol consumption levels. Further research is needed in this comorbid patient population, including the study of different types of patients and gender perspectives. PMID:29018367

Gateways to Clinical Trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2002-09-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Adalimumab, aeroDose insulin inhaler, agomelatine, alendronic acid sodium salt, aliskiren fumarate, alteplase, amlodipine, aspirin, atazanavir; Bacillus Calmette-Guérin, basiliximab, BQ-788, bupropion hydrochloride; Cabergoline, caffeine citrate, carbamazepine, carvedilol, celecoxib, cyclosporine, clopidogrel hydrogensulfate, colestyramine; Dexamethasone, diclofenac sodium, digoxin, dipyridamole, docetaxel, dutasteride; Eletriptan, enfuvirtidie, eplerenone, ergotamine tartrate, esomeprazole magnesium, estramustine phosphate sodium; Finasteride, fluticasone propionate, fosinopril sodium; Ganciclovir, GBE-761-ONC, glatiramer acetate, gliclazide, granulocyte-CSF; Heparin sodium, human isophane insulin (pyr), Hydrochlorothiazide; Ibuprofen, inhaled insulin, interferon alfa, interferon beta-1a; Laminvudine, lansoprazole, lisinopril, lonafarnib, losartan potassium, lumiracoxib; MAb G250, meloxicam methotrexate, methylprednisolone aceponate, mitomycin, mycophenolate mofetil; Naproxen sodium, natalizumab, nelfinavir mesilate, nemifitide ditriflutate, nimesulide; Omalizumab, omapatrilat, omeprazole, oxybutynin chloride; Pantoprazole sodium, paracetamol, paroxetine, pentoxifylline, pergolide mesylate, permixon, phVEGF-A165, pramipexole hydrochloride, prasterone, prednisone, probucol, propiverine hydrochloride; Rabeprazole sodium, resiniferatoxin, risedronate sodium, risperidone, rofecoxib rosiglitazone maleate, ruboxistaurin mesilate hydrate; Selegiline transdermal system, sertraline, sildenafil citrate, streptokinase; Tadalafil, tamsulosin hydrochloride, technosphere/Insulin, tegaserod maleate, tenofovir disoproxil fumarate, testosterone heptanoate, testosterone undecanoate, tipifarnib, tolterodine tartrate, topiramate, troglitazone; Ursodeoxycholic acid; Valdecoxib, valsartan, vardenafil, venlafaxine hydrochloride, VX-745.

Antidepressant Prescription Pattern in the Presence of Medical Co-morbidity: REAP-AD 2013 Study.

PubMed

Grover, S; Avasthi, A; Tripathi, A; Tanra, A J; Chee, K Y; He, Y L; Chiu, H Fk; Kuga, H; Lee, M S; Chong, M Y; Udormatn, P; Kanba, S; Yang, S Y; Si, T M; Sim, K; Tan, C H; Shen, W W; Xiang, Y T; Sartorius, N; Shinfuku, N

2015-09-01

To evaluate the prescription pattern of antidepressants in patients with medical co-morbidity from major psychiatric centres in Asia. The Research on Asian Psychotropic Prescription Pattern for Antidepressants (REAP-AD 2013) collected data from 42 psychiatric centres in 10 Asian countries and regions. Antidepressant prescriptions of 2320 patients with various psychiatric disorders were evaluated. Of these, 370 patients who had specified medical co-morbidities formed the study cohort. Escitalopram (20%) and mirtazapine (20%) were the most commonly prescribed antidepressants in patients with medical co-morbidity followed by sertraline (16%), trazodone (15%), and paroxetine (12%). Overall, more than half (52%; 247/476) of prescriptions comprised selective serotonin reuptake inhibitors. Slightly less than two-thirds (63%; n = 233) of patients received at least 1 selective serotonin reuptake inhibitor. In addition, 79% of patients were prescribed only 1 antidepressant. The mean number of antidepressants used per patient was 1.25 (standard deviation, 0.56). There were subtle differences in the most preferred antidepressant across medical illnesses such as diabetes mellitus, liver dysfunction, acid peptic disease, and cerebrovascular disease. Differences were also seen in prescription patterns across different countries. Although selective serotonin reuptake inhibitors formed the bulk of antidepressant prescriptions in the presence of medical co-morbidity, mirtazapine was also commonly used in the presence of medical co-morbidities. Specified medical morbidities do influence the selection of antidepressants.

Antidepressants detection and quantification in whole blood samples by GC-MS/MS, for forensic purposes.

PubMed

Truta, Liliana; Castro, André L; Tarelho, Sónia; Costa, Pedro; Sales, M Goreti F; Teixeira, Helena M

2016-09-05

Depression is among the most prevalent psychiatric disorders of our society, leading to an increase in antidepressant drug consumption that needs to be accurately determined in whole blood samples in Forensic Toxicology Laboratories. For this purpose, this work presents a new gas chromatography tandem mass spectrometry (GC-MS/MS) method targeting the simultaneous and rapid determination of 14 common Antidepressants in whole blood: 13 Antidepressants (amitriptyline, citalopram, clomipramine, dothiepin, fluoxetine, imipramine, mianserin, mirtazapine, nortryptiline, paroxetine, sertraline, trimipramine and venlafaxine) and 1 Metabolite (N-desmethylclomipramine). Solid-phase extraction was used prior to chromatographic separation. Chromatographic and MS/MS parameters were selected to improve sensitivity, peak resolution and unequivocal identification of the eluted analyte. The detection was performed on a triple quadrupole tandem MS in selected ion monitoring (SIM) mode in tandem, using electronic impact ionization. Clomipramine-D3 and trimipramine-D3 were used as deutered internal standards. The validation parameters included linearity, limits of detection, lower limit of quantification, selectivity/specificity, extraction efficiency, carry-over, precision and robustness, and followed internationally accepted guidelines. Limits of quantification and detection were lower than therapeutic and sub-therapeutic concentration ranges. Overall, the method offered good selectivity, robustness and quick response (<16min) for typical concentration ranges, both for therapeutic and lethal levels. Copyright © 2016 Elsevier B.V. All rights reserved.

Post-traumatic stress disorder.

PubMed

Bisson, Jonathan I

2007-08-01

Post-traumatic stress disorder (PTSD) may affect 10% of women and 5% of men at some stage, and symptoms may persist for several years. Risk factors include major trauma, lack of social support, peritraumatic dissociation, and psychiatric or personality factors. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent; and to treat PTSD? We searched: Medline, Embase, The Cochrane Library and other important databases up to December 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 36 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: affect management, antiepileptic drugs, antihypertensive drugs, benzodiazepines, brofaromine, carbamazepine, CBT, drama therapy, eye movement desensitisation and reprocessing, fluoxetine, group therapy, hydrocortisone, hypnotherapy, inpatient treatment programmes, internet-based psychotherapy, mirtazepine, multiple-session CBT, multiple-session collaborative trauma support, multiple-session education, nefazodone, olanzapine, paroxetine, phenelzine, propranolol, psychodynamic psychotherapy, risperidone, SSRIss, sertraline, single-session group debriefing, single-session individual debriefing, supportive psychotherapy, supportive counselling, temazepam, tricyclic antidepressants, venlafaxine.

Pindolol potentiates the panicolytic effect of paroxetine in the elevated T-maze.

PubMed

Sela, Vânia R; Roncon, Camila M; Zangrossi, Hélio; Graeff, Frederico G; Audi, Elisabeth A

2010-09-25

the β-adrenergic and 5-HT(1A) receptor antagonist pindolol has been used in combination with antidepressant drugs, to shorten the time of onset of clinical efficacy and/or increase the proportion of responders in depressive and anxiety disorders. The aim of this study was to examine the interaction between pindolol and the selective serotonin reuptake inhibitor (SSRI), paroxetine in rats submitted to the elevated T-maze (ETM). for assessing the drug combination effect, rats were administered with pindolol before paroxetine, using oral or intraperitoneal (i.p.) routes of acute administration, and were submitted to the ETM model. the highest dose of pindolol used (15.0mg/kg, i.p.) increased both inhibitory avoidance and escape latencies in the ETM, probably due to nonspecific motor deficit, since locomotion in a circular arena was also significantly decreased. The highest dose of paroxetine (3.0mg/kg, i.p.) selectively impaired escape, considered a panicolytic effect. Combination of pindolol (5.0mg/kg, i.p.) with an ineffective dose of paroxetine (1.5mg/kg, i.p.) impaired escape, indicating a potentiation of the panicolytic effect of paroxetine. By the oral route, neither paroxetine (3.0mg/kg) nor pindolol (5.0mg/kg) alone were effective, but the combination treatment had a marked panicolytic effect, again indicating drug potentiation. the present results show that the combination of the ineffective doses of pindolol and paroxetine significantly increased escape latency, indicating a selective panicolytic effect. These findings give preclinical support for the use of this drug combination in the treatment of panic disorder (PD). 2010 Elsevier Inc. All rights reserved.

Paroxetine-induced reduction of sexual incentive motivation in female rats is not modified by 5-HT1B or 5-HT2C antagonists.

PubMed

Kaspersen, Helge; Agmo, Anders

2012-03-01

Clinical data show that paroxetine causes sexual dysfunction in a substantial proportion of women taking this compound. This work was conducted to determine whether chronic paroxetine reduces sexual incentive motivation in female rats and whether this compound can modify any aspect of paced mating. The role of the 5-HT(1B) and 5-HT(2C) receptors in any potential effects was also evaluated. Ovariectomized female rats were implanted with osmotic minipumps releasing 10 mg/kg per day of paroxetine or vehicle for 28 days. Tests for sexual incentive motivation and paced mating were performed just before implantation and at regular intervals thereafter. The females were primed with estradiol benzoate (25 μg/rat) and progesterone (1 mg/rat) before each of these tests. On days 25-27 of treatment, the females were injected with the 5-HT(1B) antagonist GR125,743 (5 mg/kg), the 5-HT(2C) antagonist SB206,553 (5 mg/kg) and vehicle in counterbalanced order. Preinjection time was 30 min. Paroxetine reduced sexual incentive motivation on day 20 of treatment without affecting any aspect of paced mating. None of the antagonists modified the inhibitory effect of paroxetine on sexual incentive motivation. In the group chronically treated with vehicle, SB206,553 reduced proceptive behaviors in the paced mating test. No other effect was obtained. The effects of paroxetine seen in female rats are similar to those observed in women, suggesting that disturbances of sexual incentive motivation in rats are predictive of sexual dysfunction in women. The 5-HT(1B) and 5-HT(2C) receptors do not seem to be of any importance for paroxetine's inhibitory effect.

Euprolactinemic Gynecomastia and Galactorrhea with Risperidone-Fluvoxamine Combination

PubMed Central

P.J., Pratheesh; Praharaj, Samir Kumar; Srivastava, Ashish

2011-01-01

Risperidone is associated with hyperprolactinemia and its consequent symptoms such as gynnecomastia, galactorrhea and sexual dysfunction in adults, and less so in adolescents. Rarely, serotonin reuptake inhibitors are also associated with such adverse effects. We report a case of gynecomastia and galactorrhea in an adolescent male while on a combination of risperidone and fluvoxamine, although the serum prolactin was within normal range. PMID:22506441

A case of serial nightmares and oneiroid state under paroxetine for senile depression.

PubMed

Kobayashi, Toshiyuki; Yamauchi, Mina

2012-03-01

We report on rare side effects of paroxetine. A 67-year-old female patient who had been suffering from prolonged depression for over a year but had not received appropriate treatment was administered 20-mg paroxetine daily. However, the patient required hospital admission after 16 days because of behavioural disturbances and delusions that she was being chased by evil persons from a religious group. The delusions were ultimately confirmed to be serial nightmares and an oneiroid state. The nightmares gradually disappeared following discontinuation of paroxetine. The Adverse Drug Reaction Probability Scale showed a score of 6 (probable). Reports on paroxetine-induced nightmares are rare, and there is a possibility that, in this case, parexetine caused the nightmares in association with depression and assumed underlying brain dysfunction due to ageing. © 2012 The Authors. Psychogeriatrics © 2012 Japanese Psychogeriatric Society.

Paroxetine Treatment of Problematic Pornography Use: A Case Series

PubMed Central

Gola, Mateusz; Potenza, Marc N.

2016-01-01

Background How best to conceptualize problematic pornography use (PPU) and intervene most effectively remain debated, with obsessive–compulsive disorder (OCD) and addiction frameworks. We investigated the efficacy of the serotonin-reuptake inhibitor paroxetine in combination with cognitive-behavioral therapy in the treatment of problematic pornography use (PPU). Case presentation Three heterosexual males with PPU were treated with cognitive-behavioral therapy and paroxetine. Frequency of pornography use, other sexual behaviors, and anxiety were assessed during treatment. Discussion Paroxetine treatment, although seemingly initially effective in reducing pornography use and anxiety, appeared related to new compulsive sexual behaviors after 3 months. Conclusions Paroxetine may hold promise for short-term reduction of PPU and related anxiety, but new potentially distressing sexual behaviors may emerge. The cases suggest that PPU may arise from multiple domains. We propose an explanation of the effects based on recent neuroscientific research on sexual behaviors and alcohol use. PMID:27440474

Paroxetine Treatment of Problematic Pornography Use: A Case Series.

PubMed

Gola, Mateusz; Potenza, Marc N

2016-09-01

Background How best to conceptualize problematic pornography use (PPU) and intervene most effectively remain debated, with obsessive-compulsive disorder (OCD) and addiction frameworks. We investigated the efficacy of the serotonin-reuptake inhibitor paroxetine in combination with cognitive-behavioral therapy in the treatment of problematic pornography use (PPU). Case presentation Three heterosexual males with PPU were treated with cognitive-behavioral therapy and paroxetine. Frequency of pornography use, other sexual behaviors, and anxiety were assessed during treatment. Discussion Paroxetine treatment, although seemingly initially effective in reducing pornography use and anxiety, appeared related to new compulsive sexual behaviors after 3 months. Conclusions Paroxetine may hold promise for short-term reduction of PPU and related anxiety, but new potentially distressing sexual behaviors may emerge. The cases suggest that PPU may arise from multiple domains. We propose an explanation of the effects based on recent neuroscientific research on sexual behaviors and alcohol use.

Mechanism of synergistic action following co-treatment with pramipexole and fluoxetine or sertraline in the forced swimming test in rats.

PubMed

Rogóz, Zofia; Skuza, Grazyna

2006-01-01

The aim of the present study was to examine the effect of combined treatment of male Wistar rats with pramipexole and fluoxetine or sertraline in the forced swimming test. The obtained results showed that co-treatment with pramipexole (0.1 mg/kg) and fluoxetine (10 mg/kg) or sertraline (5 mg/kg) (in doses inactive per se) exhibited antidepressant-like activity in the forced swimming test. Sulpiride (a dopamine D(2/3) receptor antagonist) and WAY 100635 (a 5-HT(1A) receptor antagonist), either being ineffective in the forced swimming test, inhibited the antidepressant-like effect induced by co-administration of pramipexole and fluoxetine or sertraline. However, SCH 23390 (a dopamine D(1) receptor antagonist) only partly did not alter the effect of pramipexole given jointly with antidepressant drugs; on the other hand, S 33084 (a dopamine D(3) receptor antagonist) only partly decreased (in a statistically insignificant manner) that effect. Moreover, progesterone and BD 1047 (a sigma(1) receptor antagonist) counteracted the antidepressant-like effect induced by co-administration of pramipexole and sertraline (but not pramipexole and fluoxetine). In that test, active behavior did not reflect the increases in general activity, since combined administration of pramipexole and fluoxetine or sertraline failed to enhance the locomotor activity of rats. None of the tested drugs (SCH 23390, sulpiride, S 33084, WAY 100635, BD 1047 and progesterone) - alone or in combination with pramipexole and fluoxetine or sertraline - changed locomotor activity. The results described in the present paper indicate that co-administration of pramipexole and fluoxetine or sertraline may induce a more pronounced antidepressive activity than does treatment with pramipexole alone, and that in addition to other mechanisms, dopamine D(2/3) and 5-HT(1A) receptors may contribute to the antidepressant-like activity of pramipexole and fluoxetine or sertraline in the forced swimming test in rats. Moreover, sigma(1) receptors may constitute one of the possible mechanisms by which co-administration of pramipexole and sertraline induces antidepressant-like activity in that test.

Sertraline and its iodine product: Experimental and theoretical vibrational studies. Potential in vitro anti-thyroid activity of sertraline and iodine product toxicity with respect to male Wistar rats

NASA Astrophysics Data System (ADS)

Escudero, Graciela E.; Ferraresi Curotto, Verónica; Laino, Carlos H.; Pis Diez, Reinaldo; Williams, Patricia A. M.; Ferrer, Evelina G.

2013-03-01

Mayor depression, obsessive-compulsive panic, social anxiety disorders are common diseases that are usually treated with sertraline hydrochloride which is the active ingredient of the well known drugs as Zoloft and Lustral. In this work, we presented a more complete vibrational characterization of the solid phase FT-IR spectra of Sertraline hydrochloride and its sertraline-iodine product in which the conformational space of the molecules was investigated performing molecular dynamic simulations within an NVT ensemble. Geometrical, electronic and vibrational properties were calculated with the density functional theory. Comparison of the simulated spectra with the experimental spectra provides important information about the ability of the computational method to describe the vibrational modes of both molecules. In addition, for the first time we present the evaluation of anti-thyroid activity of sertraline hydrochloride by using the Lang's method. Also, with the aim to evaluate the antidepressant effect of its iodine product we demonstrated for this compound the toxic effect towards the male Wistar rats.

Improvement in verbal memory following SSRI augmentation of antipsychotic treatment is associated with changes in the expression of mRNA encoding for the GABA-A receptor and BDNF in PMC of schizophrenic patients.

PubMed

Silver, Henry; Mandiuk, Nina; Einoch, Reef; Susser, Ehud; Danovich, Lena; Bilker, Warren; Youdim, Moussa; Weinreb, Orly

2015-05-01

Verbal memory impairment in schizophrenia is associated with abnormalities in gamma-aminobutyric acid (GABA)-ergic and brain-derived neurotrophic factor (BDNF) systems. Recent evidence from animal and clinical studies that adding fluvoxamine to antipsychotics alters the expression of transcripts encoding for the GABA-A receptor and BDNF led us to postulate that fluvoxamine augmentation may improve memory in schizophrenia. To test this, we examined the effect of add-on fluvoxamine on verbal memory and other cognitive functions and related it to the expression of mRNA coding for the GABA-A receptor and BDNF in peripheral mononuclear cells (PMC) of schizophrenic patients. Twenty-nine patients completed a 6-week study in which fluvoxamine (100 mg/day) was added to ongoing antipsychotic treatment. Verbal memory, abstraction working memory, object and face recognition, and psychomotor speed and clinical symptoms were assessed at baseline and after 3 and 6 weeks of treatment. Blood samples were taken at baseline and weeks 1, 3, and 6 and PMC was assayed for the GABA-A beta3 receptor and BDNF mRNA by quantitative real-time reverse transcription-PCR. Associative and logical verbal memory improved significantly and showed a significant correlation with changes in PMC BDNF and GABA-A beta3 receptor mRNA, which increased during treatment. Abstraction and object recognition improved, but this did not correlate with PMC measures. Negative and positive symptoms improved significantly; the latter showed significant correlations with changes in PMC measures. Addition of fluvoxamine to antipsychotics improves verbal memory. It is postulated that the mechanism involves enhanced GABA-A receptor/BDNF-dependent synaptic plasticity in the hippocampus.

Paroxetine Treatment in Children and Adolescents with Major Depressive Disorder: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial

ERIC Educational Resources Information Center

Emslie, Graham J.; Wagner, Karen Dineen; Kutcher, Stan; Krulewicz, Stan; Fong, Regan; Carpenter, David J.; Lipschitz, Alan; Machin, Andrea; Wilkinson, Christel

2006-01-01

Objective: To assess the efficacy and tolerability of paroxetine in pediatric major depressive disorder. Method: Subjects 7 to 17 years old with major depressive disorder received paroxetine (10-50 mg/day) or placebo for 8 weeks from 2000 to 2001. The primary efficacy measure was change from baseline in the Children's Depression Rating…

Ethanol intake and sup 3 H-serotonin uptake II: A study in alcoholic patients using platelets sup 3 H-paroxetine binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daoust, M.; Boucly, P.; Ernouf, D.

1991-01-01

The kinetic parameters of {sup 3}H-paroxetine binding and {sup 3}H-serotonin uptake were studied in platelets of alcoholic patients. There was no difference between alcoholic and non alcoholic subjects in {sup 3}H-paroxetine binding. When binding and {sup 3}H-serotonin uptake were studied, in the same plasma of the same subjects, the Vmax of serotonin uptake was increased in alcoholics. The data confirm the involvement of serotonin uptake system in alcohol dependance and suggest that serotonin uptake and paroxetine binding sites may be regulated independently in this pathology.

The influence of metoprolol dosage release formulation on the pharmacokinetic drug interaction with paroxetine

PubMed Central

Stout, Stephen M.; Nielsen, Jace; Welage, Lynda S.; Shea, Michael; Brook, Robert; Kerber, Kevin; Bleske, Barry E.

2010-01-01

Studies have demonstrated an influence of dosage release formulations on drug interactions and enantiomeric plasma concentrations. Metoprolol is a commonly used β-adrenergic antagonist metabolized by CYP2D6. The CYP2D6 inhibitor paroxetine has previously been shown to interact with metoprolol tartrate. This open-label, randomized, 4 phase crossover study assessed the potential differential effects of paroxetine on stereoselective pharmacokinetics of immediate release (IR) tartrate and extended release (ER) succinate metoprolol formulations. Ten healthy subjects received metoprolol IR (50 mg) and ER (100 mg) with and without paroxetine coadministration. Blood samples were collected over 24 hours for determination of metoprolol plasma enantiomer concentrations. Paroxetine coadministration significantly increased S and R metoprolol AUC0–24h by 4 and 5 fold, respectively for IR, and 3 and 4 fold, respectively for ER. S/R AUC ratios significantly decreased. These results demonstrate a pharmacokinetic interaction between paroxetine and both formulations of metoprolol. The interaction is greater with R metoprolol and stereoselective metabolism is lost. This could theoretically result in greater β-blockade and lost cardioselectivity. The magnitude of the interaction was similar between metoprolol formulations, which may be attributable to low doses / drug input rates employed. PMID:20400652

Paroxetine prevents loss of nigrostriatal dopaminergic neurons by inhibiting brain inflammation and oxidative stress in an experimental model of Parkinson's disease.

PubMed

Chung, Young C; Kim, Sang R; Jin, Byung K

2010-07-15

The present study examined whether the antidepressant paroxetine promotes the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. MPTP induced degeneration of nigrostriatal DA neurons and glial activation as visualized by tyrosine hydroxylase, macrophage Ag complex-1, and/or glial fibrillary acidic protein immunoreactivity. Real-time PCR, Western blotting, and immunohistochemistry showed upregulation of proinflammatory cytokines, activation of microglial NADPH oxidase and astroglial myeloperoxidase, and subsequent reactive oxygen species production and oxidative DNA damage in the MPTP-treated substantia nigra. Treatment with paroxetine prevented degeneration of nigrostriatal DA neurons, increased striatal dopamine levels, and improved motor function. This neuroprotection afforded by paroxetine was associated with the suppression of astroglial myeloperoxidase expression and/or NADPH oxidase-derived reactive oxygen species production and reduced expression of proinflammatory cytokines, including IL-1beta, TNF-alpha, and inducible NO synthase, by activated microglia. The present findings show that paroxetine may possess anti-inflammatory properties and inhibit glial activation-mediated oxidative stress, suggesting that paroxetine and its analogues may have therapeutic value in the treatment of aspects of Parkinson's disease related to neuroinflammation.

Potassium permanganate-acridine yellow chemiluminescence system for the determination of fluvoxamine, isoniazid and ceftriaxone.

PubMed

Abolhasani, Jafar; Hassanzadeh, Javad

2014-12-01

Based on the oxidation of acridine yellow by permanganate in basic medium, a new chemiluminescence system was developed for the sensitive determination of some important drugs. The remarkable inhibiting effect of fluvoxamine, ceftriaxone and isoniazid on this reaction was applied to their detection. A possible mechanism was proposed for this system based on chemiluminescence emission wavelengths and experimental observations. Under optimum conditions, calibration graphs were obtained for 1 × 10(-9) to 1 × 10(-6) mol/L of fluvoxamine; 2 × 10(-8) to 8 × 10(-6) mol/L of ceftriaxone and 5 × 10(-8) to 4 × 10(-5) mol/L of isoniazid. This proposed method was satisfactorily used in the determination of these drugs in pharmaceutical samples and human urine and serum. Copyright © 2014 John Wiley & Sons, Ltd.

Fresh onion juice enhanced copulatory behavior in male rats with and without paroxetine-induced sexual dysfunction.

PubMed

Allouh, Mohammed Z; Daradka, Haytham M; Al Barbarawi, Mohammed M; Mustafa, Ayman G

2014-02-01

Onion (Allium cepa) is one of the most commonly cultivated species of the family Liliaceae, and has long been used in dietary and therapeutic applications. Treatment with fresh onion juice has been reported to promote testosterone production in male rats. Testosterone is the male sex hormone responsible for enhancing sexual libido and potency. This study aimed to investigate the effects of onion juice on copulatory behavior of sexually potent male rats and in male rats with paroxetine-induced sexual dysfunction. Sexually experienced male rats were divided into seven groups: a control group, three onion juice-treated groups, a paroxetine-treated group, and two groups treated with paroxetine plus different doses of onion juice. At the end of the treatments, sexual behavior parameters and testosterone levels were measured and compared among the groups. Administration of onion juice significantly reduced mount frequency and latency and increased the copulatory efficacy of potent male rats. In addition, administration of onion juice attenuated the prolonged ejaculatory latency period induced by paroxetine and increased the percentage of ejaculating rats. Serum testosterone levels increased significantly by onion juice administration. However, a significant reduction in testosterone because of paroxetine therapy was observed. This reduction was restored to normal levels by administration of onion juice. This study conclusively demonstrates that fresh onion juice improves copulatory behavior in sexually potent male rats and in those with paroxetine-induced sexual dysfunction by increasing serum testosterone levels.

In vivo investigation on the chronic hepatotoxicity induced by sertraline.

PubMed

Almansour, Mansour I; Jarrar, Yazun B; Jarrar, Bashir M

2018-05-30

Although sertraline is widely prescribed as relatively safe antidepressant drug, hepatic toxicity was reported in some patients with sertraline treatment. The present study was conducted to investigate the morphometric, hepatotoxicity, and change in gene expression of drug metabolizing enzymes. Male healthy adult rabbits (Oryctolagus cuniculus) ranging from 1050 to 1100 g were exposed to oral daily doses of sertraline (0, 1, 2, 4, 8 mg/kg) for 9 weeks. The animals were subjected to morphometric, hepatohistological, histochemical and quantitative real-time polymerase chain reaction analyses. Sertraline chronic exposure induced morphometric changes and provoked histological and histochemical alterations including: hepatocytes hydropic degeneration, necrosis, nuclear alteration, sinusoidal dilation, bile duct hyperplasia, inflammatory cells infiltration, portal vessel congestion, Kupffer cells hyperplasia, portal fibrosis and glycogen depletion. In addition, the gene expression of drug and arachidonic acid metabolizing enzymes were reduced significantly (p value <0.05). The most affected genes were cyp4a12, ephx2, cyp2d9 and cyp1a2, demonstrating 5 folds or more down-regulation. These findings suggest that chronic sertraline treatment induced toxic histological alterations in the hepatic tissues and reduced the gene expression of drug metabolizing enzymes. Patients on chronic sertraline treatment may be on risk of hepatotoxicity with reduced capacity to metabolize drugs and fatty acids. Copyright © 2018 Elsevier B.V. All rights reserved.

Treatment with high-dose antidepressants severely exacerbates the pathological outcome of experimental Escherichia coli infections in poultry.

PubMed

Kromann, Sofie; Kudirkiene, Egle; Li, Lili; Thoefner, Ida; Daldorph, Elisabeth; Christensen, Jens Peter; Meng, Hecheng; Olsen, Rikke Heidemann

2017-01-01

There is an urgent need for novel antibiotics as the current antibiotics are losing their value due to increased resistance among clinically important bacteria. Sertraline, an on-marked anti-depressive drug, has been shown to modify bacterial activity in vitro, including increasing the susceptibility of Escherichia coli to antibiotics. The aim of the present study was to investigate if the antimicrobial activity of sertraline could be documented under clinical settings, hereunder if sertraline could potentiate the effect of tetracycline in treatment of an experimentally induced ascending infection in poultry. A total of 40 chickens were divided in four groups of 10 chickens each. All chickens were challenged with 4x103 colony forming units (CFU) of a tetracycline resistant E. coli strain using a surgical infection model, and subsequently treated with either high-dose sertraline, tetracycline, a combination hereof or received no treatment. Seven days post challenge all birds were submitted to necropsy and scored pathologically for lesions. The average lesion scores were significantly higher (P<0.05) in the groups that were treated with high-dose sertraline or high-dose sertraline combined with tetracycline. In conclusion high-dose treatments (four times the maximum therapeutic dose for treating human depression) with sertraline as an adjuvant for treatment of antibiotic resistant E. coli infections exacerbate the pathological outcome of infection in chickens.

Treatment with high-dose antidepressants severely exacerbates the pathological outcome of experimental Escherichia coli infections in poultry

PubMed Central

Kromann, Sofie; Kudirkiene, Egle; Li, Lili; Thoefner, Ida; Daldorph, Elisabeth; Christensen, Jens Peter; Meng, Hecheng

2017-01-01

There is an urgent need for novel antibiotics as the current antibiotics are losing their value due to increased resistance among clinically important bacteria. Sertraline, an on-marked anti-depressive drug, has been shown to modify bacterial activity in vitro, including increasing the susceptibility of Escherichia coli to antibiotics. The aim of the present study was to investigate if the antimicrobial activity of sertraline could be documented under clinical settings, hereunder if sertraline could potentiate the effect of tetracycline in treatment of an experimentally induced ascending infection in poultry. A total of 40 chickens were divided in four groups of 10 chickens each. All chickens were challenged with 4x103 colony forming units (CFU) of a tetracycline resistant E. coli strain using a surgical infection model, and subsequently treated with either high-dose sertraline, tetracycline, a combination hereof or received no treatment. Seven days post challenge all birds were submitted to necropsy and scored pathologically for lesions. The average lesion scores were significantly higher (P<0.05) in the groups that were treated with high-dose sertraline or high-dose sertraline combined with tetracycline. In conclusion high-dose treatments (four times the maximum therapeutic dose for treating human depression) with sertraline as an adjuvant for treatment of antibiotic resistant E. coli infections exacerbate the pathological outcome of infection in chickens. PMID:29020098

Treatment benefit and the risk of suicidality in multicenter, randomized, controlled trials of sertraline in children and adolescents.

PubMed

March, John S; Klee, Brian J; Kremer, Charlotte M E

2006-01-01

The aim of this study was to examine the balance between the benefits of treatment and the risk of suicidality in children and adolescents in multicenter, randomized, controlled trials of sertraline versus placebo. The published literature was searched for multicenter, randomized, placebo-controlled trials of sertraline for pediatric mental disorders. Four trials were identified: Two (pooled) in pediatric major depressive disorder (MDD; Wagner 2003) and two in obsessive-compulsive disorder (OCD; March et al. 1998; POTS Team 2004). Using intent-to-treat (ITT) analysis populations, the authors calculated the number needed to treat (NNT) for response and remission and the number needed to harm (NNH) for suicidality, and their ratio, for each clinical trial. NNTs ranged from 2 to 10, indicating clinically meaningful benefits. Benefit was greater for OCD than for MDD, and for adolescents as compared with children in MDD. No age effect was apparent for OCD. Suicidality was reported in 8 patients (5 assigned to sertraline and 3 assigned to placebo). All but 1 (a placebo-treated patient in the Pfizer OCD trial) were enrolled in the sertraline MDD trial. The NNH for suicidality in MDD was 64. Treatment emergent suicidality was more common in children (NNH 28.7) than in adolescents (NNH 706.3). Because no patient developed suicidality in sertraline-treated OCD patients, the NNH for sertraline in OCD approaches infinity. With the stipulation that doctor and patient preferences necessarily play a critical role in the choice of treatment, NNT to NNH ratios indicate a positive benefit-to-risk ratio for sertraline in adolescents with MDD and in patients of all ages with OCD.

Onset of major depression associated with acute coronary syndromes: relationship of onset, major depressive disorder history, and episode severity to sertraline benefit.

PubMed

Glassman, Alexander H; Bigger, J Thomas; Gaffney, Michael; Shapiro, Peter A; Swenson, J Robert

2006-03-01

Depression observed following acute coronary syndrome (ACS) is common and associated with an increased risk of death. The Sertraline Antidepressant Heart Attack Trial (SADHART) tested the safety and efficacy of a selective serotonin reuptake inhibitor in this population. No evidence of harm was seen, and sertraline hydrochloride had an overall beneficial effect on mood that occurred primarily in patients with a history of episodes of major depressive disorder (MDD). To determine how frequently the MDD began before ACS and whether onset of the current MDD episode before or after the ACS event influenced response to sertraline. A randomized, double-blind, placebo-controlled treatment of 369 patients with ACS and MDD was conducted in 40 outpatient clinics in 10 countries between April 1, 1997, and April 30, 2001. Diagnosis of MDD, number of previous episodes of depression, and episode onset before or after hospitalization were established using the Diagnostic Interview Schedule. Treatment response was measured with the Clinical Global Impression-Improvement scale. Fifty-three percent of MDD episodes began before hospitalization for the index episode of ACS (for 197 of 369 patients), and 94% of the MDD episodes began more than 30 days before the index ACS episode. Episodes of MDD that began prior to ACS responded more frequently to sertraline than to placebo (63% vs 46%, respectively; odds ratio, 2.0; 95% confidence interval, 1.13-3.55) whereas depression with onset beginning after hospitalization showed a high placebo response rate (69% vs 60%, respectively) and low sertraline-placebo response ratio (1.15). Multivariate analysis indicated that time of onset of the current episode, history of MDD, and baseline severity independently predicted the sertraline-placebo response ratio. Half of the episodes of major depression associated with ACS began long before ACS and therefore were not caused by ACS. Patients whose current episodes of MDD begin before ACS, those with a history of MDD, and those whose episodes are severe should be treated because they will benefit considerably from sertraline. Since these 3 predictors of sertraline response are independent, having more than 1 of them substantially increases the benefit of sertraline while reducing the chance of spontaneous recovery.

SSRIs and ejaculation: a double-blind, randomized, fixed-dose study with paroxetine and citalopram.

PubMed

Waldinger, M D; Zwinderman, A H; Olivier, B

2001-12-01

Selective serotonin reuptake inhibitors (SSRIs) are known to induce delayed orgasm and ejaculation. However, different SSRIs may differentially delay ejaculation. A double-blind, fixed-dose study in healthy men with lifelong rapid ejaculation was performed to evaluate potential differences between clinically relevant doses of two selective serotonin reuptake inhibitors, paroxetine and citalopram, in their effects on ejaculation. Thirty men with an intravaginal ejaculation latency time (IELT) less than 1 minute were randomly assigned to receive paroxetine (20 mg/day) and citalopram (20 mg/day) for 5 weeks, after taking half the dosage in the first week. During the 1-month baseline and 6-week treatment period, IELTs were measured at home by using a stopwatch procedure. The trial was completed by 23 men. Analysis of variance revealed a between-group difference in the evolution of IELT delay over time (p = 0.0004); the IELT after paroxetine and citalopram gradually increased from 18 and 21 seconds to approximately 170 and 44 seconds, respectively. Paroxetine 20 mg/day exerted a strong delay (8.9-fold increase), whereas citalopram 20 mg/day mildly delayed ejaculation (1.8-fold increase). These results indicate that paroxetine leads to a significant delay in orgasm and ejaculation, whereas citalopram seems to have less of an effect on it.

Neural Correlates of Antidepressant-Related Sexual Dysfunction: A Placebo-Controlled fMRI Study on Healthy Males Under Subchronic Paroxetine and Bupropion

PubMed Central

Abler, Birgit; Seeringer, Angela; Hartmann, Antonie; Grön, Georg; Metzger, Coraline; Walter, Martin; Stingl, Julia

2011-01-01

Sexual dysfunction is a common side effect of selective serotonin reuptake inhibitors (SSRIs) like paroxetine in the treatment of depression, imposing a considerable risk on medication adherence and hence therapeutic success. Bupropion, a norepinephrine and dopamine reuptake inhibitor, is recommended as an alternative treatment without adverse effects concerning sexual arousal and libido. We investigated the neural bases of paroxetine-related subjective sexual dysfunction when compared with bupropion and placebo. We scanned 18 healthy, heterosexual males in a randomized, double-blind, within-subject design while watching video clips of erotic and nonerotic content under steady-state conditions after taking 20 mg of paroxetine, 150 mg of bupropion, and placebo for 7 days each. Under paroxetine, ratings of subjective sexual dysfunction increased compared with placebo or bupropion. Activation along the anterior cingulate cortex (ACC), including subgenual, pregenual, and midcingulate cortices, in the ventral striatum and midbrain was decreased when compared with placebo. In contrast, bupropion let subjective ratings and ACC activations unchanged and increased activity of brain regions including posterior midcingulate cortex, mediodorsal thalamus, and extended amygdala relative to placebo and paroxetine. Brain regions that have been related to the processing of motivational (ventral striatum), emotional, and autonomic components of erotic stimulation (anterior cingulate) in previous studies showed reduced responsiveness under paroxetine in our study. Drug effects on these regions may be part of the mechanism underlying SSRI-related sexual dysfunction. Increased activation under bupropion may point to an opposite effect that may relate to the lack of impaired sexual functioning. PMID:21544071

Modulation of appetite and feeding behavior of the larval mosquito Aedes aegypti by the serotonin-selective reuptake inhibitor paroxetine: shifts between distinct feeding modes and the influence of feeding status.

PubMed

Kinney, Michael P; Panting, Nicholas D; Clark, Thomas M

2014-03-15

The effects of the serotonin-selective reuptake inhibitor paroxetine (2×10(-5) mol l(-1)) on behavior of the larval mosquito Aedes aegypti are described. Four discrete behavioral states dominate larval behavior: wriggling, two distinct types of feeding, and quiescence. Feeding behaviors consist of foraging along the bottom of the container (substrate browsing), and stationary filter feeding while suspended from the surface film. Fed larvae respond to paroxetine with increased wriggling, and reductions in both feeding behaviors. In contrast, food-deprived larvae treated with paroxetine show no change in the proportion of time spent wriggling or feeding, but shift from stationary filter feeding to substrate browsing. Thus, actions of paroxetine in fed larvae are consistent with suppression of appetite and stimulation of wriggling, whereas paroxetine causes food-deprived larvae to switch from one feeding behavior to another. Further analysis of unfed larvae revealed that paroxetine decreased the power stroke frequency during wriggling locomotion, but had no effect on the swimming velocity during either wriggling or substrate browsing. These data suggest that: (1) serotonergic pathways may trigger shifts between distinct behaviors by actions on higher level (brain) integrating centers where behaviors such as feeding and locomotion are coordinated; (2) these centers in fed and food-deprived larvae respond differently to serotonergic stimulation suggesting sensory feedback from feeding status; and (3) serotonergic pathways also modulate central pattern generators of the nerve cord where the bursts of action potentials originate that drive the rhythmic muscle contractions of wriggling.

Neural correlates of antidepressant-related sexual dysfunction: a placebo-controlled fMRI study on healthy males under subchronic paroxetine and bupropion.

PubMed

Abler, Birgit; Seeringer, Angela; Hartmann, Antonie; Grön, Georg; Metzger, Coraline; Walter, Martin; Stingl, Julia

2011-08-01

Sexual dysfunction is a common side effect of selective serotonin reuptake inhibitors (SSRIs) like paroxetine in the treatment of depression, imposing a considerable risk on medication adherence and hence therapeutic success. Bupropion, a norepinephrine and dopamine reuptake inhibitor, is recommended as an alternative treatment without adverse effects concerning sexual arousal and libido. We investigated the neural bases of paroxetine-related subjective sexual dysfunction when compared with bupropion and placebo. We scanned 18 healthy, heterosexual males in a randomized, double-blind, within-subject design while watching video clips of erotic and nonerotic content under steady-state conditions after taking 20 mg of paroxetine, 150 mg of bupropion, and placebo for 7 days each. Under paroxetine, ratings of subjective sexual dysfunction increased compared with placebo or bupropion. Activation along the anterior cingulate cortex (ACC), including subgenual, pregenual, and midcingulate cortices, in the ventral striatum and midbrain was decreased when compared with placebo. In contrast, bupropion let subjective ratings and ACC activations unchanged and increased activity of brain regions including posterior midcingulate cortex, mediodorsal thalamus, and extended amygdala relative to placebo and paroxetine. Brain regions that have been related to the processing of motivational (ventral striatum), emotional, and autonomic components of erotic stimulation (anterior cingulate) in previous studies showed reduced responsiveness under paroxetine in our study. Drug effects on these regions may be part of the mechanism underlying SSRI-related sexual dysfunction. Increased activation under bupropion may point to an opposite effect that may relate to the lack of impaired sexual functioning.

Selective serotonin reuptake inhibitor exposure during early pregnancy and the risk of fetal major malformations: focus on paroxetine.

PubMed

Gentile, Salvatore; Bellantuono, Cesario

2009-03-01

To analyze all studies reporting primary data on the rate of fetal malformations after early in utero exposure to paroxetine, investigated either specifically or jointly with other antidepressant medications. Medical literature was identified through searches of MEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library (1980 through September 2008). Search terms were pregnancy, antidepressants, SSRIs, paroxetine, and fetal malformations. Additional studies were identified from the reference lists of published articles. Twenty-five articles reporting primary data on the rate of fetal structural malformations following exposure to paroxetine or selective serotonin reuptake inhibitors as a group during the first trimester of pregnancy were electronically or manually selected. Studies on the teratogenic risk of paroxetine show a high degree of heterogeneity. Moreover, research studies performed with the same methodology and thus showing the same level of evidence report conflicting results. Given the inconsistency of the findings and limitations of the methodology of the published studies, the teratogenic potential of paroxetine that has been reported in some studies remains unproven. This relevant safety question is likely to remain unanswered until large, prospective studies are conducted. Such studies should be designed to include a control group of untreated mothers with similar psychiatric diagnosis so as to differentiate effects of drug exposure from impact of underlying mental disorder on the fetus. Moreover, further experimental studies are warranted to definitively assess clinical consequences of the impact on fetal development related to physiologic effects of prenatal paroxetine exposure on different maternal and fetal parameters. ©Copyright 2009 Physicians Postgraduate Press, Inc.

The influence of paroxetine on the pharmacokinetics of atomoxetine and its main metabolite.

PubMed

Todor, Ioana; Popa, Adina; Neag, Maria; Muntean, Dana; Bocsan, Corina; Buzoianu, Anca; Vlase, Laurian; Gheldiu, Ana-Maria; Chira, Ruxandra; Briciu, Corina

2015-01-01

To evaluate the effects of paroxetine on the pharmacokinetics of atomoxetine and its main metabolite, 4-hydroxyatomoxetine-O-glucuronide, after coadministration of atomoxetine and paroxetine in healthy volunteers. 22 healthy volunteers, extensive metabolizers, took part in this open-label, non-randomized, clinical trial. The study consisted of two periods: Reference, when a single oral dose of 25 mg atomoxetine was administrated to each subject and Test, when 25 mg atomoxetine and 20 mg paroxetine were coadministered. Between the two periods, the volunteers received an oral daily dose of 20-40 mg paroxetine, for 6 days. Atomoxetine and 4-hydroxyatomoxetine-O-glucuronide plasma concentrations were determined within the first 48 hours following drug administration. The pharmacokinetic parameters of both compounds were assessed using a non-compartmental method and the analysis of variance aimed at identifying any statistical significant differences between the pharmacokinetic parameters of atomoxetine and its main metabolite, corresponding to each study period. Paroxetine modified the pharmacokinetic parameters of atomoxetine. Cmax increased from 221.26±94.93 to 372.53±128.28 ng/mL, while AUC0-t and AUC0-∞ also increased from 1151.19±686.52 to 6452.37±3388.76 ng*h/mL, and from 1229.15±751.04 to 7111.74±4195.17 ng*h/mL respectively. The main metabolite pharmacokinetics was also influenced by paroxetine intake, namely Cmax, AUC0-t and AUC0-∞ decreased from 688.76±270.27 to 131.01±100.43 ng*h/mL, and from 4810.93±845.06 to 2606.04±923.88 and from 4928.55±853.25 to 3029.82 ±941.84 respectively. Multiple-dose paroxetine intake significantly influenced atomoxetine and its active metabolite pharmacokinetics, causing a 5.8-fold increased exposure to atomoxetine and 1.6-fold reduced exposure to 4-hydroxyatomoxetine-O-glucuronide.

Effect of sertraline on complications and survival after hematopoietic stem-cell transplantation, a double-blind, placebo-controlled clinical study.

PubMed

Tavakoli-Ardakani, Maria; Kheshti, Raziyeh; Maryam, Mehrpooya

2017-12-01

Previous studies have found a connection between psychiatric problems and post-hematopoietic stem-cell transplantation (HSCT) complications. We sought to evaluate the effect of sertraline on engraftment time, hospitalization period, mortality, and post-transplantation complications in HSCT recipients with depression and/or anxiety. We recruited adults aged 18-60, who were candidates for autologous or allogeneic HSCT with major depression and/or anxiety disorder. They were administered 50 mg of sertraline or placebo daily for the first week, and then 100 mg for the following seven weeks. We documented occurrence and severity of early post-HSCT complications, including infection, mucositis, nausea and vomiting, diarrhea, pain, renal toxicities and liver complications, acute graft-versus-host disease, and veno-occlusive disease, as well as time to engraftment, length of hospitalization and 6-month mortality. Overall, 56 patients participated in the study (sertraline group n = 30, placebo group n = 26). Of the complications, only mortality and readmission up to 6 months post-transplantation were significantly higher in the placebo group compared to sertraline group (P values = 0.040, 0.028, respectively). There were no significant differences for other complications between the groups. Mean engraftment time was significantly lower in the sertraline group (P value = 0.048). This study provides evidence that sertraline positively influences engraftment time, readmission, and mortality after HSCT.

Switch Rates During Acute Treatment for Bipolar II Depression With Lithium, Sertraline, or the Two Combined: A Randomized Double-Blind Comparison.

PubMed

Altshuler, Lori L; Sugar, Catherine A; McElroy, Susan L; Calimlim, Brian; Gitlin, Michael; Keck, Paul E; Aquino-Elias, Ana; Martens, Brian E; Fischer, E Grace; English, Teri L; Roach, Janine; Suppes, Trisha

2017-03-01

The authors compared medication-induced mood switch risk (primary outcome), as well as treatment response and side effects (secondary outcomes) with three acute-phase treatments for bipolar II depression. In a 16-week, double-blind, multisite comparison study, 142 participants with bipolar II depression were randomly assigned to receive lithium monotherapy (N=49), sertraline monotherapy (N=45), or combination treatment with lithium and sertraline (N=48). At each visit, mood was assessed using standardized rating scales. Rates of switch were compared, as were rates of treatment response and the presence and severity of treatment-emergent side effects. Twenty participants (14%) experienced a switch during the study period (hypomania, N=17; severe hypomania, N=3). Switch rates did not differ among the three treatment groups, even after accounting for dropout. No patient had a manic switch or was hospitalized for a switch. Most switches occurred within the first 5 weeks of treatment. The treatment response rate for the overall sample was 62.7% (N=89), without significant differences between groups after accounting for dropout. The lithium/sertraline combination group had a significantly higher overall dropout rate than the monotherapy groups but did not have an accelerated time to response. Lithium monotherapy, sertraline monotherapy, and lithium/sertraline combination therapy were associated with similar switch and treatment response rates in participants with bipolar II depression. The dropout rate was higher in the lithium/sertraline combination treatment group, without any treatment acceleration advantage.

Treatment of trauma-affected refugees with venlafaxine versus sertraline combined with psychotherapy - a randomised study.

PubMed

Sonne, Charlotte; Carlsson, Jessica; Bech, Per; Elklit, Ask; Mortensen, Erik Lykke

2016-11-08

The prevalence of trauma-related psychiatric disorders is high among refugees. Despite this, little is known about the effect of pharmacological treatment for this patient group. The objective of the present study was therefore to examine differences in the effects of venlafaxine and sertraline on Post-Traumatic Stress Disorder (PTSD), depression and functional impairment in trauma-affected refugees. The study was a randomised pragmatic trial comparing venlafaxine and sertraline in combination with psychotherapy and social counselling. PTSD symptoms were measured on the Harvard Trauma Questionnaire - part IV, which was the primary outcome measure. Other outcome measures included: Hopkins Symptom Check List-25 (depression and anxiety), Social Adjustment Scale - short version (social functioning), WHO-5 Well-being Index (quality of life), Crisis Support Scale (support from social network), Sheehan Disability Scale (disability in three areas of functioning), Hamilton Depression and Anxiety scale, the somatisation items of the Symptoms Checklist-90, Global Assessment of Functioning scales and the summarised score of pain in four body areas rated on visual analogue scales. Two hundred seven adult refugee patients were included in the trial (98 in the venlafaxine and 109 in the sertraline group). Of these, 195 patients were eligible for intention-to-treat analyses. Small but significant pre-treatment to post-treatment differences were found on the Harvard Trauma Questionnaire and a number of other ratings in both groups. On the primary outcome measure, no difference was found in treatment effect between the sertraline and venlafaxine group. A significant group difference was found in favour of sertraline on the Sheehan Disability Scale. Sertraline had a slightly better outcome than venlafaxine on some of the secondary outcome measures, but not on the primary outcome measure. Furthermore, a higher percentage of dropouts was found in the venlafaxine group compared to the sertraline group. Although this could indicate that sertraline was better tolerated, which is supported by other studies, a final conclusion on tolerability cannot be drawn from the current study due to lack of systematic reporting of side effects. ClinicalTrials.gov NCT01569685 . Registration date: 28/2/12.

Cost-effectiveness analyses for mirtazapine and sertraline in dementia: randomised controlled trial.

PubMed

Romeo, Renee; Knapp, Martin; Hellier, Jennifer; Dewey, Michael; Ballard, Clive; Baldwin, Robert; Bentham, Peter; Burns, Alistair; Fox, Chris; Holmes, Clive; Katona, Cornelius; Lawton, Claire; Lindesay, James; Livingston, Gill; McCrae, Niall; Moniz-Cook, Esme; Murray, Joanna; Nurock, Shirley; O'Brien, John; Poppe, Michaela; Thomas, Alan; Walwyn, Rebecca; Wilson, Kenneth; Banerjee, Sube

2013-02-01

Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes. To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia. A pragmatic, multicentre, randomised placebo-controlled trial with a parallel cost-effectiveness analysis (trial registration: ISRCTN88882979 and EudraCT 2006-000105-38). The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline, mirtazapine or placebo with differences in effectiveness measured by the primary outcome, total Cornell Scale for Depression in Dementia (CSDD) score, over two time periods: 0-13 weeks and 0-39 weeks. The secondary evaluation was a cost-utility analysis using quality-adjusted life years (QALYs) computed from the Euro-Qual (EQ-5D) and societal weights over those same periods. There were 339 participants randomised and 326 with costs data (111 placebo, 107 sertraline, 108 mirtazapine). For the primary outcome, decrease in depression, mirtazapine and sertraline were not cost-effective compared with placebo. However, examining secondary outcomes, the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo (6.74 v. 12.27 hours per week) or sertraline (6.74 v. 12.32 hours per week). Informal care costs over 39 weeks were £1510 and £1522 less for the mirtazapine group compared with placebo and sertraline respectively. In terms of reducing depression, mirtazapine and sertraline were not cost-effective for treating depression in dementia. However, mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome. Unpaid (family) carer costs were lower with mirtazapine than sertraline or placebo. This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety. Given the priority and the potential value of supporting family carers of people with dementia, further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers.

Structure investigation of sertraline drug and its iodine product using mass spectrometry, thermal analyses and MO-calculations

NASA Astrophysics Data System (ADS)

Zayed, M. A.; Hawash, M. F.; Fahmey, M. A.; El-Habeeb, Abeer A.

2007-11-01

Sertraline (C 17H 17Cl 2N) as an antidepressant drug was investigated using thermal analysis (TA) measurements (TG/DTG and DTA) in comparison with electron impact (EI) mass spectral (MS) fragmentation at 70 eV. Semi-empirical MO-calculations, using PM3 procedure, has been carried out on neutral molecule and positively charged species. These calculations included bond length, bond order, bond strain, partial charge distribution and heats of formation (Δ Hf). Also, in the present work sertraline-iodine product was prepared and its structure was investigated using elemental analyses, IR, 1H NMR, 13C NMR, MS and TA. It was also subjected to molecular orbital calculations (MOC) in order to confirm its fragmentation behavior by both MS and TA in comparison with the sertraline parent drug. In MS of sertraline the initial rupture occurred was CH 3NH 2+ fragment ion via H-rearrangement while in sertraline-iodine product the initial rupture was due to the loss of I + and/or HI + fragment ions followed by CH 2dbnd NH + fragment ion loss. In thermal analyses (TA) the initial rupture in sertraline is due to the loss of C 6H 3Cl 2 followed by the loss of CH 3-NH forming tetraline molecule which thermally decomposed to give C 4H 8, C 6H 6 or the loss of H 2 forming naphthalene molecule which thermally sublimated. In sertraline-iodine product as a daughter the initial thermal rupture is due to successive loss of HI and CH 3NH followed by the loss of C 6H 5HI and HCl. Sertraline biological activity increases with the introduction of iodine into its skeleton. The activities of the drug and its daughter are mainly depend upon their fragmentation to give their metabolites in vivo systems, which are very similar to the identified fragments in both MS and TA. The importance of the present work is also due to the decision of the possible mechanism of fragmentation of the drug and its daughter and its confirmation by MOC.

Identifying Treatment Response of Sertraline in a Teenager with Selective Mutism using Electrophysiological Neuroimaging

PubMed Central

Eugene, Andy R.; Masiak, Jolanta

2016-01-01

Background Selective Mutism is described as the inability to verbally express oneself in anxiety provoking social situations and may result in awkward social interactions in school-aged children. In this case-report we present the baseline electrophysiological neuroimaging results and after treatment with Sertraline for 6-weeks. Methods A 20-channel EEG event-related potential recording was acquired during an internal voice task at baseline prior to the initiation of 50mg of Sertraline and then repeated 6-weeks after treatment with Sertraline. EEG signals were processed for movement, eye-blink, and muscle artifacts and ERP signal averaging was completed. ERPs were analyzed using Standard Low Resolution Brain Electromagnetic Tomography (sLORETA). Results At baseline, Sertraline increased the neuronal activation in the middle temporal gyrus and the anterior cingulate gyrus from baseline in the patient following 6-weeks of treatment. Conclusion Our findings suggest that electrophysiological neuroimaging may provide a creative approach for personalizing medicine by providing insight to the pharmacodynamics of antidepressants. PMID:27468379

Identifying Treatment Response of Sertraline in a Teenager with Selective Mutism using Electrophysiological Neuroimaging.

PubMed

Eugene, Andy R; Masiak, Jolanta

2016-06-01

Selective Mutism is described as the inability to verbally express oneself in anxiety provoking social situations and may result in awkward social interactions in school-aged children. In this case-report we present the baseline electrophysiological neuroimaging results and after treatment with Sertraline for 6-weeks. A 20-channel EEG event-related potential recording was acquired during an internal voice task at baseline prior to the initiation of 50mg of Sertraline and then repeated 6-weeks after treatment with Sertraline. EEG signals were processed for movement, eye-blink, and muscle artifacts and ERP signal averaging was completed. ERPs were analyzed using Standard Low Resolution Brain Electromagnetic Tomography (sLORETA). At baseline, Sertraline increased the neuronal activation in the middle temporal gyrus and the anterior cingulate gyrus from baseline in the patient following 6-weeks of treatment. Our findings suggest that electrophysiological neuroimaging may provide a creative approach for personalizing medicine by providing insight to the pharmacodynamics of antidepressants.

In vitro-in vivo extrapolation of CYP2D6 inactivation by paroxetine: prediction of nonstationary pharmacokinetics and drug interaction magnitude.

PubMed

Venkatakrishnan, Karthik; Obach, R Scott

2005-06-01

Attempts at predicting drug-drug interactions perpetrated by paroxetine from in vitro data have utilized reversible enzyme inhibition models and have been unsuccessful to date, grossly underpredicting interaction magnitude. Recent data have provided evidence for mechanism-based inactivation of CYP2D6 by paroxetine. We have predicted the pharmacokinetic consequences of CYP2D6 inactivation by paroxetine from in vitro inactivation kinetics (kinact 0.17 min(-1), unbound KI 0.315 microM), in vivo inhibitor concentrations, and an estimated CYP2D6 degradation half-life of 51 h, using a mathematical model of mechanism-based inhibition. The model-predicted accumulation ratio of paroxetine was 5 times that expected from single-dose kinetics and in excellent agreement with the observed 5- to 6-fold greater accumulation. Magnitudes of interactions produced by paroxetine (20-30 mg/day) with desipramine, risperidone, perphenazine, atomoxetine, (S)-metoprolol, and (R)-metoprolol were predicted, considering the contribution of CYP2D6 to their oral clearance. Predicted fold-increases in victim drug AUC were 5-, 6-, 5-, 6-, 4-, and 6-fold, respectively, and are in reasonable agreement with observed values of 5-, 6-, >7-, 7-, 5-, and 8-fold, respectively. Failure to consider microsomal binding in vitro adversely affected predictive accuracy. Simulation of the sensitivities of these predictions to model inputs suggests a 2-fold underprediction of interaction magnitude when a CYP2D6 degradation half-life of 14 h (reported for rat CYP3A) is used. In summary, the scaling model for mechanism-based inactivation successfully predicted the pharmacokinetic consequences of CYP2D6 inactivation by paroxetine from in vitro data.

Development of HPTLC-UV absorption densitometry method for the analysis of alprazolam and sertraline in combination and its application in the evaluation of marketed preparations.

PubMed

Venkateswarlu, K; Venisetty, R K; Yellu, N R; Keshetty, S; Pai, M G

2007-09-01

A new simple, sensitive, and reproducible high-performance thin-layer chromatography method for the estimation of alprazolam and sertraline in combination is developed using silica gel plates with fluorescent indicators. The system is equipped with an automated sample applicator, and the detection was performed at 254 nm by using UV absorption densitometry. The mobile phase consists of carbon tetrachloride, methanol, acetone, and ammonia in the ratio 12:3:5:0.1. The retention factor values for alprazolam and sertraline are found to be 0.52 and 0.70, respectively. The limit of detection of alprazolam and sertraline in the mixture of given proportion is observed to be 0.05 microg/mL and 2.5 microg/mL and the limit of quantitation is 0.2 microg/mL and 10 microg/mL, respectively. The method has shown good linearity in the range of 0.2 microg/mL to 0.65 pg/mL for alprazolam (R2 > 0.9953) and 10 pg/mL to 32.5 microg/mL for sertraline (R2 > 0.9942). The intra- and inter-assay (n=5) variations in the linear range are less than 4% for alprazolam and 6% for sertraline. Three pharmaceutical products containing this combination are analyzed to test the applicability of the new method. The percentage of alprazolam and sertraline in the tablets studied range from 97.7% to 102.82% and 96.5% to 99.9%, respectively.

The combination of triiodothyronine (T3) and sertraline is not superior to sertraline monotherapy in the treatment of major depressive disorder☆

PubMed Central

Garlow, Steven J.; Dunlop, Boadie W.; Ninan, Philip T.; Nemeroff, Charles B.

2013-01-01

Objective To determine whether the combination of triiodothyronine (T3) plus sertraline at treatment initiation confers greater antidepressant efficacy than sertraline plus placebo in patients with major depressive disorder. Method Eight-week, double blind, randomized placebo controlled clinical trial of 153 adult outpatients between 18 and 60 years of age, with DSM-IV defined major depressive disorder. Patients were treated with sertraline flexibly adjusted for tolerability and in a double blind fashion with placebo or T3 (25 μg/day in week 1 and increasing to 50 μg/day in week 2). Response was defined categorically as 50% reduction and total score less than 15 in 21-item Hamilton Rating Scale for Depression (HRSD-21) at week 8 and remission as HRSD-21 less than 8. Results There was no difference between treatment groups at final assessment; 65% of placebo and 61.8% of T3 treated subjects achieved response and 50.6% of placebo and 40.8% of T3 treated patients achieved remission. The mean daily dose at final assessment of sertraline and T3, respectively was 144.7 mg (±48.7 mg) and 48.2 μg (±7 μg). Median time to response did not differ between treatment groups. Baseline thyroid function tests did not predict response to sertraline treatment or T3 augmentation. Conclusions These results do not support the routine use of T3 to enhance or accelerate onset of antidepressant response in patients with major depressive disorder. PMID:22964160

Cognitive Behavioral Therapy, Sertraline, or a Combination in Childhood Anxiety

PubMed Central

Walkup, John T.; Albano, Anne Marie; Piacentini, John; Birmaher, Boris; Compton, Scott N.; Sherrill, Joel T.; Ginsburg, Golda S.; Rynn, Moira A.; McCracken, James; Waslick, Bruce; Iyengar, Satish; March, John S.; Kendall, Philip C.

2009-01-01

Background Anxiety disorders are common psychiatric conditions affecting children and adolescents. Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders, little is known about their relative or combined efficacy. Methods In this randomized, controlled trial, we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder, generalized anxiety disorder, or social phobia to receive 14 sessions of cognitive behavioral therapy, sertraline (at a dose of up to 200 mg per day), a combination of sertraline and cognitive behavioral therapy, or a placebo drug for 12 weeks in a 2:2:2:1 ratio. We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4, 8, and 12. Results The percentages of children who were rated as very much or much improved on the Clinician Global Impression-Improvement scale were 80.7% for combination therapy (P<0.001), 59.7% for cognitive behavioral therapy (P<0.001), and 54.9% for sertraline (P<0.001); all therapies were superior to placebo (23.7%). Combination therapy was superior to both monotherapies (P<0.001). Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response; combination therapy had a greater response than cognitive behavioral therapy, which was equivalent to sertraline, and all therapies were superior to placebo. Adverse events, including suicidal and homicidal ideation, were no more frequent in the sertraline group than in the placebo group. No child attempted suicide. There was less insomnia, fatigue, sedation, and restlessness associated with cognitive behavioral therapy than with sertraline. Conclusions Both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders; a combination of the two therapies had a superior response rate. (ClinicalTrials.gov number, NCT00052078.) PMID:18974308

The effect of sertraline and 8-OH-DPAT on the PTZ_induced seizure threshold: Role of the nitrergic system.

PubMed

Heydari, Azhdar; Davoudi, Shima

2017-02-01

Serotonin is a key regulatory neurotransmitter in the CNS which plays an important role in seizure through different receptors, especially the 5HT 1A subtype. The role of sertraline through the 5HT 1A receptor and nitric oxide interaction on the PTZ-induced seizure threshold was investigated in this study. In this study, 70 white male mice were randomly divided into 10 groups including intact control, sham-control and eight experimental groups which received sertraline, 8-OH-DPAT, WAY100635, WAY100635+sertraline, WAY100635+8-OH-DPAT, L-NAME, L-NAME+sertraline and L-NAME+8-OH-DPAT. After 14days of treatment in different groups, the PTZ-induced seizure threshold was assessed and the measurement of nitric oxide metabolites in the brain tissue was done with the Greiss method. The seizure threshold was significantly increased in the sertraline and 8OH-DPAT receiving groups compared to the sham group (P<0.001). In the presence of WAY100635, the effect of both sertraline and 8-OH-DPAT in raising the seizure threshold was more prominent (P<0.001) but on the other hand, in the presence of L-NAME, an increase in the anticonvulsant effect of 8-OH-DPAT was observed, while L-NAME alone had no effect on the seizure threshold (P<0.001). The NO X concentration was significantly decreased in the 8-OH-DPAT_treated group (P<0.01), while the WAY100657 reversed it and the combination of 8-OH-DPAT with L-NAME reduced the NO X levels (P<0.001). These findings support the anticonvulsant effect of SSRIs and selective 5HT 1A receptors, although serotonin receptors other than 5HT 1A subtype may be involved and also it is probable that some anticonvulsant effects of the sertraline and 8-OH-DPAT are through the modulation of nitrergic system. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Sertraline for Preventing Mood Disorders Following Traumatic Brain Injury: A Randomized Clinical Trial.

PubMed

Jorge, Ricardo E; Acion, Laura; Burin, Debora I; Robinson, Robert G

2016-10-01

Prevention is more effective than treatment to decrease the burden of significant medical conditions such as depressive disorders, a major cause of disability worldwide. Traumatic brain injury (TBI) is a candidate for selective strategies to prevent depression given the incidence, prevalence, and functional effect of depression that occurs after TBI. To assess the efficacy of sertraline treatment in preventing depressive disorders following TBI. A double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted at a university hospital from July 3, 2008, to September 17, 2012, with 24 weeks of follow-up. A consecutive sample of 534 patients aged 18 to 85 years, hospitalized for mild, moderate, or severe TBI, was eligible for the study. Ninety-four patients consented to participate and were randomized (46 to placebo and 48 to sertraline), of whom 79 (84%) completed the study. Intention-to-treat data analysis was conducted from July 1, 2014, to December 31, 2015. Placebo or sertraline, 100 mg/d, for 24 weeks or until development of a mood disorder. Time to onset of depressive disorders, as defined by the DSM-IV, associated with TBI. Of the 94 patients in the study (38 female and 56 male; 92 white), the number needed to treat to prevent depression after TBI at 24 weeks was 5.9 (95% CI, 3.1-71.1; χ2 = 4.6; P = .03) for sertraline treatment vs placebo. The influence of sertraline in the course of neuropsychological variables was not detected. The intervention was well tolerated, and adverse effects were mild in both the sertraline and placebo groups. Sertraline appears to be efficacious to prevent the onset of depressive disorders following TBI. Future studies should replicate these findings in a large sample of patients with TBI and depict their long-term physical, cognitive, behavioral, and functional outcomes. clinicaltrials.gov Identifier: NCT00704379.

Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety.

PubMed

Walkup, John T; Albano, Anne Marie; Piacentini, John; Birmaher, Boris; Compton, Scott N; Sherrill, Joel T; Ginsburg, Golda S; Rynn, Moira A; McCracken, James; Waslick, Bruce; Iyengar, Satish; March, John S; Kendall, Philip C

2008-12-25

Anxiety disorders are common psychiatric conditions affecting children and adolescents. Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders, little is known about their relative or combined efficacy. In this randomized, controlled trial, we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder, generalized anxiety disorder, or social phobia to receive 14 sessions of cognitive behavioral therapy, sertraline (at a dose of up to 200 mg per day), a combination of sertraline and cognitive behavioral therapy, or a placebo drug for 12 weeks in a 2:2:2:1 ratio. We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4, 8, and 12. The percentages of children who were rated as very much or much improved on the Clinician Global Impression-Improvement scale were 80.7% for combination therapy (P<0.001), 59.7% for cognitive behavioral therapy (P<0.001), and 54.9% for sertraline (P<0.001); all therapies were superior to placebo (23.7%). Combination therapy was superior to both monotherapies (P<0.001). Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response; combination therapy had a greater response than cognitive behavioral therapy, which was equivalent to sertraline, and all therapies were superior to placebo. Adverse events, including suicidal and homicidal ideation, were no more frequent in the sertraline group than in the placebo group. No child attempted suicide. There was less insomnia, fatigue, sedation, and restlessness associated with cognitive behavioral therapy than with sertraline. Both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders; a combination of the two therapies had a superior response rate. (ClinicalTrials.gov number, NCT00052078.) 2008 Massachusetts Medical Society

Paroxetine Is a Direct Inhibitor of G Protein-Coupled Receptor Kinase 2 and Increases Myocardial Contractility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thal, David M.; Homan, Kristoff T.; Chen, Jun

2012-08-10

G protein-coupled receptor kinase 2 (GRK2) is a well-established therapeutic target for the treatment of heart failure. In this paper we identify the selective serotonin reuptake inhibitor (SSRI) paroxetine as a selective inhibitor of GRK2 activity both in vitro and in living cells. In the crystal structure of the GRK2·paroxetine–Gβγ complex, paroxetine binds in the active site of GRK2 and stabilizes the kinase domain in a novel conformation in which a unique regulatory loop forms part of the ligand binding site. Isolated cardiomyocytes show increased isoproterenol-induced shortening and contraction amplitude in the presence of paroxetine, and pretreatment of mice withmore » paroxetine before isoproterenol significantly increases left ventricular inotropic reserve in vivo with no significant effect on heart rate. Neither is observed in the presence of the SSRI fluoxetine. Our structural and functional results validate a widely available drug as a selective chemical probe for GRK2 and represent a starting point for the rational design of more potent and specific GRK2 inhibitors.« less

Relative potency of varenicline or fluvoxamine to reduce responding for ethanol versus food depends on the presence or absence of concurrently earned food.

PubMed

Ginsburg, Brett C; Lamb, Richard J

2014-03-01

Varenicline, a nicotinic partial agonist, selectively reduces ethanol (EtOH)- versus sucrose-maintained behavior when tested in separate groups, yet like the indirect agonist fluvoxamine, this selectively inverts when EtOH and food are concurrently available. Here, we extend these findings by examining varenicline and fluvoxamine effects under a multiple concurrent schedule where food and EtOH are concurrently available in different components: Component 1 where the food fixed-ratio was 25 and Component 2 where the food fixed-ratio was 75. The EtOH fixed-ratio was always 5. Food-maintained responding predominated in Component 1, while EtOH-maintained responding predominated in Component 2. In a second experiment, varenicline effects were assessed under a multiple schedule where food, then EtOH, then again food were available in separate 5-minute components with fixed-ratios of 5 for each reinforcement. In the multiple concurrent schedule, varenicline was more potent at reducing food- versus EtOH-maintained responding in both components and reduced EtOH-maintained responding more potently during Component 1 (when food was almost never earned) than in Component 2 (where food was often earned). Fluvoxamine was similarly potent at reducing food- and EtOH-maintained responding. Under the multiple schedule, varenicline, like fluvoxamine, more potently decreases EtOH- versus food maintained responding when only food or EtOH is available in separate components. These results demonstrate that selective effects on drug- versus alternative-maintained behavior depend on the schedule arrangement, and assays in which EtOH or an alternative is the only programmed reinforcement may overestimate the selectivity of treatments to decrease EtOH self-administration. Thus selective effects obtained under one assay may not generalize to another. Better understanding the behavioral mechanisms responsible for these results may help to guide pharmaco-therapeutic development for substance use disorders.

