Relationships between serum BDNF and the antidepressant effect of acute exercise in depressed women.

PubMed

Meyer, Jacob D; Koltyn, Kelli F; Stegner, Aaron J; Kim, Jee-Seon; Cook, Dane B

2016-12-01

Brain-derived neurotrophic factor (BDNF) has recently emerged as one potential mechanism with which exercise improves mood in major depressive disorder (MDD). This study examined the relationship between changes in serum total BDNF and mood following acute exercise in MDD. It was hypothesized that acute exercise would increase BDNF in an intensity-dependent manner and that changes in BDNF would be significantly related to improvement in depressed mood post-exercise. Twenty-four women (age: 38.6±14.0years) with MDD exercised for 30min on a stationary bicycle at light, moderate and hard exercise intensities and performed a quiet rest session using a within-subjects, randomized and counter-balanced design. Before, 10 and 30min after each session, participants completed the profile of mood states (POMS). Blood was drawn before and within 10min after completion of each session and serum total BDNF (sBDNF) was measured by enzyme-linked immunosorbent assay. Acute exercise-induced changes in POMS Depression and sBDNF were analyzed via 4 session (quiet rest, light, moderate, hard) by 2 measurement (pre, post) ANOVA. Secondary analyses examined the effects of baseline mood and antidepressant usage on sBDNF. Exercise resulted in an acute improvement in depressed mood that was not intensity dependent (p>0.05), resulting in significant acute increases in sBDNF (p=0.006) that were also not intensity-dependent (p>0.05). Acute changes in sBDNF were not significantly correlated to changes in POMS depression at 10m (r=-0.171, p=0.161) or 30m (r=-0.151, p=0.215) post-exercise. The fourteen participants taking antidepressant medications exhibited lower post-exercise sBDNF (p=0.015) than the participants not currently taking antidepressants, although mood responses were similar. Acute exercise is an effective mood-enhancing stimulus, although sBDNF does not appear to play a role in this short-term response. Patients who are not currently taking antidepressant medications and those who

Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial.

PubMed

Mohamed, Somaia; Johnson, Gary R; Chen, Peijun; Hicks, Paul B; Davis, Lori L; Yoon, Jean; Gleason, Theresa C; Vertrees, Julia E; Weingart, Kimberly; Tal, Ilanit; Scrymgeour, Alexandra; Lawrence, David D; Planeta, Beata; Thase, Michael E; Huang, Grant D; Zisook, Sidney; Rao, Sanjai D; Pilkinton, Patricia D; Wilcox, James A; Iranmanesh, Ali; Sapra, Mamta; Jurjus, George; Michalets, James P; Aslam, Muhammed; Beresford, Thomas; Anderson, Keith D; Fernando, Ronald; Ramaswamy, Sriram; Kasckow, John; Westermeyer, Joseph; Yoon, Gihyun; D'Souza, D Cyril; Larson, Gunnar; Anderson, William G; Klatt, Mary; Fareed, Ayman; Thompson, Shabnam I; Carrera, Carlos J; Williams, Solomon S; Juergens, Timothy M; Albers, Lawrence J; Nasdahl, Clifford S; Villarreal, Gerardo; Winston, Julia L; Nogues, Cristobal A; Connolly, K Ryan; Tapp, Andre; Jones, Kari A; Khatkhate, Gauri; Marri, Sheetal; Suppes, Trisha; LaMotte, Joseph; Hurley, Robin; Mayeda, Aimee R; Niculescu, Alexander B; Fischer, Bernard A; Loreck, David J; Rosenlicht, Nicholas; Lieske, Steven; Finkel, Mitchell S; Little, John T

2017-07-11

Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1

Milnacipran versus other antidepressive agents for depression.

PubMed

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

2009-07-08

Although pharmacological and psychological interventions are both effective for major depression, antidepressant drugs are frequently used as first-line treatment in primary and secondary care settings. Milnacipran, a dual serotonin-norepinephrine reuptake inhibitor (SNRI), is one of the antidepressant drugs that clinicians use for routine depression care. To assess the evidence for the efficacy, acceptability and tolerability of milnacipran in comparison with tricyclic antidepressants (TCAs), heterocyclics, SSRIs and other newer antidepressive agents in the acute-phase treatment of major depression. The Cochrane Collaboration Depression, Anxiety & Neurosis review group Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) were electronically searched in August 2008. References of relevant trials and other reviews were also checked. Trial databases of the drug-approving agencies and ongoing clinical trial registers for all published and unpublished trials were hand-searched in 2007. All relevant authors were contacted for supplemental data. No language restriction was applied. Randomised controlled trials comparing milnacipran with any other active antidepressive agents (including non-conventional agents such as herbal products like hypericum) as monotherapy in the acute phase of major depression were selected. Two reviewers independently checked eligibility, assessed methodological quality and extracted data from the eligible trials using a standardised data extraction form. The number of participants who responded to treatment or those who achieved remission were calculated on an intention-to-treat basis. Random-effects meta-analyses were conducted, combining data from the included trials. A total of 16 randomised controlled trials (n=2277) were included in the meta-analysis.Despite the size of this sample, the pooled 95% confidence intervals were rather wide and there were no statistically significant differences in efficacy, acceptability and

Relationship of pharmaceutical promotion to antidepressant switching and adherence: a retrospective cohort study.

PubMed

Hansen, Richard A; Chen, Shih-Yin; Gaynes, Bradley N; Maciejewski, Matthew L

2010-12-01

Patient nonadherence and early discontinuation of antidepressant treatment are common. Pharmaceutical promotion to consumers and physicians may influence this behavior. The objectives of this study were to explore whether promotional spending is related to early antidepressant switching, acute-phase adherence, and continuation-phase adherence. A retrospective cohort study was conducted with national promotional expenditure data merged with medical and prescription claims data from a large national health plan affiliated with i3 Innovus. Included were records for continuously insured adults with major depression who received a new prescription for an antidepressant: 5,010 were in the cohort assessed for switching, 4,457 were in the cohort assessed for acute-phase adherence, and 1,772 were in the cohort assessed for continuation-phase adherence. National promotional efforts were estimated by examining inflation-adjusted spending on direct-to-consumer advertising (DTCA) and physician detailing. Clinical guidelines were used to create proxies for aspects of treatment outcomes, including antidepressant switching and adherence in the acute phase and adherence in the continuation phase. Logistic regression models estimated the association between promotional variables and these outcomes. Patients taking medications that were more highly promoted to physicians were less likely to switch medications (odds ratio [OR]=.61) and were more likely to be adherent during the acute phase of treatment (OR=1.13). DTCA had little effect on switching or antidepressant adherence. Detailing to physicians was associated with lower rates of medication switching and had a positive relationship with patient adherence during early antidepressant treatment. This finding indicates that certain aspects of promotion may have beneficial effects on antidepressant use.

Continued antidepressant treatment and suicide in patients with depressive disorder.

PubMed

Søndergård, Lars; Lopez, Ana Garcia; Andersen, Per Kragh; Kessing, Lars Vedel

2007-01-01

Antidepressant use in Denmark, as in many developed countries, has substantially increased during recent years, coinciding with a decreasing suicide rate. In a nationwide observational cohort study with linkage of registers of all prescribed antidepressants and recorded suicides in Denmark from 1995 to 2000, we investigated the relation between continued treatment with antidepressants and suicide in a population of all patients discharged from hospital psychiatry with a diagnosis of depressive disorder. Patients discharged from hospital psychiatry with a diagnosis of depressive disorder had a highly increased rate of suicide. Those who continued treatment with antidepressants had a decreased rate of suicide compared with those who purchased antidepressants once (rate ratio: 0.31, 95% confidence interval: 0.26-0.36). Further, the rate of suicide decreased consistently with the number of prescriptions. On individualized data from a cohort of patients with a known history of depressive disorder, continued antidepressant treatment was associated with reduced risk of suicide.

Milnacipran versus other antidepressive agents for depression

PubMed Central

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

2014-01-01

Background Although pharmacological and psychological interventions are both effective for major depression, antidepressant drugs are frequently used as first-line treatment in primary and secondary care settings. Milnacipran, a dual serotonin-norepinephrine reuptake inhibitor (SNRI), is one of the antidepressant drugs that clinicians use for routine depression care. Objectives To assess the evidence for the efficacy, acceptability and tolerability of milnacipran in comparison with tricyclic antidepressants (TCAs), heterocyclics, SSRIs and other newer antidepressive agents in the acute-phase treatment of major depression. Search methods The Cochrane Collaboration Depression, Anxiety & Neurosis review group Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) were electronically searched in August 2008. References of relevant trials and other reviews were also checked. Trial databases of the drug-approving agencies and ongoing clinical trial registers for all published and unpublished trials were handsearched in 2007. All relevant authors were contacted for supplemental data. No language restriction was applied. Selection criteria Randomised controlled trials comparing milnacipran with any other active antidepressive agents (including non-conventional agents such as herbal products like hypericum) as monotherapy in the acute phase of major depression were selected. Data collection and analysis Two reviewers independently checked eligibility, assessed methodological quality and extracted data from the eligible trials using a standardised data extraction form. The number of participants who responded to treatment or those who achieved remission were calculated on an intention-to-treat basis. Random-effects meta-analyses were conducted, combining data from the included trials. Main results A total of 16 randomised controlled trials (n=2277) were included in the meta-analysis. Despite the size of this sample, the pooled 95% confidence intervals were

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 CRD

Personalized Antidepressant Selection and Pathway to Novel Treatments: Clinical Utility of Targeting Inflammation

PubMed Central

Jha, Manish K.; Trivedi, Madhukar H.

2018-01-01

Major depressive disorder (MDD) is a chronic condition that affects one in six adults in the US during their lifetime. The current practice of antidepressant medication prescription is a trial-and-error process. Additionally, over a third of patients with MDD fail to respond to two or more antidepressant treatments. There are no valid clinical markers to personalize currently available antidepressant medications, all of which have similar mechanisms targeting monoamine neurotransmission. The goal of this review is to summarize the recent findings of immune dysfunction in patients with MDD, the utility of inflammatory markers to personalize treatment selection, and the potential of targeting inflammation to develop novel antidepressant treatments. To personalize antidepressant prescription, a c-reactive protein (CRP)-matched treatment assignment can be rapidly implemented in clinical practice with point-of-care fingerstick tests. With this approach, 4.5 patients need to be treated for 1 additional remission as compared to a CRP-mismatched treatment assignment. Anti-cytokine treatments may be effective as novel antidepressants. Monoclonal antibodies against proinflammatory cytokines, such as interleukin 6, interleukin 17, and tumor necrosis factor α, have demonstrated antidepressant effects in patients with chronic inflammatory conditions who report significant depressive symptoms. Additional novel antidepressant strategies targeting inflammation include pharmaceutical agents that block the effect of systemic inflammation on the central nervous system. In conclusion, inflammatory markers offer the potential not only to personalize antidepressant prescription but also to guide the development of novel mechanistically-guided antidepressant treatments. PMID:29329256

Treatment of Fibromyalgia with Antidepressants

PubMed Central

O'Malley, Patrick G; Balden, Erin; Tomkins, Glen; Santoro, James; Kroenke, Kurt; Jackson, Jeffrey L

2000-01-01

BACKGROUND Fibromyalgia is a common, poorly understood musculoskeletal pain syndrome with limited therapeutic options. OBJECTIVE To systematically review the efficacy of antidepressants in the treatment of fibromyalgia and examine whether this effect was independent of depression. DESIGN Meta-analysis of English-language, randomized, placebo-controlled trials. Studies were obtained from searching medline, embase, and psyclit(1966-1999), the Cochrane Library, unpublished literature, and bibliographies. We performed independent duplicate review of each study for both inclusion and data extraction. MAIN RESULTS Sixteen randomized, placebo-controlled trials were identified, of which 13 were appropriate for data extraction. There were 3 classes of antidepressants evaluated: tricyclics (9 trials), selective serotonin reuptake inhibitors (3 trials), and S-adenosylmethionine (2 trials). Overall, the quality of the studies was good (mean score 5.6, scale 0-8). The odds ratio for improvement with therapy was 4.2 (95% confidence interval [95% CI], 2.6 to 6.8). The pooled risk difference for these studies was 0.25 (95% CI, 0.16 to 0.34), which calculates to 4 (95% CI, 2.9 to 6.3) individuals needing treatment for 1 patient to experience symptom improvement. When the effect on individual symptoms was combined, antidepressants improved sleep, fatigue, pain, and well-being, but not trigger points. In the 5 studies where there was adequate assessment for an effect independent of depression, only 1 study found a correlation between symptom improvement and depression scores. Outcomes were not affected by class of agent or quality score using meta-regression. CONCLUSION Antidepressants are efficacious in treating many of the symptoms of fibromyalgia. Patients were more than 4 times as likely to report overall improvement, and reported moderate reductions in individual symptoms, particularly pain. Whether this effect is independent of depression needs further study. PMID:11029681

Treatment decisions on antidepressants in nursing homes: a qualitative study.

PubMed

Iden, Kristina Riis; Hjørleifsson, Stefan; Ruths, Sabine

2011-12-01

To explore decision-making on treatment with antidepressants among doctors and nurses in nursing homes. A qualitative study based on interviews with three focus groups comprising eight physicians engaged full time, eight physicians engaged part time, and eight registered nurses, respectively. The interview guide comprised questions on initiating, evaluating, and withdrawing treatment with antidepressants. The interviews were audio-recorded, transcribed, and analysed by systematic text condensation. The first theme was the diagnostic process. The informants expressed difficulty in differentiating between depression and sorrow resulting from loss in old age. Further, the doctors reported that they relied on nurses' observations and rarely carried out systematic diagnostic work and follow-up of patients with depression. The second theme was treatment. Antidepressants were usually the only type of treatment provided, and patients were kept on medication even though staff felt uncertain whether this was effective. The third theme was who really determines the treatment. Registered nurses reported that unskilled and auxiliary nursing staff requested drug treatment, and doctors felt some pressure from the nurses to prescribe antidepressants. This study suggests that the quality of diagnosis and treatment for depression in nursing homes needs to be improved in Norway. Doctors should be more available and take responsibility and leadership in medical decisions.

Inflammation and Immune Regulation as Potential Drug Targets in Antidepressant Treatment

PubMed Central

Schmidt, Frank M.; Kirkby, Kenneth C.; Lichtblau, Nicole

2016-01-01

Growing evidence supports a mutual relationship between inflammation and major depression. A variety of mechanisms are outlined, indicating how inflammation may be involved in the pathogenesis, course and treatment of major depression. In particular, this review addresses 1) inflammatory cytokines as markers of depression and potential predictors of treatment response, 2) findings that cytokines interact with antidepressants and non-pharmacological antidepressive therapies, such as electroconvulsive therapy, deep brain stimulation and physical activity, 3) the influence of cytokines on the cytochrome (CYP) p450-system and drug efflux transporters, and 4) how cascades of inflammation might serve as antidepressant drug targets. A number of clinical trials have focused on agents with immunmodulatory properties in the treatment of depression, of which this review covers nonsteroidal anti-inflammatory drugs (NSAIDs), cytokine inhibitors, ketamine, polyunsaturated fatty acids, statins and curcumin. A perspective is also provided on possible future immune targets for antidepressant therapy, such as toll-like receptor-inhibitors, glycogen synthase kinase-3 inhibitors, oleanolic acid analogs and minocycline. Concluding from the available data, markers of inflammation may become relevant factors for more personalised planning and prediction of response of antidepressant treatment strategies. Agents with anti-inflammatory properties have the potential to serve as clinically relevant antidepressants. Further studies are required to better define and identify subgroups of patients responsive to inflammatory agents as well as to define optimal time points for treatment onset and duration. PMID:26769225

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.

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.

Risk of injurious road traffic crash after prescription of antidepressants.

PubMed

Orriols, Ludivine; Queinec, Raphaëlle; Philip, Pierre; Gadegbeku, Blandine; Delorme, Bernard; Moore, Nicholas; Suissa, Samy; Lagarde, Emmanuel

2012-08-01

To estimate the risk of road traffic crash associated with prescription of antidepressants. Data were extracted and matched from 3 French national databases: the national health care insurance database, police reports, and the national police database of injurious crashes. A case-control analysis comparing 34,896 responsible versus 37,789 nonresponsible drivers was conducted. Case-crossover analysis was performed to investigate the acute effect of medicine exposure. 72,685 drivers, identified by their national health care number, involved in an injurious crash in France from July 2005 to May 2008 were included. 2,936 drivers (4.0%) were exposed to at least 1 antidepressant on the day of the crash. The results showed a significant association between the risk of being responsible for a crash and prescription of antidepressants (odds ratio [OR] = 1.34; 95% CI, 1.22-1.47). The case-crossover analysis showed no association with treatment prescription, but the risk of road traffic crash increased after an initiation of antidepressant treatment (OR = 1.49; 95% CI, 1.24-1.79) and after a change in antidepressant treatment (OR = 1.32; 95% CI, 1.09-1.60). Patients and prescribers should be warned about the risk of crash during periods of treatment with antidepressant medication and about particularly high vulnerability periods such as those when a treatment is initiated or modified. © Copyright 2012 Physicians Postgraduate Press, Inc.

[Influence of interleukin-1 beta gene polymorphism and childhood maltreatment on antidepressant treatment].

PubMed

Chen, Ying; Zhang, Zhijun; Xu, Zhi; Pu, Mengjia; Geng, Leiyu

2015-12-01

To explore the influence of interleukin-1 beta (IL1B) gene polymorphism and childhood maltreatment on antidepressant treatment. Two hundred and four patients with major depressive disorder (MDD) have received treatment with single antidepressant drugs and were followed up for 8 weeks. Hamilton depression scale-17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effect. Childhood maltreatment was assessed using Childhood Trauma Questionnaire, a 28-item Short Form (CTQ-SF). Single nucleotide polymorphism (SNP) of the IL1B gene was determined using a SNaPshot method. Correlation of rs16944 gene polymorphism with response to treatment was analyzed using Unphased 3.0.13 software. The main and interactive effects of SNP and childhood maltreatment on the antidepressant treatment were analyzed using Logistic regression analysis. No significant difference of gender, age, year of education, family history, episode time, and antidepressant agents was detected between the remitters and non-remitters. Association analysis has found that the SNP rs16944 in the IL1B AA genotype carriers antidepressant response was poorer (χ2=3.931, P=0.047). No significant difference was detected in the CTQ scores between the two groups. Genetic and environmental interaction analysis has demonstrated a significant correlation between rs16944 AA genotype and childhood maltreatment and poorer response to antidepressant treatment. The SNP rs16944 in the IL1B gene and its interaction with childhood maltreatment may influence the effect of antidepressant treatment for patients with MDD.

Acute focal dystonia induced by a tricyclic antidepressant in a patient with Wilson disease: a case report.

PubMed

Litwin, T; Chabik, G; Członkowska, A

2013-01-01

The authors present the case of a 19-year-old patient with Wilson disease (WD) who developed symptoms of acute focal dystonia of the left hand (a 'starfish' hand presentation) shortly after treatment with the tricyclic antidepressant clomipramine. The diagnosis of WD was made 8 months earlier based on abnormal copper metabolism parameters and was confirmed by genetic testing. Initially, the patient presented with akathisia, sialorrhea, oromandibular dystonia (occasionally grimacing) and slight dysarthria. The patient's symptoms diminished after treatment with d-penicillamine was initiated. No further deterioration was observed after copper-chelating therapy was started. The authors diagnosed acute focal dystonia induced by clomipramine. Botulinum toxin and intensive rehabilitation was initiated; complete regression of hand dystonia was observed. Based on the case, the authors suggest that care should be exercised with regard to starting medications that could potentially impact the extrapyramidal system in WD patients.

Antidepressants for the treatment of depression in people with cancer.

PubMed

Ostuzzi, Giovanni; Matcham, Faith; Dauchy, Sarah; Barbui, Corrado; Hotopf, Matthew

2018-04-23

for the aims of this review. The two authors compared the data extracted and then entered data into Review Manager 5 using a double-entry procedure. Information extracted included study and participant characteristics, intervention details, outcome measures for each time point of interest, cost analysis and sponsorship by a drug company. We used the standard methodological procedures expected by Cochrane. We retrieved a total of 10 studies (885 participants), seven of which contributed to the meta-analysis for the primary outcome. Four of these compared antidepressants and placebo, two compared two antidepressants, and one three-armed study compared two antidepressants and placebo. In this update we included one additional unpublished study. These new data contributed to the secondary analysis, while the results of the primary analysis remained unchanged.For acute-phase treatment response (6 to 12 weeks), we found no difference between antidepressants as a class and placebo on symptoms of depression measured both as a continuous outcome (standardised mean difference (SMD) -0.45, 95% confidence interval (CI) -1.01 to 0.11, five RCTs, 266 participants; very low certainty evidence) and as a proportion of people who had depression at the end of the study (risk ratio (RR) 0.82, 95% CI 0.62 to 1.08, five RCTs, 417 participants; very low certainty evidence). No trials reported data on follow-up response (more than 12 weeks). In head-to-head comparisons we only retrieved data for selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants, showing no difference between these two classes (SMD -0.08, 95% CI -0.34 to 0.18, three RCTs, 237 participants; very low certainty evidence). No clear evidence of a beneficial effect of antidepressants versus either placebo or other antidepressants emerged from our analyses of the secondary efficacy outcomes (dichotomous outcome, response at 6 to 12 weeks, very low certainty evidence). In terms of dropouts due to any

Antidepressant and anxiolytic-like activity of sodium selenite after acute treatment in mice.

PubMed

Kędzierska, Ewa; Dudka, Jarosław; Poleszak, Ewa; Kotlińska, Jolanta H

2017-04-01

Selenium (Se) is an essential trace element for humans and animals, that is needed for a broad variety of physiological functions including thyroid hormone metabolism, protection against oxidative stress, and immunity associated functions. Human nutritional Se deficiencies are associated with neuropsychiatric diseases, like Alzheimer's disease, Parkinson's disease, obsessive - compulsive disorder, stroke, epilepsy as well as depressive behaviours. In this study we examined antidepressant- and anxiolytic-like activity of Se in the inorganic form of sodium selenite and investigated whether Se influence on the locomotor activity in mice. The antidepressant-like and anxiolytic-like activity of Se was assessed using forced swim test (FST) and elevated plus-maze test (EPM), respectively. Spontaneous locomotor activity was measured using photoresistor actimeters. Sodium selenite administered at the doses of 0.5, 1, and 2mg/kg, ip reduced immobility time in the FST exerting antidepressant-like activity. In the EPM test, sodium selenite at the same doses, produced anxiolytic-like effect; the doses active in both tests did not affect locomotor activity, indicating that these effects of Se are specific. These potential antidepressant- and anxiolytic-like effects of Se require more detailed experimental study using animal models to approach a clear conclusion regarding the potential mechanism of the observed effect. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Differential behavioral effects of the antidepressants reboxetine, fluoxetine, and moclobemide in a modified forced swim test following chronic treatment.

PubMed

Cryan, John F; Page, Michelle E; Lucki, Irwin

2005-11-01

The forced swim test (FST) is the most widely used model for assessing potential antidepressant activity in rodents following acute or short-term treatment. However, few studies have compared the effects of short- and long-term antidepressant treatment on behaviors in the test, despite the need to treat patients chronically to produce clinical effects. The current studies examined whether antidepressants from different classes produce different behavioral effects following short-term treatment and whether such effects change following administration for a longer duration. The effects of administering short-term (3 days) and long-term (14 days) treatments of antidepressants from three different chemical classes with distinct mechanisms of action via osmotic minipump were examined: the selective norepinephrine reuptake inhibitor reboxetine (10 and 60 mg kg(-1) day(-1)), the selective serotonin reuptake inhibitor fluoxetine (2.5 and 15 mg kg(-1) day(-1)), and the reversible inhibitor of monoamine oxidase moclobemide (2.5 and 15 mg kg(-1) day(-1)). All testing was carried out in a 15-min test with no preswim session in order to negate any confounding aspect of an induction procedure. The majority of antidepressant-sensitive behavioral changes were observed in the first 5 min of the test. The low dose of reboxetine failed to alter behavior in the test after 3 days but significantly decreased immobility and increased climbing behavior following administration for 14 days, whereas the high dose of reboxetine was equally effective following 3 and 14 days of treatment. In a similar fashion, the low dose of fluoxetine failed to alter behavior in the test following 3 days, but showed an augmented response on immobility and increased swimming following administration for 14 days. The high dose of fluoxetine was slightly more effective at reducing immobility following administration for 14 days than 3 days. The low dose of moclobemide decreased immobility and increased climbing

Antidepressant-associated sexual dysfunction: impact, effects, and treatment

PubMed Central

Higgins, Agnes; Nash, Michael; Lynch, Aileen M

2010-01-01

Sexual dysfunction is a common side effect of antidepressants and can have significant impact on the person’s quality of life, relationships, mental health, and recovery. The reported incidence of sexual dysfunction associated with antidepressant medication varies considerably between studies, making it difficult to estimate the exact incidence or prevalence. The sexual problems reported range from decreased sexual desire, decreased sexual excitement, diminished or delayed orgasm, to erection or delayed ejaculation problems. There are a number of case reports of sexual side effects, such as priapism, painful ejaculation, penile anesthesia, loss of sensation in the vagina and nipples, persistent genital arousal and nonpuerperal lactation in women. The focus of this article is to explore the incidence, pathophysiology, and treatment of antidepressant iatrogenic sexual dysfunction. PMID:21701626

Antidepressant treatment and suicide attempts and self-inflicted injury in children and adolescents.

PubMed

Gibbons, Robert D; Coca Perraillon, Marcelo; Hur, Kwan; Conti, Rena M; Valuck, Robert J; Brent, David A

2015-02-01

In the 2004, FDA placed a black box warning on antidepressants for risk of suicidal thoughts and behavior in children and adolescents. The purpose of this paper is to examine the risk of suicide attempt and self-inflicted injury in depressed children ages 5-17 treated with antidepressants in two large observational datasets taking account time-varying confounding. We analyzed two large US medical claims databases (MarketScan and LifeLink) containing 221,028 youth (ages 5-17) with new episodes of depression, with and without antidepressant treatment during the period of 2004-2009. Subjects were followed for up to 180 days. Marginal structural models were used to adjust for time-dependent confounding. For both datasets, significantly increased risk of suicide attempts and self-inflicted injury were seen during antidepressant treatment episodes in the unadjusted and simple covariate adjusted analyses. Marginal structural models revealed that the majority of the association is produced by dynamic confounding in the treatment selection process; estimated odds ratios were close to 1.0 consistent with the unadjusted and simple covariate adjusted association being a product of chance alone. Our analysis suggests antidepressant treatment selection is a product of both static and dynamic patient characteristics. Lack of adjustment for treatment selection based on dynamic patient characteristics can lead to the appearance of an association between antidepressant treatment and suicide attempts and self-inflicted injury among youths in unadjusted and simple covariate adjusted analyses. Marginal structural models can be used to adjust for static and dynamic treatment selection processes such as that likely encountered in observational studies of associations between antidepressant treatment selection, suicide and related behaviors in youth. Copyright © 2014 John Wiley & Sons, Ltd.

[Adherence to patients antidepressant treatment and the factors associated of non-compiance].

PubMed

Párraga Martínez, Ignacio; López-Torres Hidalgo, Jesús; del Campo del Campo, José M; Villena Ferrer, Alejandro; Morena Rayo, Susana; Escobar Rabadán, Francisco

2014-01-01

To know the adherence to treatment in patients who initiate antidepressant drugs and to analyze the determinant factors of non-compliance, so much clinical as sociodemographic. Prospective longitudinal observational study. Primary Health Care and Mental Health Surgeries of three Castilla-La Mancha Areas. 185 adults patients who were started in antidepressant treatment were evaluated. Treatment adherence (test Haynes-Sackett, test Morisky-Green, count of tablets and MEMS), adverse effects, intensity of depressive symptoms, sociodemographic characteristics and other characteristics related to antidepressants or participants. After 6months of beginning antidepressing treatment, 46.9% (95%IC: 36.5-57.3) showed an inadequate fulfilment by pill count method and 28.6% (95%IC: 19.1-38.0) with Morisky-Green's questionnaire. To 15 days the lack of adherence was 48.5% (95%IC: 40.6-56.4) and of 33.5% (95%IC: 26.1-41.0). The 38.4% (95%IC: 31.1-45.7) demonstrated some side effect during the follow-up. Using proportional risk model of Cox the variables related to compliance were: younger age, level of instruction lower than secondary studies, free medicines for pensioner, no psychotherapeutic treatment, consume a fewer antidepressants drugs and a frequency ≤ 3 visits to the family doctor 3 months previous to the study. The non-compliance of antidepressant treatment in primary care is high from the first weeks after initiating it. The conditioning factors are related to sociodemographic characteristics and other patient characteristics as type of financing of pharmaceutical benefit and frequentness at primary care. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Citalopram versus other anti-depressive agents for depression

PubMed Central

Cipriani, Andrea; Purgato, Marianna; Furukawa, Toshi A; Trespidi, Carlotta; Imperadore, Giuseppe; Signoretti, Alessandra; Churchill, Rachel; Watanabe, Norio; Barbui, Corrado

2014-01-01

Background Recent US and UK clinical practice guidelines recommend that second-generation antidepressants should be considered amongst the best first-line options when drug therapy is indicated for a depressive episode. Systematic reviews have already highlighted some differences in efficacy between second-generation antidepressants. Citalopram, one of the first selective serotonin reuptake inhibitors (SSRI) introduced in the market, is one of these antidepressant drugs that clinicians use for routine depression care. Objectives To assess the evidence for the efficacy, acceptability and tolerability of citalopram in comparison with tricyclics, heterocyclics, other SSRIs and other conventional and non-conventional antidepressants in the acute-phase treatment of major depression. Search methods We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to February 2012. No language restriction was applied. We contacted pharmaceutical companies and experts in this field for supplemental data. Selection criteria Randomised controlled trials allocating patients with major depression to citalopram versus any other antidepressants. Data collection and analysis Two reviewers independently extracted data. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), patient acceptability (the number of patients who failed to complete the study) and tolerability (side-effects). Main results Thirty-seven trials compared citalopram with other antidepressants (such as tricyclics, heterocyclics, SSRIs and other antidepressants, either conventional ones, such as mirtazapine, venlafaxine and reboxetine, or non-conventional, like hypericum). Citalopram was shown to be significantly less effective than escitalopram in achieving acute response (odds

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.

Antidepressant treatment of depression in rural nursing home residents.

PubMed

Kerber, Cindy Sullivan; Dyck, Mary J; Culp, Kennith R; Buckwalter, Kathleen

2008-09-01

Under-diagnosis and under-treatment of depression are major problems in nursing home residents. The purpose of this study was to determine antidepressant use among nursing home residents who were diagnosed with depression using three different methods: (1) the Geriatric Depression Scale, (2) Minimum Data Set, and (3) primary care provider assessments. As one would expect, the odds of being treated with an antidepressant were about eight times higher for those diagnosed as depressed by the primary care provider compared to the Geriatric Depression Scale or the Minimum Data Set. Men were less likely to be diagnosed and treated with antidepressants by their primary care provider than women. Depression detected by nurses through the Minimum Data Set was treated at a lower rate with antidepressants, which generates issues related to interprofessional communication, nursing staff communication, and the need for geropsychiatric role models in nursing homes.

Nitric Oxide Synthase Inhibitors as Antidepressants

PubMed Central

Wegener, Gregers; Volke, Vallo

2010-01-01

Affective and anxiety disorders are widely distributed disorders with severe social and economic effects. Evidence is emphatic that effective treatment helps to restore function and quality of life. Due to the action of most modern antidepressant drugs, serotonergic mechanisms have traditionally been suggested to play major roles in the pathophysiology of mood and stress-related disorders. However, a few clinical and several pre-clinical studies, strongly suggest involvement of the nitric oxide (NO) signaling pathway in these disorders. Moreover, several of the conventional neurotransmitters, including serotonin, glutamate and GABA, are intimately regulated by NO, and distinct classes of antidepressants have been found to modulate the hippocampal NO level in vivo. The NO system is therefore a potential target for antidepressant and anxiolytic drug action in acute therapy as well as in prophylaxis. This paper reviews the effect of drugs modulating NO synthesis in anxiety and depression. PMID:27713253

The role of patient experience and its influence on adherence to antidepressant treatment.

PubMed

Johnston, Brenda J

2013-12-01

Major depression can be a very challenging illness and although antidepressant agents are shown to provide benefit, many patients do not adhere to antidepressant treatment guidelines. Multiple factors contribute to adherence, including the influence of patient experience. The purpose of this article is to conduct a systematic review on the influence of patient experience with depression and antidepressant agents on treatment adherence. Thirteen research articles were selected for the review and revealed that patient past experience with depression and antidepressant agents, vicarious experiences, beliefs and attitudes, and the treatment experience itself can impact adherence. It is important for providers to be vigilant with assessment and include patient experience when developing a plan of care. This approach encourages shared decision making and a patient-centered focus for improved management of depression. Copyright 2013, SLACK Incorporated.

Trait anxiety levels before and after antidepressant treatment: a 3-wave cohort study.

PubMed

Nabi, Hermann; Virtanen, Marianna; Singh-Manoux, Archana; Hagger-Johnson, Gareth; Pentti, Jaana; Kivimäki, Mika; Vahtera, Jussi

2013-06-01

The aim of this study was to examine change in "trait anxiety" levels assessed repeatedly before and after antidepressant treatment in a large cohort of men and women. A total of 18,732 participants of the Finnish Public Sector Study with no initial record of depression or self-reported doctor diagnosis of depression completed the short form of the Spielberger Trait-Anxiety Inventory in 2000-2002 (T1), 2004-2005 (T2), and 2008-2009 (T3). We used prescription data from the nationwide Drug Prescription Register to identify antidepressant treatment between T1 and T2 (n = 710). Both men (β = 0.435, P < 0.001) and women (β = 0.300, P < 0.001) who received antidepressant treatment had higher trait anxiety levels at T1. Mixed models analyses of repeated measures showed a small but statistically significant decrease in trait anxiety scores for the overall sample of men (β = 0.023, P = 0.033) and women (β = 0.011, P = 0.031) between T1 and T3. The interaction term between time and antidepressant treatment status suggested a greater decrease in trait anxiety levels among men receiving antidepressant treatment, with an adjusted excess decrease in mean trait anxiety scores of 0.163 (P = 0.012) between T1 and T3. We found some evidence suggesting that this is also the case in women, although the evidence in our data was less consistent for women. This large-scale study provides evidence suggesting that antidepressant treatment is associated with a reduction in trait anxiety levels, particularly in men.

Randomized Trial of Behavioral Activation, Cognitive Therapy, and Antidepressant Medication in the Acute Treatment of Adults with Major Depression

ERIC Educational Resources Information Center

Dimidjian, Sona; Hollon, Steven D.; Dobson, Keith S.; Schmaling, Karen B.; Kohlenberg, Robert J.; Addis, Michael E.; Gallop, Robert; McGlinchey, Joseph B.; Markley, David K.; Gollan, Jackie K.; Atkins, David C.; Dunner, David L.; Jacobson, Neil S.

2006-01-01

Antidepressant medication is considered the current standard for severe depression, and cognitive therapy is the most widely investigated psychosocial treatment for depression. However, not all patients want to take medication, and cognitive therapy has not demonstrated consistent efficacy across trials. Moreover, dismantling designs have…

Effectiveness of Antidepressants and Predictors of Treatment Response for Depressed HIV Patients in Uganda

PubMed Central

Ngo, Victoria K.; Wagner, Glenn J.; Nakasujja, Noeline; Dickens, Akena; Aunon, Frances; Musisi, Seggane

2015-01-01

Antidepressant medication is well-established for the treatment of depression, but little is known about its effectiveness for HIV populations in sub-Saharan Africa. This study examined the effectiveness of antidepressant treatment and predictors of treatment response among depressed HIV patients in Uganda. Data was obtained from two open label trials in which 184 HIV patients were diagnosed with depression and started on antidepressants. Data at treatment baseline and month 6 were compared to assess treatment response, and baseline predictors of response were assessed. 154 completed Month 6, of whom 122 (79%) had responded to treatment and were no longer depressed (Patient Health Questionnaire-9 score < 5). Bivariate analysis found that education, CD4 count, general health functioning, physical health, pain, quality of life, and social support variables were associated with antidepressant treatment response; however, only secondary education and social support independently predicted treatment response in logistic multiple regression analysis. Baseline depression severity was not associated with treatment response. In conclusion, antidepressants are effective in treating both moderate and more severe depression among persons living with HIV in Uganda, and education [O.R. (95% C.I.) = 4.33 (1.33 – 14.11)] and social support [O.R. (95% C.I.) = 1.54 (1.03 – 2.30)] were most predictive of treatment response. PMID:25525053

CD-1 and Balb/cJ mice do not show enduring antidepressant-like effects of ketamine in tests of acute antidepressant efficacy.

PubMed

Bechtholt-Gompf, Anita J; Smith, Karen L; John, Catherine S; Kang, Hannah H; Carlezon, William A; Cohen, Bruce M; Ongür, Dost

2011-06-01

In patients, ketamine is a fast-acting antidepressant that can induce long-lasting symptom relief. Similar rapid effects have been reported in rodents, but reports of lasting effects are limited. We sought to extend past findings by examining dose-response curves that overlap with the individual doses previously reported to induce lasting effects in rodents and determining whether effects generalize to the tail suspension test (TST) and Balb/cJ mice. Using common tests of antidepressant efficacy we first confirmed our ability to detect the effects of desipramine, a well-characterized antidepressant drug. Next, we sought to determine whether two non-competitive NMDA antagonists, ketamine and MK-801, had long-lasting antidepressant-like effects in CD-1 mice, a strain that has often been used to demonstrate the short-term antidepressant-like effects of ketamine. Finally, we examined the short- and long-term effects of ketamine in a mouse strain that is more sensitive to antidepressant-like effects, Balb/cJ mice. In CD-1 mice, desipramine treatment yielded significant short-term antidepressant-like effects in the TST and the forced swimming test (FST). However, no significant enduring effects of ketamine or MK-801 were observed 1 week later. Short-term effects of ketamine in the TST were observed in Balb/cJ mice, but lasting effects were absent 1 week later. Although the TST and FST have been widely used to detect antidepressant-like effects in mice, they do not appear to be sensitive to long-lasting antidepressant-like effects of ketamine in mice and, therefore, do not model the therapeutic effects of ketamine that have been reported in humans with major depression.

A systematic review of the utility of antidepressant pharmacotherapy in the treatment of vulvodynia pain.

PubMed

Leo, Raphael J; Dewani, Seema

2013-10-01

  Antidepressants have often been recommended as a potential treatment for the management of vulvodynia. However, review of the evidence supporting this recommendation has not been systematically assessed.   To evaluate the efficacy of antidepressant pharmacotherapy in the treatment of vulvodynia.   An assessment of the methodological quality of published reports addressing the utility of antidepressants in the treatment of vulvodynia was undertaken. Several secondary outcomes generated in the existing literature were also examined.   A comprehensive search of the available literature was conducted.   The search yielded 13 published reports, i.e., 2 randomized controlled trials, 1 quasi-experimental trial, 7 non-experimental studies, and 3 case reports. A number of methodological shortcomings were identified in several of the reports with respect to study design including lack of clear inclusion/exclusion criteria, small sample sizes, lack of comparison groups, insufficient blinding, among others. The vast majority of studies utilized tricyclic antidepressants (TCAs). Evidence supporting the benefits of TCAs studied to date was limited, i.e., based largely upon descriptive reports but unsubstantiated by randomized controlled trials. There were no systematic investigations into the comparative efficacy of different antidepressant classes in the treatment of vulvodynia.   There is insufficient evidence to support the recommendation of antidepressant pharmacotherapy in the treatment of vulvodynia. Although some vulvodynia-afflicted patients derive symptom relief from antidepressants, additional research is required to identify those characteristics that would predict those patients for whom antidepressants are more likely to be effective. © 2012 International Society for Sexual Medicine.

Physiological Bases of Bulimia, and Antidepressant Treatment.

ERIC Educational Resources Information Center

Getzfeld, Andrew R.

This paper reviews the literature on the physiological causes of bulimia and investigates the rationale behind the usage of antidepressant medication in the treatment of bulimia nervosa. No definite conclusions can be stated regarding the physiology of bulimia, but a number of hypotheses are suggested. It appears that the hypothalamus is involved…

Duloxetine versus other anti-depressive agents for depression

PubMed Central

Cipriani, Andrea; Koesters, Markus; Furukawa, Toshi A; Nosè, Michela; Purgato, Marianna; Omori, Ichiro M; Trespidi, Carlotta; Barbui, Corrado

2014-01-01

Background Although pharmacological and psychological interventions are both effective for major depression, in primary and secondary care settings antidepressant drugs remain the mainstay of treatment. Amongst antidepressants many different agents are available. Duloxetine hydrochloride is a dual reuptake inhibitor of serotonin and norepinephrine and has been licensed by the Food and Drug Administration in the US for major depressive disorder (MDD), generalised anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia and chronic musculoskeletal pain. Objectives To assess the evidence for the efficacy, acceptability and tolerability of duloxetine in comparison with all other antidepressant agents in the acute-phase treatment of major depression. Search methods MEDLINE (1966 to 2012), EMBASE (1974 to 2012), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to March 2012. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical company marketing duloxetine and experts in this field were contacted for supplemental data. Selection criteria Randomised controlled trials allocating patients with major depression to duloxetine versus any other antidepressive agent. Data collection and analysis 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. Main results A total of 16 randomised controlled trials (overall 5735 participants) were included in this systematic review. Of these, three trials were unpublished. We found 11 studies (overall 3304 participants) comparing duloxetine with one selective serotonin reuptake inhibitor (SSRI) (six studies versus paroxetine, three 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

2010-04-14

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

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

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

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

Antidepressants, antimicrobials or both? Gut microbiota dysbiosis in depression and possible implications of the antimicrobial effects of antidepressant drugs for antidepressant effectiveness.

PubMed

Macedo, Danielle; Filho, Adriano José Maia Chaves; Soares de Sousa, Caren Nádia; Quevedo, João; Barichello, Tatiana; Júnior, Hélio Vitoriano Nobre; Freitas de Lucena, David

2017-01-15

The first drug repurposed for the treatment of depression was the tuberculostatic iproniazid. At present, drugs belonging to new classes of antidepressants still have antimicrobial effects. Dysbiosis of gut microbiota was implicated in the development or exacerbation of mental disorders, such as major depressive disorder (MDD). Based on the current interest in the gut-brain axis, the focus of this narrative review is to compile the available studies regarding the influences of gut microbiota in behavior and depression and to show the antimicrobial effect of antidepressant drugs. A discussion regarding the possible contribution of the antimicrobial effect of antidepressant drugs to its effectiveness/resistance is included. The search included relevant articles from PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge. MDD is associated with changes in gut permeability and microbiota composition. In this respect, antidepressant drugs present antimicrobial effects that could also be related to the effectiveness of these drugs for MDD treatment. Conversely, some antimicrobials present antidepressant effects. Both antidepressants and antimicrobials present neuroprotective/antidepressant and antimicrobial effects. Further studies are needed to evaluate the participation of antimicrobial mechanisms of antidepressants in MDD treatment as well as to determine the contribution of this effect to antidepressant resistance. Copyright © 2016 Elsevier B.V. All rights reserved.

[Unpredictable chronic mild stress effects on antidepressants activities in forced swim test].

PubMed

Kudryashov, N V; Kalinina, T S; Voronina, T A

2015-02-01

The experiments has been designed to study unpredictable chronic mild stress effect on anti-depressive activities of amitriptyline (10 mg/kg) and fluoxetine (20 mg/kg) in forced swim test in male outbred mice. It is shown that acute treatment with fluoxetine does not produce any antidepressant effects in mice following stress of 14 days while the sub-chronic injections of fluoxetine result in more deep depressive-like behavior. In 28 daily stressed mice, antidepressant effect of fluoxetine is observed independently of the injection rates. Amitriptyline demonstrates the antidepressant activity regardless of the duration of stress or administration scheduling, but at the same time the severity of anti-immobilization effect of amitriptyline in stressed mice is weaker in compare to non-stressed trails. Thus, the injection rates and duration of unpredictable mild chronic stress are the parameters that determine the efficiency of antidepressants in the mouse forced swimming test.