Luteal phase administration of agents for the treatment of premenstrual dysphoric disorder.

PubMed

Freeman, Ellen W

2004-01-01

This review focuses on current information about luteal phase administration (i.e. typically for the last 2 weeks of the menstrual cycle) of pharmacological agents for the treatment of premenstrual dysphoric disorder (PMDD). Compared with continuous administration, a luteal phase administration regimen reduces the exposure to medication and lowers the costs of treatment. Based on evidence from randomised clinical trials, SSRIs are the first-line treatment for PMDD at this time. Of these agents, sertraline, fluoxetine and paroxetine (as an extended-release formulation) are approved by the US FDA for luteal phase, as well as continuous, administration. Clinical trials of these agents and citalopram have demonstrated that symptom reduction is similar with both administration regimens. When used to treat PMDD, SSRI doses are consistent with those used for major depressive disorder. The medications are well tolerated; discontinuation symptoms with this intermittent administration regimen have not been reported. Other medications that have been examined in clinical trials for PMDD or severe premenstrual syndrome (PMS) using luteal phase administration include buspirone, alprazolam, tryptophan and progesterone. Buspirone and alprazolam show only modest efficacy in PMS (in some but not all studies), but there may be a lower incidence of sexual adverse effects with these medications than with SSRIs. Symptom reduction with tryptophan was significantly greater than with placebo, but the availability of this medication is strictly limited because of safety concerns. Progesterone has consistently failed to show efficacy for severe PMS/PMDD in large, randomised, placebo-controlled trials.

Post-traumatic stress disorder.

PubMed

Bisson, Jonathan I

2010-02-03

Post-traumatic stress disorder (PTSD) may affect 10% of women and 5% of men at some stage, and symptoms may persist for several years. Risk factors include major trauma, lack of social support, peritraumatic dissociation, and previous psychiatric history or personality factors. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent PTSD? What are the effects of interventions to treat PTSD? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 46 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: affect management; antiepileptic drugs; antihypertensive drugs; benzodiazepines; brofaromine; CBT; drama therapy; eye movement desensitisation and reprocessing; fluoxetine; group therapy; hydrocortisone; hypnotherapy; inpatient treatment programmes; Internet-based psychotherapy; mirtazapine; multiple-session CBT; multiple-session collaborative trauma support; multiple-session education; nefazodone; olanzapine; paroxetine; phenelzine; psychodynamic psychotherapy; risperidone; SSRIs (versus other antidepressants); sertraline; single-session group debriefing; single-session individual debriefing; supportive psychotherapy; supportive counselling; temazepam; tricyclic antidepressants; and venlafaxine.

Post-traumatic stress disorder

PubMed Central

2010-01-01

Introduction Post-traumatic stress disorder (PTSD) may affect 10% of women and 5% of men at some stage, and symptoms may persist for several years. Risk factors include major trauma, lack of social support, peritraumatic dissociation, and previous psychiatric history or personality factors. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent PTSD? What are the effects of interventions to treat PTSD? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 46 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: affect management; antiepileptic drugs; antihypertensive drugs; benzodiazepines; brofaromine; CBT; drama therapy; eye movement desensitisation and reprocessing; fluoxetine; group therapy; hydrocortisone; hypnotherapy; inpatient treatment programmes; Internet-based psychotherapy; mirtazapine; multiple-session CBT; multiple-session collaborative trauma support; multiple-session education; nefazodone; olanzapine; paroxetine; phenelzine; psychodynamic psychotherapy; risperidone; SSRIs (versus other antidepressants); sertraline; single-session group debriefing; single-session individual debriefing; supportive psychotherapy; supportive counselling; temazepam; tricyclic antidepressants; and venlafaxine. PMID:21718580

Monitoring of adherence to headache treatments by means of hair analysis.

PubMed

Ferrari, Anna; Licata, Manuela; Rustichelli, Cecilia; Baraldi, Carlo; Vandelli, Daniele; Marchesi, Filippo; Palazzoli, Federica; Verri, Patrizia; Silingardi, Enrico

2017-02-01

The aim of this study was to evaluate the potential of hair analysis to monitor medication adherence in headache patients undergoing chronic therapy. For this purpose, the following parameters were analyzed: the detection rate of 23 therapeutic drugs in headache patients' hair, the degree of agreement between the self-reported drug and the drug found in hair, and whether the levels found in hair reflected the drug intake reported by the patients. The study included 93 patients suffering from primary headaches declaring their daily intake of at least one of the following drugs during the 3 months before the hair sampling: alprazolam, amitriptyline, citalopram, clomipramine, clonazepam, delorazepam, diazepam, duloxetine, fluoxetine, flurazepam, levomepromazine, levosulpiride, lorazepam, lormetazepam, mirtazapine, paroxetine, quetiapine, sertraline, topiramate, trazodone, triazolam, venlafaxine, and zolpidem. A detailed pharmacological history and a sample of hair were collected for each patient. Hair samples were analyzed by liquid chromatography-electrospray tandem mass spectrometry, using a previously developed method. All 23 drugs were detected in the examined hair samples. The agreement between the self-reported drug and the drug found in hair was excellent for most analytes (P < 0.001, Cohen's kappa); a statistically significant relationship (P < 0.05, linear regression analysis) between dose and hair level was found for amitriptyline, citalopram, delorazepam, duloxetine, lorazepam, and venlafaxine. Hair analysis proved to be a unique matrix to document chronic drug use in headache patients, and the level found for each individual drug can represent a reliable marker of adherence to pharmacological treatments.

Cognitive Behavior Therapy as Augmentation for Sertraline in Treating Patients with Persistent Postural-Perceptual Dizziness.

PubMed

Yu, Yi-Chuan; Xue, Hui; Zhang, Ying-Xin; Zhou, Jiying

2018-01-01

Persistent postural-perceptual dizziness (PPPD) is a common vestibular disorder. This study was conducted to assess whether the addition of cognitive behavior therapy (CBT) could significantly improve the efficacy and acceptability of sertraline in treating PPPD. PPPD patients were recruited and randomly assigned to control and experiment groups. Patients in both groups received sertraline 50-200 mg/day, and only patients in the experiment group received CBT (twice a week, one hour per time). The treatment was continued for eight weeks. At baseline, week 2, week 4, and week 8, the 25-item Dizziness Handicap Inventory (DHI), Hamilton Anxiety Rating Scale (HARS), and Hamilton Depression Rating Scale (HDRS) were used to assess the self-perceived handicapping effects caused by PPPD, anxiety, and depressive symptoms, respectively. The dose of sertraline used and the adverse events in both groups were recorded and analyzed. In total, 91 PPPD patients were randomly assigned to the control group ( n = 45) and experiment group ( n = 46). After eight weeks of treatment, the average DHI scores, HDRS scores, and HARS scores were significantly decreased in both groups. But compared to the control group, the experiment group had significantly lower average DHI score, HDRS score, and HARS score at weeks 4 and 8. Moreover, the dose of sertraline used in the experiment group was significantly lower than that in the control group, and adverse events occurred more frequently in the control group than in the experiment group (48.9% versus 26.1%, p = 0.025). These results demonstrated that the addition of CBT could significantly improve the efficacy and acceptability of sertraline in treating PPPD and reduce the dose of sertraline used.

Antidepressant-selective gynecomastia.

PubMed

Kaufman, Kenneth R; Podolsky, Dina; Greenman, Danielle; Madraswala, Rehman

2013-01-01

To describe what we believe is the first reported case of synergistic gynecomastia during treatment of depressive and anxiety disorders when sertraline was added to a stable medication regimen including duloxetine, rosuvastatin, and amlodipine. A 67-year-old male with major depression, dysthymia, obsessive-compulsive disorder, social anxiety, hypertension, diabetes, and hyperlipidemia presented with new-onset gynecomastia and breast tenderness. Mammography revealed bilateral gynecomastia (fibroglandular tissue posterior to the nipples bilaterally) without suspicious mass, calcification, or other abnormalities. These new symptoms developed after sertraline was added to his stable medication regimen (duloxetine, alprazolam, rosuvastatin, metoprolol, amlodipine, hydrochlorothiazide/triamterene, metformin, and sitagliptin). These symptoms were dose-dependent, with gynecomastia and breast tenderness more severe as sertraline was titrated from 25 mg/day to 50 mg/day and then to 75 mg/day. When sertraline was discontinued, gynecomastia and breast tenderness rapidly resolved. Mammoplasia and gynecomastia are associated with altered dopamine neurotransmission and/or perturbations in sexual hormones. These adverse effects may be medication induced. Selective serotonin reuptake inhibitors (sertraline), serotonin-norepinephrine reuptake inhibitors (duloxetine), rosuvastatin, and amlodipine have been reported to cause these adverse effects. This case was unique, since the patient had been on both sertraline and duloxetine previously as independent psychotropics without the development of gynecomastia. In the context of an additive drug adverse effect, the probability of sertraline as the precipitant drug was determined by both the Naranjo probability scale and the Horn drug interaction probability scale as probable. Gynecomastia is associated with antidepressants and other medications but is rarely addressed. Gynecomastia may be antidepressant selective or may be the result of additive adverse effects. Clinicians are advised to question patients regarding this potential adverse effect. Further education of clinicians is indicated.

Comparison of the antidepressant sertraline on differential depression-like behaviors elicited by restraint stress and repeated corticosterone administration.

PubMed

Ulloa, J L; Castañeda, P; Berríos, C; Díaz-Veliz, G; Mora, S; Bravo, J A; Araneda, K; Menares, C; Morales, P; Fiedler, J L

2010-12-01

Depressive disorder involves emotional, cognitive, autonomic and endocrine alterations and also evidences support the role of stress in the development of this disorder. Because the hypothalamic-pituitary-adrenal axis is involved in the stress response with a concomitant rise in plasma corticoids, the present study compares the antidepressant effects of sertraline (10mg/kg, i.p.) on behavioral changes elicited by (i) restraint stress (2.5h/day for 13days) and (ii) corticosterone injections (30mg/kg, s.c., for 13days). Stressed animals, but not corticosterone-treated animals displayed anxiety behavior and a reduction in the acquisition of a conditioned avoidance response to 25% of control levels (8.0±2.2 vs. 31.7±3.2), being this effect partly sensitive to sertraline. Stressed, but not corticosterone-treated, animals displayed an increased escape failure compared with the control group (24.6%±3.5 vs. 1.6±0.7), an effect partly prevented by sertraline treatment (7.3%±2.0). Both stressed rats and corticosterone-treated rats showed an increase in immobility in the forced swim test, an effect prevented by sertraline. These results suggest that the altered behaviors elicited by stress and corticosterone can be explained by neural modifications that are sensitive to the sertraline antidepressant. Copyright © 2010 Elsevier Inc. All rights reserved.

Comparison of Saffron and Fluvoxamine in the Treatment of Mild to Moderate Obsessive-Compulsive Disorder: A Double Blind Randomized Clinical Trial

PubMed Central

Esalatmanesh, Sophia; Biuseh, Mojtaba; Noorbala, Ahmad Ali; Mostafavi, Seyed-Ali; Rezaei, Farzin; Mesgarpour, Bita; Mohammadinejad, Payam; Akhondzadeh, Shahin

2017-01-01

Objective: There are different pathophysiological mechanisms for obsessive- compulsive disorder (OCD) as suggested by the serotonergic, dopaminergic, and glutamatergic hypotheses. The present study aimed at comparing the efficacy and safety of saffron (stigma of Crocus sativus) and fluvoxamine in the treatment of mild to moderate obsessive- compulsive disorder. Method: In this study, 50 males and females, aged 18 to 60 years, with mild to moderate OCD, participated. The patients were randomly assigned to receive either saffron (30 mg/day, 15 mg twice a day) or fluvoxamine (100 mg/day) for 10 weeks. Using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Adverse Event Checklist, we assessed the patients at baseline, and at the second, fourth, sixth, eighth, and tenth week. Finally, the data were analyzed using general linear repeated measures. Results: In this study, 46 patients completed the trial. General linear repeated measures demonstrated no significant effect for time-treatment interaction on the Y-BOCS total scores [F (2.42, 106.87) = 0.70, P = 0.52], obsession Y-BOCS subscale scores [F (2.47, 108.87) = 0.77, p = 0.49], and compulsion Y-BOCS subscale scores [F (2.18, 96.06) = 0.25, P = 0.79]. Frequency of adverse events was not significantly different between the 2 groups. Conclusion: Our findings suggest that saffron is as effective as fluvoxamine in the treatment of patients with mild to moderate OCD. PMID:29062366

Association of serotonin receptor 2a haplotypes with obsessive-compulsive disorder and its treatment response in Iranian patients: a genetic and pharmacogenetic study.

PubMed

Sina, Marzie; Ahmadiani, Abolhassan; Asadi, Sareh; Shams, Jamal

2018-01-01

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder causing intrusive thoughts or repetitive behaviors. Serotonin reuptake inhibitors are used for OCD treatment, but 40%-60% of patients do not respond to them adequately. In this study, the associations of serotonin receptor 2a polymorphisms rs6311 and rs6313 with OCD, its familial form and fluvoxamine treatment response in Iranian population were investigated. Association analyses were conducted in 293 OCD cases fulfilling the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR and 245 controls. Pharmacotherapy was defined as 12 weeks of treatment with fluvoxamine (150-300 mg). Treatment response was considered as >25% reduction in Yale-Brown Obsessive Compulsive Scale score. Genotyping was performed by means of PCR-RFLP. The results showed no association of rs6311 or rs6313 with OCD, but their haplotypes had different distribution patterns in cases and controls. Moreover, rs6313 was associated with the familial form of OCD in females significantly ( P =0.005) under the recessive genetic model. Moreover, rs6311-rs6313 haplotypes were associated with fluvoxamine treatment response in OCD patients with more AC and less AT in responders. HTR2A haplotypes are associated with OCD and its treatment response with a fluvoxamine in Iranian patients. Furthermore, the observed association of rs6313 with the familial form of OCD in females suggests different genetic background of OCD familial and non-familial forms, which needs further investigation.

Contrasting effects of vortioxetine and paroxetine on pineal gland biochemistry in a tryptophan-depletion model of depression in female rats.

PubMed

Franklin, M; Hlavacova, N; Li, Y; Bermudez, I; Csanova, A; Sanchez, C; Jezova, D

2017-10-03

We studied the effects of the multi-modal antidepressant, vortioxetine and the SSRI, paroxetine on pineal melatonin and monoamine synthesis in a sub-chronic tryptophan (TRP) depletion model of depression based on a low TRP diet. Female Sprague-Dawley rats were randomised to groups a) control, b) low TRP diet, c) low TRP diet+paroxetine and d) low TRP diet+vortioxetine. Vortioxetine was administered via the diet (0.76mg/kg of food weight) and paroxetine via drinking water (10mg/kg/day) for 14days. Both drugs resulted in SERT occupancies >90%. Vortioxetine significantly reversed TRP depletion-induced reductions of pineal melatonin and serotonin (5-HT) and significantly increased pineal noradrenaline NA. Paroxetine did none of these things. Other studies suggest pineal melatonin synthesis may involve N-methyl-d-aspartate (NMDA) receptors and glutamatergic modulation. Here observed changes may be mediated via vortioxetine's strong 5-HT reuptake blocking action together with possible additional effects on glutamate neurotransmission in the pineal via NMDA receptor-modulation and possibly with added impetus from increased NA output. Copyright © 2017 Elsevier Inc. All rights reserved.

Serotonin toxicity caused by moclobemide too soon after paroxetine-selegiline.

PubMed

Wu, Ming-Ling; Deng, Jou-Fang

2009-08-01

Serotonin toxicity is an iatrogenic complication of serotonergic drug therapy. It is due to an overstimulation of central and peripheral serotonin receptors that lead to neuromuscular, mental and autonomic changes. Moclobemide is a reversible inhibitor of monoamine oxidase (MAO)-A, selegiline is an irreversible selective inhibitor of MAO-B, and paroxetine is a selective serotonin reuptake inhibitor. Combined use of these agents is known to cause serotonin toxicity. A 53-year-old woman had been treated with paroxetine and selegiline. After moclobemide was prescribed in place of paroxetine without a washout period, she quickly developed confusion, agitation, ataxia, diaphoresis, tremor, mydriasis, ocular clonus, hyperreflexia, tachycardia, moderately elevated blood pressure and high fever, symptoms that were consistent with serotonin toxicity. Discontinuation of the drugs, hydration and supportive care were followed by remarkable improvement of baseline status within 3 days. This case demonstrates that serotonin toxicity may occur even with small doses of paroxetine, selegiline and moclobemide in combination. Physicians managing patients with depression must be aware of the potential for serotonin toxicity and should be able to recognize and treat or, ideally, anticipate and avoid this pharmacodynamically-mediated interaction that may occur between prescribed drugs.

Treatment of ballism and pseudobulbar affect with sertraline.

PubMed

Okun, M S; Riestra, A R; Nadeau, S E

2001-10-01

The pathogenesis of ballism is uncertain and may involve more than one mechanism; treatment is not always efficacious. To provide evidence of a nondopaminergic mechanism and the potential for a prompt and nearly complete response to a serotonergic agent. Report of 2 separate trials of sertraline hydrochloride in a single patient. Complete remission of symptoms within 48 hours of each drug trial. Sertraline may offer an alternative with a better adverse effect profile than dopamine receptor blockers in the treatment of patients with ballism.

Pharmacokinetic interaction of flecainide and paroxetine in relation to the CYP2D6*10 allele in healthy Korean subjects

PubMed Central

Lim, Kyoung Soo; Cho, Joo-Youn; Jang, In-Jin; Kim, Bo-Hyung; Kim, JaeWoo; Jeon, Ji-Young; Tae, Yu-Mi; Yi, SoJeong; Eum, SoYoung; Shin, Sang-Goo; Yu, Kyung-Sang

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT The only existing study of CYP2D6*10-associated alterations in flecainide pharmacokinetics was retrospective. Paroxetine has been known as a strong inhibitor of CYP2D6. WHAT THIS STUDY ADDS This study reports that the extent of drug interaction between flecainide and paroxetine is influenced by the CYP2D6*10 allele in healthy subjects, which is frequent in Asians. AIMS The objectives were to evaluate the effect of CYP2D6 genetic polymorphism on the pharmacokinetics of flecainide, and also on the extent of drug interaction with paroxetine as a CYP2D6 inhibitor after a single oral administration in healthy subjects. METHODS An open-label, two-period, single-sequence, cross-over study was performed in 21 healthy Korean male volunteers (seven for CYP2D6*1/*1 or *1/*2, group 1; seven for CYP2D6*1/*10, group 2; seven for CYP2D6*10/*10 or *10/*36, group 3). Subjects were administered 200 mg of flecainide on day 1. After a 7-day wash-out period, subjects were administered 20 mg of paroxetine from day 8 to 14, and 200 mg of flecainide on day 15. Blood sampling was performed up to 72 h after flecainide administration. RESULTS Terminal elimination half-life and mean residence time (MRT) were significantly different among three genotype groups after a single oral administration of flecainide (P = 0.021, 0.011, respectively). Area under the concentration–time curve, terminal elimination half-life and MRT increased significantly after paroxetine co-administration only in groups 1 and 2. CONCLUSIONS This study reports that the extent of drug interaction between flecainide and paroxetine is influenced by the CYP2D6*10 allele in healthy subjects, which is frequent in Asians. PMID:18754843

Effects of periadolescent fluoxetine and paroxetine on elevated plus-maze, acoustic startle, and swimming immobility in rats while on and off-drug.

PubMed

Vorhees, Charles V; Morford, LaRonda R; Graham, Devon L; Skelton, Matthew R; Williams, Michael T

2011-10-05

Whether selective serotonin reuptake inhibitors (SSRIs) exposure during adolescent brain development causes lasting effects remains unresolved. Assess the effects of fluoxetine and paroxetine 60 days after adolescent exposure compared with when on-drug. Male Sprague-Dawley littermates (41 litters) were gavaged on postnatal days 33-53 with fluoxetine (3 or 10 mg/kg/day), paroxetine (3, 10 or, 17 mg/kg/day), or water; half were tested while on-drug (21 litters) and half after 60 days off-drug (20 litters). The highest dose of the drugs reduced body weight gain during treatment that rebounded 1 week post-treatment. On-drug, no significant group differences were found on elevated plus maze time-in-open, zone entries, or latency to first open entry; however, the high dose of paroxetine significantly reduced head-dips (N=20/group). No significant effects were found on-drug for acoustic startle response/prepulse inhibition (ASR/PPI) although a trend (p<0.10) was seen, which after combining dose levels, showed a significant increase in ASR amplitude for both fluoxetine and paroxetine (N=20-21/group). No differences on immobility time were seen in the Porsolt forced swim test or in plasma corticosterone at the end of forced swim (N-19-21/group). Off-drug, no effects were seen in the elevated plus maze (N=16/group), ASR/PPI (N=20/group), forced swim (N=19-20/group), or plasma corticosterone (N=19/group). At the doses tested, fluoxetine and paroxetine induced minor effects with drug on-board but no residual, long-term adverse effects in rats 60 days after drug discontinuation. The data provide no evidence that fluoxetine or paroxetine have long-term adverse effects on the behaviors measured here after adolescent to young adult exposure.

Association analysis of SIGMAR1 with major depressive disorder and SSRI response.

PubMed

Kishi, Taro; Yoshimura, Reiji; Okochi, Tomo; Fukuo, Yasuhisa; Kitajima, Tsuyoshi; Okumura, Takenori; Tsunoka, Tomoko; Kawashima, Kunihiro; Yamanouchi, Yoshio; Kinoshita, Yoko; Umene-Nakano, Wakako; Naitoh, Hiroshi; Nakamura, Jun; Ozaki, Norio; Iwata, Nakao

2010-06-01

Several investigations have suggested the possible involvement of sigma 1 non-opioid intracellular receptor 1 (sigma 1 receptor) in the pathophysiology of major depressive disorder (MDD). Sigma 1 receptors are also one of the major pharmacological therapeutic targets of selective serotonin reuptake inhibitors (SSRIs). To evaluate the association of sigma 1 receptor gene (SIGMAR1) and MDD and SSRIs therapeutic response in MDD, we conducted a case-control study of Japanese samples (466 MDD patients, 516 controls and 208 MDD patients treated by fluvoxamine or sertraline). We defined a clinical response as a decrease of more than 50% in baseline the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D) within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. Therefore, we selected rs1800866 in SIGMAR1 for the following association analysis. In the logistic regression analysis, we detected an association of the phenotypes (MDD or controls) with rs1800866 genotype. However, we did not detect an association between rs1800866 and SSRI therapeutic response in Japanese MDD. In addition, remission with SSRI was not associated with rs1800866. Also, we did not detect a novel polymorphism in SIGMAR1 when we performed a mutation search using MDD treated by SSRIs samples. Our results suggest that rs1800866 in SIGMAR1 may play a role in the pathophysiology of MDD in the Japanese population. Also, SIGMAR1 does not play a role in the therapeutic response to SSRI in Japanese MDD patients. However, because our sample was small, a replication study using another population and larger sample will be required for conclusive results. (c) 2010. Published by Elsevier Ltd. All rights reserved.

Paroxetine reduces social anxiety in individuals with a co-occurring alcohol use disorder

PubMed Central

Book, Sarah W.; Thomas, Suzanne E.; Randall, Patrick K.; Randall, Carrie L.

2008-01-01

Patients with social anxiety disorder who are seen in clinical practice commonly have additional psychiatric comorbidity, including alcohol use disorders. The first line treatment for social anxiety disorder is selective-serotonin-reuptake-inhibitors (SSRIs), such as paroxetine. However, the efficacy of SSRIs has been determined with studies that excluded alcoholics. Forty two subjects with social anxiety and a co-occurring alcohol use disorder participated in a 16-week, double-blind, placebo-controlled clinical trial to determine the efficacy of paroxetine for social anxiety in patients with co-occurring alcohol problems. Paroxetine was superior to placebo in reducing social anxiety, as measured by the Liebowitz Social Anxiety Scale total and subscale scores and additional measures of social anxiety. This study provides the first evidence-based recommendation for the use of an SSRI to treat social anxiety in this patient population. PMID:17448631

Effect of proton pump inhibitors on the serum concentrations of the selective serotonin reuptake inhibitors citalopram, escitalopram, and sertraline.

PubMed

Gjestad, Caroline; Westin, Andreas A; Skogvoll, Eirik; Spigset, Olav

2015-02-01

The selective serotonin reuptake inhibitors (SSRIs) citalopram, escitalopram, and sertraline are all metabolized by the cytochrome P-450 isoenzyme CYP2C19, which is inhibited by the proton pump inhibitors (PPIs) omeprazole, esomeprazole, lansoprazole, and pantoprazole. The aim of the present study was to evaluate the effect of these PPIs on the serum concentrations of citalopram, escitalopram, and sertraline. Serum concentrations from patients treated with citalopram, escitalopram, or sertraline were obtained from a routine therapeutic drug monitoring database, and samples from subjects concomitantly using PPIs were identified. Dose-adjusted SSRI serum concentrations were calculated to compare data from those treated and those not treated with PPIs. Citalopram concentrations were significantly higher in patients treated with omeprazole (+35.3%; P < 0.001), esomeprazole (+32.8%; P < 0.001), and lansoprazole (+14.7%; P = 0.043). Escitalopram concentrations were significantly higher in patients treated with omeprazole (+93.9%; P < 0.001), esomeprazole (+81.8%; P < 0.001), lansoprazole (+20.1%; P = 0.008), and pantoprazole (+21.6%; P = 0.002). Sertraline concentrations were significantly higher in patients treated with esomeprazole (+38.5%; P = 0.0014). The effect of comedication with PPIs on the serum concentration of SSRIs is more pronounced for omeprazole and esomeprazole than for lansoprazole and pantoprazole, and escitalopram is affected to a greater extent than are citalopram and sertraline. When omeprazole or esomeprazole are used in combination with escitalopram, a 50% dose reduction of the latter should be considered.

Sertraline treatment for depression associated with acute coronary syndromes: a cost analysis from the viewpoint of the Italian Healthcare System.

PubMed

Lattanzio, Fabrizia; Cherubini, Antonio; Furneri, Gianluca; Di Bari, Mauro; Marchionni, Niccolò

2008-02-01

Depressive disorders (DD) are independent risk factors for rehospitalization after acute coronary syndromes (ACS) and, hence, for increased healthcare costs. A placebo-controlled safety trial of 24 weeks of treatment with sertraline after ACS (Sertraline Anti-Depressant Heart Attack Randomized Trial, SADHART) suggested that active treatment was associated with reduced rehospitalization due to coronary and non-coronary events. With the SADHART database, a cost analysis was carried out to determine the economic consequences of treating DD after ACS in the perspective of the Italian Healthcare System. Clinical information on medical events and rehospitalizations recorded over the study period was drawn from the original SADHART database, which did not contain information necessary for estimating indirect costs. Analysis was therefore limited to direct medical costs due to rehospitalizations, emergency room visits and hospital procedures, and the average Italian Diagnosis-Related Group (DRG) tariffs were applied. With the exclusion of the cost of sertraline treatment, the average direct cost per patient over the study period was 3,418+/-8,290 euro in the active treatment group and 4,409+/-9,439 euro in the placebo group (p=0.3). After including the cost of 24 weeks of sertraline treatment, the average cost in sertraline-treated patients was only modestly increased, to 3,524+/-8,290 euro. Treatment of major DD in patients with recent ACS can improve patient care without additional costs, and possibly with some savings, to the healthcare system.

Mouse strain differences in immobility and sensitivity to fluvoxamine and desipramine in the forced swimming test: analysis of serotonin and noradrenaline transporter binding.

PubMed

Sugimoto, Yumi; Kajiwara, Yoshinobu; Hirano, Kazufumi; Yamada, Shizuo; Tagawa, Noriko; Kobayashi, Yoshiharu; Hotta, Yoshihiro; Yamada, Jun

2008-09-11

Strain differences in immobility time in the forced swimming test were investigated in five strains of mice, namely, ICR, ddY, C57BL/6, DBA/2 and BALB/c mice. There were significant strain differences. The immobility times of ICR, ddY and C57BL/6 mice were longer than those of DBA/2 and BALB/c mice. Immobility times were not significantly related to locomotor activity in these strains. There were also differences in sensitivity to the selective serotonin reuptake inhibitor (SSRI) fluvoxamine. In ICR, ddY and C57BL/6 mice, fluvoxamine did not affect immobility time, while it reduced the immobility time of DBA/2 and BALB/c mice dose-dependently. The noradrenaline reuptake inhibitor desipramine decreased immobility time in all strains of mice. Serotonin (5-HT) transporter binding in the brains of all five strains of mice was also investigated. Analysis of 5-HT transporter binding revealed significant strain differences, being lower in DBA/2 and BALB/c mice than in other strains of mice. The amount of 5-HT transporter binding was correlated to baseline immobility time. However, there was no significant relation between noradrenaline transporter binding and immobility time. These results suggest that the duration of baseline immobility depends on the levels of 5-HT transporter binding, leading to apparent strain differences in immobility time in the forced swimming test. Furthermore, differences in 5-HT transporter binding may cause variations in responses to fluvoxamine.

Association of serotonin receptor 2a haplotypes with obsessive–compulsive disorder and its treatment response in Iranian patients: a genetic and pharmacogenetic study

PubMed Central

Sina, Marzie; Ahmadiani, Abolhassan; Asadi, Sareh; Shams, Jamal

2018-01-01

Introduction Obsessive–compulsive disorder (OCD) is a debilitating psychiatric disorder causing intrusive thoughts or repetitive behaviors. Serotonin reuptake inhibitors are used for OCD treatment, but 40%–60% of patients do not respond to them adequately. In this study, the associations of serotonin receptor 2a polymorphisms rs6311 and rs6313 with OCD, its familial form and fluvoxamine treatment response in Iranian population were investigated. Patients and methods Association analyses were conducted in 293 OCD cases fulfilling the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR and 245 controls. Pharmacotherapy was defined as 12 weeks of treatment with fluvoxamine (150–300 mg). Treatment response was considered as >25% reduction in Yale–Brown Obsessive Compulsive Scale score. Genotyping was performed by means of PCR-RFLP. Results The results showed no association of rs6311 or rs6313 with OCD, but their haplotypes had different distribution patterns in cases and controls. Moreover, rs6313 was associated with the familial form of OCD in females significantly (P=0.005) under the recessive genetic model. Moreover, rs6311–rs6313 haplotypes were associated with fluvoxamine treatment response in OCD patients with more AC and less AT in responders. Conclusion HTR2A haplotypes are associated with OCD and its treatment response with a fluvoxamine in Iranian patients. Furthermore, the observed association of rs6313 with the familial form of OCD in females suggests different genetic background of OCD familial and non-familial forms, which needs further investigation. PMID:29785111

Serotonin-1A receptors in the dorsal periaqueductal gray matter mediate the panicolytic-like effect of pindolol and paroxetine combination in the elevated T-maze.

PubMed

Sela, Vânia Ramos; Biesdorf, Carla; Ramos, Diego Henrique; Zangrossi, Hélio; Graeff, Frederico Guilherme; Audi, Elisabeth Aparecida

2011-05-09

The β-adrenergic blocker and 5-HT(1A) receptor antagonist pindolol has been combined with selective serotonin reuptake inhibitors (SSRIs) in patients with depressive and anxiety disorders to shorten the onset of the clinical action and/or increase the proportion of responders. The results of a previous study have shown that pindolol potentiates the panicolytic effect of paroxetine in rats submitted to the elevated T-maze (ETM). Since reported evidence has implicated the 5-HT(1A) receptors of the dorsal periaqueductal gray matter (DPAG) in the panicolytic effect of antidepressants, rats treated with pindolol (5.0mg/kg, i.p.) and paroxetine (1.5mg/kg, i.p.) received a previous intra-DPAG injection of the selective 5-HT(1A) antagonist, WAY-100635 (0.4 μg) and were submitted to the ETM. Pretreatment with WAY-100635 reversed the increase in escape latency, a panicolytic effect, determined by the pindolol-paroxetine combination. These results implicate the 5-HT(1A) receptors of the DPAG in the panicolytic effect of the pindolol-paroxetine combination administered systemically. They also give further preclinical support for the use of this drug combination in the treatment of panic disorder. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Neonatal intraventricular haemorrhage associated with maternal use of paroxetine

PubMed Central

Duijvestijn, Yvonne C M; Kalmeijer, Mathijs D; Passier, Anneke L M; Dahlem, Peter; Smiers, Frans

2003-01-01

Selective serotonin reuptake inhibitors (SSRIs) have been reported to inhibit serotonin uptake into platelets, resulting in decreased platelet function. We report a case of a large intraventricular haemorrhage in a 6-h-old boy, whose mother used paroxetine during pregnancy. PMID:14651736

Effect of Proton Pump Inhibitors on the Serum Concentrations of the Selective Serotonin Reuptake Inhibitors Citalopram, Escitalopram, and Sertraline

PubMed Central

Gjestad, Caroline; Westin, Andreas A.; Skogvoll, Eirik

2015-01-01

Background: The selective serotonin reuptake inhibitors (SSRIs) citalopram, escitalopram, and sertraline are all metabolized by the cytochrome P-450 isoenzyme CYP2C19, which is inhibited by the proton pump inhibitors (PPIs) omeprazole, esomeprazole, lansoprazole, and pantoprazole. The aim of the present study was to evaluate the effect of these PPIs on the serum concentrations of citalopram, escitalopram, and sertraline. Methods: Serum concentrations from patients treated with citalopram, escitalopram, or sertraline were obtained from a routine therapeutic drug monitoring database, and samples from subjects concomitantly using PPIs were identified. Dose-adjusted SSRI serum concentrations were calculated to compare data from those treated and those not treated with PPIs. Results: Citalopram concentrations were significantly higher in patients treated with omeprazole (+35.3%; P < 0.001), esomeprazole (+32.8%; P < 0.001), and lansoprazole (+14.7%; P = 0.043). Escitalopram concentrations were significantly higher in patients treated with omeprazole (+93.9%; P < 0.001), esomeprazole (+81.8%; P < 0.001), lansoprazole (+20.1%; P = 0.008), and pantoprazole (+21.6%; P = 0.002). Sertraline concentrations were significantly higher in patients treated with esomeprazole (+38.5%; P = 0.0014). Conclusions: The effect of comedication with PPIs on the serum concentration of SSRIs is more pronounced for omeprazole and esomeprazole than for lansoprazole and pantoprazole, and escitalopram is affected to a greater extent than are citalopram and sertraline. When omeprazole or esomeprazole are used in combination with escitalopram, a 50% dose reduction of the latter should be considered. PMID:24887634

Effect of Sertraline on Current-Source Distribution of the High Beta Frequency Band: Analysis of Electroencephalography under Audiovisual Erotic Stimuli in Healthy, Right-Handed Males.

PubMed

Lee, Seung Hyun; Hyun, Jae Seog; Kwon, Oh-Young

2010-08-01

The purpose of this study was to examine the cerebral changes in high beta frequency oscillations (22-30 Hz) induced by sertraline and by audiovisual erotic stimuli in healthy adult males. Scalp electroencephalographies (EEGs) were conducted twice in 11 healthy, right-handed males, once before sertraline intake and again 4 hours thereafter. The EEGs included four sessions recorded sequentially while the subjects were resting, watching a music video, resting, and watching an erotic video for 3 minutes, 5 minutes, 3 minutes, and 5 minutes, respectively. We performed frequency-domain analysis using the EEGs with a distributed model of current-source analysis. The statistical nonparametric maps were obtained from the sessions of watching erotic and music videos (p<0.05). The erotic stimuli decreased the current-source density of the high beta frequency band in the middle frontal gyrus, the precentral gyrus, the postcentral gyrus, and the supramarginal gyrus of the left cerebral hemisphere in the baseline EEGs taken before sertraline intake (p<0.05). The erotic stimuli did not induce any changes in current-source distribution of the brain 4 hours after sertraline intake. It is speculated that erotic stimuli may decrease the function of the middle frontal gyrus, the precentral gyrus, the postcentral gyrus, and the supramarginal gyrus of the left cerebral hemisphere in healthy adult males. This change may debase the inhibitory control of the brain against erotic stimuli. Sertraline may reduce the decrement in inhibitory control.

Effect of Sertraline on Current-Source Distribution of the High Beta Frequency Band: Analysis of Electroencephalography under Audiovisual Erotic Stimuli in Healthy, Right-Handed Males

PubMed Central

Lee, Seung Hyun; Hyun, Jae Seog

2010-01-01

Purpose The purpose of this study was to examine the cerebral changes in high beta frequency oscillations (22-30 Hz) induced by sertraline and by audiovisual erotic stimuli in healthy adult males. Materials and Methods Scalp electroencephalographies (EEGs) were conducted twice in 11 healthy, right-handed males, once before sertraline intake and again 4 hours thereafter. The EEGs included four sessions recorded sequentially while the subjects were resting, watching a music video, resting, and watching an erotic video for 3 minutes, 5 minutes, 3 minutes, and 5 minutes, respectively. We performed frequency-domain analysis using the EEGs with a distributed model of current-source analysis. The statistical nonparametric maps were obtained from the sessions of watching erotic and music videos (p<0.05). Results The erotic stimuli decreased the current-source density of the high beta frequency band in the middle frontal gyrus, the precentral gyrus, the postcentral gyrus, and the supramarginal gyrus of the left cerebral hemisphere in the baseline EEGs taken before sertraline intake (p<0.05). The erotic stimuli did not induce any changes in current-source distribution of the brain 4 hours after sertraline intake. Conclusions It is speculated that erotic stimuli may decrease the function of the middle frontal gyrus, the precentral gyrus, the postcentral gyrus, and the supramarginal gyrus of the left cerebral hemisphere in healthy adult males. This change may debase the inhibitory control of the brain against erotic stimuli. Sertraline may reduce the decrement in inhibitory control. PMID:20733961

Serotonin Transporter Promoter Region (5-HTTLPR) Polymorphism Is Not Associated With Paroxetine-Induced Ejaculation Delay in Dutch Men With Lifelong Premature Ejaculation

PubMed Central

Janssen, Paddy K.C.; Zwinderman, Aeilko H.; Olivier, Berend

2014-01-01

Purpose To investigate the association between the 5-HT-transporter-gene-linked promoter region (5-HTTLPR) polymorphism and 20-mg paroxetine-induced ejaculation delay in men with lifelong premature ejaculation (LPE). Materials and Methods This was a prospective study of 10 weeks of paroxetine treatment in 54 men with LPE. Intravaginal ejaculation latency time (IELT) was measured by stopwatch. Controls consisted of 92 Caucasian men. All men with LPE were genotyped for the 5-HTTLPR polymorphism. Allele frequencies and genotypes of short (S) and long (L) variants of the polymorphism were compared between patients and controls. Associations between the LL, SL, and SS genotypes and fold increase of mean IELT were investigated. Results Of the 54 patients, 43 (79.6%) responded to 20-mg paroxetine treatment with an ejaculation delay, whereas 11 patients (20.4%) did not respond; 44%, 18%, and 18% of the patients showed a fold increase in mean IELT of 2-10, 10-20, and more than 20, respectively. Of the 54 men, 14 (25.9%) had the LL genotype, 29 (53.7%) had the SL genotype, and 11 (20.4%) had the SS genotype. In the 92 controls, the LL, SL, and SS genotypes were present in 27 (29.3%), 41 (44.6%), and 24 (26.1%), respectively. No statistically significant differences were found in 5-HTTLPR allelic variations or in 5-HTTLPR gene variations. In all men treated with 20 mg paroxetine, analysis of variance of the natural logarithm of fold increase in the IELT showed no statistically significant difference according to genotype (p=0.83). Conclusions The 5-HTTLPR polymorphism is not associated with daily 20-mg paroxetine treatment-induced ejaculation delay in men with LPE. PMID:24578810

Intranasal delivery of paroxetine nanoemulsion via the olfactory region for the management of depression: formulation, behavioural and biochemical estimation

NASA Astrophysics Data System (ADS)

Pandey, Yogendra Raj; Kumar, Shobhit; Gupta, Bijay Kumar; Ali, Javed; Baboota, Sanjula

2016-01-01

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) and is used for the treatment of depression and anxiety problems, but suffers from the drawback of poor oral bioavailability (less than 50%) due to its extensive first pass metabolism. The objective of the present study was to develop a paroxetine loaded nanoemulsion (o/w type) for direct nose-to-brain delivery. Nanoemulsions were prepared by the spontaneous emulsification technique using Capmul MCM, Solutol HS 15 and propylene glycol as oil phase, surfactant and co-surfactant, respectively, for delivery of drug directly to the brain through the nasal route for better management of depression. Formulations were studied for droplet size, polydispersity index (PDI), percentage transmittance, refractive index, viscosity, zeta potential, surface morphology and in vitro permeation study. TEM images of optimized formulation showed spherical droplets with a mean diameter of 58.47 ± 3.02 nm, PDI of 0.339 ± 0.007 and zeta potential values of -33 mV. The formulation showed good results for transmittance (100.60 ± 0.577%), refractive index (1.412 ± 0.003) and viscosity (40.85 ± 6.40 cP). Permeation studies revealed a 2.57-fold enhancement in permeation as compared to the paroxetine suspension. Behavioural studies such as the forced swimming test and locomotor activity test were done on Wistar rats to study the antidepressant effect of the optimized formulation. Treatment of depressed rats with paroxetine nanoemulsion (administered intranasally) significantly improved the behavioural activities in comparison to paroxetine suspension (orally administered). Biochemical estimation results revealed that the prepared nanoemulsion was effective in enhancing the depressed levels of glutathione and decreasing the elevated levels of TBARS.

Heart rate variability in major depressive disorder and after antidepressant treatment with agomelatine and paroxetine: Findings from the Taiwan Study of Depression and Anxiety (TAISDA).

PubMed

Yeh, Ta-Chuan; Kao, Lien-Cheng; Tzeng, Nian-Sheng; Kuo, Terry B J; Huang, San-Yuan; Chang, Chuan-Chia; Chang, Hsin-An

2016-01-04

Evidence from previous studies suggests that heart rate variability (HRV) is reduced in major depressive disorder (MDD). However, whether this reduction is attributable to the disorder per se or to medication, since antidepressants may also affect HRV, is still debated. There is a dearth of information regarding the effects of agomelatine, a novel antidepressant, on HRV. Here, we investigated whether HRV is reduced in MDD and compared the effects of agomelatine and paroxetine on HRV. We recruited 618 physically healthy unmedicated patients with MDD and 506 healthy volunteers aged 20-65 years. Frequency-domain measures of resting HRV were obtained at the time of enrollment for all participants. For patients with MDD, these measures were obtained again after 6 weeks of either agomelatine or paroxetine monotherapy. Compared with healthy subjects, unmedicated patients with MDD exhibited significantly lower variance (total HRV), low frequency (LF), and high frequency (HF) HRV, and a higher LF/HF ratio. Depression severity independently contributed to decreased HRV and vagal tone. Fifty-six patients completed the open-label trial (n=29 for agomelatine, n=27 for paroxetine). Between-group analyses showed a significant group-by-time interaction for LF-HRV and HF-HRV, driven by increases in LF-HRV and HF-HRV only after agomelatine treatment. Within the paroxetine-treated group, there were no significant changes in mean R-R intervals or any HRV indices. We therefore concluded that MDD is associated with reduced HRV, which is inversely related to depression severity. Compared with paroxetine, agomelatine has a more vagotonic effect, suggesting greater cardiovascular safety. Clinicians should consider HRV effects while selecting antidepressants especially for depressed patients who already have decreased cardiac vagal tone. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of low-dose paroxetine 7.5 mg on weight and sexual function during treatment of vasomotor symptoms associated with menopause

PubMed Central

Portman, David J.; Kaunitz, Andrew M.; Kazempour, Kazem; Mekonnen, Hana; Bhaskar, Sailaja; Lippman, Joel

2014-01-01

Abstract Objective Two phase 3, randomized, placebo-controlled trials demonstrated that low-dose paroxetine 7.5 mg reduced the frequency and severity of vasomotor symptoms (VMS) associated with menopause and had a favorable tolerability profile. The impact of paroxetine 7.5 mg on body weight and sexual function was evaluated in a pooled analysis. Methods Postmenopausal women aged 40 years or older who had moderate to severe VMS were randomly assigned to receive paroxetine 7.5 mg or placebo once daily for 12 or 24 weeks. Assessments included changes in body mass index (BMI) and weight, Arizona Sexual Experiences Scale score, Hot Flash–Related Daily Interference Scale sexuality subscore, and adverse events related to weight or sexual dysfunction. Results Pooled efficacy and safety populations comprised 1,174 and 1,175 participants, respectively. Baseline values were similar for median weight (∼75 kg), median BMI (∼28 kg/m2), and the proportion of women with sexual dysfunction (∼58%). No clinically meaningful or statistically significant changes from baseline in weight or sexual function assessments occurred in the paroxetine 7.5 mg group. Small but statistically significant increases in weight and BMI were observed in the placebo group only on week 4. No significant difference between treatment groups was observed in the proportion of participants who had 7% or higher gain in body weight on week 4, 12, or 24. Rates of adverse events suggestive of sexual dysfunction were low and similar in both treatment groups. Conclusions Paroxetine 7.5 mg does not cause weight gain or negative changes in libido when used to treat menopause-associated VMS in postmenopausal women. PMID:24552977

Functional effects of chronic paroxetine versus placebo on the fear, stress and anxiety brain circuit in Social Anxiety Disorder: initial validation of an imaging protocol for drug discovery.

PubMed

Giménez, Mónica; Ortiz, Hector; Soriano-Mas, Carles; López-Solà, Marina; Farré, Magí; Deus, Joan; Martín-Santos, Rocio; Fernandes, Sofia; Fina, Paolo; Bani, Massimo; Zancan, Stefano; Pujol, Jesús; Merlo-Pich, Emilio

2014-01-01

Recent studies suggest that pharmacologic effects of anxiolytic agents can be mapped as functional changes in the fear, stress and anxiety brain circuit. In this work we investigated the effects of a standard treatment, paroxetine (20mg/day), in subjects with Social Anxiety Disorder (SAD) versus placebo using different fMRI paradigms. The fMRI sessions, performed before and after the treatment, consisted of a public exposition of recorded performance task (PERPT), an emotional face processing task (EFPT) and a 6-min resting state followed by an off-scanner public speaking test. Paroxetine significantly improved the clinical conditions of SAD patients (n=17) vs. placebo (n=16) as measured with Clinical Global Inventory - Improvement (CGI-I) while no change was seen when using Liebowitz Social Anxiety Scale, as expected given the small size of the study population. Paroxetine reduced the activation of insula, thalamus and subgenual/anterior cingulate cortex (ACC) in PERPT. Resting-state fMRI assessment using Independent Component Analysis indicated that paroxetine reduced functional connectivity in insula, thalamus and ACC when compared with placebo. Both paradigms showed significant correlation with CGI-I in rostral prefrontal cortex. Conversely, paroxetine compared to placebo produced activation of right amygdala and bilateral insula and no effects in ACC when tested with EFPT. No treatment effects on distress scores were observed in the off-scanner Public Speaking Test. Overall this study supports the use of fMRI as sensitive approach to explore the neurobiological substrate of the effects of pharmacologic treatments and, in particular, of resting state fMRI given its simplicity and task independence. © 2013 Elsevier B.V. and ECNP. All rights reserved.

[A five-year-old girl with epilepsy showing forced normalization due to zonisamide].

PubMed

Hirose, Mieko; Yokoyama, Hiroyuki; Haginoya, Kazuhiro; Iinuma, Kazuie

2003-05-01

A case of forced normalization in childhood is presented. When zonisamide was administered to a five-year-old girl with intractable epilepsy, disappearance of seizures was accompanied by severe psychotic episodes such as communication disturbance, personal relationship failure, and stereotyped behavior, which continued after the withdrawal of zonisamide. These symptoms gradually improved by administration of fluvoxamine, however epileptic attacks reappeared. Although most patients with forced normalization are adult and teenager, attention should be paid to this phenomenon as adverse psychotic effects of zonisamide even in young children. Fluvoxamine may be effective for the symptoms.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, D.R.; Palmer, K.J.; Johnson, A.M.

The effects of prolonged oral administration of the antidepressants paroxetine and amitriptyline on rat brain cortical {beta}{sub 1}- and {beta}{sub 2}-adrenoceptor numbers and affinities were investigated using ({sup 3}H)-CGP 12177. Although amitriptyline, 27 mg/kg, caused a significant 20% reduction in the number of {beta}{sub 1}-adrenoceptors, paroxetine, at does up to 8.9 mg/kg p.o., did not influence binding of ({sup 3}H)-CGP 12177 to cortical {beta}{sub 1}- or {beta}{sub 2}-adrenoceptors. This study with paroxetine provides further evidence that the down-regulation of central {beta}{sub 1}-adrenoceptors in rat brain after repeated administration is not a property of all antidepressant drugs.

A comparative trial of psychotherapy and pharmacotherapy for "pure" dysthymic patients.

PubMed

Markowitz, John C; Kocsis, James H; Bleiberg, Kathryn L; Christos, Paul J; Sacks, Michael

2005-12-01

Psychotherapy of "pure" dysthymic disorder remains understudied. This article reports outcomes of an acute randomized trial of 94 subjects treated for 16 weeks with either interpersonal psychotherapy (IPT), brief supportive psychotherapy (BSP), sertraline, or sertraline plus IPT. Recruited by clinical referral and advertising, subjects met DSM-IV criteria for early onset dysthymic disorder, with no episode of major depression in the prior six months. They were randomly assigned to one of four 16-week treatments, with options for crossover or continuation treatment. Results were analyzed from the intention-to-treat sample by ANCOVA, controlling for baseline depressive severity. Subjects improved in all conditions over time, with the cells including sertraline pharmacotherapy showing superiority over psychotherapy alone for response and remission. Response rates were 58% for sertraline alone, 57% for combined treatment, 35% for IPT, and 31% for BSP. The study was underpowered and may have employed too "active" a control condition. Follow-up data were unobtainable. In this acute trial for "pure" dysthymic disorder, sertraline with or without IPT showed advantages relative to IPT and BSP. Methodological difficulties may have limited differential outcome findings. This study bolsters a small but growing literature on the treatment of dysthymic disorder, suggesting that pharmacotherapy may acutely benefit patients more than psychotherapy.

Comparative efficacy and acceptability of pharmacological treatments for post-traumatic stress disorder in adults: a network meta-analysis.

PubMed

Cipriani, Andrea; Williams, Taryn; Nikolakopoulou, Adriani; Salanti, Georgia; Chaimani, Anna; Ipser, Jonathan; Cowen, Phil J; Geddes, John R; Stein, Dan J

2017-12-19

Guidelines about post-traumatic stress disorder (PTSD) recommend broad categories of drugs, but uncertainty remains about what pharmacological treatment to select among all available compounds. Cochrane Central Register of Controlled Trials register, MEDLINE, PsycINFO, National PTSD Center Pilots database, PubMed, trial registries, and databases of pharmaceutical companies were searched until February 2016 for double-blind randomised trials comparing any pharmacological intervention or placebo as oral therapy in adults with PTSD. Initially, we performed standard pairwise meta-analyses using a random effects model. We then carried out a network meta-analysis. The main outcome measures were mean change on a standardised scale and all-cause dropout rate. Acute treatment was defined as 8-week follow up. Desipramine, fluoxetine, paroxetine, phenelzine, risperidone, sertraline, and venlafaxine were more effective than placebo; phenelzine was better than many other active treatments and was the only drug, which was significantly better than placebo in terms of dropouts (odds ratio 7.50, 95% CI 1.72-32.80). Mirtazapine yielded a relatively high rank for efficacy, but the respective value for acceptability was not among the best treatments. Divalproex had overall the worst ranking. The efficacy and acceptability hierarchies generated by our study were robust against many sources of bias. The differences between drugs and placebo were small, with the only exception of phenelzine. Considering the small amount of available data, these results are probably not robust enough to suggest phenelzine as a drug of choice. However, findings from this review reinforce the idea that phenelzine should be prioritised in future trials in PTSD.

Guidelines on treatment of perinatal depression with antidepressants: An international review

PubMed Central

Kamperman, Astrid M; Boyce, Philip; Bergink, Veerle

2018-01-01

Objective: Several countries have developed Clinical Practice Guidelines regarding treatment of perinatal depressive symptoms and perinatal use of antidepressant. We aimed to compare guidelines to guide clinicians in best clinical practice. Methods: An extensive search in guideline databases, MEDLINE and PsycINFO was performed. When no guidelines were (publicly) available online, we contacted psychiatric-, obstetric-, perinatal- and mood disorder societies of all first world countries and the five largest second world countries. Only Clinical Practice Guidelines adhering to quality criteria of the Appraisal of Guidelines for Research and Evaluation instrument and including a systematic review of evidence were included. Data extraction focussed on recommendations regarding continuation or withdrawal of antidepressants and preferred treatment in newly depressed patients. Results: Our initial search resulted in 1094 articles. After first screening, 40 full-text articles were screened. Of these, 24 were excluded for not being an official Clinical Practice Guidelines. In total, 16 Clinical Practice Guidelines were included originating from 12 countries. Eight guidelines were perinatal specific and eight were general guidelines. Conclusion: During pregnancy, four guidelines advise to continue antidepressants, while there is a lack of evidence supporting this recommendation. Five guidelines do not specifically advise or discourage continuation. For new episodes, guidelines agree on psychotherapy (especially cognitive behavioural therapy) as initial treatment for mild to moderate depression and antidepressants for severe depression, with a preference for sertraline. Paroxetine is not preferred treatment for new episodes but switching antidepressants for ongoing treatment is discouraged (three guidelines). If mothers use antidepressants, observation of the neonate is generally recommended and breastfeeding encouraged. PMID:29506399

Guidelines on treatment of perinatal depression with antidepressants: An international review.

PubMed

Molenaar, Nina M; Kamperman, Astrid M; Boyce, Philip; Bergink, Veerle

2018-04-01

Several countries have developed Clinical Practice Guidelines regarding treatment of perinatal depressive symptoms and perinatal use of antidepressant. We aimed to compare guidelines to guide clinicians in best clinical practice. An extensive search in guideline databases, MEDLINE and PsycINFO was performed. When no guidelines were (publicly) available online, we contacted psychiatric-, obstetric-, perinatal- and mood disorder societies of all first world countries and the five largest second world countries. Only Clinical Practice Guidelines adhering to quality criteria of the Appraisal of Guidelines for Research and Evaluation instrument and including a systematic review of evidence were included. Data extraction focussed on recommendations regarding continuation or withdrawal of antidepressants and preferred treatment in newly depressed patients. Our initial search resulted in 1094 articles. After first screening, 40 full-text articles were screened. Of these, 24 were excluded for not being an official Clinical Practice Guidelines. In total, 16 Clinical Practice Guidelines were included originating from 12 countries. Eight guidelines were perinatal specific and eight were general guidelines. During pregnancy, four guidelines advise to continue antidepressants, while there is a lack of evidence supporting this recommendation. Five guidelines do not specifically advise or discourage continuation. For new episodes, guidelines agree on psychotherapy (especially cognitive behavioural therapy) as initial treatment for mild to moderate depression and antidepressants for severe depression, with a preference for sertraline. Paroxetine is not preferred treatment for new episodes but switching antidepressants for ongoing treatment is discouraged (three guidelines). If mothers use antidepressants, observation of the neonate is generally recommended and breastfeeding encouraged.

A Pilot Study: Cardiac Parameters in Children Receiving New-Generation Antidepressants.

PubMed

Uchida, Mai; Spencer, Andrea E; Kenworthy, Tara; Chan, James; Fitzgerald, Maura; Rosales, Ana Maria; Kagan, Elana; Saunders, Alexandra; Biederman, Joseph

2017-06-01

Because of concerns about potential associations between high doses of citalopram and QTc prolongation in adults, this study examined whether such associations are operant in children. We hypothesized that therapeutic doses of nontricyclic antidepressant medications (non-TCAs) prescribed to children would be cardiovascularly safe. The sample consisted of 49 psychiatrically referred children and adolescents 6 to 17 years old of both sexes treated with a non-TCA (citalopram, escitalopram, fluoxetine, paroxetine, sertraline, bupropion, duloxetine, venlafaxine, mirtazapine). To standardize the doses of different antidepressants, we converted doses of individual medicines into "citalopram equivalent doses" (CEDs) based on dosing recommendation for individual antidepressants. Correlation analysis was carried out to compare the continuous and weight-based CED to variables of interest. A QTc grouping was defined as normal, borderline, or abnormal, and CED was compared across QTc groupings using linear regression. An antidepressant dosage group was defined as low or high dose, and a t test compared variables of interest across dosage groups. No significant associations were found between total or weight-corrected CEDs of any antidepressant examined and QTc or any other electrocardiogram or blood pressure parameters. In patients taking citalopram or escitalopram, a significant correlation was found between PR interval and total daily dose, which disappeared when weight-based doses were used or when corrected by age. Although limited by a relatively small sample size, these results suggest that therapeutic doses of non-TCA antidepressants when used in children do not seem to be associated with prolonged QTc interval or other adverse cardiovascular effects.

The Efficacy and Safety of On-demand Tramadol and Paroxetine Use in Treatment of Life Long Premature Ejaculation: A Randomized Double-blind Placebo-controlled Clinical Trial

PubMed Central

Hamidi-Madani, Ali; Motiee, Reza; Mokhtari, Gholamreza; Nasseh, Hamidreza; Esmaeili, Samaneh; Kazemnezhad, Ehsan

2018-01-01

Background: Several medical therapies have been proposed for the treatment of premature ejaculation (PE). Paroxetine and tramadol were both reported to be effective in treatment of PE. In this study, the therapeutic effects of tramadol, paroxetine and placebo were compared in treatment of primary PE. Methods: In this randomized, double-blind, placebo-controlled clinical trial, 150 patients were divided into 3 groups. One group was treated with tramadol 50 mg ondemand, the other group took paroxetine 20 mg on-demand and the third group was treated with placebo. Before starting treatment and after 12 weeks, patients were asked to measure their average intravaginal ejaculation latency time (IELT) and fill the PEP (Premature Ejaculation Profile) questionnaire. Results: At the end of the 12th week, the mean IELT and average of PEP scores improved in all 3 groups. The increase in tramadol group was significantly higher than the paroxetine and placebo groups (p<0.0001). There were no significant differences in terms of side effects between the 3 groups. Conclusion: The results showed that despite an increase in mean IELT and PEP scores in all 3 groups, the rate of improvement in tramadol group was significantly more than the others. Thus, tramadol may be considered as an appropriate alternative therapeutic option for lifelong PE. PMID:29850442

Aging, estradiol and time of day differentially affect serotonin transporter binding in the central nervous system of female rats.

PubMed

Krajnak, Kristine; Rosewell, Katherine L; Duncan, Marilyn J; Wise, Phyllis M

2003-11-14

Estrogen-related changes in serotonergic neuronal transmission, including changes in the number of serotonin transporter (SERT) binding sites, have been cited as a possible cause for changes in mood, memory and sleep that occur during the menopausal transition. However, both aging and estradiol regulate SERT binding sites in the brain. The goal of this experiment was to determine how aging and estrogen interact to regulate SERT levels in the forebrain of young and reproductively senescent female Sprague-Dawley rats using [3H]paroxetine. The density of specific [3H]paroxetine binding in various brain regions was compared in young (2-4 months) and reproductively senescent (10-12 months) female rats at three times of day. In most brain regions examined, estrogen and aging independently increased the number of [3H]paroxetine binding sites. The only region that displayed a reduction in [3H]paroxetine binding with age was the suprachiasmatic nucleus (SCN). Time of day influenced [3H]paroxetine binding in the SCN and the paraventricular thalamus (PVT), two regions known to be involved in the regulation of circadian rhythms. Aging and/or estrogen also altered the pattern of binding in these regions. Thus, based on the results of this study, we conclude that aging and estrogen both act to regulate SERT binding sites in the forebrain of female rats, and that this regulation is region specific.

The Efficacy and Safety of On-demand Tramadol and Paroxetine Use in Treatment of Life Long Premature Ejaculation: A Randomized Double-blind Placebo-controlled Clinical Trial.

PubMed

Hamidi-Madani, Ali; Motiee, Reza; Mokhtari, Gholamreza; Nasseh, Hamidreza; Esmaeili, Samaneh; Kazemnezhad, Ehsan

2018-01-01

Several medical therapies have been proposed for the treatment of premature ejaculation (PE). Paroxetine and tramadol were both reported to be effective in treatment of PE. In this study, the therapeutic effects of tramadol, paroxetine and placebo were compared in treatment of primary PE. In this randomized, double-blind, placebo-controlled clinical trial, 150 patients were divided into 3 groups. One group was treated with tramadol 50 mg ondemand, the other group took paroxetine 20 mg on-demand and the third group was treated with placebo. Before starting treatment and after 12 weeks, patients were asked to measure their average intravaginal ejaculation latency time (IELT) and fill the PEP (Premature Ejaculation Profile) questionnaire. At the end of the 12th week, the mean IELT and average of PEP scores improved in all 3 groups. The increase in tramadol group was significantly higher than the paroxetine and placebo groups (p<0.0001). There were no significant differences in terms of side effects between the 3 groups. The results showed that despite an increase in mean IELT and PEP scores in all 3 groups, the rate of improvement in tramadol group was significantly more than the others. Thus, tramadol may be considered as an appropriate alternative therapeutic option for lifelong PE.

Benefit of slow titration of paroxetine to treat depression in the elderly.

PubMed

Olgiati, Paolo; Bajo, Emanuele; Serretti, Alessandro

2014-11-01

Paroxetine is commonly used to treat depression in the elderly; however, titration issues have been raised. Rapid titration may lead to increased anxiety and early dropout. The aim of this cost-utility analysis was to compare the potential benefit of standard (10 mg the first day) versus slow titration (2.5 mg gradually increased). Clinical analysis was based on a naturalistic trial integrated with a decision-analytic model representing second treatments for those who initially did not respond and for dropout cases. Treatment setting was a public outpatient center for mental disorders in Italy. Service use data were estimated from best practice guidelines, whereas costs (Euros; 2012) were retrieved from Italian official sources. Slow titration approach produced 0.031 more quality-adjusted life years (remission rate: 57% vs 44% in standard titration group) at an incremental cost of €5.53 (generic paroxetine) and €54.54 (brand paroxetine syrup). Incremental cost-effectiveness ratio (ICER) values were €159 and €1768, respectively, in favor of slow titration approach. Cost-effectiveness threshold, defined as ICER < 1 GDP per capita according to World Health Organization criteria, is about €25 000 in Italy. Our results are consistent with a superiority of slow titration of paroxetine in older depressed patients. However, these findings, in part based on simulated data, need to be replicated in clinical trials. Copyright © 2014 John Wiley & Sons, Ltd.

The effects of tianeptine or paroxetine on 35% CO2 provoked panic in panic disorder.

PubMed

Schruers, Koen; Griez, Eric

2004-12-01

Antidepressants that inhibit the reuptake of serotonin (5-HT) are particularly effective in the treatment of panic disorder. Evidence suggests that increased 5-HT availability is important for the anti-panic effect of serotonergic drugs and in maintaining the response to selective serotonin reuptake inhibitors (SSRIs). Tianeptine is an antidepressant with 5-HT reuptake enhancing properties (i.e. the opposite pharmacological profile to that of SSRIs). Therefore, no effect would be expected in panic disorder. The aim of the present study was to compare the effect of tianeptine with that of paroxetine, a selective 5-HT reuptake inhibitor with demonstrated efficacy in panic disorder, on the vulnerability to a laboratory panic challenge in panic disorder patients. Twenty panic disorder patients were treated with either tianeptine or paroxetine for a period of 6 weeks, in a randomized, double-blind, separate group design. The reaction to a 35% CO(2) panic challenge was assessed at baseline and after treatment. Improvement on several clinical scales was also monitored. Tianeptine, as well as paroxetine, showed a significant reduction in vulnerability to the 35% CO(2) panic challenge. In spite of their opposite influence on 5-HT uptake, both tianeptine and paroxetine appeared to reduce the reaction to the panic challenge. These results raise questions about the necessity of 5-HT uptake for the therapeutic efficacy of anti-panic drugs.

Clinical Subtypes of Premenstrual Syndrome and Responses to Sertraline Treatment

PubMed Central

Freeman, Ellen W.; Sammel, Mary D.; Lin, Hui; Rickels, Karl; Sondheimer, Steven J.

2011-01-01

OBJECTIVE To estimate response of diagnosis and symptom-based subtypes to sertraline treatment. METHODS This was a secondary data analysis for women who were diagnosed with premenstrual syndrome (PMS) or premenstrual dysphoric disorder and treated in three National Institutes of Health-supported clinical trials (N=447). Three PMS subtypes were identified based on predominance of psychological, physical, or both symptom types. Scores for each symptom and a total premenstrual score at baseline and endpoint were calculated from daily symptom diaries. Change from baseline after three treated menstrual cycles (or endpoint if sooner) was estimated using linear regression models adjusted for baseline severity. RESULTS The PMS and premenstrual dysphoric disorder diagnoses improved similarly with sertraline relative to placebo, while symptom-based subtypes had differential responses to treatment. The mixed symptom subtype had the strongest response to sertraline relative to placebo (Daily Symptom Rating [DSR] difference 33.80, 95% CI: 17.16, 50.44, P<0.001), and the physical symptom subtype had the poorest response to sertraline (DSR difference 9.50, 95% CI: −16.29, 35.28, P=0.470). Results based on clinical improvement (50% decrease from baseline) indicated that 8.3 participants in the mixed symptom subtype, 3.9 in the psychological subtype, and 7.1 in the physical subtype are needed to observe one woman in the subtype who would achieve clinical improvement. CONCLUSION The PMS and premenstrual dysphoric disorder diagnoses have similar response to sertraline treatment, but symptom-based subtypes have significantly different responses to this treatment. Mixed and psychological symptom subtypes improved while the physical symptom subtype did not improve significantly. Identifying the patient’s predominant symptoms, and their severity is important for individualized treatment and possible response to a selective serotonin reuptake inhibitor. PMID:22105258

Myxedema coma associated with combination aripiprazole and sertraline therapy.

PubMed

Church, Chelsea O; Callen, Erin C

2009-12-01

To describe a case of myxedema coma (MC) associated with combination aripiprazole and sertraline therapy. A 41-year-old male presented to the emergency department with confusion, right-sided numbness and tingling, slurred speech, dizziness, and facial edema. His blood pressure was 160/113 mm Hg, with a pulse of 56 beats/min and temperature of 35.4 degrees C. Initial abnormal laboratory values included creatine kinase (CK) 439 U/L; serum creatinine 1.6 mg/dL; aspartate aminotransferase 85 U/L; and alanine aminotransferase 35 U/L. Repeat cardiac markers revealed an elevated CK level of 3573 U/L with a CK-MB of 24 ng/mL. Thyroid function tests showed thyroid-stimulating hormone 126.4 microIU/mL and free thyroxine 0.29 ng/dL. Home medications of unknown duration were sertraline 200 mg and aripiprazole 20 mg daily. He was admitted to the intensive care unit and initially treated with intravenous levothyroxine and dexamethasone. By hospital day 4, the patient was clinically stable and discharged to home. Myxedema coma, the most significant form of hypothyroidism (HT), is a rare but potentially fatal condition. The known precipitating causes of MC were ruled out in this patient, which left his home medications as the likely cause. Cases of HT caused by certain atypical antipsychotics and antidepressants are found in the literature, but none was reported with aripiprazole therapy. There are also no reported cases of sertraline or aripiprazole inducing MC. Use of the Naranjo probability scale indicates that the combination of aripiprazole and sertraline was a probable inducer of MC in this patient. Due to the widespread use of psychotropic medications, clinicians should be reminded of the rare, yet life-threatening, occurrence of MC when treating patients, especially with combination therapies such as sertraline and aripiprazole.

Possibility of Database Research as a Means of Pharmacovigilance in Japan Based on a Comparison with Sertraline Postmarketing Surveillance.

PubMed

Hirano, Yoko; Asami, Yuko; Kuribayashi, Kazuhiko; Kitazaki, Shigeru; Yamamoto, Yuji; Fujimoto, Yoko

2018-05-01

Many pharmacoepidemiologic studies using large-scale databases have recently been utilized to evaluate the safety and effectiveness of drugs in Western countries. In Japan, however, conventional methodology has been applied to postmarketing surveillance (PMS) to collect safety and effectiveness information on new drugs to meet regulatory requirements. Conventional PMS entails enormous costs and resources despite being an uncontrolled observational study method. This study is aimed at examining the possibility of database research as a more efficient pharmacovigilance approach by comparing a health care claims database and PMS with regard to the characteristics and safety profiles of sertraline-prescribed patients. The characteristics of sertraline-prescribed patients recorded in a large-scale Japanese health insurance claims database developed by MinaCare Co. Ltd. were scanned and compared with the PMS results. We also explored the possibility of detecting signals indicative of adverse reactions based on the claims database by using sequence symmetry analysis. Diabetes mellitus, hyperlipidemia, and hyperthyroidism served as exploratory events, and their detection criteria for the claims database were reported by the Pharmaceuticals and Medical Devices Agency in Japan. Most of the characteristics of sertraline-prescribed patients in the claims database did not differ markedly from those in the PMS. There was no tendency for higher risks of the exploratory events after exposure to sertraline, and this was consistent with sertraline's known safety profile. Our results support the concept of using database research as a cost-effective pharmacovigilance tool that is free of selection bias . Further investigation using database research is required to confirm our preliminary observations. Copyright © 2018. Published by Elsevier Inc.

Joint effects of salinity and the antidepressant sertraline on the estuarine decapod Carcinus maenas.

PubMed

Rodrigues, Aurélie P; Santos, Lúcia H M L M; Oliva-Teles, Maria Teresa; Delerue-Matos, Cristina; Guimarães, Laura

2014-11-01

Concurrent exposure of estuarine organisms to man-made and natural stressors has become a common occurrence. Numerous interactions of multiple stressors causing synergistic or antagonistic effects have been described. However, limited information is available on combined effects of emerging pharmaceuticals and natural stressors. This study investigated the joint effects of the antidepressant sertraline and salinity on Carcinus maenas. To improve knowledge about interactive effects and potential vulnerability, experiments were performed with organisms from two estuaries with differing histories of exposure to environmental contamination. Biomarkers related to mode of action of sertraline were employed to assess effects of environmentally realistic concentrations of sertraline at two salinity levels. Synergism and antagonism were identified for biomarkers of cholinergic neurotransmission, energy production, anti-oxidant defences and oxidative damage. Different interactions were found for the two study sites highlighting the need to account for differences in tolerance of local ecological receptors in risk evaluations. Copyright © 2014 Elsevier B.V. All rights reserved.

Bupropion versus sertraline in the treatment of depressive patients with binge eating disorder: retrospective cohort study.

PubMed

Calandra, Carmela; Russo, Rina Giuseppa; Luca, Maria

2012-06-01

This study sought to compare Bupropion versus Sertraline in the treatment of depressed patients with Binge Eating Disorder (BED) prescribed off-label. Medical records of outpatients with diagnosis of BED and Depression (DSM-IV-TR criteria) were selected: 15 patients were treated with bupropion 150 mg/per day, and 15 with sertraline 200 mg/per day. During the screening and control visits (2°-6°-14°-24° week), the selected patients were first weighed and then evaluated using the following questionnaires: Binge Eating Disorder-Clinical Interview (BEDCI), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory X (STAI-X) and Arizona Sexual Experience Scale (ASEX). Both drugs reduced anxious-depressive symptoms and binge frequency: Bupropion showed a better effectiveness in reducing weight and improving sexual performances; weight loss related to it was proportional to the body mass index. Bupropion may be associated with more weight loss in BED, depressed patients than sertraline.

Salt Stability - The Effect of pHmax on Salt to Free Base Conversion.

PubMed

Hsieh, Yi-Ling; Merritt, Jeremy M; Yu, Weili; Taylor, Lynne S

2015-09-01

The aim of this study was to investigate how the disproportionation process can be impacted by the properties of the salt, specifically pHmax. Five miconazole salts and four sertraline salts were selected for this study. The extent of conversion was quantified using Raman spectroscopy. A mathematical model was utilized to estimate the theoretical amount of conversion. A trend was observed that for a given series of salts of a particular basic compound (both sertraline and miconazole are bases), the extent of disproportionation increases as pHmax decreases. Miconazole phosphate monohydrate and sertraline mesylate, although exhibiting significantly different pHmax values (more than 2 units apart), underwent a similar extent of disproportionation, which may be attributed to the lower buffering capacity of sertraline salts. This work shows that the disproportionation tendency can be influenced by pHmax and buffering capacity and thus highlights the importance of selecting the appropriate salt form during the screening process in order to avoid salt-to-free form conversion.

Faster onset of antidepressant effects of citalopram compared with sertraline in drug-naïve first-episode major depressive disorder in a Chinese population: a 6-week double-blind, randomized comparative study.

PubMed

Hsu, Ju-Wei; Su, Tung-Ping; Huang, Chen-Ying; Chen, Ying-Sheue; Chou, Yuan-Hwa

2011-10-01

Several previous studies, including a meta-analysis, reported no significant differences between various selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder. However, because of the different chemical structure of SSRIs and the difference in the frequency of serotonin transporter polymorphisms between ethnic groups, a head-to-head comparative study between SSRIs in different populations may be enlightening. We compared the efficacy and adverse effect profiles of citalopram and sertraline in a double-blinded randomized clinical trial in a Chinese population of drug-naïve patients with first-episode major depressive disorder. Fifty-one patients were randomly assigned to citalopram or sertraline treatment. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary outcome. Efficacy and adverse effects were analyzed in an intent-to-treat population. Efficacy was analyzed using a last-observation-carried-forward method for early terminators. There were no significant differences in demographic characteristics at baseline. No significant differences were found in MADRS scores between citalopram and sertraline at baseline (36.6 ± 5.5 vs 38.2 ± 4.9; P = 0.322) or at the end of treatment (week 6; 10.8 ± 10.0 vs 16.7 ± 11.3; P = 0.082). However, MADRS scores in the citalopram group were significantly lower at week 1 (25.2 ± 8.5 vs 30.4 ± 6.1; P = 0.029) and week 3 (15.9 ± 10.0 vs 22.1 ± 8.7; P = 0.037). Overall, treatment-emergent adverse effects were reported by 14.3% and 28.6% of patients in the citalopram and sertraline groups, respectively. In conclusion, citalopram and sertraline were both efficacious and well tolerated. However, citalopram exhibited a significantly faster onset than sertraline during the early weeks of treatment and tended to have a better efficacy in overall treatment, although the statistic was not significant.

Sertraline alleviated osmophobia caused by partial hypopituitarism with isolated ACTH deficiency.

PubMed

Kuo, Yu-Heng; Chang, Yun; Chen, Hsi-Chung; Liao, Shih-Cheng

2013-01-01

Hyperosmia may be an early manifestation of hypocortisolism and may be mistakenly diagnosed as osmophobia. However, sertraline therapy incidentally alleviated the phobic symptoms and hindered accurate diagnosis. A 41-year-old man was diagnosed as having osmophobia. Initial sertraline treatment relieved the symptoms, but its cessation resulted in recurrence of osmophobia. Endocrinological examinations revealed severe hypocortisolism and partial hypopituitarism with isolated adrenocorticotropic hormone deficiency. After prednisolone supplementation, his condition dramatically improved. We recommend that, before intervention with selective serotonin reuptake inhibitors is performed, the hypothalamic-pituitary-adrenal axis be evaluated in psychiatric patients presenting with co-occurring olfactory change. Copyright © 2013 Elsevier Inc. All rights reserved.

[Rhabdomyolysis after lifting IKEA bags in a man using sertraline].

PubMed

Kummen, Ingvild; Jensen, Thomas Giver

2016-12-12

We present a case of a 28-year-old male, using sertraline, who experienced progressive oedema in both upper extremities after having lifted two IKEA bags weighing 20 kg each from his car up to the third floor. Blood creatine kinase (CK) level was measured 5,260 U/l, and the patient was admitted for oral rehydration with the diagnosis rhabdomyolysis. The MRI showed swelling in the triceps muscles and latissimus dorsi muscles resulting in compression of the brachial vein. We discuss the pathomechanism behind the increased CK level and the swelling, and the possible effect sertraline may have had on the development of rhabdomyolysis.

Safety and efficacy of vardenafil versus sertraline in the treatment of premature ejaculation: a randomised, prospective and crossover study.

PubMed

Mathers, M J; Klotz, T; Roth, S; Lümmen, G; Sommer, F

2009-06-01

We investigated safety and efficacy of vardenafil and sertraline in premature ejaculation (PE). Seventy-two men graded their primary PE on a scale of 0-8 (0 = almost never, 8 = almost always). Intravaginal ejaculatory latency time (IELT) was measured. Patients were included if they scored their PE as 4 or greater and their IELTs were less than 1.30 min. After 6 weeks of behavioural psychosexual therapy, 49 patients still had a PE of 4 or greater and an IELT less than 1.30 min and they were randomised: 6 weeks vardenafil (10 mg) or sertraline (50 mg). After a wash-out phase for 1 week, medication was changed in a cross-over design. Initially, all 72 men with PE received behavioural therapy. Twenty-three men were satisfied with treatment and excluded. The remaining 49 men graded their PE as 5.94 +/- 1.6 and IELT was 0.59 min and patients were randomised. Four men discontinued the study. Vardenafil improved PE grading: 2.7 +/- 2.1 (P < 0.01) and IELT increased to 5.01 +/- 3.69 (P < 0.001). PE grading improved 1.92 +/- 1.32, (P < 0.01) and IELT 3.12 +/- 1.89 (P < 0.001) with sertraline. It is concluded that vardenafil and sertraline are useful agents in the pharmacological treatment of PE.

Sertraline inhibits increases in body fat and carbohydrate dysregulation in adult female cynomolgus monkeys

PubMed Central

Silverstein-Metzler, Marnie G.; Shively, Carol A.; Clarkson, Thomas B.; Appt, Susan E.; Carr, J.Jeffrey; Kritchevsky, Stephen B.; Jones, Sara R.; Register, Thomas C.

2017-01-01

Selective serotonin reuptake inhibitor (SSRI) antidepressants are widely prescribed for depression and other disorders. SSRIs have become one of the most commonly used drugs in the United States, particularly by women. Acute effects on body composition and carbohydrate metabolism have been reported, but little is known regarding the effects of chronic SSRI use. We evaluated the effects of chronic administration of a commonly prescribed SSRI, sertraline HCl, on body weight and composition, fat distribution, carbohydrate metabolism, as well as activity, in adult female depressed and nondepressed cynomolgus monkeys (Macaca fascicularis; n = 42) using a placebo-controlled, longitudinal, randomized study design. Phenotypes were evaluated prior to and after 18 months of oral sertraline (20 mg/kg) or placebo. Over the 18 month treatment period, the placebo group experienced increases in body weight, body fat (visceral and subcutaneous) fasting insulin concentrations, and homeostasis model assessment of insulin resistance scores (HOMA-IR). Sertraline treatment prevented increases in body weight, fat, insulin, and HOMA-IR (all p < 0.05), without significantly altering activity levels. Sertraline treatment altered adiponectin in an unusual way — reducing circulating adiponectin in depressed monkeys without affecting fat mass or body weight. Deleterious effects on adiponectin, a potentially insulin-sensitizing and atheroprotective protein, may result in adverse effects on cardiovascular health despite otherwise beneficial effects on body composition and carbohydrate metabolism. PMID:26939086

Segmental hair testing to disclose chronic exposure to psychoactive drugs.

PubMed

Marchei, Emilia; Palmi, Ilaria; Pichini, Simona; Pacifici, Roberta; Anton Airaldi, Ileana-Rita; Costa Orvay, Juan Antonio; García Serra, Joan; Bonet Serra, Bartolomé; García-Algar, Óscar

2016-06-15

This study presents the case of a 4-year-old healthy child admitted to the paediatric ward for suspected accidental intoxication due to ingestion of narcoleptic drugs (methylphenidate, sertraline and quetiapine), taken on a regular basis by his 8-year-old brother affected by Asperger syndrome.Intoxication can be objectively assessed by measurements of drugs and metabolites in biological matrices with short-term (blood and urine) or long-term (hair) detection windows. At the hospital, the child's blood and urine were analysed by immunoassay (confirmed by liquid chromatography-mass spectrometry), and sertraline and quetiapine and their metabolites were identified. The suspicion that the mother administered drugs chronically prompted the analysis of six, consecutive 2-cm segments of the child's hair, using ultra-high performance liquid chromatography-tandem mass spectrometry, thereby accounting for ingestion over the previous 12 months. Quetiapine was found in the first four segments with a mean concentration of 1.00 ng/mg ± 0.94 ng/mg hair while sertraline and its metabolite, desmethyl-sertraline, were found in all segments with a mean concentration of 2.65 ± 0.94 ng/mg and 1.50 ± 0.94 ng/mg hair, respectively. Hair analyses were negative for methylphenidate and its metabolite (ritalinic acid). Biological matrices testing for psychoactive drugs disclosed both acute and chronic intoxication with quetiapine and sertraline administered by the mother.

A Novel Liquid-Liquid Extraction for the Determination of Sertraline in Tap Water and Waste Water at Trace Levels by GC-MS.

PubMed

Koçoğlu, Elif Seda; Bakırdere, Sezgin; Keyf, Seyfullah

2017-09-01

A simple, green and fast analytical method was developed for the determination of sertraline in tap and waste water samples at trace levels by using supportive liquid-liquid extraction with gas chromatography-mass spectrometry. Different parameters affecting extraction efficiency such as types and volumes of extraction and supporter solvents, extraction period, salt type and amount were optimized to get lower detection limits. Ethyl acetate was selected as optimum extraction solvent. In order to improve the precision, anthracene-D10 was used as an internal standard. The calibration plot of sertraline was linear from 1.0 to 1000 ng/mL with a correlation coefficient of 0.999. The limit of detection value under the optimum conditions was found to be 0.43 ng/mL. In real sample measurements, spiking experiments were performed to check the reliability of the method for these matrices. The spiking experiments yielded satisfactory recoveries of 91.19 ± 2.48%, 90.48 ± 5.19% and 95.46 ± 6.56% for 100, 250 and 500 ng/mL sertraline for tap water, and 85.80 ± 2.15% and 92.43 ± 4.02% for 250 and 500 ng/mL sertraline for waste water.

The MAOA T941G polymorphism and short-term treatment response to mirtazapine and paroxetine in major depression.

PubMed

Tadić, André; Müller, Matthias J; Rujescu, Dan; Kohnen, Ralf; Stassen, Hans H; Dahmen, Norbert; Szegedi, Armin

2007-04-05

This study investigated the possible association of the MAOA T941G gene variant with differential antidepressant response to mirtazapine and/or paroxetine in 102 patients with major depression (DSM-IV criteria) participating in a randomized double-blind controlled clinical trial. Female mirtazapine-treated patients homozygous for the T-allele had a significantly faster and better treatment response than TG/GG-patients. In males, we failed to show an association between MAOA T941G gene variant and mirtazapine response. In the paroxetine-treated group, there were no significant differences in treatment response between MAOA T941G genotype groups. Time course of response and antidepressant efficacy of mirtazapine, but not paroxetine, seem to be influenced in a clinically relevant manner by this allelic variation within the MAOA gene, at least in female patients. An independent replication of our finding is needed. If replicated, genotyping of this locus could become a promising tool to predict response to mirtazapine treatment in females suffering from major depression. (c) 2006 Wiley-Liss, Inc.

Sex differences in the prediction of the effectiveness of paroxetine for patients with major depressive disorder identified using a receiver operating characteristic curve analysis for early response.

PubMed

Tomita, Tetsu; Yasui-Furukori, Norio; Norio, Yasui-Furukori; Sato, Yasushi; Nakagami, Taku; Tsuchimine, Shoko; Kaneda, Ayako; Kaneko, Sunao

2014-01-01

We investigated cutoff values for the early response of patients with major depressive disorder to paroxetine and their sex differences by using a receiver operating characteristic (ROC) curve analysis to predict the effectiveness of paroxetine. In total, 120 patients with major depressive disorder were enrolled and treated with 10-40 mg/day paroxetine for 6 weeks; 89 patients completed the protocol. A clinical evaluation using the Montgomery-Asberg Depression Rating Scale (MADRS) was performed at weeks 0, 1, 2, 4, and 6. In male subjects, the cutoff values for MADRS improvement rating in week 1, week 2, and week 4 were 20.9%, 34.9%, and 33.3%, respectively. The sensitivities and the specificities were 83.3% and 80.0%, 83.3% and 80.0%, and 100% and 90%, respectively. The areas under the curve (AUC) were 0.908, 0.821, and 0.979, respectively. In female subjects, the cutoff values for the MADRS improvement rating in week 1, week 2, and week 4 were 21.4%, 35.7%, and 32.3%, respectively. The sensitivities and the specificities were 71.4% and 84.6%, 73.8% and 76.9%, and 90.5% and 76.9%, respectively. The AUCs were 0.781, 0.735, and 0.904, respectively. Early improvement with paroxetine may predict the long-term response. The accuracy of the prediction for the response is higher in male subjects.

A Comparison of Sexual Side Effects of Antidepressants With and Without Naltrexone.

PubMed

Thapa, Mona; Petrakis, Ismene; Ralevski, Elizabeth

2017-01-01

The aim of the study was to compare the rate of sexual side effects of the selective serotonin reuptake inhibitor paroxetine versus the tricyclic antidepressant desipramine and to examine the effect of co-prescription of naltrexone on sexual side effects among participants in a randomized clinical trial. This was a secondary analysis (N = 88) of veterans who participated in a 12-week trial. All veterans were randomized into one of four treatment groups: (a) desipramine/naltrexone, (b) desipramine/placebo, (c) paroxetine/naltrexone, and (d) paroxetine/placebo. The main outcome measure was the frequency of sexual side effects consisting of "decreased sex drive" and/or "impotence" reported by veterans at each weekly visit. Approximately 61% of the veterans reported sexual side effects at least once during the trial, and 26.4% reported sexual side effects throughout the study. There were no significant differences in the frequency of sexual side effects among the four treatment groups. The results were similar when the comparison was made between the two antidepressant groups. There were no significant differences in the reporting of sexual side effects between those receiving desipramine and paroxetine. Also, the comparison between naltrexone and placebo did not alter the results. This is the first study to compare frequency of sexual side effect reporting between paroxetine and desipramine. We found no statistically significant differences in sexual side effect reporting between the two antidepressants. Also, the addition of naltrexone did not show any beneficial effect on the sexual side effect profile.

Effect of Imipramine, Paroxetine, and Lithium Carbonate on Neurobehavioral Changes of Streptozotocin in Rats: Impact on Glycogen Synthase Kinase-3 and Blood Glucose Level.

PubMed

Nadeem, Rania I; Ahmed, Hebatalla I; El-Denshary, Ezz-El-Din S

2015-09-01

Recent studies have demonstrated a scrutinized association of diabetes mellitus with depressive symptoms and major depression. Glycogen synthase kinase-3 (GSK-3) is a protein kinase enzyme constitutively active in non-stimulated cells and in multiple signalings. Independent lines of research provide a converging evidence for an involvement of GSK-3 in the regulation of behavior and hyperglycemia. The present study revealed that streptozotocin (STZ)-induced diabetic rats were found to show lengthened duration of immobility in the forced-swimming test (FST) and reduced locomotor and exploratory activities in the open-field test (OFT). Imipramine (15 mg/kg), Paroxetine (10 mg/kg) and lithium carbonate (36.94 mg/kg) for 14 days reduced immobility behavior in FST. Paroxetine and lithium carbonate increased the locomotor and exploratory activities, while imipramine decreased the locomotor activity in the OFT. Imipramine and lithium carbonate reduced the blood glucose level while paroxetine didn't alter it. STZ-induced diabetes increased GSK-3 gene expression which was determined using the reverse transcription-quantitative polymerase chain reaction test, while the three drugs decreased its expression. It can be concluded that lithium carbonate and imipramine can control both hyperglycemia and the associated symptoms of depression at the same time by inhibiting GSK-3 activity. On the other hand, paroxetine may only manage the depressive-like symptoms associated with diabetes through modulating the enzyme GSK-3, without changing blood glucose levels.

Effects of combined administration of 5-HT1A and/or 5-HT1B receptor antagonists and paroxetine or fluoxetine in the forced swimming test in rats.

PubMed

Tatarczyńska, Ewa; Kłodzińska, Aleksandra; Chojnacka-Wójcik, Ewa

2002-01-01

Clinical data suggest that coadministration of pindolol, a 5-HT1A/5-HT1B/beta-adrenoceptor antagonist, and selective serotonin reuptake inhibitors (SSRIs) may shorten the time of onset of a clinical action and may increase beneficial effects of the therapy of drug-resistant depression. Effects of combined administration of SSRIs and 5-HT receptor ligands are currently evaluated in animal models for the detection of an antidepressant-like activity; however, the obtained results turned out to be inconsistent. The aim of the present study was to investigate effects of a 5-HT1A antagonist (WAY 100635), 5-HT1B antagonists (SB 216641 and GR 127935) or pindolol, given in combination with paroxetine or fluoxetine (SSRIs), in the forced swimming test in rats (Porsolt test). When given alone, paroxetine (10 and 20 mg/kg), fluoxetine (10 and 20 mg/kg), WAY 100635 (0.1 and 1 mg/kg), SB 216641 (2 mg/kg), GR 127935 (10 and 20 mg/kg) and pindolol (4 and 8 mg/kg) did not shorten the immobility time of rats in that test. Interestingly, SB 216641 administered alone at a dose of 4 mg/kg produced a significant reduction of the immobility time in that test. A combination of paroxetine (20 mg/kg) and WAY 100635 or pindolol failed to reveal a significant interaction; on the other hand, when paroxetine was given jointly with SB 216641 (2 mg/kg) or GR 127935 (10 and 20 mg/kg), that combination showed a significant antiimmobility action in the forced swimming test in rats. The active behaviors in that test did not reflect increased general activity because combined administration of both the 5-HT1B antagonists and paroxetine failed to alter the locomotor activity of rats, measured in the open field test. Coadministration of fluoxetine and all the antagonists used did not affect the behavior of rats in the forced swimming test. The obtained results seem to indicate that blockade of 5-HT1B receptors, but not 5-HT1A ones, can facilitate the antidepressant-like effect of paroxetine in the forced swimming test in rats. No interaction was observed between fluoxetine and 5-HT1A/5-HT1B receptor antagonists.

The Effects of Response Interruption and Redirection and Sertraline on Vocal Stereotypy

ERIC Educational Resources Information Center

Miguel, Caio F.; Clark, Kathy; Tereshko, Lisa; Ahearn, William H.

2009-01-01

Although response interruption and redirection (RIRD) has been shown to be successful in reducing vocal stereotypy, recent reports have suggested that selective serotonin reuptake inhibitors (SSRIs) may also reduce these behaviors. The purpose of the current investigation was to examine the effects of RIRD with and without sertraline on…

Treatment of premenstrual dysphoric disorder with luteal phase dosing of sertraline.

PubMed

Halbreich, Uriel; Kahn, Linda S

2003-11-01

Sertraline (Zoloft, Pfizer Inc.) is a selective serotonin re-uptake inhibitor (SSRI) which has been approved by the US FDA for the treatment of premenstrual dysphoric disorder (PMDD). PMDD is a severe form of premenstrual syndrome (PMS) which affects at least 5 - 8% of women of reproductive age. It is characterised by cyclic appearance at the late luteal phase of the menstrual cycle, and disappearance following the beginning of menses, with no symptoms during at least 1 week of the cycle - usually during the mid-follicular phase. Due to the cyclic luteal occurrence of PMDD, luteal phase dosing of SSRIs has been suggested and proven effective for sertraline as well as several other SSRIs. The clinical response of sertraline is reported to be within several days following initiation of treatment. Despite repeated cyclic discontinuation, no significant discontinuation adverse effects have been reported. In addition to its proven clinical efficacy, luteal-phase dosing may offer the advantages of minimising adverse effects of SSRIs while reducing the personal and economic burden of taking a prescription medication continuously for long periods and thus increasing compliance.

Chronic treatment with fluoxetine and sertraline prevents forced swimming test-induced hypercontractility of rat detrusor muscle.

PubMed

Bilge, Sirri; Bozkurt, Ayhan; Bas, Duygu B; Aksoz, Elif; Savli, Evren; Ilkaya, Fatih; Kesim, Yuksel

2008-01-01

Serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors represent important targets for the development of new treatments for detrusor overactivity and urinary incontinence. The present study was undertaken to investigate the effects of the forced swimming test (FST) on the contractile response of isolated rat detrusor muscle and to examine the effects of in vivo treatments of fluoxetine and sertraline on altered detrusor muscle contractility. Fluoxetine (20 mg/kg ip) and sertraline (10 mg/kg ip) were administered once a day for 14 days. Rats were exposed to the FST on the 15th day. After the test, detrusor muscles were removed and placed in organ baths, and the contraction responses induced by carbachol, potassium chloride (KCl) and electrical field stimulation (EFS) were recorded. The contractile responses of detrusor muscle strips to carbachol and electrical field stimulation were found to be increased at all carbachol doses and frequencies, respectively. FST also increased the contractile responses to KCl, which is used to test the differences in postreceptor-mediated contractions. The hypercontractile responses of detrusor strips to carbachol, EFS and KCl were abolished by treatment with both fluoxetine and sertraline. These treatments also decreased the immobility duration in the FST consistent with an antidepressant-like effect in this test. The results of this study provide the first evidence that FST increases contractility of the rat detrusor muscle, and this hypercontractility was abolished by chronic treatments of fluoxetine and sertraline at antidepressant doses by decreasing the postreceptor-mediated events.

Naltrexone Alone and With Sertraline for the Treatment of Alcohol Dependence in Alaska Natives and Non-Natives Residing in Rural Settings: A Randomized Controlled Trial

PubMed Central

O’Malley, Stephanie S.; Robin, Robert W.; Levenson, Aryeh L.; GreyWolf, Iva; Chance, Lawrence E.; Hodgkinson, Colin A.; Romano, Denise; Robinson, Jane; Meandzija, Boris; Stillner, Verner; Wu, Ran; Goldman, David

2009-01-01

Background Access to specialty alcoholism treatment in rural environments is limited and new treatment approaches are needed. The objective was to evaluate the efficacy of naltrexone alone and in combination with sertraline among Alaska Natives and other Alaskans living in rural settings. An exploratory aim examined whether the Asn40Asp polymorphism of the μ-opioid receptor gene (OPRMI) predicted response to naltrexone, as had been reported in Caucasians. Methods Randomized, controlled trial enrolling 101 Alaskans with alcohol dependence, including 68 American Indians/Alaska Natives. Participants received 16 weeks of either (1) placebo (placebo naltrexone + placebo sertraline), (2) naltrexone monotherapy (50 mg naltrexone + sertraline placebo) and (3) naltrexone + sertraline (100 mg) plus nine sessions of medical management and supportive advice. Primary outcomes included Time to First Heavy Drinking Day and Total Abstinence. Results Naltrexone monotherapy demonstrated significantly higher total abstinence (35%) compared with placebo (12%, p = 0027) and longer, but not statistically different, Time to First Heavy Drinking Day (p = 0.093). On secondary measures, naltrexone compared with placebo demonstrated significant improvements in percent days abstinent (p = 0.024) and drinking-related consequences (p = 0.02). Combined sertraline and naltrexone did not differ from naltrexone alone. The pattern of findings was generally similar for the American Indian/Alaska Native sub-sample. Naltrexone treatment response was significant within the group of 75 individuals who were homozygous for OPRM1 Asn40 allele. There was a small number of Asp40 carriers, precluding statistical testing of the effect of this allele on response. Conclusions Naltrexone can be used effectively to treat alcoholism in remote and rural communities, with evidence of benefit for American Indians and Alaska Natives. New models of care incorporating pharmacotherapy could reduce important health disparities related to alcoholism. PMID:18482155

Efficacy and Tolerability of Two Different Kinds of Titration of Paroxetine Hydrocloride Solution: an Observational Study.

PubMed

Ielmini, Marta; Poloni, Nicola; Caselli, Ivano; Bianchi, Lucia; Diurni, Marcello; Vender, Simone; Callegari, Camilla

2018-03-13

Depressive disorders are expected to be the second highest cause of morbidity in the world until few years. Moreover, patients with depression frequently show many side effects and low compliance to therapy. To find a more tolerated and more efficacy therapy is a growing need. This observational study investigates the efficacy, safety and tolerability of paroxetine hydrochloride comparing slow versus standard titration in a population affected by Depressive Disoders (according to DSM 5). 186 outpatients were assessed throught the following scales: Hamilton Depression Rating Scale (HDRS) for depression and World Health Organization Quality of Life Scale Bref for the perceived quality of life (WHOQOL BREF). Treatment-emerged Adverse Events (TEAEs) were recorded throught self-reports. Statystical analysys was performed by GraphPad Prism Version 5.1. The efficacy of paroxetine was confirmed in both titrations by the number of clinical remitters (HDRS ≤ 7 at 12 weeks for 53% of the standard titration group and 58% of the slow titration group), without differences. About safety and tolerability there were more frequent TEAEs among the standard titration group (p < 0.01). Comparing WHOQOL BREF between the two groups at the recruitment and at the twelth week emerged a statistically significant difference (p = 0.003), with highest scores reached in slow titration group. Although the short observation period is an evident limit, this study is consistent to the literature about the efficacy of both titrations of paroxetine to improve depression and shows promising results about the increased tolerability of paroxetine slow titration.

Combined prolonged exposure therapy and paroxetine for PTSD related to the World Trade Center attack: a randomized controlled trial.

PubMed

Schneier, Franklin R; Neria, Yuval; Pavlicova, Martina; Hembree, Elizabeth; Suh, Eun Jung; Amsel, Lawrence; Marshall, Randall D

2012-01-01

Selective serotonin reuptake inhibitors (SSRIs) are often recommended in combination with established cognitive-behavioral therapies (CBTs) for posttraumatic stress disorder (PTSD), but combined initial treatment of PTSD has not been studied under controlled conditions. There are also few studies of either SSRIs or CBT in treating PTSD related to terrorism. The authors compared prolonged exposure therapy (a CBT) plus paroxetine (an SSRI) with prolonged exposure plus placebo in the treatment of terrorism-related PTSD. Adult survivors of the World Trade Center attack of September 11, 2001, with PTSD were randomly assigned to 10 weeks of treatment with prolonged exposure (10 sessions) plus paroxetine (N=19) or prolonged exposure plus placebo (N=18). After week 10, patients discontinued prolonged exposure and were offered 12 additional weeks of continued randomized treatment. Patients treated with prolonged exposure plus paroxetine experienced significantly greater improvement in PTSD symptoms (incidence rate ratio=0.50, 95% CI=0.30-0.85) and remission status (odds ratio=12.6, 95% CI=1.23-129) during 10 weeks of combined treatment than patients treated with prolonged exposure plus placebo. Response rate and quality of life were also significantly more improved with combined treatment. The subset of patients who continued randomized treatment for 12 additional weeks showed no group differences. Initial treatment with paroxetine plus prolonged exposure was more efficacious than prolonged exposure plus placebo for PTSD related to the World Trade Center attack. Combined treatment medication and prolonged exposure therapy deserves further study in larger samples with diverse forms of PTSD and over longer follow-up periods.

A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease

PubMed Central

McDermott, M.P.; Kurlan, R.; Lyness, J.M.; Como, P.G.; Pearson, N.; Factor, S.A.; Juncos, J.; Serrano Ramos, C.; Brodsky, M.; Manning, C.; Marsh, L.; Shulman, L.; Fernandez, H.H.; Black, K.J.; Panisset, M.; Christine, C.W.; Jiang, W.; Singer, C.; Horn, S.; Pfeiffer, R.; Rottenberg, D.; Slevin, J.; Elmer, L.; Press, D.; Hyson, H.C.; McDonald, W.; Richard, Irene; McDonald, William; McDermott, Michael; Como, Peter G.; Kurlan, Roger; Lyness, Jeffrey M.; Pearson, Nancy; Sommerfeld, Barbara; Deeley, Cheryl; de la Torre, Tania; Barnard, Michele; Wilson, April; Lincoln, Maryann; Damgaard, Paula; Gerstenhaber, Melissa; Dustin, Kelly; Zappala, Nancy; Swartz, Camille; Creech, Mary; Shipley, Elda; Blankenship, Samantha; Beland, Monica; Roth, Jessie; Burnette, Heather; Foxworth, Tamara; Quesada, Monica; Lloyd, Mary; Pfeiffer, Brenda; Hansen, Joy; Folie, Joy; Wagner, Renee; Spears, Julia; Taylor, Colleen; Brown, Rachel; Iguchi, Lisa; Lim, Chen; LaDonna, Kori; Megens, Julie; Menza, Matthew; Cummings, Jeffrey; Hamer, Robert; Shannon, Kathleen; Odenkirchen, Joanne; Conwit, Robin; Beck, Christopher; LaDonna, Donna; Bausch, Jan; Kim, Scott; Chismar, Ron; Quinn, Sinead; Bean, Steve; Daigneault, Susan; Lindsay, Patricia; Ross, Tori; Kompoliti, Katie

2012-01-01

Objective: To evaluate the efficacy and safety of a selective serotonin reuptake inhibitor (SSRI) and a serotonin and norepinephrine reuptake inhibitor (SNRI) in the treatment of depression in Parkinson disease (PD). Methods: A total of 115 subjects with PD were enrolled at 20 sites. Subjects were randomized to receive an SSRI (paroxetine; n = 42), an SNRI (venlafaxine extended release [XR]; n = 34), or placebo (n = 39). Subjects met DSM-IV criteria for a depressive disorder, or operationally defined subsyndromal depression, and scored >12 on the first 17 items of the Hamilton Rating Scale for Depression (HAM-D). Subjects were followed for 12 weeks (6-week dosage adjustment, 6-week maintenance). Maximum daily dosages were 40 mg for paroxetine and 225 mg for venlafaxine XR. The primary outcome measure was change in the HAM-D score from baseline to week 12. Results: Treatment effects (relative to placebo), expressed as mean 12-week reductions in HAM-D score, were 6.2 points (97.5% confidence interval [CI] 2.2 to 10.3, p = 0.0007) in the paroxetine group and 4.2 points (97.5% CI 0.1 to 8.4, p = 0.02) in the venlafaxine XR group. No treatment effects were seen on motor function. Conclusions: Both paroxetine and venlafaxine XR significantly improved depression in subjects with PD. Both medications were generally safe and well tolerated and did not worsen motor function. Classification of Evidence: This study provides Class I evidence that paroxetine and venlafaxine XR are effective in treating depression in patients with PD. PMID:22496199

BiteStrip analysis of the effect of fluoxetine and paroxetine on sleep bruxism.

PubMed

Isa Kara, M; Ertaş, Elif Tarım; Ozen, Emrullah; Atıcı, Meral; Aksoy, Selami; Erdogan, Muharrem Serif; Kelebek, Seyfi

2017-08-01

The relationship between sleep bruxism (SB) and selective serotonin reuptake inhibitors (SSRIs) is still under debate because of the lack of well-designed objective studies. The current study investigates possible effects of SSRIs, fluoxetine, and paroxetine on SB in patients with anxiety and depression. Thirty users of SSRIs for treatment of depression or anxiety were enrolled in the study. After clinical and anamnestic examination, 15 fluoxetine and 15 paroxetine users were included. For an objective evaluation of SB, a single-use disposable home screening device, BiteStrip, was used prior to the first SSRI intake and was repeated on the 7th and 15th days. Patients' self-reported data also were obtained for assessment of patient awareness. BiteStrip scores were significantly higher on the 7th and 15th days than the first measurement (p<0.01). There was an increase in 26 (86.6%) patients' bruxism scores on the 7th day. There was also an increase in 27 (90%) patients' bruxism scores on the 15th day. But according to patients' self-reports, only 6 patients had an awareness that bruxism symptoms were initiated or exacerbated 15days after starting fluoxetine or paroxetine. Fluoxetine and paroxetine, SSRIs used for the treatment of anxiety and depression, may initiate or aggravate SB. Clinicians should consider that SSRIs may be the cause of SB when SSRI users are referred to dental clinics for SB symptoms. As there is a shortage of researches on this subject, further studies are necessary to confirm the existence of SSRI-induced SB. Copyright © 2016. Published by Elsevier Ltd.

Predictors and Moderators of Treatment Outcome in the Pediatric Obsessive Compulsive Treatment Study (POTS I)

ERIC Educational Resources Information Center

Garcia, Abbe Marrs; Sapyta, Jeffrey J.; Moore, Phoebe S.; Freeman, Jennifer B.; Franklin, Martin E.; March, John S.; Foa, Edna B.

2010-01-01

Objective: To identify predictors and moderators of outcome in the first Pediatric OCD Treatment Study (POTS I) among youth (N = 112) randomly assigned to sertraline, cognitive behavioral therapy (CBT), both sertraline and CBT (COMB), or a pill placebo. Method: Potential baseline predictors and moderators were identified by literature review. The…

A Pilot Randomized Controlled Trial of Combined Trauma-Focused CBT and Sertraline for Childhood PTSD Symptoms

ERIC Educational Resources Information Center

Cohen, Judith A.; Mannarino, Anthony P.; Perel, James M.; Staron, Virginia

2007-01-01

Objective: To examine the potential benefits of adding a selective serotonin reuptake inhibitor, sertraline, versus placebo, to trauma-focused cognitive-behavioral therapy (TF-CBT) for improving posttraumatic stress disorder and related psychological symptoms in children who have experienced sexual abuse. Method: Twenty-four 10- to 17-year-old…

Risk of Ventricular Arrhythmia with Citalopram and Escitalopram: A Population-Based Study.

PubMed

Qirjazi, Elena; McArthur, Eric; Nash, Danielle M; Dixon, Stephanie N; Weir, Matthew A; Vasudev, Akshya; Jandoc, Racquel; Gula, Lorne J; Oliver, Matthew J; Wald, Ron; Garg, Amit X

2016-01-01

The risk of ventricular arrhythmia with citalopram and escitalopram is controversial. In this study we investigated the association between these two drugs and the risk of ventricular arrhythmia. We conducted a population-based retrospective cohort study of older adults (mean age 76 years) from 2002 to 2012 in Ontario, Canada, newly prescribed citalopram (n = 137 701) or escitalopram (n = 38 436), compared to those prescribed referent antidepressants sertraline or paroxetine (n = 96 620). After inverse probability of treatment weighting using a propensity score, the baseline characteristics of the comparison groups were similar. The primary outcome was a hospital encounter with ventricular arrhythmia within 90 days of a new prescription, assessed using hospital diagnostic codes. The secondary outcome was all-cause mortality within 90 days. Citalopram was associated with a higher risk of a hospital encounter with ventricular arrhythmia compared with referent antidepressants (0.06% vs. 0.04%, relative risk [RR] 1.53, 95% confidence intervals [CI]1.03 to 2.29), and a higher risk of mortality (3.49% vs. 3.12%, RR 1.12, 95% CI 1.06 to 1.18). Escitalopram was not associated with a higher risk of ventricular arrhythmia compared with the referent antidepressants (0.03% vs. 0.04%, RR 0.84, 95% CI 0.42 to 1.68), but was associated with a higher risk of mortality (2.86% vs. 2.63%, RR 1.09, 95% CI 1.01 to 1.18). Among older adults, initiation of citalopram compared to two referent antidepressants was associated with a small but statistically significant increase in the 90-day risk of a hospital encounter for ventricular arrhythmia.

Risk of Ventricular Arrhythmia with Citalopram and Escitalopram: A Population-Based Study

PubMed Central

Qirjazi, Elena; McArthur, Eric; Nash, Danielle M.; Dixon, Stephanie N.; Weir, Matthew A.; Vasudev, Akshya; Jandoc, Racquel; Gula, Lorne J.; Oliver, Matthew J.; Wald, Ron; Garg, Amit X.

2016-01-01

Background The risk of ventricular arrhythmia with citalopram and escitalopram is controversial. In this study we investigated the association between these two drugs and the risk of ventricular arrhythmia. Methods We conducted a population-based retrospective cohort study of older adults (mean age 76 years) from 2002 to 2012 in Ontario, Canada, newly prescribed citalopram (n = 137 701) or escitalopram (n = 38 436), compared to those prescribed referent antidepressants sertraline or paroxetine (n = 96 620). After inverse probability of treatment weighting using a propensity score, the baseline characteristics of the comparison groups were similar. The primary outcome was a hospital encounter with ventricular arrhythmia within 90 days of a new prescription, assessed using hospital diagnostic codes. The secondary outcome was all-cause mortality within 90 days. Results Citalopram was associated with a higher risk of a hospital encounter with ventricular arrhythmia compared with referent antidepressants (0.06% vs. 0.04%, relative risk [RR] 1.53, 95% confidence intervals [CI]1.03 to 2.29), and a higher risk of mortality (3.49% vs. 3.12%, RR 1.12, 95% CI 1.06 to 1.18). Escitalopram was not associated with a higher risk of ventricular arrhythmia compared with the referent antidepressants (0.03% vs. 0.04%, RR 0.84, 95% CI 0.42 to 1.68), but was associated with a higher risk of mortality (2.86% vs. 2.63%, RR 1.09, 95% CI 1.01 to 1.18). Conclusion Among older adults, initiation of citalopram compared to two referent antidepressants was associated with a small but statistically significant increase in the 90-day risk of a hospital encounter for ventricular arrhythmia. PMID:27513855

Switch-backs associated with generic drugs approved using product-specific determinations of therapeutic equivalence.

PubMed

Gagne, Joshua J; Polinski, Jennifer M; Jiang, Wenlei; Dutcher, Sarah K; Xie, Jing; Lii, Joyce; Fulchino, Lisa A; Kesselheim, Aaron S

2016-08-01

US Food and Drug Administration approval for generic drugs relies on demonstrating pharmaceutical equivalence and bioequivalence; however, some drug products have unique attributes that necessitate product-specific approval pathways. We evaluated rates of patients' switching back to brand-name versions from generic versions of four drugs approved via such approaches. We used data from Optum LifeSciences Research Database to identify patients using a brand-name version of a study drug (acarbose tablets, salmon calcitonin nasal spray, enoxaparin sodium injection, and venlafaxine extended release tablets) or a control drug. We followed patients to identify switching to generic versions and then followed those who switched to identify whether they switched back to brand-name versions. We calculated switch and switch-back rates and used Kaplan-Meier and log-rank tests to compare rates between study and control drugs. Our cohort included 201 959 eligible patients. Brand-to-generic switch rates ranged from 66 to 106 switches per 100 person-years for study drugs and 80 to 110 for control drugs. Rates of switch-back to brand-name versions ranged from 5 to 37 among study drugs and 3 to 53 among control drugs. Switch-back rates were higher for venlafaxine vs. sertraline (p < 0.01) and calcitonin vs. alendronate (p = 0.01). Switch-back rates were lower for venlafaxine vs. paroxetine (p < 0.01) and acarbose vs. nateglinide (p < 0.01). Rates were similar for acarbose vs. glimepiride (p = 0.97) and for enoxaparin vs. fondiparinux (p = 0.11). As compared to control drugs, patients were not more likely to systematically switch back from generic to brand-name versions of the four study drugs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Dosing of Selective Serotonin Reuptake Inhibitors Among Children and Adults Before and After the FDA Black-Box Warning.

PubMed

Bushnell, Greta A; Stürmer, Til; Swanson, Sonja A; White, Alice; Azrael, Deborah; Pate, Virginia; Miller, Matthew

2016-03-01

Prior research evaluated various effects of the 2004 black-box warning by the U.S. Food and Drug Administration (FDA) on the risk of suicidality among children associated with use of antidepressants, but the warning's effect on dosing of antidepressants has not been evaluated. This study estimated whether the initial antidepressant dose prescribed decreased and the proportion of patients who augmented the dose on the second fill increased following the 2004 warning and its 2007 expansion to young adults. The study utilized the LifeLink Health Plan Claims Database. The study cohort consisted of commercially insured children (ages 5-17), young adults (18-24), and adults (25-64) who initiated a selective serotonin reuptake inhibitor (SSRI) (citalopram, fluoxetine, paroxetine, or sertraline) from January 1, 2000, to December 31, 2009. Dose per day was determined by days' supply, strength, and quantity dispensed. Initiation with a low dose and augmentation of >1 mg/day on the second prescription before and after the 2004 warning were considered. Of 51,948 children who initiated an SSRI, 15% initiated with a low dose before the 2004 warning compared with 31% after the warning; there was a smaller change among young adults (6 percentage points) and adults (3 percentage points). The overall increase in dose augmentations among children and young adults was driven by the increase in patients initiating with a low dose. The proportion of commercially insured children initiating an SSRI with a low dose was higher after the 2004 FDA warning on the risk of suicidality among children, suggesting improved prescribing practices surrounding SSRI dosing among children.

Dosing of selective serotonin reuptake inhibitors in children and adults before and after the FDA black-box warning

PubMed Central

Bushnell, Greta A; Stürmer, Til; Swanson, Sonja A; White, Alice; Azrael, Deborah; Pate, Virginia; Miller, Matthew

2016-01-01

Objective Prior research evaluated various effects of the antidepressant black-box warning on the risk of suicidality in children, but the dosing of antidepressants has not been considered. This study estimated, relative to the FDA warnings, whether the initial antidepressant dose prescribed decreased and the proportion augmenting dose on the second fill increased. Method The study utilized the LifeLink Health Plan Claims Database. The study cohort consisted of commercially insured children (5–17 years), young adults (18–24 years), and adults (25–64 years) initiating an SSRI (citalopram, fluoxetine, paroxetine, or sertraline) from 1/1/2000 to 12/31/2009. Dose-per-day was determined by days supply, strength, and quantity dispensed. Initiation on low dose, defined based on guidelines, and dose augmentations (dose increase >1mg/day) on the second prescription were considered across time periods related to the antidepressant warnings. Results Of 51,948 children who initiated an SSRI, 15% initiated on low dose in the period before the 2004 black-box warning and 31% in the period after the warning (a 16 percentage-point change); there was a smaller percentage-point change in young adults (6%) and adults (3%). The overall increase in dose augmentations in children and young adults was driven by the increase in patients initiating on a low dose. Conclusions As guidelines recommend children initiate antidepressant treatment on low dose, findings that an increased proportion of commercially insured children initiated an SSRI on low dose after the 2004 black-box warning suggest prescribing practices surrounding SSRI dosing improved in children following the warning but dosing practices still fall short of guidelines. PMID:26567938

Minocycline combination therapy with fluvoxamine in moderate-to-severe obsessive-compulsive disorder: A placebo-controlled, double-blind, randomized trial.

PubMed

Esalatmanesh, Sophia; Abrishami, Zoha; Zeinoddini, Atefeh; Rahiminejad, Fatemeh; Sadeghi, Majid; Najarzadegan, Mohammad-Reza; Shalbafan, Mohammad-Reza; Akhondzadeh, Shahin

2016-11-01

Several lines of evidence implicate glutamatergic dysfunction in the pathophysiology of obsessive-compulsive disorder (OCD), presenting this neurotransmitter as a target for the development of novel pharmacotherapy. The objective of this study was to assess the efficacy of minocycline as an augmentative agent to fluvoxamine in the treatment of patients with OCD. One hundred and two patients with the diagnosis of moderate-to-severe OCD were recruited to this study. A randomized double-blind trial was designed and patients received either L-carnosine or placebo as adjuvant to fluvoxamine for 10 weeks. The patients randomly received either minocycline 100 mg twice per day or placebo for 10 weeks. All patients received fluvoxamine (100 mg/day) for the first 4 weeks, followed by 200 mg/day for the rest of the trial, regardless of their treatment groups. Participants were evaluated using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The main outcome measure was to assess the efficacy of minocycline in improving the OCD symptoms. General linear model repeated measures demonstrated significant effect for time × treatment interaction on the Y-BOCS total scores, F(1.49, 137.93) = 7.1, P  = 0.003, and Y-BOCS Obsession subscale score, F(1.54, 141.94) = 9.72, P = 0.001, and near significant effect for the Y-BOCS Compulsion subscale score, F(1.27, 117.47) = 2.92, P  = 0.08. A significantly greater rate of partial and complete response was observed in the minocycline group (P < 0.001). The frequency of side-effects was not significantly different between the treatment arms. The results of this study suggest that minocycline could be a tolerable and effective adjuvant in the management of patients with OCD. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Functional analysis of [methyl-(3)H]choline uptake in glioblastoma cells: Influence of anti-cancer and central nervous system drugs.

PubMed

Taguchi, Chiaki; Inazu, Masato; Saiki, Iwao; Yara, Miki; Hara, Naomi; Yamanaka, Tsuyoshi; Uchino, Hiroyuki

2014-04-01

Positron emission tomography (PET) and PET/computed tomography (PET-CT) studies with (11)C- or (18)F-labeled choline derivatives are used for PET imaging in glioblastoma patients. However, the nature of the choline transport system in glioblastoma is poorly understood. In this study, we performed a functional characterization of [methyl-(3)H]choline uptake and sought to identify the transporters that mediate choline uptake in the human glioblastoma cell lines A-172 and U-251MG. In addition, we examined the influence of anti-cancer drugs and central nervous system drugs on the transport of [methyl-(3)H]choline. High- and low-affinity choline transport systems were present in A-172 cells, U-251MG cells and astrocytes, and these were Na(+)-independent and pH-dependent. Cell viability in A-172 cells was not affected by choline deficiency. However, cell viability in U-251MG cells was significantly inhibited by choline deficiency. Both A-172 and U-251MG cells have two different choline transporters, choline transporter-like protein 1 (CTL1) and CTL2. In A-172 cells, CTL1 is predominantly expressed, whereas in U-251MG cells, CTL2 is predominantly expressed. Treatment with anti-cancer drugs such as cisplatin, etoposide and vincristine influenced [methyl-(3)H]choline uptake in U-251MG cells, but not A-172 cells. Central nervous system drugs such as imipramine, fluvoxamine, paroxetine, reboxetine, citalopram and donepezil did not affect cell viability or [methyl-(3)H]choline uptake. The data presented here suggest that CTL1 and CTL2 are functionally expressed in A-172 and U-251MG cells and are responsible for [methyl-(3)H]choline uptake that relies on a directed H(+) gradient as a driving force. Furthermore, while anti-cancer drugs altered [methyl-(3)H]choline uptake, central nervous system drugs did not affect [methyl-(3)H]choline uptake. Copyright © 2014 Elsevier Inc. All rights reserved.

Obsessive-compulsive disorder with bipolar diathesis following isotretinoin therapy remitting upon treatment with olanzapine and fluvoxamine

PubMed Central

Fornaro, Michele

2010-01-01

Isotretinoin, a drug used for moderate to severe acne, has been repeatedly associated with various psychiatric complications, although a definitive causal relationship has not been established to date. This case report describes a 25-year-old male who developed obsessive-compulsive disorder at the age of 23 years following isotretinoin treatment for acne (10–20 mg/day) since the age of 16 years. Although standard treatment for obsessive-compulsive disorder caused mood swings, the combination of fluvoxamine 300 mg/day and olanzapine 15 mg/day significantly improves the clinical picture. Although rare, severe adulthood psychiatric complications may occur following isotretinoin treatment, requiring management which is individually tailored to the patient. PMID:21127690

Analysis of Sertraline in Postmortem Fluids and Tissues in 11 Aviation Accident Victims

DTIC Science & Technology

2012-11-01

likely undergoes significant postmortem redistribution. 17. Key Words 18. Distribution Statement Forensic Toxicology , Sertraline, Norsertraline... Toxicology .. Forensic Sci Int,.142:.75-100.(2004) . 29 .. Skopp,.G ..Postmortem.Toxicology .. Forensic Sci Med Pathol,.6:.314-25.(2010) . ... toxicological . analysis. on. specimens.from.….aircraft.accident.fatalities”.and.“in- vestigate.….general.aviation.and.air.carrier.accidents. and. search

Persistent benefits of slow titration of paroxetine in a six-month follow-up.

PubMed

Olgiati, Paolo; Serretti, Alessandro

2015-09-01

Paroxetine titration may be difficult in older individuals as they are more sensitive to side effects. The current study extends to 6 months our previously published report in which paroxetine was started at 2.5 mg/day and slowly increased by 2.5 mg on alternate days (slow titration) or rapidly titrated to target dose from 10 mg/day (standard titration) in a naturalistic setting. Here, the follow-up period was extended to 26 weeks. We performed an intent-to-treat analysis of 47 subjects from the original sample (major depressive disorder and/or generalized anxiety disorder (GAD); >60 years of age). Missing evaluations were replaced by last observations carried forward. GAD was included as a stratification factor. Patients in whom paroxetine was slowly up-titrated were more likely to remit (84.0% vs 54.5%; p = 0.028) and had lower core depression (p = 0.0015) and psychic anxiety levels (p = 0.006) after 26 weeks. Dropout rate was 20% in the slow titration group compared with 77.3% in the standard titration arm (p < 0.001). Patients with GAD accounted for all significant associations. No substantial differences were reported between slow and standard titration groups in the subsample without GAD. Despite some limitations, these findings suggest that paroxetine treatment should be started at lower doses in older depressed patients and slowly up-titrated. This strategy would allow to increase antidepressant response and the likelihood of completing treatment cycle in patients with high anxiety levels and GAD comorbidity. Copyright © 2015 John Wiley & Sons, Ltd.

The combined use of virtual reality exposure in the treatment of agoraphobia.

PubMed

Pitti, Carmen T; Peñate, Wenceslao; de la Fuente, Juan; Bethencourt, Juan M; Roca-Sánchez, María J; Acosta, Leopoldo; Villaverde, María L; Gracia, Ramón

2015-01-01

This study compares the differential efficacy of three groups of treatments for agoraphobia: paroxetine combined with cognitive-behavioral therapy, paroxetine combined with cognitive-behavioral therapy and virtual reality exposure, and a group with only paroxetine. 99 patients with agoraphobia were finally selected. Both combined treatment groups received 11 sessions of cognitive-behavioral therapy, and one of the groups was also exposed to 4 sessions of virtual reality treatment. Treatments were applied in individual sessions once a week for 3 months. The three treatment groups showed statistically significant improvements. In some measures, combined treatment groups showed greater improvements. The virtual reality exposure group showed greater improvement confronting phobic stimuli. Treatments combining psychopharmacological and psychological therapy showed greater efficacy. Although the use of new technologies led to greater improvement, treatment adherence problems still remain.

Ab initio and density functional computations of the vibrational spectrum, molecular geometry and some molecular properties of the antidepressant drug sertraline (Zoloft) hydrochloride

NASA Astrophysics Data System (ADS)

Sagdinc, Seda; Kandemirli, Fatma; Bayari, Sevgi Haman

2007-02-01

Sertraline hydrochloride is a highly potent and selective inhibitor of serotonin (5HT). It is a basic compound of pharmaceutical application for antidepressant treatment (brand name: Zoloft). Ab initio and density functional computations of the vibrational (IR) spectrum, the molecular geometry, the atomic charges and polarizabilities were carried out. The infrared spectrum of sertraline is recorded in the solid state. The observed IR wave numbers were analysed in light of the computed vibrational spectrum. On the basis of the comparison between calculated and experimental results and the comparison with related molecules, assignments of fundamental vibrational modes are examined. The X-ray geometry and experimental frequencies are compared with the results of our theoretical calculations.

Measuring the serotonin uptake site using (/sup 3/H)paroxetine--a new serotonin uptake inhibitor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gleiter, C.H.; Nutt, D.J.

1988-01-01

Serotonin is an important neurotransmitter that may be involved in ethanol preference and dependence. It is possible to label the serotonin uptake site in brain using the tricyclic antidepressant imipramine, but this also binds to other sites. We have used the new high-affinity uptake blocker paroxetine to define binding to this site and report it to have advantages over imipramine as a ligand.

Long-Term Treatment with Paroxetine Increases Verbal Declarative Memory and Hippocampal Volume in Posttraumatic Stress Disorder

PubMed Central

Vermetten, Eric; Vythilingam, Meena; Southwick, Steven M.; Charney, Dennis S.; Bremner, J. Douglas

2011-01-01

Background Animal studies have shown that stress is associated with damage to the hippocampus, inhibition of neurogenesis, and deficits in hippocampal-based memory dysfunction. Studies in patients with posttraumatic stress disorder (PTSD) found deficits in hippocampal-based declarative verbal memory and smaller hippocampal volume, as measured with magnetic resonance imaging (MRI). Recent preclinical evidence has shown that selective serotonin reuptake inhibitors promote neurogenesis and reverse the effects of stress on hippocampal atrophy. This study assessed the effects of long-term treatment with paroxetine on hippocampal volume and declarative memory performance in PTSD. Methods Declarative memory was assessed with the Wechsler Memory Scale–Revised and Selective Reminding Test before and after 9–12 months of treatment with paroxetine in PTSD. Hippocampal volume was measured with MRI. Of the 28 patients who started the protocol, 23 completed the full course of treatment and neuropsychological testing. Twenty patients were able to complete MRI imaging. Results Patients with PTSD showed a significant improvement in PTSD symptoms with treatment. Treatment resulted in significant improvements in verbal declarative memory and a 4.6% increase in mean hippocampal volume. Conclusions These findings suggest that long-term treatment with paroxetine is associated with improvement of verbal declarative memory deficits and an increase in hippocampal volume in PTSD. PMID:14512209

Generation of hydrate forms of paroxetine HCl from the amorphous state: an evaluation of thermodynamic and experimental predictive approaches.

PubMed

Pina, M Fátima; Pinto, João F; Sousa, João J; Craig, Duncan Q M; Zhao, Min

2015-03-15

In this study, we evaluate the use of theoretical thermodynamic analysis of amorphous paroxetine hydrochloride (HCl) as well as experimental assessment in order to identify the most promising approach to stability and dissolution behaviour prediction, particularly in relation to stoichiometric and nonstoichiometric hydrate formation. Differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared and X-ray diffraction techniques were used. Parameters including heat capacity, configurational thermodynamic quantities, fragility and relaxation time classified amorphous paroxetine HCl as a moderate fragile glass with a considerable degree of molecular mobility. Solubility studies indicated little advantage of the amorphous form over the crystalline due to conversion to the hydrate Form I during equilibration, while the dissolution rate was higher for the amorphous form under sink conditions. A marked difference in the physical stability of amorphous paroxetine HCl was observed between dry and low humidity storage, with the system recrystallizing to the hydrate form. We conclude that, in this particular case (amorphous conversion to the hydrate), water may be playing a dual role in both plasticizing the amorphous form and driving the equilibrium towards the hydrate form, hence prediction of recrystallization behaviour from amorphous characteristics may be confounded by the additional process of hydrate generation. Copyright © 2015 Elsevier B.V. All rights reserved.

Sertraline and periodic limb movements during sleep: an 8-week open-label study in depressed patients with insomnia.

PubMed

Zhang, Bin; Hao, Yanli; Jia, Fujun; Li, Xueli; Ren, Yanzhen; Zhou, Ping; Liu, Wuhan; Wing, Yun Kwok

2013-12-01

Previous studies have reported that selective serotonin reuptake inhibitors (SSRIs) might induce or exacerbate periodic limb movements during sleep (PLMS). However, most of these studies were retrospective and cross-sectional studies with small sample sizes on a selective SSRI, fluoxetine. Because different SSRIs have different pharmacologic profiles, it was not certain if other SSRIs also might lead to PLMS. Data were taken from an open-label 8-week trial of sertraline in depressive patients with insomnia (n=31). Depressed patients were administered sertraline 50mg at 8:00am on the first day, and the dosage was subsequently titrated up to a maximum of 200mg daily during the 8-week trial. All participants were tested by repeated polysomnography (PSG) (baseline, first day, 14th day, 28th day, and 56th day). Periodic leg movements (PLM) were visually counted and the PLM index (PLMI) was calculated. PLMS was defined as PLMI ⩾5, and significant PLMS was defined as PLMI ⩾15. Compared with baseline (PLMI, 3.6±1.5), all PLMI indices increased on the immediate administration of sertraline on the first day (PLMI, 5.1±3.9). From the 14th day onward, PLMI became stable and significantly higher than baseline and the first day (8.7±3.1 on the 14th day, 8.3±3.7 on the 28th day, and 8.5±3.6 on the 56th day; F[11.81]; P=.003). The clinical responses and PSG characteristics continuously improved during the 8-week trial. The PLMS group (PLMI ⩾5) had a higher arousal index (AI) than the non-PLMS group on the 14th day (9.4±5.5 vs 5.2±3.7; t test, 4.22; P=.03) and the 56th day (8.1±5.5 vs 4.3±3.7; z score, 3.11; P=.04); albeit, there was no significant clinical disturbances in the PLMS group. PLMS were increased during sertraline treatment, but only a few of the PLMS reached the significant level. This effect of sertraline on PLMS might be dosage dependent. Although the sertraline-induced PLMS did not seem to cause significant clinical disturbance, the PLMS group (PLMI ⩾5) had a higher AI than the non-PLMS group. Thus clinicians should pay more attention to PLMS during SSRI antidepressant treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

Sertraline Versus Placebo in Patients with Major Depressive Disorder Undergoing Hemodialysis: A Randomized, Controlled Feasibility Trial.

PubMed

Friedli, Karin; Guirguis, Ayman; Almond, Michael; Day, Clara; Chilcot, Joseph; Da Silva-Gane, Maria; Davenport, Andrew; Fineberg, Naomi A; Spencer, Benjamin; Wellsted, David; Farrington, Ken

2017-02-07

Depression is common in patients on hemodialysis, but data on the benefits and risks of antidepressants in this setting are limited. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of sertraline over 6 months in patients on hemodialysis with depression to determine study feasibility, safety, and effectiveness. Patients on hemodialysis at five United Kingdom renal centers completed the Beck Depression Inventory II. Those scoring ≥16 and not already on treatment for depression were invited to undergo diagnostic interview to confirm major depressive disorder. Eligible patients with major depressive disorder were randomized to receive the study medication-either sertraline or placebo. Outcomes included recruitment and dropout rates, change in the Montgomery-Asberg Depression Rating Scale and Beck Depression Inventory II, and qualitative information to guide design of a large-scale trial. In total, 709 patients were screened and enrolled between April of 2013 and October of 2014; 231 (32.6%) had Beck Depression Inventory II scores ≥16, and 68 (29%) of these were already receiving treatment for depression. Sixty-three underwent diagnostic interview, 37 were diagnosed with major depressive disorder, and 30 were randomized; 21 completed the trial: eight of 15 on sertraline and 13 of 15 on placebo (P=0.05). Dropouts due to adverse and serious adverse events were greater in the sertraline group. All occurred in the first 3 months. Over 6 months, depression scores improved in both groups. Beck Depression Inventory II score fell from 29.1±8.4 to 17.3±12.4 (P<0.001), and Montgomery-Asberg Depression Rating Scale score fell from 24.5±4.1 to 10.3±5.8 (P<0.001). There were no differences between sertraline and placebo groups. Although small, this is the largest randomized trial to date of antidepressant medication in patients on hemodialysis. Our results highlight recruitment issues. No benefit was observed, but trial size and the substantial dropout render consideration of benefit inconclusive. A definitive trial could use shorter follow-up and include depressed patients already taking antidepressants. Copyright © 2017 by the American Society of Nephrology.

Ondansetron and sertraline may interact with 5-HTTLPR and DRD4 polymorphisms to reduce drinking in non-treatment seeking alcohol dependent women: exploratory findings

PubMed Central

Kenna, George A.; Zywiak, William H.; Swift, Robert M.; McGeary, John E.; Clifford, James S.; Shoaff, Jessica R.; Fricchione, Samuel; Brickley, Michael; Beaucage, Kayla; Haass-Koffler, Carolina L.; Leggio, Lorenzo

2014-01-01

The purpose of this exploratory study was to examine the interaction of 5-HTTLPR and DRD4 exon III polymorphisms with gender in non-treatment seeking alcohol dependent (AD) individuals while alternately taking ondansetron and sertraline. Evidence suggests that alcohol dependence may be influenced by a genetic interaction that may be gender specific with temporal changes making pharmacological treatment with serotonergic drugs complex. The main trial was a within-subject double-blind placebo-controlled human laboratory study with 77 non-treatment-seeking AD individuals randomized (55 completed, 49 complete data) to receive 200mg/day of sertraline or 0.5mg/day of ondansetron for 3-weeks followed by an alcohol self-administration experiment (ASAE), then placebo for three weeks followed by a second ASAE, then receive the alternate drug, in a counterbalanced order, for three weeks followed by a third ASAE. Results for men were not significant. Women with the LL 5-HTTLPR genotype receiving ondansetron and SS/SL 5-HTTLPR genotypes receiving sertraline (matched), drank significantly fewer drinks per drinking day (DDD) during the 7-days prior to the first and third ASAEs than women receiving the mismatched medication (i.e. sertraline to LL and ondansetron to SS/SL). In a three-way interaction, 5-HTTLPR alleles by DRD4 alleles by medications, women with the LL genotype who received ondansetron and had DRD4 ≥7 exon III repeats drank significantly fewer DDD as did SS/SL women who received sertraline but conversely had DRD4 <7-repeats in the 7-day period leading up to the first and third ASAEs. Consistent with these data was a significant reduction of milliliters consumed ad lib during these same ASAEs. These exploratory findings add possible support to gender and genetic differences among AD individuals in response to serotonergic pharmacotherapies. Future trials should be powerful enough to take into account that endophenotypes and a targeting of serotonergic interactions may be essential to successfully treat alcohol dependence. PMID:25212749

The effects of combined sertraline and aspirin therapy on depression severity among patients with major depressive disorder: A randomized clinical trial.

PubMed

Sepehrmanesh, Zahra; Fahimi, Hosein; Akasheh, Goudarz; Davoudi, Mohamadreza; Gilasi, Hamidreza; Ghaderi, Amir

2017-11-01

Different studies have been conducted to find the best adjuvant therapies for depression management. There are controversies over the effects of aspirin as an adjuvant therapy for depression. To determine the effects of combined sertraline and aspirin therapy on depression severity among patients with major depressive disorder. This randomized clinical trial was conducted at Kargarnejad Psychiatric Hospital in Kashan, Isfahan, Iran, from September 1, 2016 to November 1, 2016. The study participants included 100 patients with major depressive disorder who were assigned to aspirin and placebo groups by the use of computer-generated random numbers. Patients in these groups respectively received sertraline-aspirin and sertraline-placebo for eight consecutive weeks. Patients were prescribed 80 milligrams of aspirin twice a day. Also, sertraline was administered at a dose of 50-200 milligrams daily. Beck Depression Inventory was employed for depression severity assessment at four time points, namely before, two, four, and eight weeks after the beginning of the intervention. Medication side effects were also assessed eight weeks after the beginning of the intervention. Data were analyzed by SPSS version 12.0, using Chi-square and the Independent-samples t-test (α=0.05). Both groups were matched in terms of age (p=0.46), gender (p=0.539), and depression severity (p=0.509, with mean score 33.5±4.1 vs. 32.8±5.9) at baseline. However, depression scores were reduced significantly four and eight weeks after initiation of therapy just in the sertraline-aspirin group (p<0.05). As an adjuvant therapy, aspirin can reduce depression severity among patients with major depressive disorder. Yet, further studies are needed to prove the effectiveness of aspirin and other anti-inflammatory agents in reducing depression severity. The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT2016082829556N1. The authors received financial support from Research Deputy of Kashan University of Medical Sciences, Kashan, Isfahan, Iran.

Fluvoxamine

MedlinePlus

... staying asleep; or pain, burning, numbness, tingling or 'electric shock' sensations in the hands or feet. Your ... thinking, or motor skills. Do not drive a car or operate machinery until you know how this ...

Exercise and Pharmacological Treatment of Depressive Symptoms in Patients with Coronary Heart Disease: Results from the UPBEAT Study

PubMed Central

Blumenthal, James A.; Sherwood, Andrew; Babyak, Michael A.; Watkins, Lana L.; Smith, Patrick J.; Hoffman, Benson M.; O’Hayer, C. Virginia F.; Mabe, Stephanie; Johnson, Julie; Doraiswamy, P. Murali; Jiang, Wei

2012-01-01

OBJECTIVE To assess the efficacy of exercise and antidepressant medication in reducing depressive symptoms and improving cardiovascular biomarkers in depressed patients with coronary heart disease (CHD). BACKGROUND Although there is good evidence that clinical depression is associated with poor prognosis, optimal therapeutic strategies are currently not well-defined. METHODS 101 outpatients with CHD and elevated depressive symptoms underwent assessment of depression including a psychiatric interview and the Hamilton Rating Scale for Depression (HAM-D). Participants were randomized to 4 months of aerobic exercise (3 times/week), sertraline (50-200 mg/day), or placebo. Additional assessments of cardiovascular biomarkers included measures of heart rate variability (HRV), endothelial function, baroreflex sensitivity, inflammation, and platelet function. RESULTS After 16 weeks, all groups showed improvement on HAM-D scores. Participants in both aerobic exercise (M= −7.5 [95% CI = −9.8, −5.0]) and sertraline (M= −6.1 [95% CI = −8.4, −3.9] achieved larger reductions in depressive symptoms compared to placebo (M= −4.5 [95% CI = −7.6, −1.5]; p = .034); exercise and sertraline were equally effective in reducing depressive symptoms (p = .607). Exercise and medication tended to result in greater improvements in HRV compared to placebo (p = .052); exercise tended to result in greater improvements in HRV compared to sertraline (p =.093) CONCLUSIONS Both exercise and sertraline resulted in greater reductions in depressive symptoms compared to placebo in CHD patients. Evidence that active treatments may also improve cardiovascular biomarkers suggests that they may have a beneficial effect on clinical outcomes as well as quality of life. PMID:22858387

Sertraline and venlafaxine improves motor performance and neurobehavioral deficit in quinolinic acid induced Huntington's like symptoms in rats: Possible neurotransmitters modulation.

PubMed

Gill, Jaskamal Singh; Jamwal, Sumit; Kumar, Puneet; Deshmukh, Rahul

2017-04-01

Huntington Disease is autosomal, fatal and progressive neurodegenerative disorder for which clinically available drugs offer only symptomatic relief. Emerging strides have indicated that antidepressants improve motor performance, restore neurotransmitters level, ameliorates striatal atrophy, increases BDNF level and may enhance neurogenesis. Therefore, we investigated sertraline and venlafaxine, clinically available drugs for depression with numerous neuroprotective properties, for their beneficial effects, if any, in quinolinic acid induced Huntington's like symptoms in rats. Rats were administered quinolinic acid (QA) (200 nmol/2μl saline) intrastriatal bilaterally on 0day. Sertraline and venlafaxine (10 and 20mg/kg, po) each were administered for 21days once a day. Motor performance was assessed using rotarod test, grip strength test, narrow beam walk test on weekly basis. On day 22, animals were sacrificed and rat striatum was isolated for biochemical (LPO, GSH and Nitrite), neuroinflammation (TNF-α, IL-1β and IL-6) and neurochemical analysis (GABA, glutamate, norepinephrine, dopamine, serotonin, DOPAC, HVA and 5-HIAA). QA treatment significantly altered body weight, motor performance, oxidative defense (increased LPO, nitrite and decreased GSH), pro-inflammatory cytokines levels (TNF-α, IL-6 and IL-1β), neurochemical level (GABA, glutamate, nor-epinephrine, dopamine, serotonin, HVA, DOPAC, 5-HIAA). Sertraline and venlafaxine at selected doses significantly attenuated QA induced alterations in striatum. The present study suggests that modulation of monoamines level, normalization of GABA and glutamatergic signaling, anti-oxidant and anti-inflammatory properties could underlie the neuroprotective effect of sertraline and venlafaxine in QA induced Huntington's like symptoms. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Sertraline inhibits formalin-induced nociception and cardiovascular responses

PubMed Central

Santuzzi, C.H.; Futuro Neto, H.A.; Pires, J.G.P.; Gonçalves, W.L.S.; Tiradentes, R.V.; Gouvea, S.A.; Abreu, G.R.