Primary Care Providers’ Initial Treatment Decisions and Antidepressant Prescribing for Adolescent Depression

PubMed Central

Radovic, Ana; Farris, Coreen; Reynolds, Kerry; Reis, Evelyn C.; Miller, Elizabeth; Stein, Bradley D.

2014-01-01

OBJECTIVE Adolescent depression is a serious and undertreated public health problem. Nonetheless, pediatric primary care providers (PCPs) may have low rates of antidepressant prescribing due to structural and training barriers. We examined the impact of symptom severity and provider characteristics on initial depression treatment decisions in a setting with fewer structural barriers, an integrated behavioral health network. METHOD We administered a cross sectional survey to 58 PCPs within a large pediatric practice network. We compared PCP reports of initial treatment decisions in response to two vignettes describing depressed adolescents with either moderate or severe symptoms. We measured PCP depression knowledge, attitudes toward addressing psychosocial concerns, demographics, and practice characteristics. RESULTS Few PCPs (25% for moderate, 32% for severe) recommended an antidepressant. Compared with treatment recommendations for moderate depression, severe depression was associated with a greater likelihood of child psychiatry referral (OR 5.50[95% CI 2.47-12.2] p<.001). Depression severity did not affect the likelihood of antidepressant recommendation (OR 1.58[95% CI 0.80-3.11] p=.19). Antidepressants were more likely to be recommended by PCPs with greater depression knowledge (OR 1.72[95% CI 1.14-2.59] p=.009) and access to an on-site mental health provider (OR 5.13[95% CI 1.24-21.2] p=.02) and less likely to be recommended by PCPs who reported higher provider burden when addressing psychosocial concerns (OR 0.85[95% CI 0.75-0.98] p=.02). CONCLUSION PCPs infrequently recommended antidepressants for adolescents, regardless of depression severity. Continued PCP support through experiential training, accounting for provider burden when addressing psychosocial concerns, and co-management with mental health providers may increase PCPs’ antidepressant prescribing. PMID:24336091

Treatment of Adults With Treatment-Resistant Depression: Electroconvulsive Therapy Plus Antidepressant or Electroconvulsive Therapy Alone? Evidence From an Indirect Comparison Meta-Analysis

PubMed Central

Song, Guo-Min; Tian, Xu; Shuai, Ting; Yi, Li-Juan; Zeng, Zi; Liu, Shuang; Zhou, Jian-Guo; Wang, Yan

2015-01-01

Abstract Electroconvulsive therapy (ECT) and antidepressant are the effective treatment alternatives for patients with treatment-resistant depression (TRD); however, the effects and safety of the ECT plus antidepressant relative to ECT alone remain controversial. We decide to assess the potential of ECT plus antidepressant compared with ECT alone by undertaking an indirect comparison meta-analysis. Databases from PubMed, ISI Web of Science, CENTRAL, Clinicaltrials.gov, EMBASE, CBM (China Biomediccal Literatures Database), and CNKI (China National Knowledge Infrastructure) were searched for relevant studies through November 21, 2014. Literature was screened, data were extracted and methodological quality of the eligible trial was assessed by 2 independent reviewers accordingly. Then, head-to-head and indirect comparison meta-analyses were carried out. A total of 17 studies which including 13 studies regarding ECT plus antidepressant versus antidepressant alone and 4 studies concerning ECT versus antidepressant alone containing a total of 1098 patients were incorporated into this meta-analysis. The head-to-head comparison suggested that response rate can be improved in the ECT plus antidepressant (RR, 1.82; 95% CI, 1.55–2.14) and ECT alone group (RR, 2.24, 95% CI, 1.51–3.33) compared with antidepressant alone, respectively; adverse complications including memory deterioration and somatization were not significantly increased except incidence of memory deterioration in ECT plus antidepressant in the 4th weeks after treatment (RR, 0.09, 95% CI, 0.02–0.49). Indirect comparison meta-analysis showed that no significant differences were detected in response rate and memory deterioration between ECT plus antidepressant and ECT alone. However, ECT plus antidepressant increased the incidence of memory deterioration relative to ECT alone. With present evidence, the regime of ECT plus antidepressant should not be preferentially recommended to treat the patients with TRD

Evaluation of antidepressant like activity of curcumin and its combination with fluoxetine and imipramine: an acute and chronic study.

PubMed

Sanmukhani, Jayesh; Anovadiya, Ashish; Tripathi, Chandrabhanu B

2011-01-01

Curcumin is the active ingredient of commonly used spice Curuma longa Linn. In the present study, the antidepressant like activity of curcumin and its combination with fluoxetine and imipramine was studied in acute model (three doses 24, 5 and 1 h before test) of forced swimming test (FST) in glass jar and tail suspension test (TST) in mice and in chronic model (14 day study) of FST with water wheel in rats. All the tests were carried out in the following seven groups (n = 6 in each group), drugs being given orally (doses for mice): Group 1 (vehicle), group 2 (curcumin 50 mg/kg), group 3 (curcumin 100 mg/kg), group 4 (fluoxetine 20 mg/kg), group 5 (imipramine 15 mg/kg), group 6 (curcumin 100 mg/kg plus fluoxetine 20 mg/kg) and group 7 (curcumin 100 mg/kg plus imipramine 15 mg/kg). Equivalent doses for rats were used. Both the acute model of FST and TST, and the chronic model of FST with water wheel showed significant antidepressant like activity of curcumin in 100 mg/kg dose as compared to vehicle control (p < 0.05). The effect of curcumin (100 mg/kg) was similar to that of fluoxetine and imipramine (p > 0.05) but its addition to fluoxetine and imipramine did not improve their antidepressant activity (p > 0.05). Curcumin increased both the swimming and climbing behavior in FST, thus its antidepressant like activity could be due to an increase in serotonin, norepinephrine and dopamine levels in the brain. Curcumin can be a useful antidepressant especially in cases which respond to drugs having mixed effects on serotonin and catecholamines levels in the brain.

Early Prediction of Acute Antidepressant Treatment Response and Remission in Pediatric Major Depressive Disorder

ERIC Educational Resources Information Center

Tao, Rongrong; Emslie, Graham; Mayes, Taryn; Nakonezny, Paul; Kennard, Betsy; Hughes, Carroll

2009-01-01

The rate of symptom improvement during the early weeks of acute fluoxetine treatment is a good indicator of remission. This finding was made after evaluating the outcome of the fluoxetine treatment on 168 children and adults with depression.

Antidepressant Studies in Parkinson’s Disease

PubMed Central

Weintraub, Daniel; Morales, Knashawn H.; Moberg, Paul J.; Bilker, Warren B.; Balderston, Catherine; Duda, John E.; Katz, Ira R.; Stern, Matthew B.

2007-01-01

The objective of this study was to determine effect sizes for both antidepressant treatment and placebo for depression in Parkinson’s disease (PD), and to compare the findings with those reported in elderly depressed patients without PD. Recent reviews have concluded that there is little empiric evidence to support the use of antidepressants in PD; however, available data has not been analyzed to determine the effect size for antidepressant treatment in PD depression. A literature review identified antidepressant studies in PD. Suitable studies were analyzed using meta-analytic techniques, and effect sizes were compared with those from antidepressant studies in elderly patients without PD. Large effect sizes were found for both active treatment and placebo in PD, but there was no difference between the two groups. In contrast, active treatment was superior to placebo in depressed elderly patients without PD. In PD, increasing age and a diagnosis of major depression were associated with better treatment response. Results also suggest that newer antidepressants are well tolerated in PD. Despite the high prevalence of depression and antidepressant use in PD, controlled treatment research has been almost non-existent. Meta-analysis results suggest a large but nonspecific effect for depression treatment in PD. In addition, PD patients may benefit less from antidepressant treatment, particularly selective serotonin reuptake inhibitors, than do elderly patients without PD. PMID:15954137

IC Treatment: Antidepressants

MedlinePlus

... prescribes you a TCA, take it in the early evening to eliminate unwanted morning drowsiness. For constipation, increase the amount of fiber in your diet. Consider taking Metamucil or a stool softener such as Colace. Pregnancy & Warnings None of the antidepressants in any of ...

Disparities in Depressive Symptoms and Antidepressant Treatment by Gender and Race/Ethnicity among People Living with HIV in the United States.

PubMed

Bengtson, Angela M; Pence, Brian W; Crane, Heidi M; Christopoulos, Katerina; Fredericksen, Rob J; Gaynes, Bradley N; Heine, Amy; Mathews, W Christopher; Moore, Richard; Napravnik, Sonia; Safren, Steven; Mugavero, Michael J

2016-01-01

To describe disparities along the depression treatment cascade, from indication for antidepressant treatment to effective treatment, in HIV-infected individuals by gender and race/ethnicity. The Center for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) cohort includes 31,000 HIV-infected adults in routine clinical care at 8 sites. Individuals were included in the analysis if they had a depressive symptoms measure within one month of establishing HIV care at a CNICS site. Depressive symptoms were measured using the validated Patient Health Questionnaire-9 (PHQ-9). Indication for antidepressant treatment was defined as PHQ-9 ≥ 10 or a current antidepressant prescription. Antidepressant treatment was defined as a current antidepressant prescription. Evidence-based antidepressant treatment was considered treatment changes based on a person's most recent PHQ-9, in accordance with clinical guidelines. We calculated the cumulative probability of moving through the depression treatment cascade within 24 months of entering CNICS HIV care. We used multivariable Cox proportional hazards models to estimate associations between gender, race/ethnicity, and a range of depression outcomes. In our cohort of HIV-infected adults in routine care, 47% had an indication for antidepressant treatment. Significant drop-offs along the depression treatment cascade were seen for the entire study sample. However, important disparities existed. Women were more likely to have an indication for antidepressant treatment (HR 1.54; 95% CI 1.34, 1.78), receive antidepressant treatment (HR 2.03; 95% CI 1.53, 2.69) and receive evidence-based antidepressant treatment (HR 1.67; 95% CI 1.03, 2.74), even after accounting for race/ethnicity. Black non-Hispanics (HR 0.47, 95% CI 0.35, 0.65), Hispanics (HR 0.63, 95% CI 0.44, 0.89) and other race/ethnicities (HR 0.35, 95% CI 0.17, 0.73) were less likely to initiate antidepressant treatment, compared to white non-Hispanics. In our cohort

Antidepressant treatment outcomes of psychogenic movement disorder.

PubMed

Voon, Valerie; Lang, Anthony E

2005-12-01

Psychogenic movement disorder (PMD) is a subtype of conversion disorder. We describe the outcomes of a series of PMD patients following antidepressant treatment. Twenty-three outpatients with chronic PMD, diagnosed using Fahn and Williams' criteria, underwent psychiatric assessment. The patients were referred for assessment and management from January 2003 to July 2004. Fifteen agreed to be treated with antidepressants. Patients received citalopram or paroxetine; those who did not respond after 4 weeks of taking an optimal dose were switched to venlafaxine. Concurrently, 3 had supportive psychotherapy, and 1 had family intervention. Assessments included the DSM-IV-based Mini-International Neuropsychiatric Interview and scales measuring depression, anxiety, and motor and global severity. Eighteen patients (78%) had at least 1 Axis I diagnosis in addition to the somatoform diagnosis, and 3 (13%) had somatization disorder. Five (22%) had previous psychiatric contact. Nine (39%) had previously been treated with antidepressants, but only 4 (17%) had adequate trials. No significant differences existed in patient characteristics between treated and untreated groups. Among treated patients, Montgomery-Asberg Depression Rating Scale scores improved from baseline (p < .01). Two treated subgroups were identified: 10 patients (67%) had primary conversion disorder, of whom 8 had marked motor and global improvements with 7 complete remissions, and 5 (33%) had primary hypochondriasis, somatization disorder, or probable factitious disorder/malingering, of whom none improved. All of the patients with primary conversion disorder had a current or previous depressive or anxiety disorder compared with 40% (N = 2) of the patients with additional somatoform diagnoses. Our preliminary findings suggest that chronic PMD with primary conversion symptoms and with recent or current depression or anxiety may respond to antidepressants. Further well-designed studies, now under way, are required

Emotional blunting with antidepressant treatments: A survey among depressed patients.

PubMed

Goodwin, G M; Price, J; De Bodinat, C; Laredo, J

2017-10-15

Emotional blunting is regularly reported in depressed patients on antidepressant treatment but its actual frequency is poorly understood. We have previously used qualitative methods to develop an appropriate scale, the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants (OQESA). Six hundred and sixty nine depressed patients on treatment and 150 recovered (formerly depressed) controls (aged ≥18 years) participated in this internet-based survey. The rate of emotional blunting in treated depressed patients was 46%, slightly more frequent in men than women (52% versus 44%) and in those with higher Hospital Anxiety and Depression (HAD) scale scores. There was no difference according to antidepressant agent, though it appeared less frequent with bupropion. Depressed patients with emotional blunting had much higher total blunting scores on OQESA than controls (42.83 ± 14.73 versus 25.73 ± 15.00, p < 0.0001) and there was a correlation between total blunting score and HAD-Depression score (r = 0.521). Thus, those with HAD-D score >7 (n = 170) had a higher total questionnaire score, 49.23±12.03, than those with HAD-D score ≤7 (n = 140), 35.07 ± 13.98, and the difference between the two groups was highly significant. However, patients with HAD-D score ≤7 (n = 140) had a higher total score (35.07 ± 13.98) than the recovered controls (n = 150) (25.73 ± 15.00), and the difference between the two groups was significant. Among the patients with emotional blunting, 37% had a negative perception of their condition and 38% positive. Men reported a more negative perception than women (p=0.008), and patients with a negative perception were more likely to have higher HAD scores. Higher levels of emotional blunting are associated with a more negative perception of it by the patient (r = -0.423). Include self-evaluation and the modest size of the sample for detection of differences between antidepressants. Emotional blunting is reported by nearly half of

Alpha2-adrenoceptor blockade accelerates the neurogenic, neurotrophic, and behavioral effects of chronic antidepressant treatment.

PubMed

Yanpallewar, Sudhirkumar U; Fernandes, Kimberly; Marathe, Swananda V; Vadodaria, Krishna C; Jhaveri, Dhanisha; Rommelfanger, Karen; Ladiwala, Uma; Jha, Shanker; Muthig, Verena; Hein, Lutz; Bartlett, Perry; Weinshenker, David; Vaidya, Vidita A

2010-01-20

Slow-onset adaptive changes that arise from sustained antidepressant treatment, such as enhanced adult hippocampal neurogenesis and increased trophic factor expression, play a key role in the behavioral effects of antidepressants. alpha(2)-Adrenoceptors contribute to the modulation of mood and are potential targets for the development of faster acting antidepressants. We investigated the influence of alpha(2)-adrenoceptors on adult hippocampal neurogenesis. Our results indicate that alpha(2)-adrenoceptor agonists, clonidine and guanabenz, decrease adult hippocampal neurogenesis through a selective effect on the proliferation, but not the survival or differentiation, of progenitors. These effects persist in dopamine beta-hydroxylase knock-out (Dbh(-/-)) mice lacking norepinephrine, supporting a role for alpha(2)-heteroceptors on progenitor cells, rather than alpha(2)-autoreceptors on noradrenergic neurons that inhibit norepinephrine release. Adult hippocampal progenitors in vitro express all the alpha(2)-adrenoceptor subtypes, and decreased neurosphere frequency and BrdU incorporation indicate direct effects of alpha(2)-adrenoceptor stimulation on progenitors. Furthermore, coadministration of the alpha(2)-adrenoceptor antagonist yohimbine with the antidepressant imipramine significantly accelerates effects on hippocampal progenitor proliferation, the morphological maturation of newborn neurons, and the increase in expression of brain derived neurotrophic factor and vascular endothelial growth factor implicated in the neurogenic and behavioral effects of antidepressants. Finally, short-duration (7 d) yohimbine and imipramine treatment results in robust behavioral responses in the novelty suppressed feeding test, which normally requires 3 weeks of treatment with classical antidepressants. Our results demonstrate that alpha(2)-adrenoceptors, expressed by progenitor cells, decrease adult hippocampal neurogenesis, while their blockade speeds up antidepressant action

α2-adrenoceptor blockade accelerates the neurogenic, neurotrophic, and behavioral effects of chronic antidepressant treatment

PubMed Central

Yanpallewar, Sudhirkumar U.; Fernandes, Kimberly; Marathe, Swananda V.; Vadodaria, Krishna C.; Jhaveri, Dhanisha; Rommelfanger, Karen; Ladiwala, Uma; Jha, Shanker; Muthig, Verena; Hein, Lutz; Bartlett, Perry; Weinshenker, David; Vaidya, Vidita A.

2010-01-01

Slow-onset adaptive changes that arise from sustained antidepressant treatment, such as enhanced adult hippocampal neurogenesis and increased trophic factor expression, play a key role in the behavioral effects of antidepressants. α2-adrenoceptors contribute to the modulation of mood and are potential targets for the development of faster acting antidepressants. We investigated the influence of α2-adrenoceptors on adult hippocampal neurogenesis. Our results indicate that α2-adrenoceptor agonists, clonidine and guanabenz, decrease adult hippocampal neurogenesis through a selective effect on the proliferation, but not the survival or differentiation, of progenitors. These effects persist in dopamine β-hydroxylase knockout (Dbh −/−) mice lacking norepinephrine, supporting a role for α2-heteroceptors on progenitor cells, rather than α2-autoreceptors on noradrenergic neurons that inhibit norepinephrine release. Adult hippocampal progenitors in vitro express all the α2-adrenoceptor subtypes, and decreased neurosphere frequency and BrdU incorporation indicate direct effects of α2-adrenoceptor stimulation on progenitors. Further, co-administration of the α2-adrenoceptor antagonist yohimbine with the antidepressant imipramine significantly accelerates effects on hippocampal progenitor proliferation, the morphological maturation of newborn neurons, and the increase in expression of brain derived neurotrophic factor and vascular endothelial growth factor implicated in the neurogenic and behavioral effects of antidepressants. Finally, short duration (7 day) yohimbine and imipramine treatment results in robust behavioral responses in the novelty suppressed feeding test, which normally requires 3 weeks of treatment with classical antidepressants. Our results demonstrate that α2-adrenoceptors, expressed by progenitor cells, decrease adult hippocampal neurogenesis, while their blockade speeds up antidepressant action, highlighting their importance as targets for

The antidepressant- and anxiolytic-like effects following co-treatment with escitalopram and risperidone in rats.

PubMed

Kaminska, K; Rogoz, Z

2016-06-01

Several clinical reports have documented a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants, in particular selective serotonin reuptake inhibitors (SSRI), in the treatment of drug-resistant depression and treatment-resistant anxiety disorders. In the present study, we investigated the effect of treatment with the antidepressant escitalopram (SSRI) given separately or jointly with a low dose of risperidone (an atypical antipsychotic) in the forced swim test and in the elevated plus-maze test in rats. The obtained results showed that escitalopram at doses of 2.5 or 5 mg/kg evoked antidepressant-like effect in the forced swim test. Moreover, risperidone at low doses (0.05 or 0.1 mg/kg) enhanced the antidepressant-like activity of escitalopram (1 mg/kg) in this test by increasing the swimming time and decreasing the immobility time in those animals. WAY 100635 (a serotonin 5-HT1A receptor antagonist) at a dose of 0.1 mg/kg abolished the antidepressant-like effect induced by co-administration of escitalopram and risperidone. The active behavior in that test did not reflect an increase in general activity, since the combined treatment with escitalopram and risperidone failed to enhance the exploratory activity of rats. In the following experiment, we showed that escitalopram (5 mg/kg) and mirtazapine (5 or 10 mg/kg) or risperidone (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze test, and the combined treatment with an ineffective dose of risperidone (0.05 mg/kg) enhanced the anxiolytic-like effects of escitalopram (2.5 mg/kg) or mirtazapine (1 and 2.5 mg/kg) in this test. The obtained results suggest that risperidone applied at a low dose enhances the antidepressant-like activity of escitalopram in the forced swim test, and that 5-HT1A receptors may play some role in these effects. Moreover, a low dose of risperidone may also enhance the anxiolytic-like action of the studied

Antidepressant prescribing and changes in antidepressant poisoning mortality and suicide in England, 1993-2004.

PubMed

Morgan, Oliver; Griffiths, Clare; Majeed, Azeem

2008-03-01

In England, the impact of increased use of antidepressant medications is unclear. We examine associations between antidepressant use, suicide and antidepressant poisoning mortality, adjusted for important covariates. Data on suicide and antidepressant poisoning mortality were provided by the Office for National Statistics. Prescription data were provided by the Department of Health. Age- and sex-specific prescribing rates were estimated from The Health Improvement Network primary care data. We measured the association between prescribing, suicide and poisoning mortality after adjusting for age, sex, calendar year, prescribing rates and use of newer antidepressants drugs. The prevalence of antidepressant treatment increased during the 1990s for all age and sex groups. Treatment prevalence remained constant from 2002 but declined among children and adolescents. Between 1993 and 2004, age-standardized rates for suicide decreased from 98.2 to 81.3 per million populations and for antidepressants from 9.2 to 7.4 per million populations. Before adjustment, increased antidepressant prescribing was associated with a decrease in suicide (r(s) = -0.90, P < 0.001) and antidepressant poisoning mortality rates (r(s) = -0.65, P = 0.023). This association disappeared after adjustment. In England, at a population level, there does not appear to be an association between antidepressant prescribing and antidepressant poisoning mortality or suicide.

S-Ketamine Mediates Its Acute and Sustained Antidepressant-Like Activity through a 5-HT1B Receptor Dependent Mechanism in a Genetic Rat Model of Depression.

PubMed

du Jardin, Kristian G; Liebenberg, Nico; Cajina, Manuel; Müller, Heidi K; Elfving, Betina; Sanchez, Connie; Wegener, Gregers

2017-01-01

Rationale: The mechanisms responsible for the unique antidepressant properties of ketamine have only been partly resolved. Recent preclinical reports implicate the neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] in the antidepressant-like response of ketamine, and modulation of 5-HT 1B receptors has been hypothesized to attain an important role. Objectives: To evaluate the role of endogenous stimulation of 5-HT 1B heteroreceptors in the antidepressant-like activity of S -ketamine. Method: Flinders sensitive line (FSL) rats, a genetic model of depression, were depleted of endogenous 5-HT by 4-chloro-DL-phenylalanine methyl ester HCl administration (pCPA; 86 mg/kg/day for 3 days). In pCPA-pretreated and control FSL rats, the acute and sustained effects of a single dose of S -ketamine (15 mg/kg) and the selective 5-HT 1B receptor agonist CP94253 (1-6 mg/kg) alone and in combination with S -ketamine were studied in the forced swim test (FST), a commonly used assay that detects antidepressant activity. Results: pCPA pretreatment decreased cortical 5-HT levels to ∼6% but did not affect the baseline behavioral phenotype of FSL rats. S -ketamine demonstrated acute and sustained antidepressant-like activity, both of which were abolished by 5-HT depletion. Combining S -ketamine with a sub-effective dose of CP94253 (1 mg/kg) rescued S -ketamine's acute and sustained antidepressant-like effects, when CP94253 was administered 2 h prior to the FST. Co-administration of S -ketamine and CP94253 did not affect the plasma level of either compound, suggesting that the observed behavioral interaction could not be ascribed to a kinetic drug-drug interaction. Conclusion: 5-HT 1B receptor activation during testing appears to be critical for S -ketamine's antidepressant-like potentials in this model.

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

The effects of drugs on human models of emotional processing: an account of antidepressant drug treatment.

PubMed

Pringle, Abbie; Harmer, Catherine J

2015-12-01

Human models of emotional processing suggest that the direct effect of successful antidepressant drug treatment may be to modify biases in the processing of emotional information. Negative biases in emotional processing are documented in depression, and single or short-term dosing with conventional antidepressant drugs reverses these biases in depressed patients prior to any subjective change in mood. Antidepressant drug treatments also modulate emotional processing in healthy volunteers, which allows the consideration of the psychological effects of these drugs without the confound of changes in mood. As such, human models of emotional processing may prove to be useful for testing the efficacy of novel treatments and for matching treatments to individual patients or subgroups of patients.

Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial.

PubMed

Nurnberg, H George; Hensley, Paula L; Gelenberg, Alan J; Fava, Maurizio; Lauriello, John; Paine, Susan

2003-01-01

Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance. To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants. Prospective, parallel-group, randomized, double-blind, placebo-controlled trial conducted between November 1, 2000, and January 1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD] age, 45 [8] years) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment. Patients were randomly assigned to take sildenafil (n = 45) or placebo (n = 45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks. The primary outcome measure was score on the Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were scores on the International Index of Erectile Function, Arizona Sexual Experience Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and Hamilton Rating Scale for Depression (HAM-D). Among the 90 randomized patients, 93% (83/89) of patients treated per protocol took at least 1 dose of study drug and 85% (76/89) completed week 6 end-point assessments with last observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or very much improved (P<.001). Erectile function, arousal, ejaculation, orgasm, and overall satisfaction domain measures improved significantly in sildenafil compared with placebo patients. Mean depression scores remained consistent with remission (HAM-D score < or =10) in both groups for the study duration. In our study, sildenafil effectively improved erectile function and other aspects of sexual function in men with sexual dysfunction associated with the use of SRI antidepressants. These improvements may allow patients

TPH-2 Polymorphisms Interact with Early Life Stress to Influence Response to Treatment with Antidepressant Drugs.

PubMed

Xu, Zhi; Reynolds, Gavin P; Yuan, Yonggui; Shi, Yanyan; Pu, Mengjia; Zhang, Zhijun

2016-11-01

Variation in genes implicated in monoamine neurotransmission may interact with environmental factors to influence antidepressant response. We aimed to determine how a range of single nucleotide polymorphisms in monoaminergic genes influence this response to treatment and how they interact with childhood trauma and recent life stress in a Chinese sample. An initial study of monoaminergic coding region single nucleotide polymorphisms identified significant associations of TPH2 and HTR1B single nucleotide polymorphisms with treatment response that showed interactions with childhood and recent life stress, respectively (Xu et al., 2012). A total of 47 further single nucleotide polymorphisms in 17 candidate monoaminergic genes were genotyped in 281 Chinese Han patients with major depressive disorder. Response to 6 weeks' antidepressant treatment was determined by change in the 17-item Hamilton Depression Rating Scale score, and previous stressful events were evaluated by the Life Events Scale and Childhood Trauma Questionnaire-Short Form. Three TPH2 single nucleotide polymorphisms (rs11178998, rs7963717, and rs2171363) were significantly associated with antidepressant response in this Chinese sample, as was a haplotype in TPH2 (rs2171363 and rs1487278). One of these, rs2171363, showed a significant interaction with childhood adversity in its association with antidepressant response. These findings provide further evidence that variation in TPH2 is associated with antidepressant response and may also interact with childhood trauma to influence outcome of antidepressant treatment. © The Author 2016. Published by Oxford University Press on behalf of CINP.

TPH-2 Polymorphisms Interact with Early Life Stress to Influence Response to Treatment with Antidepressant Drugs

PubMed Central

Reynolds, Gavin P.; Yuan, Yonggui; Shi, Yanyan; Pu, Mengjia; Zhang, Zhijun

2016-01-01

Background: Variation in genes implicated in monoamine neurotransmission may interact with environmental factors to influence antidepressant response. We aimed to determine how a range of single nucleotide polymorphisms in monoaminergic genes influence this response to treatment and how they interact with childhood trauma and recent life stress in a Chinese sample. An initial study of monoaminergic coding region single nucleotide polymorphisms identified significant associations of TPH2 and HTR1B single nucleotide polymorphisms with treatment response that showed interactions with childhood and recent life stress, respectively (Xu et al., 2012). Methods: A total of 47 further single nucleotide polymorphisms in 17 candidate monoaminergic genes were genotyped in 281 Chinese Han patients with major depressive disorder. Response to 6 weeks’ antidepressant treatment was determined by change in the 17-item Hamilton Depression Rating Scale score, and previous stressful events were evaluated by the Life Events Scale and Childhood Trauma Questionnaire-Short Form. Results: Three TPH2 single nucleotide polymorphisms (rs11178998, rs7963717, and rs2171363) were significantly associated with antidepressant response in this Chinese sample, as was a haplotype in TPH2 (rs2171363 and rs1487278). One of these, rs2171363, showed a significant interaction with childhood adversity in its association with antidepressant response. Conclusions: These findings provide further evidence that variation in TPH2 is associated with antidepressant response and may also interact with childhood trauma to influence outcome of antidepressant treatment. PMID:27521242

Ghrelin Serum Concentrations Are Associated with Treatment Response During Lithium Augmentation of Antidepressants

PubMed Central

Bopp, Sandra; Schlattmann, Peter; Himmerich, Hubertus; Bschor, Tom; Richter, Christoph; Elstner, Samuel; Stamm, Thomas J; Schulz-Ratei, Brigitte; Lingesleben, Alexandra; Reischies, Friedel M; Sterzer, Philipp; Borgwardt, Stefan; Bauer, Michael; Heinz, Andreas; Hellweg, Rainer; Lang, Undine E; Adli, Mazda

2017-01-01

Abstract Background Lithium augmentation of antidepressants is an effective strategy in treatment-resistant depression. The proteohormone ghrelin is thought to be involved in the pathophysiology of depression. The purpose of this study was to investigate the association of treatment response with the course of ghrelin levels during lithium augmentation. Method Ghrelin serum concentrations and severity of depression were measured in 85 acute depressive patients before and after 4 weeks of lithium augmentation. Results In a linear mixed model analysis, we found a significant effect of response*time interaction (F1.81=9.48; P=.0028): under treatment, ghrelin levels increased in nonresponders and slightly decreased in responders to lithium augmentation. The covariate female gender had a significant positive effect (F1.83=4.69; P=.033), whereas time, response, appetite, and body mass index (kg/m2) did not show any significant effect on ghrelin levels (P>.05). Conclusion This is the first study showing that the course of ghrelin levels separates responders and nonresponders to lithium augmentation. Present results support the hypothesis that ghrelin serum concentrations might be involved in response to pharmacological treatment of depression. PMID:28911006

Ghrelin Serum Concentrations Are Associated with Treatment Response During Lithium Augmentation of Antidepressants.

PubMed

Ricken, Roland; Bopp, Sandra; Schlattmann, Peter; Himmerich, Hubertus; Bschor, Tom; Richter, Christoph; Elstner, Samuel; Stamm, Thomas J; Schulz-Ratei, Brigitte; Lingesleben, Alexandra; Reischies, Friedel M; Sterzer, Philipp; Borgwardt, Stefan; Bauer, Michael; Heinz, Andreas; Hellweg, Rainer; Lang, Undine E; Adli, Mazda

2017-09-01

Lithium augmentation of antidepressants is an effective strategy in treatment-resistant depression. The proteohormone ghrelin is thought to be involved in the pathophysiology of depression. The purpose of this study was to investigate the association of treatment response with the course of ghrelin levels during lithium augmentation. Ghrelin serum concentrations and severity of depression were measured in 85 acute depressive patients before and after 4 weeks of lithium augmentation. In a linear mixed model analysis, we found a significant effect of response*time interaction (F1.81=9.48; P=.0028): under treatment, ghrelin levels increased in nonresponders and slightly decreased in responders to lithium augmentation. The covariate female gender had a significant positive effect (F1.83=4.69; P=.033), whereas time, response, appetite, and body mass index (kg/m2) did not show any significant effect on ghrelin levels (P>.05). This is the first study showing that the course of ghrelin levels separates responders and nonresponders to lithium augmentation. Present results support the hypothesis that ghrelin serum concentrations might be involved in response to pharmacological treatment of depression. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Obesity and Its Potential Effects on Antidepressant Treatment Outcomes in Patients with Depressive Disorders: A Literature Review

PubMed Central

Woo, Young Sup; Seo, Hye-Jin; McIntyre, Roger S.; Bahk, Won-Myong

2016-01-01

Accumulating evidence regarding clinical, neurobiological, genetic, and environmental factors suggests a bidirectional link between obesity and depressive disorders. Although a few studies have investigated the link between obesity/excess body weight and the response to antidepressants in depressive disorders, the effect of weight on treatment response remains poorly understood. In this review, we summarized recent data regarding the relationship between the response to antidepressants and obesity/excess body weight in clinical studies of patients with depressive disorders. Although several studies indicated an association between obesity/excess body weight and poor antidepressant responses, it is difficult to draw definitive conclusions due to the variability of subject composition and methodological differences among studies. Especially, differences in sex, age and menopausal status, depressive symptom subtypes, and antidepressants administered may have caused inconsistencies in the results among studies. The relationship between obesity/excess body weight and antidepressant responses should be investigated further in high-powered studies addressing the differential effects on subject characteristics and treatment. Moreover, future research should focus on the roles of mediating factors, such as inflammatory markers and neurocognitive performance, which may alter the antidepressant treatment outcome in patients with comorbid obesity and depressive disorder. PMID:26771598

Effects of Antidepressants on Sleep.

PubMed

Wichniak, Adam; Wierzbicka, Aleksandra; Walęcka, Małgorzata; Jernajczyk, Wojciech

2017-08-09

The aim of this review article was to summarize recent publications on effects of antidepressants on sleep and to show that these effects not only depend on the kind of antidepressant drugs but are also related to the dose, the time of drug administration, and the duration of the treatment. Complaints of disrupted sleep are very common in patients suffering from depression, and they are listed among diagnostic criteria for this disorder. Moreover, midnocturnal insomnia is the most frequent residual symptom of depression. Thus, all antidepressants should normalize sleep. However, at least in short-term treatment, many antidepressants with so-called activating effects (e.g. fluoxetine, venlafaxine) may disrupt sleep, while others with sedative properties (e.g., doxepin, mirtazapine, trazodone) rapidly improve sleep, but may cause problems in long-term treatment due to oversedation.For sleep-promoting action, the best effects can frequently be achieved with a very low dose, administered early enough before bedtime and importantly, always as a part of more complex interventions based on the cognitive-behavioral protocol to treat insomnia (CBT-I). For successful treatment of depression, it is necessary to understand the effects of antidepressants on sleep. Each physician should also be aware that some antidepressants may worsen or induce primary sleep disorders like restless legs syndrome, sleep bruxism, REM sleep behavior disorder, nightmares, and sleep apnea, which may result from an antidepressant-induced weight gain.

Potentiation of omega-3 fatty acid antidepressant-like effects with low non-antidepressant doses of fluoxetine and mirtazapine.

PubMed

Laino, Carlos Horacio; Fonseca, Cristina; Sterin-Speziale, Norma; Slobodianik, Nora; Reinés, Analía

2010-12-01

Despite the advances in psychopharmacology, the treatment of depressive disorders is still not satisfactory. Side effects and resistance to antidepressant drugs are the greatest complications during treatment. Based on recent evidence, omega-3 fatty acids may influence vulnerability and outcome in depressive disorders. The aim of this study was to further characterize the omega-3 antidepressant-like effect in rats in terms of its behavioral features in the depression model forced swimming test either alone or in combination with antidepressants fluoxetine or mirtazapine. Ultimately, we prompted to determine the lowest dose at which omega-3 fatty acids and antidepressant drugs may still represent a pharmacological advantage when employed in combined treatments. Chronic diet supplementation with omega-3 fatty acids produced concentration-dependent antidepressant-like effects in the forced swimming test displaying a behavioral profile similar to fluoxetine but different from mirtazapine. Fluoxetine or mirtazapine at antidepressant doses (10 and 20 mg/kg/day, respectively) rendered additive effects in combination with omega-3 fatty acid supplementation (720 mg/kg/day). Beneficial effects of combined treatment were also observed at sub-effective doses (1 mg/kg/day) of fluoxetine or mirtazapine, since in combination with omega-3 fatty acids (720 mg/kg/day), antidepressants potentiated omega-3 antidepressant-like effects. The antidepressant-like effects occurred in the absence of changes in brain phospholipid classes. The therapeutic approach of combining omega-3 fatty acids with low ineffective doses of antidepressants might represent benefits in the treatment of depression, especially in patients with depression resistant to conventional treatments and even may contribute to patient compliance by decreasing the magnitude of some antidepressant dose-dependent side effects. Copyright © 2010 Elsevier B.V. All rights reserved.

Ferulic acid chronic treatment exerts antidepressant-like effect: role of antioxidant defense system.

PubMed

Lenzi, Juliana; Rodrigues, Andre Felipe; Rós, Adriana de Sousa; de Castro, Amanda Blanski; de Castro, Bianca Blanski; de Lima, Daniela Delwing; Magro, Débora Delwing Dal; Zeni, Ana Lúcia Bertarello

2015-12-01

Oxidative stress has been claimed a place in pathophysiology of depression; however, the details of the neurobiology of this condition remains incompletely understood. Recently, treatments employing antioxidants have been thoroughly researched. Ferulic acid (FA) is a phenolic compound with antioxidant and antidepressant-like effects. Herein, we investigated the involvement of the antioxidant activity of chronic oral FA treatment in its antidepressant-like effect using the tail suspension test (TST) and the forced swimming test (FST) in mice. The modulation of antioxidant system in blood, hippocampus and cerebral cortex was assessed after stress induction through TST and FST. Our results show that FA at the dose of 1 mg/kg has antidepressant-like effect without affecting locomotor activity. The stress induced by despair tests was able to decrease significantly the activities of superoxide dismutase (SOD) in the blood, catalase (CAT) in the blood and cerebral cortex and glutathione peroxidase (GSH-Px) in the cerebral cortex. Thiobarbituric acid-reactive substances (TBA-RS) levels were increased significantly in the cerebral cortex. Furthermore, the results show that FA was capable to increase SOD, CAT and GSH-Px activities and decrease TBA-RS levels in the blood, hippocampus and cerebral cortex. These findings demonstrated that FA treatment in low doses is capable to exert antidepressant-like effect with the involvement of the antioxidant defense system modulation.

Antidepressant-like Responses to Lithium in Genetically Diverse Mouse Strains

PubMed Central

Can, Adem; Blackwell, Robert A.; Piantadosi, Sean C.; Dao, David T.; O’Donnell, Kelley C.; Gould, Todd D.

2011-01-01

A mood stabilizing and antidepressant response to lithium is only found in a subgroup of bipolar disorder and depression patients. Identifying strains of mice that are responsive and non-responsive to lithium may elucidate genomic and other biological factors that play a role in lithium responsiveness. Mouse strains were tested in the forced swim, tail suspension, and open field tests after acute and chronic systemic, and intracerebroventricular and chronic lithium treatments. Serum and brain lithium levels were measured. Three (129S6/SvEvTac, C3H/HeNHsd, C57BL/6J) of the eight inbred strains tested, and one (CD-1) of the three outbred strains, showed an antidepressant-like response in the forced swim test following acute systemic administration of lithium. The three responsive inbred strains, as well as the DBA/2J strain, were also responsive in the forced swim test after chronic administration of lithium. However, in the tail suspension test, acute lithium resulted in an antidepressant-like effect only in C3H/HeNHsd mice. Only C57BL/6J and DBA/2J were responsive in the tail suspension test after chronic administration of lithium. Intracerebroventricular lithium administration resulted in a similar response profile in BALB/cJ (non-responsive) and C57BL/6J (responsive) strains. Serum and brain lithium concentrations demonstrated that behavioral results were not due to differential pharmacokinetics of lithium in individual strains, suggesting that genetic factors likely regulate responsiveness to lithium. Our results indicate that responsiveness to lithium in tests of antidepressant efficacy varies among genetically diverse mouse strains. These results will assist in identifying genomic factors associated with lithium responsiveness and the mechanisms of lithium action. PMID:21306560

Childhood trauma predicts antidepressant response in adults with major depression: data from the randomized international study to predict optimized treatment for depression.

PubMed

Williams, L M; Debattista, C; Duchemin, A-M; Schatzberg, A F; Nemeroff, C B

2016-05-03

Few reliable predictors indicate which depressed individuals respond to antidepressants. Several studies suggest that a history of early-life trauma predicts poorer response to antidepressant therapy but results are variable and limited in adults. The major goal of the present study was to evaluate the role of early-life trauma in predicting acute response outcomes to antidepressants in a large sample of well-characterized patients with major depressive disorder (MDD). The international Study to Predict Optimized Treatment for Depression (iSPOT-D) is a randomized clinical trial with enrollment from December 2008 to January 2012 at eight academic and nine private clinical settings in five countries. Patients (n=1008) meeting DSM-IV criteria for MDD and 336 matched healthy controls comprised the study sample. Six participants withdrew due to serious adverse events. Randomization was to 8 weeks of treatment with escitalopram, sertraline or venlafaxine with dosage adjusted by the participant's treating clinician per routine clinical practice. Exposure to 18 types of traumatic events before the age of 18 was assessed using the Early-Life Stress Questionnaire. Impact of early-life stressors-overall trauma 'load' and specific type of abuse-on treatment outcomes measures: response: (⩾50% improvement on the 17-item Hamilton Rating Scale for Depression, HRSD17 or on the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated, QIDS_SR16) and remission (score ⩽7 on the HRSD17 and ⩽5 on the QIDS_SR16). Trauma prevalence in MDD was compared with controls. Depressed participants were significantly more likely to report early-life stress than controls; 62.5% of MDD participants reported more than two traumatic events compared with 28.4% of controls. The higher rate of early-life trauma was most apparent for experiences of interpersonal violation (emotional, sexual and physical abuses). Abuse and notably abuse occurring at ⩽7 years of age predicted poorer outcomes

Lanicemine: a low-trapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects.

PubMed

Sanacora, G; Smith, M A; Pathak, S; Su, H-L; Boeijinga, P H; McCarthy, D J; Quirk, M C

2014-09-01

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) channel blocker, has been found to induce rapid and robust antidepressant-like effects in rodent models and in treatment-refractory depressed patients. However, the marked acute psychological side effects of ketamine complicate the interpretation of both preclinical and clinical data. Moreover, the lack of controlled data demonstrating the ability of ketamine to sustain the antidepressant response with repeated administration leaves the potential clinical utility of this class of drugs in question. Using quantitative electroencephalography (qEEG) to objectively align doses of a low-trapping NMDA channel blocker, AZD6765 (lanicemine), to that of ketamine, we demonstrate the potential for NMDA channel blockers to produce antidepressant efficacy without psychotomimetic and dissociative side effects. Furthermore, using placebo-controlled data, we show that the antidepressant response to NMDA channel blockers can be maintained with repeated and intermittent drug administration. Together, these data provide a path for the development of novel glutamatergic-based therapeutics for treatment-refractory mood disorders.

Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study.

PubMed

Fu, Cynthia H Y; Williams, Steven C R; Cleare, Anthony J; Brammer, Michael J; Walsh, Nicholas D; Kim, Jieun; Andrew, Chris M; Pich, Emilio Merlo; Williams, Pauline M; Reed, Laurence J; Mitterschiffthaler, Martina T; Suckling, John; Bullmore, Edward T

2004-09-01

Depression is associated with interpersonal difficulties related to abnormalities in affective facial processing. To map brain systems activated by sad facial affect processing in patients with depression and to identify brain functional correlates of antidepressant treatment and symptomatic response. Two groups underwent scanning twice using functional magnetic resonance imaging (fMRI) during an 8-week period. The event-related fMRI paradigm entailed incidental affect recognition of facial stimuli morphed to express discriminable intensities of sadness. Participants were recruited by advertisement from the local population; depressed subjects were treated as outpatients. We matched 19 medication-free, acutely symptomatic patients satisfying DSM-IV criteria for unipolar major depressive disorder by age, sex, and IQ with 19 healthy volunteers. Intervention After the baseline assessment, patients received fluoxetine hydrochloride, 20 mg/d, for 8 weeks. Average activation (capacity) and differential response to variable affective intensity (dynamic range) were estimated in each fMRI time series. We used analysis of variance to identify brain regions that demonstrated a main effect of group (depressed vs healthy subjects) and a group x time interaction (attributable to antidepressant treatment). Change in brain activation associated with reduction of depressive symptoms in the patient group was identified by means of regression analysis. Permutation tests were used for inference. Over time, depressed subjects showed reduced capacity for activation in the left amygdala, ventral striatum, and frontoparietal cortex and a negatively correlated increase of dynamic range in the prefrontal cortex. Symptomatic improvement was associated with reduction of dynamic range in the pregenual cingulate cortex, ventral striatum, and cerebellum. Antidepressant treatment reduces left limbic, subcortical, and neocortical capacity for activation in depressed subjects and increases the

Is increased antidepressant exposure a contributory factor to the obesity pandemic?