2011-01-01

The objective of the present study was to determine the antihyperalgesic effect of sertraline, measured indirectly by the changes of sciatic afferent nerve activity, and its effects on cardiorespiratory parameters, using the model of formalin-induced inflammatory nociception in anesthetized rats. Serum serotonin (5-HT) levels were measured in order to test their correlation with the analgesic effect. Male Wistar rats (250-300 g) were divided into 4 groups (N = 8 per group): sertraline-treated group (Sert + Saline (Sal) and Sert + Formalin (Form); 3 mg·kg−1·day−1, ip, for 7 days) and saline-treated group (Sal + Sal and Sal + Form). The rats were injected with 5% (50 µL) formalin or saline into the right hind paw. Sciatic nerve activity was recorded using a silver electrode connected to a NeuroLog apparatus, and cardiopulmonary parameters (mean arterial pressure, heart rate and respiratory frequency), assessed after arterial cannulation and tracheotomy, were monitored using a Data Acquisition System. Blood samples were collected from the animals and serum 5-HT levels were determined by ELISA. Formalin injection induced the following changes: sciatic afferent nerve activity (+50.8 ± 14.7%), mean arterial pressure (+1.4 ± 3 mmHg), heart rate (+13 ± 6.8 bpm), respiratory frequency (+4.6 ± 5 cpm) and serum 5-HT increased to 1162 ± 124.6 ng/mL. Treatment with sertraline significantly reduced all these parameters (respectively: +19.8 ± 6.9%, -3.3 ± 2 mmHg, -13.1 ± 10.8 bpm, -9.8 ± 5.7 cpm) and serum 5-HT level dropped to 634 ± 69 ng/mL (P < 0.05). These results suggest that sertraline plays an analgesic role in formalin-induced nociception probably through a serotonergic mechanism. PMID:22086464

Army Health Promotion, Risk Reduction, Suicide Prevention: Report 2010

DTIC Science & Technology

2010-07-01

weigh the risks with potential benefits of using SSRIs when treating 18 to 29 year-old patients due to the increased risk for suicidal behavior...personnel, facilities and resources. (V,3) Paroxetine: A selective serotonin reuptake inhibitor ( SSRI ) antidepressant. Paroxetine is used to treat major...behavior. (page 30)  [MEDCOM] Clinicians need to carefully weigh the risks with potential benefits of using SSRIs when treating 18 to 29 year-old

EEG gamma synchronization is associated with response to paroxetine treatment.

PubMed

Arikan, Mehmet Kemal; Metin, Baris; Tarhan, Nevzat

2018-08-01

Resistance to medication is a significant problem in psychiatric practice, and effective methods for predicting response are needed to optimize treatment efficacy and limit morbidity. Gamma oscillations are considered as an index of the brain's general cognitive activity; however, the role of gamma oscillations in disease has not been studied sufficiently. This study aimed to determine if gamma power during rest can be used to predict response to anti-depressant medication treatment. Hamilton Depression Rating Scale (HDRS) score and resting state gamma power was measured in 18 medication-free patients during an episode of major depression. After 6 weeks of paroxetine monotherapy HDRS was administered again. Baseline gamma power at frontal, central and temporal electrodes before treatment was significantly related to post-treatment change in HDRS scores. The results indicate that gamma oscillations could be considered a marker of response to paroxetine treatment in patients with major depression. Copyright © 2018. Published by Elsevier B.V.

Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence.

PubMed

Le Noury, Joanna; Nardo, John M; Healy, David; Jureidini, Jon; Raven, Melissa; Tufanaru, Catalin; Abi-Jaoude, Elia

2015-09-16

To reanalyse SmithKline Beecham's Study 329 (published by Keller and colleagues in 2001), the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the treatment of adolescents with unipolar major depression. The reanalysis under the restoring invisible and abandoned trials (RIAT) initiative was done to see whether access to and reanalysis of a full dataset from a randomised controlled trial would have clinically relevant implications for evidence based medicine. Double blind randomised placebo controlled trial. 12 North American academic psychiatry centres, from 20 April 1994 to 15 February 1998. 275 adolescents with major depression of at least eight weeks in duration. Exclusion criteria included a range of comorbid psychiatric and medical disorders and suicidality. Participants were randomised to eight weeks double blind treatment with paroxetine (20-40 mg), imipramine (200-300 mg), or placebo. The prespecified primary efficacy variables were change from baseline to the end of the eight week acute treatment phase in total Hamilton depression scale (HAM-D) score and the proportion of responders (HAM-D score ≤8 or ≥50% reduction in baseline HAM-D) at acute endpoint. Prespecified secondary outcomes were changes from baseline to endpoint in depression items in K-SADS-L, clinical global impression, autonomous functioning checklist, self-perception profile, and sickness impact scale; predictors of response; and number of patients who relapse during the maintenance phase. Adverse experiences were to be compared primarily by using descriptive statistics. No coding dictionary was prespecified. The efficacy of paroxetine and imipramine was not statistically or clinically significantly different from placebo for any prespecified primary or secondary efficacy outcome. HAM-D scores decreased by 10.7 (least squares mean) (95% confidence interval 9.1 to 12.3), 9.0 (7.4 to 10.5), and 9.1 (7.5 to 10.7) points, respectively, for the paroxetine, imipramine and placebo groups (P=0.20). There were clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events in the paroxetine group and cardiovascular problems in the imipramine group. Neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs. Access to primary data from trials has important implications for both clinical practice and research, including that published conclusions about efficacy and safety should not be read as authoritative. The reanalysis of Study 329 illustrates the necessity of making primary trial data and protocols available to increase the rigour of the evidence base. © Le Noury et al 2015.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for the prevention of tension-type headache in adults.

PubMed

Banzi, Rita; Cusi, Cristina; Randazzo, Concetta; Sterzi, Roberto; Tedesco, Dario; Moja, Lorenzo

2015-05-01

This is an updated version of the Cochrane review published in 2005 on selective serotonin re-uptake inhibitors (SSRIs) for preventing migraine and tension-type headache. The original review has been split in two parts and this review now only regards tension-type headache prevention. Another updated review covers migraine. Tension-type headache is the second most common disorder worldwide and has high social and economic relevance. As serotonin and other neurotransmitters may have a role in pain mechanisms, SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been evaluated for the prevention of tension-type headache. To determine the efficacy and tolerability of SSRIs and SNRIs compared to placebo and other active interventions in the prevention of episodic and chronic tension-type headache in adults. For the original review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2003, Issue 4), MEDLINE (1966 to January 2004), EMBASE (1994 to May 2003), and Headache Quarterly (1990 to 2003). For this update, we revised the original search strategy to reflect the broader type of intervention (SSRIs and SNRIs). We searched CENTRAL (2014, Issue 10) on the Cochrane Library, MEDLINE (1946 to November 2014), EMBASE (1980 to November 2014), and PsycINFO (1987 to November 2014). We also checked the reference lists of retrieved articles and searched trial registries for ongoing trials. We included randomised controlled trials comparing SSRIs or SNRIs with any type of control intervention in participants 18 years and older, of either sex, with tension-type headache. Two authors independently extracted data (headache frequency, index, intensity, and duration; use of symptomatic/analgesic medication; quality of life; and withdrawals) and assessed the risk of bias of trials. The primary outcome is tension-type headache frequency, measured by the number of headache attacks or the number of days with headache per evaluation period. The original review included six studies on tension-type headache. We now include eight studies with a total of 412 participants with chronic forms of tension-type headache. These studies evaluated five SSRIs (citalopram, sertraline, fluoxetine, paroxetine, fluvoxamine) and one SNRI (venlafaxine). The two new studies included in this update are placebo controlled trials, one evaluated sertraline and one venlafaxine. Six studies, already included in the previous version of this review, compared SSRIs to other antidepressants (amitriptyline, desipramine, sulpiride, mianserin). Most of the included studies had methodological and/or reporting shortcomings and lacked adequate power. Follow-up ranged between two and four months.Six studies explored the effect of SSRIs or SNRIs on tension-type headache frequency, the primary endpoint. At eight weeks of follow-up, we found no difference when compared to placebo (two studies, N = 127; mean difference (MD) -0.96, 95% confidence interval (CI) -3.95 to 2.03; I(2)= 0%) or amitriptyline (two studies, N = 152; MD 0.76, 95% CI -2.05 to 3.57; I(2)= 44%).When considering secondary outcomes, SSRIs reduce the symptomatic/analgesic medication use for acute headache attacks compared to placebo (two studies, N = 118; MD -1.87, 95% CI -2.09 to -1.65; I(2)= 0%). However, amitriptyline appeared to reduce the intake of analgesic more efficiently than SSRIs (MD 4.98, 95% CI 1.12 to 8.84; I(2)= 0%). The studies supporting these findings were considered at unclear risk of bias. We found no differences compared to placebo or other antidepressants in headache duration and intensity.SSRIs or SNRI were generally more tolerable than tricyclics. However, the two groups did not differ in terms of number of participants who withdrew due to adverse events or for other reasons (four studies, N = 257; odds ratio (OR) 1.04; 95% CI 0.41 to 2.60; I(2)= 25% and OR 1.55, 95% CI 0.71 to 3.38; I(2)= 0%).We did not find any study comparing SSRIs or SNRIs with pharmacological treatments other than antidepressants (e.g. botulinum toxin) or non-drug therapies (e.g. psycho-behavioural treatments, manual therapy, acupuncture). Since the last version of this review, the new included studies have not added high quality evidence to support the use of SSRIs or venlafaxine (a SNRI) as preventive drugs for tension-type headache. Over two months of treatment, SSRIs or venlafaxine are no more effective than placebo or amitriptyline in reducing headache frequency in patients with chronic tension-type headache. SSRIs seem to be less effective than tricyclic antidepressants in terms of intake of analgesic medications. Tricyclic antidepressants are associated with more adverse events; however, this did not cause a greater number of withdrawals. No reliable information is available at longer follow-up. Our conclusion is that the use of SSRIs and venlafaxine for the prevention of chronic tension-type headache is not supported by evidence.

Ultrasound effects on brain-targeting mannosylated liposomes: in vitro and blood-brain barrier transport investigations.

PubMed

Zidan, Ahmed S; Aldawsari, Hibah

2015-01-01

Delivering drugs to intracerebral regions can be accomplished by improving the capacity of transport through blood-brain barrier. Using sertraline as model drug for brain targeting, the current study aimed at modifying its liposomal vesicles with mannopyranoside. Box-Behnken design was employed to statistically optimize the ultrasound parameters, namely ultrasound amplitude, time, and temperature, for maximum mannosylation capacity, sertraline entrapment, and surface charge while minimizing vesicular size. Moreover, in vitro blood-brain barrier transport model was established to assess the transendothelial capacity of the optimized mannosylated vesicles. Results showed a dependence of vesicular size, mannosylation capacity, and sertraline entrapment on cavitation and bubble implosion events that were related to ultrasound power amplitude, temperature. However, short ultrasound duration was required to achieve >90% mannosylation with nanosized vesicles (<200 nm) of narrow size distribution. Optimized ultrasound parameters of 65°C, 27%, and 59 seconds for ultrasound temperature, amplitude, and time were elucidated to produce 81.1%, 46.6 nm, and 77.6% sertraline entrapment, vesicular size, and mannosylation capacity, respectively. Moreover, the transendothelial ability was significantly increased by 2.5-fold by mannosylation through binding with glucose transporters. Hence, mannosylated liposomes processed by ultrasound could be a promising approach for manufacturing and scale-up of brain-targeting liposomes.

Association between tryptophan hydroxylase-2 genotype and the antidepressant effect of citalopram and paroxetine on immobility time in the forced swim test in mice.

PubMed

Kulikov, Alexander V; Tikhonova, Maria A; Osipova, Daria V; Kulikov, Victor A; Popova, Nina K

2011-10-01

Tryptophan hydroxylase-2 (TPH2) is the rate limiting enzyme of serotonin synthesis in the brain. The 1473G allele of the C1473G polymorphism in mTPH2 gene is associated with reduced enzyme activity and serotonin synthesis rate in the mouse brain. Here, the influence of the 1473G allele on the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs), citalopram (2.5 or 5.0mg/kg) and paroxetine (5.0 or 10.0mg/kg), in the forced swim test was studied using B6-1473G and B6-1473C congenic mouse lines with the 1473G (decreased TPH2 activity) or 1473C (normal TPH2 activity) alleles, respectively, transferred to the genome of C57BL/6 mouse strain. Paroxetine (5.0 or 10.0mg/kg) and citalopram (2.5 or 5.0mg/kg) decreased immobility time in B6-1473C mice, while both doses of paroxetine and 2.5mg/kg of citaloprame did not alter immobility time in B6-1473G mice. However, 5.0mg/kg of citalopram reduced immobility in B6-1473G mice. The results provided genetic evidence of moderate association between 1473G allele and reduced sensitivity to SSRIs in mice. Copyright © 2011 Elsevier Inc. All rights reserved.

Balneotherapy versus paroxetine in the treatment of generalized anxiety disorder.

PubMed

Dubois, Olivier; Salamon, Roger; Germain, Christine; Poirier, Marie-France; Vaugeois, Christiane; Banwarth, Bernard; Mouaffak, Fayçal; Galinowski, André; Olié, Jean Pierre

2010-02-01

Preliminary studies have suggested that balneotherapy (BT) is an effective and well-tolerated treatment for generalized anxiety disorder (GAD) and psychotropic medication withdrawal syndrome. We carried out a study in 4 spa resorts to assess the efficacy of BT in GAD. We compared BT to paroxetine in terms of efficacy and safety in a randomized multicentre study lasting 8 weeks. Patients meeting the diagnostic criteria of GAD (DSM-IV) were recruited. Assessments were conducted using the Hamilton Rating Scale for Anxiety (HAM-A) and other scales, by a specifically trained and independent physician. The primary outcome measure was the change in the total HAM-A score between baseline and week 8. A total of 237 outpatients were enrolled in four centres; 117 were assigned randomly to BT and 120 to paroxetine. The mean change in HAM-A scores showed an improvement in both groups with a significant advantage of BT compared to paroxetine (-12.0 vs -8.7; p<0.001). Remission and sustained response rates were also significantly higher in the BT group (respectively 19% vs 7% and 51% vs 28%). BT is an interesting way of treating GAD. Due to its safety profile it could also be tested in resistant forms of generalized anxiety and in patients who do not tolerate or are reluctant to use pharmacotherapies. Copyright 2009 Elsevier Ltd. All rights reserved.

Sertraline-induced periorbital purpura: a case report.

PubMed

Kayhan, Fatih; Eken, Zahide Eriş; Uguz, Faruk

2015-08-01

The incidence of mild to severe levels of spontaneous bleeding due to the usage of selective serotonin reuptake inhibitors (SSRIs) is relatively low. Although the exact mechanism is not known, it is thought that inhibition of the serotonin transporter together with a decrease in platelet serotonin could be responsible for the bleeding. Therefore, the use of SSRIs in conjunction with anti-aggregants may predispose to or exacerbate the risk of bleeding. In this case report, we describe a 44-year-old female patient with a diagnosis of anxiety disorder who spontaneously developed periorbital purpura during treatment with sertraline. Abnormal bleeding after treatment with an SSRI should be kept in mind, and alternative non-SSRI drugs of choice in such cases would be more appropriate. More extensive and comprehensive studies focusing on hemostasis and bleeding disorders are needed for SSRIs such as sertraline. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Hippocampal synapsin I, growth-associated protein-43, and microtubule-associated protein-2 immunoreactivity in learned helplessness rats and antidepressant-treated rats.

PubMed

Iwata, M; Shirayama, Y; Ishida, H; Kawahara, R

2006-09-01

Learned helplessness rats are thought to be an animal model of depression. To study the role of synapse plasticity in depression, we examined the effects of learned helplessness and antidepressant treatments on synapsin I (a marker of presynaptic terminals), growth-associated protein-43 (GAP-43; a marker of growth cones), and microtubule-associated protein-2 (MAP-2; a marker of dendrites) in the hippocampus by immunolabeling. (1) Learned helplessness rats showed significant increases in the expression of synapsin I two days after the attainment of learned helplessness, and significant decreases in the protein expression eight days after the achievement of learned helplessness. Subchronic treatment of naïve rats with imipramine or fluvoxamine significantly decreased the expression of synapsin I. (2) Learned helplessness increased the expression of GAP-43 two days and eight days after learned helplessness training. Subchronic treatment of naïve rats with fluvoxamine but not imipramine showed a tendency to decrease the expression of synapsin I. (3) Learned helplessness rats showed increased expression of MAP-2 eight days after the attainment of learned helplessness. Naïve rats subchronically treated with imipramine showed a tendency toward increased expression of MAP-2, but those treated with fluvoxamine did not. These results indicate that the neuroplasticity-related proteins synapsin I, GAP-43, and MAP-2 may play a role in the pathophysiology of depression and the mechanisms of antidepressants.

Cost utility of maintenance treatment of recurrent depression with sertraline versus episodic treatment with dothiepin.

PubMed

Hatziandreu, E J; Brown, R E; Revicki, D A; Turner, R; Martindale, J; Levine, S; Siegel, J E

1994-03-01

The objective of this study was to model, for patients at risk of recurrent depression, the cost-utility of maintenance therapy with sertraline compared with treatment of acute episodes with dothiepin ('episodic treatment'). Using clinical decision analysis techniques, a Markov state-transition model was constructed to estimate the lifetime costs and quality-adjusted life-years (QALYs) of the 2 therapeutic strategies. The model follows 2 cohorts of 35-year-old women at high risk for recurrent depression over their lifetimes. Model construction and relevant data (probabilities) for performing the analysis were based on existing clinical knowledge. Two physician panels were used to obtain estimates of recurrence probabilities not available in the literature, health utilities, and resource consumption. Costs were obtained from published sources. The baseline analysis showed that it costs 2172 British pounds sterling ($US3692, 1991 currency) to save an additional QALY with sertraline maintenance treatment. Sensitivity analysis showed that the incremental cost-utility ratio ranged from 557 British pounds sterling to 5260 British pounds sterling per QALY. Overall, the resulting ratios are considered to be well within the range of cost-utility ratios that support the adoption and appropriate utilisation of a technology. Based on the study assumptions, long term maintenance treatment with sertraline appears to be clinically and economically justified choice for patients at high risk of recurrent depression.

Antisaccade and smooth pursuit eye movements in healthy subjects receiving sertraline and lorazepam.

PubMed

Green, J F; King, D J; Trimble, K M

2000-03-01

Patients suffering from some psychiatric and neurological disorders demonstrate abnormally high levels of saccadic distractibility when carrying out the antisaccade task. This has been particularly thoroughly demonstrated in patients with schizophrenia. A large body of evidence has been accumulated from studies of patients which suggests that such eye movement abnormalities may arise from frontal lobe dysfunction. The psychopharmacology of saccadic distractibility is less well understood, but is relevant both to interpreting patient studies and to establishing the neurological basis of their findings. Twenty healthy subjects received lorazepam 0.5 mg, 1 mg and 2 mg, sertraline 50 mg and placebo in a balanced, repeated measures study design. Antisaccade, no-saccade, visually guided saccade and smooth pursuit tasks were carried out and the effects of practice and drugs measured. Lorazepam increased direction errors in the antisaccade and no-saccade tasks in a dose-dependent manner. Sertraline had no effect on these measures. Correlation showed a statistically significant, but rather weak, association between direction errors and smooth pursuit measures. Practice was shown to have a powerful effect on antisaccade direction errors. This study supports our previous work by confirming that lorazepam reliably worsens saccadic distractibility, in contrast to other psychotropic drugs such as sertraline and chlorpromazine. Our results also suggest that other studies in this field, particularly those using parallel groups design, should take account of practice effects.

Hippocampal agenesis in an individual who engaged in violent criminal behaviors after discontinuing carbamazepine and paroxetine treatment.

PubMed

Hanada, Hiroaki; Akiyoshi, Jotaro; Kanehisa, Masayuki; Ishitobi, Yoshinobu; Tsuru, Jusen; Tanaka, Yoshihiro; Shimomura, Tsuyoshi; Kawano, Yoshihisa

2013-01-01

Antidepressant discontinuation syndrome (ADS) occurs after abrupt discontinuation of an antidepressant medication. A 23-year-old man with right hippocampal agenesis demonstrated sexual crime (hypersexuality) since the age of eight and had been successfully treated with carbamazepine since the age of 13. He had required increased doses of paroxetine and carbamazepine owing to the development of an unstable affect after quitting his job. He abruptly stopped taking his medication for 3 days and his criminal behaviors re-emerged. We examined changes in brain structure and activity before and after medication cessation, using MRI and functional MRI (fMRI). The image of a girl in a swimsuit increased activity in the thalamus only after medication discontinuation. The alteration in thalamic activity might induce hypersexuality. We conclude that a primary hypersexuality had been suppressed with carbamazepine and paroxetine treatment, and the discontinuation of the medication caused the hypersexuality. © 2012 American Academy of Forensic Sciences.

Neuron and neuroblast numbers and cytogenesis in the dentate gyrus of aged APPswe/PS1dE9 transgenic mice: Effect of long-term treatment with paroxetine.

PubMed

Olesen, Louise Ørum; Sivasaravanaparan, Mithula; Severino, Maurizio; Babcock, Alicia A; Bouzinova, Elena V; West, Mark J; Wiborg, Ove; Finsen, Bente

2017-08-01

Altered neurogenesis may influence hippocampal functions such as learning and memory in Alzheimer's disease. Selective serotonin reuptake inhibitors enhance neurogenesis and have been reported to reduce cerebral amyloidosis in both humans and transgenic mice. We have used stereology to assess the longitudinal changes in the number of doublecortin-expressing neuroblasts and number of granular neurons in the dentate gyrus of APP swe /PS1 dE9 transgenic mice. Furthermore, we investigated the effect of long-term paroxetine treatment on the number of neuroblasts and granular neurons, hippocampal amyloidosis, and spontaneous alternation behaviour, a measure of spatial working memory, in transgenic mice. We observed no difference in granular neurons between transgenic and wild type mice up till 18months of age, and no differences with age in wild type mice. The number of neuroblasts and the performance in the spontaneous alternation task was reduced in aged transgenic mice. Paroxetine treatment from 9 to 18months of age reduced hippocampal amyloidosis without affecting the number of neuroblasts or granular neurons. These findings suggest that the amyloidosis affects the differentiation of neuroblasts and spatial working memory, independent of changes in total granular neurons. Furthermore, while long-term paroxetine treatment may be able to reduce hippocampal amyloidosis, it appears to have no effect on total number of granular neurons or spatial working memory. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Levetiracetam, Carbamazepine, Phenytoin, Valproate, Lamotrigine, Oxcarbazepine, Topiramate, Vinpocetine and Sertraline on Presynaptic Hippocampal Na(+) and Ca(2+) Channels Permeability.

PubMed

Sitges, María; Chiu, Luz María; Reed, Ronald C

2016-04-01

Ion channels are targets of various antiepileptic drugs. In cerebral presynaptic nerve endings Na(+) and Ca(2+) channels are particularly abundant, as they control neurotransmitter release, including the release of glutamate (Glu), the most concentrated excitatory amino acid neurotransmitter in the brain. Several pre-synaptic channels are implicated in the mechanism of action of the pro-convulsive agent, 4-aminopyridine (4-AP). In the present study the effects of levetiracetam and other established and newer (vinpocetine) anti-epileptic drugs, as well as of the anti-depressant, sertraline on the increase in Ca(2+) induced by 4-AP in hippocampal isolated nerve endings were investigated. Also the effects of some of the anti-seizure drugs on the selective increase in Ca(2+) induced by high K(+), or on the selective increase in Na(+) induced by veratridine were tested. Sertraline and vinpocetine effectively inhibited the rise in Ca(2+) induced by 4-AP, which was dependent on the out-in Na(+) gradient and tetrodotoxin sensitive. Carbamazepine, phenytoin, lamotrigine and oxcarbazepine inhibited the rise in Ca(2+) induced by 4-AP too, but at higher concentrations than sertraline and vinpocetine, whereas levetiracetam, valproic acid and topiramate did not. The three latter antiepileptic drugs also failed in modifying other responses mediated by the activation of brain presynaptic Na(+) or Ca(2+) channels, including Glu release. This indicates that levetiracetam, valproic acid and topiramate mechanisms of action are unrelated with a decrease in presynaptic Na(+) or Ca(2+) channels permeability. It is concluded that depolarized cerebral isolated nerve endings represent a useful tool to unmask potential antiepileptic drugs targeting presynaptic Na(+) and/or Ca(2+) channels in the brain; such as vinpocetine or the anti-depressant sertraline, which high effectiveness to control seizures in the animal in vivo has been demonstrated.

History of depressive and anxiety disorders and paroxetine response in patients with irritable bowel syndrome: post hoc analysis from a placebo-controlled study.

PubMed

Marks, David M; Han, Changsu; Krulewicz, Stan; Pae, Chi-Un; Peindl, Kathleen; Patkar, Ashwin A; Masand, Prakash S

2008-01-01

Although irritable bowel syndrome (IBS) is highly comorbid with depressive and anxiety disorders, information on the clinical implications of this comorbidity is limited. We investigated whether a history of depressive and/or anxiety disorders was associated with response to treatment in a double-blind, randomized, placebo-controlled trial of paroxetine controlled release (CR) in IBS. Seventy-two IBS subjects (diagnosed using Rome II criteria) were recruited from August 2003 to November 2005 and randomly assigned to receive flexibly dosed paroxetine CR (dose, 12.5-50 mg/day) or placebo for 12 weeks. The Mini-International Neuropsychiatric Interview (MINI-Plus version) was used to ascertain current (exclusionary) or past diagnoses of depressive and anxiety disorders. Subjective depression, anxiety, and stress were assessed at entry and throughout the trial using the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Perceived Stress Scale (PSS). Severity of IBS symptoms was determined by the Composite Pain Score (CPS), administered via Interactive Voice Response System, and the Clinical Global Impressions scale (CGI). The primary outcome was treatment response defined as ≥ 25% reduction in CPS from randomization to end of treatment. A post hoc analysis (multivariate logistic regression) was done to evaluate whether a history of depressive and/or anxiety disorder was associated with response to medication. Baseline demographic and clinical characteristics (CPS, BDI, BAI, PSS, CGI scores) were similar between groups (history of depressive/anxiety disorder vs. no history). In multivariate logistic regression analysis, treatment response was not predicted by history of depressive and/or anxiety disorder (OR = 0.58, CI = 0.29 to 1.68, p = .32) or drug status (paroxetine CR vs. placebo) (OR = 1.26, CI = 0.68 to 3.21, p = .19). Drug status was significantly associated with the secondary outcome variable of treatment response as defined by a CGI improvement score of 1 to 2 (OR = 12.14, CI = 2.9 to 48.4, p < .001). Paroxetine CR was safe and well tolerated during the study. History of depressive and/or anxiety disorder was not associated with response of IBS symptoms to paroxetine CR. Conclusions are limited due to insufficient statistical power. Further research is needed to clarify the role of selective serotonin reuptake inhibitors in the treatment of IBS and to elucidate the treatment ramifications of comorbid psychiatric disorders. clinicaltrials.gov Identifier: NCT00610909.

Thermal Stability and Kinetic Study of Fluvoxamine Stability in Binary Samples with Lactose.

PubMed

Ghaderi, Faranak; Nemati, Mahboob; Siahi-Shadbad, Mohammad Reza; Valizadeh, Hadi; Monajjemzadeh, Farnaz

2017-04-01

Purpose: In the present study the incompatibility of FLM (fluvoxamine) with lactose in solid state mixtures was investigated. The compatibility was evaluated using different physicochemical methods such as differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy and mass spectrometry. Methods: Non-Isothermally stressed physical mixtures were used to calculate the solid-state kinetic parameters. Different thermal models such as Friedman, Flynn-Wall-Ozawa (FWO) and Kissinger-Akahira-Sunose (KAS) were used for the characterization of the drug-excipient interaction. Results: Overall, the incompatibility of FLM with lactose as a reducing carbohydrate was successfully evaluated and the activation energy of this interaction was calculated. Conclusion: In this research the lactose and FLM Maillard interaction was proved using physicochemical techniques including DSC and FTIR. It was shown that DSC- based kinetic analysis provides fast and versatile kinetic comparison of Arrhenius activation energies for different pharmaceutical samples.

Thermal Stability and Kinetic Study of Fluvoxamine Stability in Binary Samples with Lactose

PubMed Central

Ghaderi, Faranak; Nemati, Mahboob; Siahi-Shadbad, Mohammad Reza; Valizadeh, Hadi; Monajjemzadeh, Farnaz

2017-01-01

Purpose: In the present study the incompatibility of FLM (fluvoxamine) with lactose in solid state mixtures was investigated. The compatibility was evaluated using different physicochemical methods such as differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy and mass spectrometry. Methods: Non-Isothermally stressed physical mixtures were used to calculate the solid–state kinetic parameters. Different thermal models such as Friedman, Flynn–Wall–Ozawa (FWO) and Kissinger–Akahira–Sunose (KAS) were used for the characterization of the drug-excipient interaction. Results: Overall, the incompatibility of FLM with lactose as a reducing carbohydrate was successfully evaluated and the activation energy of this interaction was calculated. Conclusion: In this research the lactose and FLM Maillard interaction was proved using physicochemical techniques including DSC and FTIR. It was shown that DSC- based kinetic analysis provides fast and versatile kinetic comparison of Arrhenius activation energies for different pharmaceutical samples. PMID:28507936

Drug administration adjustments for elderly patients with dysphagia: A case report.

PubMed

Mastroianni, Patrícia de Carvalho; Forgerini, Marcela

2018-01-01

An elderly patient, aged 76 years, diagnosed with dysphagia, depression, hypothyroidism, Alzheimer's disease and mild cognitive deficit, was identified with sertraline and levothyroxine- drug-related problems. Medication Therapy Management (MTM) was used to adjust therapy to the patient's needs by macerating sertraline tablets and solubilizing them in 10-30 mL of orange juice. The patient was advised to take levothyroxine after fasting. Six months later, pharmaceutical follow-up identified an increase in the Mini-Mental State Exam score from 22 to 26 and a decrease in the Clinical Dementia Rating (CDR) scale score from 1.0 to 0.5 in conjunction with mood and physical improvements, as well as a significant decrease in aggressiveness and agitation. Cognitive deficit may be a result of poor drug administration procedures, leading to drug ineffectiveness. Optimizing levothyroxine and sertraline administration, based on knowledge of their physicochemical properties, improves their clinical effectiveness, including the cognition of patients with Alzheimer's disease and dysphagia.

Analytical and ecotoxicological studies on degradation of fluoxetine and fluvoxamine by potassium ferrate.

PubMed

Drzewicz, Przemysław; Drobniewska, Agata; Sikorska, Katarzyna; Nałęcz-Jawecki, Grzegorz

2018-05-14

A large amount of pharmaceuticals are flushed to environment via sewage system. The compounds are persistent in environment and are very difficult to remove in drinking water treatment processes. Degradation of fluoxetine (FLU) and fluvoxamine (FLX) by ferrate(VI) were investigated. For the 10 mg/L of FLU and FLX, 35% and 50% of the compounds were degraded in the presence of 50 mg/L FeO 4 2- within 10 minutes, respectively. After 10 minutes of the reaction, degradation of FLU and FLX is affected by formation of by-products which were likely more reactive with ferrate and competed in the reaction with FeO 4 2- . In the case of FLU, the identified degradation by-products were hydrofluoxetine, N-methyl-3-phenyl-2-propen-1-amine, 4-(trifluoromethyl)phenol and 1-{[(1R,S)-1-Phenyl-2-propen-1-yl]oxy}-4-(trifluoromethyl)benzene. In the case of FLX, the degradation by-products were fluvoxamine acid and 5-methoxy-1-[4-(trifluoromethyl)phenyl]pent-2-en-1-imine. The results of the ecotoxicological study based on protozoa Spirostomum ambiguum have shown that 50 mg/L FeO 4 2- reduced toxicity of 10 mg/L of FLU and FLX by around 50%. However, in the case of FLX, the results of the ecotoxicological study suggested formation of slightly more toxic compound(s) than FLX during reaction with FeO 4 2- . Application of ferrate(VI) is a viable option for drinking water treatment process; however, caution is needed due to formation of by-products with unknown human health risk.

Dysfunction of serotoninergic and dopaminergic neuronal systems in the antidepressant-resistant impairment of social behaviors induced by social defeat stress exposure as juveniles.

PubMed

Hasegawa, Sho; Miyake, Yuriko; Yoshimi, Akira; Mouri, Akihiro; Hida, Hirotake; Yamada, Kiyofumi; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

2018-03-29

Extensive studies have been performed on the role of monoaminergic neuronal systems in rodents exposed to social defeat stress as adults. In the present study, we investigated the role of monoaminergic neuronal systems in the impairment of social behaviors induced by social defeat stress exposure as juveniles. Juvenile, male C57BL/6J mice were exposed to social defeat stress for 10 consecutive days. From 1 day after the last stress exposure, desipramine, sertraline, and aripiprazole, were administered for 15 days. Social behaviors were assessed at 1 and 15 days after the last stress exposure. Monoamine turnover was determined in specific regions of the brain in the mice exposed to the stress. Stress exposure as juveniles induced the impairment of social behaviors in adolescent mice. In mice that showed the impairment of social behaviors, turnover of the serotonin and dopamine, but not noradrenaline was decreased in specific brain regions. Acute and repeated administration of desipramine, sertraline, and aripiprazole failed to attenuate the impairment of social behaviors, whereas repeated administration of a combination of sertraline and aripiprazole showed additive attenuating effects. These findings suggest that social defeat stress exposure as juveniles induces the treatment-resistant impairment of social behaviors in adolescents through dysfunction in the serotoninergic and dopaminergic neuronal systems. The combination of sertraline and aripiprazole may be used as a new treatment strategy for treatment-resistant stress-related psychiatric disorders in adolescents with adverse juvenile experiences.

Paroxetine and Low-dose Risperidone Induce Serotonin 5-HT1A and Dopamine D2 Receptor Heteromerization in the Mouse Prefrontal Cortex.

PubMed

Kolasa, Magdalena; Solich, Joanna; Faron-Górecka, Agata; Żurawek, Dariusz; Pabian, Paulina; Łukasiewicz, Sylwia; Kuśmider, Maciej; Szafran-Pilch, Kinga; Szlachta, Marta; Dziedzicka-Wasylewska, Marta

2018-05-01

Recently, it has been shown that serotonin 5-HT 1A receptor interacts with dopamine D2 receptor in vitro. However, the existence of 5-HT 1A -D2 heteromers in native tissue remains unexplored. In the present study, we investigated 5-HT 1A -D2 receptor heteromerization in mice treated acutely or chronically with paroxetine (10 mg/kg) or risperidone (0.05 mg/kg). Receptor heteromerization was visualized and quantified in the mouse brain by in situ proximity ligation assay (PLA). Additionally, we aimed to determine the cellular localization of 5-HT 1A -D2 receptor heteromers in mouse adult primary neuronal cells by immunofluorescent staining with markers for astrocytes (GFAP) and neurons (NeuN and MAP2). The results from the current study demonstrated that 5-HT 1A and D2 receptor co-localization and heteromerization occurred in the mouse prefrontal cortex. Counterstaining after PLA confirmed neuronal (pyramidal and GABAergic) as well as astrocytal localization of 5-HT 1A -D2 receptor heteromers. Chronic administration of paroxetine or risperidone increased the level of 5-HT 1A -D2 receptor heteromers in the prefrontal cortex. These changes were not accompanied by any changes in the expression of mRNAs (measured by in situ hybridization) or densities of 5-HT 1A and D2 receptors (quantified by receptor autoradiography with [3H]8-OH-DPAT and [3H]domperidone, respectively), what all indicated that paroxetine and risperidone facilitated 5-HT 1A -D2 heteromer formation independently of the receptor expression. In vitro homogenous time-resolved FRET (HTRF) study confirmed the ability of tested drugs to influence the human 5-HT 1A -D2 heteromer formation. The obtained data indicate that the increase in 5-HT 1A -D2 receptor heteromerization is a common molecular characteristic of paroxetine and low-dose risperidone treatment. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Mood- and restraint-based antecedents to binge episodes in bulimia nervosa: possible influences of the serotonin system.

PubMed

Steiger, Howard; Gauvin, Lise; Engelberg, Marla J; Ying Kin, N M K Ng; Israel, Mimi; Wonderlich, Stephen A; Richardson, Jodie

2005-11-01

In bulimic syndromes, binge episodes are thought to be caused by dietary restraint and negative moods. However, as central serotonin (5-hydroxytryptamine: 5-HT) mechanisms regulate appetite and mood, the 5-HT system could be implicated in diet- and mood-based binge antecedents. We used hand-held computers to obtain repeated "online" measurements of eating behaviors, moods, and self-concepts in 21 women with bulimic syndromes, and modeled 5-HT system activity with a measure of platelet [3H]paroxetine-binding density. Mood and self-concept ratings were found to be worse before binge episodes (than at other moments), and cognitive restraint was increased. After binges, mood and self-concept deteriorated further, and thoughts of dieting became more intense. Intriguingly, lower paroxetine-binding density predicted poorer mood and self-concept before a binge, larger post-binge decrements in mood and self-concept, and larger post-binge increases in dietary restraint. Paroxetine binding thus seemed to reflect processes that impacted upon mood-related antecedents to binge episodes, and consequences implicating mood and dietary restraint.

Hybrid silica monolith for microextraction by packed sorbent to determine drugs from plasma samples by liquid chromatography-tandem mass spectrometry.

PubMed

de Souza, Israel D; Domingues, Diego S; Queiroz, Maria E C

2015-08-01

The present study (1) reports on the synthesis of two hybrid silica monoliths functionalized with aminopropyl or cyanopropyl groups by the sol-gel process; (2) evaluates these monoliths as selective stationary phase for microextraction by packed sorbent (MEPS) to determine drugs in plasma samples via liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the multiple reactions monitoring (MRM) mode; and (3) discusses important factors related to the optimization of MEPS efficiency as well as the carryover effect. The prepared hybrid silica monoliths consisted of a uniform, porous, and continuous silica monolithic network. The structure of the aminopropyl hybrid silica monolith was more compact than the structure of the cyanopropyl hybrid silica monolith. The Fourier-transform infrared spectroscopy (FTIR) spectra of the hybrid silica monoliths displayed readily identifiable peaks, characteristic of the cyanopropyl and aminopropyl groups. Compared with the aminopropyl hybrid silica phase, the cyanopropyl hybrid silica phase exhibited higher binding capacity for most of the target drugs. The developed method afforded adequate linearity at concentrations ranging from the lower limit of quantification (0.05-1.00 ng mL(-1)) to the upper limit of quantification (40-10,500 ng mL(-1)); the coefficients of determination (r(2)) were higher than 0.9955. The precision of the method presented coefficients of variation (CV) lower than 14%; the relative standard error (RSE) of the accuracy ranged from -12% to 14%. The developed method allowed for simultaneous analysis of five antipsychotics (olanzapine, quetiapine, clozapine, haloperidol, and chlorpromazine) in combination with seven antidepressants (mirtazapine, paroxetine, citalopram, sertraline, imipramine, clomipramine, fluoxetine), two anticonvulsants (carbamazepine and lamotrigine), and two anxiolytics (diazepam and clonazepam) in plasma samples from schizophrenic patients, which should be valuable for therapeutic drug monitoring purposes. Copyright © 2015 Elsevier B.V. All rights reserved.

Prediction of Long-Term Treatment Response to Selective Serotonin Reuptake Inhibitors (SSRIs) Using Scalp and Source Loudness Dependence of Auditory Evoked Potentials (LDAEP) Analysis in Patients with Major Depressive Disorder

PubMed Central

Lee, Bun-Hee; Park, Young-Min; Lee, Seung-Hwan; Shim, Miseon

2015-01-01

Background: Animal and clinical studies have demonstrated that the loudness dependence of auditory evoked potentials (LDAEP) is inversely related to central serotonergic activity, with a high LDAEP reflecting weak serotonergic neurotransmission and vice versa, though the findings in humans have been less consistent. In addition, a high pretreatment LDAEP appears to predict a favorable response to antidepressant treatments that augment the actions of serotonin. The aim of this study was to test whether the baseline LDAEP is correlated with response to long-term maintenance treatment in patients with major depressive disorder (MDD). Methods: Scalp N1, P2 and N1/P2 LDAEP and standardized low resolution brain electromagnetic tomography-localized N1, P2, and N1/P2 LDAEP were evaluated in 41 MDD patients before and after they received antidepressant treatment (escitalopram (n = 32, 10.0 ± 4.0 mg/day), sertraline (n = 7, 78.6 ± 26.7 mg/day), and paroxetine controlled-release formulation (n = 2, 18.8 ± 8.8 mg/day)) for more than 12 weeks. A treatment response was defined as a reduction in the Beck Depression Inventory (BDI) score of >50% between baseline and follow-up. Results: The responders had higher baseline scalp P2 and N1/P2 LDAEP than nonresponders (p = 0.017; p = 0.036). In addition, changes in total BDI score between baseline and follow-up were larger in subjects with a high baseline N1/P2 LDAEP than those with a low baseline N1/P2 LDAEP (p = 0.009). There were significantly more responders in the high-LDAEP group than in the low-LDAEP group (p = 0.041). Conclusions: The findings of this study reveal that a high baseline LDAEP is associated with a clinical response to long-term antidepressant treatment. PMID:25794285

Management strategies for premenstrual syndrome/premenstrual dysphoric disorder.

PubMed

Jarvis, Courtney I; Lynch, Ann M; Morin, Anna K

2008-07-01

To evaluate the current nonpharmacologic and pharmacologic treatment options for symptoms of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). Literature was obtained through searches of MEDLINE Ovid (1950-March week 3, 2008) and EMBASE Drugs and Pharmacology (all years), as well as a bibliographic review of articles identified by the searches. Key terms included premenstrual syndrome, premenstrual dysphoric disorder, PMS, PMDD, and treatment. All pertinent clinical trials, retrospective studies, and case reports in human subjects published in the English language were identified and evaluated for the safety and efficacy of pharmacologic and nonpharmacologic treatments of PMS/PMDD. Data from these studies and information from review articles were included in this review. Selective serotonin-reuptake inhibitors (SSRIs) have been proven safe and effective for the treatment of PMDD and are recommended as first-line agents when pharmacotherapy is warranted. Currently fluoxetine, controlled-release paroxetine, and sertraline are the only Food and Drug Administration-approved agents for this indication. Suppression of ovulation using hormonal therapies is an alternative approach to treating PMDD when SSRIs or second-line psychotropic agents are ineffective; however, adverse effects limit their use. Anxiolytics, spironolactone, and nonsteroidal antiinflammatory drugs can be used as supportive care to relieve symptoms. Despite lack of specific evidence, lifestyle modifications and exercise are first-line recommendations for all women with PMS/PMDD and may be all that is needed to treat mild-to-moderate symptoms. Herbal and vitamin supplementation and complementary and alternative medicine have been evaluated for use in PMS/PMDD and have produced unclear or conflicting results. More controlled clinical trials are needed to determine their safety and efficacy and potential for drug interactions. Healthcare providers need to be aware of the symptoms of PMS and PMDD and the treatment options available. Treatment selection should be based on individual patient symptoms, concomitant medical history, and need for contraception.

The Cognitive Effects of Antidepressants in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

PubMed Central

Rosenblat, Joshua D; Kakar, Ron

2016-01-01

Background: Cognitive dysfunction is often present in major depressive disorder (MDD). Several clinical trials have noted a pro-cognitive effect of antidepressants in MDD. The objective of the current systematic review and meta-analysis was to assess the pooled efficacy of antidepressants on various domains of cognition in MDD. Methods: Trials published prior to April 15, 2015, were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, Embase, PsychINFO, Clinicaltrials.gov, and relevant review articles. Data from randomized clinical trials assessing the cognitive effects of antidepressants were pooled to determine standard mean differences (SMD) using a random-effects model. Results: Nine placebo-controlled randomized trials (2 550 participants) evaluating the cognitive effects of vortioxetine (n = 728), duloxetine (n = 714), paroxetine (n = 23), citalopram (n = 84), phenelzine (n = 28), nortryptiline (n = 32), and sertraline (n = 49) were identified. Antidepressants had a positive effect on psychomotor speed (SMD 0.16; 95% confidence interval [CI] 0.05–0.27; I2 = 46%) and delayed recall (SMD 0.24; 95% CI 0.15–0.34; I2 = 0%). The effect on cognitive control and executive function did not reach statistical significance. Of note, after removal of vortioxetine from the analysis, statistical significance was lost for psychomotor speed. Eight head-to-head randomized trials comparing the effects of selective serotonin reuptake inhibitors (SSRIs; n = 371), selective serotonin and norepinephrine reuptake inhibitors (SNRIs; n = 25), tricyclic antidepressants (TCAs; n = 138), and norepinephrine and dopamine reuptake inhibitors (NDRIs; n = 46) were identified. No statistically significant difference in cognitive effects was found when pooling results from head-to-head trials of SSRIs, SNRIs, TCAs, and NDRIs. Significant limitations were the heterogeneity of results, limited number of studies, and small sample sizes. Conclusions: Available evidence suggests that antidepressants have a significant positive effect on psychomotor speed and delayed recall. PMID:26209859

Depression drug treatment outcomes in pregnancy and the postpartum period: a systematic review and meta-analysis.

PubMed

McDonagh, Marian S; Matthews, Annette; Phillipi, Carrie; Romm, Jillian; Peterson, Kim; Thakurta, Sujata; Guise, Jeanne-Marie

2014-09-01

To evaluate the comparative benefits and harms in both mother and child of antidepressant treatment for depression in pregnant or postpartum women. MEDLINE, the Cochrane Library, CINAHL, Scopus, ClinicalTrials.gov (inception to July 2013), manufacturers, and reference lists. Two reviewers independently selected studies of pregnant women with depression comparing antidepressants with each other, placebo or no treatment, or nondrug treatments. Studies making comparisons among women taking antidepressants for any reason and those not taking antidepressants (depression status unknown) were used to fill gaps in the evidence. Dual study data extraction and quality assessment were used. Six randomized controlled trials and 15 observational studies provided evidence. Low-strength evidence suggested neonates of pregnant women with depression taking selective serotonin reuptake inhibitors had higher risk of respiratory distress than did neonates of untreated women (13.9% compared with 7.8%; P<.001) but no difference in risk of neonatal convulsions (0.14% compared with 0.11%; P=.64) or preterm birth (17% compared with 10%; P=.07). Indirect evidence from studies of pregnant women receiving antidepressants for mixed or unreported reasons compared with pregnant women not taking antidepressants (depression status unknown) suggested future research should focus on congenital anomalies and autism spectrum and attention deficit disorders in the child. In postpartum depression, low-strength evidence suggested symptom response was not improved when sertraline was added to psychotherapy or when cognitive-behavioral therapy was added to paroxetine. Evidence was insufficient for other outcomes, including depression symptoms, functional capacity, breastfeeding, and infant and child development. A serious limitation is the lack of study populations of exclusively depressed pregnant and postpartum women. Evidence about the comparative benefits and harms of pharmacologic treatment of depression in pregnant and postpartum women was largely inadequate to allow informed decisions about treatment. Considering the prevalence of depression, filling this gap is essential.

PHOTO-ISOMERIZATION OF FLUVOXAMINE IN AQUATIC SOLUTIONS. (R829006)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

[Efficacy of Qilin Pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation].

PubMed

Li, Jian-xin; Lu, Qing-ge

2015-05-01

To observe the clinical effectiveness of Qilin Pills combined with sertraline in the treatment of secondary non-consolidated kidney qi premature ejaculation (PE). A total of 120 patients with secondary non-consolidated kidney qi PE were randomly assigned to groups A (aged [35.5 ± 5.4] yr), B (aged [36.2 ± 5.7] yr), and C (aged [35.2 ± 5.3] yr) in the ratio of 1:1:1 to receive Qilin Pills (once 6 g, bid), sertraline (once 50 mg, qd), and Qilin Pills plus sertraline, respectively, all for 4 weeks. The intravaginal ejaculatory latency time (IELT) and PE diagnostic tool (PEDT) scores were obtained before and after medication and at 1 month after drug withdrawal, and comparative analyses were made among the three groups of patients. The IELT was dramatically prolonged in groups A, B, and C after treatment ([3.23 ± 1.84], [3.87 ± 2.43], and [5.92 ± 3.11] min) and at 1 month after drug withdrawal ([1.85 ± 1.27], [1.52 ± 1.06], and [ 4.26 ± 1.88 ] min) as compared with the baseline ([0.88 ± 0.45], [0.84 ± 0.47], and [0.85 ± 0.50] min) (P < 0.01), even longer in group C than in A and B (P < 0.01). The PEDT scores of the three groups were 5.1 ± 1.8, 4.9 ± 1.7, and 3.8 ± 1.2 after treatment and 8.2 ± 2.4, 8.1 ± 2.4, and 6.5 ± 2.1 at 1 month after drug withdrawal, significantly improved in comparison with 13.2 ± 3.2, 12.8 ± 3.1, and 13.1 ± 3.4 before treatment (P < 0.01), even more significantly in group C than in A and B (P < 0.01). Qilin Pills combined with sertraline has a definite efficacy in the treatment of secondary non-consolidated kidney qi PE and therefore deserves wide clinical application.

Study protocol: a phase III randomised, double-blind, parallel arm, stratified, block randomised, placebo-controlled trial investigating the clinical effect and cost-effectiveness of sertraline for the palliative relief of breathlessness in people with chronic breathlessness.

PubMed

Watts, Gareth J; Clark, Katherine; Agar, Meera; Davidson, Patricia M; McDonald, Christine; Lam, Lawrence T; Sajkov, Dimitar; McCaffrey, Nicola; Doogue, Matthew; Abernethy, Amy P; Currow, David C

2016-11-29

Breathlessness remains a highly prevalent and distressing symptom for many patients with progressive life-limiting illnesses. Evidence-based interventions for chronic breathlessness are limited, and there is an ongoing need for high-quality research into developing management strategies for optimal palliation of this complex symptom. Previous studies have suggested that selective serotonin reuptake inhibitors such as sertraline may have a role in reducing breathlessness. This paper presents the protocol for a large, adequately powered randomised study evaluating the use of sertraline for chronic breathlessness in people with progressive life-limiting illnesses. A total of 240 participants with modified Medical Research Council Dyspnoea Scale breathlessness of level 2 or higher will be randomised to receive either sertraline or placebo for 28 days in this multisite, double-blind study. The dose will be titrated up every 3 days to a maximum of 100 mg daily. The primary outcome will be to compare the efficacy of sertraline with placebo in relieving the intensity of worst breathlessness as assessed by a 0-100 mm Visual Analogue Scale. A number of other outcome measures and descriptors of breathlessness as well as caregiver assessments will also be recorded to ensure adequate analysis of participant breathlessness and to allow an economic analysis to be performed. Participants will also be given the option of continuing blinded treatment until either study data collection is complete or net benefit ceases. Appropriate statistical analysis of primary and secondary outcomes will be used to describe the wealth of data obtained. Ethics approval was obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals and the key findings presented at national and international conferences. ACTRN12610000464066. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Effects of single and combined gabapentin use in elevated plus maze and forced swimming tests.

PubMed

Kilic, Fatma Sultan; Ismailoglu, Sule; Kaygisiz, Bilgin; Oner, Setenay

2014-10-01

Gabapentin, a third-generation antiepileptic drug, is a structural analogue of γ-aminobutyric acid, which is an important mediator of central nervous system. There is clinical data indicating its effectiveness in the treatment of psychiatric illnesses such as bipolar disorder and anxiety disorders. We aimed to investigate the antidepressant and anxiolytic-like effects and mechanisms of gabapentin in rats. Female Spraque-Dawley rats weighing 250±20 g were used. A total of 13 groups were formed, each containing 8 rats: gabapentin (5, 10, 20, 40 mg/kg), amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg), ketamine (10 mg/kg), gabapentin 20 mg/kg was also combined with amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg) and ketamine (10 mg/kg). All the drugs were used intraperitoneally as single dose. Saline was administered to the control group. Elevated plus maze and forced swimming tests were used as experimental models of anxiety and depression, respectively. It was observed that gabapentin showed an anxiolytic-like and antidepressant-like effect in all doses in rats. Its antidepressant effect was found to be the same as the antidepressant effects of amitriptyline and sertraline. There was no change in the antidepressant effect when gabapentin was combined with amitriptyline and ketamine, but there was an increase when combined with sertraline and diazepam. Gabapentin and amitriptyline showed similar anxiolytic effect, whereas ketamine and diazepam had more potent anxiolytic effect compared with them. These data suggest that gabapentin may possess antidepressant- and anxiolytic-like effects.

Molecular biomarkers predictive of sertraline treatment response in young children with fragile X syndrome

PubMed Central

AlOlaby, Reem Rafik; Sweha, Stefan R; Silva, Marisol; Durbin-Johnson, Blythe; Yrigollen, Carolyn M; Pretto, Dalyir; Hagerman, Randi J; Tassone, Flora

2017-01-01

Objectives Several neurotransmitters involved in brain development are altered in fragile X syndrome (FXS), the most common monogenic cause of autism spectrum disorder (ASD). Serotonin plays a vital role in synaptogenesis and postnatal brain development. Deficits in serotonin synthesis and abnormal neurogenesis were shown in young children with autism, suggesting that treating within the first years of life with a selective serotonin reuptake inhibitor might be the most effective time. In this study we aimed to identify molecular biomarkers involved in the serotonergic pathway that could predict the response to sertraline treatment in young children with FXS. Methods Genotypes were determined for several genes involved in serotonergic pathway in 51 children with FXS, ages 24 to 68 months. Correlations between genotypes and deviations from baseline in primary and secondary outcome measures were modeled using linear regression models. Results A significant association was observed between a BDNF polymorphism and improvements for several clinical measures, including the Clinical Global Impression scale (P= 0.008) and the Cognitive T Score (P= 0.017) in those treated with sertraline compared to those in the placebo group. Additionally, polymorphisms in the MAOA, Cytochrome P450 2C19 and 2D6, and in the 5-HTTLPR gene showed a significant correlation with some of the secondary measures included in this study. Conclusion This study shows that polymorphisms of genes involved in the serotonergic pathway could play a potential role in predicting response to sertraline treatment in young children with FXS. Larger studies are warranted to confirm these initial findings. PMID:28242040

Heart rate variability is a trait marker of major depressive disorder: evidence from the sertraline vs. electric current therapy to treat depression clinical study.

PubMed

Brunoni, Andre Russowsky; Kemp, Andrew H; Dantas, Eduardo M; Goulart, Alessandra C; Nunes, Maria Angélica; Boggio, Paulo S; Mill, José Geraldo; Lotufo, Paulo A; Fregni, Felipe; Benseñor, Isabela M

2013-10-01

Decreased heart rate variability (HRV) is a cardiovascular predictor of mortality. Recent debate has focused on whether reductions in HRV in major depressive disorder (MDD) are a consequence of the disorder or a consequence of pharmacotherapy. Here we report on the impact of transcranial direct current stimulation (tDCS), a non-pharmacological intervention, vs. sertraline to further investigate this issue. The employed design was a double-blind, randomized, factorial, placebo-controlled trial. One hundred and eighteen moderate-to-severe, medication-free, low-cardiovascular risk depressed patients were recruited for this study and allocated to either active/sham tDCS (10 consecutive sessions plus two extra sessions every other week) or placebo/sertraline (50 mg/d) for 6 wk. Patients were age and gender-matched to healthy controls from a concurrent cohort study [the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)]. The impact of disorder, treatment and clinical response on HRV (root mean square of successive differences and high frequency) was examined. Our findings confirmed that patients displayed decreased HRV relative to controls. Furthermore, HRV scores did not change following treatment with either a non-pharmacological (tDCS) or pharmacological (sertraline) intervention, nor did HRV increase with clinical response to treatment. Based on these findings, we discuss whether reduced HRV is a trait-marker for MDD, which may predispose patients to a host of conditions and disease even after response to treatment. Our findings have important implications for our understanding of depression pathophysiology and the relationship between MDD, cardiovascular disorders and mortality.

Urinary serotonin level is associated with serotonin syndrome after moclobemide, sertraline, and citalopram overdose.

PubMed

Brvar, Miran; Stajer, Dusan; Kozelj, Gordana; Osredkar, Josko; Mozina, Martin; Bunc, Matjaz

2007-01-01

Altered mental status, autonomic dysfunction, and neuromuscular abnormalities are a characteristic triad of serotonin syndrome. No laboratory tests confirm the diagnosis of serotonin syndrome. A 35-year-old woman took moclobemide, sertraline, and citalopram in a suicide attempt. She was conscious with mild tachycardia, hypertension, and tachypnea one hour after ingestion. In the second hour after ingestion diaphoresis, mydriasis, horizontal nystagmus, trismus, hyperreflexia, clonus, and tremor appeared. She became agitated and unresponsive. In the third hour after ingestion she became comatose and hyperthermic. She was anesthetized, paralyzed, intubated, and ventilated for 24 hours. Serum moclobemide, sertraline, and citalopram levels were above therapeutic levels. The serum serotonin level was within normal limits and the urinary 5-hydroxyindoleacetic acid:creatinine ratio was below the average daily value. The urinary serotonin:creatinine ratio was increased on arrival (1 mg/g). The urinary serotonin level is increased in serotonin syndrome due to a monoamine oxidase inhibitor and selective serotonin-reuptake inhibitors overdose. It is possible that urinary serotonin concentration could be used as a biochemical marker of serotonin syndrome.

Global measures of outcome in a controlled comparison of pharmacological and psychological treatment of panic disorder and agoraphobia in primary care.

PubMed Central

Sharp, D M; Power, K G; Simpson, R J; Swanson, V; Anstee, J A

1997-01-01

BACKGROUND: Panic disorder, with and without agoraphobia, is a prevalent condition which presents primarily in general practice. Previous clinical outcome studies have been conducted mainly in specialist university departments or hospital settings, and have tended to employ complex rating scales that are not well suited for use as outcome measures in primary care. AIM: To evaluate the outcome, in a primary care setting, of fluvoxamine versus cognitive behaviour therapy, each used alone and in combination in a double-blind placebo-controlled framework, balanced for therapist contact. METHOD: A total of 149 patients satisfying DSMIII-R criteria for panic disorder were randomly allocated to receive one of the following: fluvoxamine, placebo, fluvoxamine plus cognitive behaviour therapy, placebo plus cognitive behaviour therapy, and cognitive behaviour therapy alone. These five treatment groups represent the minimum number acceptable for such a comparison to be made. All patients received an identical schedule of contact over 13 weeks. Measures of symptom severity, general health and social disruption were taken at entry point and end point; measures of change in symptoms were taken at end point only. Outcome was reported in terms of brief global ratings of severity of illness and change in symptoms, and of ratings of general health and social disruption that are suitable for use in general practice. RESULTS: All active treatment groups showed statistically significant advantages over placebo over a range of outcome ratings. The groups employing cognitive behaviour therapy showed the most robust and consistent response. CONCLUSION: The brief global measures reported here proved adequate to the task of assessing treatment outcome. Results indicate that treatments including cognitive behaviour therapy can be effective in the treatment of panic disorder and agoraphobia in primary care. PMID:9167318

Clinical evaluation of paroxetine in post-traumatic stress disorder (PTSD): 52-week, non-comparative open-label study for clinical use experience.

PubMed

Kim, Yoshiharu; Asukai, Nozomu; Konishi, Takako; Kato, Hiroshi; Hirotsune, Hideto; Maeda, Masaharu; Inoue, Hirotaka; Narita, Hiroyasu; Iwasaki, Masaru

2008-12-01

The present study was a 52-week, non-comparative, open-label study of flexible dose paroxetine (20-40 mg) in 52 Japanese post-traumatic stress disorder (PTSD) patients in order to obtain clinical experience regarding efficacy and safety in regular clinical practice. Efficacy was measured using the Clinician-Administered PTSD Scale One Week Symptom Status Version (CAPS-SX). The mean change from baseline in CAPS-SX total score was -19.1, -22.8 and -32.3 at weeks 4, 12 and 52, respectively, and that in the Clinical Global Impression (CGI) Severity of Illness score was -1.1 at week 12 and -1.7 at week 52. A total of 46.9% were CGI responders at week 12, while 67.3% were improved on the CGI at week 52. Of 52 subjects who entered into the drug treatment, 25 completed the study. Only one patient withdrew from the study due to lack of efficacy. In patients who were rated as 'moderately ill' or less at baseline, the proportion of CGI responders at end-point was higher at a dose of 20 mg/day than at higher doses, whereas in patients rated as 'markedly ill' or more, it was higher at 30 and 40 mg/day, suggesting that severely ill patients could benefit from higher doses. Paroxetine appeared generally tolerated in short- and long-term use, and the safety profile in this study was consistent with international trials and other Japanese populations (i.e. patients suffering from depression, panic disorder or obsessive-compulsive disorder). Although the study was not conducted in double-blind fashion, the current findings suggest that paroxetine may contribute to clinically meaningful improvement that is maintained during long-term use and is generally well tolerated.

Aphrodisiac effect of aqueous root extract of Lecaniodiscus cupanioides in sexually impaired rats.

PubMed

Ajiboye, Taofeek O; Nurudeen, Quadri O; Yakubu, Musa T

2014-05-01

The phytochemical constituents of the aqueous root extract of Lecaniodiscus cupanioides Planch. Ex Bth. and its aphrodisiac activity on male rat sexual behavior and reproductive hormones in paroxetine-induced sexual dysfunction were evaluated. The extract was screened for the presence of phytochemicals. The extract (25, 50, and 100 mg/kg body weight) and the reference herbal drug PowmaxM (7.14 mg/kg body weight) were administered orally to paroxetine-induced sexually impaired male rats, once daily for 5 days, and their sexual behavior parameters were monitored and computed. The serum hormones (testosterone, follicle-stimulating hormone, and luteinizing hormone) were determined at the end of treatment period. Phytochemical screening revealed the presence of alkaloids, anthraquinones, phenolics, saponins, and tannins. Mount frequency (MF), intromission frequency (IF), ejaculatory frequency (EF), and testosterone, follicle-stimulating hormone, and luteinizing hormone concentrations were reduced significantly (p<0.05) in paroxetine-treated rats. Administration of 25, 50, and 100 mg/kg body weight of the aqueous root extract of L. cupanioides significantly (p<0.05) reversed the paroxetine-mediated alterations in MF, IF, EF, mount latency (ML), intromission latency (IL), ejaculatory latency (EL), postejaculatory interval (PEI), and testosterone, follicle-stimulating hormone, and luteinizing hormone concentrations dose-dependently. The reversal of the male sexual behavior parameters by the extract compared well (p<0.05) with the PowmaxM-treated animals. Data obtained from this study revealed that the aqueous root extract of L. cupanioides restored sexual competence in sexually impaired rats possibly by increasing sexual drive through enhanced reproductive hormones concentration, particularly testosterone, thus supporting the folkloric claim of the plant for the management of sexual disorder in males.

Evaluation of Krebs cycle enzymes in the brain of rats after chronic administration of antidepressants.

PubMed

Scaini, Giselli; Santos, Patricia M; Benedet, Joana; Rochi, Natália; Gomes, Lara M; Borges, Lislaine S; Rezin, Gislaine T; Pezente, Daiana P; Quevedo, João; Streck, Emilio L

2010-05-31

Several works report brain impairment of metabolism as a mechanism underlying depression. Citrate synthase and succinate dehydrogenase are enzymes localized within cells in the mitochondrial matrix and are important steps of Krebs cycle. In addition, citrate synthase has been used as a quantitative enzyme marker for the presence of intact mitochondria. Thus, we investigated citrate synthase and succinate dehydrogenase activities from rat brain after chronic administration of paroxetine, nortriptiline and venlafaxine. Adult male Wistar rats received daily injections of paroxetine (10mg/kg), nortriptiline (15mg/kg), venlafaxine (10mg/kg) or saline in 1.0mL/kg volume for 15 days. Twelve hours after the last administration, the rats were killed by decapitation, the hippocampus, striatum and prefrontal cortex were immediately removed, and activities of citrate synthase and succinate dehydrogenase were measured. We verified that chronic administration of paroxetine increased citrate synthase activity in the prefrontal cortex, hippocampus, striatum and cerebral cortex of adult rats; cerebellum was not affected. Chronic administration of nortriptiline and venlafaxine did not affect the enzyme activity in these brain areas. Succinate dehydrogenase activity was increased by chronic administration of paroxetine and nortriptiline in the prefrontal cortex, hippocampus, striatum and cerebral cortex of adult rats; cerebellum was not affected either. Chronic administration of venlafaxine increased succinate dehydrogenase activity in prefrontal cortex, but did not affect the enzyme activity in cerebellum, hippocampus, striatum and cerebral cortex. Considering that metabolism impairment is probably involved in the pathophysiology of depressive disorders, an increase in these enzymes by antidepressants may be an important mechanism of action of these drugs. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Comparative Efficacy of Newer Antidepressants in Combination with Pregabalin for Fibromyalgia Syndrome: A Controlled, Randomized Study.

PubMed

Ramzy, Eiad A

2017-01-01

This controlled, randomized study investigated the hypothesis that the combined use of pregabalin plus paroxetine for fibromyalgia management would be associated with comparable Somatic Symptoms Scale-8 (SSS-8) and Center for Epidemiological Studies Depression Scale (CESDS) scores, but higher tolerability than the combined use of pregabalin plus either amitriptyline or venlafaxine. After institutional ethics committee approval, 75 female subjects diagnosed with fibromyalgia and in receipt of pregabalin (75 mg/day) were randomly allocated to concurrently receive amitriptyline (25 mg/day; n = 24), venlafaxine (75 mg/day; n = 25), or paroxetine (25 mg/day; n = 26). All patients were assessed bimonthly for 6 consecutive months for changes in SSS-8 and CESDS scores, life satisfaction, mood, sleep quality, fatigue, medication tolerability, and adverse events. Compared with pregabalin plus amitriptyline or venlafaxine, the combined use of pregabalin plus paroxetine in fibromyalgia patients resulted in significantly lower SSS-8 and CESDS scores from 18 (P < 0.05) and 10 weeks (P < 0.001) after the initiation of study medications, respectively; higher medication tolerability (P < 0.001); improved life satisfaction, mood, and sleep quality at most observation times (P < 0.05); and fewer instances of dry mouth and elevated blood pressure (P < 0.02). Medication termination due to poor tolerability was observed most frequently in the venlafaxine group (P < 0.05), while drowsiness, dizziness, blurred vision, abnormal taste, hunger, hallucination, urination problems, and sexual dysfunction were observed most frequently in the amitriptyline group (P < 0.02). The combined use of pregabalin plus paroxetine offers an effective method with increased tolerability to reduce the somatic and depressive symptoms of fibromyalgia and to enhance the quality of life in affected individuals. © 2016 World Institute of Pain.

Fluvoxamine alleviates ER stress via induction of Sigma-1 receptor

PubMed Central

Omi, T; Tanimukai, H; Kanayama, D; Sakagami, Y; Tagami, S; Okochi, M; Morihara, T; Sato, M; Yanagida, K; Kitasyoji, A; Hara, H; Imaizumi, K; Maurice, T; Chevallier, N; Marchal, S; Takeda, M; Kudo, T

2014-01-01

We recently demonstrated that endoplasmic reticulum (ER) stress induces sigma-1 receptor (Sig-1R) expression through the PERK pathway, which is one of the cell's responses to ER stress. In addition, it has been demonstrated that induction of Sig-1R can repress cell death signaling. Fluvoxamine (Flv) is a selective serotonin reuptake inhibitor (SSRI) with a high affinity for Sig-1R. In the present study, we show that treatment of neuroblastoma cells with Flv induces Sig-1R expression by increasing ATF4 translation directly, through its own activation, without involvement of the PERK pathway. The Flv-mediated induction of Sig-1R prevents neuronal cell death resulting from ER stress. Moreover, Flv-induced ER stress resistance reduces the infarct area in mice after focal cerebral ischemia. Thus, Flv, which is used frequently in clinical practice, can alleviate ER stress. This suggests that Flv could be a feasible therapy for cerebral diseases caused by ER stress. PMID:25032855

Potential benefits of slow titration of paroxetine treatment in an elderly population: eight-week results from a naturalistic setting.

PubMed

Gibiino, Sara; Mori, Elisa; De Ronchi, Diana; Serretti, Alessandro

2013-08-01

Late-life depression, often in association with anxiety, affects approximately 15% of individuals older than 65 years. Selective serotonin reuptake inhibitors are the first-line treatment but could be responsible of an early exacerbation of anxiety, possibly reduced by a very gradual titration of drugs. The main aim of this study is to compare gradual and rapid (standard) titration of paroxetine in an elderly population. In a naturalistic setting, 50 elderly (≥60 years old) outpatients with unipolar mood disorder or anxiety disorder were naturalistically assigned to abrupt initiation of 10 mg of paroxetine or to a gradual increase with 2.5 mg on alternate days up to 10 mg in 7 days. Then dosage could be maintained at 10 mg or increased according to clinical response. Primary outcome was efficacy as assessed by the Hamilton Depression Rating Scale (HAM-D) 21, HAM-D symptom subscales (core, psychic anxiety, somatic anxiety cluster), and Hamilton Anxiety Rating Scale changes. Secondary outcome was evaluation of overall dropouts at eighth week and evaluation of most common adverse effects through the global judgment of the Dosage Record and Treatment Emergent Symptom Scale. All data were recorded weekly for the first 8 weeks of treatment (with 1 more evaluation after 3 days from the baseline). Samples were comparable at baseline, with patients in gradual titration showing a higher level of psychic anxiety. During the first 3 days of treatment, a significant worsening in psychic anxiety was observed in patients treated abruptly with 10 mg of paroxetine (difference in HAM-D psychic anxiety subscale from baseline: 110.61% vs 89.38% with rapid and slow titration, respectively; t test P = 0.03). Overall, a significantly greater improvement in depressive and anxious symptoms favored gradual titration (HAM-D core cluster and HAM-D psychic anxiety cluster, respectively, P = 0.014 and P < 0.001, also when controlling for confounders). At the eighth week, significant higher dropouts in patients administered with abrupt dosage was observed (12.00% vs 40.91%, P = 0.02, respectively for slow and rapid titration). Our results suggest that a gradual titration of paroxetine could avoid the initial treatment anxiety worsening and dropout at the beginning of the treatment.

Mixed Approach Retrospective Analyses of Suicide and Suicidal Ideation for Brand Compared with Generic Central Nervous System Drugs.

PubMed

Cheng, Ning; Rahman, Md Motiur; Alatawi, Yasser; Qian, Jingjing; Peissig, Peggy L; Berg, Richard L; Page, C David; Hansen, Richard A

2018-04-01

Several different types of drugs acting on the central nervous system (CNS) have previously been associated with an increased risk of suicide and suicidal ideation (broadly referred to as suicide). However, a differential association between brand and generic CNS drugs and suicide has not been reported. This study compares suicide adverse event rates for brand versus generic CNS drugs using multiple sources of data. Selected examples of CNS drugs (sertraline, gabapentin, zolpidem, and methylphenidate) were evaluated via the US FDA Adverse Event Reporting System (FAERS) for a hypothesis-generating study, and then via administrative claims and electronic health record (EHR) data for a more rigorous retrospective cohort study. Disproportionality analyses with reporting odds ratios and 95% confidence intervals (CIs) were used in the FAERS analyses to quantify the association between each drug and reported suicide. For the cohort studies, Cox proportional hazards models were used, controlling for demographic and clinical characteristics as well as the background risk of suicide in the insured population. The FAERS analyses found significantly lower suicide reporting rates for brands compared with generics for all four studied products (Breslow-Day P < 0.05). In the claims- and EHR-based cohort study, the adjusted hazard ratio (HR) was statistically significant only for sertraline (HR 0.58; 95% CI 0.38-0.88). Suicide reporting rates were disproportionately larger for generic than for brand CNS drugs in FAERS and adjusted retrospective cohort analyses remained significant only for sertraline. However, even for sertraline, temporal confounding related to the close proximity of black box warnings and generic availability is possible. Additional analyses in larger data sources with additional drugs are needed.

Effect of the Anti-depressant Sertraline, the Novel Anti-seizure Drug Vinpocetine and Several Conventional Antiepileptic Drugs on the Epileptiform EEG Activity Induced by 4-Aminopyridine.

PubMed

Sitges, Maria; Aldana, Blanca Irene; Reed, Ronald Charles

2016-06-01

Seizures are accompanied by an exacerbated activation of cerebral ion channels. 4-aminopyridine (4-AP) is a pro-convulsive agent which mechanism of action involves activation of Na(+) and Ca(2+) channels, and several antiepileptic drugs control seizures by reducing these channels permeability. The antidepressant, sertraline, and the anti-seizure drug vinpocetine are effective inhibitors of cerebral presynaptic Na(+) channels. Here the effectiveness of these compounds to prevent the epileptiform EEG activity induced by 4-AP was compared with the effectiveness of seven conventional antiepileptic drugs. For this purpose, EEG recordings before and at three intervals within the next 30 min following 4-AP (2.5 mg/kg, i.p.) were taken in anesthetized animals; and the EEG-highest peak amplitude values (HPAV) calculated. In control animals, the marked increase in the EEG-HPAV observed near 20 min following 4-AP reached its maximum at 30 min. Results show that this epileptiform EEG activity induced by 4-AP is prevented by sertraline and vinpocetine at a dose of 2.5 mg/kg, and by carbamazepine, phenytoin, lamotrigine and oxcarbazepine at a higher dose (25 mg/kg). In contrast, topiramate (25 mg/kg), valproate (100 mg/kg) and levetiracetam (100 mg/kg) failed to prevent the epileptiform EEG activity induced by 4-AP. It is concluded that 4-AP is a useful tool to elicit the mechanism of action of anti-seizure drugs at clinical meaningful doses. The particular efficacy of sertraline and vinpocetine to prevent seizures induced by 4-AP is explained by their high effectiveness to reduce brain presynaptic Na(+) and Ca(2+) channels permeability.

Molecular biomarkers predictive of sertraline treatment response in young children with fragile X syndrome.

PubMed

AlOlaby, Reem Rafik; Sweha, Stefan R; Silva, Marisol; Durbin-Johnson, Blythe; Yrigollen, Carolyn M; Pretto, Dalyir; Hagerman, Randi J; Tassone, Flora

2017-06-01

Several neurotransmitters involved in brain development are altered in fragile X syndrome (FXS), the most common monogenic cause of autism spectrum disorder (ASD). Serotonin plays a vital role in synaptogenesis and postnatal brain development. Deficits in serotonin synthesis and abnormal neurogenesis were shown in young children with autism, suggesting that treating within the first years of life with a selective serotonin reuptake inhibitor might be the most effective time. In this study we aimed to identify molecular biomarkers involved in the serotonergic pathway that could predict the response to sertraline treatment in young children with FXS. Genotypes were determined for several genes involved in serotonergic pathway in 51 children with FXS, ages 24-72months. Correlations between genotypes and deviations from baseline in primary and secondary outcome measures were modeled using linear regression models. A significant association was observed between a BDNF polymorphism and improvements for several clinical measures, including the Clinical Global Impression scale (P=0.008) and the cognitive T score (P=0.017) in those treated with sertraline compared to those in the placebo group. Additionally, polymorphisms in the MAOA, Cytochrome P450 2C19 and 2D6, and in the 5-HTTLPR gene showed a significant correlation with some of the secondary measures included in this study. This study shows that polymorphisms of genes involved in the serotonergic pathway could play a potential role in predicting response to sertraline treatment in young children with FXS. Larger studies are warranted to confirm these initial findings. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Comparison of the Effects of Religious Cognitive Behavioral Therapy (RCBT), Cognitive Behavioral Therapy (CBT), and Sertraline on Depression and Anxiety in Patients after Coronary Artery Bypass Graft Surgery: Study Protocol for a Randomized Controlled Trial.

PubMed

Hosseini, Seyed Hamzeh; Rafiei, Alireza; Gaemian, Ali; Tirgari, Abdolhakim; Zakavi, Aliasghar; Yazdani, Jamshid; Bolhari, Jafar; Golzari, Mahmood; Esmaeili Douki, Zahra; Vaezzadeh, Nazanin

2017-07-01

Objective: The present study aimed at comparing the effects of Religious Cognitive Behavioral Therapy (RCBT), Cognitive Behavioral Therapy (CBT), and sertraline on depression, anxiety, biomarker levels, and quality of life in patients after coronary artery bypass graft (CABG) surgery. Method: This was a randomized controlled trial with parallel groups. A total of 160 patients after CABG surgery will be screened for anxiety and depression according to clinical interviews based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria and Hospital Anxiety Depression Scale (HADS) scores (≥ 8). To assess religious attitude, Golriz and Baraheni's Religious Attitude questionnaire will be used. Participants will be randomly allocated to 4 groups of 40 including 3 intervention groups (RCBT, CBT, and sertraline) and 1 control group (usual care). RCBT and CBT programs will consist of 12 one-hour weekly sessions. The participants in the pharmacological intervention group will receive 25-200 mg/d of sertraline for 3 months. The Short Form-36 Health Survey (SF-36) will be administered to assess the patients' quality of life. Blood samples will be taken and biomarker levels will be determined using the enzyme-linked immunosorbent assay (ELISA). The primary outcome will be reduction in anxiety and depression scores after the interventions. The secondary outcomes will be increase in quality of life scores and normalized biomarker levels after the interventions. Discussion: If RCBT is found to be more effective than the other methods; it can be used to improve patients' health status after CABG surgery. Irct ID: IRCT201404122898N5.

Cognitive outcomes after sertaline treatment in patients with depression of Alzheimer disease.

PubMed

Munro, Cynthia A; Longmire, Crystal Flynn; Drye, Lea T; Martin, Barbara K; Frangakis, Constantine E; Meinert, Curtis L; Mintzer, Jacobo E; Porsteinsson, Anton P; Rabins, Peter V; Rosenberg, Paul B; Schneider, Lon S; Weintraub, Daniel; Lyketsos, Constantine G

2012-12-01

Although many depressed patients with Alzheimer disease (AD) are treated with antidepressants, the effect of such treatment on cognitive performance in these patients is not known. The authors report cognitive outcomes in patients with depression of AD (dAD) after a 24-week trial of sertraline or placebo. Placebo-controlled, randomized, double-blind trial. Outpatient memory clinics at five academic medical centers in the United States. A total of 131 patients with dAD (60 men) and Mini-Mental State Examination scores of 10-26. Sertraline (n = 67), target dose of 100 mg daily or matching placebo (n = 64). Caregivers received standardized psychosocial intervention throughout the trial. Mini-Mental State Examination, cognitive subscale of the Alzheimer's Disease Assessment Scale, letter fluency, backward digit span, Symbol Digit Modalities Test, and Finger Tapping Test, administered at baseline, and 8, 16, and 24 weeks following baseline. A series of linear models indicated no effect of treatment or of depression remission on cognitive test performance at 24 weeks. Regardless of treatment condition, very little change in cognitive test performance was noted in general. Treatment with sertraline in patients with dAD is not associated with greater improvement in cognition at week 24 than treatment with placebo.

Sertraline for the treatment of depression in Alzheimer disease: genetic influences.

PubMed

Peters, Matthew E; Vaidya, Vijay; Drye, Lea T; Rosenberg, Paul B; Martin, Barbara K; Porsteinsson, Anton P; Frangakis, Constantine E; Mintzer, Jacobo; Weintraub, Daniel; Schneider, Lon S; Rabins, Peter V; Munro, Cynthia A; Meinert, Curtis L; Lyketsos, Constantine G; Avramopoulos, Dimitri; Dimitri, Avramopoulos

2011-12-01

To assess the potential for genetic influences on sertraline treatment efficacy for depression of Alzheimer disease (dAD). Four functional genetic variants were studied: 2 serotonin receptors (HTR2A-T102C and HTR2C-Cys23Ser), the serotonin transporter (5HTT-LPR), and brain-derived neurotrophic factor (BDNF-Val66Met). Treatment response by genotype was measured by (1) the modified Alzheimer's Disease Cooperative Study Clinical Global Impression of Change, (2) the Cornell scale for Depression in Dementia, and (3) remission of depression. We utilized data from the Depression in Alzheimer's Disease Study 2 (DIADS-2), a 24-week, randomized, multicenter trial showing no significant treatment effect of sertraline on dAD. Proportional odds logistic regression and mixed effects models were used to examine the above mentioned outcome measures. No significant interactions were seen between any of the genetic polymorphisms and the selected outcomes above at 12 or 24 weeks. Treatment outcomes in the DIADS-2 trial were not significantly influenced by genetic variation at the loci that were assessed. Future studies should continue to examine the interaction of depression-related genetic variants with antidepressant treatment in Alzheimer disease patients with depression.

Alterations in Stress Reactivity After Long-Term Treatment with Paroxetine in Women with Posttraumatic Stress Disorder

PubMed Central

Vermetten, Eric; Vythilingam, Meena; Schmahl, Christian; De Kloet, Carien; Southwick, Steven M.; Charney, Dennis S.; Bremner, J. Douglas

2011-01-01

Posttraumatic stress disorder (PTSD) is typically accompanied by both acute and chronic alterations in the stress response. These alterations have mostly been described in individuals under baseline conditions, but studies have also used a challenge model to assess the role of the hypothalamic-pituitary-adrenal (HPA) axis in the stress response. The purpose of this article was to assess the effect of long-term treatment with the selective reuptake inhibitor (SSRI), paroxetine, on stress reactivity in patients with PTSD. We assessed diurnal salivary cortisol and urinary cortisol as well as cortisol, heart rate, and behavioral responses to a standardized cognitive stress challenge, in 13 female patients with chronic PTSD before and after 12 months of paroxetine treatment. Treatment resulted in a significant decrease in PTSD symptoms. Twenty-four-hour urinary cortisol was lower compared to base line after successful treatment. Treatment resulted in a decrease of salivary cortisol levels on all time points on a diurnal curve. Despite similar stress perception, cortisol response to the cognitive stress challenge resulted in a 26.5% relative decrease in stress-induced salivary cortisol with treatment. These results suggest that successful treatment with SSRI in chronic PTSD is associated with a trend for a decrease in baseline diurnal cortisol and with reduced cortisol reactivity to stress. PMID:16891570

Somatic Symptoms in Children and Adolescents with Anxiety Disorders

ERIC Educational Resources Information Center

Ginsburg, Golda S.; Riddle, Mark A.; Davies, Mark

2006-01-01

Objective: To evaluate the prevalence of somatic symptoms (SSs) in children and adolescents with anxiety disorders; the relationship between SSs and anxiety severity, impairment, and child global functioning; and the impact of fluvoxamine (FLV) versus pill placebo (PBO) on reducing SSs. Method: As part of a double-blind, placebo-controlled trial,…

Sensitive and selective determination of fluvoxamine maleate using a sensitive chemiluminescence system based on the alkaline permanganate-Rhodamine B-gold nanoparticles reaction.

PubMed

Hassanzadeh, Javad; Amjadi, Mohammad

2015-06-01

A high-yield chemiluminescence (CL) system based on the alkaline permanganate-Rhodamine B reaction was developed for the sensitive determination of fluvoxamine maleate (Flu). Rhodamine B is oxidized by alkaline KMnO4 and a weak CL emission is produced. It was demonstrated that gold nanoparticles greatly enhance this CL emission due to their interaction with Rhodamine B molecules. It is also observed that sodium dodecyl sulfate, an anionic surfactant, can strongly increase this enhancement. In addition, it was demonstrated that a notable decrease in the CL intensity is observed in the presence of Flu. This may be related to Flu oxidation with KMnO4 . There is a linear relationship between the decrease in CL intensity and the Flu concentration over a range of 2-300 µg/L. A new simple, rapid and sensitive CL method was developed for the determination of Flu with a detection limit (3s) of 1.35 µg/L. The proposed method was used for the determination of Flu in pharmaceutical and urine samples. Copyright © 2014 John Wiley & Sons, Ltd.

Serum proBDNF/BDNF and response to fluvoxamine in drug-naïve first-episode major depressive disorder patients.

PubMed

Yoshimura, Reiji; Kishi, Taro; Hori, Hikaru; Atake, Kiyokazu; Katsuki, Asuka; Nakano-Umene, Wakako; Ikenouchi-Sugita, Atsuko; Iwata, Nakao; Nakamura, Jun

2014-01-01

We investigated the association between serum proBDNF, a precursor of brain-derived neurotrophic factor (BDNF), and response to fluvoxamine in patients with major depressive disorder (MDD) using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR): physically healthy and free of current alcohol or drug abuse, comorbid anxiety, or personality disorders. Fifty-one patients with MDD (M/F, 19:32; age, 38 ± 19 years) and 51 healthy controls (M/F, 22:29; age, 34 ± 17 years) were studied using DSM-IV-TR: physically healthy and free of current alcohol or drug abuse, comorbid anxiety, or personality disorders. Serum levels of proBDNF and MDNF were measured by sandwich enzyme-linked immunosorbent assay (ELISA). Serum mature BDNF levels in the MDD patients were significantly lower than those in the healthy controls (t = 3.046, p = 0.0018). On the other hand, no difference was found in serum proBDNF between the MDD patients and the healthy controls (t = -0.979, p = 0.833). A trend of negative correlation was found between baseline serum BDNF and baseline scores of the 17 items of the Hamilton Rating Scale for Depression (HAMD17) (r = -0.183, p = 0.071). No correlation was however found between HAMD17 scores and proBDNF at baseline (r = 0.092, p = 0.421). Furthermore, no correlation was observed between baseline HAMD17 scores and baseline proBDNF/BDNF (r = -0.130, p = 0.190). No changes were observed in serum levels of proBDNF and BDNF during the treatment periods. These results suggest that there is no association between serum proBDNF/BDNF and fluvoxamine response in MDD patients at least within 4 weeks of the treatment.

Spectrophotometric study for the reaction between fluvoxamine and 1,2-naphthoquinone-4-sulphonate: Kinetic, mechanism and use for determination of fluvoxamine in its dosage forms

NASA Astrophysics Data System (ADS)

Darwish, Ibrahim A.; Abdine, Heba H.; Amer, Sawsan M.; Al-Rayes, Lama I.

2009-05-01

Spectrophotometric study was carried out, for the first time, to investigate the reaction between the antidepressant fluvoxamine (FXM) and 1,2-naphthoquinone-4-sulphonate (NQS) reagent. In alkaline medium (pH 9), an orange-colored product exhibiting maximum absorption peak ( λmax) at 470 nm was produced. The kinetics of the reaction was investigated and its activation energy was found to be 2.65 kcal mol -1. Because of this low activation energy, the reaction proceeded easily. The stoichiometry of the reaction was determined and the reaction mechanism was postulated. This color-developing reaction was successfully employed in the development of simple and rapid spectrophotometric method for determination of FXM in its pharmaceutical dosage forms. Under the optimized reaction conditions, Beer's law correlating the absorbance ( A) with FXM concentration ( C) was obeyed in the range of 0.6-8 μg ml -1. The regression equation for the calibration data was A = 0.0086 + 0.1348 C, with good correlation coefficient (0.9996). The molar absorptivity ( ɛ) was 5.9 × 10 4 l mol -1 cm -1. The limits of detection and quantification were 0.2 and 0.6 μg ml -1, respectively. The precision of the method was satisfactory; the values of relative standard deviations did not exceed 2%. The proposed method was successfully applied to the determination of FXM in its pharmaceutical tablets with good accuracy and precisions; the label claim percentage was 100.47 ± 0.96%. The results obtained by the proposed method were comparable with those obtained by the official method. The proposed method is superior to all the previously reported spectrophotometric methods for determination of FXM in terms of its simplicity and sensitivity. The method is practical and valuable for its routine application in quality control laboratories for analysis of FXM.

Development of resistance to serotonin-induced itch in bile duct ligated mice.

PubMed

Ostadhadi, Sattar; Haddadi, Nazgol-Sadat; Foroutan, Arash; Azimi, Ehsan; Elmariah, Sarina; Dehpour, Ahmad-Reza

2017-06-01

Cholestatic itch can be severe and significantly impair the quality of life of patients. The serotonin system is implicated in cholestatic itch; however, the pruritogenic properties of serotonin have not been evaluated in cholestatic mice. Here, we investigated the serotonin-induced itch in cholestatic mice which was induced by bile duct ligation (BDL). Serotonin, sertraline or saline were administered intradermally to the rostral back area in BDL and sham operated (SHAM) mice, and the scratching behaviour was videotaped for 1 hour. Bile duct ligated mice had significantly increased scratching responses to saline injection on the seventh day after surgery. Additionally, serotonin or sertraline significantly induced scratching behaviour in BDL mice compared to saline at day 7 after surgery, while it did not induce itch at day 5. The scratching behaviour induced by serotonin or sertraline was significantly less in BDL mice compared to SHAM mice. Likewise, the locomotor activity of BDL or SHAM mice was not significantly different from unoperated (UNOP) mice on the fifth and seventh day, suggesting that the scratching behaviour was not affected by motor dysfunctions. Our data suggest that despite the potentiation of evoked itch, a resistance to serotonin-induced itch is developed in cholestatic mice. © 2017 John Wiley & Sons Australia, Ltd.

Effective use of sertraline for pathological laughing after severe vasospasm due to aneurysmal subarachnoid hemorrhage: case report.

PubMed

Takeuchi, Hayato; Iwamoto, Kazuhide; Mukai, Mao; Fujita, Tomoaki; Tsujino, Hitoshi; Iwamoto, Yoshihiro

2014-01-01

Pathological laughing, one subgroup of psuedobulbar affect, is known as laughter inappropriate to the patient's external circumstances and unrelated to the patient's internal emotional state. The authors present the case of a 76-year-old woman with no significant medical history who experienced pathological laughing after subarachnoid hemorrhage (SAH) due to rupture of an aneurysm, which was successfully treated with craniotomy for aneurysm clipping. In the acute stage after the operation she suffered from severe vasospasm and resulting middle cerebral artery territory infarction and conscious disturbance. As she regained consciousness she was afflicted by pathological laughing 6 months after the onset of SAH. Her involuntary laughter was inappropriate to the situation and was incongruent with the emotional state, and she could not control by herself. Finally the diagnosis of pathological laughing was made and treatment with sertraline, a selective serotonin reuptake inhibitor (SSRI), effectively cured the symptoms. Her pathological laughing was estimated to be consequence of infarction in the right prefrontal cortex and/or corona radiata, resulting from vasospasm. To the authors' knowledge, this is the first report of pathological laughing after aneurysmal SAH. The authors offer insight into the pathophysiology of this rare phenomenon. Effectiveness of sertraline would widen the treatment modality against pathological laughing.

Effective Use of Sertraline for Pathological Laughing after Severe Vasospasm Due to Aneurysmal Subarachnoid Hemorrhage: Case Report

PubMed Central

TAKEUCHI, Hayato; IWAMOTO, Kazuhide; MUKAI, Mao; FUJITA, Tomoaki; TSUJINO, Hitoshi; IWAMOTO, Yoshihiro

2014-01-01

Pathological laughing, one subgroup of psuedobulbar affect, is known as laughter inappropriate to the patient's external circumstances and unrelated to the patient's internal emotional state. The authors present the case of a 76-year-old woman with no significant medical history who experienced pathological laughing after subarachnoid hemorrhage (SAH) due to rupture of an aneurysm, which was successfully treated with craniotomy for aneurysm clipping. In the acute stage after the operation she suffered from severe vasospasm and resulting middle cerebral artery territory infarction and conscious disturbance. As she regained consciousness she was afflicted by pathological laughing 6 months after the onset of SAH. Her involuntary laughter was inappropriate to the situation and was incongruent with the emotional state, and she could not control by herself. Finally the diagnosis of pathological laughing was made and treatment with sertraline, a selective serotonin reuptake inhibitor (SSRI), effectively cured the symptoms. Her pathological laughing was estimated to be consequence of infarction in the right prefrontal cortex and/or corona radiata, resulting from vasospasm. To the authors' knowledge, this is the first report of pathological laughing after aneurysmal SAH. The authors offer insight into the pathophysiology of this rare phenomenon. Effectiveness of sertraline would widen the treatment modality against pathological laughing. PMID:24201096

Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression.

PubMed

Rush, A John; Trivedi, Madhukar H; Wisniewski, Stephen R; Stewart, Jonathan W; Nierenberg, Andrew A; Thase, Michael E; Ritz, Louise; Biggs, Melanie M; Warden, Diane; Luther, James F; Shores-Wilson, Kathy; Niederehe, George; Fava, Maurizio

2006-03-23

After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor (SSRI), it is not known whether switching to one antidepressant is more effective than switching to another. We randomly assigned 727 adult outpatients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram to receive one of the following drugs for up to 14 weeks: sustained-release bupropion (239 patients) at a maximal daily dose of 400 mg, sertraline (238 patients) at a maximal daily dose of 200 mg, or extended-release venlafaxine (250 patients) at a maximal daily dose of 375 mg. The study was conducted in 18 primary and 23 psychiatric care settings. The primary outcome was symptom remission, defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of the study. Scores on the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR-16), obtained at treatment visits, determined secondary outcomes, including remission (a score of 5 or less at exit) and response (a reduction of 50 percent or more on baseline scores). Remission rates as assessed by the HRSD-17 and the QIDS-SR-16, respectively, were 21.3 percent and 25.5 percent for sustained-release bupropion, 17.6 percent and 26.6 percent for sertraline, and 24.8 percent and 25.0 percent for extended-release venlafaxine. QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion, 26.7 percent for sertraline, and 28.2 percent for extended-release venlafaxine. These treatments did not differ significantly with respect to outcomes, tolerability, or adverse events. After unsuccessful treatment with an SSRI, approximately one in four patients had a remission of symptoms after switching to another antidepressant. Any one of the medications in the study provided a reasonable second-step choice for patients with depression. (ClinicalTrials.gov number, NCT00021528.). Copyright 2006 Massachusetts Medical Society.

Physicians' prescribing preferences were a potential instrument for patients' actual prescriptions of antidepressants☆

PubMed Central

Davies, Neil M.; Gunnell, David; Thomas, Kyla H.; Metcalfe, Chris; Windmeijer, Frank; Martin, Richard M.

2013-01-01

Objectives To investigate whether physicians' prescribing preferences were valid instrumental variables for the antidepressant prescriptions they issued to their patients. Study Design and Setting We investigated whether physicians' previous prescriptions of (1) tricyclic antidepressants (TCAs) vs. selective serotonin reuptake inhibitors (SSRIs) and (2) paroxetine vs. other SSRIs were valid instruments. We investigated whether the instrumental variable assumptions are likely to hold and whether TCAs (vs. SSRIs) were associated with hospital admission for self-harm or death by suicide using both conventional and instrumental variable regressions. The setting for the study was general practices in the United Kingdom. Results Prior prescriptions were strongly associated with actual prescriptions: physicians who previously prescribed TCAs were 14.9 percentage points (95% confidence interval [CI], 14.4, 15.4) more likely to prescribe TCAs, and those who previously prescribed paroxetine were 27.7 percentage points (95% CI, 26.7, 28.8) more likely to prescribe paroxetine, to their next patient. Physicians' previous prescriptions were less strongly associated with patients' baseline characteristics than actual prescriptions. We found no evidence that the estimated association of TCAs with self-harm/suicide using instrumental variable regression differed from conventional regression estimates (P-value = 0.45). Conclusion The main instrumental variable assumptions held, suggesting that physicians' prescribing preferences are valid instruments for evaluating the short-term effects of antidepressants. PMID:24075596

Plasma catecholamine levels before and after paroxetine treatment in patients with panic disorder.

PubMed

Oh, Jae-Young; Yu, Bum-Hee; Heo, Jung-Yoon; Yoo, Ikki; Song, Hyemin; Jeon, Hong Jin

2015-02-28

Catecholamines such as norepinephrine, epinephrine, and dopamine are closely related to the autonomic nervous system, suggesting that panic disorder may involve elevated catecholamine levels. This study investigated basal and posttreatment catecholamine levels in patients with panic disorder. A total of 29 patients with panic disorder and 23 healthy controls participated in the study. Panic disorder patients received paroxetine treatment for 12 weeks after clinical tests and examination had been conducted. We investigated the difference in basal levels of catecholamine and measured the changes in catecholamine levels before and after drug treatment in panic disorder patients. The basal plasma epinephrine (48.87±6.18 pg/ml) and dopamine (34.87±3.57 pg/ml) levels of panic disorder patients were significantly higher than those (34.79±4.72 pg/ml and 20.40±3.53 pg/ml) of the control group. However, basal plasma norepinephrine levels did not show statistically significant differences between patients and controls. After drug therapy, plasma catecholamine levels were nonsignificantly decreased and norepinephrine levels showed a tendency toward a decrease that did not reach significance. In conclusion, this study suggests the possibility of a baseline increase of plasma catecholamine levels and activation of sympathetic nervous systems in patients with panic disorder which may normalize after treatment with paroxetine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Paroxetine

MedlinePlus

... sleepiness or feeling ''drugged'' nausea vomiting diarrhea constipation gas stomach pain heartburn changes in ability to taste ... symptoms yellowing of the skin and eyes aggressive behavior muscle pain, stiffness, or weakness sudden muscle twitching ...

Effect of mirtazapine versus selective serotonin reuptake inhibitors on benzodiazepine use in patients with major depressive disorder: a pragmatic, multicenter, open-label, randomized, active-controlled, 24-week trial.

PubMed

Hashimoto, Tasuku; Shiina, Akihiro; Hasegawa, Tadashi; Kimura, Hiroshi; Oda, Yasunori; Niitsu, Tomihisa; Ishikawa, Masatomo; Tachibana, Masumi; Muneoka, Katsumasa; Matsuki, Satoshi; Nakazato, Michiko; Iyo, Masaomi

2016-01-01

This study aimed to evaluate whether selecting mirtazapine as the first choice for current depressive episode instead of selective serotonin reuptake inhibitors (SSRIs) reduces benzodiazepine use in patients with major depressive disorder (MDD). We concurrently examined the relationship between clinical responses and serum mature brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF. We conducted an open-label randomized trial in routine psychiatric practice settings. Seventy-seven MDD outpatients were randomly assigned to the mirtazapine or predetermined SSRIs groups, and investigators arbitrarily selected sertraline or paroxetine. The primary outcome was the proportion of benzodiazepine users at weeks 6, 12, and 24 between the groups. We defined patients showing a ≥50 % reduction in Hamilton depression rating scale (HDRS) scores from baseline as responders. Blood samples were collected at baseline, weeks 6, 12, and 24. Sixty-five patients prescribed benzodiazepines from prescription day 1 were analyzed for the primary outcome. The percentage of benzodiazepine users was significantly lower in the mirtazapine than in the SSRIs group at weeks 6, 12, and 24 (21.4 vs. 81.8 %; 11.1 vs. 85.7 %, both P  < 0.001; and 12.5 vs. 81.8 %, P  = 0.0011, respectively). No between-group difference was observed in HDRS score changes. Serum proBDNF levels were significantly decreased ( χ 2  = 8.5, df  = 3, P  = 0.036) and serum mature BDNF levels were temporarily significantly decreased ( F  = 3.5, df  = 2.4, P  = 0.027) in the responders of both groups at week 24. This study demonstrated mirtazapine as the first-choice antidepressant for current depressive episodes may reduce benzodiazepine use in patients with MDD. Trial registration UMIN000004144. Registered 2nd September 2010. The date of enrolment of the first participant to the trial was 24th August 2010. This study was retrospectively registered 9 days after the first participant was enrolled.

Effect of Vortioxetine vs. Escitalopram on Sexual Functioning in Adults with Well-Treated Major Depressive Disorder Experiencing SSRI-Induced Sexual Dysfunction.

PubMed

Jacobsen, Paula L; Mahableshwarkar, Atul R; Chen, Yinzhong; Chrones, Lambros; Clayton, Anita H

2015-10-01

Sexual dysfunction is common with serotonergic antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), and does not resolve in most patients. Vortioxetine, an antidepressant with a multimodal mechanism of action, has shown low rates of sexual dysfunction in previous major depressive disorder (MDD) trials. This study compared the effects of vortioxetine and escitalopram on sexual functioning in adults with well-treated MDD experiencing treatment-emergent sexual dysfunction (TESD). Participants treated with, and responding to, citalopram, paroxetine, or sertraline were randomized to switch to either vortioxetine (10/20 mg; n = 225) or escitalopram (10/20 mg; n = 222) for 8 weeks. Sexual function was assessed using the Changes in Sexual Functioning Questionnaire Short Form (CSFQ-14), and antidepressant efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impressions (CGI) scale, and Profile of Mood States brief form (POMS-brief). Safety and tolerability were also assessed. The primary endpoint was change from baseline in the CSFQ-14 total score after 8 weeks of treatment. The MADRS, CGI, and POMS-brief were used to assess antidepressant efficacy. Safety was assessed via adverse events, vital signs, electrocardiograms, laboratory values, weight, and physical examination findings. Vortioxetine showed significantly greater improvements in CSFQ-14 total score (8.8 ± 0.64, mean ± standard error) vs. escitalopram (6.6 ± 0.64; P = 0.013). Benefits vs. escitalopram were significant on four of five dimensions and all three phases of sexual functioning assessed by the CSFQ-14 (P < 0.05). Antidepressant efficacy continued in both groups, with similar, but slight, improvements in MADRS and CGI scores. Vortioxetine and escitalopram had similar clinical efficacy profiles in this study, with safety profiles similar to previous trials. Nausea (n = 9, 4.0%) was the most common treatment-emergent adverse event leading to discontinuation of vortioxetine. Switching antidepressant therapy to vortioxetine may be beneficial for patients experiencing sexual dysfunction during antidepressant therapy with SSRIs. © 2015 International Society for Sexual Medicine.

A distinct pattern of memory and attention deficiency in patients with depression.

PubMed

Luo, Lan-Lan; Chen, Xin; Chai, Yan; Li, Jin-Hong; Zhang, Mian; Zhang, Jian-Ning

2013-03-01

Depression related cognitive deficits are frequently considered as simple epiphenomena of the disorder. However, whether or not the depression might directly bring about cognitive deficits is still under investigation. This study was to investigate the distinct pattern of cognitive deficits in patients with depression by comparing the cognitive function before and after anti-depressive drug therapy. Sixty cases of patients, first-time diagnosed with depression, were assessed by 17-item Hamilton Rating Scale for Depression (HAMD17scale). The memory ability was tested by quantitatively clinical memory scale, while the attention ability by modified Ruff 2&7 Selective Attention Test. Forty-two healthy volunteers were recruited as controls. The depressive patients were treated with Venlafaxine (75 - 300 mg/d), Fluoxetine (20 - 40 mg/d), Paroxetine (20 - 40 mg/d), and Sertraline (50 - 150 mg/d). After 12 weeks treatment, patients were tested again by HAMD17scale, quantitatively clinical memory scale, and modified Ruff 2&7 selective attention test to assess the effect of anti-depressive drugs on cognitive deficits. The memory quotient (MQ) was significantly lowered in depressive patients. The selection speed was also significantly decreased and the number of missing and error hits increased in the depression group as compared to control. However, there was no significant difference in clinical memory scale and Ruff 2&7 selective attention test between mild-to-moderate and severe depression group. Importantly, after anti-depressive drug therapy, the HAMD17 scale scores in depressive patients were significantly decreased, but the MQ, directional memory (DM), free recall (FR), associative learning (AL), and face recognition were comparable with those before the treatment. Furthermore, the selection speed and the number of missing and error hits were also not significantly different after anti-depressive drugs treatment. Depressive patients suffer from short-term memory deficits, and attention extent, stability and rearrangement deficiency. Even though anti-depressive drugs sufficiently relieve the cardinal presentation of depression, they could not successfully alleviate the accompanying cognitive deficits. This might indicate a distinct pattern of cognitive deficits in patients with depression.

Changes in personality traits during treatment with sertraline or citalopram.

PubMed

Ekselius, L; Von Knorring, L

1999-05-01

Recent studies indicate that selective serotonin re-uptake inhibitors (SSRIs) reduce the symptoms accompanying personality disorders and modulate a normal personality. To examine the effect of two SSRIs, sertraline and citalopram, on personality traits in major depressed patients. Personality traits were evaluated at baseline and after six months using the Karolinska Scales of Personality (KSP). After treatment, significant changes in the direction of normalisation were seen in all scales. To determine whether the observed changes could be explained by improved depressive symptoms, multiple stepwise regressions with the separate KSP as dependent variables were performed. Improvements in depressive symptoms only accounted for 0-8.4% of the observed variance. In depressed patients treated with SSRIs significant effects are seen on personality traits measured by the KSP.

Propranolol (Cardiovascular)

MedlinePlus

... is also used to prevent angina (chest pain), migraine headaches, and to improve survival after a heart ... paroxetine (Brisdelle, Paxil, Pexeva); fluconazole (Diflucan); medications for migraine headaches such as rizatriptan (Maxalt) and zolmitriptan (Zomig); ...

A Selective Mutism Arising from First Language Attrition, Successfully Treated with Paroxetine-CBT Combination Treatment.

PubMed

Serra, Agostino; Di Mauro, Paola; Andaloro, Claudio; Maiolino, Luigi; Pavone, Piero; Cocuzza, Salvatore

2015-10-01

After immersion in a foreign language, speakers often have difficulty retrieving native-language words and may experience a decrease in its proficiency, this phenomenon, in the non-pathological form, is known as first language attrition. Self-perception of this low native-language proficiency and apprehension occurring when speaking is expected and, may sometimes lead these people to a state of social anxiety and, in extreme forms, can involve the withholding of speech as a primitive tool for self-protection, linking them to selective mutism. We report an unusual case of selective mutism arising from first language attrition in an Italian girl after attending a two-year "German language school", who successfully responded to a paroxetine-cognitive behavioral treatment (CBT) combination treatment.

A Selective Mutism Arising from First Language Attrition, Successfully Treated with Paroxetine-CBT Combination Treatment

PubMed Central

Serra, Agostino; Di Mauro, Paola; Andaloro, Claudio; Maiolino, Luigi; Pavone, Piero

2015-01-01

After immersion in a foreign language, speakers often have difficulty retrieving native-language words and may experience a decrease in its proficiency, this phenomenon, in the non-pathological form, is known as first language attrition. Self-perception of this low native-language proficiency and apprehension occurring when speaking is expected and, may sometimes lead these people to a state of social anxiety and, in extreme forms, can involve the withholding of speech as a primitive tool for self-protection, linking them to selective mutism. We report an unusual case of selective mutism arising from first language attrition in an Italian girl after attending a two-year "German language school", who successfully responded to a paroxetine-cognitive behavioral treatment (CBT) combination treatment. PMID:26508972

Psychotropic drugs in mixture alter swimming behaviour of Japanese medaka (Oryzias latipes) larvae above environmental concentrations.

PubMed

Chiffre, Axelle; Clérandeau, Christelle; Dwoinikoff, Charline; Le Bihanic, Florane; Budzinski, Hélène; Geret, Florence; Cachot, Jérôme

2016-03-01

Psychiatric pharmaceuticals, such as anxiolytics, sedatives, hypnotics and antidepressors, are among the most prescribed active substances in the world. The occurrence of these compounds in the environment, as well as the adverse effects they can have on non-target organisms, justifies the growing concern about these emerging environmental pollutants. This study aims to analyse the effects of six psychotropic drugs, valproate, cyamemazine, citalopram, sertraline, fluoxetine and oxazepam, on the survival and locomotion of Japanese medaka Oryzias latipes larvae. Newly hatched Japanese medaka were exposed to individual compounds for 72 h, at concentrations ranging from 10 μg L(-1) to 10 mg L(-1). Lethal concentrations 50 % (LC50) were estimated at 840, 841 and 9,136 μg L(-1) for fluoxetine, sertraline and citalopram, respectively, while other compounds did not induce any significant increase in mortality. Analysis of the swimming behaviour of larvae, including total distance moved, mobility and location, provided an estimated lowest observed effect concentration (LOEC) of 10 μg L(-1) for citalopram and oxazepam, 12.2 μg L(-1) for cyamemazine, 100 μg L(-1) for fluoxetine, 1,000 μg L(-1) for sertraline and >10,000 μg L(-1) for valproate. Realistic environmental mixture of the six psychotropic compounds induced disruption of larval locomotor behaviour at concentrations about 10- to 100-fold greater than environmental concentrations.

Interface between authorship, industry and science in the domain of therapeutics.

PubMed

Healy, David; Cattell, Dinah

2003-07-01

Changes in the character of medical authorship. Aims To compare the impact of industry-linked and non-industry linked articles. We compared articles on sertraline being coordinated by a medical writing agency with articles not coordinated in this way. We calculated numbers of Medline-listed articles per author, journal impact factors, literature profiles and citation rates of both sets of articles. Non-agency-linked articles on sertraline had an average of 2.95 authors per article, a mean length of 3.4 pages, a mean Medline listing of 37 articles per author (95% CI 27-47) and a mean literature profile of 283 per article (95% CI 130-435). Agency-linked articles on sertraline had an average of 6.6 authors per article, a mean length of 10.7 pages, a mean Medline listing of 70 articles per author (95% CI 62-79) and a mean literature profile of 1839 per article (95% CI 1076-2602). The citation rate for agency articles was 20.2 (95% CI 13.4-27.0) and for non-agency articles it was 3.7 (95% CI 3.3-8.1). The literature profiles and citation rates of industry-linked and non-industry-linked articles differ. The emerging style of authorship in industry-linked articles can deliver good-quality articles, but it raises concerns for the scientific base of therapeutics.

Clinical study of duloxetine hydrochloride combined with doxazosin for the treatment of pain disorder in chronic prostatitis/chronic pelvic pain syndrome: An observational study.

PubMed

Zhang, Mingxin; Li, Hanzhong; Ji, Zhigang; Dong, Dexin; Yan, Su

2017-03-01

To explore the safety and efficacy of the selective 5-serotonin and norepinephrine reuptake inhibitor duloxetine hydrochloride and alpha-adrenergic receptor blocker (alpha-blocker) doxazosin mesylate-controlled tablets in the treatment of pain disorder in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).In all, 150 patients were enrolled and 126 patients completed the study (41 patients in the doxazosin group, 41 patients in the sertraline group, and 44 patients in the duloxetine group). This was an open randomized 6-month study. CP/CPPS patients who met the diagnostic criteria were randomized into 3 groups. The patients in the duloxetine group received doxazosin 4 mg + duloxetine 30 mg once a day, and the dosage of duloxetine was increased to 60 mg after a week. The patients in the doxazosin group received doxazosin 4 mg once a day. The patients in the sertraline group received doxazosin 4 mg + sertraline 50 mg once a day. National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, the short-form McGill Pain questionnaire (SF-MPQ), and the hospital anxiety and depression scale (HAD) were applied for evaluations during follow-up of 1, 3, and 6 months after treatment.There were slight positive significant correlations between NIH-CPSI scores and HAD scores, moderate positive significant correlations between the quality of life (QOL) and SF-MPQ, and slight positive significant correlations between HAD and QOL. The effective rate in the doxazosin group was 4.88%, 19.51%, and 56.10% after 1, 3, and 6 months, respectively (P < 0.05). The SF-MPQ score in the doxazosin group decreased to 1.80 ± 1.29, 2.66 ± 1.57, and 3.24 ± 1.67 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the doxazosin group decreased to 2.24 ± 2.17, 4 ± 2.11, and 4.90 ± 2.62 after 1, 3, and 6 months, respectively (P < 0.05). The effective rate in the sertraline group was 9.76%, 36.59%, and 63.41% after 1, 3, and 6 months, respectively. The SF-MPQ score in the sertraline group decreased to 1.76 ± 1.28, 3.07 ± 2, and 3.93 ± 2.53 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the sertraline group decreased to 3.56 ± 4.11, 5.73 ± 5.26, and 7.27 ± 6.50 after 1, 3, and 6 months, respectively (P < 0.05). The effective rate in the duloxetine group was 36.36%, 88.64%, and 88.64% after 1, 3, and 6 months, respectively. The SF-MPQ score in the duloxetine group decreased to 3.61 ± 2.54, 6.05 ± 3.66, and 7.41 ± 4.26 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the duloxetine group decreased to 3.14 ± 3.28, 6.93 ± 3.90, and 9.43 ± 4.67 after 1, 3, and 6 months, respectively (P < 0.05). There were significant differences in the reduction of the NIH-CPSI score and the SF-MPQ score between the duloxetine group and the sertraline group and between the duloxetine group and the doxazosin group (P < 0.01). There were significant differences in the reduction of the HAD score at 3 months between the duloxetine group and the doxazosin group, and there were significant differences in the reduction of the HAD score at 6 months among the groups (P < 0.05). The incidence rates of adverse reactions in the duloxetine group, the sertraline group, and the duloxetine group were 29.5%, 17%, and 7.3%, respectively, with adverse events ranging from mild to moderate.There was a clear relationship between the extent of pain and mental factors in CP/CPPS with the main symptom of pain. Doxazosin combined with duloxetine exhibited good safety and efficacy in the treatment of pain disorder in CP/CPPS.

Systemic modulation of serotonergic synapses via reuptake blockade or 5HT1A receptor antagonism does not alter perithreshold taste sensitivity in rats.

PubMed

Mathes, Clare M; Spector, Alan C

2014-09-01

Systemic blockade of serotonin (5HT) reuptake with paroxetine has been shown to increase sensitivity to sucrose and quinine in humans. Here, using a 2-response operant taste detection task, we measured the effect of paroxetine and the 5HT1A receptor antagonist WAY100635 on the ability of rats to discriminate sucrose, NaCl, and citric acid from water. After establishing individual psychometric functions, 5 concentrations of each taste stimulus were chosen to represent the dynamic portion of the concentration-response curve, and the performance of the rats to these stimuli was assessed after vehicle, paroxetine (7mg/kg intraperitoneally), and WAY100635 (0.3mg/kg subcutaneously; 1mg/kg intravenously) administration. Although, at times, overall performance across concentrations dropped, at most, 5% from vehicle to drug conditions, no differences relative to vehicle were seen on the parameters of the psychometric function (asymptote, slope, or EC50) after drug administration. In contrast to findings in humans, our results suggest that modulation of 5HT activity has little impact on sucrose detectability at perithreshold concentrations in rats, at least at the doses used in this task. In the rat model, the purported paracrine/neurocrine action of serotonin in the taste bud may work in a manner that does not impact overt taste detection behavior. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Modulation of frontostriatal interaction aligns with reduced primary reward processing under serotonergic drugs.

PubMed

Abler, Birgit; Grön, Georg; Hartmann, Antonie; Metzger, Coraline; Walter, Martin

2012-01-25

Recently, functional interactions between anteroventral prefrontal cortex and nucleus accumbens (NAcc) have been shown to relate to behavior counteracting reward-desiring (Diekhof and Gruber, 2010). Downregulation of the reward system by serotonin has also been suggested as the mode of action accounting for unsatisfactory effects of serotonin reuptake inhibitors (SSRIs) such as insufficient alleviation or even increase of anhedonia, and loss of interest. However, understanding of the in vivo mechanisms of SSRI-related alteration of the human reward system is still incomplete. Using functional magnetic resonance imaging (fMRI) within a double-blind cross-over within-subjects study design and administering the SSRI paroxetine, the dopamine/norepinephrine reuptake inhibitor bupropione, and placebo for 7 d each, we investigated a group of 18 healthy male subjects. Under paroxetine, subjects showed significantly decreased activation of the bilateral NAcc during processing of primary rewards (erotic videos), but not under bupropion. Similar to the previous study, analysis of psychophysiological interactions revealed that this downregulation relied on negative interactions between left and right NAcc fMRI signals and the bilateral anteroventral prefrontal cortex that now were significantly enhanced under paroxetine and reduced under bupropion. Individual drug-dependent modulations of interacting brain regions were significantly associated with individual expressions of impulsivity as a personality trait. Our results corroborate and extend previous insights on interregional crosstalk from secondary to primary rewards and demonstrate parallels between active inhibitory control of and serotonergic effects on the dopaminergic reward system's activity.

When Medication Is Prescribed

MedlinePlus

... or combination of medications for the patient. Selective serotonin reuptake inhibitors (SSRIs): citalopram (brand name: Celexa) escitalopram ( ... brand names: Paxil, Pexeva) sertraline (brand name: Zoloft) Serotonin and norepinephrine reuptake inhibitors (SNRIs): venlafaxine (brand name: ...

The Influence of the Menstrual Cycle on Lithium and Sertraline Blood Levels

ClinicalTrials.gov

2017-02-17

Bipolar Affective Disorders; Cyclothymic Disorder; Schizoaffective Disorder; Major Depressive Disorder; Dysthymic Disorder; Obsessive-Compulsive Disorder; Panic Disorder; Posttraumatic Stress Disorder; Premenstrual Dysphoric Disorder; Social Anxiety Disorder

Pilot pharmacologic randomized controlled trial for psychogenic nonepileptic seizures(e–Pub ahead of print)(LOE Classification)

PubMed Central

LaFrance, W.C.; Keitner, G.I.; Papandonatos, G.D.; Blum, A.S.; Machan, J.T.; Ryan, C.E.; Miller, I.W.

2010-01-01

Objective: There have been few treatment trials for psychogenic nonepileptic seizures (PNES). Some psychotherapies have been shown to improve PNES and comorbid symptom outcomes. We evaluated a pharmacologic intervention to test the hypothesis that sertraline would reduce PNES. Methods: We conducted a pilot, double-blind, randomized, placebo-controlled trial in an academic medical hospital with epilepsy center outpatients. Subjects aged 18 to 65 years diagnosed with video-EEG–confirmed PNES were treated with flexible-dose sertraline or placebo over 12 weeks. Seizure calendars and symptom scales were charted prospectively. Secondary outcome measures included psychiatric symptom scales and psychosocial variables. Results: Thirty-eight subjects enrolled, and 26 (68%) completed the trial. Thirty-three subjects with nonzero nonepileptic seizure rates at baseline were included in intent-to-treat analysis of the primary outcome. Subjects assigned to the sertraline arm experienced a 45% reduction in seizure rates from baseline to final visit (p = 0.03) vs an 8% increase in placebo (p = 0.78). Secondary outcome scales revealed no significant between-group differences in change scores from baseline to final visit, after adjustment for differences at baseline. Conclusions: PNES were reduced in patients treated with a serotonin selective reuptake inhibitor, whereas those treated with placebo slightly increased. This study provides feasibility data for a larger-scale study. Level of evidence: This study provides Class II evidence that flexible-dose sertraline up to a maximum dose of 200 mg is associated with a nonsignificant reduction in PNES rate compared with a placebo control arm (risk ratio 0.51, 95% confidence interval 0.25–1.05, p = 0.29), adjusting for differences at baseline. GLOSSARY AED = antiepileptic drug; CI = confidence interval; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; ES = epileptic seizures; ITT = intent to treat; PNES = psychogenic nonepileptic seizures; PTSD = posttraumatic stress disorder; QOL = quality of life; RCT = randomized controlled trial; RIH = Rhode Island Hospital; RR = risk ratio; SSRI = serotonin selective reuptake inhibitor; vEEG = video-EEG. PMID:20739647

Ondansetron reduces naturalistic drinking in non-treatment seeking alcohol dependent individuals with the LL 5′-HTTLPR genotype: a laboratory study

PubMed Central

Kenna, George A.; Zywiak, William H.; Swift, Robert M.; McGeary, John E.; Clifford, James S.; Shoaff, Jessica R.; Vuittonet, Cynthia; Fricchione, Samuel; Brickley, Michael; Beaucage, Kayla; Haass-Koffler, Carolina L.; Leggio, Lorenzo

2014-01-01

Background One hypothesis suggests that the differential response to ondansetron and serotonin specific re-uptake inhibitors (SSRIs) may be due to a functional polymorphism of the 5′-HTTLPR promoter region in SLC6A4, the gene that codes for the serotonin transporter (5-HTT). The LL 5′-HTTLPR genotype is postulated to be specifically sensitive to the effects of ondansetron with SS/SL 5′-HTTLPR genotypes sensitive to SSRIs. This study tests this hypothesis by matching non-treatment seeking alcohol dependent (AD) individuals with LL genotype to ondansetron and SS/SL genotypes to the SSRI sertraline, and mis-matching them assessing naturalistic and bar-laboratory alcohol drinking. Methods Seventy-seven AD individuals were randomized to one of two counterbalanced arms to receive sertraline 200mg/day or ondansetron 0.5 mg/day for three weeks followed by an alcohol self-administration experiment (ASAE), then received placebo for three weeks followed by a second ASAE. Individuals then received the alternate drug for three weeks followed by a third ASAE. Drinks per drinking day (DDD with drinks in SDUs) for 7 days prior to each ASAE and milliliters consumed during each ASAE were the primary outcomes. Results Fifty-five participants completed the study. The genotype x order interaction was significant [F(1,47) = 8.42, p = .006] for DDD. Three ANCOVAs were conducted for DDD during the week before each ASAE. Ondansetron compared to sertraline resulted in a significant reduction in DDD during the week before the first [F(1,47) = 7.64, p = .008] but not the third ASAE. There was no difference in milliliters consumed during each ASAE. Conclusion This study modestly supports the hypothesis that ondansetron may reduce DDD in AD individuals with the LL genotype as measured naturalistically. By contrast there was no support that ondansetron reduces drinking during the ASAEs or that sertraline reduces alcohol use in individuals who have SS/SL genotypes. We provide limited support that ondansetron may reduce drinking in non-treatment seeking individuals with the LL genotype. PMID:24773166

Sertraline (Zoloft) and Pregnancy

MedlinePlus

... or motor skills compared to other children. Another study evaluated behaviors in children ages 4-5 years old. This study found no difference in behavior between children whose mothers took an SSRI and those children ...

St. John's Wort

MedlinePlus

... Berner MM, Kriston L. St. John’s wort for major depression. Cochrane Database of Systematic Reviews. 2008;(4):CD000448 [ ... Hypericum perforatum) versus sertraline and placebo in major depressive disorder: continuation data from a 26-week RCT . Pharmacopsychiatry. ...

Presence of pharmaceuticals in benthic fauna living in a small stream affected by effluent from a municipal sewage treatment plant.

PubMed

Grabicova, Katerina; Grabic, Roman; Blaha, Martin; Kumar, Vimal; Cerveny, Daniel; Fedorova, Ganna; Randak, Tomas

2015-04-01

Aquatic organisms can be affected not only via polluted water but also via their food. In the present study, we examined bioaccumulation of seventy pharmaceuticals in two benthic organisms, Hydropsyche sp. and Erpobdella octoculata in a small stream affected by the effluent from a sewage treatment plant (STP) in Prachatice (South Bohemia region, Czech Republic). Furthermore, water samples from similar locations were analyzed for all seventy pharmaceuticals. In water samples from a control locality situated upstream of the STP, ten of the seventy pharmaceuticals were found with average total concentrations of 200 ng L(-1). In water samples collected at STP-affected sites (downstream the STP's effluent), twenty-nine, twenty-seven and twenty-nine pharmaceuticals were determined at average total concentrations of 2000, 2100 and 1700 ng L(-1), respectively. Six of the seventy pharmaceuticals (azithromycin, citalopram, clarithromycin, clotrimazole, sertraline, and verapamil) were found in Hydropsyche. Four pharmaceuticals (clotrimazole, diclofenac, sertraline, and valsartan) were detected in Erpobdella. Using evaluation criterion bioconcentration factor (BCF) is higher than 2000 we can assign azithromycin and sertraline as bioaccumulative pharmaceuticals. Even pharmaceuticals present at low levels in water were found in benthic organisms at relatively high concentrations (up to 85 ng g(-1) w.w. for azithromycin). Consequently, the uptake of pharmaceuticals via the food web could be an important exposure pathway for the wild fish population. Copyright © 2014. Published by Elsevier Ltd.

Danish physicians' preferences for prescribing escitalopram over citalopram and sertraline to treatment-naïve patients: a national, register-based study.

PubMed

Poulsen, Karen Killerup; Glintborg, Dorte; Moreno, Søren Ilsøe; Thirstrup, Steffen; Aagaard, Lise; Andersen, Stig Ejdrup

2013-05-01

To investigate whether general practitioners, hospital physicians and specialized practitioners in psychiatry have similar preferences for initiating treatment with expensive serotonin-specific reuptake inhibitors (SSRIs). All first-time prescriptions for the SSRIs escitalopram, citalopram and sertraline reported to the Danish National Register of Medicinal Product Statistics from April 1, 2009 until March 31, 2010 were analysed with regard to treatment naivety and type of prescriber. A prescription was considered as first time if the patient had not received a prescription for the same drug within the last 2 years. Patients who had not received a prescription for an antidepressant within 6 months prior to the date of redemption were classified as treatment-naïve. We included 82,702 first-time prescriptions, 65,313 (79 %) of which were for treatment-naïve patients. Of the treatment-naïve patients, 19 % were initially prescribed escitalopram. Hospital physicians prescribed escitalopram to 34 % of their treatment-naïve patients, while practitioners specialized in psychiatry prescribed it to 25 %, and general practitioners prescribed it to 17 %. General practitioners, however, were responsible for initiating 87 % of all treatment-naïve patients. The most expensive SSRI, escitalopram, is prescribed as first choice to one in five patients receiving their first antidepressant of escitalopram, citalopram or sertraline. General practitioners made the bulk of all first-time SSRI prescriptions to treatment-naïve patients.

[Sibutramine-related panic attack: a clinical case of apparent resolution with paroxetine].

PubMed

Fiorentini, Samantha; Russo, Daniele; D'Amato, Antonella; Limpido, Lucilla; Bersani, Giuseppe

2009-01-01

The authors report the case of a patient arrived in psychiatric ambulatory with a panic-like symptomatology. The patient refers that the symptomatology appeared after taking sibutramine. She took it with the intent to lose weight. After the disturbance beginning, the patient interrupted the sibutramine treatment but the psychiatric symptomatology didn't regress completely. It is supposed, in the light of this new evidence and in conformity of DSM-IV criteria, the diagnosis of substance-induced anxiety disorder with panic attack. Paroxetine and alprazolam were administered to the patient, with the resolution of the anxious symptoms. After eight months the treatment was suspended, since the patient referred to be pregnant; in any case, during the pregnancy no other panic attacks occurred. After six months from the suspension of the drugs, the patient can no longer be classified as affected by panic attack according to the DSM-IV criteria.

X-Ray diffraction, spectroscopy and thermochemical characterization of the pharmaceutical paroxetine nitrate salt

NASA Astrophysics Data System (ADS)

Carvalho, Paulo S.; de Melo, Cristiane C.; Ayala, Alejandro P.; Ellena, Javier

2016-08-01

A comprehensive solid state study of Paroxetine nitrate hydrate, (PRX+·NO3-)H2O, is reported. This salt was characterized by a combination of methods, including Single crystal X-ray diffraction, Thermal analysis, Fourier transform infrared spectroscopy (FTIR) and Solubility measurements. (PRX+·NO3-)H2O crystallizes in the monoclinic C2 space group (Z‧ = 1) and its packing was analyzed in details, showing that the main supramolecular motif consists in a C22(4) chain formed by charge-assisted N+-H⋯O- hydrogen bonds. The salt formation and conformation features were also accuracy established via FTIR spectra. In comparison with the pharmaceutical approved (PRX+ṡCl-)ṡ0.5H2O, (PRX+ṡNO3-)ṡH2O showed a decrease of 24 °C in the drug melting peak and a slight reduction in its water solubility value.

Determination of fluvoxamine maleate in human urine and human serum using alkaline KMnO4 -rhodamine B chemiluminescence.

PubMed

Yang, Dongqin; He, Yanyan; Chen, Funan

2017-09-01

The flow-injection chemiluminescence (FI-CL) behavior of a gold nanocluster (Au NC)-enhanced rhodamine B-KMnO 4 system was studied under alkaline conditions for the first time. In the present study, the as-prepared bovine serum albumin-stabilized Au NCs showed excellent stability and reproducibility. The addition of trace levels of fluvoxamine maleate (Flu) led to an obvious decline in CL intensity in the rhodamine B-KMnO 4 -Au NCs system, which could be used for quantitative detection of Flu. Under optimized conditions, the proposed CL system exhibited a favorable analytical performance for Flu determination in the range 2 to 100 μg ml -1 . The detection limit for Flu measurement was 0.021 μg ml -1 . Moreover, this newly developed system revealed outstanding selectivity for Flu detection when compared with a multitude of other species, such as the usual ions, uric acid and a section of hydroxy compounds. Additionally, CL spectra, UV-visible spectroscopes and fluorescence spectra were measured in order to determine the possible reaction mechanism. This approach could be used to detect Flu in human urine and human serum samples with the desired recoveries and could have promising application under physiological conditions. Copyright © 2017 John Wiley & Sons, Ltd.

Interaction of different antidepressants with acute and chronic methadone in mice, and possible clinical implications.

PubMed

Schreiber, Shaul; Barak, Yonatan; Hostovsky, Avner; Baratz-Goldstein, Renana; Volis, Ina; Rubovitch, Vardit; Pick, Chaim G

2014-04-01

We studied the interaction of a single dose of different antidepressant medications with a single (acute) dose or implanted mini-pump (chronic) methadone administration in mice, using the hotplate assay. For the acute experiment, subthreshold doses of six antidepressant drugs were administered separately with a single dose of methadone. The addition of a subthreshold dose of desipramine or clomipramine to methadone produced significant augmentation of the methadone effect with each drug (p < 0.05). Fluvoxamine given at a fixed subthreshold dose induced a synergistic effect only with a low methadone dose. Escitalopram, reboxetine and venlafaxine given separately, each at a fixed subthreshold dose, induced no interaction. Possible clinical implications of these findings are that while escitalopram, reboxetine and venlafaxine do not affect methadone's antinociception in mice and are safe to be given together with methadone when indicated, fluvoxamine, clomipramine and desipramine considerably augment methadone-induced effects and should be avoided in this population due to the risk of inducing opiate overdose. For the chromic experiment, when a subthreshold dose of either escitalopram, desipramine or clomipramine was injected to mice following 2 weeks of methadone administration with the mini-pump, none of the antidepressant drugs strengthened methadone's analgesic effect. Further studies are needed before possible clinical implications can be drawn.

Olfactory Reference Syndrome with Suicidal Attempt Treated with Pimozide and Fluvoxamine

PubMed Central

Virk, Inderpreet; Cherukupally, Karthik; Germain, Wil; Fouron, Patricia; Olupona, Tolu; Jolayemi, Ayodeji

2018-01-01

The core symptomatology of the Olfactory Reference Syndrome (ORS) is characterized by a preoccupation with the belief that one emits an offensive odor, albeit not perceived by others. The present case is that of a 75-year-old African American woman, with an unclear past psychiatric history, who was brought into our Emergency Room after a suicide attempt. The patient reported a three-year history of a “rotten” smell from her vagina. She adamantly believes that she smells despite being told otherwise by people. The patient reported a trial of several feminine products to get rid of this smell and multiple visits to specialists but her symptoms persisted. Her symptoms involved a significant depressed mood and deterioration in her social functioning, interpersonal relationships, and self-care. She was constantly in the shower and had stopped leaving her apartment due to worries that people might smell her vagina. The culmination of her distress was the suicidal attempt, for which she was brought to the hospital. She was admitted to the inpatient psychiatric unit and started on Pimozide and Fluvoxamine. The patient made remarkable progress within a few days on admission and in the course of her hospitalization. Follow-up in our outpatient clinic shows that the patient remains completely asymptomatic with significant progress in her social functioning.

Presidential Green Chemistry Challenge: 2002 Greener Synthetic Pathways Award

EPA Pesticide Factsheets

Presidential Green Chemistry Challenge 2002 award winner, Pfizer, improved its synthesis of sertraline, the active ingredient in its drug, Zoloft, to double the yield and reduce the use of raw materials, energy, and water.

Agomelatine versus other antidepressive agents for major depression.

PubMed

Guaiana, Giuseppe; Gupta, Sumeet; Chiodo, Debbie; Davies, Simon J C; Haederle, Katja; Koesters, Markus

2013-12-17

Major depressive disorder (MDD), or depression, is a syndrome characterised by a number of behavioural, cognitive and emotional features. It is most commonly associated with a sad or depressed mood, a reduced capacity to feel pleasure, feelings of hopelessness, loss of energy, altered sleep patterns, weight fluctuations, difficulty in concentrating and suicidal ideation. There is a need for more effective and better tolerated antidepressants to combat this condition. Agomelatine was recently added to the list of available antidepressant drugs; it is a novel antidepressant that works on melatonergic (MT1 and MT2), 5-HT 2B and 5-HT2C receptors. Because the mechanism of action is claimed to be novel, it may provide a useful, alternative pharmacological strategy to existing antidepressant drugs. The objective of this review was 1) to determine the efficacy of agomelatine in alleviating acute symptoms of major depressive disorder in comparison with other antidepressants, 2) to review the acceptability of agomelatine in comparison with other antidepressant drugs, and, 3) to investigate the adverse effects of agomelatine, including the general prevalence of side effects in adults. We searched the Cochrane Collaboration's Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to 31 July 2013. The CCDANCTR includes relevant randomised controlled trials from the following bibliographic databases: CENTRAL (the Cochrane Central Register of Controlled Trials) (all years), EMBASE (1974 onwards), MEDLINE (1950 onwards) and PsycINFO (1967 onwards). We checked reference lists of relevant studies together with reviews and regulatory agency reports. No restrictions on date, language or publication status were applied to the search. Servier Laboratories (developers of agomelatine) and other experts in the field were contacted for supplemental data. Randomised controlled trials allocating adult participants with major depression to agomelatine versus any other antidepressive agent. Two review authors independently extracted data and a double-entry procedure was employed. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability. A total of 13 studies (4495 participants) were included in this review. Agomelatine was compared to selective serotonin reuptake inhibitors (SSRIs), namely paroxetine, fluoxetine, sertraline, escitalopram, and to the serotonin-norepinephrine reuptake inhibitor (SNRI), venlafaxine. Participants were followed up for six to 12 weeks. Agomelatine did not show any advantage or disadvantage over the other antidepressants for our primary outcome, response to treatment (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.95 to 1.08, P value 0.75 compared to SSRIs, and RR 1.06; 95% CI 0.98 to 1.16, P value 0.16 compared to venlafaxine). Also, agomelatine showed no advantage or disadvantage over other antidepressants for remission (RR 0.83; 95% CI 0.68 to 1.01, P value 0.07 compared to SSRIs, and RR 1.08; 95% CI 0.94 to 1.24, P value 0.73 compared to venlafaxine). Overall, agomelatine appeared to be better tolerated than venlafaxine in terms of lower rates of drop outs (RR 0.40; 95% CI 0.24 to 0.67, P value 0.0005), and showed the same level of tolerability as SSRIs (RR 0.95; 95% CI 0.83 to 1.09, P value 0.44). Agomelatine induced a lower rate of dizziness than venlafaxine (RR 0.19, 95% CI 0.06 to 0.64, P value 0.007).With regard to the quality of the body of evidence, there was a moderate risk of bias for all outcomes, due to the number of included unpublished studies. There was some heterogeneity, particularly between published and unpublished studies. The included studies were conducted in inpatient and outpatient settings, thus limiting the generalisability of the results to primary care settings. With regard to precision, the efficacy outcomes were precise, but the tolerability outcomes were mostly imprecise. Publication bias was variable and depended on the outcome of the trial. Our review included unpublished studies, and we think that this reduced the impact of publication bias. The overall methodological quality of the studies was not very good. Almost all of the studies were sponsored by the pharmaceutical company that manufactures agomelatine (Servier), and some of these were unpublished. Attempts to contact the pharmaceutical company Servier for additional information on all unpublished studies were unsuccessful. Agomelatine did not seem to provide a significant advantage in efficacy over other antidepressive agents for the acute-phase treatment of major depression. Agomelatine was better tolerated than paroxetine and venlafaxine in terms of overall side effects, and fewer participants treated with agomelatine dropped out of the trials due to side effects compared to sertraline and venlafaxine, but data were limited because the number of included studies was small. We found evidence that compared agomelatine with only a small number of other active antidepressive agents, and there were only a few trials for each comparison, which limits the generalisability of the results. Moreover, the overall methodological quality of the studies was low, and, therefore, no firm conclusions can be drawn concerning the efficacy and tolerability of agomelatine.

Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers.

PubMed

Glue, Paul; Winter, Helen; Garbe, Kira; Jakobi, Hannah; Lyudin, Alexander; Lenagh-Glue, Zoe; Hung, C Tak

2015-06-01

Conversion of ibogaine to its active metabolite noribogaine appears to be mediated primarily by CYP2D6. We compared 168 hours pharmacokinetic profiles of both analytes after a single oral 20 mg dose of ibogaine in 21 healthy subjects who had been pretreated for 6 days with placebo or the CYP2D6 inhibitor paroxetine. In placebo-pretreated subjects, ibogaine was rapidly converted to noribogaine. Median peak noribogaine concentrations occurred at 4 hours. Compared with placebo-pretreated subjects, paroxetine-pretreated subjects had rapid (Tmax  = 1.5 hours) and substantial absorption of ibogaine, with detectable levels out to 72 hours, and an elimination half-life of 10.2 hours. In this group, ibogaine was also rapidly converted to noribogaine with a median Tmax of 3 hours. Extent of noribogaine exposure was similar in both groups. CYP2D6 phenotype was robustly correlated with ibogaine AUC0-t (r = 0.82) and Cmax (r = 0.77). Active moiety (ibogaine plus noribogaine) exposure was ∼2-fold higher in paroxetine-pretreated subjects. Single 20 mg ibogaine doses were safe and well tolerated in all subjects. The doubling of exposure to active moiety in subjects with reduced CYP2D6 activity suggests it may be prudent to genotype patients awaiting ibogaine treatment, and to at least halve the intended dose of ibogaine in CYP2D6 poor metabolizers. © 2015, The American College of Clinical Pharmacology.

[Correlations between Beck's suicidal ideation scale, suicidal risk assessment scale RSD and Hamilton's depression rating scale].

PubMed

Ducher, J-L; Dalery, J

2008-04-01

Most of the people who will attempt suicide, talk about it beforehand. Therefore, recognition of suicidal risk is not absolutely impossible. Beck's suicidal ideation scale and Ducher's suicidal risk assessment scale (RSD) are common tools to help practicians in this way. These scales and the Hamilton's depression scale were included in an international multicentric, phase IV, double-blind study, according to two parallel groups who had been administered a fixed dose of fluvoxamin or fluoxetin for six weeks. This allowed examination of the correlations between these scales and the relations, which could possibly exist between suicidal risk, depression and anxiety. (a) Relationships between the Beck's suicidal ideation scale, the suicidal risk assessment scale RSD and Hamilton's depression before treatment. Before treatment, the analysis was conducted with 108 male and female depressive outpatients, aged 18 or over. Results revealed a significant positive correlation (with a Pearson's correlation coefficient r equal to 0.69 and risk p<0.0001) between Beck's suicidal ideation scale and the suicidal risk assessment scale RSD. These scales correlate less consistently with Hamilton's depression (Beck/Hamilton's depression: r=0.34; p=0.0004-RSD/Hamilton's depression: r=0.35; p=0.0002). We observed that the clinical anxiety scale by Snaith is also strongly correlated to these two suicidal risk assessment scales (Beck/CAS: r=0.48; p<0.0001-RSD/CAS: r=0.35; p=0.0005). Besides, the item "suicide" of Hamilton's depression scale accounts for more than a third of the variability of Beck's suicidal ideation scale and the suicidal risk assessment scale RSD. According to these results, the suicidal risk evaluated by these two scales seems to be significantly correlated with anxiety as much as with depression. On the other hand, the Clinical Global Impression is fairly significantly correlated with Beck's suicidal ideation scale (r=0.22; p=0.02), unlike the suicidal risk assessment scale RSD (r=0.42; p<0.0001) and Hamilton's depression scale (r=0.58; p<0.0001); (b) Relationships between Beck's suicidal ideation scale, the suicidal risk assessment scale RSD and Hamilton's depression under treatment. The follow-up under treatment (fluvoxamin or fluoxetin) during six weeks revealed the significantly better sensitivity of the RSD in comparison with Beck's suicidal ideation scale and Hamilton's depression scale, showing the significantly faster improvement in the RSD (p<0.0001). There was no significant difference between the evolution of Beck's suicidal ideation scale and Hamilton's depression scale. So, under treatment with fluvoxamin or fluoxetin, the improvement in suicidal risk appears to be as rapid as the improvement in depression. If we look at the treatment prescribed, only the suicidal risk assessment scale RSD revealed a significant difference between the two molecules, with more rapid improvement with fluvoxamin (p=0.015) from D14. In conclusion, the results of this study hypothesize that the suicidal risk, as assessed by Beck's suicidal ideation scale and the suicidal risk assessment scale RSD, appears to be consistently correlated with both the level of anxiety and depression. The study also suggests that all antidepressants may not be equally effective on suicidal risk.

Sertraline

MedlinePlus

... to abnormally excited) or mania (frenzied, abnormally excited mood) or has thought about or attempted suicide. Talk to your doctor about your condition, symptoms, and personal and family medical history. You and your doctor will decide what type of treatment is right for you.

Dynamic potential and surface morphology study of sertraline membrane sensors

PubMed Central

Khater, M.M.; Issa, Y.M.; Hassib, H.B.; Mohammed, S.H.

2014-01-01

New rapid, sensitive and simple electrometric method was developed to determine sertraline hydrochloride (Ser-Cl) in its pure raw material and pharmaceutical formulations. Membrane sensors based on heteropolyacids as ion associating material were prepared. Silicomolybdic acid (SMA), silicotungstic acid (STA) and phosphomolybdic acid (PMA) were used. The slope and limit of detection are 50.00, 60.00 and 53.24 mV/decade and 2.51, 5.62 and 4.85 μmol L−1 for Ser-ST, Ser-PM and Ser-SM membrane sensors, respectively. Linear range is 0.01–10.00 for the three sensors. These new sensors were used for the potentiometric titration of Ser-Cl using sodium tetraphenylborate as titrant. The surface morphologies of the prepared membranes with and without the modifier (ion-associate) were studied using scanning and atomic force microscopes. PMID:26257944

Treatment of traumatized refugees with sertraline versus venlafaxine in combination with psychotherapy - study protocol for a randomized clinical trial.