PubMed Central

Lee, S H; Paz-Filho, G; Mastronardi, C; Licinio, J; Wong, M-L

2016-01-01

Major depressive disorder (MDD) and obesity are both common heterogeneous disorders with complex aetiology, with a major impact on public health. Antidepressant prescribing has risen nearly 400% since 1988, according to data from the Centers for Disease Control and Prevention (CDC). In parallel, adult obesity rates have doubled since 1980, from 15 to 30 percent, while childhood obesity rates have more than tripled. Rising obesity rates have significant health consequences, contributing to increased rates of more than thirty serious diseases. Despite the concomitant rise of antidepressant use and of the obesity rates in Western societies, the association between the two, as well as the mechanisms underlying antidepressant-induced weight gain, remain under explored. In this review, we highlight the complex relationship between antidepressant use, MDD and weight gain. Clinical findings have suggested that obesity may increase the risk of developing MDD, and vice versa. Hypothalamic–pituitary–adrenal (HPA) axis activation occurs in the state of stress; concurrently, the HPA axis is also dysregulated in obesity and metabolic syndrome, making it the most well-understood shared common pathophysiological pathway with MDD. Numerous studies have investigated the effects of different classes of antidepressants on body weight. Previous clinical studies suggest that the tricyclics amitriptyline, nortriptyline and imipramine, and the serotonin norepinephrine reuptake inhibitor mirtazapine are associated with weight gain. Despite the fact that selective serotonin reuptake inhibitor (SSRI) use has been associated with weight loss during acute treatment, a number of studies have shown that SSRIs may be associated with long-term risk of weight gain; however, because of high variability and multiple confounds in clinical studies, the long-term effect of SSRI treatment and SSRI exposure on body weight remains unclear. A recently developed animal paradigm shows that the combination

Phytochemical screening, acute toxicity, anxiolytic and antidepressant activities of the Nelumbo nucifera fruit.

PubMed

Rajput, Muhammad Ali; Khan, Rafeeq Alam

2017-06-01

Recently use of herbal therapies and diet rich in flavonoids and vitamin C have increased significantly to treat minor to modest anxiety disorders and various forms of depression. But further research and studies are necessary to evaluate the pharmacological & toxicological effects of plants. Hence present study was designed to conduct phytochemical screening, acute toxicity study, anxiolytic and antidepressant activities of the ethanol extract of Nelumbo nucifera fruit in order to ascertain its therapeutic potential. The qualitative phytochemical screening of the seed pods of the N. nucifera fruit extract exposed the existence of flavonoids, saponins, alkaloids, tannins and terpenoids in it. The acute toxicity of the N. nucifera fruit extract in mice revealed its LD 50 value to be greater than 5000 mg/kg. Antianxiety activity was determined by elevated plus maze and light and dark test using 35 male Wister rats weighing 200-220 g which were equally divided in to 5 groups. The animals used in EPM underwent testing in light and dark box just 30 min after EPM. The antidepressant effect was assessed by forced swimming test using 35 male albino mice weighing 20-25 g equally divided in to 5 groups. In elevated plus maze, N. nucifera fruit extract exhibited substantial rise in number of open arm entries and time spent in open arms at dose 50 mg/kg while highly noteworthy increase in both parameters were observed at extract doses 100 and 200 mg/kg as compared to control. In light dark test highly significant increase in the percentage of time spent in light compartment was observed as compared to control. In forced swimming test highly noteworthy decline in duration of immobility was recorded at doses 100 and 200 mg/kg on 15th day i-e after administration of 14 doses, as compared to control; whereas same doses demonstrated significant decrease as compared to control in duration of immobility after single dose administration i-e on 2nd day of experiment. Thus N

[Mirtazapine versus other antidepressive agents for depression].

PubMed

Knud Larsen, Jens

2012-11-12

A Cochrane analysis compared efficacy and side effects of mirtazapine with other antidepressants. After six weeks of treatment no reliable difference of efficacy between mirtazapine, selective serotonin reuptake inhibitors (SSRI), noradrenaline reuptake inhibitors or tricyclic antidepressants was found. The side effects like increased sleep and weight gain were compared by treatment with mirtazapine and treatment with SSRI antidepressants. The very fact of the sleep effect and the fast onset of action have probably increased the effect size compared with SSRI antidepressants. The results of the Cochrane analysis cannot for certain be generalized to inpatients, as other studies have found tricyclic antidepressants to be especially effective.

Modern molecular study of weight gain related to antidepressant treatment: clinical implications of the pharmacogenetic testing.

PubMed

Ageu, Luminiţa Ştefania; Levai, Codrina Mihaela; Andreescu, Nicoleta Ioana; Grigoraş, Mirela Loredana; Hogea, Lavinia Maria; Chiriac, Daniela Veronica; Folescu, Roxana; Bredicean, Ana Cristina; Nussbaum, Liliana Maria; Enătescu, Virgil Radu; Poroch, Vladimir; Lupu, Viorel; Puiu, Maria; Nussbaum, Laura Alexandra

2018-01-01

Antidepressant medication influences cellular lipogenesis, being associated with metabolic side effects including weight gain. Due to the increasing use of antidepressants in children and adolescents, their metabolic and endocrine adverse effects are of particular concern, especially within this pediatric population that appears to be at greater risk. Genetic factors with a possible influence on antidepressant's adverse effects include CYP [cytochrome P450 (CYP450)] polymorphisms. We target to evaluate the efficacy of the pharmacogenetic testing, when prescribing antidepressants, in correlation with the occurrence of adverse events and weight gain. Our research was performed between the years 2010 and 2016, in the University Clinic of Child and Adolescent Psychiatry, Timisoara, Romania. We recruited 80 patients, children and adolescents with depressive disorders. Our study sample was divided in two groups: G1 - 40 patients took treatment after pharmacogenetic testing, and G2 - 40 patients without pharmacogenetic testing before the treatment election. Our results show statistically significant differences concerning the weight gain for groups G1 (with pharmacogenetic testing) and G2 (without pharmacogenetic testing). The CYP genotype and the pharmacogenetic testing, for choosing the personalized antidepressant therapy in children and adolescents with depressive disorders, proved to be good predictors for the response to antidepressants and the side effects registered, especially for weight gain. The significant correlations between the CYP polymorphisms for group G2 (without pharmacogenetic testing) and the weight gain/body mass index (BMI) increase, as major side effects induced by antidepressants, proved the fact that the pharmacogenetic screening is needed in the future clinical practice, allowing for individualized, tailored treatment, especially for at-risk pediatric categories.

Convergent mechanisms underlying rapid antidepressant action

PubMed Central

Zanos, Panos; Thompson, Scott M.; Duman, Ronald S.; Zarate, Carlos A.; Gould, Todd D.

2018-01-01

Traditional pharmacological treatments for depression have a delayed therapeutic onset, ranging from several weeks to months, and there is a high percentage of individuals who never respond to treatment. In contrast, ketamine produces rapid-onset antidepressant, anti-suicidal and anti-anhedonic actions following a single administration to depressed patients. Proposed mechanisms of ketamine’s antidepressant action include N-methyl-D-aspartate receptor (NMDAR) modulation, GABAergic interneuron disinhibition, and direct actions of its hydroxynorketamine (HNK) metabolites. Downstream actions include activation of mechanistic target of rapamycin (mTOR), deactivation of glycogen synthase kinase-3 and eukaryotic elongation factor 2 (eEF2), enhanced brain-derived neurotrophic factor (BDNF) signaling, and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs). These putative mechanisms of ketamine action are not mutually exclusive and may complement each other to induce potentiation of excitatory synapses in affective-regulating brain circuits, which results in amelioration of depression symptoms. We review these proposed mechanisms of ketamine action in the context of how such mechanisms are informing the development of novel putative rapid-acting antidepressant drugs. Such drugs that have undergoing pre-clinical, and in some cases clinical, testing include the muscarinic acetylcholine receptor antagonist scopolamine, GluN2B-NMDAR antagonists (i.e., CP-101,606, MK-0657), (2R,6R)-HNK, NMDAR glycine site modulators (i.e., 4-chlorokynurenine - pro-drug of the glycineB NMDAR antagonist 7-chlorokynurenic acid), NMDAR agonists (i.e. GLYX-13 (rapastinel)), metabotropic glutamate receptor 2/3 (mGluR2/3) antagonists, GABAA receptor modulators, and drugs acting on various serotonin receptor subtypes. These ongoing studies suggest that the future acute treatment of depression will typically occur within hours, rather than months, of treatment

Meta-Analysis of the Antidepressant Effects of Acute Sleep Deprivation.

PubMed

Boland, Elaine M; Rao, Hengyi; Dinges, David F; Smith, Rachel V; Goel, Namni; Detre, John A; Basner, Mathias; Sheline, Yvette I; Thase, Michael E; Gehrman, Philip R

To provide a quantitative meta-analysis of the antidepressant effects of sleep deprivation to complement qualitative reviews addressing response rates. English-language studies from 1974 to 2016 using the keywords sleep deprivation and depression searched through PubMed and PsycINFO databases. A total of 66 independent studies met criteria for inclusion: conducted experimental sleep deprivation, reported the percentage of the sample that responded to sleep deprivation, provided a priori definition of antidepressant response, and did not seamlessly combine sleep deprivation with other therapies (eg, chronotherapeutics, repetitive transcranial magnetic stimulation). Data extracted included percentage of responders, type of sample (eg, bipolar, unipolar), type of sleep deprivation (eg, total, partial), demographics, medication use, type of outcome measure used, and definition of response (eg, 30% reduction in depression ratings). Data were analyzed with meta-analysis of proportions and a Poisson mixed-effects regression model. The overall response rate to sleep deprivation was 45% among studies that utilized a randomized control group and 50% among studies that did not. The response to sleep deprivation was not affected significantly by the type of sleep deprivation performed, the nature of the clinical sample, medication status, the definition of response used, or age and gender of the sample. These findings support a significant effect of sleep deprivation and suggest the need for future studies on the phenotypic nature of the antidepressant response to sleep deprivation, on the neurobiological mechanisms of action, and on moderators of the sleep deprivation treatment response in depression. © Copyright 2017 Physicians Postgraduate Press, Inc.

[Switching and combining strategies of antidepressant medications].

PubMed

Charpeaud, Thomas; Moliere, Fanny; Bubrovszky, Maxime; Haesebaert, Frédéric; Allaïli, Najib; Bation, Rémy; Nieto, Isabel; Richieri, Raphaëlle; Saba, Ghassen; Bellivier, Frank; Bennabi, Djamila; Holtzmann, Jérôme; Camus, Vincent; Courtet, Philippe; Courvoisier, Pierre; d'Amato, Thierry; Doumy, Olivier; Garnier, Marion; Bougerol, Thierry; Lançon, Christophe; Haffen, Emmanuel; Leboyer, Marion; Llorca, Pierre-Michel; Vaiva, Guillaume; El-Hage, Wissam; Aouizerate, Bruno

2016-03-01

Switching antidepressant medication may be helpful in depressed patients having no benefit from the initial antidepressant treatment. Before considering switching strategy, the initial antidepressant treatment should produce no therapeutic effect after at least 4 weeks of administration at adequate dosage. Choosing an antidepressant of pharmacologically distinct profile fails to consistently demonstrate a significant superiority in terms of effectiveness over the switching to another antidepressant within the same pharmacological class. Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most recommended strategy of antidepressant combinations. Augmenting SSRI with tricyclic drugs is now a less recommended strategy of antidepressant combinations given the increased risk for the occurrence of pharmacokinetic drug-drug interactions and adverse effects. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression.

PubMed

Niciu, Mark J; Shovestul, Bridget J; Jaso, Brittany A; Farmer, Cristan; Luckenbaugh, David A; Brutsche, Nancy E; Park, Lawrence T; Ballard, Elizabeth D; Zarate, Carlos A

2018-05-01

Ketamine induces rapid and robust antidepressant effects, and many patients also describe dissociation, which is associated with antidepressant response. This follow-up study investigated whether antidepressant efficacy is uniquely related to dissociative symptom clusters. Treatment-resistant patients with major depressive disorder (MDD) or bipolar disorder (BD) (n = 126) drawn from three studies received a single subanesthetic (0.5 mg/kg) ketamine infusion. Dissociative effects were measured using the Clinician-Administered Dissociative States Scale (CADSS). Antidepressant response was measured using the 17-item Hamilton Depression Rating Scale (HAM-D). A confirmatory factor analysis established the validity of CADSS subscales (derealization, depersonalization, amnesia), and a general linear model with repeated measures was fitted to test whether subscale scores were associated with antidepressant response. Factor validity was supported, with a root mean square error of approximation of .06, a comparative fit index of .97, and a Tucker-Lewis index of .96. Across all studies and timepoints, the depersonalization subscale was positively related to HAM-D percent change. A significant effect of derealization on HAM-D percent change was observed at one timepoint (Day 7) in one study. The amnesia subscale was unrelated to HAM-D percent change. Possible inadequate blinding; combined MDD/BD datasets might have underrepresented ketamine's antidepressant efficacy; the possibility of Type I errors in secondary analyses. From a psychometric perspective, researchers may elect to administer only the CADSS depersonalization subscale, given that it was most closely related to antidepressant response. From a neurobiological perspective, mechanistic similarities may exist between ketamine-induced depersonalization and antidepressant response, although off-target effects cannot be excluded. Published by Elsevier B.V.

Step-wise loss of antidepressant effectiveness with repeated antidepressant trials in bipolar II depression.

PubMed

Amsterdam, Jay D; Lorenzo-Luaces, Lorenzo; DeRubeis, Robert J

2016-11-01

This study examined the relationship between the number of prior antidepressant treatment trials and step-wise increase in pharmacodynamic tolerance (or progressive loss of effectiveness) in subjects with bipolar II depression. Subjects ≥18 years old with bipolar II depression (n=129) were randomized to double-blind venlafaxine or lithium carbonate monotherapy for 12 weeks. Responders (n=59) received continuation monotherapy for six additional months. After controlling for baseline covariates of prior medications, there was a 25% reduction in the likelihood of response to treatment with each increase in the number of prior antidepressant trials (odds ratio [OR]=0.75, unstandardized coefficient [B]=-0.29, standard error (SE)=0.12; χ 2 =5.70, P<.02], as well as a 32% reduction in the likelihood of remission with each prior antidepressant trial (OR=0.68, B=-0.39, SE=0.13; χ 2 =9.71, P=.002). This step-wise increase in pharmacodynamic tolerance occurred in both treatment conditions. Prior selective serotonin reuptake inhibitor (SSRI) therapy was specifically associated with a step-wise increase in tolerance, whereas other prior antidepressants or mood stabilizers were not associated with pharmacodynamic tolerance. Neither the number of prior antidepressants, nor the number of prior SSRIs, or mood stabilizers, were associated with an increase in relapse during continuation therapy. The odds of responding or remitting during venlafaxine or lithium monotherapy were reduced by 25% and 32%, respectively, with each increase in the number of prior antidepressant treatment trials. There was no relationship between prior antidepressant exposure and depressive relapse during continuation therapy of bipolar II disorder. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Abnormalities of P300 before and after antidepressant treatment in depression: an ERP-sLORETA study.

PubMed

Zhou, Lina; Wang, Gaohua; Wang, Huiling

2018-02-07

Despite a wide range of reports on depression-induced P300 changes, it is still debatable whether P300 can return to a pattern characteristic of healthy individuals following antidepressant treatment. Thus, the present study aims to compare P300 and its underlying neural activation in depressed patients before and after antidepressant treatment to explore the brain regions related to pathogenesis and to evaluate the prognosis after treatment. P300 was evoked by the oddball auditory paradigm and collected from 14 sex-matched, age-matched, and education level-matched patients and controls. P300 was also collected in the same patients after treatment. sLORETA was used to explore the source activation of P300 components. Depressed patients before and after antidepressant treatment tended to show lower P300 amplitudes compared with healthy controls, and their P300 amplitudes of F3 electrodes were correlated negatively to their scores on the 24-item Hamilton Depression Rating Scale, the Snaith-Hamilton Pleasure Scale, and the nine-item Patient Health Questionnaire. P300 amplitudes of P4 electrodes were correlated negatively with their scores on the Dysfunctional Attitude Scale. P300 source activation of depressed patients before antidepressant treatment was reduced in the left superior parietal lobule and the precuneus compared with healthy controls and depressed patients after treatment. No difference was found between healthy controls and depressed patients after treatment. The left superior parietal lobule and the precuneus might be therapeutic targets of depression.

Garcinia mangostana Linn displays antidepressant-like and pro-cognitive effects in a genetic animal model of depression: a bio-behavioral study in the Flinders Sensitive Line rat.

PubMed

Oberholzer, Inge; Möller, Marisa; Holland, Brendan; Dean, Olivia M; Berk, Michael; Harvey, Brian H

2018-04-01

There is abundant evidence for both disorganized redox balance and cognitive deficits in major depressive disorder (MDD). Garcinia mangostana Linn (GM) has anti-oxidant activity. We studied the antidepressant-like and pro-cognitive effects of raw GM rind in Flinders Sensitive Line (FSL) rats, a genetic model of depression, following acute and chronic treatment compared to a reference antidepressant, imipramine (IMI). The chemical composition of the GM extract was analysed for levels of α- and γ-mangostin. The acute dose-dependent effects of GM (50, 150 and 200 mg/kg po), IMI (20 mg/kg po) and vehicle were determined in the forced swim test (FST) in FSL rats, versus Flinders Resistant Line (FRL) control rats. Locomotor testing was conducted using the open field test (OFT). Using the most effective dose above coupled with behavioral testing in the FST and cognitive assessment in the novel object recognition test (nORT), a fixed dose 14-day treatment study of GM was performed and compared to IMI- (20 mg/kg/day) and vehicle-treated animals. Chronic treated animals were also assessed with respect to frontal cortex and hippocampal monoamine levels and accumulation of malondialdehyde. FSL rats showed significant cognitive deficits and depressive-like behavior, with disordered cortico-hippocampal 5-hydroxyindole acetic acid (5-HIAA) and noradrenaline (NA), as well as elevated hippocampal lipid peroxidation. Acute and chronic IMI treatment evoked pronounced antidepressant-like effects. Raw GM extract contained 117 mg/g and 11 mg/g α- and γ-mangostin, respectively, with acute GM demonstrating antidepressant-like effects at 50 mg/kg/day. Chronic GM (50 mg/kg/d) displayed significant antidepressant- and pro-cognitive effects, while demonstrating parity with IMI. Both behavioral and monoamine assessments suggest a more prominent serotonergic action for GM as opposed to a noradrenergic action for IMI, while both IMI and GM reversed hippocampal lipid peroxidation in

Genistein, a dietary soy isoflavone, exerts antidepressant-like effects in mice: Involvement of serotonergic system.

PubMed

Hu, Pei; Ma, Li; Wang, Yan-Gui; Ye, Feng; Wang, Chuang; Zhou, Wen-Hua; Zhao, Xin

2017-09-01

Genistein, a principal isoflavone property of soybeans, possesses multiple pharmacological activities such as neuroprotection. Recently, it was reported that genistein exerted antidepressant-like effects in animal models, but the mechanism of action remains ambiguous. The purpose of this study was to investigate the antidepressant-like effect of genistein in mice and explore the underlying mechanism(s), using two mouse models of depression, i.e. forced swim test (FST) and tail suspension test (TST). Chronic, but not acute (single dose), genistein treatment (5, 15 or 45 mg/kg, p.o., once per day for three weeks) exerted dose-dependently antidepressant-like effect in mice, concomitant with escalated levels of brain monoamines and suppressed monoamine oxidase (MAO) activity. Chemical depletion of brain serotonin by PCPA abrogated the antidepressant-like action of genistein, but it was not the case for ablation of NA by DSP-4. Moreover, the anti-depression by genistein was preferentially counteracted by co-administration of 5-HT 1A receptor antagonist WAY-100635, suggesting a pivotal role for 5-HT system coupled with 5-HT 1A receptors in mediating such genistein anti-depression. This point was further validated by the fact that genistein action was potentiated by co-treatment with 8-OH-DPAT, a selective 5-HT 1A receptor agonist. Collectively, these findings confirm that chronic genistein administration to mice engenders antidepressant-like efficacy evidenced by lessened behavioral despair. Serotonergic system that preferentially couples with 5-HT 1A receptors may be critically responsible for the present genistein anti-depression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Challenges in the Treatment of Major Depressive Disorder With Psychotic Features

PubMed Central

Rothschild, Anthony J.

2013-01-01

Psychotic depression is associated with significant morbidity and mortality but is underdiagnosed and undertreated. In recent years, there have been several studies that have increased our knowledge regarding the optimal treatment of patients with psychotic depression. The combination of an antidepressant and antipsychotic is significantly more effective than either antidepressant monotherapy or antipsychotic monotherapy for the acute treatment of psychotic depression. Most treatment guidelines recommend either the combination of an antidepressant with an antipsychotic or ECT for the treatment of an acute episode of unipolar psychotic depression. The optimal maintenance treatment after a person responds to either the antidepressant/antipsychotic combination or the ECT is unclear particularly as it pertains to length of time the patient needs to take the antipsychotic medication. Little is known regarding the optimal treatment of a patient with bipolar disorder who has an episode of psychotic depression or the clinical characteristics of responders to medication treatments vs ECT treatments. PMID:23599251

Challenges in the treatment of major depressive disorder with psychotic features.

PubMed

Rothschild, Anthony J

2013-07-01

Psychotic depression is associated with significant morbidity and mortality but is underdiagnosed and undertreated. In recent years, there have been several studies that have increased our knowledge regarding the optimal treatment of patients with psychotic depression. The combination of an antidepressant and antipsychotic is significantly more effective than either antidepressant monotherapy or antipsychotic monotherapy for the acute treatment of psychotic depression. Most treatment guidelines recommend either the combination of an antidepressant with an antipsychotic or ECT for the treatment of an acute episode of unipolar psychotic depression. The optimal maintenance treatment after a person responds to either the antidepressant/antipsychotic combination or the ECT is unclear particularly as it pertains to length of time the patient needs to take the antipsychotic medication. Little is known regarding the optimal treatment of a patient with bipolar disorder who has an episode of psychotic depression or the clinical characteristics of responders to medication treatments vs ECT treatments.

Cognitive behavior therapy may sustain antidepressant effects of intravenous ketamine in treatment-resistant depression

PubMed Central

Wilkinson, Samuel T.; Wright, DaShaun; Fasula, Madonna K.; Fenton, Lisa; Griepp, Matthew; Ostroff, Robert B.; Sanacora, Gerard

2017-01-01

Introduction Ketamine has shown rapid though short-lived antidepressant effects. The possibility of concerning neurobiological changes following repeated exposure to the drug motivate the development of strategies that obviate or minimize the need for longer-term treatment with ketamine. In this open-label trial, we investigated whether cognitive behavioral therapy (CBT) can sustain or extend ketamine's antidepressant effects. Methods Patients who were pursuing ketamine infusion therapy for treatment-resistant depression (TRD) were invited to participate in the study. If enrolled, the subjects initiated a 12-session, 10-week course of CBT concurrently with a short 4-treatment, 2-week course of intravenous ketamine (0.5mg/kg infused over 40 mins) provided under a standardized clinical protocol. Results Sixteen participants initiated the protocol, with 8 (50%) attaining a response to the ketamine and 7 (43.8%) achieving remission during the first two weeks of protocol. Among ketamine responders, the relapse rate at the end of the CBT course (8 weeks following the last ketamine exposure) was 25% (2/8). On longer-term follow up, 5 of 8 subjects eventually relapsed, the median time-to-relapse being 12 weeks following ketamine exposure. Among ketamine remitters, 3 of 7 retained remission until at least 4 weeks following the last ketamine exposure, with 2 retaining remission through 8 weeks following ketamine exposure. Ketamine non-responders did not appear to benefit from CBT. Conclusions CBT may sustain the antidepressant effects of ketamine in TRD. Well-powered randomized controlled trials are warranted to further investigate this treatment combination as a way to sustain ketamine's antidepressant effects. PMID:28490030

Use of antidepressants in dentistry: A systematic review.

PubMed

Lino, P A; Martins, C C; Miranda, Gfpc; de Souza E Silva, M E; de Abreu, Mhng

2017-08-24

Previous research has suggested that antidepressants can be used in oral health care. The aim of this systematic review was to search for scientific evidence of the efficacy of the use of antidepressants in dentistry. The clinical question was as follows (PICO question): dentistry patients (Patients); antidepressants (Intervention); no use or placebo or other drug (Comparison); and efficacy in oral health problems (Outcome). An electronic search was conducted in seven databases, as well as a manual search without restriction regarding language and date of publication. Two independent reviewers selected studies based on eligibility criteria, extracted data and assessed methodological quality based on the PEDro scale. The PROSPERO record is number CRD42016037442. A total of 15 randomized controlled trials were associated with the use of antidepressants to control chronic or acute pain in dentistry, among other conditions such as bruxism and burning mouth syndrome. The most commonly used drug in clinical trials was amitriptyline (more than 50% of studies). Antidepressants may be effective in dentistry for acute and chronic pain, but there is a large amount of methodological heterogeneity among the evaluated studies. In summary, there is rationality for the indication of this class of medicine in dentistry in specific clinical situations. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

Childhood trauma predicts antidepressant response in adults with major depression: data from the randomized international study to predict optimized treatment for depression

PubMed Central

Williams, L M; Debattista, C; Duchemin, A-M; Schatzberg, A F; Nemeroff, C B

2016-01-01

Few reliable predictors indicate which depressed individuals respond to antidepressants. Several studies suggest that a history of early-life trauma predicts poorer response to antidepressant therapy but results are variable and limited in adults. The major goal of the present study was to evaluate the role of early-life trauma in predicting acute response outcomes to antidepressants in a large sample of well-characterized patients with major depressive disorder (MDD). The international Study to Predict Optimized Treatment for Depression (iSPOT-D) is a randomized clinical trial with enrollment from December 2008 to January 2012 at eight academic and nine private clinical settings in five countries. Patients (n=1008) meeting DSM-IV criteria for MDD and 336 matched healthy controls comprised the study sample. Six participants withdrew due to serious adverse events. Randomization was to 8 weeks of treatment with escitalopram, sertraline or venlafaxine with dosage adjusted by the participant's treating clinician per routine clinical practice. Exposure to 18 types of traumatic events before the age of 18 was assessed using the Early-Life Stress Questionnaire. Impact of early-life stressors—overall trauma ‘load' and specific type of abuse—on treatment outcomes measures: response: (⩾50% improvement on the 17-item Hamilton Rating Scale for Depression, HRSD17 or on the 16-item Quick Inventory of Depressive Symptomatology—Self-Rated, QIDS_SR16) and remission (score ⩽7 on the HRSD17 and ⩽5 on the QIDS_SR16). Trauma prevalence in MDD was compared with controls. Depressed participants were significantly more likely to report early-life stress than controls; 62.5% of MDD participants reported more than two traumatic events compared with 28.4% of controls. The higher rate of early-life trauma was most apparent for experiences of interpersonal violation (emotional, sexual and physical abuses). Abuse and notably abuse occurring at ⩽7 years of age predicted poorer

Risk factors for non-adherence to antidepressant treatment in patients with mood disorders.

PubMed

De las Cuevas, Carlos; Peñate, Wenceslao; Sanz, Emilio J

2014-01-01

Adherence to antidepressant therapy by patients with depressive disorders is essential not only to achieve a positive patient outcome but also to prevent a relapse. The aim of this study was to identify potential modelling factors influencing adherence to antidepressant treatment by patients with mood disorders in the community mental health care setting A total of 160 consecutive psychiatric outpatients attending two Community Mental Health Centres on Tenerife Island between September 2011 and May 2012 were asked to participate in the study; of these, 145 accepted. The Morisky self-report scale was used to assess adherence. The potential predictors examined included socio-demographic, clinical and therapeutic variables. The Clinical Global Impression-Severity and -Improvement scales and the Beck Depression Inventory were used for clinical assessment. Drug treatment side-effects were assessed using the "Self-report Antidepressant Side-Effect Checklist." All participants were also asked to complete the "Drug Attitude Inventory" (DAI), "Beliefs about Medicine Questionnaire" (BMQ), and "Leeds Attitude towards concordance Scale". Discriminant analyses were performed to predict non-adherence. There was no clear correlation between adherence and the socio-demographic variables examined, but adherence was related to a positive attitude of the patients towards his/her treatment (DAI) and low scores in the BMQ-Harm and -Concern subscales. Non-adherence was also related to an increasing severity of depression and to the presence and severity of side-effects. Among our study cohort, the profiles of adherent patients to antidepressant treatment were more closely associated with each patient's attitudes and beliefs than to objective socio-demographic variables. The severity of depression played a relevant role in adherence, but whether this role is direct or an interaction with several concurrent factors is not yet clear. Side-effects were also closely related to adherence, as

Opiates as antidepressants.

PubMed

Berrocoso, Esther; Sánchez-Blázquez, Pilar; Garzón, Javier; Mico, Juan A

2009-01-01

The pathophysiology of mood disorders involves several genetic and social predisposing factors, as well as a dysregulated response to a chronic stressor, i.e. chronic pain. Our present view that depression involves a dysfunction of the monoaminergic system is a result of important clinical and preclinical observations over the past 40 years. In fact, current pharmacological treatment for depression is based on the use of drugs that act mainly by enhancing brain serotonin and noradrenaline neurotransmission by the blockade of the active reuptake mechanism for these neurotransmitters. However, a substantial number of patients do not respond adequately to antidepressant drugs. In view of this, there is an intense search to identify novel targets (receptors) for antidepressant therapy. Opioid peptides and their receptors are potential candidates for the development of novel antidepressant treatment. In this context, endogenous opioid peptides are co-expressed in brain areas known to play a major role in affective disorders and in the action of antidepressant drugs. The actions of endogenous opioids and opiates are mediated by three receptor subtypes (mu, delta and kappa), which are coupled to different intracellular effector systems. Also, antidepressants which increase the availability of noradrenaline and serotonin through the inhibition of the reuptake of both monoamines lead to the enhancement of the opioid pathway. Tricyclic antidepressants show an analgesic effect in neuropathic and inflammatory pain that is blocked by the opioid antagonist naloxone. A compilation of the most significant studies will illustrate the actual and potential value of the opioid system for clinical research and drug development.

Trends in the prescribing of antidepressants following acute myocardial infarction, 1993-2002.

PubMed

Benazon, Nili R; Mamdani, Muhammad M; Coyne, James C

2005-01-01

There has been a substantial increase in the prescribing of antidepressants on a population basis and in particular serotonin reuptake inhibitors (SSRIs). SSRIs have lower cardiac toxicity than tricyclic antidepressants (TCAs). We examined how the prescribing of antidepressants to patients post-myocardial infarction (MI) changed in the decade 1993 to 2002, including the proportion accounted for by TCAs. A population-based study cross-sectional time series analysis was conducted in which quarterly antidepressant prescription data were obtained for 1993 to 2002 for elderly Ontarians who had experienced an MI, as well as for age- and sex-matched controls with no history of MI. The number of patients varied per quarter, for a total of 68,870 post-MI patients and an equal number of matched controls. Covariates included age, gender, income, and number of medications dispensed in the past year. Post-MI patients were more likely to receive an antidepressant relative to controls, with an overall odds ratio (OR) of 1.34; 95% confidence interval (CI), 1.29-1.38. However, with adjustment for the number of medications received, post-MI patients were 20% less likely to receive an antidepressant relative to controls, adjusted OR = 0.81; 95% CI, 0.78-0.84. The proportion of antidepressants prescribed to post-MI patients accounted for by TCAs decreased, but the proportion of post-MI patients receiving a TCA remained stable at approximately 6%. Increases in the prescription of antidepressants, and in particular SSRIs, to post-MI patients reflect general population trends rather than any special importance attached to treating post-MI depression. The apparent greater likelihood that post-MI patients will receive an antidepressant is reversed when total number of medications is controlled, a proxy for medical utilization and comorbidity.

Prescription for antidepressant in reducing future alcohol-related readmission in patients suffering from depression and alcohol use disorder: a retrospective medical record review.

PubMed

Chan, Patrick; Yomen, Katie; Turcios, Jennifer; Richman, Mark

2015-12-21

Patients suffering from major depressive disorder are more likely to suffer from alcohol use disorder. The data is inconclusive for the effectiveness of antidepressant treatment of patients suffering from both illnesses in regards to improving sobriety and reducing alcohol-related healthcare expenses such as hospitalizations. The objective of this study is to determine if a new prescription of an antidepressant upon inpatient discharge is associated with a reduction in the number of future acute alcohol-related hospital readmissions to the same institution in patients suffering from major depressive disorder and alcohol-use disorder. A retrospective, medical record review study was conducted at a publicly-supported hospital in Sylmar, CA. A query was performed for adult patients admitted between 1/1/2005-12/31/2013 who had ICD-9 codes for both alcohol-use disorder and depression. Index admission was the first hospitalization in which the patient was currently consuming alcohol and had depression as identified by physician documentation as a problem. Acute alcohol-related admissions were those for alcohol intoxication or withdrawal (indicating current alcohol use). Patients were excluded if they were receiving an antidepressant on index admission, <18 years old, no patient data available, or not currently consuming alcohol; 139 patients met inclusion criteria. Multivariate logistical regression analysis was performed on the primary predictive variable of discharge prescription of an antidepressant along with other independent variables for alcohol readmissions: homelessness, family history of alcohol use disorder, and smoking. Discharging patients with a prescription of an antidepressant was not associated with a reduction in acute alcohol-related readmission. There was no difference in acute alcohol-related readmissions between patients discharged with (44.6 %) versus without (47.0 %) a prescription for an antidepressant (p = 0.863). The median number of days

Antidepressant effects, of magnetic seizure therapy and electroconvulsive therapy, in treatment-resistant depression.

PubMed

Kayser, Sarah; Bewernick, Bettina H; Grubert, Christiane; Hadrysiewicz, Barbara L; Axmacher, Nikolai; Schlaepfer, Thomas E

2011-05-01

Major depression is a common mental health problem and associated with significant morbidity and mortality, including impaired social and physical functioning and increased risk for suicide. Electroconvulsive therapy (ECT) is highly efficacious in treatment-resistant depressive disorders, but cognitive side effects are frequently associated with the treatment. Magnetic seizure therapy (MST) is a form of convulsive therapy, using magnetic fields in order to induce therapeutic seizures. First studies suggested that cognitive side effects of MST, including postictal recovery time, are more benign than those resulting from ECT treatment. In this open-label study we tested the hypothesis that MST is associated with clinically significant antidepressant effects in treatment-resistant depression (TRD) as an add-on therapy to a controlled pharmacotherapy. Twenty patients suffering from TRD were randomly assigned to receive either MST or ECT starting from July 2006 until November 2008. Primary outcome measure was antidepressant response assessed by Montgomery Åsberg Depression Scale. Secondary outcome measures included Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Beck Depression Inventory and 90-Item Symptom Checklist. Antidepressant response (improvement of 50% in MADRS ratings) was statistically significant and of similar size in both treatment groups. Cognitive side effects were observed in neither group. Characteristics in MST- and ECT-induced seizures were comparable, especially regarding ictal activity and postictal suppression. Thus, MST may be a potential alternative to ECT if efficacy and safety are validated in larger clinical trials. Copyright © 2010 Elsevier Ltd. All rights reserved.

Antidepressant-like behavioral effects of impaired cannabinoid receptor type 1 signaling coincide with exaggerated corticosterone secretion in mice

PubMed Central

Steiner, Michel A; Marsicano, Giovanni; Nestler, Eric J; Holsboer, Florian; Lutz, Beat; Wotjak, Carsten T

2008-01-01

Summary Hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity is associated with major depressive disorders, and treatment with classical antidepressants ameliorates not only psychopathological symptoms, but also the dysregulation of the HPA axis. Here, we further elucidated the role of impaired cannabinoid type 1 (CB1) receptor signaling for neuroendocrine and behavioral stress coping in the mouse forced swim test (FST). We demonstrate that the genetic inactivation of CB1 is accompanied by increased plasma corticosterone levels both under basal conditions and at different time points following exposure to the FST. The latter effect could be mimicked in C57BL/6N mice by acute, subchronic and chronic administration of the selective CB1 antagonist SR141716. Further experiments confirmed the specificity of corticosterone-elevating SR141716 actions for CB1 in CB1-deficient mice. Subchronic and chronic pharmacological blockade of CB1, but not its genetic deletion, induced antidepressant-like behavioral responses in the FST that were characterized by decreased floating and/or increased struggling behavior. The antidepressant-like behavioral effects of acute desipramine treatment in the FST were absent in CB1-deficient mice, but the dampening effects of desipramine on FST stress-induced corticosterone secretion were not compromised by CB1-deficiency. However, antidepressant-like behavioral desipramine effects were intact in C57BL/6N mice pre-treated with SR141716, indicating potential developmental deficits in CB1-deficient mice. We conclude that pharmacological blockade of CB1 signaling shares antidepressant-like behavioral effects with desipramine, but reveals opposite effects on HPA axis activity. PMID:17976922

On categorizing gestational, birth, and neonatal complications following late pregnancy exposure to antidepressants: the prenatal antidepressant exposure syndrome.

PubMed

Gentile, Salvatore

2010-03-01

Late in utero exposure to antidepressants has been suspected of adversely impacting pregnancy outcome and compromising neonatal adaptation. Hence, the necessity exists to analyze published information on antidepressant use during late pregnancy to individuate potential recurrent patterns of iatrogenic complications. Computerized searches on MEDLINE, PsycINFO, ENBASE, and Cochrane Library through February 10, 2010 were performed for selecting literature information and investigating the safety of antidepressants when used during late pregnancy. Antidepressant treatment during late pregnancy may increase the rates of poor pregnancy outcome and neonatal withdrawal/toxic reactions. Because both gestational complications and neonatal adverse events acknowledge the same etiology, the author suggests including such iatrogenic events under the definition of prenatal antidepressant exposure syndrome, in order to increase clinicians' awareness about the spectrum of risks which may concern the mother-infant pair when antidepressant treatment is deemed indispensable during late pregnancy.

Antidepressant Drug Treatment in Association with Multiple Sclerosis Disease-Modifying Therapy: Using Explorys in the MS Population.

PubMed

Mirsky, Matthew M; Marrie, Ruth Ann; Rae-Grant, Alexander

2016-01-01

Background: The Explorys Enterprise Performance Management (EPM) database contains de-identified clinical data for 50 million patients. Multiple sclerosis (MS) disease-modifying therapies (DMTs), specifically interferon beta (IFNβ) treatments, may potentiate depression. Conflicting data have emerged, and a large-scale claims-based study by Patten et al. did not support such an association. This study compares the results of Patten et al. with those using the EPM database. Methods: "Power searches" were built to test the relationship between antidepressant drug use and DMT in the MS population. Searches were built to produce a cohort of individuals diagnosed as having MS in the past 3 years taking a specific DMT who were then given any antidepressant drug. The antidepressant drug therapy prevalence was tested in the MS population on the following DMTs: IFNβ-1a, IFNβ-1b, combined IFNβ, glatiramer acetate, natalizumab, fingolimod, and dimethyl fumarate. Results: In patients with MS, the rate of antidepressant drug use in those receiving DMTs was 40.60% to 44.57%. The rate of antidepressant drug use for combined IFNβ DMTs was 41.61% (males: 31.25%-39.62%; females: 43.10%-47.33%). Antidepressant drug use peaked in the group aged 45 to 54 years for five of six DMTs. Conclusions: We found no association between IFNβ treatment and antidepressant drug use in the MS population compared with other DMTs. The EPM database has been validated against the Patten et al. data for future use in the MS population.

Effects of ketamine and N-methyl-D-aspartate on fluoxetine-induced antidepressant-related behavior using the forced swimming test.

PubMed

Owolabi, Rotimi Adegbenga; Akanmu, Moses Atanda; Adeyemi, Oluwole Isaac

2014-04-30

This study investigated the effects of ketamine on fluoxetine-induced antidepressant behavior using the forced swimming test (FST) in mice. In order to understand the possible role of N-methyl-d-aspartate (NMDA) neurotransmission in the antidepressant effect of fluoxetine, different groups of mice (n=10) were administered with acute ketamine (3mg/kg, i.p.), acute NMDA (75mg/kg and 150mg/kg, i.p.) and a 21-day chronic ketamine (15mg/kg, i.p./day) were administered prior to the administration of fluoxetine (20mg/kg, i.p.) in the mice. Antidepressant related behavior (immobility score) was measured using the forced swimming test. The results showed that the acute ketamine and fluoxetine alone treatments elicited a significant (p<0.05) reduction in immobility score compared with saline control. Furthermore, pre-treatment with acute ketamine significantly enhanced by the fluoxetine-induced decrease in immobility score. In contrast, pre-treatment with NMDA (150mg/kg) significantly (p<0.05) reversed fluoxetine-induced decrease in immobility score. On the other hand, chronic administration of ketamine significantly elicited an increase in immobility score as well as reversed the reduction induced by fluoxetine. Similarly, NMDA administration at both 75mg/kg and 150mg/kg increased immobility score in chronically administered ketamine groups. Furthermore, chronic administration of ketamine, followed by NMDA (75mg/kg) and fluoxetine significantly elevated the immobility score when compared with the group that received NMDA and fluoxetine but not chronically treated with ketamine. It can be suggested) that facilitation of NMDA transmission blocked fluoxetine-induced reduction in immobility score, while down-regulation of NMDA transmission is associated with increase in fluoxetine-induced antidepressant-related behavior in mice. Down-regulation of the NMDA transmission is proposed as an essential component of mechanism of suppression of depression related behaviors by

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

Acute reversible inactivation of the bed nucleus of stria terminalis induces antidepressant-like effect in the rat forced swimming test

PubMed Central

2010-01-01

Background The bed nucleus of stria terminalis (BNST) is a limbic forebrain structure involved in hypothalamo-pituitary-adrenal axis regulation and stress adaptation. Inappropriate adaptation to stress is thought to compromise the organism's coping mechanisms, which have been implicated in the neurobiology of depression. However, the studies aimed at investigating BNST involvement in depression pathophysiology have yielded contradictory results. Therefore, the objective of the present study was to investigate the effects of temporary acute inactivation of synaptic transmission in the BNST by local microinjection of cobalt chloride (CoCl2) in rats subjected to the forced swimming test (FST). Methods Rats implanted with cannulae aimed at the BNST were submitted to 15 min of forced swimming (pretest). Twenty-four hours later immobility time was registered in a new 5 min forced swimming session (test). Independent groups of rats received bilateral microinjections of CoCl2 (1 mM/100 nL) before or immediately after pretest or before the test session. Additional groups received the same treatment and were submitted to the open field test to control for unspecific effects on locomotor behavior. Results CoCl2 injection into the BNST before either the pretest or test sessions reduced immobility in the FST, suggesting an antidepressant-like effect. No significant effect of CoCl2 was observed when it was injected into the BNST immediately after pretest. In addition, no effect of BNST inactivation was observed in the open field test. Conclusion These results suggest that acute reversible inactivation of synaptic transmission in the BNST facilitates adaptation to stress and induces antidepressant-like effects. PMID:20515458

Antidepressants and changes in concentration of endocannabinoids and N-acylethanolamines in rat brain structures.