PubMed

Sonne, Charlotte; Carlsson, Jessica; Elklit, Ask; Mortensen, Erik Lykke; Ekstrøm, Morten

2013-05-11

Sufficient evidence is lacking to draw final conclusions on the efficiency of medical and psychological treatments of traumatized refugees with PTSD. The pharmacological treatments of choice today for post-traumatic stress disorder are antidepressants from the subgroup selective serotonin reuptake inhibitors, especially sertraline. The evidence for the use of selective serotonin reuptake inhibitors in the treatment of complex post-traumatic stress disorder in traumatized refugees is very limited. Venlafaxine is a dual-action antidepressant that works on several pathways in the brain. It influences areas in the brain which are responsible for the enhanced anxiety and hyper-arousal experienced by traumatized refugees and which some studies have found to be enlarged among patients suffering from post-traumatic stress disorder. This study will include approximately 150 patients, randomized into two different groups treated with either sertraline or venlafaxine. Patients in both groups will receive the same manual-based cognitive behavioral therapy, which has been especially adapted to this group of patients. The treatment period will be 6 to 7 months. The trial endpoints will be post-traumatic stress disorder and depressive symptoms and social functioning, all measured on validated ratings scales. Furthermore the study will examine the relation between a psycho-social resources and treatment outcome based on 15 different possible outcome predictors. This study is expected to bring forward new knowledge on treatment and clinical evaluation of traumatized refugees and the results are expected to be used in reference programs and clinical guidelines. ClinicalTrials.gov NCT01569685.

Treatment of traumatized refugees with Sertraline versus Venlafaxine in combination with psychotherapy – study protocol for a randomized clinical trial

PubMed Central

2013-01-01

Background Sufficient evidence is lacking to draw final conclusions on the efficiency of medical and psychological treatments of traumatized refugees with PTSD. The pharmacological treatments of choice today for post-traumatic stress disorder are antidepressants from the subgroup selective serotonin reuptake inhibitors, especially Sertraline. The evidence for the use of selective serotonin reuptake inhibitors in the treatment of complex post-traumatic stress disorder in traumatized refugees is very limited. Venlafaxine is a dual-action antidepressant that works on several pathways in the brain. It influences areas in the brain which are responsible for the enhanced anxiety and hyper-arousal experienced by traumatized refugees and which some studies have found to be enlarged among patients suffering from post-traumatic stress disorder. Design This study will include approximately 150 patients, randomized into two different groups treated with either Sertraline or Venlafaxine. Patients in both groups will receive the same manual-based cognitive behavioral therapy, which has been especially adapted to this group of patients. The treatment period will be 6 to 7 months. The trial endpoints will be post-traumatic stress disorder and depressive symptoms and social functioning, all measured on validated ratings scales. Furthermore the study will examine the relation between a psycho-social resources and treatment outcome based on 15 different possible outcome predictors. Discussion This study is expected to bring forward new knowledge on treatment and clinical evaluation of traumatized refugees and the results are expected to be used in reference programs and clinical guidelines. Trial registration ClinicalTrials.gov NCT01569685 PMID:23663588

Rationale and design of A Trial of Sertraline vs. Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression (ASCEND).

PubMed

Hedayati, S Susan; Daniel, Divya M; Cohen, Scott; Comstock, Bryan; Cukor, Daniel; Diaz-Linhart, Yaminette; Dember, Laura M; Dubovsky, Amelia; Greene, Tom; Grote, Nancy; Heagerty, Patrick; Katon, Wayne; Kimmel, Paul L; Kutner, Nancy; Linke, Lori; Quinn, Davin; Rue, Tessa; Trivedi, Madhukar H; Unruh, Mark; Weisbord, Steven; Young, Bessie A; Mehrotra, Rajnish

2016-03-01

Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes. Published by Elsevier Inc.

Rationale and Design of A Trial of Sertraline vs. Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression (ASCEND)

PubMed Central

Hedayati, S. Susan; Daniel, Divya M.; Cohen, Scott; Comstock, Bryan; Cukor, Daniel; Diaz-Linhart, Yaminette; Dember, Laura M.; Dubovsky, Amelia; Greene, Tom; Grote, Nancy; Heagerty, Patrick; Katon, Wayne; Kimmel, Paul L.; Kutner, Nancy; Linke, Lori; Quinn, Davin; Rue, Tessa; Trivedi, Madhukar H.; Unruh, Mark; Weisbord, Steven; Young, Bessie A.; Mehrotra, Rajnish

2015-01-01

Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes. PMID:26621218

Dynamical Systems in Neuropharmacology

DTIC Science & Technology

1992-04-15

induced hyperactivity with the selective serotonin uptake blockers fluoxetine , sertraline, or zimelidine or with the serotonin synthesis inhibitor PCPA. By...Conversely, the catecholamine synthesis inhibitor AMPT, which blocks the effects of amphetamine, did not affect the response to MDMA. We applied our scaling

Study protocol of the Diabetes and Depression Study (DAD): a multi-center randomized controlled trial to compare the efficacy of a diabetes-specific cognitive behavioral group therapy versus sertraline in patients with major depression and poorly controlled diabetes mellitus.

PubMed

Petrak, Frank; Herpertz, Stephan; Albus, Christian; Hermanns, Norbert; Hiemke, Christoph; Hiller, Wolfgang; Kronfeld, Kai; Kruse, Johannes; Kulzer, Bernd; Ruckes, Christian; Müller, Matthias J

2013-08-06

Depression is common in diabetes and associated with hyperglycemia, diabetes related complications and mortality. No single intervention has been identified that consistently leads to simultaneous improvement of depression and glycemic control. Our aim is to analyze the efficacy of a diabetes-specific cognitive behavioral group therapy (CBT) compared to sertraline (SER) in adults with depression and poorly controlled diabetes. This study is a multi-center parallel arm randomized controlled trial currently in its data analysis phase. We included 251 patients in 70 secondary care centers across Germany. Key inclusion criteria were: type 1 or 2 diabetes, major depression (diagnosed with the Structured Clinical Interview for DSM-IV, SCID) and hemoglobin A1C >7.5% despite current insulin therapy. During the initial phase, patients received either 50-200 mg/d sertraline or 10 CBT sessions aiming at the remission of depression and enhanced adherence to diabetes treatment and coping with diabetes. Both groups received diabetes treatment as usual. After 12 weeks of this initial open-label therapy, only the treatment-responders (50% depression symptoms reduction, Hamilton Depression Rating Scale, 17-item version [HAMD]) were included in the subsequent one year study phase and represented the primary analysis population. CBT-responders received no further treatment, while SER-responders obtained a continuous, flexible-dose SER regimen as relapse prevention. Adherence to treatment was analyzed using therapeutic drug monitoring (measurement of sertraline and N-desmethylsertraline concentrations in blood serum) and by counting the numbers of CBT sessions received. Outcome assessments were conducted by trained psychologists blinded to group assignment. Group differences in HbA1c (primary outcome) and depression (HAMD, secondary outcome) between 1-year follow-up and baseline will be analyzed by ANCOVA controlling for baseline values. As primary hypothesis we expect that CBT leads to significantly greater improvement of glycemic control in the one year follow-up in treatment responders of the short term phase. The DAD study is the first randomized controlled trial comparing antidepressants to a psychological treatment in diabetes patients with depression. Current controlled trials ISRCTN89333241.

Pilot of a randomised controlled trial of the selective serotonin reuptake inhibitor sertraline versus cognitive behavioural therapy for anxiety symptoms in people with generalised anxiety disorder who have failed to respond to low-intensity psychological treatments as defined by the National Institute for Health and Care Excellence guidelines.

PubMed

Buszewicz, Marta; Cape, John; Serfaty, Marc; Shafran, Roz; Kabir, Thomas; Tyrer, Peter; Clarke, Caroline S; Nazareth, Irwin

2017-08-01

Generalised anxiety disorder (GAD) is common, causing unpleasant symptoms and impaired functioning. The National Institute for Health and Care Excellence (NICE) guidelines have established good evidence for low-intensity psychological interventions, but a significant number of patients will not respond and require more intensive step 3 interventions, recommended as either high-intensity cognitive behavioural therapy (CBT) or a pharmacological treatment such as sertraline. However, there are no head-to-head comparisons evaluating which is more clinically effective and cost-effective, and current guidelines suggest that treatment choice at step 3 is based mainly on patient preference. To assess clinical effectiveness and cost-effectiveness at 12 months of treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline compared with CBT for patients with persistent GAD not improved with NICE-defined low-intensity psychological interventions. Participant randomised trial comparing treatment with sertraline with high-intensity CBT for patients with GAD who had not responded to low-intensity psychological interventions. Community-based recruitment from local Improving Access to Psychological Therapies (IAPT) services. Four pilot services located in urban, suburban and semirural settings. People considered likely to have GAD and not responding to low-intensity psychological interventions identified at review by IAPT psychological well-being practitioners (PWPs). Those scoring ≥ 10 on the Generalised Anxiety Disorder-7 (GAD-7) anxiety measure were asked to consider involvement in the trial. Aged ≥ 18 years, a score of ≥ 10 on the GAD-7, a primary diagnosis of GAD diagnosed on the Mini International Neuropsychiatric Interview questionnaire and failure to respond to NICE-defined low-intensity interventions. Inability to participate because of insufficient English or cognitive impairment, current major depression, comorbid anxiety disorder(s) causing greater distress than GAD, significant dependence on alcohol or illicit drugs, comorbid psychotic disorder, received antidepressants in past 8 weeks or high-intensity psychological therapy in previous 6 months and any contraindications to treatment with sertraline. Consenting eligible participants randomised via an independent, web-based, computerised system. (1) The SSRI sertraline prescribed in therapeutic doses by the patient's general practitioner for 12 months and (2) 14 (± 2) CBT sessions delivered by high-intensity IAPT psychological therapists in accordance with a standardised manual designed for GAD. The primary outcome was the Hospital Anxiety and Depression Scale - Anxiety component at 12 months. Secondary outcomes included measures of depression, social functioning, comorbid anxiety disorders, patient satisfaction and economic evaluation, collected by postal self-completion questionnaires. Only seven internal pilot participants were recruited against a target of 40 participants at 7 months. Far fewer potential participants were identified than anticipated from IAPT services, probably because PWPs rarely considered GAD the main treatment priority. Of those identified, three-quarters declined participation; the majority (30/45) were reluctant to consider the possibility of randomisation to medication. Poor recruitment was the main limiting factor, and the trial closed prematurely. It is unclear how much of the recruitment difficulty was a result of conducting the trial within a psychological therapy service and how much was possibly a result of difficulty identifying participants with primary GAD. It may be easier to answer this important question by recruiting people from primary care rather than from those already engaged in a psychological treatment service. Current Controlled Trials ISCRTN14845583. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 45. See the NIHR Journals Library website for further project information.

The CRF₁ receptor antagonist SSR125543 prevents stress-induced long-lasting sleep disturbances in a mouse model of PTSD: comparison with paroxetine and d-cycloserine.

PubMed

Philbert, Julie; Beeské, Sandra; Belzung, Catherine; Griebel, Guy

2015-02-15

The selective CRF₁ (corticotropin releasing factor type 1) receptor antagonist SSR125543 has been previously shown to attenuate the long-term behavioral and electrophysiological effects produced by traumatic stress exposure in mice. Sleep disturbances are one of the most commonly reported symptoms by people with post-traumatic stress disorder (PTSD). The present study aims at investigating whether SSR125543 (10 mg/kg/day/i.p. for 2 weeks) is able to attenuate sleep/wakefulness impairment induced by traumatic stress exposure in a model of PTSD in mice using electroencephalographic (EEG) analysis. Effects of SSR125543 were compared to those of the 5-HT reuptake inhibitor, paroxetine (10 mg/kg/day/i.p.), and the partial N-methyl-d-aspartate (NMDA) receptor agonist, d-cycloserine (10 mg/kg/day/i.p.), two compounds which have demonstrated clinical efficacy against PTSD. Baseline EEG recording was performed in the home cage for 6h prior to the application of two electric foot-shocks of 1.5 mA. Drugs were administered from day 1 post-stress to the day preceding the second EEG recording session, performed 14 days later. Results showed that at day 14 post-stress, shocked mice displayed sleep fragmentation as shown by an increase in the occurrence of both non-rapid eye movement (NREM) sleep and wakefulness bouts. The duration of wakefulness, NREM and REM sleep were not significantly affected. The stress-induced effects were prevented by repeated administration of SSR125543, paroxetine and D-cycloserine. These findings confirm further that the CRF₁ receptor antagonist SSR125543 is able to attenuate the deleterious effects of traumatic stress exposure. Copyright © 2014 Elsevier B.V. All rights reserved.

Chaperoning epigenetics: FKBP51 decreases the activity of DNMT1 and mediates epigenetic effects of the antidepressant paroxetine.

PubMed

Gassen, Nils C; Fries, Gabriel R; Zannas, Anthony S; Hartmann, Jakob; Zschocke, Jürgen; Hafner, Kathrin; Carrillo-Roa, Tania; Steinbacher, Jessica; Preißinger, S Nicole; Hoeijmakers, Lianne; Knop, Matthias; Weber, Frank; Kloiber, Stefan; Lucae, Susanne; Chrousos, George P; Carell, Thomas; Ising, Marcus; Binder, Elisabeth B; Schmidt, Mathias V; Rüegg, Joëlle; Rein, Theo

2015-11-24

Epigenetic processes, such as DNA methylation, and molecular chaperones, including FK506-binding protein 51 (FKBP51), are independently implicated in stress-related mental disorders and antidepressant drug action. FKBP51 associates with cyclin-dependent kinase 5 (CDK5), which is one of several kinases that phosphorylates and activates DNA methyltransferase 1 (DNMT1). We searched for a functional link between FKBP51 (encoded by FKBP5) and DNMT1 in cells from mice and humans, including those from depressed patients, and found that FKBP51 competed with its close homolog FKBP52 for association with CDK5. In human embryonic kidney (HEK) 293 cells, expression of FKBP51 displaced FKBP52 from CDK5, decreased the interaction of CDK5 with DNMT1, reduced the phosphorylation and enzymatic activity of DNMT1, and diminished global DNA methylation. In mouse embryonic fibroblasts and primary mouse astrocytes, FKBP51 mediated several effects of paroxetine, namely, decreased the protein-protein interactions of DNMT1 with CDK5 and FKBP52, reduced phosphorylation of DNMT1, and decreased the methylation and increased the expression of the gene encoding brain-derived neurotrophic factor (Bdnf). In human peripheral blood cells, FKBP5 expression inversely correlated with both global and BDNF methylation. Peripheral blood cells isolated from depressed patients that were then treated ex vivo with paroxetine revealed that the abundance of BDNF positively correlated and phosphorylated DNMT1 inversely correlated with that of FKBP51 in cells and with clinical treatment success in patients, supporting the relevance of this FKBP51-directed pathway that prevents epigenetic suppression of gene expression. Copyright © 2015, American Association for the Advancement of Science.

Early-life Exposure to the SSRI Paroxetine Exacerbates Depression-like Behavior in Anxiety/Depression-prone rats

PubMed Central

Glover, Matthew E.; Pugh, Phyllis C.; Jackson, Nateka L.; Cohen, Joshua L.; Fant, Andrew D.; Akil, Huda; Clinton, Sarah M.

2014-01-01

Selective serotonin reuptake inhibitor (SSRI) antidepressants are the mainstay treatment for the 10–20% of pregnant and postpartum women who suffer major depression, but the effects of SSRIs on their children’s developing brain and later emotional health are poorly understood. SSRI use during pregnancy can elicit antidepressant withdrawal in newborns and increase toddlers’ anxiety and social avoidance. In rodents, perinatal SSRI exposure increases adult depression- and anxiety-like behavior, although certain individuals are more vulnerable to these effects than others. Our study establishes a rodent model of individual differences in susceptibility to perinatal SSRI exposure, utilizing selectively-bred Low Responder (bLR) and High Responder (bHR) rats that were previously bred for high versus low behavioral response to novelty. Pregnant bHR/bLR females were chronically treated with the SSRI paroxetine (10 mg/kg/day p.o.) to examine its effects on offspring’s emotional behavior and gene expression in the developing brain. Paroxetine treatment had minimal effect on bHR/bLR dams’ pregnancy outcomes or maternal behavior. We found that bLR offspring, naturally prone to an inhibited/anxious temperament, were susceptible to behavioral abnormalities associated with perinatal SSRI exposure (which exacerbated their Forced Swim test immobility), while high risk-taking bHR offspring were resistant. Microarray studies revealed robust perinatal SSRI-induced gene expression changes in the developing bLR hippocampus and amygdala (postnatal days 7–21), including transcripts involved in neurogenesis, synaptic vesicle components, and energy metabolism. These results highlight the bLR/bHR model as a useful tool to explore the neurobiology of individual differences in susceptibility to perinatal SSRI exposure. PMID:25451292

alpha2-Adrenergic agonists antagonise the anxiolytic-like effect of antidepressants in the four-plate test in mice.

PubMed

Massé, Fabienne; Hascoët, Martine; Bourin, Michel

2005-10-14

Selective serotonin reuptake inhibitors (SSRIs) and serotonin/noradrenaline reuptake inhibitors (SNRIs) has been reported to be efficient in anxiety disorders. Some animal models have demonstrated an anxiolytic-like effect following acute administration, however, it is not yet known how noradrenergic receptors are implicated in the therapeutic effects of antidepressants (ADs) in anxiety. The effects of two alpha(2)-adrenoceptor agonists (clonidine, guanabenz) on anxiolytic-like effect of two SSRIs (paroxetine and citalopram) and two SNRIs (venlafaxine and milnacipran) were evaluated in the four-plate test (FPT) in mice. Paroxetine (4 mg/kg), citalopram (8 mg/kg), venlafaxine (8 mg/kg), and milnacipran (8 mg/kg) administered intraperitoneally (i.p.) increased the number of punishments accepted by mice in the FPT. Clonidine (0.0039-0.5 mg/kg) and guanabenz (0.03-0.5mg/kg) had no effect on the number of punishments accepted by mice. Clonidine (0.03 and 0.06 mg/kg) and guanabenz (0.125 and 0.5 mg/kg) (i.p. -45 min) reversed the anti-punishment effect of paroxetine, citalopram, venlafaxine and milnacipran (i.p. -30 min). But if the antidepressants are administered 45 min before the test and alpha(2)-adrenoceptor agonists 30 min before the test, alpha(2)-adrenoceptor agonists failed to alter the anti-punishment effect of antidepressants. The results of this present study indicate that alpha(2)-adrenoceptor agonists antagonise the anxiolytic-like effect of antidepressants in mice when they are administered 15 min before the administration of antidepressant suggesting a close inter-regulation between noradrenergic and serotoninergic system in the mechanism of SSRIs and SNRIs in anxiety-like behaviour.

The effects of vortioxetine on cognitive performance in working patients with major depressive disorder: A short-term, randomized, double-blind, exploratory study.

PubMed

Baune, Bernhard T; Sluth, Lasse B; Olsen, Christina K

2018-03-15

Major Depressive Disorder (MDD) is a complex disease characterized by emotional, physical and cognitive symptoms. We explored the efficacy of vortioxetine versus placebo on outcomes of cognition, functioning and mood symptoms in working patients with depression, using paroxetine as an active reference. Gainfully employed patients (18-65 years, N = 152) with MDD were randomized 1:1:1 to 8 weeks' double-blind, parallel treatment either with vortioxetine (10mg/day) or paroxetine (20mg/day), or with placebo. The primary efficacy measure was the Digit Symbol Substitution Test (DSST), analyzed using a mixed model for repeated measurements, and the key secondary efficacy measure was the University of San Diego Performance-based Skills Assessment - Brief (UPSA-B), analyzed using analysis of covariance (last observation carried forward). At week 8, DSST and UPSA-B performance had improved relative to baseline in all treatment groups, with no statistically significant differences between treatment groups. While improvements in mood were comparable for vortioxetine and paroxetine, numerical improvements in cognitive performance (DSST) were larger with vortioxetine. Vortioxetine significantly improved overall cognitive performance and clinician-rated functioning relative to placebo. The majority of adverse events were mild or moderate, with nausea being the most common adverse event for vortioxetine. Small sample sizes implied limited statistical power. This explorative study showed no significant differences versus placebo in DSST or UPSA-B performance at week 8. However, secondary results support vortioxetine as an effective and well-tolerated antidepressant, supporting an added benefit for cognition and functioning, which could have particular therapeutic relevance for the working patient population. Copyright © 2017 H Lundbeck A/S. Published by Elsevier B.V. All rights reserved.

Laxative use and clinical correlates in hospitalized patients with obsessive-compulsive disorder: a retrospective descriptive study.

PubMed

Lai, Jianbo; Zhou, Weihua; Lu, Qiaoqiao; Huang, Tingting; Xu, Yi; Hu, Shaohua

2018-01-01

Constipation is a common clinical problem with insufficient attention. Medication-emergent constipation is a rarely studied adverse reaction in patients with obsessive-compulsive disorder (OCD). In this descriptive study, we retrospectively investigated the prevalence of laxative use and its relationship with clinical characteristics in hospitalized OCD patients. A total of 51 OCD patients were included in the final analysis. The proportion of patients using laxatives was 31.4%, and the commonly used laxatives were phenolphthalein tablet, lactulose and congrongtongbian oral liquid (a patent herbal medicine). In the laxative group, hospital stays were longer when compared to the nonlaxative group. Moreover, the dose of paroxetine was higher in patients treated with laxatives than in those without laxative use. Correlation analysis indicated that laxative use was positively associated with hospital stays, as well as the dose of paroxetine. The current study provided a preliminary picture of constipation and laxative use in hospitalized OCD patients. Close monitoring and treatment of constipation are recommended in OCD patients with pharmacotherapy.

Personality disorders and traits in patients with body dysmorphic disorder.

PubMed

Phillips, K A; McElroy, S L

2000-01-01

Individuals with body dysmorphic disorder (BDD) have been postulated to have schizoid, narcissistic, and obsessional personality traits and to be sensitive, introverted, perfectionistic, and insecure. However, data on personality traits and disorders in BDD are limited. This study assessed 148 subjects with BDD, 26 of whom participated in a fluvoxamine treatment study; 74 subjects were assessed for personality disorders with the Structured Clinical Interview for DSMIII-R Personality Disorders (SCID-II), 100 subjects completed the NEO-Five Factor Inventory (NEO-FFI), and 51 subjects completed the Rathus Assertiveness Scale. Forty-two subjects (57%) had one or more personality disorders, with avoidant personality disorder (43%) being most common, followed by dependent (15%), obsessive-compulsive (14%), and paranoid (14%) personality disorders. On the NEO-FFI, the mean scores were in the very high range for neuroticism, the low range for extraversion and conscientiousness, the low-average range for agreeableness, and the average range for openness to experience. On the Rathus Assertiveness Scale, the mean score was -17.1 +/- 32.0 for women and -17.0 +/- 32.3 for men. Among fluvoxamine responders, the number of personality disorders significantly decreased between the study baseline and endpoint. These findings suggest that the rate of personality disorders in BDD is relatively high, with avoidant personality disorder being most common. The high neuroticism scores and low extraversion scores are consistent with this finding.

HYDROLYSIS AND PHOTOLYSIS OF PAROXETINE, A SELECTIVE SEROTONIN REUPTAKE INHIBITOR, IN AQUEOUS SOLUTIONS. (R829006)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Pharmacologic management of comorbid post-traumatic stress disorder and addictions.

PubMed

Shorter, Daryl; Hsieh, John; Kosten, Thomas R

2015-12-01

Post-traumatic Stress Disorder (PTSD) and substance use disorders (SUD) frequently co-occur, and their combination can increase poor health outcomes as well as mortality. Using PUBMED and the list of references from key publications, this review article covered the epidemiology, neurobiology and pharmacotherapy of PTSD with comorbid alcohol, opiate, and cannabis use disorders. These SUD represent two with and one without FDA approved pharmacotherapies. SUD is two to three times more likely among individuals with lifetime PTSD, and suicide, which is made more likely by both of these disorders, appears to be additively increased by having this comorbidity of SUD and PTSD. The shared neurobiological features of these two illnesses include amygdalar hyperactivity with hippocampal, medial prefrontal and anterior cingulate cortex dysfunction. Medications for comorbid PTSD and SUD include the PTSD treatment sertraline, often used in combination with anticonvulsants, antipsychotics, and adrenergic blockers. When PTSD is comorbid with alcohol use disorder (AUD), naltrexone, acamprosate or disulfiram may be combined with PTSD treatments. Disulfiram alone may treat both PTSD and AUD. For PTSD combined with opiate use disorder methadone or buprenorphine are most commonly used with sertraline. Marijuana use has been considered by some to be a treatment for PTSD, but no FDA treatment for this addiction is approved. Pregabalin and D-cycloserine are two innovations in pharmacotherapy for PTSD and SUD. Comorbid PTSD and SUD amplifies their lethality and treatment complexity. Although they share important neurobiology, these patients uncommonly respond to a single pharmacotherapy such as sertraline or disulfiram and more typically require medication combinations and consideration of the specific type of SUD. © American Academy of Addiction Psychiatry.

Racial differences in adherence and response to combined treatment for full and subthreshold post-traumatic stress disorder and alcohol use disorders: A secondary analysis.

PubMed

Ruglass, Lesia M; Pedersen, Annelisa; Cheref, Soumia; Hu, Mei-Chen; Hien, Denise A

2016-01-01

We conducted a secondary data analysis to examine whether there were racial differences in adherence and treatment outcomes for participants with co-occurring full and subthreshold post-traumatic stress disorder (PTSD) and alcohol/substance use disorders (A/SUD) who were treated with Seeking Safety (a cognitive-behavioral therapy) and sertraline or Seeking Safety and placebo as part of a clinical trial. Bivarate analyses examined the association between race and adherence, and generalized estimating equations assessed whether race moderated the effect of combination treatment on PTSD and alcohol use outcomes. Except for education, there were no statistically significant racial differences in baseline demographic and psychiatric characteristics. African Americans and Caucasians were equally adherent in number of psychotherapy and medication sessions attended and medication compliance. After controlling for baseline demographics and psychiatric symptoms, however, a race by treatment condition interaction emerged suggesting that African Americans who received the Seeking Safety and sertraline treatment had significantly lower PTSD symptom severity posttreatment and at six months follow-up compared to their counterparts who received Seeking Safety and placebo. No differential effect of treatment condition was found for Caucasians. Moreover, results indicated that a diagnosis of major depressive disorder negatively impacted PTSD symptom recovery for African American participants but not for Caucasians. In conclusion, no differences emerged between African Americans and Caucasians in adherence to combination treatments for PTSD and A/SUD. Findings also suggest assessment and treatment of MDD among African Americans may improve treatment outcomes. More research is needed to determine whether the differential response to Seeking Safety and sertraline among African Americans compared to Caucasians can be replicated.

Environmental risk assessment of three selective serotonin reuptake inhibitors in the aquatic environment: a case study including a cocktail scenario.

PubMed

Styrishave, Bjarne; Halling-Sørensen, Bent; Ingerslev, Flemming

2011-01-01

We present an environmental risk assessment of three selective serotonin reuptake inhibitors (SSRIs; citalopram, sertraline, and fluoxetine) in the aquatic environment based on two case scenarios. Abiotic and biotic degradation experiments and sorption estimates were used to predict environmental concentrations of three SSRIs from the wastewater of two psychiatric hospitals, the primary sector, and wastewater entering and leaving wastewater treatment plants (WWTPs). Assuming a sewage treatment retention time of 8 h, abiotic degradation was low, for all three SSRIs inhibitors, ranging between 0 and 2% for hydrolysis and 0 and 6% for photolysis. The biodegradation was also slow, ranging from 0 to 3% within an 8-h period. In untreated sewage, citalopram (CIT) and sertraline (SER) concentrations may be high enough to exert effects on the aquatic biota (CIT: 0.19-10.3 µg/L; SER: 0.14-17.1 µg/L). Removal of the pharmaceuticals is due primarily to sorption in the WWTP. Sertraline was estimated to have the highest concentrations in the sewage effluents, 4.4 and 19.9 ng/L for the two cases, respectively. In treated wastewater, individual SSRI concentrations are probably too low to exert effects on biota. By using concentration addition, a cocktail exposure scenario was estimated. The predicted concentration in the biota calculated from the cocktail effect was 0.05 and 0.16 nmol/g for the two cases, respectively, and SER was found to give the highest contribution to this cocktail effect. The results indicate that the concentrations in the wastewater effluents are one to two orders of magnitude lower than the concentrations likely to cause an effect in the aquatic biota. © 2010 SETAC.

Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis.

PubMed

Greenberg, Gian D; Laman-Maharg, Abigail; Campi, Katharine L; Voigt, Heather; Orr, Veronica N; Schaal, Leslie; Trainor, Brian C

2013-01-01

Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males. We examined the effects of social defeat in monogamous California mice (Peromyscus californicus), a species in which both males and females defend territories. We demonstrate that defeat stress increases mature brain-derived neurotrophic factor (BDNF) protein but not mRNA in the bed nucleus of the stria terminalis (BNST) in females but not males. Changes in BDNF protein were limited to anterior subregions of the BNST, and there were no changes in the adjacent nucleus accumbens (NAc). The effects of defeat on social withdrawal behavior and BDNF were reversed by chronic, low doses of the antidepressant sertraline. However, higher doses of sertraline restored social withdrawal and elevated BDNF levels. Acute treatment with a low dose of sertraline failed to reverse the effects of defeat. Infusions of the selective tyrosine-related kinase B receptor (TrkB) antagonist ANA-12 into the anterior BNST specifically increased social interaction in stressed females but had no effect on behavior in females naïve to defeat. These results suggest that stress-induced increases in BDNF in the anterior BNST contribute to the exaggerated social withdrawal phenotype observed in females.

Broken heart: depression in cardiovascular disease

PubMed Central

Krishnan, K. Ranga R.

2003-01-01

Heart disease and depression are among the most common diseases seen in developed countries. The relation-ship between heart disease and depression has been the subject of both popular interest and scientific research. Sadness is often portrayed as a feeling of heaviness in the chest or as a “broken heart.” Interestingly as we learn more about the expression of emotions, it appears that these perceptions may simply be the language representation of somatic feelings. Large, prospective, longitudinal studies that have examined the relationship between depression and development of coronary artery disease (CAD) have shown that depression is a risk factor for the development of CAD. Depression also increases mortality in patients with stable CAD or myocardial infarction compared with patients without depression. The recent Sertraline AntiDepressant HeARt attack Trial (SADHART) has shown that selective serotonin reuptake inhibitors like sertraline can be safely used in patients with depression following myocardial infarction. There is also intriguing evidence that treating depression with antidepressants may improve outcomes, including mortality. PMID:22034195

Severe Hypernatremic Dehydration and Lower Limb Gangrene in an Infant Exposed to Lamotrigine, Aripiprazole, and Sertraline in Breast Milk.

PubMed

Morin, Caroline; Chevalier, Isabelle

Hypernatremic dehydration is well described in exclusively breastfed neonates, although life-threatening complications are rarely reported. The present article describes a case of severe hypernatremic dehydration in a previously healthy term neonate. Other published cases of severe complications of hypernatremic dehydration are discussed. The exclusively breastfed neonate described had severe hypernatremic dehydration because of inadequate milk intake, with disseminated intravascular coagulation and right lower limb gangrene that required amputation of all five toes and surgical debridement of the metatarsals. The usual etiology of hypernatremic dehydration in this age group is insufficient breast milk intake. Here, the infant's mother was treated for bipolar disorder with lamotrigine 250 mg orally once daily, aripiprazole 15 mg orally once daily, and sertraline 100 mg orally once daily. Awareness of these complications should prompt close follow-up of the infant with poor weight gain. The role of maternal medication as a risk factor for hypernatremic dehydration among exclusively breastfed infants needs to be further explored.

The Therapeutic Relationship in Cognitive-Behavioral Therapy and Pharmacotherapy for Anxious Youth

PubMed Central

Cummings, Colleen M.; Caporino, Nicole E.; Settipani, Cara A.; Read, Kendra L.; Compton, Scott N.; March, John; Sherrill, Joel; Piacentini, John; McCracken, James; Walkup, John; Ginsburg, Golda; Albano, Anne Marie; Rynn, Moira; Birmaher, Boris; Sakolsky, Dara; Gosch, Elizabeth; Keeton, Courtney; Kendall, Philip C.

2014-01-01

Objective Examine the therapeutic relationship with cognitive-behavioral therapists and with pharmacotherapists for youth from the Child/Adolescent Anxiety Multimodal Study (CAMS; Walkup et al., 2008). The therapeutic relationship was examined in relation to treatment outcomes. Method Participants were 488 youth (ages 7-17; 50% male) randomized to cognitive-behavioral therapy (CBT; Coping cat), pharmacotherapy (SRT; sertraline), their combination, or pill placebo. Participants met DSM-IV criteria for generalized anxiety disorder, social phobia, and/or separation anxiety disorder. The therapeutic relationship was assessed by youth-report at weeks 6 and 12 of treatment using the Child's Perception of Therapeutic Relationship scale. Outcome measures (Pediatric Anxiety Rating Scale; Clinical Global Impressions Scales) were completed by Independent Evaluators blind to condition. Results For youth who received CBT only, a stronger therapeutic relationship predicted positive treatment outcome. In contrast, the therapeutic relationship did not predict outcome for youth receiving sertraline, combined treatment, or placebo. Conclusions A therapeutic relationship may be important for anxious youth who receive CBT alone. PMID:23750468

“How Will It Help Me?”: Reasons Underlying Treatment Preferences Between Sertraline and Prolonged Exposure in PTSD

PubMed Central

Chen, Jessica A.; Keller, Stephanie M.; Zoellner, Lori A.; Feeny, Norah C.

2014-01-01

Individuals with posttraumatic stress disorder (PTSD) often wait years before seeking treatment. Improving treatment initiation and adherence requires a better understanding patient beliefs that lead to treatment preferences. Using a treatment-seeking sample (N = 200) with chronic PTSD, qualitative reasons underlying treatment preferences for either prolonged exposure (PE) or sertraline (SER) were examined. Reasons for treatment preference primarily focused on how the treatment was perceived to reduce PTSD symptoms rather than practical ones. Patients were more positive about PE than SER. Individual differences did not reliably predict underlying preference reasons, suggesting that what makes a treatment desirable is not strongly determined by current functioning, treatment, or trauma history. Taken together, this information is critical for treatment providers, arguing for enhancing psychoeducation about how treatment works and acknowledging pre-existing biases against pharmacotherapy for PTSD that should be addressed. This knowledge has the potential to optimize and better personalize PTSD patient care. PMID:23896851

Is Trauma Memory Special? Trauma Narrative Fragmentation in PTSD: Effects of Treatment and Response.

PubMed

Bedard-Gilligan, Michele; Zoellner, Lori A; Feeny, Norah C

2017-03-01

Seminal theories posit that fragmented trauma memories are critical to posttraumatic stress disorder (PTSD; van der Kolk & Fisler, 1995; Brewin, 2014) and that elaboration of the trauma narrative is necessary for recovery (e.g., Foa, Huppert, & Cahill, 2006). According to fragmentation theories, trauma narrative changes, particularly for those receiving trauma-focused treatment, should accompany symptom reduction. Trauma and control narratives in 77 men and women with chronic PTSD were examined pre- and post-treatment, comparing prolonged exposure (PE) and sertraline. Utilizing self-report, rater coding, and objective coding of narrative content, fragmentation was compared across narrative types (trauma, negative, positive) by treatment modality and response, controlling for potential confounds. Although sensory components increased with PE ( d = 0.23 - 0.44), there were no consistent differences in fragmentation from pre- to post-treatment between PE and sertraline or treatment responders and non-responders. Contrary to theories, changes in fragmentation may not be a crucial mechanism underlying PTSD therapeutic recovery.

Unreported Medications Used in Incapacitating Medical Conditions Found in Fatal Civil Aviation Accidents

DTIC Science & Technology

1994-08-01

Carbamazepine 62 = Verapamil 21 = Diazepam 13 = Lidocaine 96 = Fluoxetine 72 = Propranolol 113 = Trazodone 30 = Metoprolol 116 = Sertraline 41 = Procainamid...examined by an aviation medi- Lopressor ( Metoprolol ) for the treatment of high cal examiner, the majority of the cardiovascular drugs blood pressure. In

Study protocol of the Diabetes and Depression Study (DAD): a multi-center randomized controlled trial to compare the efficacy of a diabetes-specific cognitive behavioral group therapy versus sertraline in patients with major depression and poorly controlled diabetes mellitus

PubMed Central

2013-01-01

Background Depression is common in diabetes and associated with hyperglycemia, diabetes related complications and mortality. No single intervention has been identified that consistently leads to simultaneous improvement of depression and glycemic control. Our aim is to analyze the efficacy of a diabetes-specific cognitive behavioral group therapy (CBT) compared to sertraline (SER) in adults with depression and poorly controlled diabetes. Methods/Design This study is a multi-center parallel arm randomized controlled trial currently in its data analysis phase. We included 251 patients in 70 secondary care centers across Germany. Key inclusion criteria were: type 1 or 2 diabetes, major depression (diagnosed with the Structured Clinical Interview for DSM-IV, SCID) and hemoglobin A1C >7.5% despite current insulin therapy. During the initial phase, patients received either 50–200 mg/d sertraline or 10 CBT sessions aiming at the remission of depression and enhanced adherence to diabetes treatment and coping with diabetes. Both groups received diabetes treatment as usual. After 12 weeks of this initial open-label therapy, only the treatment-responders (50% depression symptoms reduction, Hamilton Depression Rating Scale, 17-item version [HAMD]) were included in the subsequent one year study phase and represented the primary analysis population. CBT-responders received no further treatment, while SER-responders obtained a continuous, flexible-dose SER regimen as relapse prevention. Adherence to treatment was analyzed using therapeutic drug monitoring (measurement of sertraline and N-desmethylsertraline concentrations in blood serum) and by counting the numbers of CBT sessions received. Outcome assessments were conducted by trained psychologists blinded to group assignment. Group differences in HbA1c (primary outcome) and depression (HAMD, secondary outcome) between 1-year follow-up and baseline will be analyzed by ANCOVA controlling for baseline values. As primary hypothesis we expect that CBT leads to significantly greater improvement of glycemic control in the one year follow-up in treatment responders of the short term phase. Discussion The DAD study is the first randomized controlled trial comparing antidepressants to a psychological treatment in diabetes patients with depression. The study is investigator initiated and was supported by the ‘Förderprogramm Klinische Studien (Clinical Trials)’ and the ‘Competence Network for Diabetes mellitus’ funded by the Federal Ministry of Education and Research (FKZ 01KG0505). Trial registration Current controlled trials ISRCTN89333241. PMID:23915015

Treatment Preferences Affect the Therapeutic Alliance: Implications for Randomized Controlled Trials

ERIC Educational Resources Information Center

Iacoviello, Brian M.; McCarthy, Kevin Scott; Barrett, Marna S.; Rynn, Moira; Gallop, Robert; Barber, Jacques P.

2007-01-01

The influence of treatment preferences on the development of the therapeutic alliance was investigated. Seventy-five patients were followed while participating in a randomized controlled trial comparing supportive-expressive psychotherapy with sertraline or pill placebo in the treatment of major depressive disorder. Therapeutic alliance was…

A Comparison of Cognitive-Behavioral Therapy, Sertraline, and Their Combination for Adolescent Depression

ERIC Educational Resources Information Center

Melvin, Glenn A.; Tonge, Bruce J.; King, Neville J.; Heyne, David; Gordon, Michael S.; Klimkeit, Ester

2006-01-01

Objective: To evaluate cognitive-behavioral therapy, antidepressant medication alone, and combined CBT and antidepressant medication in the treatment of depressive disorders in adolescents. Method: Seventy-three adolescents (ages 12-18 years) with a primary diagnosis of DSM-IV major depressive disorder, dysthymic disorder, or depressive disorder…

Recent NIMH Clinical Trials and Implications for Practice

ERIC Educational Resources Information Center

Vitiello, Benedetto; Kratochvil, Christopher J.

2008-01-01

Optimal treatment of adolescent depression requires the use of antidepressants such as fluoxetine, and the addition of cognitive-behavioral therapy (CBT) offers better potential. Second-step pharmacological treatment of the disorder offers a success rate of around 50%. Clinical trial for the use of sertraline and CBT in treating…

Evaluation of the Potential Pharmacokinetic Interaction between Atomoxetine and Fluvoxamine in Healthy Volunteers.

PubMed

Todor, Ioana; Popa, Adina; Neag, Maria; Muntean, Dana; Bocsan, Corina; Buzoianu, Anca; Vlase, Laurian; Gheldiu, Ana-Maria; Briciu, Corina

2017-01-01

Attention deficit hyperactivity disorder (ADHD) is frequently associated with other psychiatric pathologies. Therefore, the present study investigated a possible pharmacokinetic interaction between atomoxetine (ATX), a treatment option for ADHD, and an antidepressant, namely, fluvoxamine (FVX). Designed as an open-label, non-randomized clinical trial, the study included 2 periods. In period 1 (reference), each subject received ATX 25 mg (single-dose), whereas in period 2 (test), all subjects were given a combination of ATX 25 mg + FVX 100 mg, following a 6-day pretreatment regimen with the enzymatic inhibitor. Non-compartmental methods were employed to determine the pharmacokinetic parameters of ATX and its main active metabolite (glucuronidated form), 4-hydroxyatomoxetine-O-glucuronide. The results revealed significant differences between the study periods for Cmax, AUC0-t and AUC0-∞ values corresponding to ATX and its metabolite. Small, but statistically significant increases in AUC values were reported for both parent drug (1,583.05 ± 1,040.29 vs. 2,111.55 ± 1,411.59 ng*h/ml) and 4-hydroxyatomoxetine-O-glucuronide (5,754.71 ± 1,235.5 vs. 6,293.17 ± 1,219.34 ng*h/ml) after combined treatment of ATX and the enzymatic inhibitor. FVX had a modest effect on the pharmacokinetics of ATX and 4-hydroxyatomoxetine-O-glucuronide. The presence or absence of any clinical consequences associated with this pharmacokinetic drug-drug interaction needs to be established in future studies. © 2016 S. Karger AG, Basel.

Narcolepsy induced by chronic heavy alcohol consumption: a case report

PubMed Central

Wang, Xinyuan

2012-01-01

Summary Narcolepsy is a chronic neurological disorder, characterized by uncontrollable excessive daytime sleepiness, cataplectic episodes, sleep paralysis, hypnagogic hallucinations, and night time sleep disruption. The paper reviewed the related literature and reported a case of long-term drinking induced narcolepsy which was significantly improved after treatment with paroxetine and dexzopiclone. PMID:25328357

Effects of paroxetine on intravaginal ejaculatory latency time in Egyptian patients with lifelong premature ejaculation as a function of serotonin transporter polymorphism.

PubMed

Salem, A M; Kamel, I I; Rashed, L A; GamalEl Din, S F

2017-01-01

Premature ejaculation (PE) is a common ejaculatory complaint. The estimated rates among Turkish men reached 20%, although the severest type of PE (lifelong PE) usually does not exceed 2.3%. This could be seen in line with two survey studies involving five nations. They revealed that 2.5% of men had an intravaginal ejaculation latency time of <1 min and 6% of <2 min. Rapid ejaculation may be treated pharmacologically with a variety of different medications that act either centrally or locally to delay ejaculation and subsequent orgasm. Antidepressants, particularly members of the selective serotonin reuptake inhibitor class, retard ejaculation significantly. Recently, it was postulated that men with lifelong PE might result from a combination of polymorphisms of the serotonergic transporter and receptors, and other neurotransmitters and/or receptors. Our findings augment the significant effect of paroxetine in delaying ejaculation in the responders (P<0.001). Meanwhile, the findings do not suggest a positive association between such response and serotonin transporter gene promoter polymorphism.

Randomized Controlled Trial of Sertraline, Prolonged Exposure Therapy and Their Combination in OEF/OIF with PTSD

DTIC Science & Technology

2015-12-01

et al., Association of posttraumatic stress disorder with somatic symptoms, health care visits, and absenteeism among Iraq War veterans. The...American Journal of Psychiatry, 2007. 164(1): p. 150-153. 8. Marciniak, M., et al. Medical and productivity costs of anxiety disorders: Case control study

Pharmacological Management of Treatment-Resistant Pediatric Depression

ERIC Educational Resources Information Center

Kratochvil, Christopher J.; Wagner, Karen Dineen; Emslie, Graham; March, John

2005-01-01

A 13-year-old boy presents with treatment-resistant symptoms of major depression. This is his first episode of depression, initially treated with 200 mg sertraline for 12 weeks with no significant benefit. The severe depression has shown a partial response to weekly cognitive-behavioral therapy (CBT) and fluoxetine, which was titrated up to 60 mg…

Adverse effects of the SSRI antidepressant sertraline on early life stages of marine invertebrates.

PubMed

Estévez-Calvar, Noelia; Canesi, Laura; Montagna, Michele; Faimali, Marco; Piazza, Veronica; Garaventa, Francesca

2017-07-01

Widespread contamination of coastal environments by emerging compounds includes low concentrations of pharmaceuticals. These pollutants are not currently incorporated in monitoring programs despite their effects on non-target organisms are very little documented. Among the selective serotonin reuptake inhibitor (SSRI) antidepressants, sertraline (SRT) is one of the most prescribed globally. In this work, earlier life stages of Amphibalanus amphitrite, Brachionus plicatilis and Mytilus galloprovincialis were exposed to environmental concentrations of SRT in order to study both sub-lethal and lethal responses in 24/48 h-tests. Low concentrations of SRT altered significantly swimming behavior in A. amphitrite and B. plicatilis giving 48 h-EC 50 (μg/L) of 113.88 and 282.23, respectively whereas higher values were observed for mortality and immobilization. EC 50 embryotoxicity with M. galloprovincialis was 206.80 μg/L. This work add new data about SRT ecotoxicity on marine invertebrates and confirms the applicability of behavioral endpoints to evaluate the environmental impact of antidepressants in marine organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antidepressant Specificity of Serotonin Transporter Suggested by Three LeuT-SSRI Structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Z.; Zhen, J; Karpowich, N

2009-01-01

Sertraline and fluoxetine are selective serotonin re-uptake inhibitors (SSRIs) that are widely prescribed to treat depression. They exert their effects by inhibiting the presynaptic plasma membrane serotonin transporter (SERT). All SSRIs possess halogen atoms at specific positions, which are key determinants for the drugs' specificity for SERT. For the SERT protein, however, the structural basis of its specificity for SSRIs is poorly understood. Here we report the crystal structures of LeuT, a bacterial SERT homolog, in complex with sertraline, R-fluoxetine or S-fluoxetine. The SSRI halogens all bind to exactly the same pocket within LeuT. Mutation at this halogen-binding pocket (HBP)more » in SERT markedly reduces the transporter's affinity for SSRIs but not for tricyclic antidepressants. Conversely, when the only nonconserved HBP residue in both norepinephrine and dopamine transporters is mutated into that found in SERT, their affinities for all the three SSRIs increase uniformly. Thus, the specificity of SERT for SSRIs is dependent largely on interaction of the drug halogens with the protein's HBP.« less

Treatment with Medications Affecting Dopaminergic and Serotonergic Mechanisms: Effects on Fluency and Anxiety in Persons Who Stutter

ERIC Educational Resources Information Center

Stager, Sheila V.; Calis, Karim; Grothe, Dale; Bloch, Meir; Berensen, Nannette M.; Smith, Paul J.; Braun, Allen

2005-01-01

Medications with dopamine antagonist properties, such as haloperidol, and those with serotonin reuptake inhibitor properties, such as clomipramine, have been shown to improve fluency. To examine the degree to which each of these two pharmacological mechanisms might independently affect fluency, a selective serotonin reuptake inhibitor, paroxetine,…

Searching for moderators and mediators of pharmacological treatment effects in children and adolescents with anxiety disorders.

PubMed

Walkup, John T; Labellarte, Michael J; Riddle, Mark A; Pine, Daniel; Greenhill, Laurence; Klein, Rachel; Davies, Mark; Sweeney, Michael; Fu, Caifeng; Abikoff, Howard; Hack, Sabine; Klee, Brain; McCracken, James; Bergman, Lindsey; Piacentini, John; March, John; Compton, Scott; Robinson, James; O'Hara, Thomas; Baker, Sheryl; Vitiello, Benedetto; Ritz, Louise; Roper, Margaret

2003-01-01

To examine whether age, gender, ethnicity, type of anxiety disorder, severity of illness, comorbidity, intellectual level, family income, or parental education may function as moderators and whether treatment adherence, medication dose, adverse events, or blinded rater's guess of treatment assignment may function as mediators of pharmacological treatment effect in children and adolescents with anxiety disorders. The database of a recently reported double-blind placebo-controlled trial of fluvoxamine in 128 youths was analyzed. With a mixed-model random-effects regression analysis of the Pediatric Anxiety Rating Scale total score, moderators and mediators were searched by testing for a three-way interaction (strata by treatment by time). A two-way interaction (strata by time) identified predictors of treatment outcome. No significant moderators of efficacy were identified, except for lower baseline depression scores, based on parent's (but not child's) report, being associated with greater improvement (p < .001). Patients with social phobia (p < .05) and greater severity of illness (p < .001) were less likely to improve, independently of treatment assignment. Blinded rater's guess of treatment assignment acted as a possible mediator (p < .001), but improvement was attributed to fluvoxamine, regardless of actual treatment assignment. Treatment adherence tended to be associated (p = .05) with improvement. In this exploratory study, patient demographics, illness characteristics, family income, and parental education did not function as moderators of treatment effect. Social phobia and severity of illness predicted less favorable outcome. Attribution analyses indicated that study blindness remained intact. The presence of concomitant depressive symptoms deserves attention in future treatment studies of anxious children.

Ritualistic chewing behavior induced by mCPP in the rat is an animal model of obsessive compulsive disorder.

PubMed

Kreiss, Deborah S; Coffman, Catherine F; Fiacco, Nicholas R; Granger, Jason C; Helton, Bernadette M; Jackson, Jennifer C; Kim, Leonid V; Mistry, Rishi S; Mizer, Tammie M; Palmer, Lolita V; Vacca, Jay A; Winkler, Stuart S; Zimmer, Benjamin A

2013-03-01

Obsessive Compulsive Disorder (OCD) is characterized by recurrent, anxiety-producing thoughts accompanied by unwanted, overwhelming urges to perform ritualistic behaviors. Pharmacological treatments for this disorder (serotonin uptake inhibitors) are problematic because there is a 6-8 week delayed onset and half of the patients do not adequately respond. The present study evaluated whether Ritualistic Chewing Behaviors (RCBs) induced by the serotonin agonist mCPP in the rat is a behavioral model for OCD. The effects upon the RCBs induced by mCPP (1 mg/kg) were evaluated following treatments with either the serotonin antagonist mianserin (3 mg/kg), the dopamine antagonist haloperidol (1 mg/kg), the GABA modulator diazepam (10 mg/kg), or the serotonin uptake inhibitors clomipramine and fluvoxamine (15 mg/kg). The response to mCPP was blocked by acute treatment with mianserin, but not with acute haloperidol or diazepam. Further experiments revealed that the effects of mCPP were blocked by chronic, but not acute, treatment with clomipramine and fluvoxamine. A time-course demonstrated that 14 days of chronic treatment were required for blockade of the mCPP-evoked response. The current study demonstrates that mCPP-evoked RCBs may be a rodent model for OCD that can be used to predict the clinical efficacy and time course of novel OCD treatment. Future investigations may be able to use the current model as a tool for bench-marking corresponding changes in other measures of neurological activity that may provide insight into the mechanisms underlying OCD. Copyright © 2013. Published by Elsevier Inc.

Fluvoxamine moderates reduced voluntary activity following chronic dexamethasone infusion in mice via recovery of BDNF signal cascades.

PubMed

Terada, Kazuki; Izumo, Nobuo; Suzuki, Biora; Karube, Yoshiharu; Morikawa, Tomomi; Ishibashi, Yukiko; Kameyama, Toshiki; Chiba, Koji; Sasaki, Noriko; Iwata, Keiko; Matsuzaki, Hideo; Manabe, Takayuki

2014-04-01

Major depression is a complex disorder characterized by genetic and environmental interactions. Selective serotonin reuptake inhibitors (SSRIs) effectively treat depression. Neurogenesis following chronic antidepressant treatment activates brain derived neurotrophic factor (BDNF) signaling. In this study, we analyzed the effects of the SSRI fluvoxamine (Flu) on locomotor activity and forced-swim behavior using chronic dexamethasone (cDEX) infusions in mice, which engenders depression-like behavior. Infusion of cDEX decreased body weight and produced a trend towards lower locomotor activity during darkness. In the forced-swim test, cDEX-mice exhibited increased immobility times compared with mice administered saline. Flu treatment reversed decreased locomotor activity and mitigated forced-swim test immobility. Real-time polymerase chain reactions using brain RNA samples yielded significantly lower BDNF mRNA levels in cDEX-mice compared with the saline group. Endoplasmic reticulum stress-associated X-box binding protein-1 (XBP1) gene expression was lower in cDEX-mice compared with the saline group. However, marked expression of the XBP1 gene was observed in cDEX-mice treated with Flu compared with mice given saline and untreated cDEX-mice. Expression of 5-HT2A and Sigma-1 receptors decreased after cDEX infusion compared with the saline group, and these decreases normalized to control levels upon Flu treatment. Our results indicate that the Flu moderates reductions in voluntary activity following chronic dexamethasone infusions in mice via recovery of BDNF signal cascades. Copyright © 2014 Elsevier Ltd. All rights reserved.

Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports.

PubMed

Sharma, Tarang; Guski, Louise Schow; Freund, Nanna; Gøtzsche, Peter C

2016-01-27

To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.Design Systematic review and meta-analysis. Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia. Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly's website. Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms. Two researchers extracted data independently; the outcomes were meta-analysed by Peto's exact method (fixed effect model). We included 70 trials (64,381 pages of clinical study reports) with 18,526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly's website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was incomplete. Because of the shortcomings identified and having only partial access to appendices with no access to case report forms, the harms could not be estimated accurately. In adults there was no significant increase in all four outcomes, but in children and adolescents the risk of suicidality and aggression doubled. To elucidate the harms reliably, access to anonymised individual patient data is needed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Granisetron adjunct to fluvoxamine for moderate to severe obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial.

PubMed

Askari, Neda; Moin, Mahdieh; Sanati, Mohammad; Tajdini, Masih; Hosseini, Seyed-Mohammad-Reza; Modabbernia, Amirhossein; Najand, Babak; Salimi, Samrand; Tabrizi, Mina; Ashrafi, Mandana; Hajiaghaee, Reza; Akhondzadeh, Shahin

2012-10-01

Several small studies have shown beneficial effects of ondansetron, a serotonin 5-HT(3) receptor antagonist, in the treatment of obsessive-compulsive disorder (OCD). The efficacy of other 5-HT(3) receptor antagonists in patients with OCD is still unclear. Granisetron does not alter cytochrome P450 activity and might have a lower risk of drug interactions, a longer duration of action and a better tolerability profile than other 5-HT(3) receptor antagonists. The objective of this study was to assess the efficacy and tolerability of granisetron augmentation of fluvoxamine in patients with OCD. This was a two-centre, randomized, double-blind, placebo-controlled, parallel-group study conducted from November 2011 to March 2012. The study setting was outpatient clinics of two large referral centres. Study participants were men and women, aged 18-60 years, who met the diagnostic criteria of OCD based on the DSM-IV-TR and who had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of at least 21. Participants were randomly assigned to granisetron (Kytril(®); SmithKline Beecham, Philadelphia, PA, USA) 1 mg every 12 hours or placebo every 12 hours in addition to fluvoxamine for 8 weeks. Patients were assessed using the Y-BOCS at baseline, second, fourth, sixth and eighth weeks. The primary outcome measure was the difference in the score change of Y-BOCS total score from baseline to week 8 between the two groups. We also compared changes in the obsession and compulsion subscales of the Y-BOCS, and frequencies of partial response (≥25% reduction in Y-BOCS score), complete response (≥35% reduction in Y-BOCS score) and remission (Y-BOCS score ≤16) between the two groups. Of the 42 included patients, 39 (20 in the placebo group, 19 in the granisetron group) completed the study. Significant time X treatment interaction was observed for total Y-BOCS (F [2.097, 79.678] = 4.941, p = 0.009), obsession (F [2.337, 88.799] = 4.938, p = 0.006) and compulsion (F [2.050, 77.899] = 4.674, p = 0.012) subscales. By week 8, complete response and remission were achieved by 20 (100%) and 18 (90%) patients in the granisetron group and by 7 (35%) patients in the placebo group (p-value of Fisher's exact test <0.001, risk ratio (RR) [95% CI] = 3.857 [2.039, 7.297]). There was no significant difference in the tolerability between the two regimens. Granisetron is an efficacious adjunct for the short-term treatment of patients with moderate to severe OCD and is well tolerated. IRCT201202041556N32.

Generic penetration in the retail antidepressant market.

PubMed

Ventimiglia, Jeffrey; Kalali, Amir H

2010-06-01

In this article, we explore the accelerated penetration of generic antidepressants in the United States market following the availability of generic citalopram and sertraline. Analysis suggests that overall, generic penetration into the antidepressant market has grown from approximately 41 percent in January 2004 to over 73 percent in January 2010. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty.

Down Syndrome and Fragile X Syndrome in a Colombian Woman: Case Report.

PubMed

Saldarriaga, Wilmar; Ruiz, Fabian Andres; Tassone, Flora; Hagerman, Randi

2017-09-01

Down syndrome (DS) and Fragile X syndrome (FXS) are the major genetic causes of intellectual disabilities. Here, we present a case of a 32-year-old woman with the diagnosis of both FXS and DS. She is the daughter of a 47-year-old pre-mutation woman who also has three sons with FXS. Cytogenetic testing detected the presence of a complete trisomy 21. A combination of PCR and Southern blot analysis was utilized to document the presence of the FMR1 full mutation. The patient has physical characteristics and behavioural disturbances typical of both FXS and DS, which were confirmed by molecular testing. Her treatment plan included a trial of sertraline because of the severity of her shyness and lack of language. She had an excellent response to sertraline with improvement in shyness and social interactions, particularly with family members. In this study, we report the case of a woman with both FXS and DS, which is the fifth case of FXS and DS in the world's literature. The patient is from Ricaurte, a small town in Colombia, South America, where there is the world's highest prevalence for FXS. © 2016 John Wiley & Sons Ltd.

First-Generation H1 Antihistamines Found in Pilot Fatalities of Civil Aviation Accidents, 1990-2005

DTIC Science & Technology

2007-05-01

ephedrine, paroxetine, phenylpropanolamine, pseudoephedrine , quinine, and/or tetrahydrocannabinol carboxylic acid—were also present in the fatalities...antihistamine (Table II). Chlorpheniramine, ephedrine, phenylpropanolamine, and pseudoephedrine were also detected in one case and pheniramine and...detected in both cases and pseudoephedrine in 1. Blood was not available in either case. Pheniramine: This antihistamine was found in just 1 fatality

Role of hyperthermia in the protective action of clomethiazole against MDMA (‘ecstasy')-induced neurodegeneration, comparison with the novel NMDA channel blocker AR-R15896AR

PubMed Central

Colado, M I; Granados, R; O'Shea, E; Esteban, B; Green, A R

1998-01-01

The immediate effect of administration of 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy') on rectal temperature and the effect of putative neuroprotective agents on this change has been examined in rats. The influence of the temperature changes on the long term MDMA-induced neurodegeneration of cerebral 5-hydroxytryptamine (5-HT) nerve terminals was also examined.The novel low affinity N-methyl-D-aspartate (NMDA) receptor channel blocker AR-R15896AR (20 mg kg−1, i.p.) given 5 min before and 55 min after MDMA (15 mg kg−1, i.p.) did not prevent the MDMA-induced hyperthermia and did not alter either the MDMA-induced neurodegenerative loss of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in cortex, striatum and hippocampus or loss of [3H]-paroxetine binding in cortex 7 days later.The neuroprotective agent clomethiazole (50 mg kg−1, i.p.) given 5 min before and 55 min after MDMA (15 mg kg−1) abolished the MDMA-induced hyperthermic response and markedly attenuated the loss of 5-HT, 5-HIAA and [3H]-paroxetine binding in the brain regions examined 7 days later.When rats treated with MDMA plus clomethiazole were kept at high ambient temperature for 5 h post-MDMA, thereby keeping their body temperature elevated to near that seen in rats given MDMA alone, the MDMA-induced loss of 5-HT, 5-HIAA and [3H]-paroxetine was still attenuated. However, the protection (39%) afforded by the clomethiazole administration was less than seen in rats kept at normal ambient temperature (75%).These data support the proposals of others that NMDA receptor antagonists are neuroprotective against MDMA-induced degeneration only if they induce hypothermia and further suggest that increased glutamate activity may not be involved in the neurotoxic action of MDMA.These data further demonstrate that a proportion of the neuroprotective action of clomethiazole is due to an effect on body temperature but that, in addition, the compound protects against MDMA-induced damage by an unrelated mechanism. PMID:9647471

Drug effects on multiple and concurrent schedules of ethanol- and food-maintained behaviour: context-dependent selectivity

PubMed Central

Ginsburg, B C; Lamb, R J

2014-01-01

BACKGROUND AND PURPOSE Drugs that more potently or effectively reduce ethanol-maintained behaviour versus an alternative are considered selective and are considered promising pharmacotherapies for alcoholism. Such results are often obtained using separate groups or multiple schedules where ethanol and the alternative are available alone or sequentially. Recently, we observed that when ethanol and food were available sequentially under a multiple schedule, fluvoxamine and varenicline were selective; yet this selectivity disappeared when ethanol and food were concurrently available. EXPERIMENTAL APPROACH We examined the generality of these findings by comparing doses of several drugs required to decrease ethanol- and food-maintained responding under a multiple schedule and under a concurrent schedule. Effects were determined for chlordiazepoxide, 2,5-dimethoxy-4-iodoamphetamine (DOI), meta-chlorophenylpiperazine (mCPP), morphine, naltrexone and d-amphetamine. KEY RESULTS Under the multiple schedule, ED50 values for decreases in ethanol-maintained responding were significantly different and lower than ED50s for decreases in food-maintained responding (demonstrating selectivity) for each drug except for chlordiazepoxide (which was equipotent) and naltrexone (which did not affect responding). However, this selectivity vanished or even inverted under the concurrent schedule, such that ED50 values for decreasing ethanol- and food-maintained responding were not different (or, following DOI, the ED50 for food-maintained responding was lower than for ethanol-maintained responding). CONCLUSIONS AND IMPLICATIONS Results are consistent with those seen following fluvoxamine and varenicline administration, and suggest that selectivity is assay-dependent. These results indicate the need for careful interpretation of selective drug effects, especially when obtained in situations where ethanol or the alternative is the only programmed reinforcement available. PMID:24697498

Drug effects on multiple and concurrent schedules of ethanol- and food-maintained behaviour: context-dependent selectivity.

PubMed

Ginsburg, B C; Lamb, R J

2014-07-01

Drugs that more potently or effectively reduce ethanol-maintained behaviour versus an alternative are considered selective and are considered promising pharmacotherapies for alcoholism. Such results are often obtained using separate groups or multiple schedules where ethanol and the alternative are available alone or sequentially. Recently, we observed that when ethanol and food were available sequentially under a multiple schedule, fluvoxamine and varenicline were selective; yet this selectivity disappeared when ethanol and food were concurrently available. We examined the generality of these findings by comparing doses of several drugs required to decrease ethanol- and food-maintained responding under a multiple schedule and under a concurrent schedule. Effects were determined for chlordiazepoxide, 2,5-dimethoxy-4-iodoamphetamine (DOI), meta-chlorophenylpiperazine (mCPP), morphine, naltrexone and d-amphetamine. Under the multiple schedule, ED50 values for decreases in ethanol-maintained responding were significantly different and lower than ED50 s for decreases in food-maintained responding (demonstrating selectivity) for each drug except for chlordiazepoxide (which was equipotent) and naltrexone (which did not affect responding). However, this selectivity vanished or even inverted under the concurrent schedule, such that ED50 values for decreasing ethanol- and food-maintained responding were not different (or, following DOI, the ED50 for food-maintained responding was lower than for ethanol-maintained responding). Results are consistent with those seen following fluvoxamine and varenicline administration, and suggest that selectivity is assay-dependent. These results indicate the need for careful interpretation of selective drug effects, especially when obtained in situations where ethanol or the alternative is the only programmed reinforcement available. © 2014 The British Pharmacological Society.

Generic Penetration in the Retail Antidepressant Market

PubMed Central

Kalali, Amir H.

2010-01-01

In this article, we explore the accelerated penetration of generic antidepressants in the United States market following the availability of generic citalopram and sertraline. Analysis suggests that overall, generic penetration into the antidepressant market has grown from approximately 41 percent in January 2004 to over 73 percent in January 2010. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty. PMID:20622940

Plasma Methylphenidate Levels in Youths With Attention Deficit Hyperactivity Disorder Treated With OROS Formulation.

PubMed

Yorbik, Ozgur; Mutlu, Caner; Ozilhan, Selma; Eryilmaz, Gul; Isiten, Nuket; Alparslan, Serdar; Saglam, Esra

2015-06-01

There are limited studies investigating the relationship between oral release osmotic system-methylphenidate (OROS-MPH) doses and plasma methylphenidate (MPH) concentrations in children and adolescents. The aim of this study was to investigate the relationship between the doses of OROS-MPH and the plasma levels of the drug. We also examined the effects of the other drugs including aripiprazole, risperidone, fluoxetine, and sertraline on the levels of the MPH in the plasma. The files of 100 attention deficit hyperactivity disorder (ADHD) subjects (76 male, 24 female) who were diagnosed as ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria, were screened. The ages of subjects were between 6 and 18 years (mean = 11.5 ± 3.8 years). Plasma MPH levels were determined by high-performance liquid chromatography-tandem mass spectrometry assay. Daily mean OROS-MPH dose used in ADHD children was 0.7 ± 0.2 mg/kg (range: 0.3-1.3 mg/kg). The mean plasma OROS-MPH was 11.6 ± 7.3 ng/mL (range: 0.5-43.4 ng/mL). There was no group difference in the mean plasma MPH and dose-related MPH levels between the groups that used any additional drug including aripiprazole (n = 25), risperidone (n = 10), fluoxetine (n = 16), sertraline (n = 10), and did not use these drugs (P > 0.05). There was a positive correlation between the OROS-MPH doses (mg/kg) and the blood MPH levels (Pearson correlation = 0.40; P < 0.001). The plasma levels of MPH were found to be less than 13 ng/mL in 65% of the subjects. Our findings point to the fact that plasma levels of MPH show a wide range of changes at similar doses, correlate positively with the doses and, as expected, are not affected by using risperidone, sertraline, fluoxetine, and aripiprazole. Therapeutic drug monitoring may help to optimize MPH dose in patients not responding to treatment or in those experiencing serious side effects, but not in routine clinical practice. The presence of intermediate dose formulations such as 45-mg tablets for OROS-MPH may contribute to the optimization.

Effect of memantine combination therapy on symptoms in patients with moderate-to-severe depressive disorder: randomized, double-blind, placebo-controlled study.

PubMed

Amidfar, M; Khiabany, M; Kohi, A; Salardini, E; Arbabi, M; Roohi Azizi, M; Zarrindast, M-R; Mohammadinejad, P; Zeinoddini, A; Akhondzadeh, S

2017-02-01

Current treatments for depressive disorders are far from optimum. This study was planned to evaluate possible antidepressant effects and safety of memantine, a selective N-methyl-d-aspartate receptor antagonist, in humans. Sixty-six outpatients with the diagnosis of moderate-to-severe major depressive disorder, based on DSM-V diagnostic criteria, were recruited to participate in a parallel, randomized, controlled trial. Sixty-two participants completed 6 weeks of treatment with either memantine (20 mg/day) plus sertraline (200 mg/day) or placebo plus sertraline (200 mg/day). Patients were evaluated using the Hamilton Depression Rating Scale (HDRS) at baseline and at weeks 2, 4 and 6. Comparison of treatment efficacy in improving depressive symptoms between the two groups was the principal outcome measure. A repeated-measures analysis demonstrated significant time × treatment interaction on HDRS score [F (2·09, 125·67) = 5·09, P = 0·007]. Significantly greater improvement was seen at all three follow-up sessions as well as significantly greater response rates at weeks 4 and 6 (P = 0·018 and P < 0·001, respectively) in the memantine group. Significantly more early improvers and more rapid response to treatment were observed in the memantine group (P = 0·001 and P < 0·001, respectively). A significant reduction was observed in HDRS score from baseline to the study endpoint in both memantine (P < 0·001, Cohen's d = 12·71) and placebo groups (P < 0·001, Cohen's d = 5·13). No serious adverse event occurred. No significantly greater remission rate was seen in the adjunctive memantine therapy. A 6-week course of treatment with memantine as adjunct to sertraline showed a favourable safety and efficacy profile in patients with major depressive disorder. Nonetheless, larger controlled studies of longer duration are necessary to assess long-term safety, efficacy and optimal dosing. © 2016 John Wiley & Sons Ltd.

Quality of Life After Prophylactic Oophorectomy

DTIC Science & Technology

2005-09-01

such as Effexor® (ventafaxine), Paxil® (paroxetine), and Prozac ® (fluoxetine), given in lower doses than those used to treat depression, can reduce...NSABP BCPT Quality of Life Questionnaire. This instrument was used by over 13,000 women in the Tamoxifen prevention trial. It includes the Medical...Outcomes Study (MOS) 36-item short form, a generic measure of health-related QOL, the Center for Epidemiologic Studies-Depression Scale, used widely in

Transient serotonin syndrome by concurrent use of electroconvulsive therapy and selective serotonin reuptake inhibitor: a case report and review of the literature.

PubMed

Okamoto, Nagahisa; Sakamoto, Kota; Yamada, Maki

2012-01-01

The serotonin syndrome, which is characterized by psychiatric, autonomic nervous and neurological symptoms, is considered to be caused by excessive stimulation of the 5-HT1A and 5-HT2 receptors in the gray matter and spinal cord of the central nervous system, after the start of dosing or increase of the dose of a serotoninergic drug. There have been hardly any reports of induction of serotonin syndrome by electroconvulsive therapy (ECT) in combination with antidepressant. We present the case of a female patient with major depressive disorder (MDD) who developed transient serotonin syndrome soon after the first session of ECT in combination with paroxetine. Paroxetine was discontinued, and her psychiatric, autonomic nervous and neurological symptoms were gradually relieved and disappeared within 2 days. We performed the second ECT session 5 days after the initial session and performed 12 sessions of ECT without any changes in the procedure of ECT and anesthesia, but no symptoms of SS were observed. Finally, her MDD remitted. ECT might cause transiently increased blood-brain barrier (BBB) permeability and enhance the transmissivity of the antidepressant in BBB. Therefore, it is necessary to pay attention to rare side effect of serotonin syndrome by ECT in combination with antidepressant.

Low density and high affinity of platelet [3H]paroxetine binding in women with bulimia nervosa.

PubMed

Ekman, Agneta; Sundblad-Elverfors, Charlotta; Landén, Mikael; Eriksson, Tomas; Eriksson, Elias

2006-06-15

Impaired serotonin transmission has been suggested to be implicated in the pathophysiology of bulimia nervosa. As an indirect measure of brain serotonergic activity, the binding of tritiated ligands to platelet serotonin transporters has been studied in bulimia nervosa as well as in other putatively serotonin-related psychiatric disorders. In this study, the density and affinity of platelet serotonin transporters were assessed in 20 women meeting the DSM-IV criteria for bulimia nervosa and in 14 controls without previous or ongoing eating disorder using [(3)H]paroxetine as a ligand. In comparison to controls, women with bulimia nervosa had a significantly reduced number of platelet binding sites (B(max) = 721 +/- 313 vs. 1145 +/- 293 fmol/mg protein) and an increase in the affinity for the ligand demonstrated by a lower dissociaton constant (K(d) = 33 +/- 10 vs. 44 +/- 10 pM). A significant correlation between B(max) and K(d) values was found in patients but not in controls. Our results support the notion that bulimia nervosa is associated with a reduction in platelet serotonin transporter density. In addition, our study is the first to report that this reduced transporter density in women with bulimia nervosa is accompanied by an increase in the affinity of the transporter for the ligand.

The Rodent-versus-wild Snake Paradigm as a Model for Studying Anxiety- and Panic-like Behaviors: Face, Construct and Predictive Validities.

PubMed

Paschoalin-Maurin, Tatiana; Dos Anjos-Garcia, Tayllon; Falconi-Sobrinho, Luiz Luciano; de Freitas, Renato Leonardo; Coimbra, Jade Pissamiglio Cysne; Laure, Carlos Júlio; Coimbra, Norberto Cysne

2018-01-15

Using an innovative approach to study the neural bases of psychiatric disorders, this study investigated the behavioral, morphological and pharmacological bases of panic attack-induced responses in a prey-versus-coral snake paradigm. Mesocricetus auratus was chronically treated with intraperitoneal administration of the selective serotonin uptake inhibitor paroxetine or the gamma aminobutyric acid (GABA)/benzodiazepine receptor agonist alprazolam at three different doses and were then confronted with a venomous coral snake (Micrurus frontalis, Reptilia, Elapidae). The threatened rodents exhibited defensive attention, flat back approaches, defensive immobility, and escape defensive responses in the presence of the venomous snake, followed by increases in Fos protein in limbic structure neurons. Chronic administration of both paroxetine and alprazolam decreased these responses with morphological correlates between the panicolytic effect of both drugs administered at the highest dose and decreases in Fos protein-immunolabeled perikarya found in the amygdaloid complex, hypothalamus and periaqueductal gray matter columns, which are structures that make up the encephalic aversion system. These findings provide face, construct and predictive validities of this new experimental model of anxiety- and panic attack-like behavioral responses displayed by threatened prey confronted with venomous coral snakes. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Clinical Presentation and Pharmacotherapy Response in Social Anxiety Disorder: The Effect of Etiological Beliefs

PubMed Central

Cohen, Jonah N.; Potter, Carrie M.; Drabick, Deborah A.G.; Blanco, Carlos; Schneier, Franklin R.; Liebowitz, Michael R.; Heimberg, Richard G.

2015-01-01

Therapies for social anxiety disorder (SAD) leave many patients symptomatic at the end of treatment and little is known about predictors of treatment response. This study investigated the predictive relationship of patients’ etiological attributions to initial clinical features and response to pharmacotherapy. Methods One hundred thirty-seven individuals seeking treatment for SAD received 12 weeks of open treatment with paroxetine. Participants completed the Attributions for the Etiology of Social Anxiety Scale at baseline in addition to measures of social anxiety and depression at baseline and over the course of treatment. Results A latent class analysis suggested four profiles of etiological beliefs about one’s SAD that may be characterized as: Familial Factors, Need to be Liked, Bad Social Experiences, and Diffuse Beliefs. Patients in the more psychosocially-driven classes, Need to be Liked and Bad Social Experiences, had the most severe social anxiety and depression at baseline. Patients in the Familial Factors class, who attributed their SAD to genetic, biological, and early life experiences, had the most rapid response to paroxetine. Conclusions These results highlight the effect of biological and genetically-oriented etiological beliefs on pharmacological intervention, have implications for person-specific treatment selection, and identify potential points of intervention to augment treatment response. PMID:25920804

Fluctuating serotonergic function in premenstrual dysphoric disorder and premenstrual syndrome: findings from neuroendocrine challenge tests.

PubMed

Inoue, Y; Terao, T; Iwata, N; Okamoto, K; Kojima, H; Okamoto, T; Yoshimura, R; Nakamura, J

2007-02-01

Premenstrual dysphoric disorder (PMDD) has been assumed to be a subtype of premenstrual syndrome (PMS) with depressive symptoms, such as depressive mood, tension, anxiety, and mood liability during luteal phase. At present, no conclusion has been established about serotonergic function in PMDD. The purpose of this study was to investigate the serotonergic function of PMDD subjects in comparison to PMS without PMDD subjects and normal controls via neuroendocrine challenge tests. Twenty-four women (seven with PMDD, eight with PMS without PMDD, and nine normal controls) were tested on three occasions (follicular phase, early luteal phase, and late luteal phase) receiving paroxetine 20 mg orally as a serotonergic probe at 8:00 A: .M: . Plasma ACTH and cortisol were measured prior to the administration and every hour for 6 h thereafter. As a whole, there were significant differences in serotonergic function measured by ACTH and cortisol responses to paroxetine challenge across these three groups. PMDD subjects showed higher serotonergic function in follicular phase but lower serotonergic function in luteal phase, compared with women with PMS without PMDD and normal controls. The present findings suggest that PMDD women have fluctuating serotonergic function across their menstrual cycles and that the pattern may be different from PMS without PMDD.

Do drug warnings and market withdrawals have an impact on the number of calls to teratogen information services?

PubMed

Sheehy, O; Gendron, M-P; Martin, B; Bérard, A

2012-06-01

IMAGe provides information on risks and benefits of medication use during pregnancy and lactation. The aim of this study was to determine the impact of Health Canada warnings on the number of calls received at IMAGe. We analyzed calls received between January 2003 and March 2008. The impact of the following warning/withdrawal were studied: paroxetine and risk of cardiac malformations (09/29/2005), selective serotonin reuptake inhibitors (SSRIs) and risk of persistent pulmonary hypertension of the newborn (PPHN) (03/10/2006), and impact of rofecoxib market withdrawal (09/30/2004). Interrupted auto-regressive integrated -moving average (ARIMA) analyses were used to test the impact of each warning on the number of calls received to IMAGe. 61,505 calls were analyzed. The paroxetine warning had a temporary impact increasing the overall number of calls to IMAGe, and an abrupt permanent effect on the number of calls related to antidepressant exposures. The PPHN warning had no impact but we observed a significant increase in the number of calls following rofecoxib market withdrawal. Health Canada needs to consider the increase in the demand of information to IMAGe following warnings on the risk of medication use during pregnancy. © Georg Thieme Verlag KG Stuttgart · New York.

Clinical presentation and pharmacotherapy response in social anxiety disorder: The effect of etiological beliefs.

PubMed

Cohen, Jonah N; Potter, Carrie M; Drabick, Deborah A G; Blanco, Carlos; Schneier, Franklin R; Liebowitz, Michael R; Heimberg, Richard G

2015-07-30

Therapies for social anxiety disorder (SAD) leave many patients symptomatic at the end of treatment and little is known about predictors of treatment response. This study investigated the predictive relationship of patients' etiological attributions to initial clinical features and response to pharmacotherapy. One hundred thirty-seven individuals seeking treatment for SAD received 12 weeks of open treatment with paroxetine. Participants completed the Attributions for the Etiology of Social Anxiety Scale at baseline in addition to measures of social anxiety and depression at baseline and over the course of treatment. A latent class analysis suggested four profiles of etiological beliefs about one's SAD that may be characterized as: Familial Factors, Need to be Liked, Bad Social Experiences, and Diffuse Beliefs. Patients in the more psychosocially-driven classes, Need to be Liked and Bad Social Experiences, had the most severe social anxiety and depression at baseline. Patients in the Familial Factors class, who attributed their SAD to genetic, biological, and early life experiences, had the most rapid response to paroxetine.These results highlight the effect of biological and genetically-oriented etiological beliefs on pharmacological intervention, have implications for person-specific treatment selection, and identify potential points of intervention to augment treatment response. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Social phobia: diagnosis and epidemiology, neurobiology and pharmacology, comorbidity and treatment.

PubMed

Brunello, N; den Boer, J A; Judd, L L; Kasper, S; Kelsey, J E; Lader, M; Lecrubier, Y; Lepine, J P; Lydiard, R B; Mendlewicz, J; Montgomery, S A; Racagni, G; Stein, M B; Wittchen, H U

2000-10-01

Social phobia is a common disorder associated with significant psychosocial impairment, representing a substantial public health problem largely determined by the high prevalence, and the lifelong chronicity. Social phobia starts in early childhood or adolescence and is often comorbid with depression, other anxiety disorders, alcohol and substance abuse or eating disorders. This cascade of comorbidity, usually secondary to social phobia, increases the disability associated with the condition. The possibility that social phobia may be a trigger for later developing comorbid disorders directs attention to the need for early effective treatment as a preventive measure. The most recent drug class to be investigated for the psychopharmacological treatment of social phobia is the SSRI group for which there is growing support. The other drug classes that have been evaluated are monoamine oxidase inhibitors (MAOIs), benzodiazepines, and beta-blockers. The SSRIs represent a new and attractive therapeutic choice for patients with generalized social phobia. Recently the first, large scale, placebo-controlled study to assess the efficacy of drug treatment in generalized social phobia has been completed with paroxetine. Paroxetine was more effective in reducing the symptoms than placebo and was well tolerated. Many now regard SSRIs as the drugs of choice in social phobia because of their effectiveness and because they avoid the problems of treatment with benzodiazepines or classical MAOIs.

Antidepressants in Parkinson's disease. Recommendations by the movement disorder study group of the Neurological Association of Madrid.

PubMed

Peña, E; Mata, M; López-Manzanares, L; Kurtis, M; Eimil, M; Martínez-Castrillo, J C; Navas, I; Posada, I J; Prieto, C; Ruíz-Huete, C; Vela, L; Venegas, B

2016-03-19

Although antidepressants are widely used in Parkinson's disease (PD), few well-designed studies to support their efficacy have been conducted. These clinical guidelines are based on a review of the literature and the results of an AMN movement disorder study group survey. Evidence suggests that nortriptyline, venlafaxine, paroxetine, and citalopram may be useful in treating depression in PD, although studies on paroxetine and citalopram yield conflicting results. In clinical practice, however, selective serotonin reuptake inhibitors are usually considered the treatment of choice. Duloxetine may be an alternative to venlafaxine, although the evidence for this is less, and venlafaxine plus mirtazapine may be useful in drug-resistant cases. Furthermore, citalopram may be indicated for the treatment of anxiety, atomoxetine for hypersomnia, trazodone and mirtazapine for insomnia and psychosis, and bupropion for apathy. In general, antidepressants are well tolerated in PD. However, clinicians should consider the anticholinergic effect of tricyclic antidepressants, the impact of serotonin-norepinephrine reuptake inhibitors on blood pressure, the extrapyramidal effects of antidepressants, and any potential interactions between monoamine oxidase B inhibitors and other antidepressants. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened

PubMed Central

Friedman, Gary D.; Udaltsova, Natalia; Chan, James; Quesenberry, Charles P; Habel, Laurel A.

2010-01-01

Objective We screened commonly used prescription drugs for possible carcinogenic effects. Methods In a large health care program we identified 105 commonly used drugs, not previously screened. Recipients were followed for up to 12½ years for incident cancer. Nested case-control analyses of 55 cancer sites and all combined included up to ten matched controls per case, with lag of at least two years between drug dispensing and cancer. Positive associations entailed a relative risk (RR) of 1.50, with p≤ 0.01 and higher risk for three or more, than for one prescription. Evaluation included further analyses, searches of the literature, and clinical judgment. Results There were 101 associations of interest for 61 drugs. Sixty-six associations were judged to have involved substantial confounding. We found evidence that of the remaining 35, the following associations may not be due to chance: sulindac with gallbladder cancer and leukemia, hyoscyamine with non-Hodgkin lymphoma, nortriptyline with esophageal and hepatic cancer, oxazepam with lung cancer, both fluoxetine and paroxetine with testicular cancer, hydrochlorothiazide with renal and lip cancer, and nifedipine with lip cancer. Conclusions These preliminary findings suggest that further studies are indicated regarding sulindac, hyoscyamine, nortriptyline, oxazepam, fluoxetine, paroxetine, hydrochlorothiazide and nifedipine. PMID:19582585

Antidepressants and the risk of suicidal behaviors.

PubMed

Jick, Hershel; Kaye, James A; Jick, Susan S

2004-07-21

The relation between use of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), and suicidal ideation and behaviors has received considerable public attention recently. The use of such drugs among teenagers has been of particular concern. To estimate the relative risks (RRs) of nonfatal suicidal behavior in patients starting treatment with 1 of 3 antidepressant drugs compared with patients starting treatment with dothiepin. Matched case-control study of patients treated in UK general practices using the UK General Practice Research Database for 1993-1999. The base population included 159,810 users of the 4 antidepressant drugs. Participants could have used only 1 of these antidepressants and had to have received at least 1 prescription for the study antidepressant within 90 days before their index date (the date of suicidal behavior or ideation for cases and the same date for matched controls). Frequency of first-time exposure to amitriptyline, fluoxetine, paroxetine, and dothiepin of patients with a recorded diagnosis of first-time nonfatal suicidal behavior or suicide compared with comparable patients who did not exhibit suicidal behavior. After controlling for age, sex, calendar time, and time from first antidepressant prescription to the onset of suicidal behavior, the relative risks for newly diagnosed nonfatal suicidal behavior in 555 cases and 2062 controls were 0.83 (95% confidence interval, [CI] 0.61-1.13) for amitriptyline, 1.16 (95% CI, 0.90-1.50) for fluoxetine, and 1.29 (95% CI, 0.97-1.70) for paroxetine compared with those using dothiepin. The RR for suicidal behavior among patients first prescribed an antidepressant within 1 to 9 days before their index date was 4.07 (95% CI, 2.89-5.74) compared with patients who were first prescribed an antidepressant 90 days or more before their index date. Time since first antidepressant prescription was not, however, a confounder of the relation between specific antidepressants and suicidal behavior since its relation to suicidal behavior was not materially different among users of the 4 study drugs. Similarly for fatal suicide, the RR among patients who were first prescribed an antidepressant within 1 to 9 days before their index date was 38.0 (95% CI, 6.2-231) compared with those who were first prescribed an antidepressant 90 days or more before their index date. There were no significant associations between the use of a particular study antidepressant and the risk of suicide. The risk of suicidal behavior after starting antidepressant treatment is similar among users of amitriptyline, fluoxetine, and paroxetine compared with the risk among users of dothiepin. The risk of suicidal behavior is increased in the first month after starting antidepressants, especially during the first 1 to 9 days. A possible small increase in risk (bordering statistical significance) among those starting the newest antidepressant, paroxetine, is of a magnitude that could readily be due to uncontrolled confounding by severity of depression. Based on limited information, we also conclude that there is no substantial difference in effect of the 4 drugs on people aged 10 to 19 years.

Intranasal Cotinine Plus Krill Oil Facilitates Fear Extinction, Decreases Depressive-Like Behavior, and Increases Hippocampal Calcineurin A Levels in Mice.

PubMed

Alvarez-Ricartes, Nathalie; Oliveros-Matus, Patricia; Mendoza, Cristhian; Perez-Urrutia, Nelson; Echeverria, Florencia; Iarkov, Alexandre; Barreto, George E; Echeverria, Valentina

2018-02-27

Failure in fear extinction is one of the more troublesome characteristics of posttraumatic stress disorder (PTSD). Cotinine facilitates fear memory extinction and reduces depressive-like behavior when administered 24 h after fear conditioning in mice. In this study, it was investigated the behavioral and molecular effects of cotinine, and other antidepressant preparations infused intranasally. Intranasal (IN) cotinine, IN krill oil, IN cotinine plus krill oil, and oral sertraline were evaluated on depressive-like behavior and fear retention and extinction after fear conditioning in C57BL/6 mice. Since calcineurin A has been involved in facilitating fear extinction in rodents, we also investigated changes of calcineurin in the hippocampus, a region key on contextual fear extinction. Short-term treatment with cotinine formulations was superior to krill oil and oral sertraline in reducing depressive-like behavior and fear consolidation and enhancing contextual fear memory extinction in mice. IN krill oil slowed the extinction of fear. IN cotinine preparations increased the levels of calcineurin A in the hippocampus of conditioned mice. In the light of the results, the future investigation of the use of IN cotinine preparations for the extinction of contextual fear memory and treatment of treatment-resistant depression (TRD) in PTSD is discussed.

The Effects of Positive Patient Testimonials on PTSD Treatment Choice

PubMed Central

Pruitt, Larry D.; Zoellner, Lori A.; Feeny, Norah C.; Caldwell, Daniel; Hanson, Robert

2012-01-01

Despite the existence of effective treatment options for PTSD, these treatments are failing to reach those that stand to benefit from PTSD treatment. Understanding the processes underlying an individual’s treatment seeking behavior holds the potential for reducing treatment-seeking barriers. The current study investigates the effects that positive treatment testimonials have on decisions regarding PTSD treatment. An undergraduate (N = 439) and a trauma-exposed community (N = 203) sample were provided with videotaped treatment rationales for prolonged exposure (PE) and sertraline treatments of PTSD. Half of each sample also viewed testimonials, detailing a fictional patient’s treatment experience. All participants then chose among treatment options and rated the credibility of- and personal reactions toward- those options. Among treatment naïve undergraduates, testimonials increased the proportion choosing PE alone; and among treatment naïve members of the trauma-exposed community sample, testimonials increased the proportion choosing a combined PE plus sertraline treatment. These effects were not observed for those with prior history of either psychotherapeutic or pharmacological treatment. Major barriers exist that prevent individuals with PTSD from seeking treatment. For a critical unreached treatment sample, those who are treatment naïve, positive patient testimonials offer a mechanism in which to make effective treatments more appealing and accessible. PMID:23103234

Antidepressants in paediatric depression: do not look back in anger but around in awareness.

PubMed

Brent, David A; Gibbons, Robert D; Wilkinson, Paul; Dubicka, Bernadka

2018-02-01

In this paper, we summarise and critique a network meta-analysis (NMA) of antidepressant efficacy and tolerability for paediatric depression and an accompanying editorial. Although we agree that many of the extant studies are flawed, this meta-analysis showed clear efficacy of fluoxetine in the NMA, and for sertraline and escitalopram in pairwise analyses. Consequently, these papers underestimate the benefits of antidepressants for paediatric depression, and provide support for current practice guideline, which recommends the use of an antidepressant if the patient does not respond to psychotherapy. In these circumstances, fluoxetine should be the first choice, with escitalopram and sertraline as alternatives. Declaration of interest D.A.B. receives royalties from Guilford Press, has or will receive royalties from the electronic self-rated version of the C-SSRS from eResearch Technology, Inc., is on the editorial board of UpToDate, and is a reviewer for Healthwise. R.D.G. serves as an expert witness for the US Department of Justice, Pfizer, Wyeth and GSK; and is the founder of Adaptive Testing Technologies. P.W. receives personal fees from Lundbeck and Takeda. B.D. reports a licensing agreement with Lundbeck for a psychosocial treatment manual for depression. No other disclosures were reported.

Mediators of Change in the Child/Adolescent Anxiety Multimodal Treatment Study

PubMed Central

Kendall, Philip C.; Cummings, Colleen M.; Villabø, Marianne A.; Narayanan, Martina K.; Treadwell, Kimberli; Birmaher, Boris; Compton, Scott; Piacentini, John; Sherrill, Joel; Walkup, John; Gosch, Elizabeth; Keeton, Courtney; Ginsburg, Golda; Suveg, Cindy; Albano, Anne Marie

2015-01-01

Objective Test changes in (a) coping efficacy and (b) anxious self-talk as potential mediators of treatment gains at 3-month follow-up in the Child/Adolescent Anxiety Multimodal Treatment Study (CAMS). Method Participants were 488 youth (ages 7-17; 50.4% male) randomized to cognitive-behavioral therapy (CBT; Coping cat program), pharmacotherapy (sertraline), their combination, or pill placebo. Participants met DSM-IV criteria for generalized anxiety disorder, social phobia, and/or separation anxiety disorder. Coping efficacy (reported ability to manage anxiety provoking situations) was measured by youth and parent reports on the Coping Questionnaire, and anxious self-talk was measured by youth report on the Negative Affectivity Self-Statement Questionnaire. Outcome was measured using the Pediatric Anxiety Rating Scale (completed by Independent Evaluators blind to condition). For temporal precedence, residualized treatment gains were assessed at 3-month follow-up. Results Residualized gains in coping efficacy mediated gains in the CBT, sertraline, and combination conditions. In the combination condition, some unique effect of treatment remained. Treatment assignment was not associated with a reduction in anxious self-talk, nor did anxious self-talk predict changes in anxiety symptoms. Conclusions The findings suggest that improvements in coping efficacy are a mediator of treatment gains. Anxious self-talk did not emerge as a mediator. PMID:26460572

Heart Rate Variability and Cardiovascular Reactivity in Panic Disorder

DTIC Science & Technology

1999-04-01

pharmacological treatment with alprazolam or clonidine (Klein, Cnaani et al., 1995), or paroxetine (Tucker et al., 1997) were found not to differ...of Cardiology, 60, 86-89. Mcleod, D. R., Hoehn-Saric, R., Zimmerli, W.D. De Souza, E. B. & Oliver, L. K. (1990). Treatment effects of alprazolam and...and alprazolam effects on stress test reactivity in panic disorder. Biological Psychiatry. 31, 35-51. Roth, W. T., Margraf, J., Ehlers, A., Taylor

Co-occurring depressive symptoms in the older patient with schizophrenia.

PubMed

Kasckow, John W; Zisook, Sidney

2008-01-01

Clinicians treating older patients with schizophrenia are often challenged by patients presenting with both depressive and psychotic features. The presence of co-morbid depression impacts negatively on quality of life, functioning, overall psychopathology and the severity of co-morbid medical conditions. Depressive symptoms in patients with schizophrenia include major depressive episodes (MDEs) that do not meet criteria for schizoaffective disorder, MDEs that occur in the context of schizoaffective disorder and subthreshold depressive symptoms that do not meet criteria for MDE. Pharmacological treatment of patients with schizophrenia and depression involves augmenting antipsychotic medications with antidepressants. Recent surveys suggest that clinicians prescribe antidepressants to 30% of inpatients and 43% of outpatients with schizophrenia and depression at all ages. Recent trials addressing the efficacy of this practice have evaluated selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, sertraline, fluvoxamine and citalopram. These trials have included only a small number of subjects and few older subjects participated; furthermore, the efficacy results have been mixed. Although no published controlled psychotherapeutic studies have specifically targeted major depression or depressive symptoms in older patients with schizophrenia, psychosocial interventions likely play a role in any comprehensive management plan in this population of patients.Our recommendations for treating the older patient with schizophrenia and major depression involve a stepwise approach. First, a careful diagnostic assessment to rule out medical or medication causes is important as well as checking whether patients are adherent to treatments. Clinicians should also consider switching patients to an atypical antipsychotic if they are not taking one already. In addition, dose optimization needs to be targeted towards depressive as well as positive and negative psychotic symptoms. If major depression persists, adding an SSRI is a reasonable next step; one needs to start with a low dose and then cautiously titrate upward to reduce depressive symptoms. If remission is not achieved after an adequate treatment duration (8-12 weeks) or with an adequate dose (similar to that used for major depression without schizophrenia), switching to another agent or adding augmenting therapy is recommended.We recommend treating an acute first episode of depression for at least 6-9 months and consideration of longer treatment for patients with residual symptoms, very severe or highly co-morbid major depression, ongoing episodes or recurrent episodes. Psychosocial interventions aimed at improving adherence, quality of life and function are also recommended. For patients with schizophrenia and subsyndromal depression, a similar approach is recommended.Psychosis accompanying major depression in patients without schizophrenia is common in elderly patients and is considered a primary mood disorder; for these reasons, it is an important syndrome to consider in the differential diagnosis of older patients with mood and thought disturbance. Treatment for this condition has involved electroconvulsive therapy (ECT) as well as combinations of antidepressant and antipsychotic medications. Recent evidence suggests that combination treatment may not be any more effective than antidepressant treatment alone and ECT may be more efficacious overall.

Regulation of the kynurenine metabolism pathway by Xiaoyao San and the underlying effect in the hippocampus of the depressed rat.

PubMed

Wang, Jiajia; Li, Xiaofang; He, Shugui; Hu, Lijun; Guo, Jiewen; Huang, Xiangning; Hu, Jinqing; Qi, Yaoqun; Chen, Bin; Shang, Dewei; Wen, Yuguan

2018-03-25

Xiaoyao San (XYS) is a classic Chinese herbal formula for treatment of depression. The present study aimed to investigate the antidepressant effects of XYS in a rat model of chronic unpredictable mild stress (CUMS) and the underlying mechanisms. A CUMS rat model of depression was established via 4 weeks of unpredictable stimulation. Then the rats were orally administered paroxetine and XYS for 2 weeks with continued stress. Behavioral assessments, including an open field test (OFT), sucrose preference test (SPT) and forced swim test (FST), were conducted to evaluate the antidepressant effects of XYS. The concentrations in rat plasma of tryptophan (Trp) and its metabolic products, including kynurenine (Kyn) and quinolinic acid (QUIN), were determined using high performance liquid chromatography tandem mass spectrometry with electrochemical detection (HPLC-MS/MS). The mRNA and protein levels in rat hippocampus of depression-related brain derived neurotrophic factor (BDNF), cyclic AMP response element binding protein (CREB) and nerve cell adhesion molecule (NCAM) were determined by real-time qPCR and Western blot, respectively. Enzyme Linked Immunosorbent Assay (ELISA) was used to detect the activities of indoleamine 2,3-dioxygenase (IDO) and kynurenine-3-monooxygenase (KMO) in rat plasma. The results showed that a successful CUMS rat model was established through 4 weeks of continuous unpredictable stimulation, as indicated by the significant decrease in locomotor activity and increase in immobility time in the OFT, reduction in body weight and food intake etc. Compared with the normal group, the concentrations of Kyn and QUIN had significantly (p < 0.05) decreased at day 28 in the control group, but then improved after drug treatment with paroxetine and XYS. There were no obvious changes in the activities of IDO and KMO. Compared with the normal group, the mRNA of NCAM, CREB and BDNF were significantly down-regulated (p < 0.001) in the control group, BDNF gene was up-regulated by paroxetine or XYS treatment, NCAM and CREB gene did not change in XYS group, protein expressions of BDNF and CREB were significantly increased, and NCAM was significantly reduced (p < 0.05). XYS reversed the abnormalities of the tryptophan-kynurenine metabolic pathways in depressed rats and achieved an excellent antidepressant effect. Its direct impact may be observed as changes in biological indicators in rat hippocampus tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessing the efficiency of an unplanted horizontal flow constructed wetland to reduce some emerging organic micropollutants. Preliminary results

NASA Astrophysics Data System (ADS)

Tapias, Josefina C.; Vila, Marta; Himi, Mahjoub; Salvadó, Victoria; Casas, Albert; Hidalgo, Manuela

2017-04-01

The presence of emerging organic contaminants (EOC) such as pharmaceutical and personal care products, pesticides or antiseptics in wastewater is an increasing concern worldwide due to their potential toxicological effects for humans and other living organisms. Because of their low concentration and persistence their removal using conventional treatment technologies is often incomplete and for this reason there is a growing interest for assessing the efficiency of alternative wastewater treatment technologies such as constructed wetlands (CWs). CWs are engineered systems for wastewater treatment plant (WWTP) designed to take advantage of many of the same processes that occur in natural wetlands, but within a more controlled environment. CWs are a cost-effective alternative to conventional wastewater treatment plants especially in the context of small communities with less than 2000 people equivalent. Our study has been conducted at the Verdú WWTP (Lleida, Catalonia, NE Spain). This system has a primary treatment consisting on three septic tanks in parallel with a volume of 50 m3 and three chambers each one. The primary effluent is distributed to four parallel horizontal subsurface flow (HSSF) CWs. Originally the system was planted with common reed (Phragmites australis), but currently after twelve years of service the system show evidences of clogging and then gravel bed was replaced and plants removed. After the HSSF CWs, there are two wastewater stabilization ponds (WSPs) followed by two smaller polishing horizontal HSSF CWs. Excellent overall treatment performance was exhibited on the elimination of conventional water quality parameters (93-98% average removal efficiency for TSS, COD, BOD5 and NTK), and its final effluent proved to comply with existing Spanish guidelines. Sampling has been conducted along two years at different seasons and examined EOC substances included analgesic and anti-inflammatory drugs (ibuprofen, diclofenac, and naproxene), antidepressants (sertraline, paroxetine, fluoxetine and citalopram) and in addition carbamazepine and triclosan. For the analysis of water samples, a 200 mL volume was filtrated through 0.45µm nylon filters, acidified, and extracted with Oasis HLB cartridges. The analytes were recovered with 3mL methanol followed by 3 mL acetonitrile. The extract was evaporated under a gentle nitrogen stream, reconstituted with 500 µL MeOH:ACN (1:1) and analyzed by LC/MS/MS. Highest influent concentrations of studied EOCs in raw wastewater were for naproxene (ranging 2.1 - 24.76µg/L) and iboprufene (ranging 4.2 - 11.74 µg/L) and final effluent concentrations of these same compounds showed high but variable removal efficiencies depending on environmental temperature. Additionally to the reductions within the wetland beds attributed to sorption by particulate matter and biofilm, further reduction was completed at the waste water stabilization ponds by photodegradation.

Effects of antidepressants on alternations in serum cytokines and depressive-like behavior in mice after lipopolysaccharide administration.

PubMed

Ohgi, Yuta; Futamura, Takashi; Kikuchi, Tetsuro; Hashimoto, Kenji

2013-02-01

Accumulating evidence suggests that inflammation may play a role in the pathophysiology of major depressive disorder (MDD). Antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), possess anti-inflammatory effects in vitro. Here, we examined the effects of SSRIs and SNRIs on lipopolysaccharide (LPS)-induced inflammation and depressive-like behavior in male mice. A single administration of LPS (0.5mg/kg, i.p.) increased serum levels of the pro-inflammatory cytokine, tumor necrosis factor-α (TNFα) and the anti-inflammatory cytokine, interleukin-10 (IL-10) in mice. Pretreatment with SSRIs (fluoxetine and paroxetine), SNRIs (venlafaxine and duloxetine), or 5-hydroxytryptophan (5-HTP), a precursor of serotonin, attenuated LPS-induced increases in TNFα, whereas it increased serum levels of IL-10, in mice treated with LPS. In the tail suspension test (TST), LPS increased the immobility time without affecting spontaneous locomotor activity, suggesting that LPS induced depressive-like behavior in mice. Treatment with fluoxetine (30 mg/kg) or paroxetine (10mg/kg) significantly shortened LPS-induced increases of immobility time. These results suggested that antidepressants exert anti-inflammatory effects in vivo, and that the serotonergic system may partially mediate these effects. In addition, the anti-inflammatory effects of antidepressants may help alleviate the symptoms of LPS-induced depression in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

Trazodone Addition to Paroxetine and Mirtazapine in a Patient with Treatment-Resistant Depression: The Pros and Cons of Combining Three Antidepressants

PubMed Central

Alves, José Carlos; Rego, Raquel Garcia

2016-01-01

Dual antidepressant combination for treatment-resistant depression is a strategy well supported by literature and accepted in clinical practice. Rather, the usefulness of the combination of more than two antidepressants is controversial. This may be related to the possibility of higher side-effect burden and to doubts about its pharmacological effectiveness and therapeutic advantage compared to other standard treatment options. We report a relapse of moderate-to-severe depressive symptoms with insomnia that successfully remitted after the addition of trazodone to a dual combination of paroxetine and mirtazapine (in standard effective doses) in a patient with treatment-resistant depression. We also review the literature and discuss the utility of triple antidepressant combination in treatment-resistant depression. This clinical case highlights the utility of combining trazodone as a third antidepressant for the relapse of depressive symptoms after the failure of a dual antidepressant combination. Trazodone may be advantageous in patients presenting recurrence of moderate-to-severe depressive symptoms that include sleep problems and/or insomnia and may be particularly useful when benzodiazepines are not recommended. Although its use may be controversial and associated with higher risk of side-effects, more investigation is needed to determine the efficacy and safety for triple antidepressant combinations as reliable strategies for treatment-resistant depression in clinical practice. PMID:27807450

Partial lesion of the serotonergic system by a single dose of MDMA results in behavioural disinhibition and enhances acute MDMA-induced social behaviour on the social interaction test.

PubMed

Ando, Romeo D; Benko, Anita; Ferrington, Linda; Kirilly, Eszter; Kelly, Paul A T; Bagdy, Gyorgy

2006-06-01

The acute effects of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) on anxiety-related behaviours were studied using indices of social interaction in Dark Agouti (DA) both drug naive rats and those pretreated with MDMA (15 mg/kg i.p.) 3 weeks earlier. The functional neuroanatomy of these MDMA effects was visualised using 2-deoxyglucose imaging of local cerebral glucose use (LCMRglu), whilst MDMA-induced serotonergic neurotoxicity was measured by radioligand binding with [3H]paroxetine. Acute MDMA alone markedly decreased most typical elements of social interaction but increased adjacent lying, a behaviour that also contains social elements. In animals pre-exposed to MDMA, decreased [3H]paroxetine binding indicated serotonergic terminal depletion, and in these animals significant increases in locomotor activity, exploratory behaviour and aggressive behaviour were found. Both behavioural effects and also the metabolic activation induced by acute MDMA were potentiated in rats previously exposed to the drug. In conclusion, a single dose of MDMA caused marked changes in social behaviour acutely that might be interpreted either as a decrease or increase in anxiety. Three weeks after MDMA a behavioural disinhibition similar to psychomotor agitation, a symptom connected to depression or mania, and a sensitization to the acute effects of MDMA are apparent in both the behavioural and brain metabolic effects of the drug.

Gingival bleeding, a possible "serious" adverse drug reaction: An observational study in the French PharmacoVigilance Database.

PubMed

Bondon-Guitton, Emmanuelle; Mourgues, Thibaut; Rousseau, Vanessa; Cousty, Sarah; Cottin, Judith; Drablier, Guillaume; Micallef, Joëlle; Montastruc, Jean-Louis

2017-09-01

Antithrombotic drugs are known to increase the risk of gingival bleeding because they affect coagulation. However, other drugs could also be involved in gingival bleeding. We performed a pharmacoepidemiological study to identify the drugs most frequently "suspected" in the occurrence of gingival bleeding. We selected reports of "gingival bleeding" from 1 January 1985 to 30 September 2014 in the French PharmacoVigilance Database. Among 523,808 reports of adverse drug reactions, we identified 454 reports of gingival bleeding (0.09%). Most of them were "serious" (58.4%) and occurred in females (54.6%). The frequency of gingival bleeding increased with age. The most frequently "suspected" drugs were antithrombotics (67.8%), particularly fluindione. Other drugs frequently involved were furosemide followed by paracetamol, amiodarone, amoxicillin, paroxetine, ketoprofen, zolpidem, enalapril and ramipril. Thirty-nine reports involved a drug-drug interaction with antithrombotics, mainly with anti-infectives. Gingival bleeding can be an adverse drug reaction, often "serious" and rarely fatal. Patients older than 50 years and women are particularly at risk. Among drugs known to increase the risk of gingival bleeding, the most frequently involved were fluindione, furosemide, paracetamol, amiodarone, amoxicillin, paroxetine or ketoprofen. We also identified signal for drugs not usually known to be involved in bleeding, like zolpidem, enalapril or ramipril. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prolonged anticholinergic delirium following antihistamine overdose.

PubMed

Scott, James; Pache, David; Keane, Greg; Buckle, Helen; O'Brien, Natalie

2007-06-01

A case of anticholinergic delirium in a female adolescent is described, exploring the pharmacokinetic reasons for the prolonged time course and reviewing the management provided. A 14 year old female hospitalised for depression ingested large quantities of promethazine and cyproheptadine. A severe anticholinergic delirium ensued which resolved after six days, much longer than the expected duration. The likely cause of the prolonged delirium was the interaction of promethazine and fluvoxamine through the inhibition of the CYP2D6 enzyme. The patient's young age, the severity of the poisoning and the use of drugs with anticholinergic properties to manage the delirium may also have contributed. The delirium may have been reversed had a cholinesterase inhibitor been provided soon after the overdose.

A study of sertraline in dialysis (ASSertID): a protocol for a pilot randomised controlled trial of drug treatment for depression in patients undergoing haemodialysis.

PubMed

Friedli, Karin; Almond, Michael; Day, Clara; Chilcot, Joseph; Gane, Maria da Silva; Davenport, Andrew; Guirguis, Ayman; Fineberg, Naomi; Spencer, Benjamin; Wellsted, David; Farrington, Ken

2015-10-26

The prevalence of depression in people receiving haemodialysis is high with estimates varying between 20 and 40 %. There is little research on the effectiveness of antidepressants in dialysis patients with the few clinical trials suffering significant methodological issues. We plan to carry out a study to evaluate the feasibility of conducting a randomised controlled trial in patients on haemodialysis who have diagnosed Major Depressive Disorder. The study has two phases, a screening phase and the randomised controlled trial. Patients will be screened initially with the Beck Depression Inventory to estimate the number of patients who score 16 or above. These patients will be invited to an interview with a psychiatrist who will invite those with a diagnosis of Major Depressive Disorder to take part in the trial. Consenting patients will be randomised to either Sertraline or placebo. Patients will be followed-up for 6 months. Demographic and clinical data will be collected at screening interview, baseline interview and 2 weeks, and every month (up to 6 months) after baseline. The primary outcome is to evaluate the feasibility of conducting a randomised, double blind, placebo pilot trial in haemodialysis patients with depression. Secondary outcomes include estimation of the variability in the outcome measures for the treatment and placebo arms, which will allow for a future adequately powered definitive trial. Analysis will primarily be descriptive, including the number of patients eligible for the trial, drug exposure of Sertraline in haemodialysis patients and the patient experience of participating in this trial. There is an urgent need for this research in the dialysis population because of the dearth of good quality and adequately powered studies. Research with renal patients is particularly difficult as they often have complex medical needs. This research will therefore not only assess the outcome of anti-depressants in haemodialysis patients with depression but also the process of running a randomised controlled trial in this population. Hence, the outputs of this feasibility study will be used to inform the design and methodology of a definitive study, adequately powered to determine the efficacy of anti-depressants in patient on haemodialysis with depression. ISRCTN registry ISRCTN06146268 and EudraCT reference: 2012-000547-27.

The STRONG STAR Multidisciplinary PTSD Research Consortium

DTIC Science & Technology

2011-09-01

NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b . ABSTRACT U c. THIS PAGE U UU 24 19b. TELEPHONE NUMBER...measures are made. 4. To determine the effects of treatments with the SSRI sertraline in adults exposed to early life stress. B . BODY: During the last...Program no. 190.06. Bingham B , Kaddapakam S, Strong R, Morilak DA (2011) Potential role of corticosterone in the long-lasting effects of prenatal stress

What would you choose? Sertraline or prolonged exposure in community and PTSD treatment seeking women.

PubMed

Feeny, Norah C; Zoellner, Lori A; Mavissakalian, Matig R; Roy-Byrne, Peter P

2009-01-01

Both sertraline (SER) and prolonged exposure (PE) are empirically supported treatments for chronic posttraumatic stress disorder (PTSD). While efficacious, these treatments are quite different in approach, and such differences may influence both treatment choice and treatment outcome. To date, we know very little about the relative efficacy of pharmacological and psychological treatments for chronic PTSD. In Study 1, we compared rates of treatment choice (SER or PE) in 74 trauma-exposed women. In Study 2, we extended this work to an open-choice treatment trial, in which 31 female assault survivors with chronic PTSD received their choice of SER or PE for ten weeks and were followed over time. In Study 1 (82%) and Study 2 (74.2%), the majority of women chose PE. In Study 2, both SER and PE evidenced moderate to large unadjusted effect sizes, with evidence of an advantage for PE in propensity adjusted analyses at posttreatment. Women with co-occurring major depressive disorder (MDD) were more likely to choose SER than those without MDD. However, among those with MDD, the advantage of PE was particularly evident. Our results highlight the presence of clear treatment preferences for PTSD and their potential impact on outcome. This study underscores the importance of systematic study of patient preferences and encourages a rethinking of one-size fits all approaches to treatment for mental disorders. (c) 2009 Wiley-Liss, Inc.

CUSP9* treatment protocol for recurrent glioblastoma: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, sertraline augmenting continuous low dose temozolomide

PubMed Central

Kast, Richard E.; Karpel-Massler, Georg; Halatsch, Marc-Eric

2014-01-01

CUSP9 treatment protocol for recurrent glioblastoma was published one year ago. We now present a slight modification, designated CUSP9*. CUSP9* drugs- aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, sertraline, ritonavir, are all widely approved by regulatory authorities, marketed for non-cancer indications. Each drug inhibits one or more important growth-enhancing pathways used by glioblastoma. By blocking survival paths, the aim is to render temozolomide, the current standard cytotoxic drug used in primary glioblastoma treatment, more effective. Although esthetically unpleasing to use so many drugs at once, the closely similar drugs of the original CUSP9 used together have been well-tolerated when given on a compassionate-use basis in the cases that have come to our attention so far. We expect similarly good tolerability for CUSP9*. The combined action of this suite of drugs blocks signaling at, or the activity of, AKT phosphorylation, aldehyde dehydrogenase, angiotensin converting enzyme, carbonic anhydrase -2,- 9, -12, cyclooxygenase-1 and -2, cathepsin B, Hedgehog, interleukin-6, 5-lipoxygenase, matrix metalloproteinase -2 and -9, mammalian target of rapamycin, neurokinin-1, p-gp efflux pump, thioredoxin reductase, tissue factor, 20 kDa translationally controlled tumor protein, and vascular endothelial growth factor. We believe that given the current prognosis after a glioblastoma has recurred, a trial of CUSP9* is warranted. PMID:25211298

Multivariate therapeutic approach to binge-eating disorder: combined nutritional, psychological and pharmacological treatment.

PubMed

Brambilla, Francesca; Samek, Lorenzo; Company, Marta; Lovo, Francesca; Cioni, Luisa; Mellado, Carmen

2009-11-01

Treatment for binge-eating disorder (BED) is directed towards either the physical or psychopathological impairments, and often does not cover all the alterations characterizing the disease. In 30 BED patients, we monitored the effects of three types of 6-month treatment, randomly assigned to one of the three treatment groups, each consisting of 10 patients. Group 1 received a 1700-kcal diet (21% proteins, 27% lipids, 52% carbohydrate), cognitive-behavioural therapy (CBT), sertraline (50-150 mg/day) and topiramate (25-150 mg/day); group 2 received the same diet, CBT, sertraline; and group 3 received nutritional counselling and CBT. Binge frequency and weight were assessed every month. The Eating Disorder Inventory-2, the Symptoms Check List-90-Revised (SCL-90-R) and the Personality Diagnostic Questionnaire-4-Revised (PDQ-4-R) were administered before and after treatment. Binge frequency and excessive weight decreased significantly only in group 1 patients, in whom improvement was noted in total Eating Disorder Inventory-2 scores and the subitems 'bulimia', 'drive for thinness', 'maturity fear', 'ascetism', in total SCL-90-R scores and in the subitem 'somatization', in PDQ-4-R subitems 'schizotypic personality' and 'dependent personality'. Group 2 patients improved on the SCL-90-R subitems 'depression' and 'interpersonal relationship' and in the PDQ-4-R 'schizoid personality'. Combination therapy seems to be the only fully effective treatment in BED patients.

CUSP9* treatment protocol for recurrent glioblastoma: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, sertraline augmenting continuous low dose temozolomide.

PubMed

Kast, Richard E; Karpel-Massler, Georg; Halatsch, Marc-Eric

2014-09-30

CUSP9 treatment protocol for recurrent glioblastoma was published one year ago. We now present a slight modification, designated CUSP9*. CUSP9* drugs--aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, sertraline, ritonavir, are all widely approved by regulatory authorities, marketed for non-cancer indications. Each drug inhibits one or more important growth-enhancing pathways used by glioblastoma. By blocking survival paths, the aim is to render temozolomide, the current standard cytotoxic drug used in primary glioblastoma treatment, more effective. Although esthetically unpleasing to use so many drugs at once, the closely similar drugs of the original CUSP9 used together have been well-tolerated when given on a compassionate-use basis in the cases that have come to our attention so far. We expect similarly good tolerability for CUSP9*. The combined action of this suite of drugs blocks signaling at, or the activity of, AKT phosphorylation, aldehyde dehydrogenase, angiotensin converting enzyme, carbonic anhydrase -2,- 9, -12, cyclooxygenase-1 and -2, cathepsin B, Hedgehog, interleukin-6, 5-lipoxygenase, matrix metalloproteinase -2 and -9, mammalian target of rapamycin, neurokinin-1, p-gp efflux pump, thioredoxin reductase, tissue factor, 20 kDa translationally controlled tumor protein, and vascular endothelial growth factor. We believe that given the current prognosis after a glioblastoma has recurred, a trial of CUSP9* is warranted.

Therapeutic Drug Monitoring of Fluoxetine, Norfluoxetine and Paroxetine: A New Tool Based on Microextraction by Packed Sorbent Coupled to Liquid Chromatography.

PubMed

Magalhães, Paulo; Alves, Gilberto; Llerena, Adrián; Falcão, Amílcar

2017-09-01

The present article reports the first liquid chromatography (LC) assay for the simultaneous quantification of fluoxetine (FLU), its metabolite norfluoxetine (NFLU) and paroxetine (PAR) in human plasma, applying the microextraction by packed sorbent (MEPS) technology in sample preparation. Chromatographic analysis of FLU, NFLU and PAR was achieved in <13 min on a reverse-phase C18 column using isocratic elution and fluorescence detection (FLD). The mobile phase was composed by an aqueous solution of 25 mM sodium phosphate monobasic anhydrous and 7.5 mM di-potassium hydrogen phosphate anhydrous (pH 3.0)/acetonitrile/methanol (70:23:7, v/v/v). The detector was set at 240/312 nm for FLU, NFLU and IS and at 295/350 nm for PAR. The method showed linearity in the ranges of 20-750 ng mL-1 for FLU and NFLU, and 5-750 ng mL-1 for PAR (r2 ≥ 0.9919). The overall intra- and interday precision did not exceed 13.6% and the corresponding accuracy (bias) ranged from 0.02 to 16.7%. The method was successfully applied in the analysis of authentic plasma samples. Hence, this new MEPS/LC-FLD assay ensures robust and low-cost analyses representing, therefore, a good alternative to support therapeutic drug monitoring and clinical studies involving these antidepressant drugs. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Bidirectional Relationship Between Body Mass Index and Treatment Outcome in Adolescents with Treatment-Resistant Depression

PubMed Central

Mansoor, Brandon; Rengasamy, Manivel; Hilton, Robert; Porta, Giovanna; He, Jiayan; Spirito, Anthony; Emslie, Graham J.; Mayes, Taryn L.; Clarke, Gregory; Wagner, Karen Dineen; Shamseddeen, Wael; Birmaher, Boris; Ryan, Neal

2013-01-01

Abstract Objective Depression and obesity are associated, but the impact of obesity on depression treatment outcome, or, conversely, the impact of treatment on body mass index (BMI) in depressed adolescents has not been reported. In this article, we examine the bidirectional relationships between BMI and treatment response in adolescents with treatment-resistant depression. Method Participants in the Treatment of Selective Serotonin Reuptake Inhibitor (SSRI) Resistant Depression in Adolescents (TORDIA) study had height and weight assessed at baseline, weekly for the first 6 weeks, biweekly for the next 6 weeks, and monthly from weeks 12 through 24. The impact of baseline BMI as a predictor and moderator of treatment response was assessed. In addition, participants' changes in BMI were assessed as a function of specific treatment assignment and treatment response. Results Participants assigned to SSRIs had a greater increase in BMI-for-age-sex z-score and weight than did those assigned to venlafaxine. Post-hoc, those treated with paroxetine or citalopram had the biggest increases in BMI, relative to fluoxetine or venlafaxine. Overweight or obesity was neither a predictor nor a moderator of treatment outcome, nor of subsequent BMI change. Conclusions Overweight status does not appear to affect treatment response in adolescents with resistant depression. The successful treatment of depression does not appear to favorably affect weight or BMI. Fluoxetine and venlafaxine are less likely to cause an increase in BMI than paroxetine or citalopram. PMID:24024532

A systematic review of treatments for anxiety in youth with autism spectrum disorders.

PubMed

Vasa, Roma A; Carroll, Laura M; Nozzolillo, Alixandra A; Mahajan, Rajneesh; Mazurek, Micah O; Bennett, Amanda E; Wink, Logan K; Bernal, Maria Pilar

2014-12-01

This study systematically examined the efficacy and safety of psychopharmacological and non-psychopharmacological treatments for anxiety in youth with autism spectrum disorders (ASD). Four psychopharmacological, nine cognitive behavioral therapy (CBT), and two alternative treatment studies met inclusion criteria. Psychopharmacological studies were descriptive or open label, sometimes did not specify the anxiety phenotype, and reported behavioral activation. Citalopram and buspirone yielded some improvement, whereas fluvoxamine did not. Non-psychopharmacological studies were mainly randomized controlled trials (RCTs) with CBT demonstrating moderate efficacy for anxiety disorders in youth with high functioning ASD. Deep pressure and neurofeedback provided some benefit. All studies were short-term and included small sample sizes. Large scale and long term RCTs examining psychopharmacological and non-psychopharmacological treatments are sorely needed.

EEG alpha asymmetry as a gender-specific predictor of outcome to acute treatment with different antidepressant medications in the randomized iSPOT-D study.

PubMed

Arns, Martijn; Bruder, Gerard; Hegerl, Ulrich; Spooner, Chris; Palmer, Donna M; Etkin, Amit; Fallahpour, Kamran; Gatt, Justine M; Hirshberg, Laurence; Gordon, Evian

2016-01-01

To determine whether EEG occipital alpha and frontal alpha asymmetry (FAA) distinguishes outpatients with major depression (MDD) from controls, predicts antidepressant treatment outcome, and to explore the role of gender. In the international Study to Predict Optimized Treatment in Depression (iSPOT-D), a multi-center, randomized, prospective open-label trial, 1008 MDD participants were randomized to escitalopram, sertraline or venlafaxine-extended release. The study also recruited 336 healthy controls. Treatment response was established after eight weeks and resting EEG was measured at baseline (two minutes eyes open and eyes closed). No differences in EEG alpha for occipital and frontal cortex, or for FAA, were found in MDD participants compared to controls. Alpha in the occipital and frontal cortex was not associated with treatment outcome. However, a gender and drug-class interaction effect was found for FAA. Relatively greater right frontal alpha (less cortical activity) in women only was associated with a favorable response to the Selective Serotonin Reuptake Inhibitors escitalopram and sertraline. No such effect was found for venlafaxine-extended release. FAA does not differentiate between MDD and controls, but is associated with antidepressant treatment response and remission in a gender and drug-class specific manner. Future studies investigating EEG alpha measures in depression should a-priori stratify by gender. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Do early changes in the HAM-D-17 anxiety/somatization factor items affect treatment outcome among depressed outpatients? Comparison of two controlled trials of St John’s Wort (Hypericum Perforatum) versus an SSRI

PubMed Central

Bitran, Stella; Farabaugh, Amy H; Ameral, Victoria E; LaRocca, Rachel A; Clain, Alisabet J; Fava, Maurizio; Mischoulon, David

2011-01-01

Objective To assess whether early changes in HAM-D-17 anxiety/somatization items predict remission in two controlled studies of hypericum perforatum (St. John’s wort) versus an SSRI for major depressive disorder (MDD). Methods The Hypericum Depression Trial Study Group (NIMH) study randomized 340 subjects to hypericum, sertraline, or placebo for 8 weeks. The MGH study randomized 135 subjects to hypericum, fluoxetine, or placebo for 12 weeks. We examined whether remission was associated with early changes in anxiety/somatization symptoms. Results In the NIMH study, significant associations were observed between remission and early improvement in the anxiety-psychic item (sertraline arm), somatic-gastrointestinal item (hypericum arm), and somatic symptoms-general (placebo arm). None of the three treatment arms of the MGH study showed significant associations between anxiety/somatization symptoms and remission. When both study samples were pooled, we found associations for anxiety-psychic (SSRI arm), somatic-gastrointestinal and hypochondriasis (hypericum arm), and anxiety-psychic and somatic symptoms-general (placebo arm). In the entire sample, remission was associated with improvement in the anxiety-psychic, somatic-gastrointestinal, and somatic symptoms-general items. Conclusions The number and type of anxiety/somatization items associated with remission varied depending on the intervention. Early scrutiny of the HAM-D-17 anxiety/somatization items may help predict remission of MDD. PMID:21278577

Strategic use of new generation antidepressants for depression: SUN(^_^)D study protocol

PubMed Central

2011-01-01

Background After more than half a century of modern psychopharmacology, with billions of dollars spent on antidepressants annually world-wide, we lack good evidence to guide our everyday decisions in conducting antidepressant treatment of patients with major depression. First we did not know which antidepressant to use as first line treatment. Second we do not know which dosage we should be aiming at with that antidepressant. Because more than half of the patients with major depression starting treatment do not remit after adequate trial with the first agent, they will need a second line treatment. Dose escalation, augmentation and switching are the three often recommended second line strategies but we do not know which is better than the others. Moreover, we do not know when to start considering this second line treatment. The recently published multiple-treatments meta-analysis of 12 new generation antidepressants has provided some partial answers to the first question. Starting with these findings, this proposed trial aims to establish the optimum 1st line and 2nd line antidepressant treatment strategy among adult patients with a non-psychotic unipolar major depressive episode. Methods SUN(^_^)D, the Strategic Use of New generation antidepressants for Depression, is an assessor-blinded, parallel-group, multi-centre randomised controlled trial. Step I is a cluster-randomised trial comparing titration up to the minimum vs maximum of the recommended dose range among patients starting with sertraline. The primary outcome is the change in the Patient Health Questionnaire (PHQ)-9 scores administered by a blinded rater via telephone at week 1 through 3. Step II is an individually randomised trial comparing staying on sertraline, augmentation of sertraline with mirtazapine, and switching to mirtazapine among patients who have not remitted on the first line treatment by week 3. The primary outcome is the change in the PHQ-9 scores at week 4 through 9. Step III represents a continuation phase to Steps I and II and aims to establish longer-term effectiveness and acceptability of the above-examined treatment strategies up to week 25. The trial is supported by the Grant-in-Aid by the Ministry of Health, Labour and Welfare, Japan. Discussion SUN(^_^)D promises to be a pragmatic large trial to answer important clinical questions that every clinician treating patients with major depression faces in his/her daily practices concerning its first- and second-line treatments. Trial registration ClinicalTrials.gov: NCT01109693 PMID:21569309

Factors Influencing Depression Endpoints Research (FINDER): baseline results of Italian patients with depression

PubMed Central

Grassi, Luigi; Rossi, Andrea; Barraco, Alessandra

2009-01-01

Background Factors Influencing Depression Endpoints Research (FINDER) is a 6-month, prospective, observational study carried out in 12 European countries aimed at investigating health-related quality of life (HRQoL) in outpatients receiving pharmacological treatment for a first or new depressive episode. Baseline characteristics of patients enrolled in Italy are presented. Methods All treatment decisions were at the discretion of the investigator. Data were collected at baseline and after 3 and 6 months of treatment. Baseline evaluations included demographics, medical and psychiatric history, and medications used in the last 24 months and prescribed at enrolment. The Hospital Anxiety and Depression Scale (HADS), was adopted to evaluate depressive symptoms, while somatic and painful physical symptoms were assessed by using the Somatic Symptom Inventory (SSI) and a 0 to 100 mm visual analogue scale (VAS), HRQoL via 36-item Short Form Health Survey (SF-36), and the European Quality of Life 5-Dimensions (EQ-5D) instrument. Results A total of 513 patients were recruited across 38 sites. The mean ± standard deviation (SD) age at first depressive episode was 38.7 ± 15.9 years, the mean duration of depression 10.6 ± 12.3 years. The most common psychiatric comorbidities in the previous 24 months were anxiety/panic (72.6%) and obsessive/compulsive disorders (13.4%), while 35.9% had functional somatic syndromes. Most patients (65.1%) reported pain from any cause. Monotherapy with selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) was prescribed at enrolment in 64.5% and 6.4% of the cases, respectively. The most commonly prescribed agents were sertraline (17.3%), escitalopram (16.2%), venlaflaxine (15.6%) and paroxetine (14.8%). The mean HADS subscores for depression and anxiety were 13.3 ± 4.2 and 12.2 ± 3.9, respectively; 76.4% of patients could be defined as being 'probable cases' for depression and 66.2% for anxiety. The mean total score of VAS-pain in the last week was 42.9 ± 27.1, with highest scores reported in the 'interference of pain with daily activities' and in 'amount of time patient was awake and had pain'. From SF-36, the worst health status was found for role limitations due to emotional problem, mental health and social functioning. A mean score < 50 (that is, below the standardised population norm) was also found in all remaining domains. The SF-36 summary scores and EQ-5D (health status and VAS) were lower in patients with moderate/severe pain than in those with no or mild pain. Conclusion The baseline results of patients enrolled in the FINDER study in Italy show clinical and functional impairments, and poor HRQoL. The results obtained after 6 months of therapy will permit better understanding the effects of different variables on clinical outcomes and HRQoL. PMID:19480684

Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis.

PubMed

Cipriani, Andrea; Zhou, Xinyu; Del Giovane, Cinzia; Hetrick, Sarah E; Qin, Bin; Whittington, Craig; Coghill, David; Zhang, Yuqing; Hazell, Philip; Leucht, Stefan; Cuijpers, Pim; Pu, Juncai; Cohen, David; Ravindran, Arun V; Liu, Yiyun; Michael, Kurt D; Yang, Lining; Liu, Lanxiang; Xie, Peng

2016-08-27

Major depressive disorder is one of the most common mental disorders in children and adolescents. However, whether to use pharmacological interventions in this population and which drug should be preferred are still matters of controversy. Consequently, we aimed to compare and rank antidepressants and placebo for major depressive disorder in young people. We did a network meta-analysis to identify both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LiLACS, regulatory agencies' websites, and international registers for published and unpublished, double-blind randomised controlled trials up to May 31, 2015, for the acute treatment of major depressive disorder in children and adolescents. We included trials of amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine. Trials recruiting participants with treatment-resistant depression, treatment duration of less than 4 weeks, or an overall sample size of less than ten patients were excluded. We extracted the relevant information from the published reports with a predefined data extraction sheet, and assessed the risk of bias with the Cochrane risk of bias tool. The primary outcomes were efficacy (change in depressive symptoms) and tolerability (discontinuations due to adverse events). We did pair-wise meta-analyses using the random-effects model and then did a random-effects network meta-analysis within a Bayesian framework. We assessed the quality of evidence contributing to each network estimate using the GRADE framework. This study is registered with PROSPERO, number CRD42015016023. We deemed 34 trials eligible, including 5260 participants and 14 antidepressant treatments. The quality of evidence was rated as very low in most comparisons. For efficacy, only fluoxetine was statistically significantly more effective than placebo (standardised mean difference -0·51, 95% credible interval [CrI] -0·99 to -0·03). In terms of tolerability, fluoxetine was also better than duloxetine (odds ratio [OR] 0·31, 95% CrI 0·13 to 0·95) and imipramine (0·23, 0·04 to 0·78). Patients given imipramine, venlafaxine, and duloxetine had more discontinuations due to adverse events than did those given placebo (5·49, 1·96 to 20·86; 3·19, 1·01 to 18·70; and 2·80, 1·20 to 9·42, respectively). In terms of heterogeneity, the global I(2) values were 33·21% for efficacy and 0% for tolerability. When considering the risk-benefit profile of antidepressants in the acute treatment of major depressive disorder, these drugs do not seem to offer a clear advantage for children and adolescents. Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated. National Basic Research Program of China (973 Program). Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantitative Prediction of Drug–Drug Interactions Involving Inhibitory Metabolites in Drug Development: How Can Physiologically Based Pharmacokinetic Modeling Help?

PubMed Central

Chen, Y; Mao, J; Lin, J; Yu, H; Peters, S; Shebley, M

2016-01-01

This subteam under the Drug Metabolism Leadership Group (Innovation and Quality Consortium) investigated the quantitative role of circulating inhibitory metabolites in drug–drug interactions using physiologically based pharmacokinetic (PBPK) modeling. Three drugs with major circulating inhibitory metabolites (amiodarone, gemfibrozil, and sertraline) were systematically evaluated in addition to the literature review of recent examples. The application of PBPK modeling in drug interactions by inhibitory parent–metabolite pairs is described and guidance on strategic application is provided. PMID:27642087

Informing hot flash treatment decisions for breast cancer survivors: a systematic review of randomized trials comparing active interventions.

PubMed

Johns, Claire; Seav, Susan M; Dominick, Sally A; Gorman, Jessica R; Li, Hongying; Natarajan, Loki; Mao, Jun James; Irene Su, H

2016-04-01

Patient-centered decision making about hot flash treatments often incorporates a balance of efficacy and side effects in addition to patient preference. This systematic review examines randomized controlled trials (RCTs) comparing at least two non-hormonal hot flash treatments in breast cancer survivors. In July 2015, PubMed, SCOPUS, CINAHL, Cochrane, and Web of Science databases were searched for RCTs comparing active, non-hormonal hot flash treatments in female breast cancer survivors. Thirteen trials were included after identifying 906 potential studies. Four trials were dose comparison studies of pharmacologic treatments citalopram, venlafaxine, gabapentin, and paroxetine. Hot flash reduction did not differ by tamoxifen or aromatase inhibitor use. Citalopram 10, 20, and 30 mg daily had comparable outcomes. Venlafaxine 75 mg daily improved hot flashes without additional side effects from higher dosing. Gabapentin 900 mg daily improved hot flashes more than 300 mg. Paroxetine 10 mg daily had fewer side effects than 20 mg. Among four trials comparing different pharmacologic treatments, venlafaxine alleviated hot flash symptoms faster than clonidine; participants preferred venlafaxine over gabapentin. Five trials compared pharmacologic to non-pharmacologic treatments. Acupuncture had similar efficacy to venlafaxine and gabapentin but may have longer durability after completing treatment and fewer side effects. We could not perform a pooled meta-analysis because outcomes were not reported in comparable formats. Clinical trial data on non-hormonal hot flash treatments provide comparisons of hot flash efficacy and other patient important outcomes to guide clinical management. Clinicians can use the information to help patients select hot flash interventions.

Treatment of panic in chest pain patients from emergency departments: efficacy of different interventions focusing on panic management.

PubMed

Marchand, André; Belleville, Geneviève; Fleet, Richard; Dupuis, Gilles; Bacon, Simon L; Poitras, Julien; Chauny, Jean-Marc; Vadeboncoeur, Alain; Lavoie, Kim L

2012-01-01

The aim was to assess the efficacy of two brief cognitive-behavioral therapy (CBT)-based interventions (7×1-h sessions and 1×2-h session) and a pharmacological treatment (paroxetine), compared to supportive usual care, initiated in the emergency department (ED) for individuals suffering from panic disorder (PD) with a chief complain of noncardiac chest pain (NCCP). We hypothesized that the interventions would be more efficacious than supportive usual care on all outcomes. A 12-month follow-up study of patients who received a diagnosis of NCCP in the ED and who met diagnostic criteria for PD (n=71) was performed. Assessments included several psychological questionnaires and a structured interview. A series of repeated-measures analyses of variances, using a split-plot design, were conducted, as well as planned comparisons to examine the differences. The seven-session CBT (n=19), one-session panic management (n=24) and pharmacotherapy (n=13) led to greater improvements in PD severity (primary outcome) compared to supportive usual care (n=15) at posttest, and no significant difference was noted between the three active interventions. On the other measures, patients improved in all conditions, and the therapeutic gains were maintained up to 1 year following the visit to the ED. These results suggests that early intervention, in particular seven sessions of CBT, one session of PM or pharmacotherapy (generic paroxetine), should be considered for the treatment of PD patients consulting the ED with a discharge diagnosis of NCCP. Copyright © 2012 Elsevier Inc. All rights reserved.

3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of (/sup 3/H)paroxetine-labeled serotonin uptake sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Battaglia, G.; Yeh, S.Y.; O'Hearn, E.

1987-09-01

This study examines the effects of repeated systemic administration (20 mg/kg s.c., twice daily for 4 days) of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on levels of brain monoamines, their metabolites and on the density of monoamine uptake sites in various regions of rat brain. Marked reductions (30-60%) in the concentration of 5-hydroxyindoleacetic acid were observed in cerebral cortex, hippocampus, striatum, hypothalamus and midbrain at 2 weeks after a 4-day treatment regimen of MDMA or MDA; less consistent reductions in serotonin (5-HT) content were observed in these brain regions. In addition, both MDMA and MDA caused comparable and substantial reductions (50-75%)more » in the density of (/sup 3/H)paroxetine-labeled 5-HT uptake sites in all brain regions examined. In contrast, neither MDMA nor MDA caused any widespread or long-term changes in the content of the catecholaminergic markers (i.e., norepinephrine, dopamine, 3,4 dihydroxyphenylacetic acid and homovanillic acid) or in the number of (/sup 3/H)mazindol-labeled norepinephrine or dopamine uptake sites in the brain regions examined. These data demonstrate that MDMA and MDA cause long-lasting neurotoxic effects with respect to both the functional and structural integrity of serotonergic neurons in brain. Furthermore, our measurement of reductions in the density of 5-HT uptake sites provides a means for quantification of the neurodegenerative effects of MDMA and MDA on presynaptic 5-HT terminals.« less

Depression in Parkinson's disease: symptom improvement and residual symptoms after acute pharmacologic management.

PubMed

Dobkin, Roseanne DeFronzo; Menza, Matthew; Bienfait, Karina L; Gara, Michael; Marin, Humberto; Mark, Margery H; Dicke, Allison; Friedman, Jill

2011-03-01

Parkinson's disease (PD) is frequently complicated by depression and there is a paucity of controlled research that can inform the management of this disabling nonmotor complaint. A randomized controlled trial of nortriptyline, paroxetine, and placebo for the treatment of depression in PD (dPD) was recently completed. The purpose of this article is to describe the baseline pattern of depressive symptom presentation in PD, the specific symptoms of dPD that improve with pharmacotherapy, and the residual symptoms that remain in patients who meet a priori criteria for response or remission after acute treatment (8 weeks). The Departments of Psychiatry and Neurology at Robert Wood Johnson Medical School, New Jersey. : Fifty-two depressed patients (major depression or dysthymia based on Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria) with Parkinson's disease (by research criteria). A randomized controlled trial of nortriptyline, paroxetine, and placebo. The four subscales (core mood, anxiety, insomnia, and somatic) and individual items from the Hamilton Rating Scale for Depression-17 were the focus of this study. These measures were assessed at baseline and Week 8. Baseline depressive symptoms were unrelated to motor functioning. Treatment response was associated with significant improvements in the core mood, anxiety, insomnia, and somatic symptoms seen in dPD. Residual symptoms, such as sadness and loss of interest, persisted in treatment responders in a milder form than was initially present. Antidepressants may influence all symptoms of dPD, including those that share great overlap with the physical disease process. Additional research regarding adjunctive interventions is needed to help optimize the management of dPD.

Serotonergic antidepressants decrease hedonic signals but leave learning signals in the nucleus accumbens unaffected.

PubMed

Graf, Heiko; Metzger, Coraline D; Walter, Martin; Abler, Birgit

2016-01-06

Investigating the effects of serotonergic antidepressants on neural correlates of visual erotic stimulation revealed decreased reactivity within the dopaminergic reward network along with decreased subjective sexual functioning compared with placebo. However, a global dampening of the reward system under serotonergic drugs is not intuitive considering clinical observations of their beneficial effects in the treatment of depression. Particularly, learning signals as coded in prediction error processing within the dopaminergic reward system can be assumed to be rather enhanced as antidepressant drugs have been demonstrated to facilitate the efficacy of psychotherapeutic interventions relying on learning processes. Within the same study sample, we now explored the effects of serotonergic and dopaminergic/noradrenergic antidepressants on prediction error signals compared with placebo by functional MRI. A total of 17 healthy male participants (mean age: 25.4 years) were investigated under the administration of paroxetine, bupropion and placebo for 7 days each within a randomized, double-blind, within-subject cross-over design. During functional MRI, we used an established monetary incentive task to explore neural prediction error signals within the bilateral nucleus accumbens as region of interest within the dopaminergic reward system. In contrast to diminished neural activations and subjective sexual functioning under the serotonergic agent paroxetine under visual erotic stimulation, we revealed unaffected or even enhanced neural prediction error processing within the nucleus accumbens under this antidepressant along with unaffected behavioural processing. Our study provides evidence that serotonergic antidepressants facilitate prediction error signalling and may support suggestions of beneficial effects of these agents on reinforced learning as an essential element in behavioural psychotherapy.

Modulation of attention network activation under antidepressant agents in healthy subjects.