PubMed

Smaga, Irena; Bystrowska, Beata; Gawliński, Dawid; Pomierny, Bartosz; Stankowicz, Piotr; Filip, Małgorzata

2014-08-01

The endocannabinoid (eCB) system has recently been implicated in both the pathogenesis of depression and the action of antidepressants. Here, we investigated the effect of acutely or chronically administering antidepressants [imipramine (IMI) (15 mg/kg), escitalopram (ESC) (10 mg/kg), and tianeptine (10 mg/kg)] on the levels of both eCBs [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)] and N-acylethanolamines (NAEs) [palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)] in various rat brain regions. We also examined the ability of the acute and chronic administration of N-acetylcysteine (NAC) (a mucolytic drug; 100 mg/kg) or URB597 (a fatty acid amide hydrolase inhibitor; 0.3 mg/kg), which have both elicited antidepressant activity in preclinical studies, to affect eCB and NAE levels. Next, we determined whether the observed effects are stable 10 days after the chronic administration of these drugs was halted. We report that the chronic administration of all investigated drugs increased AEA levels in the hippocampus and also increased both AEA and 2-AG levels in the dorsal striatum. NAE levels in limbic regions also increased after treatment with IMI (PEA/OEA), ESC (PEA), and NAC (PEA/OEA). Removing chronic ESC treatment for 10 days affected eCB and NAE levels in the frontal cortex, hippocampus, dorsal striatum, and cerebellum, while a similar tianeptine-free period enhanced accumbal NAE levels. All other drugs maintained their effects after the 10-day washout period. Therefore, the eCB system appears to play a significant role in the mechanism of action of clinically effective and potential antidepressants and may serve as a target for drug design and discovery.

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.

Managing antidepressant treatment in pregnancy and puerperium. Careful with that axe, Eugene.

PubMed

Gentile, Salvatore

2015-07-01

Until 2005, selective serotonin reuptake inhibitors (SSRIs), the class of antidepressants most frequently used in clinical practice, had been deemed devoid of any teratogenic effects. However, in recent years several concerns have been raised about their reproductive safety, including: disturbed fetal development, increased rates of congenital anomalies, increased risks of neonatal complications, neuro-motor delay and even autism. Specific concerns are also arising about the safety of SSRIs for infants breastfed by mothers who take such medications in puerperium. Such considerations have led to the 'bad reproductive reputation' of SSRIs, whose utilization during pregnancy and breastfeeding is deemed incautious. Specific reproductive problems also involve tricyclic antidepressants, especially clomipramine. Thus, any conclusion about what antidepressant should be considered the safest during pregnancy must be stated and read with great caution. However, the risks associated with pharmacological treatment must be balanced with the effects of untreated antenatal maternal depression on the mother-fetus dyad, which are likely to be devastating. During puerperium, it is mandatory to weigh the risks to the infant of antidepressant exposure through breast milk against the disadvantage of not receiving mother's milk and being exposed to a relapse of maternal mood symptoms (which may also have tragic consequences for the patient).

Early improvement as a resilience signal predicting later remission to antidepressant treatment in patients with Major Depressive Disorder: Systematic review and meta-analysis.

PubMed

Wagner, Stefanie; Engel, Alice; Engelmann, Jan; Herzog, David; Dreimüller, Nadine; Müller, Marianne B; Tadić, André; Lieb, Klaus

2017-11-01

Early improvement of depressive symptoms during the first two weeks of antidepressant treatment has been discussed to be a resilience signal predicting a later positive treatment outcome in patients with Major Depressive Disorder (MDD). However, the predictive value of early improvement varies between studies, and the use of different antidepressants may explain heterogeneous results. The objective of this review was to assess the predictive value of early improvement on later response and remission and to identify antidepressants with the highest chance of early improvement. We included 17 randomized controlled trials investigating early improvement in 14,779 adult patients with MDD comparing monotherapy with an antidepressant against placebo or another antidepressant drug. 62% (range: 35-85%) of patients treated with an antidepressant and 47% (range: 21-69%) with placebo were early improver, defined as a >20%/25% symptom reduction after two weeks of treatment. Early improvement predicted response and remission after 5-12 weeks of treatment with high sensitivity (85%; 95%-CI: 84.3 to 85.7) and low to moderate specificity (54%; 95%-CI: 53.1 to 54.9). Early improver had a 8.37 fold (6.97-10.05) higher likelihood to become responder and a 6.38 fold (5.07-8.02) higher likelihood to be remitter at endpoint than non-improver. The highest early improver rates were achieved in patients treated with mirtazapine or a tricyclic antidepressant. This finding of a high predictive value of early improvement on treatment outcome may be important for treatment decisions in the early course of antidepressant treatment. Further studies should test the efficacy of such early treatment decisions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Subchronic treatment with fluoxetine and ketanserin increases hippocampal brain-derived neurotrophic factor, β-catenin and antidepressant-like effects.

PubMed

Pilar-Cuéllar, F; Vidal, R; Pazos, A

2012-02-01

5-HT(2A) receptor antagonists improve antidepressant responses when added to 5-HT-selective reuptake inhibitors (SSRIs) or tricyclic antidepressants. Here, we have studied the involvement of neuroplasticity pathways and/or the 5-hydroxytryptaminergic system in the antidepressant-like effect of this combined treatment, given subchronically. Expression of brain-derived neurotrophic factor (BDNF) and its receptor (TrkB), 5-bromo-2'-deoxyuridine (BrdU) incorporation, and β-catenin protein expression in different cellular fractions, as well as 5-HT(1A) receptor function were measured in the hippocampus of rats treated with fluoxetine, ketanserin and fluoxetine + ketanserin for 7 days, followed by a forced swimming test (FST) to analyse antidepressant efficacy. mRNA for BDNF was increased in the CA3 field and dentate gyrus of the hippocampus by combined treatment with fluoxetine + ketanserin. Expression of β-catenin was increased in total hippocampal homogenate and in the membrane fraction, but unchanged in the nuclear fraction after combined treatment with fluoxetine + ketanserin. These effects were paralleled by a decreased immobility time in the FST. There were no changes in BrdU incorporation, TrkB expression and 5-HT(1A) receptor function in any of the groups studied. The antidepressant-like effect induced by subchronic co-treatment with a SSRI and a 5-HT(2A) receptor antagonist may mainly be because of modifications in hippocampal neuroplasticity (BDNF and membrane-associated β-catenin), without a significant role for other mechanisms involved in chronic antidepressant response, such as hippocampal neuroproliferation or 5-HT(1A) receptor desensitization in the dorsal raphe nucleus. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

How fast are antidepressants?

PubMed

Gelenberg, A J; Chesen, C L

2000-10-01

For years, investigators have tried to determine the speed of onset of antidepressant drugs. Claims that particular drugs may produce a faster response in patients than other agents have been made, but such claims have never been confirmed. The authors reviewed reports from studies of the speed of onset of antidepressant therapies and other studies that revealed information on this topic. We compiled a list of factors that can affect the results of such studies and interpretations of study results. In addition, we reviewed literature concerned with methods of speeding up antidepressant responses. No antidepressant medication currently available has been shown conclusively to have a more rapid onset of action than any other. However, some methods of augmentation may have the potential to speed responses. Somatic therapies such as electroconvulsive therapy, phototherapy, and therapeutic sleep deprivation may be the fastest options available at this time. All available antidepressant medications are usually taken for several weeks before future responders will display a significant therapeutic benefit. If a patient does not show at least a 20% improvement within the first 2 to 4 weeks of treatment, the treatment regimen should be altered. For patients who do show early benefits from a medication trial, one can expect additional benefits to accrue over an 8- to 12-week period and to improve overall outcome compared with those slower to respond. Future trials need to address methodological confounds, but a truly "faster antidepressant" will probably require new neuroscience technology.

Paliperidone for the treatment of schizoaffective disorder.

PubMed

Alphs, Larry; Fu, Dong-Jing; Turkoz, Ibrahim

2016-01-01

Schizoaffective disorder (SCA) is a complex mental illness characterized by psychosis and affective symptoms. Treatment usually involves concomitant therapy with antipsychotics, mood stabilizers, and/or antidepressants. Effective treatment must address acute symptoms, maintain long-term stability, promote recovery, and improve patient functioning. Data from 3 pivotal studies evaluating the acute and maintenance treatment of SCA with paliperidone are reviewed. Two formulations of paliperidone have been studied for these indications: an extended-release oral formulation (NCT00397033, NCT00412373) and long-acting injectable once-monthly paliperidone palmitate (NCT01193153). The reported effects of these formulations on psychotic, depressive, and manic symptoms are discussed. Both formulations were found to be safe and effective for the acute and maintenance treatment of SCA. Of critical importance for this treatment population is that rapid improvement was seen in all major symptoms of SCA, including psychosis, depression, and mania. Mediation analyses suggest that the known antipsychotic effects of paliperidone occur independently of its antidepressant effects. Both formulations of the drug are effective when used as monotherapy or adjunctively with antidepressants or mood stabilizers. Beyond symptom control, both formulations improved patient functioning and increased patient satisfaction.

Antidepressant activity of nociceptin/orphanin FQ receptor antagonists in the mouse learned helplessness.

PubMed

Holanda, Victor A D; Medeiros, Iris U; Asth, Laila; Guerrini, Remo; Calo', Girolamo; Gavioli, Elaine C

2016-07-01

Pharmacological and genetic evidence support antidepressant-like effects elicited by the blockade of the NOP receptor. The learned helplessness (LH) model employs uncontrollable and unpredictable electric footshocks as a stressor stimulus to induce a depressive-like phenotype that can be reversed by classical antidepressants. The present study aimed to evaluate the action of NOP receptor antagonists in helpless mice. Male Swiss mice were subjected to the three steps of the LH paradigm (i.e., (1) induction, (2) screening, and (3) test). Only helpless animals were subjected to the test session. During the test session, animals were placed in the electrified chamber and the latency to escape after the footshock and the frequency of escape failures were recorded. The effect of the following treatments administered before the test session were evaluated: nortriptyline (30 mg/kg, ip, 60 min), fluoxetine (30 mg/kg, ip, four consecutive days of treatment), and NOP antagonists SB-612111 (1-10 mg/kg, ip, 30 min) and UFP-101 (1-10 nmol, icv, 5 min). To rule out possible biases, the effects of treatments on controllable stressful and non stressful situations were assessed. In helpless mice, nortriptyline, fluoxetine, UFP-101 (3-10 nmol), and SB-612111 (3-10 mg/kg) significantly reduced escape latencies and escape failures. No effects of drug treatments were observed in mice subjected to the controllable electric footshocks and non stressful situations. Acute treatment with NOP antagonists reversed helplessness similarly to the classical antidepressants. These findings support the proposal that NOP receptor antagonists are worthy of development as innovative antidepressant drugs.

Recognition of depression and appropriateness of antidepressant treatment in Italian primary care.

PubMed

Balestrieri, Matteo; Carta, Mauro G; Leonetti, Sabina; Sebastiani, Giuseppe; Starace, Fabrizio; Bellantuono, Cesario

2004-03-01

A significant proportion of primary care patients are affected by a depressive disorder and about half of these patients are undetected and undertreated. Twenty-five primary care physicians (PCPs) were recruited in five Italian centres. All consecutive patients who attended the PCPs' clinics in a 2-week period completed the Personal Health Questionnaire (PHQ), and those scoring more than nine on the PHQ were interviewed with the Hamilton Rating Scale for Depression-17 items (HDRS-17). The appropriateness of antidepressant drug treatment was assessed according to the decision to treat, the coverage, the type of drug and the dosage prescribed. The adjusted prevalence for ICD-10 depression in 2093 patients was 18.7%, while the conspicuous morbidity was 10.7%. The ability of PCPs to detect a depression increased proportionally with HDRS scores. The coverage, i. e. the proportion of patients who would benefit from an antidepressant (AD) and who actually received such drugs, was 20.9%. The drugs most frequently prescribed were SSRI (36 %), followed by TCA (21%) and by other AD. Most SSRI were prescribed at therapeutic dosage, while two-thirds of TCA were at sub-therapeutic dosage. About 37% of patients started a non-pharmacological treatment. The severity of depression at the first consultation predicted the persistence of a depressive state in the longer term. The ability of Italian PCPs to detect depression is satisfactory when the patient's depressive state is moderate or severe. The appropriateness of antidepressant drug treatment still needs to be improved.

Chronic treatment with escitalopram but not R-citalopram translocates Galpha(s) from lipid raft domains and potentiates adenylyl cyclase: a 5-hydroxytryptamine transporter-independent action of this antidepressant compound.

PubMed

Zhang, Lanqiu; Rasenick, Mark M

2010-03-01

Chronic antidepressant treatment has been shown to increase adenylyl cyclase activity, in part, due to translocation of Galpha(s) from lipid rafts to a nonraft fraction of the plasma membrane where they engage in a more facile stimulation of adenylyl cyclase. This effect holds for multiple classes of antidepressants, and for serotonin uptake inhibitors, it occurs in the absence of the serotonin transporter. In the present study, we examined the change in the amount of Galpha(s) in lipid raft and whole cell lysate after exposing C6 cells to escitalopram. The results showed that chronic (but not acute) escitalopram decreased the content of Galpha(s) in lipid rafts, whereas there was no change in overall Galpha(s) content. These effects were drug dose- and exposure time-dependent. Although R-citalopram has been reported to antagonize some effects of escitalopram, this compound was without effect on Galpha(s) localization in lipid rafts, and R-citalopram did not inhibit these actions of escitalopram. Escitalopram treatment increased cAMP accumulation, and this seemed due to increased coupling between Galpha(s) and adenylyl cyclase. Thus, escitalopram is potent, rapid and efficacious in translocating Galpha(s) from lipid rafts, and this effect seems to occur independently of 5-hydroxytryptamine transporters. Our results suggest that, although antidepressants display distinct affinities for well identified targets (e.g., monoamine transporters), several presynaptic and postsynaptic molecules are probably modified during chronic antidepressant treatment, and these additional targets may be required for clinical efficacy of these drugs.

Chronic Treatment with Escitalopram but Not R-Citalopram Translocates Gαs from Lipid Raft Domains and Potentiates Adenylyl Cyclase: A 5-Hydroxytryptamine Transporter-Independent Action of This Antidepressant Compound

PubMed Central

Zhang, Lanqiu

2010-01-01

Chronic antidepressant treatment has been shown to increase adenylyl cyclase activity, in part, due to translocation of Gαs from lipid rafts to a nonraft fraction of the plasma membrane where they engage in a more facile stimulation of adenylyl cyclase. This effect holds for multiple classes of antidepressants, and for serotonin uptake inhibitors, it occurs in the absence of the serotonin transporter. In the present study, we examined the change in the amount of Gαs in lipid raft and whole cell lysate after exposing C6 cells to escitalopram. The results showed that chronic (but not acute) escitalopram decreased the content of Gαs in lipid rafts, whereas there was no change in overall Gαs content. These effects were drug dose- and exposure time-dependent. Although R-citalopram has been reported to antagonize some effects of escitalopram, this compound was without effect on Gαs localization in lipid rafts, and R-citalopram did not inhibit these actions of escitalopram. Escitalopram treatment increased cAMP accumulation, and this seemed due to increased coupling between Gαs and adenylyl cyclase. Thus, escitalopram is potent, rapid and efficacious in translocating Gαs from lipid rafts, and this effect seems to occur independently of 5-hydroxytryptamine transporters. Our results suggest that, although antidepressants display distinct affinities for well identified targets (e.g., monoamine transporters), several presynaptic and postsynaptic molecules are probably modified during chronic antidepressant treatment, and these additional targets may be required for clinical efficacy of these drugs. PMID:19996298

Changes in the neural correlates of implicit emotional face processing during antidepressant treatment in major depressive disorder.

PubMed

Victor, Teresa A; Furey, Maura L; Fromm, Stephen J; Öhman, Arne; Drevets, Wayne C

2013-11-01

An emerging hypothesis regarding the mechanisms underlying antidepressant pharmacotherapy suggests that these agents benefit depressed patients by reversing negative emotional processing biases (Harmer, 2008). Neuropsychological indices and functional neuroimaging measures of the amygdala response show that antidepressant drugs shift implicit and explicit processing biases away from the negative valence and toward the positive valence. However, few studies have explored such biases in regions extensively connected with the amygdala, such as the pregenual anterior cingulate cortex (pgACC) area, where pre-treatment activity consistently has predicted clinical outcome during antidepressant treatment. We used functional magnetic resonance imaging (fMRI) to investigate changes in haemodynamic response patterns to positive vs. negative stimuli in patients with major depressive disorder (MDD) under antidepressant treatment. Participants with MDD (n = 10) underwent fMRI before and after 8 wk sertraline treatment; healthy controls (n = 10) were imaged across an equivalent interval. A backward masking task was used to elicit non-conscious neural responses to sad, happy and neutral face expressions. Haemodynamic responses to emotional face stimuli were compared between conditions and groups in the pgACC. The response to masked-sad vs. masked-happy faces (SN-HN) in pgACC in the depressed subjects was higher in the pre-treatment condition than in the post-treatment condition and this difference was significantly greater than the corresponding change across time in the controls. The treatment-associated difference was attributable to an attenuated response to sad faces and an enhanced response to happy faces. Pre-treatment pgACC responses to SN-HN correlated positively with clinical improvement during treatment. The pgACC participates with the amygdala in processing the salience of emotional stimuli. Treatment-associated functional changes in this limbic network may influence

[Antidepressive agents and suicidal tendencies].

PubMed

Gründer, G; Veselinović, T; Paulzen, M

2014-09-01

In the last 2 years the discussions on the question whether antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) can lead to suicidality, aggression and violence, flared up again. The available data on the problem, which has been discussed since the introduction of this substance group in the late 1980s, is presented in this article. A systematic literature search showed that a scientific consensus exists that the benefits of antidepressant pharmacotherapy in general, and of treatment with SSRIs and selective serotonin/norepinephrine reuptake inhibitors (SSNRIs) in particular, outweigh the risks of their use. This also applies to the treatment of children, adolescents and young adults. The agitation occasionally occurring at the beginning of treatment, which can be experienced as aversive in susceptible patients, can intensify or even trigger suicidal thoughts or impulses. This has to be paid particular attention to especially at the beginning of treatment. It is recommended that the indications for antidepressant pharmacotherapy of children, adolescents and young adults are assessed by a specialist.

Amygdala response to explicit sad face stimuli at baseline predicts antidepressant treatment response to scopolamine in major depressive disorder.

PubMed

Szczepanik, Joanna; Nugent, Allison C; Drevets, Wayne C; Khanna, Ashish; Zarate, Carlos A; Furey, Maura L

2016-08-30

The muscarinic antagonist scopolamine produces rapid antidepressant effects in individuals with major depressive disorder (MDD). In healthy subjects, manipulation of acetyl-cholinergic transmission modulates attention in a stimulus-dependent manner. This study tested the hypothesis that baseline amygdalar activity in response to emotional stimuli correlates with antidepressant treatment response to scopolamine and could thus potentially predict treatment outcome. MDD patients and healthy controls performed an attention shifting task involving emotional faces while undergoing functional magnetic resonance imaging (fMRI). We found that blood oxygenation level dependent (BOLD) signal in the amygdala acquired while MDD patients processed sad face stimuli correlated positively with antidepressant response to scopolamine. Amygdalar response to sad faces in MDD patients who did not respond to scopolamine did not differ from that of healthy controls. This suggests that the pre-treatment task elicited amygdalar activity that may constitute a biomarker of antidepressant treatment response to scopolamine. Furthermore, in MDD patients who responded to scopolamine, we observed a post-scopolamine stimulus processing shift towards a pattern demonstrated by healthy controls, indicating a change in stimulus-dependent neural response potentially driven by attenuated cholinergic activity in the amygdala. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Anticonvulsants or Antidepressants in Combination Pharmacotherapy for Treatment of Neuropathic Pain in Cancer Patients: A Systematic Review and Meta-analysis.

PubMed

Guan, Jia; Tanaka, Shiro; Kawakami, Koji

2016-08-01

To investigate the efficacy of anticonvulsants or antidepressants in combination pharmacotherapy for treatment of neuropathic pain in cancer patients. We systematically searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the metaRegister of Controlled Trials for randomized controlled trials that compared anticonvulsants or antidepressants in combination pharmacotherapy (experimental group) with treatments without anticonvulsants or antidepressants (control group) for neuropathic pain in cancer patients. Risk of bias was evaluated in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was a mean difference (MD) in change in global pain analyzed by a random-effects model. Eight trials met the inclusion criteria with a total of 1359 participants of whom 698 received an experimental intervention. The MD in change in global pain suggested a favorable association with anticonvulsants or antidepressants in combination pharmacotherapy compared with control groups (MD, -0.41; 95% confidence interval, -0.70 to -0.12) with no heterogeneity across trials (I=0%). The MD in change estimated in all sensitivity analyses ranged from -0.36 to -0.47, suggesting that these effects were consistent across different study designs and statistical assumptions. Anticonvulsants or antidepressants in combination pharmacotherapy reduce neuropathic pain in cancer patients compared with treatments without anticonvulsants or antidepressants. Limited evidence precludes a recommendation on specific adjuvants in combination pharmacotherapy.

Personality traits predict treatment outcome with an antidepressant in patients with functional gastrointestinal disorder.

PubMed

Tanum, L; Malt, U F

2000-09-01

We investigated the relationship between personality traits and response to treatment with the tetracyclic antidepressant mianserin or placebo in patients with functional gastrointestinal disorder (FGD) without psychopathology. Forty-eight patients completed the Buss-Durkee Hostility Inventory, Neuroticism Extroversion Openness -Personality Inventory (NEO-PI), and Eysenck Personality Questionnaire (EPQ), neuroticism + lie subscales, before they were consecutively allocated to a 7-week double-blind treatment study with mianserin or placebo. Treatment response to pain and target symptoms were recorded daily with the Visual Analogue Scale and Clinical Global Improvement Scale at every visit. A low level of neuroticism and little concealed aggressiveness predicted treatment outcome with the antidepressant drug mianserin in non-psychiatric patients with FGD. Inversely, moderate to high neuroticism and marked concealed aggressiveness predicted poor response to treatment. These findings were most prominent in women. Personality traits were better predictors of treatment outcome than serotonergic sensitivity assessed with the fenfluramine test. Assessment of the personality traits negativism, irritability, aggression, and neuroticism may predict response to drug treatment of FGD even when serotonergic sensitivity is controlled for. If confirmed in future studies, the findings point towards a more differential psychopharmacologic treatment of FGD.

Combining clinical variables to optimize prediction of antidepressant treatment outcomes.

PubMed

Iniesta, Raquel; Malki, Karim; Maier, Wolfgang; Rietschel, Marcella; Mors, Ole; Hauser, Joanna; Henigsberg, Neven; Dernovsek, Mojca Zvezdana; Souery, Daniel; Stahl, Daniel; Dobson, Richard; Aitchison, Katherine J; Farmer, Anne; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

2016-07-01

The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction. We used elastic net regularized regression to optimize prediction of symptom improvement and remission during treatment with escitalopram or nortriptyline and to identify contributing predictors from a range of demographic and clinical variables in 793 adults with major depressive disorder. A combination of demographic and clinical variables, with strong contributions from symptoms of depressed mood, reduced interest, decreased activity, indecisiveness, pessimism and anxiety significantly predicted treatment outcomes, explaining 5-10% of variance in symptom improvement with escitalopram. Similar combinations of variables predicted remission with area under the curve 0.72, explaining approximately 15% of variance (pseudo R(2)) in who achieves remission, with strong contributions from body mass index, appetite, interest-activity symptom dimension and anxious-somatizing depression subtype. Escitalopram-specific outcome prediction was more accurate than generic outcome prediction, and reached effect sizes that were near or above a previously established benchmark for clinical significance. Outcome prediction on the nortriptyline arm did not significantly differ from chance. These results suggest that easily obtained demographic and clinical variables can predict therapeutic response to escitalopram with clinically meaningful accuracy, suggesting a potential for individualized prescription of this antidepressant drug. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effects of BDNF polymorphisms on antidepressant action.

PubMed

Tsai, Shih-Jen; Hong, Chen-Jee; Liou, Ying-Jay

2010-12-01

Evidence suggests that the down-regulation of the signaling pathway involving brain-derived neurotrophic factor (BDNF), a molecular element known to regulate neuronal plasticity and survival, plays an important role in the pathogenesis of major depression. The restoration of BDNF activity induced by antidepressant treatment has been implicated in the antidepressant therapeutic mechanism. Because there is variability among patients with major depressive disorder in terms of response to antidepressant treatment and since genetic factors may contribute to this inter-individual variability in antidepressant response, pharmacogenetic studies have tested the associations between genetic polymorphisms in candidate genes related to antidepressant therapeutic action. In human BDNF gene, there is a common functional polymorphism (Val66Met) in the pro-region of BDNF, which affects the intracellular trafficking of proBDNF. Because of the potentially important role of BDNF in the antidepressant mechanism, many pharmacogenetic studies have tested the association between this polymorphism and the antidepressant therapeutic response, but they have produced inconsistent results. A recent meta-analysis of eight studies, which included data from 1,115 subjects, suggested that the Val/Met carriers have increased antidepressant response in comparison to Val/Val homozygotes, particularly in the Asian population. The positive molecular heterosis effect (subjects heterozygous for a specific genetic polymorphism show a significantly greater effect) is compatible with animal studies showing that, although BDNF exerts an antidepressant effect, too much BDNF may have a detrimental effect on mood. Several recommendations are proposed for future antidepressant pharmacogenetic studies of BDNF, including the consideration of multiple polymorphisms and a haplotype approach, gene-gene interaction, a single antidepressant regimen, controlling for age and gender interactions, and pharmacogenetic

Sexual dysfunction, depression, and the impact of antidepressants.

PubMed

Kennedy, Sidney H; Rizvi, Sakina

2009-04-01

Sexual dysfunction is a common symptom of depression. Although decreased libido is most often reported, difficulties with arousal, resulting in vaginal dryness in women and erectile dysfunction in men, and absent or delayed orgasm are also prevalent. Sexual dysfunction is also a frequent adverse effect of treatment with most antidepressants and is one of the predominant reasons for premature drug discontinuation. Selective serotonin reuptake inhibitors are the most widely prescribed antidepressants and have significant effects on arousal and orgasm compared with antidepressants that target norepinephrine, dopamine, and melatonin systems. The availability of an antidepressant that does not cause or exacerbate sexual dysfunction represents an advance in pharmacotherapy for mood disorders and should reduce treatment noncompliance and decrease the need for switching antidepressants or adding antidotes. The purpose of this review was to provide an update on the prevalence, psychobiology, and relative adverse effect burden of sexual dysfunction associated with different antidepressants.

Antidepressant, anxiolytic and procognitive effects of subacute and chronic ketamine in the chronic mild stress model of depression.

PubMed

Papp, Mariusz; Gruca, Piotr; Lason-Tyburkiewicz, Magdalena; Willner, Paul

2017-02-01

Ketamine is the prototype of a new generation of antidepressant drugs, which is reported in clinical studies to be effective in treatment-resistant patients, with an effect that appears within hours and lasts for a few days. Chronic mild stress (CMS) is a well-established and widely used animal model of depression, in which anhedonia, anxiogenesis and cognitive dysfunction can be observed reliably. Studies using acute or brief ketamine treatment following withdrawal from CMS have replicated the clinical finding of a rapid onset of antidepressant action. However, there have been no CMS studies of chronic daily ketamine treatment or continued stress following ketamine treatment, which would have greater translational potential in relation to the long-term maintenance of antidepressant effects. Wistar rats were drug treated following an initial 2 weeks of CMS exposure, which continued alongside daily drug treatment. A first experiment tested a range of chronic (5 weeks) ketamine doses (5-30 mg/kg); a second compared the effects of subacute (3-5 days) and chronic (5 weeks) treatment. CMS-induced anhedonic, anxiogenic and dyscognitive effects, as measured, respectively, by decreased sucrose intake, avoidance of open arms in the elevated plus maze and loss of discrimination in the novel object recognition test. A sustained antidepressant-like effect of ketamine in the sucrose intake test was observed in both experiments, with an onset at around 1 week, faster than imipramine, and an optimum dose of 10 mg/kg. Anxiogenic and dyscognitive effects of CMS, in the elevated plus maze and novel object recognition test, respectively, were fully reversed by both subacute and chronic ketamine treatment. Daily treatment with ketamine in the CMS model causes sustained long-term antidepressant, anxiolytic and procognitive effects. The demonstration of a procognitive effect of ketamine may have particular translational value.

Differential Antidepressant-Like Response to Lithium Treatment between Mouse Strains: Effects of Sex, Maternal Care, and Mixed Genetic Background

PubMed Central

Can, Adem; Piantadosi, Sean C.; Gould, Todd D.

2013-01-01

Background Lithium is a mood stabilizer with both antidepressant and antimanic properties, though its mechanism of action is unclear. Identifying the genetic factors that influence lithium's therapeutic actions will be an important step to assist in identifying such mechanisms. We previously reported that lithium treatment of male mice has antidepressant-like effects in the C57BL/6J strain but that such effects were absent in the BALB/cJ strain. Objectives To assess the roles of both genetic, and non-genetic factors such as sex and non-shared environmental factors that may mediate differential behavioral responses to lithium. Methods Mice were treated with lithium for ten days and then tested in the forced swim test followed by lithium discontinuation and retesting to assess effects of lithium withdrawal. We also assessed effects of sex and cross-fostering on lithium response between the C57BL/6J and BALB/cJ strains, and antidepressant-like effects of lithium in the hybrid CB6F1/J strain that is derived from C57BL/6J and BALB/cJ parental strains. Results Neither sex nor maternal care significantly influenced the differential antidepressant-like profile of lithium. Withdrawal from lithium treatment reversed antidepressant-like effects in the C57BL/6J strain, but had no effects in BALB/cJ mice. Lithium treatment did not result in antidepressant-like effects in the CB6F1/J strain. Conclusions Genetic factors are likely primarily responsible for differential antidepressant-like effects of lithium in the C57BL/6J and BALB/cJ strains. Future studies identifying such genetic factors may help to elucidate the neurobiological mechanisms of lithium's therapeutic actions. PMID:23503701

Review of Evidence for Use of Antidepressants in Bipolar Depression

PubMed Central

McInerney, Shane J.

2014-01-01

Objective: Depressive episodes predominate over the course of bipolar disorder and cause considerable functional impairment. Antidepressants are frequently prescribed in the treatment of bipolar depression, despite concerns about efficacy and risk of switching to mania. This review provides a critical examination of the evidence for and against the use of antidepressants in bipolar depression. Data Sources: English-language peer-reviewed literature and evidence-based guidelines published between January 1, 1980, and March 2014, were identified using PubMed, MEDLINE, PsycINFO/PsycLIT, and EMBASE. All searches contained the terms antidepressants, bipolar depression, depressive episodes in bipolar disorder, and treatment guidelines for bipolar depression. Meta-analyses, randomized controlled trials, systematic reviews, and practice guidelines were included. Bibliographies from these publications were used to identify additional articles of interest. Data Extraction: Studies involving treatment of bipolar depression with antidepressant monotherapy, adjunctive use of antidepressant with a mood stabilizer, and meta-analysis of such studies combined were reviewed. Conclusions: The body of evidence on the use of antidepressant monotherapy to treat patients with bipolar depression is contentious, but the recommendations from evidence-based guidelines do not support antidepressant monotherapy for bipolar depression. Only when mood stabilizer or atypical antipsychotic monotherapy has failed should adjunctive treatment with an antidepressant be considered. PMID:25667812

Sexual side effects of serotonergic antidepressants: mediated by inhibition of serotonin on central dopamine release?

PubMed

Bijlsma, Elisabeth Y; Chan, Johnny S W; Olivier, Berend; Veening, Jan G; Millan, Mark J; Waldinger, Marcel D; Oosting, Ronald S

2014-06-01

Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducibility of our standardized test procedure that assesses the acute, subchronic and chronic effects of psychoactive compounds in a 30 minute mating test. In addition, we present an overview of the effects of several different (putative) antidepressants on male rat sexual behavior, as tested in our standardized test procedure. By comparing the effects of these mechanistically distinct antidepressants (paroxetine, venlafaxine, bupropion, buspirone, DOV 216,303 and S32006), this review discusses the putative mechanism underlying sexual side effects of antidepressants and their normalization. This review shows that sexual behavior is mainly inhibited by antidepressants that increase serotonin neurotransmission via blockade of serotonin transporters, while those that mainly increase the levels of dopamine and noradrenaline are devoid of sexual side effects. Those sexual disturbances cannot be normalized by simultaneously increasing noradrenaline neurotransmission, but are normalized by increasing both noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that the sexual side effects of selective serotonin reuptake inhibitors may be mediated by their inhibitory effects on dopamine signaling in sex brain circuits. Clinical development of novel antidepressants should therefore focus on compounds that simultaneously increase both serotonin and dopamine signaling. © 2013 Elsevier Inc. All rights reserved.

Altered brain concentrations of citalopram and escitalopram in P-glycoprotein deficient mice after acute and chronic treatment.

PubMed

Karlsson, Louise; Carlsson, Björn; Hiemke, Christoph; Ahlner, Johan; Bengtsson, Finn; Schmitt, Ulrich; Kugelberg, Fredrik C

2013-11-01

According to both in vitro and in vivo data P-glycoprotein (P-gp) may restrict the uptake of several antidepressants into the brain, thus contributing to the poor success rate of current antidepressant therapies. The therapeutic activity of citalopram resides in the S-enantiomer, whereas the R-enantiomer is practically devoid of serotonin reuptake potency. To date, no in vivo data are available that address whether the enantiomers of citalopram and its metabolites are substrates of P-gp. P-gp knockout (abcb1ab (-/-)) and wild-type (abcb1ab (+/+)) mice underwent acute (single-dose) and chronic (two daily doses for 10 days) treatment with citalopram (10mg/kg) or escitalopram (5mg/kg) Serum and brain samples were collected 1-6h after the first or last i.p. injection for subsequent drug analysis by an enantioselective HPLC method. In brain, 3-fold higher concentrations of S- and R-citalopram, and its metabolites, were found in abcb1ab (-/-) mice than in abcb1ab (+/+) mice after both acute and chronic citalopram treatments. After escitalopram treatment, the S-citalopram brain concentration was 3-5 times higher in the knockout mice than in controls. The results provide novel evidence that the enantiomers of citalopram are substrates of P-gp. Possible clinical and toxicological implications of this finding need to be further elucidated. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Antidepressant use and mortality in very old people.

PubMed

Boström, Gustaf; Hörnsten, Carl; Brännström, Jon; Conradsson, Mia; Nordström, Peter; Allard, Per; Gustafson, Yngve; Littbrand, Håkan

2016-07-01

Antidepressant treatment may increase the risk of death. The association between antidepressants and mortality has been evaluated in community-dwelling older people, but not in representative samples of very old people, among whom dementia, multimorbidity, and disability are common. Umeå 85+/GERDA study participants (n = 992) aged 85, 90, and ≥95 years were followed for up to five years. Cox proportional hazard regression models were used to analyze mortality risk associated with baseline antidepressant treatment, adjusted for potential confounders. Mean age was 89 years; 27% of participants had dementia, 20% had stroke histories, 29% had heart failure, and 16% used antidepressants. In age- and sex-adjusted analyses, antidepressant use was associated with a 76% increased mortality risk (hazard ratio [HR] = 1.76; 95% confidence interval [CI], 1.41-2.19). Adding adjustment for Geriatric Depression Scale score, HR was 1.62 (95% CI, 1.29-2.03). The association was not significant when adjusting for additional confounding factors (HR = 1.08; 95% CI, 0.85-1.38). Interaction analyses in the fully adjusted model revealed a significant interaction between sex and antidepressant use (HR: 1.76; 95% CI, 1.05-2.94). Among male and female antidepressant users, the HRs for death were 0.76 (95% CI, 0.47-1.24) and 1.28 (95% CI, 0.97-1.70), respectively. Among very old people, baseline antidepressant treatment does not seem to be independently associated with increased mortality risk. However, the risk may be different in men and women. This difference and the potential risk of initial treatment require further investigation in future cohort studies of very old people.

Pharmacogenetics and Imaging-Pharmacogenetics of Antidepressant Response: Towards Translational Strategies.

PubMed

Lett, Tristram A; Walter, Henrik; Brandl, Eva J

2016-12-01

Genetic variation underlies both the response to antidepressant treatment and the occurrence of side effects. Over the past two decades, a number of pharmacogenetic variants, among these the SCL6A4, BDNF, FKBP5, GNB3, GRIK4, and ABCB1 genes, have come to the forefront in this regard. However, small effects sizes, mixed results in independent samples, and conflicting meta-analyses results led to inherent difficulties in the field of pharmacogenetics translating these findings into clinical practice. Nearly all antidepressant pharmacogenetic variants have potentially pleiotropic effects in which they are associated with major depressive disorder, intermediate phenotypes involved in emotional processes, and brain areas affected by antidepressant treatment. The purpose of this article is to provide a comprehensive review of the advances made in the field of pharmacogenetics of antidepressant efficacy and side effects, imaging findings of antidepressant response, and the latest results in the expanding field of imaging-pharmacogenetics studies. We suggest there is mounting evidence that genetic factors exert their impact on treatment response by influencing brain structural and functional changes during antidepressant treatment, and combining neuroimaging and genetic methods may be a more powerful way to detect biological mechanisms of response than either method alone. The most promising imaging-pharmacogenetics findings exist for the SCL6A4 gene, with converging associations with antidepressant response, frontolimbic predictors of affective symptoms, and normalization of frontolimbic activity following antidepressant treatment. More research is required before imaging-pharmacogenetics informed personalized medicine can be applied to antidepressant treatment; nevertheless, inroads have been made towards assessing genetic and neuroanatomical liability and potential clinical application.

[Tricyclic antidepressant therapy in headache].

PubMed

Magyar, Máté; Csépány, Éva; Gyüre, Tamás; Bozsik, György; Bereczki, Dániel; Ertsey, Csaba

2015-12-01

The two most important representatives of the primary headaches are migraine and tension-type headache. More than 10% of the population suffer from migraine and even a greater part, approximately 30-40% from tension-type headache. These two headache types have a great effect both on the individual and on the society. There are two types of therapeutic approaches to headaches: the abortive and the prophylactic therapy. Prophylactic treatment is used for frequent and/or difficult-to-treat headache attacks. Although both migraine and tension-type headache are often associated with depression, for their treatment - in contrast to the widespread medical opinion - not all antidepressants were found to be effective. Amitriptyline, which is a tricyclic antidepressant, is used as a prophylactic therapy for headache since 1968. Its efficacy has been demonstrated in several double-blind, placebo-controlled studies. Although the newer types of antidepressant, such as selective serotonin reuptake inhibitors and selective serotonin-norepinephrine reuptake inhibitor, have a more favorable side-effect profile than tricyclic antidepressants, their headache prophylactic effect has not been proven yet.

Antidepressants for the treatment of abdominal pain-related functional gastrointestinal disorders in children and adolescents.

PubMed

Kaminski, Angela; Kamper, Adrian; Thaler, Kylie; Chapman, Andrea; Gartlehner, Gerald

2011-07-06

Abdominal pain-related functional gastrointestinal disorders (FGIDs) are among the most common medical problems in paediatric medicine. Frequently, physicians prescribe antidepressants as a second-line treatment for children and adolescents with FGIDs. To date, the evidence on the benefits and harms of antidepressants for the treatment of abdominal pain-related FGIDs has not been assessed systematically. The primary objectives were to conduct a systematic review to evaluate the efficacy and safety of antidepressants for the treatment of abdominal pain-related FGIDs in children and adolescents. We searched The Cochrane Library, PubMed, EMBASE, IPA, CINAHL, PsycINFO, ISI Web of Science, Biosis Previews and the International Clinical Trials Registry Platform of the World Health Organization with appropriate filters (from inception to January 31, 2011). For efficacy we included double-blind, randomised controlled trials (RCTs) of antidepressants for treatment of abdominal pain-related FGIDs in children and adolescents 18 years or younger. Open-label and uncontrolled experimental studies, as well as observational studies were eligible for the assessment of harms. The minimum study duration was 4 weeks. The minimum study size was 30 participants. Two authors independently assessed all abstracts and full text articles, and rated the risk of bias for included studies. Data were extracted independently by one author and checked for accuracy by another author. Data were analysed using RevMan 5. Two RCTs (123 participants), both using amitriptyline, met the pre-specified inclusion criteria. These studies provided mixed findings on the efficacy of amitriptyline for the treatment of abdominal pain-related FGIDs. The larger, publicly-funded study reported no statistically significant difference in efficacy between amitriptyline and placebo in 90 children and adolescents with FGIDs after 4 weeks of treatment. On intention-to-treat (ITT)- analysis, 59% of the children reported

VGF function in depression and antidepressant efficacy.

PubMed

Jiang, C; Lin, W-J; Sadahiro, M; Labonté, B; Menard, C; Pfau, M L; Tamminga, C A; Turecki, G; Nestler, E J; Russo, S J; Salton, S R

2017-11-21

Brain-derived neurotrophic factor (BDNF) is a critical effector of depression-like behaviors and antidepressant responses. Here, we show that VGF (non-acronymic), which is robustly regulated by BDNF/TrkB signaling, is downregulated in hippocampus (male/female) and upregulated in nucleus accumbens (NAc) (male) in depressed human subjects and in mice subjected to chronic social defeat stress (CSDS). Adeno-associated virus (AAV)-Cre-mediated Vgf ablation in floxed VGF mice, in dorsal hippocampus (dHc) or NAc, led to pro-depressant or antidepressant behaviors, respectively, while dHc- or NAc-AAV-VGF overexpression induced opposite outcomes. Mice with reduced VGF levels in the germ line (Vgf+/-) or in dHc (AAV-Cre-injected floxed mice) showed increased susceptibility to CSDS and impaired responses to ketamine treatment in the forced swim test. Floxed mice with conditional pan-neuronal (Synapsin-Cre) but not those with forebrain (αCaMKII-Cre) Vgf ablation displayed increased susceptibility to subthreshold social defeat stress, suggesting that neuronal VGF, expressed in part in inhibitory interneurons, regulates depression-like behavior. Acute antibody-mediated sequestration of VGF-derived C-terminal peptides AQEE-30 and TLQP-62 in dHc induced pro-depressant effects. Conversely, dHc TLQP-62 infusion had rapid antidepressant efficacy, which was reduced in BDNF floxed mice injected in dHc with AAV-Cre, and in NBQX- and rapamycin-pretreated wild-type mice, these compounds blocking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and mammalian target of rapamycin (mTOR) signaling, respectively. VGF is therefore a critical modulator of depression-like behaviors in dHc and NAc. In hippocampus, the antidepressant response to ketamine is associated with rapid VGF translation, is impaired by reduced VGF expression, and as previously reported, requires coincident, rapid BDNF translation and release.Molecular Psychiatry advance online publication, 21 November

Use of antidepressants in the treatment of depression in Asia: guidelines, clinical evidence, and experience revisited.

PubMed

Treuer, Tamás; Liu, Chia-Yih; Salazar, Gerardo; Kongsakon, Ronnachai; Jia, Fujun; Habil, Hussain; Lee, Min-Soo; Lowry, Amanda; Dueñas, Héctor

2013-12-01

Major depressive disorder is prevalent worldwide, and only about half of those affected will experience no further episodes or symptoms. Additionally, depressive symptoms can be challenging to identify, with many patients going undiagnosed despite a wide variety of available treatment options. Antidepressants are the cornerstone of depression treatment; however, a large number of factors must be considered in selecting the treatment best suited to the individual. To help support physicians in this process, international and national treatment guidelines have been developed. This review evaluates the current use of antidepressant treatment for major depressive disorder in six Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No remarkable differences were noted between Asian and international treatment guidelines or among those from within Asia as these are adapted from western guidelines, although there were some local variations. Importantly, a shortage of evidence-based information at a country level is the primary problem in developing guidelines appropriate for Asia, so most of the guidelines are consensus opinions derived from western research data utilized in western guidelines. Treatment guidelines need to evolve from being consensus based to evidence based when evidence is available, taking into consideration cost/effectiveness or cost/benefit with an evidence-based approach that more accurately reflects clinical experience as well as the attributes of each antidepressant. In everyday practice, physicians must tailor their treatment to the patient's clinical needs while considering associated external factors; better tools are needed to help them reach the best possible prescribing decisions which are of maximum benefit to patients. Copyright © 2013 Wiley Publishing Asia Pty Ltd.

Predicting persistence to antidepressant treatment in administrative claims data: Considering the influence of refill delays and prior persistence on other medications

PubMed Central

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

2016-01-01

Background Many patients with major depressive disorder (MDD) who begin antidepressant treatment discontinue use before for six months, the recommended minimum treatment length. This study sought to identify predictors of six-month antidepressant persistence including predictors utilizing patients’ electronic prescription records. Methods Commercially insured children (3–17 years) and adults (18–64 years) with MDD who initiated antidepressant treatment, 1/1/2003–2/28/2010, were assessed for six-month persistence (based on prescriptions’ days supply, allowing a 30-day grace period). Antidepressant persistence prediction models were developed separately for children and adults. Two additional measures, days without medication between the first and second antidepressant fill (children and adults) and prior persistence on other medications (adults only), were added to the models, concordance (c) statistics were compared and risk reclassification evaluated. Results Among children (n=8,837 children) and adults (n=47,495) with MDD, six-month antidepressant persistence was low and varied by age (37%, 18–24 years to 52%, 3–12 and 50–64 years, respectively). Independent baseline predictors of persistence were identified, with model c-statistics: children=0.582, adults=0.584. Patients with more days without medication between fills were less likely to be persistent (10–30 vs. 0 days, children: RR=0.72, adults: RR=0.74), as were adults not previously persistent to other medications (RR=0.73). Limitations The definition of 6-month persistence is dependent on correct days supply values and the grace period utilized; potential predictors were limited to measures available in claims data. Conclusions Six-month antidepressant persistence was low and overall prediction of persistence was poor; however, days without medication between fills and prior persistence on other medications marginally improved the ability to predict antidepressant persistence. PMID:26921866

Methodological Flaws, Conflicts of Interest, and Scientific Fallacies: Implications for the Evaluation of Antidepressants' Efficacy and Harm.

PubMed

Hengartner, Michael P

2017-01-01

In current psychiatric practice, antidepressants are widely and with ever-increasing frequency prescribed to patients. However, several scientific biases obfuscate estimates of antidepressants' efficacy and harm, and these are barely recognized in treatment guidelines. The aim of this mini-review is to critically evaluate the efficacy and harm of antidepressants for acute and maintenance treatment with respect to systematic biases related to industry funding and trial methodology. Narrative review based on a comprehensive search of the literature. It is shown that the pooled efficacy of antidepressants is weak and below the threshold of a minimally clinically important change once publication and reporting biases are considered. Moreover, the small mean difference in symptom reductions relative to placebo is possibly attributable to observer effects in unblinded assessors and patient expectancies. With respect to trial dropout rates, a hard outcome not subjected to observer bias, no difference was observed between antidepressants and placebo. The discontinuation trials on the efficacy of antidepressants in maintenance therapy are systematically flawed, because in these studies, spontaneous remitters are excluded, whereas half of all patients who remitted on antidepressants are abruptly switched to placebo. This can cause a severe withdrawal syndrome that is easily misdiagnosed as a relapse when assessed on subjective symptom rating scales. In accordance, the findings of naturalistic long-term studies suggest that maintenance therapy has no clear benefit, and non-drug users do not show increased recurrence rates. Moreover, a growing body of evidence from hundreds of randomized controlled trials suggests that antidepressants cause suicidality, but this risk is underestimated because data from industry-funded trials are systematically flawed. Unselected, population-wide observational studies indicate that depressive patients who use antidepressants are at an increased

Antidepressant augmentation with anti-inflammatory agents.

PubMed

Andrade, Chittaranjan

2014-09-01

Antidepressant augmentation strategies are commonly employed to treat depressed patients who do not respond to antidepressant monotherapy. Neuroinflammatory mechanisms have been implicated in depression, and nonsteroidal anti-inflammatory drugs (NSAIDs) have been found effective in animal models of depression both in monotherapy and when used to augment antidepressant drugs. However, results with NSAIDs have been mixed in human observational studies, with both better and worse depression outcomes reported. Four small (pooled N = 160) randomized controlled trials suggest that celecoxib (200-400 mg/d) augmentation of antidepressant medication improves 4-6 week outcomes in major depressive disorder. There are no data, however, to support the use of celecoxib or other NSAIDs in antidepressant-resistant depression. There are also concerns about adverse events associated with NSAID treatment, and about pharmacodynamic drug interactions between these drugs and serotonin reuptake inhibitors. A reasonable conclusion for the present is that NSAID augmentation of antidepressants is, at best, a tentative approach in nonrefractory major depression. © Copyright 2014 Physicians Postgraduate Press, Inc.

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

Burnout as a risk factor for antidepressant treatment - a repeated measures time-to-event analysis of 2936 Danish human service workers.

PubMed

Madsen, Ida E H; Lange, Theis; Borritz, Marianne; Rugulies, Reiner

2015-06-01

Burnout is a state of emotional exhaustion, feelings of reduced personal accomplishment, and withdrawal from work thought to occur as a consequence of prolonged occupational stress. The condition is not included in the diagnostic classifications, but is considered likely to develop into depressive disorder in some cases. We examined the prospective association between burnout and antidepressant treatment, as an indicator of clinically significant mental disorder. We further investigated potential effect-modifiers of the association, to identify factors that may prevent this progression of burnout. We used questionnaire data from a three-wave study of Danish human service workers conducted during 1999-2005, linked with national register data on purchases of antidepressants (ATC: N06A). We included 4788 observations from 2936 individuals (81% women) and analysed data by Aalens additive hazards modeling, examining the risk of entering antidepressant treatment in relation to the level of work-related burnout measured by the Copenhagen Burnout inventory. As effect-modifiers we examined both sociodemographic factors and a range of psychosocial work environment factors. The level of burnout predicted antidepressant treatment. This association was modified by sex (p < 0.01). In men, high vs. intermediate burnout was associated with a 5% increased risk of antidepressant treatment per year of follow-up. This risk difference was 1% for women. Due to the sex specific patterns, we restricted effect modification analyses to women. We found no effect-modification by the examined work environment factors, though a sensitivity analysis indicated a possible stronger association in women of lower occupational position. In conclusion, burnout predicted antidepressant treatment, with a stronger association in men than women. We found no evidence of effect-modification by any of the examined psychosocial work environment factors. Copyright © 2015 The Authors. Published by Elsevier

Pregnanolone Glutamate, a Novel Use-Dependent NMDA Receptor Inhibitor, Exerts Antidepressant-Like Properties in Animal Models.

PubMed

Holubova, Kristina; Nekovarova, Tereza; Pistovcakova, Jana; Sulcova, Alexandra; Stuchlík, Ales; Vales, Karel

2014-01-01

A number of studies demonstrated a rapid onset of an antidepressant effect of non-competitive N-methyl-d-aspartic acid receptor (NMDAR) antagonists. Nonetheless, its therapeutic potential is rather limited, due to a high coincidence of negative side-effects. Therefore, the challenge seems to be in the development of NMDAR antagonists displaying antidepressant properties, and at the same time maintaining regular physiological function of the NMDAR. Previous results demonstrated that naturally occurring neurosteroid 3α5β-pregnanolone sulfate shows pronounced inhibitory action by a use-dependent mechanism on the tonically active NMDAR. The aim of the present experiments is to find out whether the treatment with pregnanolone 3αC derivatives affects behavioral response to chronic and acute stress in an animal model of depression. Adult male mice were used throughout the study. Repeated social defeat and forced swimming tests were used as animal models of depression. The effect of the drugs on the locomotor/exploratory activity in the open-field test was also tested together with an effect on anxiety in the elevated plus maze. Results showed that pregnanolone glutamate (PG) did not induce hyperlocomotion, whereas both dizocilpine and ketamine significantly increased spontaneous locomotor activity in the open field. In the elevated plus maze, PG displayed anxiolytic-like properties. In forced swimming, PG prolonged time to the first floating. Acute treatment of PG disinhibited suppressed locomotor activity in the repeatedly defeated group-housed mice. Aggressive behavior of isolated mice was reduced after the chronic 30-day administration of PG. PG showed antidepressant-like and anxiolytic-like properties in the used tests, with minimal side-effects. Since PG combines GABAA receptor potentiation and use-dependent NMDAR inhibition, synthetic derivatives of neuroactive steroids present a promising strategy for the treatment of mood disorders. -3α5�

Clinical variables related to antidepressant-induced mania in bipolar disorder.

PubMed

Mundo, Emanuela; Cattaneo, Elisabetta; Russo, Michela; Altamura, A Carlo

2006-06-01

The development of mania or hypomania during antidepressant treatment is a serious complication of the clinical management of bipolar disorder (BP). The primary aim of this study was to evaluate the clinical variables related to antidepressant-induced mania or hypomania (AIM) in patients with BP. DSM-IV BP-I or BP-II patients who had had at least one depressive episode treated with antidepressants were considered. Patients were subdivided into two groups according to the presence (n = 30) or absence (n = 106) of manic or hypomanic episodes occurring during antidepressant treatment. Possible predictive clinical variables of AIM were considered: gender, diagnostic subtype, age at onset, duration of illness, duration of untreated illness, type of antidepressant administered, number of previous spontaneous hypomanic or manic episodes, number of previous depressive episodes, presence of lifetime suicide attempts, presence of mood stabilizer treatments, presence of psychotic symptoms during spontaneous episodes, family history for psychiatric disorders in first degree relatives. Data were compared between the two groups, with (AIM+) and without (AIM-) antidepressant-induced mania, using Student's t tests and chi-square tests. The lack of mood stabilizer treatments during antidepressant therapy (chi-square = 37.602, df = 1, p < 0.001) and the exposure to tricyclic antidepressants (chi-square = 4.901, df = 1, p < 0.05) resulted significantly associated to the development of AIM. This study was not done under controlled conditions and the relatively small sample studied warrants further replications. These results point out the risk of mania induction associated to the use of tricyclic antidepressants in BP patients, mainly in absence of adequate mood stabilizers.

Hippocampal astrocytes are necessary for antidepressant treatment of learned helplessness rats.

PubMed

Iwata, Masaaki; Shirayama, Yukihiko; Ishida, Hisahito; Hazama, Gen-i; Nakagome, Kazuyuki

2011-08-01

The astrocyte is a major component of the neural network and plays a role in brain function. Previous studies demonstrated changes in the number of astrocytes in depression. In this study, we examined alterations in the number of astrocytes in the learned helplessness (LH) rat, an animal model of depression. The numbers of activated and nonactivated astrocytes in the dentate gyrus (molecular layer, subgranular zone, and hilus), and CA1 and CA3 regions of the hippocampus were significantly increased 2 and 8 days after attainment of LH. Subchronic treatment with imipramine showed a tendency (although not statistically significant) to decrease the LH-induced increment of activated astrocytes in the CA3 region and dentate gyrus. Furthermore, subchronic treatment of naïve rats with imipramine did not alter the numbers of activated and nonactivated astrocytes. However, the antidepressant-like effects of imipramine in the LH paradigm were blocked when fluorocitrate (a reversible inhibitor of astrocyte function) was injected into the dentate gyrus or CA3 region. Injection of fluorocitrate into naive rats failed to induce behavioral deficits in the conditioned avoidance test. These results indicate that astrocytes are responsive to the antidepressant-like effect of imipramine in the dentate gyrus and CA3 region of the hippocampus. Copyright © 2010 Wiley-Liss, Inc.

Possible involvement of ATP-sensitive potassium channels in the antidepressant-like effects of gabapentin in mouse forced swimming test.

PubMed

Ostadhadi, Sattar; Akbarian, Reyhaneh; Norouzi-Javidan, Abbas; Nikoui, Vahid; Zolfaghari, Samira; Chamanara, Mohsen; Dehpour, Ahmad-Reza

2017-07-01

Gabapentin as an anticonvulsant drug also has beneficial effects in treatment of depression. Previously, we showed that acute administration of gabapentin produced an antidepressant-like effect in the mouse forced swimming test (FST) by a mechanism that involves the inhibition of nitric oxide (NO). Considering the involvement of NO in adenosine triphosphate (ATP)-sensitive potassium channels (K ATP ), in the present study we investigated the involvement of K ATP channels in antidepressant-like effect of gabapentin. Gabapentin at different doses (5-10 mg/kg) and fluoxetine (20 mg/kg) were administrated by intraperitoneal route, 60 and 30 min, respectively, before the test. To clarify the probable involvement of K ATP channels, mice were pretreated with K ATP channel inhibitor or opener. Gabapentin at dose 10 mg/kg significantly decreased the immobility behavior of mice similar to fluoxetine (20 mg/kg). Co-administration of subeffective dose (1 mg/kg) of glibenclamide (inhibitor of K ATP channels) with gabapentin (3 mg/kg) showed a synergistic antidepressant-like effect. Also, subeffective dose of cromakalim (opener of K ATP channels, 0.1 mg/kg) inhibited the antidepressant-like effect of gabapentin (10 mg/kg). None of the treatments had any impact on the locomotor movement. Our study, for the first time, revealed that antidepressant-like effect of gabapentin in mice is mediated by blocking the K ATP channels.

Inhibition of the L-arginine-nitric oxide pathway mediates the antidepressant effects of ketamine in rats in the forced swimming test.

PubMed

Zhang, Guang-Fen; Wang, Nan; Shi, Jin-Yun; Xu, Shi-Xia; Li, Xiao-Min; Ji, Mu-Huo; Zuo, Zhi-Yi; Zhou, Zhi-Qiang; Yang, Jian-Jun

2013-09-01

Converging evidence shows that the acute administration of a sub-anaesthetic dose ketamine produces fast-acting and robust antidepressant properties in patients suffering from major depressive disorder. However, the underlying mechanisms have not been fully elucidated. The present study aimed to investigate the role of the L-arginine-nitric oxide pathway in the antidepressant effects of ketamine in rats performing the forced swimming test (FST). Ketamine (10 mg/kg) significantly decreased immobility times in the FST and the activities of total nitric oxide synthases (T-NOS), inducible NOS (iNOS), and endothelial NOS (eNOS) in the rat hippocampus. Interestingly, the plasma activities of T-NOS, iNOS, and eNOS increased after administration of ketamine. Furthermore, the activities of neuronal NOS (nNOS) did not change significantly in either the hippocampus or plasma after ketamine administration. The antidepressant effects of ketamine were prevented by pre-treatment with l-arginine (750 mg/kg). Pre-treatment with the NOS inhibitor L-NG-nitroarginine methyl ester at a sub-antidepressant dose of 50 mg/kg and ketamine at a sub-antidepressant dose of 3 mg/kg reduced immobility time in the FST compared to treatment with either drug alone. None of the drugs affected crossing and rearing scores in the open field test. These results suggest that the L-arginine-nitric oxide pathway is involved in the antidepressant effects of ketamine observed in rats in the FST and this involvement is characterised by the inhibition of brain T-NOS, iNOS, and eNOS activities. Copyright © 2013 Elsevier Inc. All rights reserved.

Tricyclic Antidepressants and Tetracyclic Antidepressants

MedlinePlus

... dangerous reactions when combined with certain medications or herbal supplements. Serotonin syndrome. Rarely, an antidepressant can cause high ... antidepressants, certain pain or headache medications, and the herbal supplement St. John's wort. Signs and symptoms of serotonin ...

Prevalence and patterns of antidepressant switching amongst primary care patients in the UK.

PubMed

Mars, Becky; Heron, Jon; Gunnell, David; Martin, Richard M; Thomas, Kyla H; Kessler, David

2017-05-01

Non-response to antidepressant treatment is a substantial problem in primary care, and many patients with depression require additional second-line treatments. This study aimed to examine the prevalence and patterns of antidepressant switching in the UK, and identify associated demographic and clinical factors. Cohort analysis of antidepressant prescribing data from the Clinical Practice Research Datalink, a large, anonymised UK primary care database. The sample included 262,844 patients who initiated antidepressant therapy between 1 January 2005 and 31 June 2011. 9.3% of patients switched to a different antidepressant product, with most switches (60%) occurring within 8 weeks of the index date. The proportion switching was similar for selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants and other antidepressants (9.3%, 9.8% and 9.2%, respectively). Most switches were to an SSRI (64.5%), and this was the preferred option regardless of initial antidepressant class. Factors predictive of switching included male gender, age, and history of self-harm and psychiatric illness. Over one in every 11 patients who initiates antidepressant therapy will switch medication, suggesting that initial antidepressant treatment has been unsatisfactory. Evidence to guide choice of second-line treatment for individual patients is currently limited. Additional research comparing different pharmacological and psychological second-line treatment strategies is required in order to inform guidelines and improve patient outcomes.

Antioxidant and antidepressant-like activities of semi-synthetic α-phenylseleno citronellal.

PubMed

Victoria, Francine Novack; Anversa, Roberta; Penteado, Filipe; Castro, Micheli; Lenardão, Eder João; Savegnago, Lucielli

2014-11-05

In this study, the antioxidant and antidepressant-like activities of the semi-synthetic compound α-phenylseleno citronellal (PhSeCIT) and the natural terpenoid R-citronellal (CIT) were evaluated. The biological potential of PhSeCIT and CIT was evaluated by antioxidant in vitro assays, such as 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS), ferric ion reducing antioxidant power (FRAP) and linoleic acid oxidation. The compounds were also assessed by ex vivo tests to determine the acute toxicity, levels of thiobarbituric acid reactive species (TBARS), δ-aminolevulinate dehydratase (δ-Ala-D) and Na(+)/K(+) ATPase activities. The antidepressant-like activity of compounds in the tail suspension test (TST) and forced swimming test (FST) was also investigated. The results demonstrated that the addition of an organoselenium group to (R)-citronellal increased its antioxidant properties, since PhSeCIT showed better activity than CIT. The treatment of mice with both compounds did not cause death of any animals. The levels of TBARS were significantly reduced by PhSeCIT in liver and cortex of animals, whereas CIT did not alter these parameters. In the TST and FST, PhSeCIT showed promising antidepressant-like activity, while CIT was not active in this test. Taken together, these data demonstrate the role of selenium in the antioxidant and antidepressant-like activities of (R)-citronellal. Copyright © 2014 Elsevier B.V. All rights reserved.

Progress and prospects in pharmacogenetics of antidepressant drugs.

PubMed

Fabbri, Chiara; Crisafulli, Concetta; Calabrò, Marco; Spina, Edoardo; Serretti, Alessandro

2016-10-01

Depression is responsible for the most part of the personal and socio-economic burden due to psychiatric disorders. Since antidepressant response clusters in families, pharmacogenetics represents a meaningful tool to provide tailored treatments and improve the prognosis of depression. This review aims to summarize and discuss the pharmacogenetics of antidepressant drugs in major depressive disorder, with a focus on the most replicated genes, genome-wide association studies (GWAS), but also on the findings provided by new and promising analysis methods. In particular, multimarker tests such as pathway analysis and polygenic risk scores increase the power of detecting associations compared to the analysis of individual polymorphisms. Since genetic variants are not necessarily associated with a change in protein level, gene expression studies may provide complementary information to genetic studies. Finally, the pharmacogenetic tests that have been investigated for clinical application are discussed. Despite the lack of widespread clinical applications, preliminary results suggest that pharmacogenetics may be useful to guide antidepressant treatment. The US Food and Drug Administration included pharmacogenetic indications in the labeling of several antidepressants. This represented an important official recognition of the clinical relevance of genetic polymorphisms in antidepressant treatment.

Effects of amantadine and budipine on antidepressant drug-evoked changes in extracellular 5-HT in the frontal cortex of freely moving rats

PubMed Central

Owen, Jenny C E; Whitton, Peter S

2005-01-01

Evidence has recently suggested that NMDA receptors may play a role in the aetiology and possible treatment of depression and that weak noncompetitive NMDA receptor antagonists such as amantadine can synergize with conventional antidepressants in a model of the illness. To try to obtain a neurochemical rationale for these findings, we have studied the effects of acute and chronic administration of amantadine or the related drug budipine on cortical release of 5-hydroxytryptamine (5-HT) following the antidepressants reboxitine (REB), paroxetine (PAROX) and clomipramine (CLOM) in freely moving rats by using microdialysis. Acute administration of amantadine (40 mg kg−1), budipine (10 mg kg−1), REB (10 mg kg−1), PAROX (10 mg kg−1) or CLOM (10 mg kg−1) all failed to significantly alter extracellular 5-HT in the cortex. However, when either amantadine or budipine was administered 30 min prior to any of the three antidepressants, a significant rise in 5-HT was observed. For chronic studies, the effects of the drugs were studied at 4, 7, 14 and 21 days. Amantadine and budipine did not significantly alter extracellular 5-HT at any time point. The three antidepressant drugs all elicited a gradual increase in 5-HT, which became significant after 14 days and tended to plateau thereafter. When either amantadine (20 mg kg−1) or budipine (5 mg kg−1) was coadministered with any of the three antidepressants, two differences were seen compared with the effects of the antidepressants alone. Firstly, the time required for significant increases in cortical 5-HT was reduced with elevated levels now being observed by 7 days. Secondly, the absolute magnitude of the increase in extracellular 5-HT was markedly greater in these rats from day 7 until the end of the experiment. If, as is widely considered, an increase in extracellular 5-HT represents a critical step in the mechanism of action of antidepressants, these data suggest that combined

Managing inadequate antidepressant response in depressive illness.

PubMed

Haddad, Peter M; Talbot, Peter S; Anderson, Ian M; McAllister-Williams, R Hamish

2015-09-01

Depression frequently fails to respond to initial treatment. Predominantly meta-analyses and RCTs but supplemented where necessary by additional data and the authors' clinical experience. A systematic assessment to identify remedial causes of poor response should be followed by planned sequential treatment trials. Joint decision making by the patient and clinician is essential. Strategies with the strongest support are antidepressant augmentation with lithium or second generation antipsychotics and adding cognitive behavioural treatment. Electroconvulsive therapy is highly effective in resistant depression but there is a high relapse rate when treatment ends. Some pharmacological strategies have inconsistent data (e.g. antidepressant combinations, T3 augmentation) or limited preliminary data (e.g. ketamine, antidepressant augmentation with pramipexole). The efficacy of vagus nerve stimulation, deep brain stimulation and repetitive transcranial magnetic stimulation is unclear. A greater understanding of the causes of depression may assist the development of more effective treatments. Role of glutamate antagonists and psychological treatments, other than cognitive behavioural therapy, as adjunctive treatments. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Impact of Medicare Part D on Antidepressant Treatment, Medication Choice and Adherence among Older Adults with Depression

PubMed Central

Donohue, Julie M.; Zhang, Yuting; Men, Aiju; Perera, Subashan; Lave, Judith R.; Hanlon, Joseph T.; Reynolds, Charles F.

2010-01-01

Objectives Depression in older adults is often undertreated due, in part, to medication costs. We examined the impact of improved prescription drug coverage under Medicare Part D on use of antidepressants, medication choice and adherence. Design, Setting and Participants Observational claims-based study of older adults with depression (ICD-9: 296.2, 296.3, 311, 300.4) continuously enrolled in a Medicare managed care plan between 2004–2007. Three groups with limited ($150 or $350 quarterly caps) or no drug coverage in 2004–2005 obtained Part D benefits in 2006. A comparison group had stable employer-sponsored coverage throughout. Measurements Any antidepressant prescription fill, antidepressant choice (tricyclics or monoamine oxidase inhibitors vs. newer antidepressants), and adherence (80% of days covered) in the first 6 months of treatment. Results Part D was associated with increased odds of any antidepressant use among those who previously lacked coverage [Odds Ratio (OR) 1.61, 95% confidence interval (CI) 1.41–1.85] but odds of use did not change among those with limited prior coverage. Use of older antidepressant agents did not change with Part D. All three groups whose coverage improved with Part D had significantly higher odds of 80% of days covered with an antidepressant [OR=1.86 (95% CI, 1.44–2.39) for No coverage, 1.74 (95% CI, 1.25–3.42) for $150 cap; and 1.19 (95% CI 1.06–1.34) for the $350 cap groups]. Conclusions Medicare Part D was associated with improvements in antidepressant use and adherence in depressed older adults who previously had no or limited drug coverage but not with changes in use of older agents. PMID:22123272

Antidepressants differentially affect striatal amphetamine-stimulated dopamine and serotonin release in rats with high and low novelty-oriented behaviour.

PubMed

O'Leary, Aet; Kõiv, Kadri; Raudkivi, Karita; Harro, Jaanus

2016-11-01

In the studies of depression pathogenesis and antidepressant action, the monoaminergic hypothesis of depression has mainly focused on the serotonergic and noradrenergic mechanisms. However, dopaminergic neurotransmission is also linked to both depressive symptomatology as well as antidepressant effects. We have previously shown that persistent inter-individual differences in the rat behavioural activity in novel environments is associated with differences in the striatal extracellular levels of dopamine and serotonin, depressive-like behaviour and the expression of several depression-related genes. The aim of the current study was to investigate the relative potency of the tricyclic antidepressant imipramine, the selective serotonin re-uptake inhibitor fluoxetine, and the selective noradrenaline re-uptake inhibitor reboxetine (all drugs administered in the dose of 10mg/kg, i.p.) to enhance amphetamine-stimulated dopamine and serotonin release in the striatum using in vivo microdialysis in awake, freely-moving rats, categorized into high explorers (HE) and low explorers (LE) based on their spontaneous novelty-oriented behaviour. The basal extracellular dopamine and serotonin concentration in the striatum did not differ between the LE- and HE-rats. None of the antidepressants alone were able to modify baseline striatal dopamine levels, but the amphetamine-stimulated dopamine release was significantly higher in the HE-rats after acute and chronic imipramine (but not fluoxetine or reboxetine). Acute imipramine and fluoxetine, but not reboxetine, increased both the basal and amphetamine-stimulated levels of serotonin in the striatum. Again, the HE-rats had higher amphetamine-stimulated serotonin release after fluoxetine administration. These findings suggest that rats with depressive-like phenotype are less sensitive to the neurochemical effects of antidepressants in the striatum. These results may have relevance in understanding the neurobiological bases for inter

Clinical and psychopathological features associated with treatment-emergent mania in bipolar-II depressed outpatients exposed to antidepressants.

PubMed

Fornaro, Michele; Anastasia, Annalisa; Monaco, Francesco; Novello, Stefano; Fusco, Andrea; Iasevoli, Felice; De Berardis, Domenico; Veronese, Nicola; Solmi, Marco; de Bartolomeis, Andrea

2018-07-01

Treatment-emergent affective switch (TEAS), including treatment-emergent mania (TEM), carry significant burden in the clinical management of bipolar depression, whereas the use of antidepressants raises both efficacy, safety and tolerability concerns. The present study assesses the prevalence and clinical correlates of TEM in selected sample of Bipolar Disorder (BD) Type-II (BD-II) acute depression outpatients. Post-hoc analysis of the clinical and psychopathological features associated with TEM among 91 BD-II depressed outpatients exposed to antidepressants. Second-generation antipsychotics (SGA) (p = .005), lithium (≤ .001), cyclothymic/irritable/hyperthymic temperaments (p = ≤ .001; p = .001; p = .003, respectively), rapid-cycling (p = .005) and depressive mixed features (p = .003) differed between TEM + cases vs. TEM - controls. Upon multinomial logistic regression, the accounted psychopathological features correctly classified as much as 88.6% of TEM + cases (35/91 overall sample, or 38.46% of the sample), yet not statistically significantly [Exp(B) = .032; p = ns]. Specifically, lithium [B = - 2.385; p = .001], SGAs [B = - 2.354; p = .002] predicted lower rates of TEM + in contrast to the number of lifetime previous psychiatric hospitalizations [B = 2.380; p = .002], whereas mixed features did not [B = 1.267; p = ns]. Post-hoc analysis. Lack of systematic pharmacological history record; chance of recall bias and Berkson's biases. Permissive operational criterion for TEM. Relatively small sample size. Cyclothymic temperament and mixed depression discriminated TEM + between TEM - cases, although only lithium and the SGAs reliably predicted TEM +/- grouping. Larger-sampled/powered longitudinal replication studies are warranted to allow firm conclusions on the matter, ideally contributing to the identification of clear-cut sub-phenotypes of BD towards patient-tailored-pharmacotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Enhanced sensitivity of muscarinic cholinergic receptor associated with dopaminergic receptor subsensitivity after chronic antidepressant treatment

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

Koide, T.; Matsushita, H.

1981-03-09

The chronic effects of antidepressant treatment on striatal dopaminergic (DA) and muscarinic cholinergic (mACh) receptors of the rat brain have been examined comparatively in this study using /sup 3/H-spiroperidol (/sup 3/H-SPD) and /sup 3/H-quinuclidinyl benzilate (/sup 3/H-QNB) as the respective radioactive ligands. Imipramine and desipramine were used as prototype antidepressants. Although a single administration of imipramine or desipramine did not affect each receptor sensitivity, chronic treatment with each drug caused a supersensitivity of mACh receptor subsequent to DA receptor subsensitivity. Furthermore, it has been suggested that anti-mACh properties of imipramine or desipramine may not necessarily be related to the manifestationmore » of mACh receptor supersensitivity and that sustained DA receptor subsensitivity may play some role in the alterations of mACh receptor sensitivity.« less

Cipadesin A, a bioactive ingredient of Xylocarpus granatum, produces antidepressant-like effects in adult mice.

PubMed

Gao, Qiang; Gao, Yuan; Song, Han; Li, Jianli; Wu, Yibing; Shi, Xiaowei; Shi, Haishui; Ma, Yuxia

2016-10-28

Xylocarpus granatum Koenig, widely used in folk medicine in southeast countries, has been reported to exert neuropharmacological activities as well as mood regulation. The neuroprotective activities of limonoids, riches in X. granatum, are poorly understood. To investigate the potential antidepressant-like effects and the underlying mechanisms of cipadesin A, one limonoid component, extracted from X. granatum, in acute stress-induced depression mouse models. Antidepressant-like effects of cipadesin A were investigated through behavioral tests, and potential mechanism was assessed by neuroendocrine system. Antidepressant-like effects of cipadesin A (5, 15, 50mg/kg/day for 7days, intragastrically) were estimated through forced-swimming test (FST), tail suspension test (TST) and open field test (OFT). Effects of cipadesin A on hypothalamus-pituitary- adrenal (HPA) axis were evaluated by analysis of serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) using enzyme-linked immunosorbent assay (ELISA). Cipadesin A administration significantly reduced the floating time in the FST and immobility time in the TST (15-50mg/kg). Cipadesin A dose-dependently increased the time in the central zone in the OFT (5-50mg/kg), without altering the locomotor activity. Moreover, repeated cipadesin A treatment significantly inhibited the increase levels of serum CORT (5-50mg/kg), ACTH (15-50mg/kg) following the forced swimming, but not in the absence of stress. Cipadesin A has antidepressant-like activities in acute stressed mice model of depression, which likely occurs by inhibiting the HPA axis activity response to stress. These data support further exploration for developing cipadesin A as a potential agent to treat depression and anxiety disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Repeated treatment with nitric oxide synthase inhibitor attenuates learned helplessness development in rats and increases hippocampal BDNF expression.

PubMed

Stanquini, Laura Alves; Biojone, Caroline; Guimarães, Francisco Silveira; Joca, Sâmia Regiane

2017-11-20

Nitric oxide synthase (NOS) inhibitors induce antidepressant-like effects in animal models sensitive to acute drug treatment such as the forced swimming test. However, it is not yet clear if repeated treatment with these drugs is required to induce antidepressant-like effects in preclinical models. The aim of this study was to test the effect induced by acute or repeated (7 days) treatment with 7-nitroindazole (7-NI), a preferential inhibitor of neuronal NOS, in rats submitted to the learned helplessness (LH) model. In addition, we aimed at investigating if 7-NI treatment would increase brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus, similarly to the effect of prototype antidepressants. Animals were submitted to a pre-test (PT) session with inescapable footshocks or habituation (no shocks) to the experimental shuttle box. Six days later they were exposed to a test with escapable footshocks. Independent groups received acute (a single injection after PT or before test) or repeated (once a day for 7 days) treatment with vehicle or 7-NI (30 mg/kg). Repeated, but not acute, treatment with 7-NI attenuated LH development. The effect was similar to repeated imipramine treatment. Moreover, in an independent experimental group, only repeated treatment with 7-NI and imipramine increased BDNF protein levels in the hippocampus. The results suggest the nitrergic system could be a target for the treatment of depressive-like conditions. They also indicate that, similar to the positive control imipramine, the antidepressant-like effects of NOS inhibition could involve an increase in hippocampal BDNF levels.

Race, Genetic Ancestry and Response to Antidepressant Treatment for Major Depression

PubMed Central

Murphy, Eleanor; Hou, Liping; Maher, Brion S; Woldehawariat, Girma; Kassem, Layla; Akula, Nirmala; Laje, Gonzalo; McMahon, Francis J

2013-01-01

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study revealed poorer antidepressant treatment response among black compared with white participants. This racial disparity persisted even after socioeconomic and baseline clinical factors were taken into account. Some studies have suggested genetic contributions to this disparity, but none have attempted to disentangle race and genetic ancestry. Here we used genome-wide single-nucleotide polymorphism (SNP) data to examine independent contributions of race and genetic ancestry to citalopram response. Secondary data analyses included 1877 STAR*D participants who completed an average of 10 weeks of citalopram treatment and provided DNA samples. Participants reported their race as White (n=1464), black (n=299) or other/mixed (n=114). Genetic ancestry was estimated by multidimensional scaling (MDS) analyses of about 500 000 SNPs. Ancestry proportions were estimated by STRUCTURE. Structural equation modeling was used to examine the direct and indirect effects of observed and latent predictors of response, defined as change in the Quick Inventory of Depressive Symptomatology (QIDS) score from baseline to exit. Socioeconomic and baseline clinical factors, race, and anxiety significantly predicted response, as previously reported. However, direct effects of race disappeared in all models that included genetic ancestry. Genetic African ancestry predicted lower treatment response in all models. Although socioeconomic and baseline clinical factors drive racial differences in antidepressant response, genetic ancestry, rather than self-reported race, explains a significant fraction of the residual differences. Larger samples would be needed to identify the specific genetic mechanisms that may be involved, but these findings underscore the importance of including more African-American patients in drug trials. PMID:23827886

Depression, Antidepressants, and Neurogenesis: A Critical Reappraisal

PubMed Central

Hanson, Nicola D; Owens, Michael J; Nemeroff, Charles B

2011-01-01

The neurogenesis hypothesis of depression posits (1) that neurogenesis in the subgranular zone of the dentate gyrus is regulated negatively by stressful experiences and positively by treatment with antidepressant drugs and (2) that alterations in the rate of neurogenesis play a fundamental role in the pathology and treatment of major depression. This hypothesis is supported by important experimental observations, but is challenged by equally compelling contradictory reports. This review summarizes the phenomenon of adult hippocampal neurogenesis, the initial and continued evidence leading to the development of the neurogenesis hypothesis of depression, and the recent studies that have disputed and/or qualified those findings, to conclude that it can be affected by stress and antidepressants under certain conditions, but that these effects do not appear in all cases of psychological stress, depression, and antidepressant treatment. PMID:21937982

Conflict in Men’s Experiences With Antidepressants

PubMed Central

Gibson, Kerry; Cartwright, Claire; Read, John

2016-01-01

While men’s experiences of depression and help seeking are known to be shaped by gender, there is little research which examines their experience of using antidepressants to treat this. This study is based on in-depth, narrative-style interviews with 20 New Zealand men who had used antidepressants. The analysis identified a number of areas of conflict in the men’s accounts of using this medication. Conflict centered on the way taking antidepressants was seen as undermining personal control while also allowing users to take charge of their problems; facilitating general functioning while undermining sexual functioning; relieving emotional distress while undermining emotional vitality; and the tension participants felt between making autonomous judgments about the value of antidepressants and relying on the “expertise” of others. Participants negotiated these conflicts in a variety of ways. In some cases, antidepressants were positioned as being able to affirm aspects of traditional masculinity, while a smaller number of participants managed these conflicts by redefining aspects of their own masculinity in ways that contrasted with dominant constructions. This research is limited by the sample of older, more privileged men in the context of New Zealand culture which favors macho forms of masculinity. In similar contexts, mental health practitioners should be mindful of the conflicts that men might experience in relation to their antidepressant use. Facilitating men’s exploration of these issues may enable them to make better decisions about treatment options or to provide more effective support to those who have opted for antidepressant treatment. PMID:26993998

Mammalian target of rapamycin (mTOR)/nitric oxide system possibly modulate antidepressant-like effect of 17α-ethinyl estradiol in ovariectomized mice.

PubMed

Saeedi Saravi, Seyed Soheil; Arefidoust, Alireza; Saeedi Saravi, Seyed Sobhan; Yaftian, Rahele; Bayati, Mahdi; Salehi, Milad; Dehpour, Ahmad Reza

2017-05-01

Due to a close association between depressive disorders and altered estrogen levels, this study was conducted to examine the hypothesis that antidepressant-like effect of ethinyl estradiol (EE 2) in ovariectomized mice is modulated by mammalian target of rapamycin (mTOR)/nitric oxide pathways. Female mice were undergone bilateral ovariectomy and different doses of EE 2 were intraperitoenally injected alone and combined with specific mTOR inhibitor, rapamycin, non-specific NOS inhibitor, L-NAME, nNOS inhibitor, 7-NI, NO precursor, l-arginine, and selective PDE5I, sildenafil. After locomotion assessment, immobility times were recorded in FST and TST. Moreover, hippocampal mTOR expression was assessed using western blot assay. The hippocampal concentrations of nitrite, a major metabolite of NO, were measured. Although EE 2 demonstrated a significant antidepressant-like activity in OVX mice, acute rapamycin exerted an unmarked decrease of the anti-immobility effect of EE 2 in FST and TST (P>0.05). In contrast, combination of minimal effective dose of EE 2 with sub- effective doses of either L-NAME (10mg/kg) or 7-NI (25mg/kg) resulted in a robust antidepressant-like effect in OVX mice. Administration of either L-NAME or 7-NI enhanced the decreased antidepressant activity of EE 2 induced by combination with rapamycin. Moreover, decrement of hippocampal mTOR expression in OVX mice was significantly enhanced by acute EE 2 . The increased hippocampal nitrite concentrations caused by ovariectomy were also reversed by EE 2 administration. The study demonstrated that acute treatment with lowest dose of EE 2 exerts significant antidepressant-like behavior in OVX mice, possibly, through mTOR activation. This effect seems to be also mediated by the suppression of nitric oxide pathway. Copyright © 2017. Published by Elsevier Masson SAS.

The influence of patients' preference/attitude towards psychotherapy and antidepressant medication on the treatment of major depressive disorder.

PubMed

Moradveisi, Latif; Huibers, Marcus; Renner, Fritz; Arntz, Arnoud

2014-03-01

Preferences and attitudes patients hold towards treatment are important, as these can influence treatment outcome. In depression research, the influence of patients' preference/attitudes on outcome and dropout has mainly been studied for antidepressant medication, and less for psychological treatments. We investigated the effects of patients' preference and attitudes towards psychological treatment and antidepressant medication on treatment outcome and dropout, and tested specificity of effects. Data are based on a randomized trial testing the effectiveness of behavioural activation (BA) vs antidepressant medication (ADM) for major depression (MDD) in Iran. Patients with MDD (N = 100) were randomized to BA (N = 50) or ADM (N = 50). Patients' preference/attitudes towards psychotherapy and ADM were assessed at baseline and associated with dropout and treatment outcome using logistic regression and multilevel analysis. High scores on psychotherapy preference/attitude and low scores on ADM preference/attitude predicted dropout from ADM, while no association between dropout and preference/attitude was found in BA. Psychotherapy preference/attitude moderated the differential effect of BA and ADM on one outcome measure, but the association disappeared after one year. Because in Iran most patients have only access to ADM, offering a psychological treatment for depression could attract especially those patients that prefer this newly available treatment. Patients' preferences and attitudes towards depression treatments influence dropout from ADM, and moderate the short-term difference in effectiveness between BA and ADM. The fact that dropout from BA was not affected by preference/attitude speaks for its acceptability among patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Antidepressant pharmacotherapy in old-age depression-a review and clinical approach.

PubMed

Pruckner, Nathalie; Holthoff-Detto, Vjera

2017-06-01

Depression in old age is a disabling disease associated with functional and cognitive decline severely affecting quality of life. Studies specifically investigating antidepressant treatment for this special cohort of patients remain scarce and results are often conflicting. A narrative literature review was undertaken, synthesizing findings from published studies, systematic reviews, and treatment guidelines specifically conducted in elderly depressed patients to summarize implications and current recommendations as well as gaps in evidence for old-age pharmacologic treatment. PubMed and Medline databases were searched for articles from July 2011 to July 2016. Only RCTs, meta-analyses, systematic reviews, and treatment guidelines focussing on the effect of antidepressant pharmacotherapy in old-aged participants were extracted, analysed, and discussed. The search resulted in a total of 26 articles. Selective serotonin reuptake inhibitors (SSRIs) and other second-generation antidepressants are recommended for first-line treatment of old-age depression. The differences in efficacy and tolerability within different substances and substance classes are minimal or non-existent. Tricyclic antidepressants (TCAs) are only considered for second-line treatment, due to their cardiac risk profile and anticholinergic effects. In treatment-resistant depression, augmentation therapy options include lithium and atypical antipsychotics. There is convincing evidence that antidepressants are efficacious in the treatment of old-age depression and that rationales are necessary for treatment planning. However, evidence-based data on recovery and remission rates in old-age depression specific to certain antidepressant drugs are still missing in trials and are of great importance for pharmacological treatment of old-age depression in daily clinical practice.

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

Antidepressants and benzodiazepines for panic disorder in adults.

PubMed

Bighelli, Irene; Trespidi, Carlotta; Castellazzi, Mariasole; Cipriani, Andrea; Furukawa, Toshi A; Girlanda, Francesca; Guaiana, Giuseppe; Koesters, Markus; Barbui, Corrado

2016-09-12

A panic attack is a discrete period of fear or anxiety that has a rapid onset, reaches a peak within 10 minutes and in which at least four of 13 characteristic symptoms are experienced, including racing heart, chest pain, sweating, shaking, dizziness, flushing, stomach churning, faintness and breathlessness. Panic disorder is common in the general population with a lifetime prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions. Amongst pharmacological agents, antidepressants and benzodiazepines are the mainstay of treatment for panic disorder. Different classes of antidepressants have been compared; and the British Association for Psychopharmacology, and National Institute for Health and Care Excellence (NICE) consider antidepressants (mainly selective serotonin reuptake inhibitors (SSRIs)) as the first-line treatment for panic disorder, due to their more favourable adverse effect profile over monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). In addition to antidepressants, benzodiazepines are widely prescribed for the treatment of panic disorder. To assess the evidence for the effects of antidepressants and benzodiazepines for panic disorder in adults. The Specialised Register of the Cochrane Common Mental Disorders Group (CCMDCTR) to 11 September 2015. This register includes relevant randomised controlled trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950-), Embase (1974-) and PsycINFO (1967-). Reference lists of relevant papers and previous systematic reviews were handsearched. We contacted experts in this field for supplemental data. All double-blind randomised controlled trials allocating adult patients with panic disorder to antidepressants or benzodiazepines versus any other active treatment with antidepressants or benzodiazepines. Two review authors independently checked eligibility and extracted data using a standard form. Data were

Potential antidepressant-like activity of silymarin in the acute restraint stress in mice: Modulation of corticosterone and oxidative stress response in cerebral cortex and hippocampus.