PubMed

Graf, Heiko; Abler, Birgit; Hartmann, Antonie; Metzger, Coraline D; Walter, Martin

2013-07-01

While antidepressants are supposed to exert similar effects on mood and drive via various mechanisms of action, diverging effects are observed regarding side-effects and accordingly on neural correlates of motivation, emotion, reward and salient stimuli processing as a function of the drugs impact on neurotransmission. In the context of erotic stimulation, a unidirectional modulation of attentional functioning despite opposite effects on sexual arousal has been suggested for the selective serotonin reuptake-inhibitor (SSRI) paroxetine and the selective dopamine and noradrenaline reuptake-inhibitor (SDNRI) bupropion. To further elucidate the effects of antidepressant-related alterations of neural attention networks, we investigated 18 healthy males under subchronic administration (7 d) of paroxetine (20 mg), bupropion (150 mg) and placebo within a randomized placebo-controlled cross-over double-blind functional magnetic resonance imaging (fMRI) design during an established preceding attention task. Neuropsychological effects beyond the fMRI-paradigm were assessed by measuring alertness and divided attention. Comparing preceding attention periods of salient vs. neutral pictures, we revealed congruent effects of both drugs vs. placebo within the anterior midcingulate cortex, dorsolateral prefrontal cortex, anterior prefrontal cortex, superior temporal gyrus, anterior insula and the thalamus. Relatively decreased activation in this network was paralleled by slower reaction times in the divided attention task in both verum conditions compared to placebo. Our results suggest similar effects of antidepressant treatments on behavioural and neural attentional functioning by diverging neurochemical pathways. Concurrent alterations of brain regions within a fronto-parietal and cingulo-opercular attention network for top-down control could point to basic neural mechanisms of antidepressant action irrespective of receptor profiles.

Paroxetine exposure skews litter sex ratios in mice suggesting a Trivers–Willard process

PubMed Central

Gaukler, Shannon Marie; Ruff, James Steven; Potts, Wayne K.

2016-01-01

While conducting a toxicity assessment of the antidepressant paroxetine (Paxil®), in wild-derived mice (Mus musculus), we observed that exposed dams (P0) produced female biased litters (32:68 M:F). Though numerous experimental manipulations have induced sex ratio bias in mice, none have assessed the fitness of the offspring from these litters relative to controls. Here, we retrospectively analyze experimentally derived fitness data gathered for the purpose of toxicological assessment in light of 2 leading hypothesis (Trivers–Willard hypothesis [TWH] and cost of reproduction hypothesis [CRH]), seeking to test if this facultative sex ratio adjustment fits into an adaptive framework. Control F1 males were heavier than F1 females, but no differences in mass were detected between exposed F1 males and females, suggesting that exposed dams did not save energy by producing fewer males, despite producing 29.2% lighter litters relative to controls. F1 offspring of both treatments were released into seminatural enclosures where fitness was quantified. In enclosures, the relative reproductive success of F1-exposed males (compared with controls) was reduced by ~20% compared with the relative reproductive success of F1-exposed females. Thus, exposed dams increased their fitness by adjusting litters toward females who were less negatively affected by the exposure than males. Collectively, these data provide less support that the observed sex ratio bias results in energetic savings (CRH), and more support for the TWH because fitness was increased by biasing litters toward female offspring. These mammalian data are unique in their ability to support the TWH through the use of relevant fitness data. PMID:27418753

Predictors of response in generalized social phobia: effect of age of onset.

PubMed

Van Ameringen, Michael; Oakman, Jonathan; Mancini, Catherine; Pipe, Beth; Chung, Henry

2004-02-01

Selective serotonin reuptake inhibitors (SSRIs) are the gold standard for the pharmacological treatment of generalized social phobia (GSP). However, little is known about the predictors of response to treatment. Two hundred and four outpatients with GSP were randomized to sertraline (Zoloft) or placebo, for a 20-week double-blind study, with a flexible dose range of sertraline 50 to 200 mg/d. Response was defined as the percentage of patients with a Clinical Global Impression-Improvement scale (CGI-I) of 1 (very much improved) or 2 (much improved). Outcome analyses were conducted using regression models including treatment group as a categorical predictor and study visit as a repeated measure. Dependent measures included Marks Fear Questionnaire (MFQ), Brief Social Phobia Scale (BSPS), CGI-I, and Sheehan Disability Scale (SDS). We investigated several possible predictors of response to treatment including DSM-IV comorbidity, age, sex, age of onset of GSP, and duration of illness. Patients with later-onset (especially adult-onset) GSP tend to have a better response to treatment than those with earlier-onset GSP. This result generally appears in our analyses as a 2-way interaction, where the association with response is greatest for patients with adult-onset GSP (in contrast to those with child or adolescent onset). This finding is most robust for symptom measures, but is still apparent for the Sheehan measure of disability at work. This advantage for later-onset GSP can be accounted for neither by severity of illness nor by duration of illness. Superior treatment outcome for later-onset GSP may be mediated by the degree of social and family disability.

Kefir protective effects against nicotine cessation-induced anxiety and cognition impairments in rats.

PubMed

Noori, Negin; Bangash, Mohammad Yasan; Motaghinejad, Majid; Hosseini, Pantea; Noudoost, Behshad

2014-01-01

Nicotine as one of the potent psychostimulant drugs is characterized by its parasympathomimetic activity. Upon the abrupt discontinuation of nicotine intake, a number of symptoms such as anxiety, depression and cognition impairment develop. Kefir as a food supplement is rich in tryptophan. In this study, we have evaluated the effects of Kefir on nicotine cessation-induced anxiety, depression and cognition impairment. Forty adult male rats were divided into four groups. All the groups received 6 mg/kg/day of nicotine for 17 days and then the negative control groups got 5 mg/kg/day of normal saline. The positive control groups were given 40 mg/kg/day of Sertraline HCl for 7 days. The group treated with Cow Milk Kefir (CMK) and Soy Milk Kefir (SMK) received 5 mg/kg/day for 7 days. On the 25(th) day, Elevated Plus Maze (EPM), Open Field Test (OFT) and Forced Swim Test (FST) were used to investigate anxiety and depression. In addition, Moris Water Maze was applied to evaluate learning and memory in the animals between the 20(th) and 25(th) days. The results showed that administration of CMK, SMK and Sertraline had higher anti-depression and anxiolytic effects on nicotine withdrawal-induced depression and anxiety in rats (P < 0.05). Moreover, CMK and SMK improved learning and memory impairment results in the nicotine withdrawal period (P < 0.05). This study revealed that Kefir had a potential effect on the treatment of nicotine cessation-induced depression, anxiety and cognition impairment in the animal model. Kefir may be useful for adjunct therapy for nicotine abandonment treatment protocols.

Do early changes in the HAM-D-17 anxiety/somatization factor items affect the treatment outcome among depressed outpatients? Comparison of two controlled trials of St John's wort (Hypericum perforatum) versus a SSRI.

PubMed

Bitran, Stella; Farabaugh, Amy H; Ameral, Victoria E; LaRocca, Rachel A; Clain, Alisabet J; Fava, Maurizio; Mischoulon, David

2011-07-01

To assess whether early changes in Hamilton Depression Rating Scale-17 anxiety/somatization items predict remission in two controlled studies of Hypericum perforatum (St John's wort) versus selective serotonin reuptake inhibitors for major depressive disorder. The Hypericum Depression Trial Study Group (National Institute of Mental Health) randomized 340 patients to Hypericum, sertraline, or placebo for 8 weeks, whereas the Massachusetts General Hospital study randomized 135 patients to Hypericum, fluoxetine, or placebo for 12 weeks. The investigators examined whether remission was associated with early changes in anxiety/somatization symptoms. In the National Institute of Mental Health study, significant associations were observed between remission and early improvement in the anxiety (psychic) item (sertraline arm), somatic (gastrointestinal item; Hypericum arm), and somatic (general) symptoms (placebo arm). None of the three treatment arms of the Massachusetts General Hospital study showed significant associations between anxiety/somatization symptoms and remission. When both study samples were pooled, we found associations for anxiety (psychic; selective serotonin reuptake inhibitors arm), somatic (gastrointestinal), and hypochondriasis (Hypericum arm), and anxiety (psychic) and somatic (general) symptoms (placebo arm). In the entire sample, remission was associated with the improvement in the anxiety (psychic), somatic (gastrointestinal), and somatic (general) items. The number and the type of anxiety/somatization items associated with remission varied depending on the intervention. Early scrutiny of the Hamilton Depression Rating Scale-17 anxiety/somatization items may help to predict remission of major depressive disorder.

The effects of sertraline administration from adolescence to adulthood on physiological and emotional development in prenatally stressed rats of both sexes

PubMed Central

Pereira-Figueiredo, Inês; Sancho, Consuelo; Carro, Juan; Castellano, Orlando; López, Dolores E.

2014-01-01

Sertraline (SERT) is a clinically effective Selective Serotonin Reuptake Inhibitor (SSRI) known to increase and stabilize serotonin levels. This neurotransmitter plays an important role in adolescent brain development in both rodents and humans, and its dysregulation has been correlated with deficits in behavior and emotional regulation. Since prenatal stress may disturb serotoninergic homeostasis, the aim of this study was to examine the long-lasting effects of exposure to SERT throughout adolescence on behavioral and physiological developmental parameters in prenatally stressed Wistar rats. SERT was administered (5 mg/kg/day p.o.) from the age of 1–3 months to half of the progeny, of both sexes, of gestating dams stressed by use of a restraint (PS) or not stressed. Our data reveal that long-term SERT treatment slightly reduced weight gain in both sexes, but reversed the developmental disturbed “catch-up” growth found in PS females. Neither prenatal stress nor SERT treatment induced remarkable alterations in behavior and had no effects on mean startle reflex values. However, a sex-dependent effects of PS was found: in males the PS paradigm slightly increased anxiety-like behavior in the open field, while in females, it impaired startle habituation. In both cases, SERT treatment reversed the phenomena. Additionally, the PS animals exhibited a disturbed leukocyte profile in both sexes, which was reversed by SERT. The present findings are evidence that continuous SERT administration from adolescence through adulthood is safe in rodents and lessens the impact of prenatal stress in rats. PMID:25147514

Obsessions appear after the removal a brain tumor in the right frontal lobe.

PubMed

Liu, Jie; Zhang, Xinhua; Liu, Jihua

2014-01-01

A series of case reports and neuroimaging research points to the underlying neuropathological substrate for obsessive-compulsive disorder (OCD) and the underlying associations between OCD and areas of the frontal lobe. We report a patient wherein the onset of OCD occurred after resection of meningioma of the right frontal lobe and who was treated successfully with paroxetine hydrochloride. We suggest that the onset of secondary (organic) OCD is associated with the frontal lobe, and we propose that the origin of obsessions is located in the right frontal lobe. Copyright © 2014 Elsevier Inc. All rights reserved.

Environmental risk assessment of paroxetine.

PubMed

Cunningham, Virginia L; Constable, David J C; Hannah, Robert E

2004-06-15

Paroxetine hydrochloride hemihydrate (the active ingredient in Paxil) is a pharmaceutical compound used for the treatment of depression, social anxiety disorder, obsessive compulsive disorder, panic disorder, and generalized anxiety disorder. Paroxetine (PA) is extensively metabolized in humans, with about 97% of the parent compound being excreted as metabolites through the urine and feces of patients. Therefore PA and metabolites have the potential to be discharged into wastewater treatment systems after therapeutic use. PA and its major human metabolite (PM) were investigated using studies designed to describe physical/chemical characteristics and determine their fate and effects in the aquatic environment. A significant portion of the PM entering a wastewater treatment plant would be expected to biodegrade given the higher activated sludge solids concentrations present in a typical wastewater treatment plant. The potential for direct photolysis of PM is also possible based on photolysis results for PA itself. These results provide strong support for expecting that PA and PM residuals will not persist in the aquatic environment after discharge from a wastewater treatment facility. This conclusion is also supported by the results of a USGS monitoring study, where no PM was detected in any of the samples at the 260 ng/L reporting limit. The results presented here also demonstrate the importance of understanding the human metabolism of a pharmaceutical so that the appropriate molecule(s) is used for fate and effects studies. In addition to the PA fate studies, PM was investigated using studies designed to determine potential environmental effects and a predicted no effect level (PNEC). The average measured activated sludge respiration inhibition value (EC50) for PM was 82 mg/L. The measured Microtox EC50 value was 33.0 mg/L, while the Daphnia magna EC50 value was 35.0 mg/L. The PNEC for PM was calculated to be 35.0 microg/L. Fate data were then used in a new watershed-based environmental risk assessment model, PhATE, to predict environmental concentrations (PECs). Comparison of the calculated PECs with the PNEC allows an assessment of potential environmental risk. Within the 1-99% of stream segments in the PhATE model, PEC values ranged from 0.003 to 100 ng/L. The risk assessment PEC/PNEC ratios ranged from approximately 3 x 10(-8) to approximately 3 x 10(-3), indicating a wide margin of safety, since a PEC/PNEC ratio <1 is generally considered to represent a low risk to the environment. In addition, Microtox studies carried out on PM biodegradation byproducts indicated no detectable residual toxicity. Any compounds in the environment as a result of the biodegradation of PM should be innocuous polar byproducts that should not exert any toxic effects.

Emerging Hyperprolactinemic Galactorrhea in Obsessive Compulsive Disorder with a Stable Dose of Fluoxetine.

PubMed

Chatterjee, Seshadri Sekhar; Mitra, Sayantanava; Mallik, Nitu

2015-12-31

While fluoxetine (FXT) is a frequently prescribed selective serotonin reuptake inhibitor (SSRI), with few major side-effects; altered serotonergic transmissions in hypothalamic pathways might lead to a distressing, and often embarrassing, manifestation of galactorrhea by altering prolactin release in those on FXT. We report here a case of FXT-induced hyperprolactinemic galactorrhea developing late into treatment on a stable regimen, who responded well to subsequent replacement with sertraline. Based on present finding, we suggest that while SSRIs may share similar mechanisms of action, there exist individual differences in their effects on prolactin secretion pathways.

New Spectrofluorimetric Method with Enhanced Sensitivity for Determination of Paroxetine in Dosage Forms and Plasma

PubMed Central

Darwish, Ibrahim A.; Amer, Sawsan M.; Abdine, Heba H.; Al-Rayes, Lama I.

2008-01-01

New simple spectrofluorimetric method with enhanced sensitivity has been developed and validated for the determination of the antidepressant paroxetine (PXT) in its dosage forms and plasma. The method was based on nucleophilic substitution reaction of PXT with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole in an alkaline medium (pH 8) to form a highly fluorescent derivative that was measured at 545 nm after excitation at 490 nm. The factors affecting the reaction was carefully studied and optimized. The kinetics of the reaction was investigated, and the reaction mechanism was presented. Under the optimized conditions, linear relationship with good correlation coefficient (0.9993) was found between the fluorescence intensity and PXT concentration in the range of 80–800 ng ml−1. The limits of detection and quantitation for the method were 25 and 77 ng ml−1, respectively. The precision of the method was satisfactory; the values of relative standard deviations did not exceed 3%. The proposed method was successfully applied to the determination of PXT in its pharmaceutical tablets with good accuracy; the recovery values were 100.2 ± 1.61%. The results obtained by the proposed method were comparable with those obtained by the official method. The proposed method is superior to the previously reported spectrofluorimetric method for determination of PXT in terms of its higher sensitivity and wider linear range. The high sensitivity of the method allowed its successful application to the analysis of PXT in spiked human plasma. The proposed method is practical and valuable for its routine application in quality control and clinical laboratories for analysis of PXT. PMID:19609398

A study of time- and sex-dependent effects of vortioxetine on rat sexual behavior: Possible roles of direct receptor modulation.

PubMed

Li, Yan; Pehrson, Alan L; Oosting, Ronald S; Gulinello, Maria; Olivier, Berend; Sanchez, Connie

2017-07-15

Treatment-related sexual dysfunction is a common side effect of antidepressants and contributes to patient non-compliance or treatment cessation. However, the multimodal antidepressant, vortioxetine, demonstrates low sexual side effects in depressed patients. To investigate the mechanisms involved, sexual behavior was assessed in male and female rats after acute, and repeated (7 and 14 days) treatment with vortioxetine, flesinoxan (a 5-HT 1A receptor agonist), CP-94253 (a 5-HT 1B receptor agonist), or ondansetron (a 5-HT 3 receptor antagonist). These selective ligands were chosen to simulate vortioxetine's direct modulation of these receptors. Paroxetine was also included in the male study. Acute and repeated treatment with vortioxetine at doses corresponding to clinical levels (based on serotonin transporter occupancy) had minimal effects on sexual behavior in male and female rats. High dose vortioxetine plus flesinoxan (to mimic predicted clinical levels of 5-HT 1A receptor occupancy by vortioxetine) facilitated male rat sexual behavior (acutely) while inhibiting female rat proceptive behavior (both acutely and after 14 days treatment). The selective serotonin reuptake inhibitor, paroxetine, inhibited male sexual behavior after repeated administration (7 and 14 days). Flesinoxan alone facilitated male sexual behavior acutely while inhibiting female rat proceptive behavior after repeated administration (7 and 14 days). CP-94253 inhibited sexual behavior in both male and female rats after repeated administration. Ondansetron had no effect on sexual behavior. These findings underline the complex serotonergic regulation of sexual behavior and indicate that the low sexual side effects of vortioxetine found in clinical studies are likely associated with its direct modulation of serotonin receptors. Copyright © 2017. Published by Elsevier Ltd.

Tramadol: Effects on sexual behavior in male rats are mainly caused by its 5-HT reuptake blocking effects.

PubMed

Olivier, Jocelien D A; Esquivel Franco, Diana C; Oosting, Ronald; Waldinger, Marcel; Sarnyai, Zoltan; Olivier, Berend

2017-04-01

Tramadol is a well-known and effective analgesic. Recently it was shown that tramadol is also effective in human premature ejaculation. The inhibitory effect of tramadol on the ejaculation latency is probably due to its mechanism of action as a μ-opioid receptor agonist and noradrenaline/serotonin (5-HT) reuptake inhibitor. In order to test this speculation, we tested several doses of tramadol in a rat model of male sexual behavior and investigated two types of drugs interfering with the μ-opioid and the 5-HT system. First the μ-opioid receptor agonist properties of tramadol were tested with naloxone, a μ-opioid receptor antagonist. Second, the effects of WAY100,635, a 5-HT 1A receptor antagonist, were tested on the behavioral effects of tramadol. Finally the effects of paroxetine, a selective serotonin reuptake inhibitor, combined with naloxone or WAY100,635 treatment, were compared to the effects of tramadol combined with these drugs. Results showed that naloxone, at a sexually inactive dose, could only partially antagonize the inhibitory effect of tramadol. Moreover, low and behaviorally inactive doses of WAY100,635, strongly decreased sexual behavior when combined with a behaviorally inactive dose of tramadol. Finally we showed that the effects of paroxetine on sexual behavior resembled the effects of tramadol, indicating that tramadol's inhibitory effects on sexual behavior are primarily and mainly caused by its SSRI properties and that its μ-opioid receptor agonistic activity only contributes marginally. These findings support the hypothesis that tramadol exerts inhibition of premature ejaculations in men by its 5-HT reuptake inhibiting properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of high-dose fenfluramine treatment on monoamine uptake sites in rat brain: Assessment using quantitative autoradiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Appel, N.M.; Mitchell, W.M.; Contrera, J.F.

1990-01-01

Fenfluramine is an amphetamine derivative that in humans is used primarily as an anorectic agent in the treatment of obesity. In rats, subchronic high-dose d,l-fenfluramine treatment (24 mg/kg subcutaneously, twice daily for 4 days) causes long-lasting decreases in brain serotonin (5HT), its metabolite 5-hydroxyindoleacetic acid, and high-affinity 5HT uptake sites. Moreover, this high-dose treatment regimen causes both selective long-lasting decreases in fine-caliber 5HT-immunoreactive axons and appearance of other 5HT-immunoreactive axons with morphology characteristic of degenerating axons. Determination of the potential neurotoxic effects of fenfluramine treatment using immunohistochemistry is limited from the perspectives that staining is difficult to quantify and thatmore » it relies on presence of the antigen (in this case 5HT), and the 5HT-depleting effects of fenfluramine are well known. In the present study, we used quantitative in vitro autoradiography to assess, in detail, the density and regional distribution of (3H)paroxetine-labeled 5HT and (3H)mazindol-labeled catecholamine uptake sites in response to the high-dose fenfluramine treatment described above. Because monoamine uptake sites are concentrated on monoamine-containing nerve terminals, decreases in uptake site density would provide a quantitative assessment of potential neurotoxicity resulting from this fenfluramine treatment regimen. Marked decreases in densities of (3H)paroxetine-labeled 5HT uptake sites occurred in brain regions in which fenfluramine treatment decreased the density of 5HT-like immunostaining when compared to saline-treated control rats. These included cerebral cortex, caudate putamen, hippocampus, thalamus, and medial hypothalamus.« less

Effects of electro-acupuncture on personality traits in depression: a randomized controlled study.

PubMed

Wang, Wei-dong; Lu, Xue-yu; Ng, Siu-man; Hong, Lan; Zhao, Yang; Lin, Ying-na; Wang, Fang

2013-10-01

To explore the personality-adjusting effect of electro-acupuncture treatment for depression and compared this treatment with paroxetine treatment. A non-blinded, randomized controlled trial was adopted. Sixty depressed patients, who met trial criteria, were randomly assigned to the treatment and the control groups. In the treatment group, electro-acupuncture treatment was used, and paroxetine treatment was used in the control group. During the 24-week study period, 12 patients dropped out and 48 patients completed the study. The Minnesota Multiple Personality Inventory (MMPI) was adopted as the evaluation tool. At the same time, the Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS) and Montgomery-Asberg Depression Rating Scale (MADRS) were used to evaluate the psychological state. Evaluations were done before and after treatment. After treatment, patients' psychological state improved significantly in both groups (P<0.01). For the treatment group, within-group comparison between baseline and after 24 weeks of treatment showed that severity of depression had significantly decreased (P<0.01). MADRS and SDS scores decreased significantly (P<0.05) and MMPI subscale scores for hypochondriasis, depression, psychopathic deviate, psychasthenia, social introversion and fake decreased significantly (P<0.05). For the control group, severity of depression also decreased significantly. MADRS and SDS scores decreased significantly (P<0.05); and MMPI subscale scores for hypochondriasis, depression, hysteria, paranoia, and psychasthenia decreased significantly (P<0.05). Between-group comparison demonstrated that for the MMPI subscales paranoia and social introversion, the decrease of score was greater in the treatment group than in the control group (P<0.05). However, there were no other significant differences between the control group and the treatment group. Electro-acupuncture is effective for treating depression and affects personality traits.

The usefulness and scientific accuracy of private sector Arabic language patient drug information leaflets.

PubMed

Sukkari, Sana R; Al Humaidan, Abdullah S; Sasich, Larry D

2012-07-01

Inadequate access to useful scientifically accurate patient information is a major cause of the inappropriate use of drugs resulting in serious personal injury and related costs to the health care system. The definition of useful scientifically accurate patient information for prescription drugs was accepted by the US Secretary of the Department of Health and Human Services in 1996 as that derived from or consistent with the US FDA approved professional product label for a drug. Previous quality content studies found that English language patient drug information leaflets distributed by US pharmacies failed to meet minimum criteria defining useful and scientifically accurate information. Evaluation forms containing the explicit elements that define useful scientifically accurate information for three drugs with known serious adverse drug reactions were created based on the current US FDA approved professional product labels. The Arabic language patient drug information leaflets for celecoxib, paroxetine, and lamotrigine were obtained locally and evaluated using a methodology similar to that used in previous quality content patient drug information studies in the US. The Arabic leaflets failed to meet the definition of useful scientifically accurate information. The celecoxib leaflet contained 30% of the required information and the paroxetine and lamotrigine leaflets contained 24% and 20%, respectively. There are several limitations to this study. The Arabic leaflets from only one commercial North American vendor were evaluated and the evaluation included a limited number of drugs. A larger study is necessary to be able to generalize these results. The study results are consistent with those of previous quality content studies of commercially available English patient drug information leaflets. The results have important implications for patients as access to a reliable source of drug information may prevent harm or limit the suffering from serious adverse drug reactions.

Persistent cerebrovascular effects of MDMA and acute responses to the drug.

PubMed

Ferrington, Linda; Kirilly, Eszter; McBean, Douglas E; Olverman, Henry J; Bagdy, György; Kelly, Paul A T

2006-07-01

Acutely, 3,4,-methylenedioxymethamphetamine (MDMA) induces cerebrovascular dysfunction [Quate et al., (2004)Psychopharmacol., 173, 287-295]. In the longer term the same single dose results in depletion of 5-hydroxytrptamine (5-HT) nerve terminals. In this study we examined the cerebrovascular consequences of this persistent neurodegeneration, and the acute effects of subsequent MDMA exposure, upon the relationship that normally exists between local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu). Dark agouti (DA) rats were pre-treated with 15 mg/kg i.p. MDMA or saline. Three weeks later, rats from each pre-treatment group were treated with an acute dose of MDMA (15 mg/kg i.p.) or saline. Quantitative autoradiographic imaging was used to measure LCBF or LCMRglu with [(14)C]-iodoantipyrine and [(14)C]-2-deoxyglucose, respectively. Serotonergic terminal depletion was assessed using radioligand binding with [(3)H]-paroxetine and immunohistochemistry. Three weeks after MDMA pre-treatment there were significant reductions in densities of 5-HT transporter (SERT)-positive fibres (-46%) and [(3)H]-paroxetine binding (-47%). In animals pre-treated with MDMA there were widespread significant decreases in LCMRglu, but no change in LCBF indicating a persistent loss of cerebrovascular constrictor tone. In both pre-treatment groups, acute MDMA produced significant increases in LCMRglu, while LCBF was significantly decreased. In 50% of MDMA-pre-treated rats, random areas of focal hyperaemia indicated a loss of autoregulatory capacity in response to MDMA-induced hypertension. These results suggest that cerebrovascular regulatory dysfunction resulting from acute exposure to MDMA is not diminished by previous exposure, despite a significant depletion in 5-HT terminals. However, there may be a sub-population, or individual circumstances, in which this dysfunction develops into a condition that might predispose to stroke.

Chronic paroxetine treatment prevents disruption of methamphetamine-sensitive circadian oscillator in a transgenic mouse model of Huntington's disease.

PubMed

Ouk, Koliane; Aungier, Juliet; Cuesta, Marc; Morton, A Jennifer

2018-03-15

Circadian abnormalities seen in Huntington's disease (HD) patients are recapitulated in several HD transgenic mouse models. In mice, alongside the master clock located in the suprachiasmatic nucleus (SCN), two other oscillators may influence circadian behaviour. These are the food-entrainable oscillator (FEO) and the methamphetamine-sensitive circadian oscillator (MASCO). SCN- and MASCO- (but not FEO-) driven rhythms are progressively disrupted in the R6/2 mouse model of HD. MASCO-driven rhythms are induced by chronic treatment with low dose of methamphetamine and characterised by an increase in period length to greater than 24 h. Interestingly, the rhythms mediated by MASCO deteriorate earlier than those mediated by the SCN in R6/2 mice. Here, we used a pharmacological strategy to investigate the mechanisms underlying MASCO-driven rhythms in WT mice. In contrast to methamphetamine, chronic cocaine was ineffective in generating a MASCO-like component of activity although it markedly increased locomotion. Furthermore, neither blocking dopamine (DA) receptors (with the DA antagonist haloperidol) nor blocking neurotransmission by inhibiting the activity of vesicular monoamine transporter (with reserpine) prevented the expression of the MASCO-driven rhythms, although both treatments downregulated locomotor activity. Interestingly, chronic treatment with paroxetine, a serotonin-specific reuptake inhibitor commonly used as antidepressant in HD, was able to restore the expression of MASCO-driven rhythms in R6/2 mice. Thus, MASCO-driven rhythms appear to be mediated by both serotoninergic and dopaminergic systems. This supports the idea that abnormalities in MASCO output may contribute to both the HD circadian and psychiatric phenotype. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antidepressant-like activity of liposomal formulation containing nimodipine treatment in the tail suspension test, forced swim test and MAOB activity in mice.

PubMed

Moreno, Lina Clara Gayoso E Almendra Ibiapina; Rolim, Hercília Maria Lins; Freitas, Rivelilson Mendes; Santos-Magalhães, Nereide Stela

2016-09-01

Previous studies have shown that intracellular calcium ion dysfunction may be an etiological factor in affective illness. Nimodipine (NMD) is a Ca(2+) channel blocker that has been extensively investigated for therapy of central nervous system (CNS) disorders. In this work, we have evaluated the antidepressant-like activity of nimodipine encapsulated into liposomes (NMD-Lipo) in mice through tail suspension and forced swim assays, as well as MAOB activity. During the tail suspension test, the administration of NMD-Lipo at 0.1, 1 and 10mg/kg was able to promote a reduction in the immobility time of animals greater than the positive control (imipramine). In the forced swim test, the immobility time of mice treated with NMD-Lipo was reduced. This reduction was significantly greater than that found in the animals treated with imipramine and paroxetine. This may suggest that NMD-Lipo provides more antidepressant-like activity than in positive controls. The groups that received a combination of liposomal NMD and antidepressant drugs showed lower immobility time than the groups, which were treated only with imipramine or paroxetine. The mice treated with the combination of NMD-Lipo and reserpine presented an increase in the time of immobility compared with animals treated only with NMD-Lipo. There was a significant decrease in MAOB activity in animals treated with NMD-Lipo compared with untreated animals. The results of the tail suspension test, forced swim test and MAOB activity suggested that the antidepressant activity of NMD-Lipo may be related to an increase in the cerebral monoamine concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

MicroRNA-Mediated Regulation of ITGB3 and CHL1 Is Implicated in SSRI Action

PubMed Central

Oved, Keren; Farberov, Luba; Gilam, Avial; Israel, Ifat; Haguel, Danielle; Gurwitz, David; Shomron, Noam

2017-01-01

Background: Selective serotonin reuptake inhibitor (SSRI) antidepressant drugs are the first-line of treatment for major depressive disorder (MDD) but are effective in <70% of patients. Our earlier genome-wide studies indicated that two genes encoding for cell adhesion proteins, close homolog of L1 (CHL1) and integrin beta-3 (ITGB3), and microRNAs, miR-151a-3p and miR-221/222, are implicated in the variable sensitivity and response of human lymphoblastoid cell lines (LCL) from unrelated individuals to SSRI drugs. Methods: The microRNAs miR-221, miR-222, and miR-151-a-3p, along with their target gene binding sites, were explored in silico using miRBase, TargetScan, microRNAviewer, and the UCSC Genome Browser. Luciferase reporter assays were conducted for demonstrating the direct functional regulation of ITGB3 and CHL1 expression by miR-221/222 and miR-151a-3p, respectively. A human LCL exhibiting low sensitivity to paroxetine was utilized for studying the phenotypic effect of CHL1 regulation by miR-151a-3p on SSRI response. Results: By showing direct regulation of CHL1 and ITGB3 by miR-151a-3p and miR-221/222, respectively, we link these microRNAs and genes with cellular SSRI sensitivity phenotypes. We report that miR-151a-3p increases cell sensitivity to paroxetine via down-regulating CHL1 expression. Conclusions: miR-151a-3p, miR-221/222 and their (here confirmed) respective target-genes, CHL1 and ITGB3, are implicated in SSRI responsiveness, and possibly in the clinical response to antidepressant drugs. PMID:29163031

[Neurobiology and pharmacotherapy of social phobia].

PubMed

Aouizerate, B; Martin-Guehl, C; Tignol, J

2004-01-01

Social phobia (also known as social anxiety disorder) is still not clearly understood. It was not established as an authentic psychiatric entity until the diagnostic nomenclature of the American Psychiatric Association DSM III in 1980. In recent years, increasing attention among researchers has contributed to provide important information about the genetic, familial and temperamental bases of social phobia and its neurochemical, neuroendocrinological and neuroanatomical substrates, which remain to be further investigated. Up to date, there have been several findings about the possible influence of variables, including particularly genetic, socio-familial and early temperamental (eg behavioral inhibition) factors that represent risk for the later development of social phobia. Clinical neurobiological studies, based on the use of exogenous compounds such as lactate, CO2, caffeine, epinephrine, flumazenil or cholecystokinin/pentagastrin to reproduce naturally occurring phobic anxiety, have shown that patients with social phobia appear to exhibit an intermediate sensitivity between patients with panic disorder and control subjects. No difference in the rate of panic attacks in response to lactate, low concentrations of CO2 (5%), epinephrine or flumazenil was observed between patients with social phobia and normal healthy subjects, both being less reactive compared to patients with panic disorder. However, patients with social phobia had similar anxiety reactions to high concentrations of CO2 (35%), caffeine or cholecystokinin/pentagastrin than those seen in patients with panic disorder, both being more intensive than in controls. Several lines of evidence suggest specific neurotransmitter system alterations in social phobia, especially with regard to the serotoninergic, noradrenergic and dopaminergic systems. Although no abnormality in platelet serotonin transporter density has been found, patients with social phobia appear to show an enhanced sensitivity of both post-synaptic 5HT1A and 5HT2 serotonin receptor subtypes, as reflected by increased anxiety and hormonal responses to serotoninergic probes. Platelet 5HT2 receptor density has also been reported to be positively correlated to symptom severity in patients with social phobia. During anticipation of public speaking, heart rate was elevated in patients with social phobia compared to controls. Norepinephrine response to the orthostatic challenge test or to the Valsalva maneuver was also greater in patients with social phobia. While normal beta-adrenergic receptor number was observed in lymphocytes, a blunted response of growth hormone to clonidine, an a2-adrenergic agonist, was reported. This suggests reduced post-synaptic a2-adrenergic receptor functioning related to norepinephrine overactivity in social phobia. Decreased cerebrospinal fluid levels of the dopamine metabolite homovanillic acid have also been observed. There are relatively few reports of involvement of the adrenal and thyroid functions in social phobia, and all that has been noted is that patients with social phobia show an exaggerated adrenocortical response to a psychological stressor. Recent advances in neuro-imaging have contributed to find low striatal dopamine D2 receptor binding or low dopamine transporter site density in patients with social phobia. They have also demonstrated the involvement of the cortico-limbic pathways, including the prefrontal cortex, hippocampus and amygdala, which show an increased activity in different experimental conditions. These brain regions have extensively been reported to play an important role in the cognitive appraisal in determining the significance of environmental stimuli, in the emotional and mnemonic integration of information, and in the expression of contextual fear-conditioned behaviors, which might be disrupted in the light of the phenomelogical aspects of social phobia. A substantial body of literature based on case reports, open and placebo-controlled trials, has now clearly examined the efficacy of major classes of psychotropic agents including monoamine oxidase inhibitors, beta-blockers, selective serotonin reuptake inhibitors and benzodiazepines in social phobia. Until recently, irreversible non-selective monoamine oxidase inhibitors, of which phenelzine was the most extensively evaluated, were considered as the most efficacious treatment in reducing the symptomatology associated with social phobia in 50-70% of cases after 4 to 6 weeks. However, side effects and dietary restrictions limit their use. This led to the development of reversible inhibitors of monoamine oxidase A, for which careful dietary monitoring is not required. Moclobemide has been the most widely studied but produced unconvincingly therapeutic effects on social phobic symptoms. To date, selective serotonin reuptake inhibitors may be considered as a reasonable first-line pharmacotherapy for social phobia. There is growing evidence for the efficacy of the selective serotonin reuptake inhibitors fluvoxamine, fluoxetine, citalopram, paroxetine and sertraline. They have beneficial effects with response rates ranging from 50 to 80% in social phobia. It has been recommended that the treatment period should be extended at least 6 months beyond the early improvement achieved within the first 4 to 6 weeks. The overall advantages include tolerability with a low risk of adverse events. The benzodiazepines clonazepam and alprazolam have also been proposed for the treatment of social phobia. Symptomatic relief occurred in 40 to 80% of the cases with a relatively rapid onset of action within the first two weeks. Untoward effects, discontinuation-related withdrawal symptoms and abuse or dependence liability constitute major concerns about the use of benzodiazepines, so they should be reserved for cases unresponsive to the safer medications cited above. Beta-blockers such as atenolol and propanolol have commonly been employed in performance anxiety, decreasing autonomic symptoms (eg, tachycardia, sweating and dry mouth). However, they are not effective in the generalized form of social phobia. Other pharmacologic alternatives seem helpful for the management of social phobia, including venlafaxine, gabapentin, bupropion, nefazodone or augmentation with buspirone. Preliminary studies point to promising effects of these agents. Larger controlled clinical trials are now needed to confirm their potential role in the treatment of social phobia.

Occurrence of pharmaceuticals and personal care products in fish: results of a national pilot study in the United States.

PubMed

Ramirez, Alejandro J; Brain, Richard A; Usenko, Sascha; Mottaleb, Mohammad A; O'Donnell, John G; Stahl, Leanne L; Wathen, John B; Snyder, Blaine D; Pitt, Jennifer L; Perez-Hurtado, Pilar; Dobbins, Laura L; Brooks, Bryan W; Chambliss, C Kevin

2009-12-01

Pharmaceuticals and personal care products are being increasingly reported in a variety of biological matrices, including fish tissue; however, screening studies have presently not encompassed broad geographical areas. A national pilot study was initiated in the United States to assess the accumulation of pharmaceuticals and personal care products in fish sampled from five effluent-dominated rivers that receive direct discharge from wastewater treatment facilities in Chicago, Illinois; Dallas, Texas; Orlando, Florida; Phoenix, Arizona; and West Chester, Pennsylvania, USA. Fish were also collected from the Gila River, New Mexico, USA, as a reference condition expected to be minimally impacted by anthropogenic influence. High performance liquid chromatography-tandem mass spectrometry analysis of pharmaceuticals revealed the presence of norfluoxetine, sertraline, diphenhydramine, diltiazem, and carbamazepine at nanogram-per-gram concentrations in fillet composites from effluent-dominated sampling locations; the additional presence of fluoxetine and gemfibrozil was confirmed in liver tissue. Sertraline was detected at concentrations as high as 19 and 545 ng/g in fillet and liver tissue, respectively. Gas chromatography-tandem mass spectrometry analysis of personal care products in fillet composites revealed the presence of galaxolide and tonalide at maximum concentrations of 2,100 and 290 ng/g, respectively, and trace levels of triclosan. In general, more pharmaceuticals were detected at higher concentrations and with greater frequency in liver than in fillet tissues. Higher lipid content in liver tissue could not account for this discrepancy as no significant positive correlations were found between accumulated pharmaceutical concentrations and lipid content for either tissue type from any sampling site. In contrast, accumulation of the personal care products galaxolide and tonalide was significantly related to lipid content. Results suggest that the detection of pharmaceuticals and personal care products was dependent on the degree of wastewater treatment employed.

Sequenced treatment alternatives to relieve depression (STAR*D): rationale and design.

PubMed

Rush, A John; Fava, Maurizio; Wisniewski, Stephen R; Lavori, Philip W; Trivedi, Madhukar H; Sackeim, Harold A; Thase, Michael E; Nierenberg, Andrew A; Quitkin, Frederic M; Kashner, T Michael; Kupfer, David J; Rosenbaum, Jerrold F; Alpert, Jonathan; Stewart, Jonathan W; McGrath, Patrick J; Biggs, Melanie M; Shores-Wilson, Kathy; Lebowitz, Barry D; Ritz, Louise; Niederehe, George

2004-02-01

STAR*D is a multisite, prospective, randomized, multistep clinical trial of outpatients with nonpsychotic major depressive disorder. The study compares various treatment options for those who do not attain a satisfactory response with citalopram, a selective serotonin reuptake inhibitor antidepressant. The study enrolls 4000 adults (ages 18-75) from both primary and specialty care practices who have not had either a prior inadequate response or clear-cut intolerance to a robust trial of protocol treatments during the current major depressive episode. After receiving citalopram (level 1), participants without sufficient symptomatic benefit are eligible for randomization to level 2 treatments, which entail four switch options (sertraline, bupropion, venlafaxine, cognitive therapy) and three citalopram augment options (bupropion, buspirone, cognitive therapy). Those who receive cognitive therapy (switch or augment options) at level 2 without sufficient improvement are eligible for randomization to one of two level 2A switch options (venlafaxine or bupropion). Level 2 and 2A participants are eligible for random assignment to two switch options (mirtazapine or nortriptyline) and to two augment options (lithium or thyroid hormone) added to the primary antidepressant (citalopram, bupropion, sertraline, or venlafaxine) (level 3). Those without sufficient improvement at level 3 are eligible for level 4 random assignment to one of two switch options (tranylcypromine or the combination of mirtazapine and venlafaxine). The primary outcome is the clinician-rated, 17-item Hamilton Rating Scale for Depression, administered at entry and exit from each treatment level through telephone interviews by assessors masked to treatment assignments. Secondary outcomes include self-reported depressive symptoms, physical and mental function, side-effect burden, client satisfaction, and health care utilization and cost. Participants with an adequate symptomatic response may enter the 12-month naturalistic follow-up phase with brief monthly and more complete quarterly assessments.

Effects of Passion Flower Extract, as an Add-On Treatment to Sertraline, on Reaction Time in Patients ‎with Generalized Anxiety Disorder: A Double-Blind Placebo-Controlled Study

PubMed Central

Nojoumi, Mandana; Ghaeli, Padideh; Salimi, Samrand; Sharifi, Ali; Raisi, Firoozeh

2016-01-01

Objective: Because of functional impairment caused by generalized anxiety disorder and due to cognitive side ‎effects of many anti-anxiety agents, in this study we aimed to evaluate the influence of Passion ‎flower standardized extract on reaction time in patients with generalized anxiety disorder.‎ Method: Thirty patients aged 18 to 50 years of age, who were diagnosed with generalized anxiety disorder and ‎fulfilled the study criteria, entered this double-blind placebo-controlled study. Reaction time was ‎measured at baseline and after one month of treatment using computerized software. Correct ‎responses, omission and substitution errors and the mean time of correct responses (reaction time) in ‎both visual and auditory tests were collected. The analysis was performed between the two groups ‎and within each group utilizing SPSS PASW- statics, Version 18. P-value less than 0.05 was ‎considered statistically significant.‎ Results: All the participants were initiated on Sertraline 50 mg/day, and the dosage was increased to 100 ‎mg / day after two weeks. Fourteen patients received Pasipy (Passion Flower) 15 drops three times ‎daily and 16 received placebo concurrently. Inter-group comparison proved no significant difference ‎in any of the test items between assortments while a significant decline was observed in auditory ‎omission errors in passion flower group after on month of treatment using intra-group analysis.‎‎ Conclusion: This study noted that passion flower might be suitable as an add-on in the treatment of generalized ‎anxiety disorder with low side effects. Further studies with longer duration are recommended to ‎confirm the results of this study.‎ PMID:27928252

Preliminary evidence that a functional polymorphism in type 1 deiodinase is associated with enhanced potentiation of the antidepressant effect of sertraline by triiodothyronine.

PubMed

Cooper-Kazaz, Rena; van der Deure, Wendy M; Medici, Marco; Visser, Theo J; Alkelai, Ana; Glaser, Benjamin; Peeters, Robin P; Lerer, Bernard

2009-07-01

Triiodothyronine (T3) is used to potentiate the clinical effect of antidepressant drugs. Inter-individual differences in efficacy may be related to genetically-based variability in thyroid function. DNA was obtained from 64 patients treated with sertraline plus T3 (SERT-T3, N=35) or plus placebo (SERT-PLB, N=29), for 8 weeks. Antidepressant efficacy was rated with the 21 item Hamilton Rating Scale for Depression (HRSD-21). Functional polymorphisms in type 1 (DIO1-C785T, DIO1-A1814G) and type 2 deiodinase (DIO2-Thr92Ala and DIO2-ORFa-Gly3Asp) were genotyped. DIO1-C785T was associated with efficacy of T3 but not placebo supplementation, as indicated by the interaction of treatment, DIO1-C758T genotype and time (p=0.04) and a stronger effect of SERT-T3 among DIO1-758T allele carriers (p=0.01). HRSD-21 scores of DIO1-758T allele carriers declined by 68.7+26.6% (mean+SD) over 8 weeks compared to 42.9+37.8% among non-carriers (p=0.02). DIO1 plays a key-role in T4 to T3 conversion and in clearance of the inactive metabolite, rT3. Previous data associate the DIO1-785T allele with lower DIO1 activity. This is consistent with our observation that responders to T3 supplementation had lower baseline serum T3 levels than non-responders. Depressed patients, who have a genetically determined lower T4 to T3 conversion, may be more likely to benefit from T3 supplementation.

Rescue of IL-1β-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants.

PubMed

Borsini, Alessandra; Alboni, Silvia; Horowitz, Mark A; Tojo, Luis M; Cannazza, Giuseppe; Su, Kuan-Pin; Pariante, Carmine M; Zunszain, Patricia A

2017-10-01

Both increased inflammation and reduced neurogenesis have been associated with the pathophysiology of major depression. We have previously described how interleukin-1 (IL-1) β, a pro-inflammatory cytokine increased in depressed patients, decreases neurogenesis in human hippocampal progenitor cells. Here, using the same human in vitro model, we show how omega-3 (ω-3) polyunsaturated fatty acids and conventional antidepressants reverse this reduction in neurogenesis, while differentially affecting the kynurenine pathway. We allowed neural cells to proliferate for 3days and further differentiate for 7days in the presence of IL-1β (10ng/ml) and either the selective serotonin reuptake inhibitor sertraline (1µM), the serotonin and norepinephrine reuptake inhibitor venlafaxine (1µM), or the ω-3 fatty acids eicosapentaenoic acid (EPA, 10µM) or docosahexaenoic acid (DHA, 10µM). Co-incubation with each of these compounds reversed the IL-1β-induced reduction in neurogenesis (DCX- and MAP2-positive neurons), indicative of a protective effect. Moreover, EPA and DHA also reversed the IL-1β-induced increase in kynurenine, as well as mRNA levels of indolamine-2,3-dioxygenase (IDO); while DHA and sertraline reverted the IL-1β-induced increase in quinolinic acid and mRNA levels of kynurenine 3-monooxygenase (KMO). Our results show common effects of monoaminergic antidepressants and ω-3 fatty acids on the reduction of neurogenesis caused by IL-1β, but acting through both common and different kynurenine pathway-related mechanisms. Further characterization of their individual properties will be of benefit towards improving a future personalized medicine approach. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Kefir protective effects against nicotine cessation-induced anxiety and cognition impairments in rats

PubMed Central

Noori, Negin; Bangash, Mohammad Yasan; Motaghinejad, Majid; Hosseini, Pantea; Noudoost, Behshad

2014-01-01

Background: Nicotine as one of the potent psychostimulant drugs is characterized by its parasympathomimetic activity. Upon the abrupt discontinuation of nicotine intake, a number of symptoms such as anxiety, depression and cognition impairment develop. Kefir as a food supplement is rich in tryptophan. In this study, we have evaluated the effects of Kefir on nicotine cessation-induced anxiety, depression and cognition impairment. Materials and Methods: Forty adult male rats were divided into four groups. All the groups received 6 mg/kg/day of nicotine for 17 days and then the negative control groups got 5 mg/kg/day of normal saline. The positive control groups were given 40 mg/kg/day of Sertraline HCl for 7 days. The group treated with Cow Milk Kefir (CMK) and Soy Milk Kefir (SMK) received 5 mg/kg/day for 7 days. On the 25th day, Elevated Plus Maze (EPM), Open Field Test (OFT) and Forced Swim Test (FST) were used to investigate anxiety and depression. In addition, Moris Water Maze was applied to evaluate learning and memory in the animals between the 20th and 25th days. Results: The results showed that administration of CMK, SMK and Sertraline had higher anti-depression and anxiolytic effects on nicotine withdrawal-induced depression and anxiety in rats (P < 0.05). Moreover, CMK and SMK improved learning and memory impairment results in the nicotine withdrawal period (P < 0.05). Conclusion: This study revealed that Kefir had a potential effect on the treatment of nicotine cessation-induced depression, anxiety and cognition impairment in the animal model. Kefir may be useful for adjunct therapy for nicotine abandonment treatment protocols. PMID:25590029

Cognitive effects of transcranial direct current stimulation in depression: Results from the SELECT-TDCS trial and insights for further clinical trials.

PubMed

Brunoni, André Russowsky; Tortella, Gabriel; Benseñor, Isabela Martins; Lotufo, Paulo Andrade; Carvalho, André Ferrer; Fregni, Felipe

2016-09-15

Cognitive dysfunction treatment remains an unmet clinical need in major depressive disorder (MDD). Transcranial direct current stimulation (tDCS) may improve cognitive symptoms in MDD. Our aim was to investigate the cognitive effects of tDCS in the Sertraline vs. Electric Current Therapy for Treating Depression Clinical Study (SELECT-TDCS). We also explored whether tDCS could have mood-independent cognitive effects. One hundred twenty MDD patients aged from 18 to 65 years received 12 sessions of active/sham tDCS (2mA for 30min) and real/placebo 50mg/d sertraline over 6 weeks in a factorial trial. We analyzed whether changes in performance of neuropsychological tests (Trail Making, Digit Span, Stroop Task, Mini-Mental Status Exam and Montreal Cognitive Assessment) occurred over time, according to treatment group and depression improvement. Exploratory analyses were carried out to verify the influence of clinical and demographic variables on the outcomes. Cognitive improvement was showed in most tests used, although they occurred regardless of intervention type and depression improvement. Further exploratory analyses revealed that clinical response and education level could have mediated pro-cognitive tDCS effects on some of the tests used. The neuropsychological battery used might not have been sensitive to detect tDCS-induced effects on cognition. Lack of simultaneous cognitive training during application may have also limited its cognitive effects. We found no evidence of beneficial or deleterious cognitive effects of tDCS as a treatment for depression. We discussed clinical trial design considerations for further tDCS studies assessing cognitive effects, including sample and outcomes considerations. Copyright © 2016 Elsevier B.V. All rights reserved.

Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn

PubMed Central

Gien, Jason; Roe, Gates; Isenberg, Nicole; Kailey, Jenai; Abman, Steven H.

2013-01-01

Although past studies demonstrate that altered serotonin (5-HT) signaling is present in adults with idiopathic pulmonary arterial hypertension, whether serotonin contributes to the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN) is unknown. We hypothesized that 5-HT contributes to increased pulmonary vascular resistance (PVR) in a sheep model of PPHN and that selective 5-HT reuptake inhibitor (SSRI) treatment increases PVR in this model. We studied the hemodynamic effects of 5-HT, ketanserin (5-HT2A receptor antagonist), and sertraline, an SSRI, on pulmonary hemodynamics of the late gestation fetal sheep with PPHN caused by prolonged constriction of the ductus arteriosis. Brief intrapulmonary infusions of 5-HT increased PVR from 1.0 ± 0.07 (baseline) to 1.4 ± 0.22 mmHg/ml per minute of treatment (P < 0.05). Ketanserin decreased PVR from 1.1 ± 0.15 (baseline) to 0.82 ± 0.09 mmHg/ml per minute of treatment (P < 0.05). Sertraline increased PVR from 1.1 ± 0.17 (baseline) to 1.4 ± 0.17 mmHg/ml per minute of treatment (P = 0.01). In addition, we studied 5-HT production and activity in vitro in experimental PPHN. Compared with controls, pulmonary artery endothelial cells from fetal sheep with PPHN exhibited increased expression of tryptophan hydroxylase 1 and 5-HT production by twofold and 56%, respectively. Compared with controls, 5-HT2A R expression was increased in lung homogenates and pulmonary artery smooth muscle cell lysates by 35% and 32%, respectively. We concluded that increased 5-HT contributes to high PVR in experimental PPHN through activation of the 5-HT2A receptor and that SSRI infusion further increases PVR in this model. PMID:23605003

Effects of Passion Flower Extract, as an Add-On Treatment to Sertraline, on Reaction Time in Patients ‎with Generalized Anxiety Disorder: A Double-Blind Placebo-Controlled Study.

PubMed

Nojoumi, Mandana; Ghaeli, Padideh; Salimi, Samrand; Sharifi, Ali; Raisi, Firoozeh

2016-07-01

Objective: Because of functional impairment caused by generalized anxiety disorder and due to cognitive side ‎effects of many anti-anxiety agents, in this study we aimed to evaluate the influence of Passion ‎flower standardized extract on reaction time in patients with generalized anxiety disorder.‎ Method: Thirty patients aged 18 to 50 years of age, who were diagnosed with generalized anxiety disorder and ‎fulfilled the study criteria, entered this double-blind placebo-controlled study. Reaction time was ‎measured at baseline and after one month of treatment using computerized software. Correct ‎responses, omission and substitution errors and the mean time of correct responses (reaction time) in ‎both visual and auditory tests were collected. The analysis was performed between the two groups ‎and within each group utilizing SPSS PASW- statics, Version 18. P-value less than 0.05 was ‎considered statistically significant.‎ Results: All the participants were initiated on Sertraline 50 mg/day, and the dosage was increased to 100 ‎mg / day after two weeks. Fourteen patients received Pasipy (Passion Flower) 15 drops three times ‎daily and 16 received placebo concurrently. Inter-group comparison proved no significant difference ‎in any of the test items between assortments while a significant decline was observed in auditory ‎omission errors in passion flower group after on month of treatment using intra-group analysis.‎‎ Conclusion: This study noted that passion flower might be suitable as an add-on in the treatment of generalized ‎anxiety disorder with low side effects. Further studies with longer duration are recommended to ‎confirm the results of this study.‎.

Pharmacogenetically driven treatments for alcoholism: are we there yet?

PubMed

Arias, Albert J; Sewell, R Andrew

2012-06-01

Pharmacogenetic analyses of treatments for alcohol dependence attempt to predict treatment response and side-effect risk for specific medications. We review the literature on pharmacogenetics relevant to alcohol dependence treatment, and describe state-of-the-art methods of pharmacogenetic research in this area. Two main pharmacogenetic study designs predominate: challenge studies and treatment-trial analyses. Medications studied include US FDA-approved naltrexone and acamprosate, both indicated for treating alcohol dependence, as well as several investigational (and off-label) treatments such as sertraline, olanzapine and ondansetron. The best-studied functional genetic variant relevant to alcoholism treatment is rs1799971, a single-nucleotide polymorphism in exon 1 of the OPRM1 gene that encodes the μ-opioid receptor. Evidence from clinical trials suggests that the presence of the variant G allele of rs1799971 may predict better treatment response to opioid receptor antagonists such as naltrexone. Evidence from clinical trials also suggests that several medications interact pharmacogenetically with variation in genes that encode proteins involved in dopaminergic and serotonergic neurotransmission. Variation in the DRD4 gene, which encodes the dopamine D(4) receptor, may predict better response to naltrexone and olanzapine. A polymorphism in the serotonin transporter gene SLC6A4 promoter region appears related to differential treatment response to sertraline depending on the subject's age of onset of alcoholism. Genetic variation in SLC6A4 may also be associated with better treatment response to ondansetron. Initial pharmacogenetic efforts in alcohol research have identified functional variants with potential clinical utility, but more research is needed to further elucidate the mechanism of these pharmacogenetic interactions and their moderators in order to translate them into clinical practice.

Evaluation of factors affecting prescribing behaviors, in iran pharmaceutical market by econometric methods.

PubMed

Tahmasebi, Nima; Kebriaeezadeh, Abbas

2015-01-01

Prescribing behavior of physicians affected by many factors. The present study is aimed at discovering the simultaneous effects of the evaluated factors (including: price, promotion and demographic characteristics of physicians) and quantification of these effects. In order to estimate these effects, Fluvoxamine (an antidepressant drug) was selected and the model was figured out by panel data method in econometrics. We found that insurance and advertisement respectively are the most effective on increasing the frequency of prescribing, whilst negative correlation was observed between price and the frequency of prescribing a drug. Also brand type is more sensitive to negative effect of price than to generic. Furthermore, demand for a prescription drug is related with physician demographics (age and sex). According to the results of this study, pharmaceutical companies should pay more attention to the demographic characteristics of physicians (age and sex) and their advertisement and pricing strategies.

Evaluation of Factors Affecting Prescribing Behaviors, in Iran Pharmaceutical Market by Econometric Methods

PubMed Central

Tahmasebi, Nima; Kebriaeezadeh, Abbas

2015-01-01

Prescribing behavior of physicians affected by many factors. The present study is aimed at discovering the simultaneous effects of the evaluated factors (including: price, promotion and demographic characteristics of physicians) and quantification of these effects. In order to estimate these effects, Fluvoxamine (an antidepressant drug) was selected and the model was figured out by panel data method in econometrics. We found that insurance and advertisement respectively are the most effective on increasing the frequency of prescribing, whilst negative correlation was observed between price and the frequency of prescribing a drug. Also brand type is more sensitive to negative effect of price than to generic. Furthermore, demand for a prescription drug is related with physician demographics (age and sex). According to the results of this study, pharmaceutical companies should pay more attention to the demographic characteristics of physicians (age and sex) and their advertisement and pricing strategies. PMID:25901174

Historic condition in a modern child with autism.

PubMed

Berube, Megan; Hubbard, Carol; Mallory, Leah; Larsen, Eric; Morrison, Peter; Augustyn, Marilyn

2013-05-01

Haven is an 11-year-old primary care patient who you have followed since her birth. She was the 9 lb 6 oz product of a 38-week gestation complicated by maternal hypertension and seizure disorder treated with tegretol. Her delivery and neonatal course were uneventful. She was diagnosed with austistic disorder at age 2 years, at which time she used no functional language or gestures, had repetitive motor mannerisms, and limited eye contact. She had strong tactile sensory aversions. Her diet was very restricted including only banana yogurt and drinking milk and apple juice for the first several years of life. She was followed by a developmental-behavioral pediatrician approximately annually through age 8 years and then more frequently. She was healthy other than lead exposure (maximum serum level 18 at age 3 years) and multiple febrile seizures with other possible absence episodes. Her development remained very delayed with use of single words and short phrases. She developed multiple repetitive, anxious, obsessive behaviors (picking up lint, organizing, cleaning, and freezing in certain postures) that were treated with a selective serotonin reuptake inhibitors fluvoxamine. Sensory issues were ongoing, with restrictive eating (primarily peanut butter and jelly sandwiches, cereal bars, milk, and a kiwi-strawberry drink). She took a liquid multivitamin until age 8.At age 11 years, 3 weeks prior to admission, Haven developed acute loss of ambulation over the course of 1 day, initially dragging her right leg, and then refusing to walk and her parents brought her in to see you. She had fever, vomiting, and general weakness. She developed extensive bruising over her legs, especially in the popliteal fossae. She was also noted to have friability and dark discoloration of her gums. Initially, you suspected a post-viral syndrome and close monitoring. She was seen twice in the next 2 weeks in a local emergency room where her erythrocyte sedimentation rate was reported to be elevated and juvenile rheumatoid arthritis or a reaction to fluvoxamine were suspected. Antibiotics were also prescribed for gingivitis. She was seen by an orthopedist who felt it was not an orthopedic issue and leg films were unremarkable. With her second emergency room visit, she was transferred to a tertiary medical center and admitted for further evaluation. Where would you go from here?

Coexistent hypothyroidism, psychosis, and severe obsessions in an adolescent: a 10-year follow-up.

PubMed

Bhatara, Vinod; Alshari, M Ghyath; Warhol, Peter; McMillin, J Michael; Bhatara, Anjali

2004-01-01

This is the first longitudinal report on possible psychosis resulting from the juvenile onset of hypothyroidism. A 10-year follow-up in the case of a 13-year-old boy published in this journal in 1993 is presented. The patient presented with a diagnostic dilemma. Although psychosis resulting from hypothyroidism was the most parsimonious explanation of his symptoms (new-onset auditory hallucinations, severe obsessions, and severe hypothyroidism), a primary psychiatric disorder (obsessive-compulsive disorder [OCD] or psychotic depression) aggravated by hypothyroidism could not be excluded. The aim of this study was to illustrate that the diagnosis and clinical interrelationships can be clarified by longitudinal data. FOLLOW-UP DATA: The patient's symptoms responded optimally to a combination of fluvoxamine, risperidone, and levothyroxine (LT4, 300 microg daily). He was free from severe symptoms until age 21, when he discontinued all psychotropic medications while continuing with LT4. Over 2 months later, he was hospitalized for thoughts of hurting himself or others. In the hospital, his LT4 was discontinued and propranolol was started. He was discharged on multiple psychotropic medications, and was rehospitalized 6 days later for suicide risk. When LT4 (200 microg daily) was added to his psychotropic regimen, he partially responded and was discharged. The optimal response to treatment occurred only after he was placed on a combination of fluoxetine, risperidone, and LT4 (300 microg daily). The patient remained stable for up to 12 months of follow-up. This chronology suggests that the optimal treatment in this patient probably required three components: a Selective Serotonin Reuptake Inhibitor, (SSRI) risperidone, and LT4 (300 g daily). Each component was apparently necessary but not sufficient individually for the optimal response. The relapse after the discontinuation of fluvoxamine and risperidone (but not LT4) suggests the presence of a primary psychiatric disorder (OCD with depression). The failure to improve without an adequate dosage of LT4 suggests that hypothyroidism was probably an aggravating factor. This case illustrates the diagnostic difficulty in distinguishing between obsessions, depressive ruminations, and delusions in children and the need to consider hypothyroidism in the differential diagnosis of the sudden worsening of OCD, or in cases of new-onset psychosis in children and adolescents.

Antidepressants and testicular cancer: cause versus association.

PubMed

Andrade, Chittaranjan

2014-03-01

A data mining study that examined associations between 105 drugs and 55 cancer sites found significant associations between 2 selective serotonin reuptake inhibitors (fluoxetine and paroxetine) and testicular cancer. The study suggested several reasons why these associations merited further investigation. A later study tested specific relationships between 12 antidepressant drugs and testicular cancer and subtypes thereof; whereas significant relationships were again found, these disappeared after adjusting for confounding variables. These 2 studies are educative because they illustrate how false-positive results can easily arise in exploratory research and how confounding may be responsible for statistically significant relationships in study designs that are not randomized controlled trials. © Copyright 2014 Physicians Postgraduate Press, Inc.

Acute Frontal Lobe Dysfunction Following Prefrontal Low-Frequency Repetitive Transcranial Magnetic Stimulation in a Patient with Treatment-Resistant Depression

PubMed Central

Carle, Guilhem; Touat, Mehdi; Bruno, Nicolas; Galanaud, Damien; Peretti, Charles-Siegfried; Valero-Cabré, Antoni; Levy, Richard; Azuar, Carole

2017-01-01

The potential of repetitive transcranial magnetic stimulation (rTMS) to treat numerous neurological and psychiatric disorders has been thoroughly studied for the last two decades. Here, we report for the first time, the case of a 65-year-old woman suffering from treatment-resistant depression who developed an acute frontal lobe syndrome following eight sessions of low-frequency rTMS (LF-rTMS) to the right dorsolateral prefrontal cortex while also treated with sertraline and mianserin. The pathophysiological mechanisms underlying such an unexpected acute frontal lobe dysfunction are discussed in relation to the therapeutic use of LF-rTMS in combination with pharmacotherapy in depressed patients. PMID:28611694

Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter.

PubMed

Cozzi, Nicholas V; Gopalakrishnan, Anupama; Anderson, Lyndsey L; Feih, Joel T; Shulgin, Alexander T; Daley, Paul F; Ruoho, Arnold E

2009-12-01

N,N-dimethyltryptamine (DMT) is a potent plant hallucinogen that has also been found in human tissues. When ingested, DMT and related N,N-dialkyltryptamines produce an intense hallucinogenic state. Behavioral effects are mediated through various neurochemical mechanisms including activity at sigma-1 and serotonin receptors, modification of monoamine uptake and release, and competition for metabolic enzymes. To further clarify the pharmacology of hallucinogenic tryptamines, we synthesized DMT, N-methyl-N-isopropyltryptamine (MIPT), N,N-dipropyltryptamine (DPT), and N,N-diisopropyltryptamine. We then tested the abilities of these N,N-dialkyltryptamines to inhibit [(3)H]5-HT uptake via the plasma membrane serotonin transporter (SERT) in human platelets and via the vesicle monoamine transporter (VMAT2) in Sf9 cells expressing the rat VMAT2. The tryptamines were also tested as inhibitors of [(3)H]paroxetine binding to the SERT and [(3)H]dihydrotetrabenazine binding to VMAT2. Our results show that DMT, MIPT, DPT, and DIPT inhibit [(3)H]5-HT transport at the SERT with K ( I ) values of 4.00 +/- 0.70, 8.88 +/- 4.7, 0.594 +/- 0.12, and 2.32 +/- 0.46 microM, respectively. At VMAT2, the tryptamines inhibited [(3)H]5-HT transport with K ( I ) values of 93 +/- 6.8, 20 +/- 4.3, 19 +/- 2.3, and 19 +/- 3.1 muM, respectively. On the other hand, the tryptamines were very poor inhibitors of [(3)H]paroxetine binding to SERT and of [(3)H]dihydrotetrabenazine binding to VMAT2, resulting in high binding-to-uptake ratios. High binding-to-uptake ratios support the hypothesis that the tryptamines are transporter substrates, not uptake blockers, at both SERT and VMAT2, and also indicate that there are separate substrate and inhibitor binding sites within these transporters. The transporters may allow the accumulation of tryptamines within neurons to reach relatively high levels for sigma-1 receptor activation and to function as releasable transmitters.

Therapeutic options for the management of hot flashes in breast cancer survivors: an evidence-based review.

PubMed

Bordeleau, Louise; Pritchard, Kathleen; Goodwin, Pamela; Loprinzi, Charles

2007-02-01

Women with breast cancer may experience treatment-induced menopausal symptoms or natural menopause. Menopausal symptoms, particularly hot flashes, are reported at a high frequency in this group and tend to be more severe, distressing, and of greater duration than in controls. Because of the contribution of sex hormones to breast cancer, the use of hormonal agents for the control of hot flashes is problematic in these women. Safer nonhormonal alternatives are recommended for this patient group. This was a systematic review of the therapeutic options for the treatment of hot flashes in breast cancer survivors. MEDLINE was searched from 1990 to July 2006 using the disease-specific term breast neoplasms and the subheadings menopause and hot flashes. EMBASE was searched from 1990 to March 2006 using the disease-specific subject headings breast tumor/ breast cancer and menopause and the key word hot flashes. The reference lists of the identified articles and relevant review articles were examined for additional publications. Pertinent articles and abstracts of large randomized controlled trials focusing on the treatment of hot flashes in breast cancer survivors were selected for review. Pilot studies were excluded. A number of nonpharmacologic approaches are available for the treatment of hot flashes in breast cancer survivors, although they appear to be of limited effectiveness. Complementary alternative medicine therapies and vitamin E have been found to have modest effectiveness at best, and data on their long-term safety are not available. Centrally active agents such as the antidepressants venlafaxine and paroxetine and the anti seizure agent gabapentin have shown clinical effectiveness and appear to be reasonably well tolerated in this population. Centrally active agents (eg, venlafaxine, paroxetine, gabapentin) are regarded as the most promising nonhormonal treatments for hot flashes in breast cancer survivors. Nonpharmacologic and complementary alternative medicine therapies have limited effectiveness.

A case report of schizoaffective disorder with ritualistic behaviors and catatonic stupor: successful treatment by risperidone and modified electroconvulsive therapy.

PubMed

Bai, Yuanhan; Yang, Xi; Zeng, Zhiqiang; Yang, Haichen

2018-03-13

Ritualistic behaviors are common in obsessive compulsive disorder (OCD), while catatonic stupor occasionally occurs in psychotic or mood disorders. Schizoaffective disorder is a specific mental disorder involving both psychotic and affective symptoms. The syndrome usually represents a specific diagnosis, as in the case of the 10th edition of the International Classification of Diseases (ICD-10) or the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). However, symptom-based diagnosis can result in misdiagnosis and hinder effective treatment. Few cases of ritualistic behaviors and catatonic stupor associated with schizoaffective disorder have been reported. Risperidone and modified electroconvulsive therapy (MECT) were effective in our case. A 35-year-old man with schizoaffective disorder-depression was admitted to the hospital because of ritualistic behaviors, depression, and distrust. At the time of admission, prominent ritualistic behaviors and depression misled us to make the diagnosis of OCD. Sertraline add-on treatment exacerbated the psychotic symptoms, such as pressure of thoughts and delusion of control. In the presence of obvious psychotic symptoms and depression, schizoaffective disorder-depression was diagnosed according to ICD-10. Meanwhile, the patient unfortunately developed catatonic stupor and respiratory infection, which was identified by respiratory symptoms, blood tests, and a chest X-ray. To treat psychotic symptoms, catatonic stupor, and respiratory infection, risperidone, MECT, and ceftriaxone were administered. As a result, we successfully cured the patient with the abovementioned treatment strategies. Eventually, the patient was diagnosed with schizoaffective disorder-depression with ritualistic behaviors and catatonia. Risperidone and MECT therapies were dramatically effective. Making a differential diagnosis of mental disorders is a key step in treating disease. Sertraline was not recommended for treating schizoaffective disorder-depression according to our case because it could exacerbate positive symptoms. Controversy remains about whether antipsychotics should be administered for catatonic stupor. However, more case studies will be needed. Risperidone with MECT was beneficial for the patient in our case.

Possible prenatal impact of sertraline on human placental glutathione S-transferase-π.

PubMed

Dalmizrak, O; Kulaksiz-Erkmen, G; Ozer, N

2012-05-01

Sertraline (SER), a tricyclic antidepressant, is considered to belong to the group of selective amine reuptake inhibitors. Its ability to cross the blood-brain barrier and transplacental transport has been reported previously. It is widely distributed in the brain and is bound to human glutathione S-transferase-π (GST-π). If SER is taken during pregnancy, it gets accumulated in the embryo and fetus, and some studies have suggested it may cause congenital malformations, thus the study of the interaction of GST-π with antidepressants is crucial. In this study, the interaction of human placental GST-π with SER in the presence of the natural ligand, reduced glutathione (GSH) and a xenobiotic ligand, 1-chloro-2,4-dinitrobenzene (CDNB) was investigated. The V(m) values obtained at variable [CDNB] and variable [GSH] were 61.3 ± 2.3 and 46.4 ± 1.7 U/mg protein, respectively. The k(cat) and k(cat)/K(m) values for GSH and CDNB were 3.63 × 10(6) s(-1), 2.59 × 10(10) M(-1) s(-1) and 4.79 × 10(6) s(-1), 1.29 × 10(10) M(-1) s(-1), respectively. The half maximal inhibitory concentration value for SER was 4.60 mM. At constant [CDNB] and variable [GSH] the inhibition type was linear mixed-type, with K(s), α, and K(i) values of 0.14 ± 0.02, 2.90 ± 1.64, and 2.18 ± 0.80 mM, respectively. On the other hand, at fixed [GSH] and at variable [CDNB], the inhibition type was competitive, with K(i) value of 0.96 ± 0.10 mM. Thus, these findings weaken the importance of the protective role of GST against toxic electrophiles in vivo in adults, but due to its immature enterohepatic system SER may accumulate in the fetus and cause congenital malformations.