PubMed

Thakare, Vishnu N; Dhakane, Valmik D; Patel, Bhoomika M

2016-10-01

Silymarin is a polyphenolic flavanoid of Silybum marianum, elicited neuroprotection and antidepressant like activity in stressed model. It was found to increase 5-hydroxytryptamine (5-HT) levels in the cortex and dopamine (DA) and norepinephrine (NE) in the cerebellum in normal mice. The aim of the present study was to investigate the potential antidepressant-like activity of silymarin in the acute restraint stress (ARS) in mice. The ARS was induced by immobilizing the mice for a period of 7h using rodent restraint device preventing them for any physical movement. One hour prior to ARS, silymarin was administered at doses of 100mg/kg and 200mg/kg per oral to non stressed and ARS mice. Various behavioral parameters like immobility time in force swim test, locomotor activity in open field test, and biochemical alterations, serum corticosterone, 5-HT, DA, NE level, malondialdehyde (MDA), and antioxidant enzymes (GSH, CAT and SOD) in hippocampus and cerebral cortex in non stressed and ARS subjected mice were investigated. Experimental findings reveals mice subjected to ARS exhibited significant increase immobility time, serum corticosterone, MDA formation and impaired SOD and CAT activities in hippocampus and cerebral cortex as compared to non stressed mice. Silymarin treatment (100mg/kg and 200mg/kg) significantly attenuated immobility time, corticosterone and restored the antioxidant enzymes after ARS. The present experimental findings indicate that silymarin exhibits antidepressant like activity probably either through alleviating oxidative stress by modulation of corticosterone response, and antioxidant defense system in hippocampus and cerebral cortex in ARS mice. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Depression in nursing homes: prevalence, recognition, and treatment.

PubMed

Kramer, Dietmar; Allgaier, Antje-Kathrin; Fejtkova, Sabina; Mergl, Roland; Hegerl, Ulrich

2009-01-01

Depression is very common in people above 65 years living in long-term care. However, little is known about how well depression is recognized and how adequately it is treated. Therefore, the present study aimed at assessing accuracy of the unaided clinical diagnosis of the attending physicians, and the medical treatment situation in nursing home residents. A random sample of 97 residents of 10 nursing homes in Munich was examined with the Section A "Affective Syndrome" of the Structured Clinical Interview (SCID) for DSM-IV to detect depression. Information concerning clinical diagnosis and medication was obtained from the subjects' medical records. 14.4% suffered acutely from major depression, 14.4% suffered from minor depression, and 18.6% were diagnosed as depressive according to the physician and nursing records. In total, 27.8% received antidepressants. Merely 42.9% of the subjects with acute major depression were diagnosed by their attending physicians as depressive, and only half of them received an antidepressant; 17.5% received antidepressants without a diagnosis of depression in their physician and nursing records. In accordance with the guidelines, 73.3% of the antidepressants prescribed were SSRIs or newer antidepressants. Only 20.0% were tricyclic antidepressants. Findings show that depression is relatively frequent in residents of nursing homes. Moreover, it is insufficiently recognized by physicians and is even more seldom adequately treated. Also, a significant proportion of residents receive antidepressants without a documented associated indication. Therefore, the recognition and guideline-based treatment of depression should be improved in this high-risk group.

Antidepressant-like effects of aniracetam in aged rats and its mode of action.

PubMed

Nakamura, K; Tanaka, Y

2001-11-01

Aniracetam has been reported to be efficacious for treating poststroke depression, but no studies that basically examined the antidepressive effects have been made. We aimed to test the antidepressant-like property of aniracetam in rats and to clarify the mechanisms of action through the interaction studies with some receptor antagonists. Antidepressant-like effects of aniracetam and various classes of compounds including different antidepressants were examined in a forced swim test with young (9 weeks old) and aged (25-30 months old) rats. Rats were exposed to a 5-min swim in a test session on day 2 following a 15-min swim in a training session on day 1, and immobility time during the period on day 2 was measured. The test compounds were administered subacutely (three doses over 2 days) or acutely (0.5 h before the testing). Standard antidepressants except for tandospirone significantly reduced immobility time in both young and aged rats. Aniracetam (10-100 mg/kg PO) failed to decrease immobility time in young rats, but it (100 mg/kg PO) significantly shortened immobility in aged rats, the effects of which were mainly mimicked by combined treatment of the metabolites, 2-pyrrolidinone and N-anisoyl-GABA. The effects of aniracetam was reversed completely by mecamylamine (10 mg/kg IP) or haloperidol (0.1 mg/kg IP) and slightly by ketanserin (1 m/kg IP) but was potentiated by scopolamine (0.03 mg/kg IP). These results indicate that aniracetam acts more effective when the forced swim stress-induced immobility is accompanied with brain dysfunction that occurs with aging. The antidepressant-like activity of aniracetam, which is probably due to the combined effects of 2-pyrrolidinone and N-anisoyl-GABA, may be mediated by mainly facilitating dopaminergic transmission (dopamine release and dopamine D2 receptor activation) through nicotinic acetylcholine receptor stimulation.

Sexual side effects of antidepressant drugs.

PubMed

Gelenberg, A J; Delgado, P; Nurnberg, H G

2000-06-01

Sexual functioning often suffers during depression, although depressed people continue to value sex. Many popular antidepressants further impair sexual functioning, with highly serotonergic agents affecting orgasm and libido prominently. This paper addresses clinical assessment of sexual side effects from antidepressant drugs and reviews treatment strategies, including purported antidotes. We pay particular attention to sildenafil, on which there are impressive data and ongoing controlled studies.

Antidepressants normalize the default mode network in patients with dysthymia.

PubMed

Posner, Jonathan; Hellerstein, David J; Gat, Inbal; Mechling, Anna; Klahr, Kristin; Wang, Zhishun; McGrath, Patrick J; Stewart, Jonathan W; Peterson, Bradley S

2013-04-01

depressive disorder and suggest that increased connectivity within the DMN may be important in the pathophysiology of both acute and chronic manifestations of depressive illness. The normalization of DMN connectivity following antidepressant treatment suggests an important causal pathway through which antidepressants may reduce depression.

Antidepressants Normalize the Default Mode Network in Patients With Dysthymia

PubMed Central

Posner, Jonathan; Hellerstein, David J.; Gat, Inbal; Mechling, Anna; Klahr, Kristin; Wang, Zhishun; McGrath, Patrick J.; Stewart, Jonathan W.; Peterson, Bradley S.

2014-01-01

. Conclusions and Relevance The baseline imaging findings are consistent with those found in patients with major depressive disorder and suggest that increased connectivity within the DMN may be important in the pathophysiology of both acute and chronic manifestations of depressive illness. The normalization of DMN connectivity following antidepressant treatment suggests an important causal pathway through which antidepressants may reduce depression. PMID:23389382

Antidepressant-like activity of Sonchus oleraceus in mouse models of immobility tests.

PubMed

Vilela, Fabiana Cardoso; Padilha, Marina de Mesquita; Alves-da-Silva, Geraldo; Soncini, Roseli; Giusti-Paiva, Alexandre

2010-02-01

The aim of the present work is to evaluate the putative antidepressant-like effects of hydroethanolic and dichloromethanic extracts from the aerial parts of Sonchus oleraceus (Family Asteraceae) on the performance of male mice in the forced swimming test (FST) and tail suspension test (TST) models predictive of depression. The hydroethanolic and dichloromethanic extracts, both in doses of 30, 100, and 300 mg/kg, were orally administered 1 hour before carrying out the FST or the TST. The immobility time in both the FST and the TST was significantly reduced by acute oral treatment with the extracts (dose range, 100-300 mg/kg), without accompanying changes in ambulation, as assessed in an open-field test. This excluded the possibility that the effect of the extracts is due to an activation of locomotion. The efficacy of the extracts was found to be comparable to that of amitriptyline (10 mg/kg, p.o.). The present study provides evidence for an antidepressant-like effect of the active principle(s) present in the extracts of S. oleraceus in mice. Therefore, a standardized S. oleraceus extract or its purified constituents could be of potential interest for the treatment of depressive disorders.

Ketamine treatment involves medial prefrontal cortex serotonin to induce a rapid antidepressant-like activity in BALB/cJ mice.

PubMed

Pham, T H; Mendez-David, I; Defaix, C; Guiard, B P; Tritschler, L; David, D J; Gardier, A M

2017-01-01

Unlike classic serotonergic antidepressant drugs, ketamine, an NMDA receptor antagonist, exhibits a rapid and persistent antidepressant (AD) activity, at sub-anaesthetic doses in treatment-resistant depressed patients and in preclinical studies in rodents. The mechanisms mediating this activity are unclear. Here, we assessed the role of the brain serotonergic system in the AD-like activity of an acute sub-anaesthetic ketamine dose. We compared ketamine and fluoxetine responses in several behavioral tests currently used to predict anxiolytic/antidepressant-like potential in rodents. We also measured their effects on extracellular serotonin levels [5-HT] ext in the medial prefrontal cortex (mPFCx) and brainstem dorsal raphe nucleus (DRN), a serotonergic nucleus involved in emotional behavior, and on 5-HT cell firing in the DRN in highly anxious BALB/cJ mice. Ketamine (10 mg/kg i.p.) had no anxiolytic-like effect, but displayed a long lasting AD-like activity, i.e., 24 h post-administration, compared to fluoxetine (18 mg/kg i.p.). Ketamine (144%) and fluoxetine (171%) increased mPFCx [5-HT] ext compared to vehicle. Ketamine-induced AD-like effect was abolished by a tryptophan hydroxylase inhibitor, para-chlorophenylalanine (PCPA) pointing out the role of the 5-HT system in its behavioral activity. Interestingly, increase in cortical [5-HT] ext following intra-mPFCx ketamine bilateral injection (0.25 μg/side) was correlated with its AD-like activity as measured on swimming duration in the FST in the same mice. Furthermore, pre-treatment with a selective AMPA receptor antagonist (intra-DRN NBQX) blunted the effects of intra-mPFCx ketamine on both the swimming duration in the FST and mPFCx [5-HT] ext suggesting that the AD-like activity of ketamine required activation of DRN AMPA receptors and recruited the prefrontal cortex/brainstem DRN neural circuit in BALB/c mice. These results confirm a key role of cortical 5-HT release in ketamine's AD-like activity following

Treatment of major depressive disorder and dysthymic disorder with antidepressants in patients with comorbid opiate use disorders enrolled in methadone maintenance therapy: a meta-analysis.

PubMed

Pedrelli, Paola; Iovieno, Nadia; Vitali, Mario; Tedeschini, Enrico; Bentley, Kate H; Papakostas, George I

2011-10-01

Depression and opiate-use disorders (abuse, dependence) often co-occur, each condition complicating the course and outcome of the other. It has been recommended that clinicians prescribe antidepressant therapy for mood symptoms in patients with active substance-use disorders, but whether antidepressants are effective in this specific population is not entirely clear. Therefore, the aim of this study was to examine the efficacy of antidepressants in patients with unipolar major depressive disorder (MDD) and/or dysthymic disorder (DD) with comorbid opiate-use disorders currently in methadone maintenance treatment (MMT). Medline/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for the treatment of MDD/DD in patients with comorbid opiate-use disorders currently in MMT. The search was limited to articles published between January 1, 1980, and June 30, 2010 (inclusive). Four manuscripts were found eligible for inclusion in our analysis (n = 317 patients). We found no statistically significant difference in response rates between antidepressant and placebo therapy in trials of MDD/DD patients with comorbid opiate-use disorders currently in MMT (risk ratio for response, 1.182; 95% CI: 0.822-1.700; P = 0.366). These results show no difference in the depressive outcome of patients with comorbid opiate-use disorders on MMT whether they are on medication or placebo. Future studies examining the effectiveness of antidepressants while controlling for several variables such as psychosocial treatment and assessing the specific classes of antidepressants are needed.

[Mechanism of action of antidepressants and therapeutic perspectives].

PubMed

Bourin, M; David, D J P; Jolliet, P; Gardier, A

2002-01-01

Depression is an incapacitating disease which needs appropriate treatment. This article reviews the pharmacology of antidepressant drugs and the future perspectives of treating mood disorders such as depression. The foremost theory for explaining the biological basis of depression has been the monoamine hypothesis. Depression is due to a deficiency in one or other biogenic monoamines (serotonin, 5-HT; noradrenaline, NA; dopamine, DA). Antidepressant drugs are therefore classified according to their ability to improve monoaminergic transmission. Since this first theory, other explanations based on abnormal function of monoamine receptors or associated with impaired signalling pathways have been suggested. Notable progress has been accomplished in the treatment of major depressive disorders with new compounds recently discovered (selective serotonin reuptake inhibitors: SSRI; serotonin noradrenaline reuptake inhibitors: SNRI). Behavioural, electrophysiological and microdialysis studies have shown that serotonin (5-HT) receptors, mainly 5-HT1A, 5-HT1B and 5-HT2C sub-types, exert a key role in modulating antidepressant activity. Indirect activation of neurotransmitter receptors by antidepressants may also lead, via increases in endogenous levels of serotonin in synapses in specific brain regions, to activation of various G proteins coupled to a receptor, signal of transduction, transcription factors and neurotrophic factors such as brain-derived neurotrophic factor (BDNF). Thus, depression may be considered as a transduction mechanism anomaly. This hypothesis needs to be clarified by molecular biology. Although antidepressants have improved the therapeutic potential compared to tricyclics (TCA) in terms of reduced side effects, a number of problems still occur with these drugs. Clinical effects are not always observed until after this time has elapsed (4-6 weeks) and a substantial proportion of depressed patients show only partial or no response to antidepressants

Early increase in marker of neuronal integrity with antidepressant treatment of major depression: 1H-magnetic resonance spectroscopy of N-acetyl-aspartate.

PubMed

Taylor, Matthew J; Godlewska, Beata R; Norbury, Ray; Selvaraj, Sudhakar; Near, Jamie; Cowen, Philip J

2012-11-01

Increasing interest surrounds potential neuroprotective or neurotrophic actions of antidepressants. While growing evidence points to important early clinical and neuropsychological effects of antidepressants, the time-course of any effect on neuronal integrity is unclear. This study used magnetic resonance spectroscopy to assess effects of short-term treatment with escitalopram on N-acetyl-aspartate (NAA), a marker of neuronal integrity. Thirty-nine participants with major depression were randomly assigned to receive either 10 mg escitalopram or placebo daily in a double-blind, parallel group design. On the seventh day of treatment, PRESS data were obtained from a 30×30×20 mm voxel placed in medial frontal cortex. Age and gender-matched healthy controls who received no treatment were also scanned. Levels of NAA were significantly higher in patients treated with escitalopram than in either placebo-treated patients (p<0.01) or healthy controls (p<0.01). Our findings are consistent with the proposition that antidepressant treatment in depressed patients can produce early changes in neuronal integrity.

Antidepressants for major depressive disorder and dysthymic disorder in patients with comorbid alcohol use disorders: a meta-analysis of placebo-controlled randomized trials.

PubMed

Iovieno, Nadia; Tedeschini, Enrico; Bentley, Kate H; Evins, A Eden; Papakostas, George I

2011-08-01

Mood and alcohol use disorders are often co-occurring, each condition complicating the course and outcome of the other. The aim of this study was to examine the efficacy of antidepressants in patients with unipolar major depressive disorder (MDD) and/or dysthymic disorder with comorbid alcohol use disorders and to compare antidepressant and placebo response rates between depressed patients with or without comorbid alcohol use disorders. MEDLINE/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for the acute-phase treatment of MDD and/or dysthymic disorder in patients with or without alcohol use disorders. The search term placebo was cross-referenced with each of the antidepressants approved by the US, Canadian, or European Union drug regulatory agencies for the treatment of MDD and/or dysthymic disorder. 195 articles were found eligible for inclusion in our analysis, 11 of which focused on the treatment of MDD/dysthymic disorder in patients with comorbid alcohol use disorders. The search was limited to articles published between January 1, 1980, and March 15, 2009 (inclusive). We found that antidepressant therapy was more effective than placebo in patients with comorbid alcohol use disorders (risk ratio of response = 1.336; P = .021). However, this was not the case when selective serotonin reuptake inhibitor (SSRI) antidepressants were examined alone (P > .05). There was no significant difference in the relative efficacy of antidepressants (versus placebo) when comparing studies in MDD/dysthymic disorder patients with or without alcohol use disorders (P = .973). Meta-regression analyses yielded no significant differences in the risk ratio of responding to antidepressants versus placebo in trials with comorbid alcohol use disorders, whether antidepressants were used alone or adjunctively to psychotherapy, whether they were used in patients actively drinking or recently sober, or

[Antidepressants consumption in the global population in France].

PubMed

Olié, J P; Elomari, F; Spadone, C; Lépine, J P

2002-01-01

The consumption of antidepressant seems to be in France higher than in comparable countries, as well as the overall consumption of healthcare and medications. In Western countries, in recent years, the use of antidepressants has regularly increased, mainly due to the use of serotoninergic antidepressants. In France, in a week, the prevalence of antidepressant use in the overall population increased from 1.7% in 1992 to 3% in 1995. This survey addressed the overall population in the form of a representative sample focusing on subjects who indicated, at the time they were consulted, that they were taking an antidepressant. The study aimed to determine the circumstances of prescription: prescriber file, reason for prescription, type of medication prescribed, match between the prescription and the product indications stated in the marketing authorization, prescription duration and reason for discontinuing treatment. Methodology - The first stage consisted in forwarding a letter to a panel of 44 000 subjects aged 15 years or more and representative of the French population. The aim was to achieve a cross-sectional description of the population taking antidepressants. The response rate was 82% (36 036 subjects). The subjects who stated that they were taking an antidepressant were re-contacted by telephone by an interviewer trained in the use of the Composite International Diagnostic Interview - lifetime (CIDI), exploring depression and anxiety diseases with a view to potential diagnosis as per DSM criteria. Longitudinal follow-up over 8 months from the initial screening was evaluated using a monthly questionnaire on the time course of antidepressant consumption. Results - Out of 20 000 households, comprising 44 000 people aged over 15 years, 1 333 people were taking an antidepressant or had taken one in the previous 4 weeks. The sex ratio of the antidepressant consumers was 3 women to 1 man, amplifying the known sex ratio with respect to depressive disorders. The mean

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

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.

Side Effects to Antidepressant Treatment in Patients With Depression and Comorbid Panic Disorder.

PubMed

Shankman, Stewart A; Gorka, Stephanie M; Katz, Andrea C; Klein, Daniel N; Markowitz, John C; Arnow, Bruce A; Manber, Rachel; Rothbaum, Barbara O; Thase, Michael E; Schatzberg, Alan F; Keller, Martin B; Trivedi, Madhukar H; Kocsis, James H

2017-04-01

Side effects to antidepressant medication can affect the efficacy of treatment, but few predictors foretell who experiences side effects and which side effects they experience. This secondary data analysis examined whether depressed patients with comorbid panic disorder were more likely to experience side effects than those without panic disorder. The study also examined whether greater burden of side effects predicted a poorer treatment course for patients with panic disorder than those without panic disorder. To examine the specificity of these effects, analyses also examined 2 other anxiety disorders-social phobia and generalized anxiety disorder (GAD). Between 2002 and 2006, a large sample (N = 808) of chronically depressed individuals (assessed using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders [SCID-IV]) received antidepressants according to a predetermined algorithm for 12 weeks. Every 2 weeks, depressive symptoms (per the Hamilton Depression Rating Scale) and side effects (specific side effects as well as several indicators of side effect burden) were assessed. Lifetime diagnosis of panic disorder (assessed using the SCID-IV) at baseline was associated with higher likelihood of gastrointestinal (OR = 1.6 [95% CI, 1.0-2.6]), cardiac (OR = 1.8 [95% CI, 1.1-3.1]), neurologic (OR = 2.6 [95% CI, 1.6-4.2]), and genitourinary side effects (OR = 3.0 [95% CI, 1.7-5.3]) during treatment. Increases in side effect frequency, intensity, and impairment over time were more strongly associated with increases in depressive symptoms for patients with panic disorder compared to those without panic disorder. Neither social phobia nor GAD was associated with these effects. Potentially due to heighte​ned interoceptive awareness of changes in their body, chronically depressed individuals with panic disorder may be at greater risk than those without panic disorder for antidepressant side effects and to experience a worsening of depressive symptoms as a result

BDNF — a key transducer of antidepressant effects

PubMed Central

Björkholm, Carl; Monteggia, Lisa M.

2016-01-01

How do antidepressants elicit an antidepressant response? Here, we review accumulating evidence that the neurotrophin brain-derived neurotrophic factor (BDNF) serves as a transducer, acting as the link between the antidepressant drug and the neuroplastic changes that result in the improvement of the depressive symptoms. Over the last decade several studies have consistently highlighted BDNF as a key player in antidepressant action. An increase in hippocampal and cortical expression of BDNF mRNA parallels the antidepressant-like response of conventional antidepressants such as SSRIs. Subsequent studies showed that a single bilateral infusion of BDNF into the ventricles or directly into the hippocampus is sufficient to induce a relatively rapid and sustained antidepressant-like effect. Importantly, the antidepressant-like response to conventional antidepressants is attenuated in mice where the BDNF signaling has been disrupted by genetic manipulations. Low dose ketamine, which has been found to induce a rapid antidepressant effect in patients with treatment-resistant depression, is also dependent on increased BDNF signaling. Ketamine transiently increases BDNF translation in hippocampus, leading to enhanced synaptic plasticity and synaptic strength. Ketamine has been shown to increase BDNF translation by blocking NMDA receptor activity at rest, thereby inhibiting calcium influx and subsequently halting eukaryotic elongation factor 2 (eEF2) kinase leading to a desuppression of protein translation, including BDNF translation. The antidepressant-like response of ketamine is abolished in BDNF and TrkB conditional knockout mice, eEF2 kinase knockout mice, in mice carrying the BDNF met/met allele, and by intra-cortical infusions of BDNF-neutralizing antibodies. In summary, current data suggests that conventional antidepressants and ketamine mediate their antidepressant-like effects by increasing BDNF in forebrain regions, in particular the hippocampus, making BDNF an

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

The effect of flexible cognitive-behavioural therapy and medical treatment, including antidepressants on post-traumatic stress disorder and depression in traumatised refugees: pragmatic randomised controlled clinical trial.

PubMed

Buhmann, Caecilie Böck; Nordentoft, Merete; Ekstroem, Morten; Carlsson, Jessica; Mortensen, Erik Lykke

2016-03-01

Little evidence exists on the treatment of traumatised refugees. To estimate treatment effects of flexible cognitive-behavioural therapy (CBT) and antidepressants (sertraline and mianserin) in traumatised refugees. Randomised controlled clinical trial with 2 × 2 factorial design (registered with Clinicaltrials.gov, NCT00917397, EUDRACT no. 2008-006714-15). Participants were refugees with war-related traumatic experiences, post-traumatic stress disorder (PTSD) and without psychotic disorder. Treatment was weekly sessions with a physician and/or psychologist over 6 months. A total of 217 of 280 patients completed treatment (78%). There was no effect on PTSD symptoms, no effect of psychotherapy and no interaction between psychotherapy and medicine. A small but significant effect of treatment with antidepressants was found on depression. In a pragmatic clinical setting, there was no effect of flexible CBT and antidepressants on PTSD, and there was a small-to-moderate effect of antidepressants and psychoeducation on depression in traumatised refugees. © The Royal College of Psychiatrists 2016.

Antidepressant monotherapy vs sequential pharmacotherapy and mindfulness-based cognitive therapy, or placebo, for relapse prophylaxis in recurrent depression.

PubMed

Segal, Zindel V; Bieling, Peter; Young, Trevor; MacQueen, Glenda; Cooke, Robert; Martin, Lawrence; Bloch, Richard; Levitan, Robert D

2010-12-01

Mindfulness-based cognitive therapy (MBCT) is a group-based psychosocial intervention designed to enhance self-management of prodromal symptoms associated with depressive relapse. To compare rates of relapse in depressed patients in remission receiving MBCT against maintenance antidepressant pharmacotherapy, the current standard of care. Patients who met remission criteria after 8 months of algorithm-informed antidepressant treatment were randomized to receive maintenance antidepressant medication, MBCT, or placebo and were followed up for 18 months. Outpatient clinics at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada, and St Joseph's Healthcare, Hamilton, Ontario. One hundred sixty patients aged 18 to 65 years meeting DSM-IV criteria for major depressive disorder with a minimum of 2 past episodes. Of these, 84 achieved remission (52.5%) and were assigned to 1 of the 3 study conditions. Patients in remission discontinued their antidepressants and attended 8 weekly group sessions of MBCT, continued taking their therapeutic dose of antidepressant medication, or discontinued active medication and were switched to placebo. Relapse was defined as a return, for at least 2 weeks, of symptoms sufficient to meet the criteria for major depression on module A of the Structured Clinical Interview for DSM-IV. Intention-to-treat analyses showed a significant interaction between the quality of acute-phase remission and subsequent prevention of relapse in randomized patients (P = .03). Among unstable remitters (1 or more Hamilton Rating Scale for Depression score >7 during remission), patients in both MBCT and maintenance treatment showed a 73% decrease in hazard compared with placebo (P = .03), whereas for stable remitters (all Hamilton Rating Scale for Depression scores ≤7 during remission) there were no group differences in survival. For depressed patients achieving stable or unstable clinical remission, MBCT offers protection against relapse

Reversal of hippocampal neuronal maturation by serotonergic antidepressants

PubMed Central

Kobayashi, Katsunori; Ikeda, Yumiko; Sakai, Atsushi; Yamasaki, Nobuyuki; Haneda, Eisuke; Miyakawa, Tsuyoshi; Suzuki, Hidenori

2010-01-01

Serotonergic antidepressant drugs have been commonly used to treat mood and anxiety disorders, and increasing evidence suggests potential use of these drugs beyond current antidepressant therapeutics. Facilitation of adult neurogenesis in the hippocampal dentate gyrus has been suggested to be a candidate mechanism of action of antidepressant drugs, but this mechanism may be only one of the broad effects of antidepressants. Here we show a distinct unique action of the serotonergic antidepressant fluoxetine in transforming the phenotype of mature dentate granule cells. Chronic treatments of adult mice with fluoxetine strongly reduced expression of the mature granule cell marker calbindin. The fluoxetine treatment induced active somatic membrane properties resembling immature granule cells and markedly reduced synaptic facilitation that characterizes the mature dentate-to-CA3 signal transmission. These changes cannot be explained simply by an increase in newly generated immature neurons, but best characterized as “dematuration” of mature granule cells. This granule cell dematuration developed along with increases in the efficacy of serotonin in 5-HT4 receptor-dependent neuromodulation and was attenuated in mice lacking the 5-HT4 receptor. Our results suggest that serotonergic antidepressants can reverse the established state of neuronal maturation in the adult hippocampus, and up-regulation of 5-HT4 receptor-mediated signaling may play a critical role in this distinct action of antidepressants. Such reversal of neuronal maturation could affect proper functioning of the mature hippocampal circuit, but may also cause some beneficial effects by reinstating neuronal functions that are lost during development. PMID:20404165

Preferential reduction of binding of sup 125 I-iodopindolol to beta-1 adrenoceptors in the amygdala of rat after antidepressant treatments

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

Ordway, G.A.; Gambarana, C.; Tejani-Butt, S.M.

1991-05-01

This study utilized quantitative receptor autoradiography to examine the effects of repeated administration of antidepressants to rats on the binding of the beta adrenoceptor antagonist, {sup 125}I-iodopindolol ({sup 125}I-IPIN) to either beta-1 or beta-2 adrenoceptors in various regions of brain. Antidepressants were selected to represent various chemical and pharmacological classes including tricyclic compounds (desipramine and protriptyline), monoamine oxidase inhibitors (clorgyline, phenelzine and tranylcypromine), atypical antidepressants (mianserin and trazodone) and selective inhibitors of the uptake of serotonin (citalopram and sertraline). Additionally, rats were treated with various psychotropic drugs that lack antidepressant efficacy (cocaine, deprenyl, diazepam and haloperidol). Repeated treatment of ratsmore » with desipramine, protriptyline, clorgyline, phenelzine, tranylcypromine or mianserin reduced the binding of {sup 125}I-IPIN to beta-1 adrenoceptors in many brain areas. Only in the basolateral and lateral nuclei of the amygdala did all six of these antidepressants significantly reduce {sup 125}I-IPIN binding to beta-1 adrenoceptors. In these amygdaloid nuclei, the magnitude of the reduction in the binding of {sup 125}I-IPIN caused by each of these drugs was comparable to or greater than the reduction in binding produced in any other region of brain. Reductions of binding of {sup 125}I-IPIN after antidepressant treatments were not consistently observed in the cortex, the area of brain examined most often in homogenate binding studies. Only the monoamine oxidase inhibitors caused reductions in the binding of {sup 125}I-IPIN to beta-2 adrenoceptors, and this effect was generally localized to the amygdala and hypothalamus.« less

Amygdala Reactivity to Emotional Faces in the Prediction of General and Medication-Specific Responses to Antidepressant Treatment in the Randomized iSPOT-D Trial.

PubMed

Williams, Leanne M; Korgaonkar, Mayuresh S; Song, Yun C; Paton, Rebecca; Eagles, Sarah; Goldstein-Piekarski, Andrea; Grieve, Stuart M; Harris, Anthony W F; Usherwood, Tim; Etkin, Amit

2015-09-01

Although the cost of poor treatment outcomes of depression is staggering, we do not yet have clinically useful methods for selecting the most effective antidepressant for each depressed person. Emotional brain activation is altered in major depressive disorder (MDD) and implicated in treatment response. Identifying which aspects of emotional brain activation are predictive of general and specific responses to antidepressants may help clinicians and patients when making treatment decisions. We examined whether amygdala activation probed by emotion stimuli is a general or differential predictor of response to three commonly prescribed antidepressants, using functional magnetic resonance imaging (fMRI). A test-retest design was used to assess patients with MDD in an academic setting as part of the International Study to Predict Optimized Treatment in Depression. A total of 80 MDD outpatients were scanned prior to treatment and 8 weeks after randomization to the selective serotonin reuptake inhibitors escitalopram and sertraline and the serotonin-norepinephrine reuptake inhibitor, venlafaxine-extended release (XR). A total of 34 matched controls were scanned at the same timepoints. We quantified the blood oxygen level-dependent signal of the amygdala during subliminal and supraliminal viewing of facial expressions of emotion. Response to treatment was defined by ⩾50% symptom improvement on the 17-item Hamilton Depression Rating Scale. Pre-treatment amygdala hypo-reactivity to subliminal happy and threat was a general predictor of treatment response, regardless of medication type (Cohen's d effect size 0.63 to 0.77; classification accuracy, 75%). Responders showed hypo-reactivity compared to controls at baseline, and an increase toward 'normalization' post-treatment. Pre-treatment amygdala reactivity to subliminal sadness was a differential moderator of non-response to venlafaxine-XR (Cohen's d effect size 1.5; classification accuracy, 81%). Non-responders to

Amygdala Reactivity to Emotional Faces in the Prediction of General and Medication-Specific Responses to Antidepressant Treatment in the Randomized iSPOT-D Trial

PubMed Central

Williams, Leanne M; Korgaonkar, Mayuresh S; Song, Yun C; Paton, Rebecca; Eagles, Sarah; Goldstein-Piekarski, Andrea; Grieve, Stuart M; Harris, Anthony W F; Usherwood, Tim; Etkin, Amit

2015-01-01

Although the cost of poor treatment outcomes of depression is staggering, we do not yet have clinically useful methods for selecting the most effective antidepressant for each depressed person. Emotional brain activation is altered in major depressive disorder (MDD) and implicated in treatment response. Identifying which aspects of emotional brain activation are predictive of general and specific responses to antidepressants may help clinicians and patients when making treatment decisions. We examined whether amygdala activation probed by emotion stimuli is a general or differential predictor of response to three commonly prescribed antidepressants, using functional magnetic resonance imaging (fMRI). A test–retest design was used to assess patients with MDD in an academic setting as part of the International Study to Predict Optimized Treatment in Depression. A total of 80 MDD outpatients were scanned prior to treatment and 8 weeks after randomization to the selective serotonin reuptake inhibitors escitalopram and sertraline and the serotonin–norepinephrine reuptake inhibitor, venlafaxine-extended release (XR). A total of 34 matched controls were scanned at the same timepoints. We quantified the blood oxygen level-dependent signal of the amygdala during subliminal and supraliminal viewing of facial expressions of emotion. Response to treatment was defined by ⩾50% symptom improvement on the 17-item Hamilton Depression Rating Scale. Pre-treatment amygdala hypo-reactivity to subliminal happy and threat was a general predictor of treatment response, regardless of medication type (Cohen's d effect size 0.63 to 0.77; classification accuracy, 75%). Responders showed hypo-reactivity compared to controls at baseline, and an increase toward ‘normalization' post-treatment. Pre-treatment amygdala reactivity to subliminal sadness was a differential moderator of non-response to venlafaxine-XR (Cohen's d effect size 1.5; classification accuracy, 81%). Non-responders to

Cardiotoxicity of tricyclic antidepressant treated by 2650 mEq sodium bicarbonate: A case report.

PubMed

Amiri, Hassan; Zamani, Nasim; Hassanian-Moghaddam, Hossein; Shadnia, Shahin

2016-01-01

Poisoning with tricyclic antidepressants is an important cause of drug-related self-poisoning in the developed world and a very common cause of poisoning and mortality in developing countries. Electrocardiographic manifestations of most tricyclic antidepressant-poisoned patients resolve by the administration of 1-2 mEq/kg of sodium bicarbonate. Some rare cases have been reported who have been resistant to the long-term or high doses of bicarbonate administration. We present a case of acute tricyclic antidepressant toxicity referring with status epilepticus, hypotension, and refractory QRS complex widening that resolved after the intravenous administration of 2650 mEq sodium bicarbonate.

Inulin-Type Oligosaccharides Extracted from Yacon Produce Antidepressant-Like Effects in Behavioral Models of Depression.

PubMed

An, Lei; Yang, Ji-Chu; Yin, Hang; Xue, Rui; Wang, Qiong; Sun, Yu Chen; Zhang, You-Zhi; Yang, Ming

2016-12-01

Yacon (Smallanthus sonchifolius), a traditional food in the Andean diet, is attracting global attention for its medicinal properties, which are mainly because of its high content of non-digestible oligosaccharides. The purpose of this study is to evaluate the antidepressant-like effects of inulin-type oligosaccharides extracted from yacon (YOs) in behavioral models of depression. Behavioral despair models in mice including the tail suspension test (TST) and the forced swimming test (FST) were used to determine the effects of acute YOs administration. The locomotor activity was also explored to eliminate any false-positive activity. In addition, to further investigate the antidepressant-like effects of subchronic YOs administration, the learned helplessness (LH) paradigm in rats was performed. The results demonstrated that YOs (25, 50, or 100 mg/kg, p.o.) treatment significantly reduced the immobility time in the mouse TST and FST in a U-shaped, dose-dependent manner, and showed no stimulatory effect on the locomotor activity. Furthermore, subchronic YOs (25, 50, or 100 mg/kg, p.o.) treatment significantly reversed the escape deficits in LH rats, including an increased number of escape failures and prolonged escape latency. These findings suggest that the inulin-type oligosaccharides extracted from yacon may be a prospective natural source for antidepressants. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Antidepressant effects of the water extract from Taraxacum officinale leaves and roots in mice.

PubMed

Li, Yu-Cheng; Shen, Ji-Duo; Li, Yang-Yang; Huang, Qi

2014-08-01

The leaves and roots of the Taraxacum officinale F. (Asteraceae) is widely used as traditional medicinal herb in Eastern Asian countries. In the present study, the antidepressant-like effects of the water extract of T. officinale (WETO) leaves and roots were investigated in mice using forced swimming test (FST), tail suspension test (TST) and open field test (OFT). Effects of acute (1-day) and chronic treatments (14-days) with WETO (50, 100 and 200 mg/kg) on the behavioral changes in FST, TST and OFT, and the serum corticotrophin releasing factor (CRF), adrenocorticotropic hormone (ACTH) and corticosterone concentration were assessed in mice. Chronic treatment (14-days) with WETO at the doses of 50, 100 and 200 mg/kg significantly decreased the immobility time in both FST (92.6, 85.1 and 77.4 s) and TST (84.8, 72.1 and 56.9 s). Acute treatment (1-day) with WETO at a dose of 200 mg/kg also markedly decreased the immobility time in both FST (81.7 s) and TST (73.2 s). However, all treatments did not affect the locomotor activity in the OFT. Moreover, FST induced a significant increase in serum CRF (5.8 ng/ml), ACTH (104.7 pg/ml) and corticosterone levels (37.3 ng/ml). Chronic treatment (14-days) with WETO decreased the serum CRF (200 mg/kg: 3.9 ng/ml) and corticosterone (50 mg/kg: 29.9 ng/ml; 100 mg/kg: 22.5 ng/ml; 200 mg/kg: 19.8 ng/ml) levels. These results clearly demonstrated the antidepressant effects of WETO in animal models of behavioral despair and suggested the mechanism involved in the neuroendocrine system.

Search for biological correlates of depression and mechanisms of action of antidepressant treatment modalities. Do neuropeptides play a role?

PubMed

Mathé, Aleksander A; Husum, Henriette; El Khoury, Aram; Jiménez-Vasquez, Patricia; Gruber, Susanne H M; Wörtwein, Gitta; Nikisch, Georg; Baumann, Pierre; Agren, Hans; Andersson, Weronica; Södergren, Asa; Angelucci, Francesco

2007-09-10

Dysregulation of the monoaminergic systems is likely a sufficient but not a necessary cause of depression. A wealth of data indicates that neuropeptides, e.g., NPY, CRH, somatostatin, tachykinins and CGRP play a role in affective disorders and alcohol use/abuse. This paper focuses on NPY in etiology and pathophysiology of depression. Decreased peptide and mRNA NPY were found in hippocampus of both the genetic, e.g., the FSL strain, and environmental rat models of depression, e.g., chronic mild stress and early life maternal separation paradigms. Rat models of alcoholism also show altered NPY. Furthermore, NPY is also reduced in CSF of depressed patients. Antidepressive treatments tested so far (lithium, topiramate, SSRIs, ECT and ECS, wheel running) increase NPY selectively in rat hippocampus and in human CSF. Moreover, NPY given icv to rat has antidepressive effects which are antagonized by NPY-Y1 blockers. The data support our hypothesis that the NPY system dysregulation constitutes one of the biological underpinnings of depression and that one common mechanism of action of antidepressive treatment modalities may be effects on NPY and its receptors. In a novel paradigm, early life maternal separation was superimposed on "depressed" FSL and control rats and behavioral and brain neurochemistry changes observed in adulthood. The consequences were more deleterious in genetically vulnerable FSL. Early antidepressive treatment modulated the adult sequelae. Consequently, if these data are confirmed, the ethical and medical question that will be asked is whether it is permissible and advisable to consider prophylactically treating persons at risk.

The Effect of Sympathetic Antagonists on the Antidepressant Action of Alprazolam

PubMed Central

Al-Tubuly, RA; Aburawi, SM; Alghzewi, EA; Gorash, ZM; Errwami, S

2008-01-01

Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor antagonists with benzodiazepines, which may impact the clinical use of alprazolam, was also studied. Behavioral despair was examined in six groups of albino mice. Drugs were administered intraperitoneally. The control group received only a single dose of 1% Tween 80. The second group received a single dose of alprazolam, and the third group received an antagonist followed by alprazolam. The fourth group was treated with imipramine, and the fifth group received an antagonist followed by imipramine. The sixth group was treated with a single dose of an antagonist alone (atenolol, a β1-selective adrenoceptor antagonist; propranolol, a non selective β-adrenoceptor antagonist; and prazocin, an α1-adrenoceptor antagonist). Results confirmed the antidepressant action of alprazolam and imipramine. Prazocin treatment alone produced depression, but it significantly potentiated the antidepressant actions of imipramine and alprazolam. Atenolol alone produced an antidepressant effect and potentiated the antidepressant action of alprazolam. Propranolol treatment alone produced depression, and antagonized the effects of alprazolam and imipramine, even producing depression in combined treatments.In conclusion, our results reveal that alprazolam may produce antidepressant effects through the release of noradrenaline, which stimulates β2 receptors to produce an antidepressant action. Imipramine may act by activating β2 receptors by blocking or down-regulating β1 receptors. PMID:21499463

Azure B and a synthetic structural analogue of methylene blue, ethylthioninium chloride, present with antidepressant-like properties.

PubMed

Delport, Anzelle; Harvey, Brian H; Petzer, Anél; Petzer, Jacobus P

2014-11-11

The phenothiazinium compound, methylene blue (MB), possesses diverse pharmacological actions and is attracting attention for the treatment of bipolar disorder and Alzheimer's disease. MB acts on both monoamine oxidase (MAO) and the nitric oxide (NO)-cGMP pathway, and possesses antidepressant activity in rodents. The goal of this study was to synthesise a structural analogue of MB, ethylthioninium chloride (ETC), and to evaluate the effects of the structural changes on the MAO inhibitory and antidepressant properties of MB. This study also investigated the antidepressant properties of azure B, the major metabolite of MB, versus MB and imipramine as active comparators. ETC and azure B were firstly evaluated as inhibitors of human MAO, and secondly for antidepressant-like activity in the acute forced swim test (FST) in rats, and compared to saline, imipramine and MB. The results document that ETC is a reversible inhibitor of MAO-A and MAO-B with IC50 values of 0.510 μM and 0.592 μM, respectively, and that it is a weaker MAO-A inhibitor than MB and azure B. ETC and azure B were more effective than imipramine and MB in reversing immobility in the FST without inducing locomotor effects, with evidence supporting a serotonergic action. Of interest is the finding that ETC is more toxic for cultured cells than MB. Azure B may therefore be a contributor to the antidepressant effect of MB. Small structural changes made to MB retain its antidepressant effect, even though the resulting phenothiazinium compound possesses reduced MAO-A inhibitory potency.

Neuronal plasticity and antidepressant actions

PubMed Central

Castrén, Eero; Hen, René

2013-01-01

Antidepressant treatments enhance plasticity and increase neurogenesis in the adult brain, but it has been unclear how these effects influence mood. We propose that like environmental enrichment and exercise, antidepressant treatments enhance adaptability by increasing structural variability within the nervous system at many levels, from proliferating precursors to immature synaptic contacts. Conversely, sensory deprivation and chronic stress reduce this structural variability. Activity-dependent competition within the mood-related circuits, guided by rehabilitation, then selects for the survival and stabilization of those structures that best represent the internal or external milieu. Increased variability together with competition-mediated selection facilitates normal function, such as pattern separation within the dentate gyrus and other mood-related circuits, thereby enhancing adaptability towards novel experiences. PMID:23380665

Antidepressants versus placebo for panic disorder in adults.

PubMed

Bighelli, Irene; Castellazzi, Mariasole; Cipriani, Andrea; Girlanda, Francesca; Guaiana, Giuseppe; Koesters, Markus; Turrini, Giulia; Furukawa, Toshi A; Barbui, Corrado

2018-04-05

Panic disorder is characterised by repeated, unexpected panic attacks, which represent a discrete period of fear or anxiety that has a rapid onset, reaches a peak within 10 minutes, and in which at least four of 13 characteristic symptoms are experienced, including racing heart, chest pain, sweating, shaking, dizziness, flushing, stomach churning, faintness and breathlessness. It is common in the general population with a lifetime prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions. Amongst pharmacological agents, the National Institute for Health and Care Excellence (NICE) and the British Association for Psychopharmacology consider antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), as the first-line treatment for panic disorder, due to their more favourable adverse effect profile over monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). Several classes of antidepressants have been studied and compared, but it is still unclear which antidepressants have a more or less favourable profile in terms of effectiveness and acceptability in the treatment of this condition. To assess the effects of antidepressants for panic disorder in adults, specifically:1. to determine the efficacy of antidepressants in alleviating symptoms of panic disorder, with or without agoraphobia, in comparison to placebo;2. to review the acceptability of antidepressants in panic disorder, with or without agoraphobia, in comparison with placebo; and3. to investigate the adverse effects of antidepressants in panic disorder, with or without agoraphobia, including the general prevalence of adverse effects, compared to placebo. We searched the Cochrane Common Mental Disorders' (CCMD) Specialised Register, and CENTRAL, MEDLINE, EMBASE and PsycINFO up to May 2017. We handsearched reference lists of relevant papers and previous systematic reviews. All double-blind, randomised, controlled trials (RCTs

Psychiatric and Psychological Factors in Patient Decision Making Concerning Antidepressant Use

ERIC Educational Resources Information Center

Dijkstra, Arie; Jaspers, Merlijne; van Zwieten, Marianne

2008-01-01

The observation that the use of antidepressants has strongly increased during the past decade implies that on a micro level doctors and patients more often decide that antidepressants are the appropriate treatment. Therefore, it is important to increase insight into patients' decision making regarding the use of antidepressants. The decision…

Tricyclic Antidepressants

NASA Astrophysics Data System (ADS)

Schmidt, Gary J.

The use of tricyclic antidepressant drugs is becoming increasingly prevalent for the treatment of depressed patients. It has been suggested that, analogous to many other drug substances, the tricyclic drugs exhibit clinical effectiveness within a defined therapeutic concentration range (1-10). Very recently, both Dito (11) and Orsulak and Schildkraut (12) have summarized the usefulness of measuring serum concentrations of these drugs. These authors suggest that knowledge of the plasma concentrations of these drugs aid the physician in determining patient compliance and initiating the best possible drug treatment.

Role of the nicotinic receptor β4 subunit in the antidepressant activity of novel N,6-dimethyltricyclo[5.2.1.0²,⁶]decan-2-amine enantiomers.

PubMed

Targowska-Duda, Katarzyna M; Jozwiak, Krzysztof; Arias, Hugo R

2013-10-11

The role of the nicotinic receptor β4 subunit in the antidepressant activity of N,6-dimethyltricyclo[5.2.1.0(2,6)]decan-2-amine enantiomers was investigated using wild-type (β4+/+) and knockout (β4-/-) mice. Mice were injected (i.p.) with saline (control) or with either enantiomer (1.0mg/kg base drug) daily for the first two weeks. Forced swim tests (FST) were performed on Day 1 to determine the acute effect of each enantiomer, and on Day 7 and 14, to determine the chronic activity. To examine the remnant effects after drug treatment, a withdrawal period of two more weeks was continued with FSTs performed on Day 21 and 28. Our results indicate that: (1) the acute antidepressant effect elicited by the (S,S)-enantiomer is observed in β4+/+ mice from both sexes, whereas the effect elicited by the (R,R)-enantiomer is only observed in male β4+/+ mice. There is no antidepressant effect for both novel compounds on male and female β4-/- mice, (2) the chronic antidepressant effect elicited by both enantiomers is observed in β4+/+, but not in β4-/-, mice from both sexes, and (3) the residual antidepressant effect mediated by each enantiomer after withdrawal was observed only in female β4+/+ mice. Our results clearly indicate that β4-containing AChRs are targets for the antidepressant activity of these compounds, and that this activity is gender-dependent. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Antidepressant adherence patterns in older patients: use of a clustering method on a prescription database.

PubMed

Braunstein, David; Hardy, Amélie; Boucherie, Quentin; Frauger, Elisabeth; Blin, Olivier; Gentile, Gaétan; Micallef, Joëlle

2017-04-01

According to the World Health Organization, depression will become the second most important cause of disability worldwide by 2020. Our objective was to identify patterns of adherence to antidepressant treatments in older patients using several indicators of adherence and to characterize these patterns in terms of medication exposure. We conducted a retrospective cohort study using the French National Health Insurance reimbursement database. Incident antidepressant users aged more than 65 were included from July 1, 2010, to June 30, 2011, and followed up for 18 months. Antidepressant and other psychotropic drugs (opioids, benzodiazepines, antipsychotics, anti-epileptics) were recorded. Adherence to antidepressant treatment was assessed by several measures including proportion of days covered, discontinuation periods, persistence of treatment, and doses dispensed. Patients were classified according to their adherence patterns using a mixed clustering method. We identified five groups according to antidepressant adherence. One group (n = 7505, 26.9%) was fully adherent with regard to guidelines on antidepressant use. Two patterns of nonadherent users were identified: irregular but persistent users (n = 5131, 18.4%) and regular but nonpersistent users (n = 9037, 32.4%). Serotonin reuptake inhibitors were the most frequently dispensed antidepressant class (70.6%), followed by other antidepressants (43.3%, mainly serotonin-norepinephrine reuptake inhibitors and tianeptine) and tricyclic antidepressants (TCAs) (13.4%). Nonadherent users more frequently had a dispensing of TCA, opioid, and anti-epileptic medication than adherent users. Health policies to improve adherence to antidepressant treatment may require better training of physicians and pharmacists, insisting on the important role of the continuation period of antidepressant treatment. © 2016 Société Française de Pharmacologie et de Thérapeutique.

The use of antidepressant drugs in dermatology.

PubMed

Gupta, M A; Guptat, A K

2001-11-01

This paper provides an updated review of the use of antidepressant drugs in dermatology. Some of the psychiatric disorders that are usually comorbid with dermatological disorders and respond to antidepressants include major depressive disorder, obsessive compulsive disorder, body dysmorphic disorder, social phobia and post-traumatic stress disorder usually secondary to trauma and abuse during early life. Cutaneous symptoms may be the feature of a primary psychiatric disorder, e.g. cutaneous body image problems, dermatitis artefacta, neurotic excoriations and trichotillomania, or psychiatric syndromes may be comorbid with a primary dermatological disorder such as the association of major depressive disorder or social phobia with psoriasis and obsessive compulsive disorder with acne excoriee. Some of the salient pharmacological properties of the tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitor (SSRI) antidepressants are reviewed. The review indicates that the SSRI antidepressants are potentially beneficial in the management of all the major psychiatric syndromes that are encountered in dermatological disorders. The generally more favourable side-effect profile of the SSRIs, such as lower cardiotoxicity in contrast to the TCAs, has made them the first-line agents for the treatment of depression. Furthermore, some of the pharmacological properties of the antidepressant agents that are not related to their antidepressant activity, such as the histamine H1 blocking effect of TCAs, such as doxepin, amitriptyline and trimipramine, are of benefit in dermatological conditions such as urticaria and pruritus. This paper reviews the general guidelines for use of antidepressants and salient drug-drug interactions resulting mainly from the inhibition of the cytochrome P450 (CYP) 2D6 and 3A3/4 isoenzymes by some of the SSRI antidepressants. Before prescribing an antidepressant agent, the specific guidelines, side-effect profile, drug

Research design features and patient characteristics associated with the outcome of antidepressant clinical trials.

PubMed

Khan, Arif; Kolts, Russell L; Thase, Michael E; Krishnan, K Ranga Rama; Brown, Walter

2004-11-01

The authors examined which, if any, research design features and patient characteristics would significantly differ between successful and unsuccessful antidepressant trials. Clinical trial data were reviewed for nine antidepressants approved by the Food and Drug Administration between 1985 and 2000. From the antidepressant research programs on these medications, 52 clinical trials were included in the study. The authors evaluated trial design features, patient characteristics, and difference in response between placebo and antidepressant. Nine trial design features and patient characteristics were present in the research programs for all nine of the antidepressants. The severity of depressive symptoms before patient randomization, the dosing schedule (flexible versus fixed), the number of treatment arms, and the percentage of female patients were significantly associated with the difference in response to antidepressant and placebo. The duration of the antidepressant trial, number of patients per treatment arm, number of sites, and mean age of the patients were similar in successful trials (with a greater antidepressant-placebo difference) and less successful trials (with a smaller antidepressant-placebo difference). These findings may help in the design of future antidepressant trials.

Cognitive-behavioral therapy as continuation treatment to sustain response after electroconvulsive therapy in depression: a randomized controlled trial.

PubMed

Brakemeier, Eva-Lotta; Merkl, Angela; Wilbertz, Gregor; Quante, Arnim; Regen, Francesca; Bührsch, Nicole; van Hall, Franziska; Kischkel, Eva; Danker-Hopfe, Heidi; Anghelescu, Ion; Heuser, Isabella; Kathmann, Norbert; Bajbouj, Malek

2014-08-01

Although electroconvulsive therapy (ECT) is the most effective acute antidepressant intervention, sustained response rates are low. It has never been systematically assessed whether psychotherapy, continuation ECT, or antidepressant medication is the most efficacious intervention to maintain initial treatment response. In a prospective, randomized clinical trial, 90 inpatients with major depressive disorder (MDD) were treated with right unilateral ultra-brief acute ECT. Electroconvulsive therapy responders received 6 months guideline-based antidepressant medication (MED) and were randomly assigned to add-on therapy with cognitive-behavioral group therapy (CBT-arm), add-on therapy with ultra-brief pulse continuation electroconvulsive therapy (ECT-arm), or no add-on therapy (MED-arm). After the 6 months of continuation treatment, patients were followed-up for another 6 months. The primary outcome parameter was the proportion of patients who remained well after 12 months. Of 90 MDD patients starting the acute phase, 70% responded and 47% remitted to acute ECT. After 6 months of continuation treatment, significant differences were observed in the three treatment arms with sustained response rates of 77% in the CBT-arm, 40% in the ECT-arm, and 44% in the MED-arm. After 12 months, these differences remained stable with sustained response rates of 65% in the CBT-arm, 28% in the ECT-arm, and 33% in the MED-arm. These results suggest that ultra-brief pulse ECT as a continuation treatment correlates with low sustained response rates. However, the main finding implicates cognitive-behavioral group therapy in combination with antidepressants might be an effective continuation treatment to sustain response after successful ECT in MDD patients. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Effect of Antidepressant Medication Use on Emotional Information Processing in Major Depression

PubMed Central

Wells, Tony T.; Clerkin, Elise M.; Ellis, Alissa J.; Beevers, Christopher G.

2013-01-01

Objective Acute administration of antidepressant medication increases emotional information processing for positive information in both depressed and healthy participants. This effect is likely relevant to the therapeutic actions of these medications, but has not been studied in patients with Major Depressive Disorder (MDD) taking antidepressants as typically prescribed in the community. Method The authors examined the effects of antidepressant medication on selective attention for emotional stimuli using eye tracking in a sample of 47 participants (21 medicated; 26 non-medicated) with MDD and 47 matched, non-depressed controls. Participants completed a passive viewing eye tracking task assessing selective attention for positive, dysphoric, threatening, and neutral stimuli in addition to providing medication information and self-report measures of depression and anxiety severity. Results: Depressed participants currently taking antidepressant medication and non-depressed healthy control participants demonstrated greater total gaze duration and more fixations for positive stimuli, compared to non-medicated depressed participants. Depressed participants on medication (vs. depressed participants not on medication) also had fewer fixations for dysphoric stimuli. Conclusions Antidepressants, as prescribed in the community to depressed patients, appear to modify emotional information processing in the absence of differences in depression severity. These results are consistent with prior work and indicate a robust effect for antidepressants on positive information processing. They also provide further evidence for modification of information processing as a potential mechanism of action for antidepressant medication. PMID:24030200

Effect of antidepressant medication use on emotional information processing in major depression.

PubMed

Wells, Tony T; Clerkin, Elise M; Ellis, Alissa J; Beevers, Christopher G

2014-02-01

Acute administration of antidepressant medication increases emotional information processing for positive information in both depressed and healthy persons. This effect is likely relevant to the therapeutic actions of these medications, but it has not been studied in patients with major depressive disorder taking antidepressants as typically prescribed in the community. The authors used eye tracking to examine the effects of antidepressant medication on selective attention for emotional stimuli in a sample of 47 patients with major depressive disorder (21 medicated and 26 unmedicated) and 47 matched comparison subjects without depression. Participants completed a passive-viewing eye-tracking task assessing selective attention for positive, dysphoric, threatening, and neutral stimuli in addition to providing medication information and self-report measures of depression and anxiety severity. Depressed participants currently taking antidepressants and nondepressed comparison subjects demonstrated greater total gaze duration and more fixations for positive stimuli compared with unmedicated depressed participants. Depressed participants on medication also had fewer fixations for dysphoric stimuli compared with depressed participants not on medication. Antidepressants, as prescribed in the community to patients with depression, appear to modify emotional information processing in the absence of differences in depression severity. These results are consistent with previous work and indicate a robust effect for antidepressants on positive information processing. They also provide further evidence for modification of information processing as a potential mechanism of action for antidepressant medication.

Exploring the role of drug-metabolising enzymes in antidepressant side effects.

PubMed

Hodgson, Karen; Tansey, Katherine E; Uher, Rudolf; Dernovšek, Mojca Zvezdana; Mors, Ole; Hauser, Joanna; Souery, Daniel; Maier, Wolfgang; Henigsberg, Neven; Rietschel, Marcella; Placentino, Anna; Craig, Ian W; Aitchison, Katherine J; Farmer, Anne E; Dobson, Richard J B; McGuffin, Peter

2015-07-01

Cytochrome P450 enzymes are important in the metabolism of antidepressants. The highly polymorphic nature of these enzymes has been linked to variability in antidepressant metabolism rates, leading to hope regarding the use of P450 genotyping to guide treatment. However, evidence that P450 genotypic differences underlie the variation in treatment outcomes is inconclusive. We explored the links between both P450 genotype and serum concentrations of antidepressant with antidepressant side effects, using data from the Genome-Based Therapeutic Drugs for Depression Project (GENDEP), which is a large (n = 868), pharmacogenetic study of depressed individuals treated with escitalopram or nortriptyline. Patients were genotyped for the enzymes CYP2C19 and CYP2D6, and serum concentrations of both antidepressant and primary metabolite were measured after 8 weeks of treatment. Side effects were assessed weekly. We investigated associations between P450 genotypes, serum concentrations of antidepressants and side effects, as well as the relationship between P450 genotype and study discontinuation. P450 genotype did not predict total side effect burden (nortriptyline: n = 251, p = 0.5638, β = -0.133, standard error (SE) = 0.229; escitalopram: n = 340, p = 0.9627, β = -0.004, SE = 0.085), study discontinuation (nortriptyline n = 284, hazard ratio (HR) = 1.300, p = 0.174; escitalopram n = 376, HR = 0.870, p = 0.118) or specific side effects. Serum concentrations of antidepressant were only related to a minority of the specific side effects measured: dry mouth, dizziness and diarrhoea. In this sample where antidepressant dosage is titrated using clinical judgement, P450 genotypes do not explain differences between patients in side effects with antidepressants. Serum drug concentrations appear to only explain variability in the occurrence of a minority of specific side effects.

Design of clinical trials of antidepressants: should a placebo control arm be included?

PubMed

Fritze, J; Möller, H J

2001-01-01

There is no doubt that available antidepressants are efficacious and effective. Nevertheless, more effective drugs with improved tolerability are needed. With this need in mind, some protagonists claim that future antidepressants should be proved superior to, or at least as effective as, established antidepressants, making placebo control methodologically dispensable in clinical trials. Moreover, the use of placebo control is criticised as unethical because it might result in effective treatment being withheld. There are, however, a number of methodological reasons why placebo control is indispensable for the proof of efficacy of antidepressants. Comparing investigational antidepressants only with standard antidepressants and not placebo yields ambiguous results that are difficult to interpret, be it in superiority or equivalence testing, and this method of assessment requires larger sample sizes than those required with the use of placebo control. Experimental methodology not adhering to the optimal study design is ethically questionable. Restricting the testing of investigational antidepressants only to superiority over standard antidepressants is an obstacle to therapeutic progress in terms of tolerability and the detection of innovative mechanisms of action from which certain subgroups of future patients might benefit. The use of a methodology that requires larger samples for testing of superiority or equivalence is also ethically questionable. In view of the high placebo response rates in trials of antidepressants, placebo treatment does not mean withholding effective treatment. Accepting the necessity of the clinical evaluation of new, potentially ineffective antidepressants implicitly means accepting placebo control as ethically justified. Three- or multi-arm comparisons including placebo and an active reference represent the optimal study design.

Identification of the cortical neurons that mediate antidepressant responses

PubMed Central

Schmidt, Eric F.; Warner-Schmidt, Jennifer; Otopalik, Benjamin G.; Pickett, Sarah B.; Greengard, Paul; Heintz, Nathaniel

2012-01-01

Summary Our understanding of current treatments for depression, and the development of more specific therapies, is limited by the complexity of the circuits controlling mood and the distributed actions of antidepressants. Although the therapeutic efficacy of SSRIs is correlated with increases in cortical activity, the cell types crucial for their action remain unknown. Here we employ bacTRAP translational profiling to show that layer 5 corticostriatal pyramidal cells expressing p11 (S100a10) are strongly and specifically responsive to chronic antidepressant treatment. This response requires p11 and includes the specific induction of Htr4 expression. Cortex-specific deletion of p11 abolishes behavioral responses to SSRI’s, but does not lead to increased depression-like behaviors. Our data identify corticostriatal projection neurons as critical for the response to antidepressants, and suggest that the regulation of serotonergic tone in this single cell type plays a pivotal role in antidepressant therapy. PMID:22632977

Effects of antidepressant treatment with rTMS and fluoxetine on brain perfusion in PD.

PubMed

Fregni, F; Ono, C R; Santos, C M; Bermpohl, F; Buchpiguel, C; Barbosa, E R; Marcolin, M A; Pascual-Leone, A; Valente, K D

2006-06-13

Although depression is highly prevalent in Parkinson disease (PD), little is known about the neural correlates associated with depression and antidepressant treatment in PD. To examine the effects of fluoxetine and repetitive transcranial magnetic stimulation (rTMS) on regional cerebral blood flow (rCBF) using SPECT in patients with PD and depression. Twenty-six patients were enrolled into two groups: One received active rTMS and placebo medication and the other sham rTMS and fluoxetine 20 mg/day. Brain SPECT was performed at baseline and after 2 and 8 weeks. Changes in rCBF were compared across timepoints and correlated with clinical scores. In addition, baseline rCBF of these patients was compared with that of 29 healthy, age-matched subjects. At baseline, patients with PD and depression showed significantly lower rCBF in the left prefrontal cortex, posterior cingulate gyrus, left insula, and right parietal cortex when compared with healthy controls. Both treatments induced significant clinical improvement and increases in rCBF in the posterior cingulate gyrus and decreases in rCBF in the right medial frontal gyrus. These changes were significantly correlated to the clinical outcome. Furthermore, the comparison between these two treatments revealed that whereas rTMS treatment was associated with an increased perfusion in the right and left prefrontal cortex, fluoxetine treatment was associated with a relative rCBF increase in the occipital lobe. Depression in patients with Parkinson disease is correlated with a dysfunction of the frontal-limbic network that can be modulated by two different antidepressant therapies.

Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): a randomised controlled trial.

PubMed

Kuyken, Willem; Hayes, Rachel; Barrett, Barbara; Byng, Richard; Dalgleish, Tim; Kessler, David; Lewis, Glyn; Watkins, Edward; Brejcha, Claire; Cardy, Jessica; Causley, Aaron; Cowderoy, Suzanne; Evans, Alison; Gradinger, Felix; Kaur, Surinder; Lanham, Paul; Morant, Nicola; Richards, Jonathan; Shah, Pooja; Sutton, Harry; Vicary, Rachael; Weaver, Alice; Wilks, Jenny; Williams, Matthew; Taylor, Rod S; Byford, Sarah

2015-07-04

Individuals with a history of recurrent depression have a high risk of repeated depressive relapse or recurrence. Maintenance antidepressants for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to medication. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce risk of relapse or recurrence compared with usual care, but has not yet been compared with maintenance antidepressant treatment in a definitive trial. We aimed to see whether MBCT with support to taper or discontinue antidepressant treatment (MBCT-TS) was superior to maintenance antidepressants for prevention of depressive relapse or recurrence over 24 months. In this single-blind, parallel, group randomised controlled trial (PREVENT), we recruited adult patients with three or more previous major depressive episodes and on a therapeutic dose of maintenance antidepressants, from primary care general practices in urban and rural settings in the UK. Participants were randomly assigned to either MBCT-TS or maintenance antidepressants (in a 1:1 ratio) with a computer-generated random number sequence with stratification by centre and symptomatic status. Participants were aware of treatment allocation and research assessors were masked to treatment allocation. The primary outcome was time to relapse or recurrence of depression, with patients followed up at five separate intervals during the 24-month study period. The primary analysis was based on the principle of intention to treat. The trial is registered with Current Controlled Trials, ISRCTN26666654. Between March 23, 2010, and Oct 21, 2011, we assessed 2188 participants for eligibility and recruited 424 patients from 95 general practices. 212 patients were randomly assigned to MBCT-TS and 212 to maintenance antidepressants. The time to relapse or recurrence of depression did not differ between MBCT-TS and maintenance antidepressants over 24 months (hazard ratio 0·89, 95% CI 0·67-1·18

Antidepressant-Like Effects of Sanggenon G, Isolated from the Root Bark of Morus alba, in Rats: Involvement of the Serotonergic System.

PubMed

Lim, Dong Wook; Jung, Jae-Woo; Park, Ji-Hae; Baek, Nam-In; Kim, Yun Tai; Kim, In-Ho; Han, Daeseok

2015-01-01

The root bark of Morus alba is commonly used as an alternative medicine due to its numerous health benefits in humans. However, the antidepressant effects of various active components from M. alba have not been fully elucidated. In this study, we aimed to determine whether sanggenon G, an active compound isolated from the root bark of M. alba, exhibited antidepressant-like activity in rats subjected to forced swim test (FST)-induced depression. Acute treatment of rats with sanggenon G (30 mg/kg, intraperitoneally (i.p.)) significantly reduced immobility time and increased swimming time without any significant change in climbing. Rats treated with sanggenon G also exhibited a decrease in the limbic hypothalamic-pituitary-adrenal (HPA) axis response to the FST, as indicated by attenuation of the corticosterone response and decreased c-Fos immunoreactivity in the hypothalamic paraventricular nucleus (PVN). In addition, the antidepressant-like effects of sanggenon G were significantly inhibited by WAY100635 (1 mg/kg, i.p.; a selective 5-hydroxytryptamine1A (5-HT1A) receptor antagonist), but not SCH23390 (0.05 mg/kg, i.p.; a dopamine D1 receptor antagonist). Our findings suggested that the antidepressant-like effects of sanggenon G were mediated by an interaction with the serotonergic system. Further studies are needed to evaluate the potential of sanggenon G as an alternative therapeutic approach for the treatment of depression.

NMDAR inhibition-independent antidepressant actions of ketamine metabolites

PubMed Central

Zanos, Panos; Moaddel, Ruin; Morris, Patrick J.; Georgiou, Polymnia; Fischell, Jonathan; Elmer, Greg I.; Alkondon, Manickavasagom; Yuan, Peixiong; Pribut, Heather J.; Singh, Nagendra S.; Dossou, Katina S.S.; Fang, Yuhong; Huang, Xi-Ping; Mayo, Cheryl L.; Wainer, Irving W.; Albuquerque, Edson X.; Thompson, Scott M.; Thomas, Craig J.; Zarate, Carlos A.; Gould, Todd D.

2016-01-01

Major depressive disorder afflicts ~16 percent of the world population at some point in their lives. Despite a number of available monoaminergic-based antidepressants, most patients require many weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist, (R,S)-ketamine (ketamine), exerts rapid and sustained antidepressant effects following a single dose in depressed patients. Here we show that the metabolism of ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant actions in vivo. Notably, we demonstrate that these antidepressant actions are NMDAR inhibition-independent but they involve early and sustained α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor activation. We also establish that (2R,6R)-HNK lacks ketamine-related side-effects. Our results indicate a novel mechanism underlying ketamine’s unique antidepressant properties, which involves the required activity of a distinct metabolite and is independent of NMDAR inhibition. These findings have relevance for the development of next generation, rapid-acting antidepressants. PMID:27144355

Metabolite profiling of antidepressant drug action reveals novel drug targets beyond monoamine elevation.

PubMed

Webhofer, C; Gormanns, P; Tolstikov, V; Zieglgänsberger, W; Sillaber, I; Holsboer, F; Turck, C W

2011-12-13

Currently used antidepressants elevate monoamine levels in the synaptic cleft. There is good reason to assume that this is not the only source for antidepressant therapeutic activities and that secondary downstream effects may be relevant for alleviating symptoms of depression. We attempted to elucidate affected biochemical pathways downstream of monoamine reuptake inhibition by interrogating metabolomic profiles in DBA/2Ola mice after chronic paroxetine treatment. Metabolomic changes were investigated using gas chromatography-mass spectrometry profiling and group differences were analyzed by univariate and multivariate statistics. Pathways affected by antidepressant treatment were related to energy metabolism, amino acid metabolism and hormone signaling. The identified pathways reveal further antidepressant therapeutic action and represent targets for drug development efforts. A comparison of the central nervous system with blood plasma metabolite alterations identified GABA, galactose-6-phosphate and leucine as biomarker candidates for assessment of antidepressant treatment effects in the periphery.

An extension of hypotheses regarding rapid-acting, treatment-refractory, and conventional antidepressant activity of dextromethorphan and dextrorphan.

PubMed

Lauterbach, Edward C

2012-06-01

It was previously hypothesized that dextromethorphan (DM) and dextrorphan (DX) may possess antidepressant properties, including rapid and conventional onsets of action and utility in treatment-refractory depression, based on pharmacodynamic similarities to ketamine. These similarities included sigma-1 (σ(1)) agonist and NMDA antagonist properties, calcium channel blockade, muscarinic binding, serotonin transporter (5HTT) inhibition, and μ receptor potentiation. Here, six specific hypotheses are developed in light of additional mechanisms and evidence. Comparable potencies to ketamine for DM and DX are detailed for σ(1) (DX>DM>ketamine), NMDA PCP site (DX>ketamine>DM), and muscarinic (DX>ketamine>DM) receptors, 5HTT (DM>DX≫ketamine), and NMDA antagonist potentiation of μ receptor stimulation (DM>ketamine). Rapid acting antidepressant properties of DM include NMDA high-affinity site, NMDR-2A, and functional NMDR-2B receptor antagonism, σ(1) stimulation, putative mTOR activation (by σ(1) stimulation, μ potentiation, and 5HTT inhibition), putative AMPA receptor trafficking (by mTOR activation, PCP antagonism, σ(1) stimulation, μ potentiation, and 5HTT inhibition), and dendritogenesis, spinogenesis, synaptogenesis, and neuronal survival by NMDA antagonism and σ(1) and mTOR signaling. Those for dextrorphan include NMDA high-affinity site and NMDR-2A antagonism, σ(1) stimulation, putative mTOR activation (by σ(1) stimulation and ß adrenoreceptor stimulation), putative AMPA receptor trafficking (by mTOR activation, PCP antagonism, σ(1) stimulation, ß stimulation, and μ antagonism), and dendritogenesis, spinogenesis, synaptogenesis, and neuronal survival by NMDA antagonism and σ(1) and mTOR signaling. Conventional antidepressant properties for dextromethorphan and dextrorphan include 5HTT and norepinephrine transporter inhibition, σ(1) stimulation, NMDA and PCP antagonism, and possible serotonin 5HT1b/d receptor stimulation. Additional properties for

Timosaponin derivative YY-23 acts as a non-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice.

PubMed

Zhang, Qi; Guo, Fei; Fu, Zhi-wen; Zhang, Bing; Huang, Cheng-gang; Li, Yang

2016-02-01

N-methyl-D-aspartic acid (NMDA) receptor modulators have shown promising results as potential antidepressant agents, whereas timosaponins extracted from the Chinese herb Rhizoma Anemarrhenae exhibit antidepressant activities. In the present study we examined whether YY-23, a modified metabolite of timosaponin B-III, could affect NMDA receptors in rat hippocampal neurons in vitro, and evaluated its antidepressant-like effects in stressed mice. NMDA-induced currents were recorded in acutely dissociated rat hippocampal CA1 neurons using a whole-cell recording technique. C57BL/6 mice were exposed to a 6-week chronic mild stress (CMS) or a 10-d chronic social defeat stress (CSDS). The stressed mice were treated with YY-23 (20 mg·kg(-1)·d(-1)) or a positive-control drug, fluoxetine (10 mg·kg(-1)·d(-1)) for 3 weeks. Behavioral assessments were carried out every week. In acutely dissociated rat hippocampal CA1 neurons, YY-23 selectively and reversibly inhibited NMDA-induced currents with an EC50 value of 2.8 μmol/L. This inhibition of NMDA-induced currents by YY-23 was non-competitive, and had no features of voltage-dependency or use-dependency. Treatment of the stressed mice with YY-23 not only reversed CMS-induced deficiency of sucrose preference and immobility time, and CSDS-induced reduction of social interaction, but also had faster onset as compared to fluoxetine. YY-23 is a novel non-competitive antagonist of NMDA receptors with promising rapid antidepressant-like effects in mouse models of CMS and CSDS depression.

Comparing the quality of antidepressant pharmacotherapy in the Department of Veterans Affairs and the private sector.

PubMed

Busch, Susan H; Leslie, Douglas L; Rosenheck, Robert A

2004-12-01

Comparing quality of care between large health care systems is important for health systems management. This study compared measures of the quality of pharmacotherapy for patients with major depression across a sample of patients from the Department of Veterans Affairs (VA) and the private sector. In this observational study, all patients who were given a new prescription for an antidepressant and a diagnosis of major depression in the VA during fiscal year 2000 were identified by using administrative data (N=27,713). In the private sector, a similar sample of patients were identified by using Medstat's MarketScan database (N=4,852). For both groups, measures of the quality of antidepressant pharmacotherapy were constructed. These measures were compared across the two groups by using logistic regression models. Controls for age, gender, comorbid disorders, and initial antidepressant drug prescribed were included in some models. Although the populations had different demographic and clinical characteristics, differences in the quality measures between the two systems were few, with the VA slightly outperforming the private sector in the prescription of antidepressants during the acute phase of treatment, the first 84 days (84.7 compared with 81 percent) and during the maintenance phase of treatment, the first 181 days (53.9 compared with 50.9 percent). Patient characteristics that were associated with quality measures included being older, being female, and having a comorbid diagnosis of substance use disorder, bipolar disorder, or anxiety or adjustment disorder. Both systems had relatively high rates of adherence to pharmacotherapy guidelines. Even though the populations in the two systems were different, adjusting the analyses for clinical characteristics did little to change the measured differences between the two systems.

The 5-HTTLPR and BDNF polymorphisms moderate the association between uncinate fasciculus connectivity and antidepressants treatment response in major depression.

PubMed

Tatham, Erica L; Hall, Geoff B C; Clark, Darren; Foster, Jane; Ramasubbu, Rajamannar

2017-03-01

Symptom improvement in depression due to antidepressant treatment is highly variable and clinically unpredictable. Linking neuronal connectivity and genetic risk factors in predicting antidepressant response has clinical implications. Our investigation assessed whether indices of white matter integrity, serotonin transporter-linked polymorphism (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) val66met polymorphism predicted magnitude of depression symptom change following antidepressant treatment. Fractional anisotropy (FA) was used as an indicator of white matter integrity and was assessed in the uncinate fasciculus and superior longitudinal fasciculus using tract-based spatial statistics (TBSS) and probabilistic tractography. Forty-six medication-free patients with major depressive disorder participated in a diffusion tensor imaging scan prior to completing an 8-week treatment regime with citalopram or quetiapine XR. Indexed improvements in Hamilton Depression Rating Scale score from baseline to 8-week endpoint were used as an indicator of depression improvement. Carriers of the BDNF met allele exhibited lower FA values in the left uncinate fasciculus relative to val/val individuals [F(1, 40) = 7.314, p = 0.009]. Probabilistic tractography identified that higher FA in the left uncinate fasciculus predicted percent change in depression severity, with BDNF moderating this association [F(3, 30) = 3.923, p = 0.018]. An interaction between FA in the right uncinate fasciculus and 5-HTTLPR also predicted percent change in depression severity [F(5, 25) = 5.315, p = 0.002]. Uncorrected TBSS results revealed significantly higher FA in hippocampal portions of the cingulum bundle in responders compared to non-responders (p = 0.016). The predictive value of prefrontal and amygdala/hippocampal WM connectivity on antidepressant treatment response may be influenced by 5-HTTLPR and BDNF polymorphisms in MDD.

Toxicological analysis and antihyperalgesic, antidepressant, and anti-inflammatory effects of Campomanesia adamantium fruit barks.

PubMed

de Souza, Juliane C; Piccinelli, Ana Cláudia; Aquino, Diana F S; de Souza, Vanessa V; Schmitz, Wanderlei O; Traesel, Giseli K; Cardoso, Claudia A L; Kassuya, Candida A L; Arena, Arielle C

2017-01-01

This study evaluates the anti-inflammatory, antihyperalgesic, and antidepressive potential of the hydroalcoholic extract of Campomanesia adamantium fruit barks (CAE) on rodents and determines the safety of this plant. The acute toxicity of CAE was evaluated by oral administration to female rats as single doses of 0, 500, 1000, or 2000 mg/kg body weight. General behavior and toxic symptoms were observed for 14 days. In the subacute toxicity test, male and female rats received 125 or 250 mg/kg body weight of CAE for 28 days. The oral anti-inflammatory activity of CAE was evaluated in carrageenan-induced pleurisy in male mice. The effect of treatment with CAE (100 mg/kg) for 15 days was evaluated in mechanical hyperalgesia (electronic von Frey), depressive behavior (forced swimming test), and cold hypersensitivity in spared nerve injury (SNI) model in rats. No clinical signs of toxicity were observed in animals from the experimental groups during acute and subacute exposure to CAE. At pleurisy test, the oral administration of CAE significantly inhibited leukocyte migration and protein leakage at all doses tested when compared to control. Oral administration of CAE for 3-15 days significantly inhibited SNI-induced mechanical hyperalgesia and increased immobility in the forced swim test. Finally, on the 15th day, oral treatment with CAE prevented the increase in sensitivity to a cold stimulus induced by SNI. The present study shows that C. adamantium extract has anti-inflammatory, antihyperalgesic, and antidepressive properties in rodents without causing toxicity.

Intox, detox, antidotes - Evidence based diagnosis and treatment of acute intoxications.

PubMed

Schaper, Andreas; Ebbecke, Martin

2017-11-01

Aim of this review is to describe the role of clinical toxicology in the context of acute medicine. A special focus is put on antidotes and important aspects of diagnosis and therapy of acute intoxications. The data of the annual report of GIZ-Nord Poisons Centre is analyzed concerning the following aspects: what intoxications are relevant in acute medicine, are there special aspects in therapy, e.g. antidotes, and what antidotes are relevant? More over intoxication-related fatalities are analyzed. In 2015 the poisons centre was consulted in 33,000 cases of acute intoxications. The most important groups are drugs (e.g. antidepressants, beta blockers and calcium channel blockers), chemical products (e.g. products containing surfactant, corrosive substances and toxic alcohols like methanol), plants and recreational drugs. Intoxications are relevant in acute medicine. Some substances can cause fatal intoxications. Important antidotes are naloxone for opiods, acetylcystein for paracetamol, fomepizole and ethanol for toxic alcohols and diazepam for intoxications caused by chloroquine. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Do continued antidepressants protect against dementia in patients with severe depressive disorder?

PubMed

Kessing, Lars Vedel; Forman, Julie Lyng; Andersen, Per Kragh

2011-11-01

Studies on humans show that depressive disorder is associated with an increased risk of developing cognitive dysfunction, and animal studies suggest that antidepressants may have neuroprotective abilities. On the basis of these observations, it was hypothesized that treatment with antidepressants may decrease the risk of developing dementia in patients with depression. We investigated whether continued treatment with antidepressants is associated with a decreased rate of dementia in a population of patients discharged from psychiatric healthcare service with a diagnosis of depression. We used register data on all prescribed antidepressants in all patients discharged from psychiatric healthcare service with a diagnosis of depression and with subsequent diagnoses of dementia in Denmark from 1995 to 2005. A total of 37 658 patients with a diagnosis of depression at their first psychiatric contact and who were exposed to antidepressants after discharge were included in the study. A total of 2007 patients (5.3%) were subsequently diagnosed with dementia of any kind. The rate of dementia decreased during periods of two or more prescriptions of older antidepressants compared with the period of only one prescription of older antidepressants [relative risk (RR)=0.83 (95% confidence interval (CI)=0.70-0.98)]. This finding was replicated with Alzheimer's disease as the outcome [RR=0.66 (95% CI=0.47-0.94)] but not with dementia of other kinds as the outcome [RR=0.88 (95% CI=0.73-1.06)]. In contrast, during periods of continued use of selective serotonin reuptake inhibitors or newer nonselective serotonin reuptake inhibitors, the rate of dementia was not decreased, regardless of the subtype of dementia. It was concluded that continued long-term treatment with older antidepressants is associated with a reduced rate of dementia in patients treated in psychiatric healthcare settings, whereas continued treatment with other kinds of antidepressants is not. Methodological reasons for

Antidepressant-like effects of the cannabinoid receptor ligands in the forced swimming test in mice: mechanism of action and possible interactions with cholinergic system.

PubMed

Kruk-Slomka, Marta; Michalak, Agnieszka; Biala, Grazyna

2015-05-01

The purpose of the experiments was to explore the role of the endocannabinoid system, through cannabinoid (CB) receptor ligands, nicotine and scopolamine, in the depression-related responses using the forced swimming test (FST) in mice. Our results revealed that acute injection of oleamide (10 and 20 mg/kg), a CB1 receptor agonist, caused antidepressant-like effect in the FST, while AM 251 (0.25-3 mg/kg), a CB1 receptor antagonist, did not provoke any effect in this test. Moreover, acute administration of both CB2 receptor agonist, JWH 133 (0.5 and 1 mg/kg) and CB2 receptor antagonist, AM 630 (0.5 mg/kg), exhibited antidepressant action. Antidepressant effects of oleamide and JWH 133 were attenuated by acute injection of both non-effective dose of AM 251, as well as AM 630. Among the all CB compounds used, only the combination of non-effective dose of oleamide (2.5 mg/kg) with non-effective dose of nicotine (0.5 mg/kg) caused an antidepressant effect. However, none of the CB receptor ligands, had influence on the antidepressant effects provoked by nicotine (0.2 mg/kg) injection. In turn, the combination of non-effective dose of oleamide (2.5 mg/kg); JWH (2 mg/kg) or AM 630 (2 mg/kg), but not of AM 251 (0.25 mg/kg), with non-effective dose of scopolamine (0.1 mg/kg), exhibited antidepressant properties. Indeed, all of the CB compounds used, intensified the antidepressant-like effects induced by an acute injection of scopolamine (0.3 mg/kg). Our results provide clear evidence that the endocannabinoid system participates in the depression-related behavior and through interactions with cholinergic system modulate these kind of responses. Copyright © 2015 Elsevier B.V. All rights reserved.

The use of statins for the treatment of depression in patients with acute coronary syndrome

PubMed Central

Kim, S W; Bae, K Y; Kim, J M; Shin, I S; Hong, Y J; Ahn, Y; Jeong, M H; Berk, M; Yoon, J S

2015-01-01

This study aimed to investigate the effect of statins for the treatment of depression in individuals with acute coronary syndrome (ACS). We used 1-year follow-up data of a 24-week double-blind, placebo-controlled trial of escitalopram and a naturalistic prospective observational cohort study. Of 446 participants with comorbid depressive disorders and ACS at baseline, 300 participated in a randomised escitalopram trial and the remaining 146 participated in a naturalistic observational study. The participants in the two studies were approached for a 1-year follow-up investigation. Treatment response rates, defined as a ⩾50% reduction in the Hamilton Depression Rating Scale (HAM-D) and Beck Depression Inventory (BDI) scores, were used as the outcome variables. In the escitalopram trial, both HAM-D and BDI response rates were highest in patients taking escitalopram and statins together and lowest in patients receiving neither medication. Logistic regression analyses revealed that statin use was significantly associated with higher response rates on both the HAM-D and BDI at 1 year, whereas no such associations were found for escitalopram. In the naturalistic observational study, the response rates at 1 year did not differ significantly by statin use. Instead, the HAM-D response rate was significantly higher in patients taking lipophilic statins than in those who did not. In conclusion, statins may be effective for the treatment of depression independent of medical status and escitalopram use, and they may potentiate the antidepressant action of serotonergic antidepressants in patients with ACS. PMID:26285130

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.

[Clinical Applications of Peripheral Markers of Response in Antidepressant Treatment: Neurotrophins and Cytokines].

PubMed

Bermúdez, Constanza Mendoza

2012-03-01

Explanatory theories of depression have advanced in recent decades from the monoaminergic hypothesis to neurogenesis alterations to the neurohormonal hypothesis that includes the dysfunction of the inflammatory response. Currently there is a growing interest in the development of biomarkers that can contribute to diagnosis and proper treatment. To describe the role of neurotrophins such as brain-derived neurotrophic factor (BDNF) and cytokines in the pathophysiology of depressive disorder in addition to reviewing and analyzing evidence about their clinical application as biomarkers of antidepressant therapy. Relevant data research in several databases. In recent years evidence of alterations in neurogenesis mediated by the expression of BDNF in the hippocampus in the pathophysiology of depression has increased and there is ample evidence that BDNF is a marker of the diagnosis of depressive disorder and also of treatment effectiveness. There is little information about other neurotrophins. There has also been increased interest in relation to depression as an "inflammatory disease" and the link with cytokines in its pathogenesis. Evidence has been found for the usefulness of some cytokines especially IL-1 (interleukin 1), IL-6 (interleukin 6), and TNF (tumor necrosis factor) as biomarkers of antidepressant drug response in humans. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Attenuation of acute restraint stress-induced depressive like behavior and hippocampal alterations with protocatechuic acid treatment in mice.

PubMed

Thakare, Vishnu N; Dhakane, Valmik D; Patel, Bhoomika M

2017-04-01

Protocatechuic acid ethyl ester (PCA), a phenolic compound, exhibits neuroprotective effects through improving endogenous antioxidant enzymatic and nonezymatic system. Based on the role of oxidative stress in modulating depressive disorders and the relationship between neuroprotective and antioxidant potential of PCA, we studied if its antidepressant like effect is associated by modulation of cerebral cortex and hippocampal antioxidant alterations. Acute restraint stress (ARS) is known to induce depressive like behavior by neuronal oxidative damage in mice. Swiss albino mice subjected to ARS exhibited an increased immobility time in forced swim test, elevated serum corticosterone and produced oxidative stress dependent alterations in cerebral cortex and hippocampus mainly increased thiobarbituric acid reactive substances and reduced catalase (CAT), superoxide dismutase (SOD) activity. Treatment with PCA was able to prevent stress induced immobility time in forced swim test without altering locomotor activity in mice. Further, PCA treatment attenuated the elevation of serum corticosterone, lipid peroxidation and restored enzymatic antioxidants in cerebral cortex and hippocampus in ARS mice. Altogether, the experimental findings demonstrate the notion that PCA exhibit antidepressant like activity might be related, at least in part, to its capability of modulating antioxidant defense system and oxidative damage induced by ARS in cerebral cortex and hippocampus in mice and thus maintain the pro-/anti-oxidative homeostasis.

Antidepressant-like activity of resveratrol treatment in the forced swim test and tail suspension test in mice: the HPA axis, BDNF expression and phosphorylation of ERK.

PubMed

Wang, Zhen; Gu, Jianhua; Wang, Xueer; Xie, Kai; Luan, Qinsong; Wan, Nianqing; Zhang, Qun; Jiang, Hong; Liu, Dexiang

2013-11-01

Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities. There is only limited information about the antidepressant-like effect of resveratrol. The present study assessed whether resveratrol treatment (20, 40 and 80mg/kg, i.p., 21days) has an antidepressant-like effect on the forced swim test (FST) and tail suspension test (TST) in mice and examined what its molecular targets might be. The results showed that resveratrol administration produced antidepressant-like effects in mice, evidenced by the reduced immobility time in the FST and TST, while it had no effect on the locomotor activity in the open field test. Resveratrol treatment significantly reduced serum corticosterone levels, which had been elevated by the FST and TST. Moreover, resveratrol increased brain-derived neurotrophic factor (BDNF) protein and extracellular signal-regulated kinase (ERK) phosphorylation levels in the prefrontal cortex and hippocampus. All of these antidepressant-like effects of resveratrol were essentially similar to those observed with the clinical antidepressant, fluoxetine. These results suggest that the antidepressant-like effects of resveratrol in the FST and TST are mediated, at least in part, by modulating hypothalamic-pituitary-adrenal axis, BDNF and ERK phosphorylation expression in the brain region of mice. © 2013.

Antidepressants Increase REM Sleep Muscle Tone in Patients with and without REM Sleep Behavior Disorder.

PubMed

McCarter, Stuart J; St Louis, Erik K; Sandness, David J; Arndt, Katlyn; Erickson, Maia; Tabatabai, Grace; Boeve, Bradley F; Silber, Michael H

2015-06-01

REM sleep behavior disorder (RBD) is associated with antidepressant treatment, especially in younger patients; but quantitative REM sleep without atonia (RSWA) analyses of psychiatric RBD patients remain limited. We analyzed RSWA in adults receiving antidepressants, with and without RBD. We comparatively analyzed visual, manual, and automated RSWA between RBD and control groups. RSWA metrics were compared between groups, and regression was used to explore associations with clinical variables. Tertiary-care sleep center. Participants included traditional RBD without antidepressant treatment (n = 30, 15 Parkinson disease [PD-RBD] and 15 idiopathic); psychiatric RBD receiving antidepressants (n = 30); and adults without RBD, including antidepressant-treated psychiatric (n = 30), untreated psychiatric (n = 15), and OSA (n = 60) controls. N/A. RSWA was highest in traditional and psychiatric RBD, intermediate in treated psychiatric controls, and lowest in untreated psychiatric and OSA controls (P < 0.01). RSWA distribution and type also differed between antidepressant-treated patients having higher values in anterior tibialis, and PD-RBD with higher submentalis and tonic RSWA. Psychiatric RBD had significantly younger age at onset than traditional RBD patients (P < 0.01). Antidepressant treatment was associated with elevated REM sleep without atonia (RSWA) even without REM sleep behavior disorder (RBD), suggesting that antidepressants, not depression, promote RSWA. Differences in RSWA distribution and type were also seen, with higher anterior tibialis RSWA in antidepressant-treated patients and higher tonic RSWA in Parkinson disease-RBD patients, which could aid distinction between RBD subtypes. These findings suggest that antidepressants may mediate different RSWA mechanisms or, alternatively, that RSWA type and distribution evolve during progressive neurodegeneration. Further prospective RSWA analyses are necessary to clarify the relationships between antidepressant

Betaine enhances antidepressant-like, but blocks psychotomimetic effects of ketamine in mice.

PubMed

Lin, Jen-Cheng; Lee, Mei-Yi; Chan, Ming-Huan; Chen, Yi-Chyan; Chen, Hwei-Hsien

2016-09-01

Ketamine is emerging as a new hope against depression, but ketamine-associated psychotomimetic effects limit its clinical use. An adjunct therapy along with ketamine to alleviate its adverse effects and even potentiate the antidepressant effects might be an alternative strategy. Betaine, a methyl derivative of glycine and a dietary supplement, has been shown to have antidepressant-like effects and to act like a partial agonist at the glycine site of N-methyl-D-aspartate receptors (NMDARs). Accordingly, betaine might have potential to be an adjunct to ketamine treatment for depression. The antidepressant-like effects of ketamine and betaine were evaluated by forced swimming test and novelty suppressed feeding test in mice. Both betaine and ketamine produced antidepressant-like effects. Furthermore, we determined the effects of betaine on ketamine-induced antidepressant-like and psychotomimetic behaviors, motor incoordination, hyperlocomotor activity, and anesthesia. The antidepressant-like responses to betaine combined with ketamine were stronger than their individual effects. In contrast, ketamine-induced impairments in prepulse inhibition, novel object recognition test, social interaction, and rotarod test were remarkably attenuated, whereas ketamine-induced hyperlocomotion and loss of righting reflex were not affected by betaine. These findings revealed that betaine could enhance the antidepressant-like effects, yet block the psychotomimetic effects of ketamine, suggesting that betaine can be considered as an add-on therapy to ketamine for treatment-resistant depression and suitable for the treatment of depressive symptoms in patients with schizophrenia.

Atypical Antidepressants

MedlinePlus

... dangerous reactions when combined with certain medications or herbal supplements. Serotonin syndrome. Rarely, an antidepressant can cause high ... antidepressants, certain pain or headache medications, and the herbal supplement St. John's wort. Symptoms of serotonin syndrome include ...

Antidepressant Use among Blacks and Whites in the United States

PubMed Central

González, Hector M.; Croghan, Thomas W.; West, Brady T.; Tarraf, Wassim; Williams, David R.; Nesse, Randolph; Taylor, Robert Joseph; Hinton, Ladson; Neighbors, Harold W.; Jackson, James S.

2008-01-01

Objective The study objective was to estimate the prevalence and correlates of antidepressant use by black and white Americans. Methods Data from the Collaborative Psychiatric Epidemiology Surveys (CPES) were analyzed to calculate nationally representative estimates of antidepressant use by black and white Americans. Setting The 48 coterminous United States was the setting. Participants Household residents ages 18 years and older (N=9,723) participated in the study. Main Outcomes The primary outcome was past-year antidepressant use (n=1,004). Results Among individuals with 12-month depressive and anxiety disorders (n=516), blacks (14.6%) had significantly lower (p < 0.001) antidepressant use than whites (32.4%). Depression severity was significantly associated with higher antidepressant use for whites, but not blacks. Psychiatric disorders and vascular disease significantly increased the odds of past-year antidepressant use. The increased prevalence of antidepressant use associated with vascular disease was independent of diagnosable psychiatric disorders. Among respondents not meeting criteria for 12-month depressive and anxiety disorders, lifetime depressive and anxiety disorders and vascular disease significantly increased the odds of antidepressant use. Conclusions Few white and fewer black Americans with depressive and anxiety disorders receive antidepressant treatment. Higher depression severity was associated with more antidepressant use for whites, but not blacks. Antidepressant use was associated with medical conditions related to vascular disease, and these medical conditions were independent of coexisting psychiatric conditions. The results also indicate that many antidepressants are used for maintenance pharmacotherapy for depressive and anxiety disorders as well as common medical conditions associated with vascular disease. PMID:18832498

Early response to venlafaxine antidepressant correlates with lower ACTH levels prior to pharmacological treatment.

PubMed

Araya, A V; Rojas, P; Fritsch, R; Rojas, R; Herrera, L; Rojas, G; Gatica, H; Silva, H; Fiedler, J L

2006-12-01

A link between stressful life events and development or exacerbation of depression has been established via a large body of evidence. An alteration in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis in depression has also been associated with an increase in cortisol secretion. As arginine-vasopressin (AVP) plays an important role in the activation of HPA axis during stress, the present study investigated ACTH and cortisol secretory response induced by an AVP-related peptide desmopressin (ddAVP) in patients with major depression. Prior to antidepressant treatment, endocrinological parameters were evaluated and correlated with the clinical response to venlafaxine treatment, which offers a dual antidepressant action. Depressive patients with no other psychiatric pathology were evaluated with 17-item Hamilton Depression Scale (HAM-D) in order to follow-up the response to venlafaxine. After 1 wk of treatment, 60% of patients reduced their initial HAM-D score to at least 25%; this group was classified as early responders. The other group (40%) started to reduce significantly their HAM-D score after 3 wk of treatment and was classified as late responders. After 6 wk of treatment both groups have reduced HAM-D score to at least 25% of the baseline score. Prior to the pharmacological treatment, both early and late responders showed salivary cortisol rhythm and urinary free cortisol (UFC) in 24-h similar to healthy subjects. However, we did observe differences in basal ACTH secretion, showing that the late responder group had higher basal ACTH than both early responders and controls. The ddAVP challenge promoted a robust secretion of ACTH only in late responders, suggesting a different sensitivity of pituitary vasopressin receptor. The differences in clinical response to venlafaxine among depressive patients seem to be related to endocrinological parameters.

Antidepressant-like properties of sarizotan in experimental Parkinsonism.

PubMed

Zhang, Xiaoqun; Egeland, Martin; Svenningsson, Per

2011-12-01

Depression and anxiety are common symptoms in Parkinson's disease for which there are no optimal treatments. Sarizotan, an agonist at serotonin receptors and partial agonist at dopamine D₂-like receptors, has shown antidyskinetic effects in Parkinson's disease. Based on its pharmacological profile, we hypothesized that sarizotan could also have antidepressant-like properties. Examine effects of sarizotan on behavioral and histological measures known to be regulated by established antidepressants in normal and unilaterally 6-hydroxydopamine-lesioned rats. Sarizotan was found to significantly reduce immobility in the modified forced swim test, a measure of antidepressant-like activity, but had no effects on thigmotaxis or corner time, measures of anxiety-like behavior, in the unilaterally 6-hydroxydopamine-lesioned rats. At the same dose, sarizotan counteracted L: -DOPA/benserazide-induced supersentitized rotational behavior and dyskinesias without significantly affecting L: -DOPA/benserazide-induced locomotion. At the histological level, sarizotan alone or in combination with L: -DOPA/benserazide stimulated cell proliferation, measured by bromodeoxyuridine incorporation or Ki-67 staining, both in the subgranular zone of the dentate gyrus and in the subventricular zone of the striatum in the 6-hydroxydopamine-lesioned hemisphere. Likewise, combined sarizotan and L: -DOPA/benserazide treatment stimulated doublecortin levels in the subgranular zone of the dentate gyrus. These significant effects of sarizotan in the modified forced swim test and on cell proliferation are reminiscent of those found after various antidepressant therapies. These data suggest that sarizotan may have some antidepressant-like and restorative properties in Parkinsonism.

Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics.

PubMed

Selle, V; Schalkwijk, S; Vázquez, G H; Baldessarini, R J

2014-03-01

Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants. We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants, second-generation antipsychotics, or lithium for acute major depressive episodes in patients diagnosed with type I or II bipolar disorder and applied random-effects meta-analysis to evaluate their efficacy, comparing outcomes based on standardized mean drug-placebo differences (SMD) in improvement, relative response rates (RR), and number-needed-to-treat (NNT). We identified 24 trials of 10 treatments (lasting 7.5 weeks, with ≥ 50 collaborating sites/trial) that met eligibility criteria: lamotrigine (5 trials), quetiapine (5), valproate (4), 2 each for aripiprazole, olanzapine, ziprasidone, and 1 each for carbamazepine, lithium, lurasidone, and olanzapine-fluoxetine. Overall, pooled drug-over-placebo responder-rate superiority (RR) was moderate (29% [CI: 19-40%]), and NNT was 8.2 (CI: 6.4-11). By SMD, apparent efficacy ranked: olanzapine + fluoxetine ≥ valproate > quetiapine > lurasidone > olanzapine, aripiprazole, and carbamazepine; ziprasidone was ineffective, and lithium remains inadequately studied. Notably, drugs were superior to placebo in only 11/24 trials (5/5 with quetiapine, 2/4 with valproate), and only lamotrigine, quetiapine and valproate had > 2 trials. Treatment-associated mania-like reactions were uncommon (drugs: 3.7%; placebo: 4.7%). Controlled trials of non-antidepressant treatments for bipolar depression remain scarce, but findings with olanzapine-fluoxetine, lurasidone, quetiapine, and perhaps carbamazepine and valproate were encouraging; lithium requires adequate testing. © Georg Thieme Verlag KG Stuttgart · New York.

In vitro antioxidant activity and in vivo antidepressant-like effect of α-(phenylselanyl) acetophenone in mice.

PubMed

Gerzson, Mariana Freire Barbieri; Victoria, Francine N; Radatz, Cátia S; de Gomes, Marcelo G; Boeira, Silvana P; Jacob, Raquel G; Alves, Diego; Jesse, Cristiano Ricardo; Savegnago, Lucielli

2012-07-01

In this study, the antioxidant and antidepressant-like effects of α-(phenylselanyl) acetophenone (PSAP), an organoselenium compound, were investigated. To assess the in vitro antioxidant properties, PSAP was evaluated in four test systems (DPPH, ABTS, FRAP and inhibition of lipid peroxidation). PSAP (100-500 μM) showed potent antioxidant activity and protected against lipid peroxidation. Additionally, we investigated whether PSAP, when administered in mice (100, 200 and 400mg/kg, per oral, p.o.), could cause acute toxicity. Our results demonstrated that PSAP did not cause the death of any animal, significantly reduce body weight or cause any oxidative tissue stress following treatment. This study also evaluated the effect of PSAP (0.1-10 mg/kg, p.o) on mice in a forced swim test (FST) and tail suspension test (TST), assays that are predictive of depressant activity and motor activity in the open-field. PSAP (5-10 mg/kg) significantly reduced immobility time in the FST and TST without affecting motor activity. In addition, the antidepressant-like effect caused by PSAP (5m/kg, p.o) in mice during the TST was dependent on an interaction with the serotonergic system (5-HT(1A) receptors), but not with the noradrenergic, dopaminergic or adenosinergic system. Together, these results suggest that PSAP possesses antioxidant and antidepressant-like properties and may be of interest as a therapeutic agent for the treatment of depressive disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

Association of cerebrovascular events with antidepressant use: a case-crossover study.

PubMed

Wu, Chi-Shin; Wang, Sheng-Chang; Cheng, Yu-Cheng; Gau, Susan Shur-Fen

2011-05-01

The authors sought to assess the risk of cerebrovascular events associated with use of antidepressant medications. The authors conducted a case-crossover study of 24,214 patients with stroke enrolled in the National Health Insurance Research Database in Taiwan from 1998 to 2007. The authors compared the rates of antidepressant use during case and control time windows of 7, 14, and 28 days. Adjustments were made for time-dependent variables, such as health system utilization and proposed confounding medications. Stratified analyses were performed for valuing the interaction between the stroke risk of antidepressant use and age, sex, presence of mood disorder, stroke type, severity of chronic illness, and duration of antidepressant treatment. A conditional logistic regression model was used to determine the odds of antidepressant use during case time windows. The adjusted odds ratio of stroke risk with antidepressant exposure was 1.48 (95% confidence interval=1.37-1.59) using 14-day time windows. Stroke risk was negatively associated with the number of antidepressant prescriptions reported. Use of antidepressants with high inhibition of the serotonin transporter was associated with a greater risk of stroke than use of other types of antidepressants. These findings suggest that antidepressant use may be associated with an increased risk of stroke. However, the underlying mechanisms remain unclear.

Antidepressant drugs can modify cytotoxic action of temozolomide.

PubMed

Bielecka, A M; Obuchowicz, E

2017-09-01

Cancer patients often require antidepressant treatment due to comorbid depressive disorder. However, recent studies have demonstrated that antidepressant drugs affect the efficacy of chemotherapy and promote progression of cancer. Apart from the main mood-improving effect, antidepressant drugs also produce analgesic, anxiolytic, hypnotic and pro-cognitive actions. Patients suffering from brain cancer constitute the greatest percentage of depressive cancer patients. However, vital safety and efficacy issues related to combined therapy with temozolomide, the first-line cytostatic in patients diagnosed with glioblastoma multiforme, and antidepressant drugs have yet to be addressed. The aim of the present studies was to evaluate the effect of three antidepressant drugs (imipramine, fluoxetine and tranylcypromine) on the cytotoxic efficacy of temozolomide on T98G cells, a human glioblastoma cell line. In our experiments, we used a complex experimental in vitro system to mimic the instability of a tumour's oxygen supply, thereby reproducing conditions that occur inside the tumour. The effect of the interaction between temozolomide and antidepressant drugs on viability, apoptosis and intensity of divisions of glioblastoma cells was evaluated under different oxygen conditions. The results of our studies demonstrated that imipramine and tranylcypromine reduced the cytotoxic efficacy of temozolomide under some oxygen conditions while fluoxetine did not demonstrate such effects. © 2016 John Wiley & Sons Ltd.

Possible involvement of ATP-sensitive potassium channels in the antidepressant-like effect of baclofen in mouse forced swimming test.

PubMed

Nazari, Seyedeh Khadijeh; Nikoui, Vahid; Ostadhadi, Sattar; Chegini, Zahra Hadi; Oryan, Shahrbanoo; Bakhtiarian, Azam

2016-12-01

Previous study confirmed that the acute treatment with baclofen by inhibition of the l-arginine-nitric oxide (NO) pathway diminished the immobility behavior in the forced swimming test (FST) of mice. Considering the involvement of NO in adenosine triphosphate (ATP)-sensitive potassium channels (K ATP ), in the present study we investigated the involvement of K ATP channels in antidepressant-like effect of baclofen in the forced swimming test (FST). After assessment of locomotor behavior in the open-field test (OFT), FST was applied for evaluation of the antidepressant-like activity of baclofen in mice. Baclofen at different doses (0.1, 0.3, and 1mg/kg) and fluoxetine (20mg/kg) were administrated by intraperitoneal (ip) route, 30min before the FST or OFT. To clarify the probable involvement of K ATP channels, after determination of sub-effective doses of glibenclamide as a K ATP channel blocker and cromakalim, as an opener of these channels, they were co-administrated with the sub-effective and effective doses of baclofen, respectively. Baclofen at dose 1mg/kg significantly decreased the immobility behavior of mice similar to fluoxetine (20mg/kg). Co-administration of gelibenclamide sub-effective dose (1mg/kg) with baclofen (0.1mg/kg) showed a synergistic antidepressant-like effect in the FST. Also, sub-effective dose of cromakalim (0.1mg/kg) inhibited the antidepressant-like effect of baclofen (1mg/kg) in the FST. All aforementioned treatments had not any impact on the locomotor movement of mice in OFT. Our study for the first time revealed that antidepressant-like effect of baclofen on mice is K ATP -dependent, and baclofen seems that exert this effect by blocking the K ATP channels. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Antidepressant use and cognitive decline in community-dwelling elderly people - The Three-City Cohort.

PubMed

Carrière, Isabelle; Norton, Joanna; Farré, Amandine; Wyart, Marilyn; Tzourio, Christophe; Noize, Pernelle; Pérès, Karine; Fourrier-Réglat, Annie; Ritchie, Karen; Ancelin, Marie Laure

2017-04-19

Cognitive impairment is very common in late-life depression, principally affecting executive skills and information processing speed. The aim of the study was to examine the effect of antidepressant treatment on cognitive performances over a 10-year period. The community-based cohort included 7381 participants aged 65 years and above. Five cognitive domains (verbal fluency, psychomotor speed, executive function, visuospatial skills and global cognition) were assessed up to five times over 10 years of follow-up. Treatment groups included participants under a specific antidepressant class at both baseline and the first follow-up and their follow-up cognitive data were considered until the last consecutive follow-up with a report of antidepressant use of the same class. Linear mixed models were used to compare baseline cognitive performance and cognitive decline over time according to antidepressant treatment. The models were adjusted for multiple confounders including residual depressive symptoms assessed by the Center for Epidemiologic Studies-Depression scale. At baseline, 4.0% of participants were taking antidepressants. Compared to non-users, tricyclic antidepressant users had lower baseline performances in verbal fluency, visual memory and psychomotor speed, and selective serotonin reuptake inhibitor users in verbal fluency and psychomotor speed. For the two other cognitive abilities, executive function and global cognition, no significant differences were found at baseline irrespective of the antidepressant class. Regarding changes over time, no significant differences were observed in comparison with non-users whatever the cognitive domain, except for a slight additional improvement over the follow-up in verbal fluency skills for tricyclic antidepressant users. In this large elderly general population cohort, we found no evidence for an association between antidepressant use and post-treatment cognitive decline over 10 years of follow-up in various

Serotonin 5-HT4 receptors: A new strategy for developing fast acting antidepressants?

PubMed

Vidal, Rebeca; Castro, Elena; Pilar-Cuéllar, Fuencisla; Pascual-Brazo, Jesús; Díaz, Alvaro; Rojo, María Luisa; Linge, Raquel; Martín, Alicia; Valdizán, Elsa M; Pazos, Angel

2014-01-01

The regulation of the activity of brain monoaminergic systems has been the focus of attention of many studies since the first antidepressant drug emerged 50 years ago. The search for novel antidepressants is deeply linked to the search for fast-acting strategies, taking into account that 2-4 weeks of treatment with classical antidepressant are required before clinical remission of the symptoms becomes evident. In the recent years several hypotheses have been proposed on the basis of the existence of alterations in brain synaptic plasticity in major depression. Recent evidences support a role for 5-HT4 receptors in the pathogenesis of depression as well as in the mechanism of action of antidepressant drugs. In fact, chronic treatment with antidepressant drugs appears to modulate, at different levels, the signaling pathway associated to 5-HT4 receptors, as well as their levels of expression in the brain. Moreover, several experimental studies have identified this receptor subtype as a promising new target for fast-acting antidepressant strategy: the administration of partial agonists of this receptor induces a number of responses similar to those observed after chronic treatment with classical antidepressants, but with a rapid onset of action. They include efficacy in behavioral models of depression, rapid desensitization of 5-HT1A autoreceptors, and modifications in the expression of several molecular markers of brain neuroplasticity. Although much work remains to be done in order to clarify the real therapeutic potential of these drugs, the evidences reviewed below support the hypothesis that 5-HT4 receptor partial agonists could behave as rapid and effective antidepressants.

Vascular Endothelial Growth Factor-dependent Spinogenesis Underlies Antidepressant-like Effects of Enriched Environment*

PubMed Central

Huang, Yu-Fei; Yang, Chih-Hao; Huang, Chiung-Chun; Hsu, Kuei-Sen

2012-01-01

Current antidepressant treatments remain limited by poor efficacy and a slow onset of action. Increasing evidence demonstrates that enriched environment (EE) treatment can promote structural and behavioral plasticity in the brain and dampen stress-induced alterations of neuroplasticity. Here, we have examined whether short term exposure to EE is able to produce antidepressant-like effects. Our results show that housing adult mice in an EE cage for 7 days led to antidepressant-like behavioral profiles and a significant increase in the number of dendritic spines in hippocampal CA1 pyramidal neurons. These EE-induced antidepressant-like effects are primarily attributed to increased vascular endothelial growth factor (VEGF) expression through a hypoxia-inducible factor-1α (HIF-1α)-mediated transcriptional mechanism. Blockade of HIF-1α synthesis by lentiviral infection with HIF-1α small hairpin RNAs completely blocked the increase in expression of VEGF and the antidepressant-like effects induced by EE. Moreover, no significant antidepressant-like effects were observed with EE treatment in VEGF receptor 2 (Flk-1) knock-out mice. The increase in HIF-1α expression in the hippocampus induced by EE was associated with a decrease in endogenous levels of microRNA-107 (miR-107). Overexpression of miR-107 in the hippocampus completely blocked EE-induced HIF-1α expression and the antidepressant-like effects. These results support a model in which the down-regulation of miR-107, acting through HIF-1α, mediates VEGF-dependent spinogenesis to underlie the EE-induced antidepressant-like effects. PMID:23074224

Beyond Ketamine: New Approaches to the Development of Safer Antidepressants.

PubMed

Chaki, Shigeyuki

2017-01-01

Ketamine has been reported to exert rapid and sustained antidepressant effects in patients with depression, including patients with treatment-resistant depression. However, ketamine has several drawbacks such as psychotomimetic/dissociative symptoms, abuse potential and neurotoxicity, all of which prevent its routine use in daily clinical practice. Therefore, development of novel agents with fewer safety and usage concerns for the treatment of depression has been actively investigated. From this standpoint, searching for active substances (stereoisomers and metabolites) and agents acting on the N-methyl-D-aspartate (NMDA) receptor have recently gained much attention. The first approach includes stereoisomers of ketamine, (R)-ketamine and (S)-ketamine. Although (S)-ketamine has been considered as the active stereoisomer of racemic ketamine, recently, (R)-ketamine has been demonstrated to exert even more prolonged antidepressant effects in animal models than (S)-ketamine. Moreover, ketamine is rapidly metabolized into several metabolites, and some metabolites are speculated as being active substances exerting antidepressant effects. Of such metabolites, one in particular, namely, (2R,6R)-hydroxynorketamine, has been reported to be responsible for the antidepressant effects of ketamine. The second approach includes agents acting on the NMDA receptor, such as glycine site modulators and GluN2B subunit-selective antagonists. These agents have been tested in patients with treatment-resistant depression, and have been found to exhibit rapid antidepressant effects like ketamine. The above approaches may be useful to overcome the drawbacks of ketamine. Elucidation of the mechanisms of action of ketamine may pave the way for the development of antidepressant that are safer, but as potent and rapidly acting as ketamine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Beyond Ketamine: New Approaches to the Development of Safer Antidepressants

PubMed Central

Chaki, Shigeyuki

2017-01-01

Background: Ketamine has been reported to exert rapid and sustained antidepressant effects in patients with depression, including patients with treatment-resistant depression. However, ketamine has several drawbacks such as psychotomimetic/dissociative symptoms, abuse potential and neurotoxicity, all of which prevent its routine use in daily clinical practice. Methods: Therefore, development of novel agents with fewer safety and usage concerns for the treatment of depression has been actively investigated. From this standpoint, searching for active substances (stereoisomers and metabolites) and agents acting on the N-methyl-D-aspartate (NMDA) receptor have recently gained much attention. Results: The first approach includes stereoisomers of ketamine, (R)-ketamine and (S)-ketamine. Although (S)-ketamine has been considered as the active stereoisomer of racemic ketamine, recently, (R)-ketamine has been demonstrated to exert even more prolonged antidepressant effects in animal models than (S)-ketamine. Moreover, ketamine is rapidly metabolized into several metabolites, and some metabolites are speculated as being active substances exerting antidepressant effects. Of such metabolites, one in particular, namely, (2R,6R)-hydroxynorketamine, has been reported to be responsible for the antidepressant effects of ketamine. The second approach includes agents acting on the NMDA receptor, such as glycine site modulators and GluN2B subunit-selective antagonists. These agents have been tested in patients with treatment-resistant depression, and have been found to exhibit rapid antidepressant effects like ketamine. Conclusion: The above approaches may be useful to overcome the drawbacks of ketamine. Elucidation of the mechanisms of action of ketamine may pave the way for the development of antidepressant that are safer, but as potent and rapidly acting as ketamine. PMID:28228087

Depressed College Students and Tricyclic Antidepressant Therapy.

ERIC Educational Resources Information Center

Brown, Ben Maurice

1978-01-01

Depressed college students representing several distinct diagnostic groups were studied. Evidence indicates that patients with depressive neurosis show optimal treatment outcomes following tricyclic antidepressant therapy. (JMF)

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

Empirical testing of two models for staging antidepressant treatment resistance.

PubMed

Petersen, Timothy; Papakostas, George I; Posternak, Michael A; Kant, Alexis; Guyker, Wendy M; Iosifescu, Dan V; Yeung, Albert S; Nierenberg, Andrew A; Fava, Maurizio

2005-08-01

An increasing amount of attention has been paid to treatment resistant depression. Although it is quite common to observe nonremission to not just one but consecutive antidepressant treatments during a major depressive episode, a relationship between the likelihood of achieving remission and one's degree of resistance is not clearly known at this time. This study was undertaken to empirically test 2 recent models for staging treatment resistance. Psychiatrists from 2 academic sites reviewed charts of patients on their caseloads. Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) scales were used to measure severity of depression and response to treatment, and 2 treatment-resistant staging scores were classified for each patient using the Massachusetts General Hospital staging method (MGH-S) and the Thase and Rush staging method (TR-S). Out of the 115 patient records reviewed, 58 (49.6%) patients remitted at some point during treatment. There was a significant positive correlation between the 2 staging scores, and logistic regression results indicated that greater MGH-S scores, but not TR-S scores, predicted nonremission. This study suggests that the hierarchical manner in which the field has typically gauged levels of treatment resistance may not be strongly supported by empirical evidence. This study suggests that the MGH staging model may offer some advantages over the staging method by Thase and Rush, as it generates a continuous score that considers both number of trials and intensity/optimization of each trial.

Utility of event-related potentials in predicting antidepressant treatment response: An iSPOT-D report.

PubMed

van Dinteren, Rik; Arns, Martijn; Kenemans, Leon; Jongsma, Marijtje L A; Kessels, Roy P C; Fitzgerald, Paul; Fallahpour, Kamran; Debattista, Charles; Gordon, Evian; Williams, Leanne M

2015-11-01

It is essential to improve antidepressant treatment of major depressive disorder (MDD) and one way this could be achieved is by reducing the number of treatment steps by employing biomarkers that can predict treatment outcome. This study investigated differences between MDD patients and healthy controls in the P3 and N1 component from the event-related potential (ERP) generated in a standard two-tone oddball paradigm. Furthermore, the P3 and N1 are investigated as predictors for treatment outcome to three different antidepressants. In the international Study to Predict Optimized Treatment in Depression (iSPOT-D)--a multi-center, international, randomized, prospective practical trial--1008 MDD participants were randomized to escitalopram, sertraline or venlafaxine-XR. The study also recruited 336 healthy controls. Treatment response and remission were established after eight weeks using the 17-item Hamilton Rating Scale for Depression. P3 and N1 latencies and amplitudes were analyzed using a peak-picking approach and further replicated by using exact low resolution tomography (eLORETA). A reduced P3 was found in MDD patients compared to controls by a peak-picking analysis. This was validated in a temporal global field power analysis. Source density analysis revealed that the difference in cortical activity originated from the posterior cingulate and parahippocampal gyrus. Male non-responders to venlafaxine-XR had significantly smaller N1 amplitudes than responders. This was demonstrated by both analytical methods. Male non-responders to venlafaxine-XR had less activity originating from the left insular cortex. The observed results are discussed from a neural network viewpoint. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Suppressive immunoregulatory effects of three antidepressants via inhibition of the nuclear factor-κB activation assessed using primary macrophages of carp (Cyprinus carpio)

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

Qiu, Wenhui

Antidepressants, having been applied for the treatment of major depressive disorder and other conditions for decades, are among the most commonly detected human pharmaceuticals in the aquatic environment. This study evaluated the immunotoxicity of acute exposure to environmentally relevant concentrations of amitriptyline, fluoxetine and mianserin using an in vitro primary macrophage model isolated from red common carp (Cyprinus carpio), and also explored their potential mechanisms of action. A potential suppressive immunoregulatory effect of antidepressant exposure was suggested based on the observed suppressive effects on oxidative stress parameters, bactericidal activity, NO production, and NO synthase activity, as well as pro-inflammatory cytokinemore » gene expression, and a significant stimulatory effect on anti-inflammatory interleukin-10 and interferon cytokine gene expression and ATPase activities in macrophages after 6 h-exposure to three individual antidepressants and a combination thereof. Notably, we also found these effects were significantly associated with a corresponding decrease in nuclear factor-κB (NF-κB) activity after antidepressants exposure, and the NF-κB antagonist significantly restrained the effects of antidepressants on gene expression of cytokines, indicating that antidepressants could alter the response of various immune-associated components via the inhibition of NF-κB. Moreover, time-dependent lethal concentrations of three antidepressants on primary macrophages were firstly determined at mg/L levels, and the synergetic effects of antidepressant mixtures were suggested and in particular, for some parameters including total antioxidant capacity and cytokine genes expression, they could be significantly affected by antidepressants exposure at concentrations as low as 10 ng/L, which together thereby revealed the potential risk of antidepressants to aquatic life. - Highlights: • Three different antidepressants all have

Antidepressant drugs and the risk of suicide in children and adolescents.

PubMed

Isacsson, Göran; Rich, Charles L

2014-04-01

Government agencies have issued warnings about the use of antidepressant medications in children, adolescents, and young adults since 2003. The statements warn that such medications may cause de novo 'suicidality' in some people. This review explores the data on the treatment of depression that led to these warnings and subsequent data that are relevant to the warnings. It also addresses the effectiveness of antidepressant treatment in general and the relationship of suicide rates to antidepressant treatment. It concludes that the decisions for the 'black box' warnings were based on biased data and invalid assumptions. Furthermore, the decisions were unsupported by the observational data regarding suicide in young people that existed in 2003. The following recommendations would seem to follow from these observations. First, drug authorities should re-evaluate the basis for their imposed warnings on antidepressant medicines, and analyze the actual public health consequences the warnings have had. In the absence of substantial evidence supporting the warnings, they should be removed. Second, physicians and other providers with prescription privileges should continue to be educated regarding the importance of aggressively treating depression in young people, using antidepressants when indicated. Third, physicians and other professionals who treat depressed young people must always be aware of the risk of suicide (albeit quite low) and observe them closely for any signs of increased risk of suicide. This is necessary regardless of the type of treatment being provided.

Cordance derived from REM sleep EEG as a biomarker for treatment response in depression--a naturalistic study after antidepressant medication.

PubMed

Adamczyk, Marek; Gazea, Mary; Wollweber, Bastian; Holsboer, Florian; Dresler, Martin; Steiger, Axel; Pawlowski, Marcel

2015-04-01

To evaluate whether prefrontal cordance in theta frequency band derived from REM sleep EEG after the first week of antidepressant medication could characterize the treatment response after 4 weeks of therapy in depressed patients. 20 in-patients (15 females, 5 males) with a depressive episode and 20 healthy matched controls were recruited into 4-week, open label, case-control study. Patients were treated with various antidepressants. No significant differences in age (responders (mean ± SD): 45 ± 22) years; non-responders: 49 ± 12 years), medication or Hamilton Depression Rating Scale (HAM-D) score (responders: 23.8 ± 4.5; non-responders 24.5 ± 7.6) at inclusion into the study were found between responders and non-responders. Response to treatment was defined as a ≥50% reduction of HAM-D score at the end of four weeks of active medication. Sleep EEG of patients was recorded after the first and the fourth week of medication. Cordance was computed for prefrontal EEG channels in theta frequency band during tonic REM sleep. The group of 8 responders had significantly higher prefrontal theta cordance in relation to the group of 12 non-responders after the first week of antidepressant medication. This finding was significant also when controlling for age, gender and number of previous depressive episodes (F1,15 = 6.025, P = .027). Furthermore, prefrontal cordance of all patients showed significant positive correlation (r = 0.52; P = .019) with the improvement of HAM-D score between the inclusion week and fourth week of medication. The results suggest that prefrontal cordance derived from REM sleep EEG could provide a biomarker for the response to antidepressant treatment in depressed patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Degradation and acute toxicity removal of the antidepressant Fluoxetine (Prozac(®)) in aqueous systems by electron beam irradiation.

PubMed

Silva, Vanessa Honda Ogihara; Dos Santos Batista, Ana Paula; Silva Costa Teixeira, Antonio Carlos; Borrely, Sueli Ivone

2016-06-01

Electron beam irradiation (EBI) has been considered an advanced technology for the treatment of water and wastewater, whereas very few previous investigations reported its use for removing pharmaceutical pollutants. In this study, the degradation of fluoxetine (FLX), an antidepressant marketed as Prozac(®), was investigated by using EBI at FLX initial concentration of 19.4 ± 0.2 mg L(-1). More than 90 % FLX degradation was achieved at 0.5 kGy, with FLX below the detection limit (0.012 mg L(-1)) at doses higher than 2.5 kGy. The elucidation of organic byproducts performed using direct injection mass spectrometry, along with the results of ion chromatography, indicated hydroxylation of FLX molecules with release of fluoride and nitrate anions. Nevertheless, about 80 % of the total organic carbon concentration remained even for 7.5 kGy or higher doses. The decreases in acute toxicity achieved 86.8 and 9.6 % for Daphnia similis and Vibrio fischeri after EBI exposure at 5 kGy, respectively. These results suggest that EBI could be an alternative to eliminate FLX and to decrease residual toxicity from wastewater generated in pharmaceutical formulation facilities, although further investigation is needed for correlating the FLX degradation mechanism with the toxicity results.

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

Antidepressants in the treatment of depression/depressive symptoms in cancer patients: a systematic review and meta-analysis

PubMed Central

2013-01-01

Background Over the past thirty years a number of studies have suggested that antidepressants can be effective in the treatment of depressive symptoms in patients with cancer. The aim of this paper was to review randomized controlled trials (RCTs) and to perform a meta-analysis in order to quantify their overall effect. Methods Pubmed and the Cochrane libraries were searched for the time period between 1980 and 2010. Results Nine RCTs were identified and reviewed. Six of them (with a total of 563 patients) fulfilled the criteria for meta-analysis, but exhibited an unclear risk for bias. The estimated effect size was 1.56 with 95% CI: 1.07- 2.28 (p= 0.021). There were no differences in discontinuation rates between antidepressants and placebo groups (RR= 0.86 with 95% CI 0.47- 1.56, p=0.62). Conclusions This meta-analysis suggests that antidepressants can be effective in treating depressive symptoms beside clinical depression. When considering the risk of side effects and interactions and the heterogeneity among the mostly small studies, a general recommendation cannot be made until well-controlled studies are conducted. PMID:23679841

Impaired heart rate variability and altered cardiac sympathovagal balance after antidepressant overdose.

PubMed

Waring, W S; Rhee, J Y; Bateman, D N; Leggett, G E; Jamie, H

2008-11-01

Antidepressant overdose may be associated with significant cardiotoxicity, and recent data have shown that acute toxic effects are associated with impaired heart rate variability. This study was designed to examine the feasibility of non-invasive heart rate variability recording in patients that present to hospital after deliberate antidepressant ingestion. This was a prospective study of 72 consecutive patients attending the Emergency Department after deliberate antidepressant overdose and 72 age-matched patients that ingested paracetamol, as a control group. Single time-point continuous electrocardiographic recordings were used to allow spectral analyses of heart rate variability determined in low-frequency (LF) and high-frequency (HF) domains. The LF:HF ratio was used to represent overall sympathovagal cardiac activity. Antidepressant overdose was associated with reduced overall heart rate variability: 1329 vs. 2018 ms(2) (P = 0.0239 by Mann-Whitney test). Variability in the LF domain was higher (64.8 vs. 49.8, P = 0.0006), whereas that in the HF domain was lower (24.3 vs. 36.4, P = 0.0001), and the LF:HF ratio was higher in the antidepressant group (2.4 vs. 1.2, P = 0.0003). Antidepressant overdose is associated with impaired heart rate variability in a pattern consistent with excess cardiac sympathetic activity. Further work is required to establish the significance of these findings and to explore whether the impairment of heart rate variability may be used to predict the development of arrhythmia in this patient group.

ANTIDEPRESSANTS ARE NOT OVER-PRESCRIBED FOR MILD DEPRESSION

PubMed Central

Simon, Gregory E; Rossom, Rebecca C; Beck, Arne; Waitzfelder, Beth E; Coleman, Karen J; Stewart, Christine; Operskalski, Belinda; Penfold, Robert B; Shortreed, Susan M

2016-01-01

Objective Evaluate over-prescribing of antidepressant medication for minimal or mild depression. Method Electronic records data from four large healthcare systems identified outpatients aged 18 or older starting a new episode of antidepressant treatment with an ICD9 diagnosis of depressive disorder (296.2, 296.3, 311, or 300.4). PHQ9 depression severity scores at time of treatment initiation were used to examine the distribution of baseline severity and the association between baseline severity and patients' demographic and clinical characteristics. Results Of 19,751 adults beginning treatment in 2011, baseline PHQ9 scores were available for 7051. In those with a baseline score, 85% reported moderate or severe symptoms (PHQ9 score 10 or more), 12% reported mild symptoms (PHQ score 5 to 9), and 3% reported minimal symptoms (PHQ9 score less than 5). The proportion reporting minimal or mild symptoms when starting treatment increased with age, ranging from 11% in those under age 30 to 26% in those aged 65 and older. The proportion with minimal or mild symptoms was also moderately higher among patients living in wealthier neighborhoods and those treated by psychiatrists. Nevertheless, across all subgroups defined by sex, race/ethnicity, prescriber specialty, and treatment history, the proportions with minimal or mild symptoms did not exceed 18%. Secondary analyses, including weighting and subgroup analyses, found no evidence that estimates of baseline severity were biased by missing PHQ9 scores. Conclusions In these health systems, prescribing of antidepressant medication for minimal or mild depression is much less common than suggested by previous reports. Given that this practice may sometimes be clinically appropriate, our findings indicate that over-prescribing of antidepressants for mild depression is not a significant public health concern. PMID:26580702

Antidepressant-like effect of Kyllinga brevifolia rhizomes in male mice and chemical characterization of the components of the active ethyl acetate fraction.

PubMed

Hellión-Ibarrola, M C; Montalbetti, Y; Heinichen, O Y; Kennedy, M L; Campuzano, M A; Alvarenga, N; Ibarrola, D A

2016-12-24

Kyllinga brevifolia rhizomes (Cyperaceae) are used in Paraguayan traditional medicine as a refreshing beverage, and is claimed to own digestive, diuretic, sedative, tonic, antispasmodic and sudorific properties. We have previously reported that its hydro- ethanolic rhizome extract possess sedative, anxiolytic and anti-aggressive-like effects in mice. However, information on its potential for treatment of syndromes associated with mood disorders is scarce. The purpose of this study is to characterize the putative antidepressant-like effects of the hydro-ethanolic extract (CEKb) and the ethyl acetate fraction (KbF-ethyl-ac) obtained from the rhizome of K. brevifolia (Rottb) on male mice exposed to forced swimming test. Also, chemical characterization of the components of the active ethyl acetate fraction was described. The antidepressant-like effects of CEKb and KbF-ethyl-ac were measured using the forced swimming test (FST) performance of male mice in single (acute), short-term and chronic modalities. Treatments in all modalities were made 1h before swimming test. The KbF-ethyl-ac was analyzed by LC-DAD-ESI-MS and LC-ESI-MS/MS in order to identify the active components. A single doses (1.0, 10.0 and 100.0mg/kg, p.o; p<0.05) of CEKb, in male mice provoked a significant reduction of the immobility time. Such effect was also observed with oral short-term treatment (7 days) with doses of 10.0 and 100.0mg/kg/day (p<0.05) of CEKb. Moreover, in the treatments during 14 days with doses of 1.0 (p<0.05), 10.0 (p<0.05), and 100.0 (p<0.001) mg/kg, p.o, of CEKb, a statistically significant reduction of the immobility time were induced. Additionally, in a different set of experiments acute dose of 1.0 (p<0.05) and 10.0 (p<0.01) mg/kg, p.o, of KbF-ethyl-ac in male mice, a significant reduction of the immobility time were provoked. Likewise, short-term treatment (7 days) with 1.0, and 10.0mg/kg (p<0.05); and after 14 days of treatment with 0.01 (p<0.01) 0.1 (p<0.001), 1.0 (p<0

Less is More in Antidepressant Clinical Trials: A Meta-Analysis of the Effect of Visit Frequency on Treatment Response and Drop-out

PubMed Central

Rutherford, Bret R; Cooper, Timothy M.; Persaud, Amanda; Brown, Patrick J.; Sneed, Joel R.; Roose, Steven P.

2014-01-01

Objective We investigated how the number of follow-up visits affects response rates and drop-out among patients in antidepressant trials for Major Depressive Disorder (MDD). Data Sources Medline, PsycINFO, and PubMed were searched to identify trials contrasting antidepressants to placebo or active comparator in adults with depression. The index terms “depression—drug therapy,” “depressive disorder—drug therapy,” and “antidepressant agents,” in addition to the class and individual generic name of all antidepressants were combined using the ‘or’ operator. Results were limited to 1) English language articles, 2) publication year 1985 or later, 3) age group ≥ 18, and 4) publication types including clinical trials, controlled clinical trials, meta-analysis, multi-center study, randomized controlled trial, or review. Study Selection Included articles reported trials of approved antidepressant medications for MDD in outpatients aged 18–65, were 6–12 weeks in duration, and had response rates specified using a standardized measure. Trials were excluded for enrolling inpatients, pregnant women, psychotic subjects, or those with treatment-resistant depression. These criteria allowed 9,189 articles identified in the literature review to be narrowed to 111 reports. Data extraction Demographic characteristics, the number of study visits planned in each treatment cell, duration of active treatment, attrition rates, and response rates to medication and placebo were entered into a database. Results In a multilevel meta-analysis, active medication vs. placebo (OR 1.96, p < 0.001), active comparator vs. placebo-controlled study design (OR 1.82, p < 0.001), and longer vs. shorter duration (OR 1.87, p < 0.001) were associated with significantly increased odds of treatment response. After controlling for these variables, the number of study visits did not significantly influence response rates (OR 0.97, p = 0.877). The odds of drop-out were significantly

Combined treatment with subchronic lithium and acute intracerebral mirtazapine microinjection into the median raphe nucleus exerted an anxiolytic-like effect synergistically.

PubMed

An, Yan; Inoue, Takeshi; Kitaichi, Yuji; Chen, Chong; Nakagawa, Shin; Wang, Ce; Kusumi, Ichiro

2016-07-15

Although preclinical and clinical studies have established the efficacy of lithium augmentation of antidepressant drugs, the mechanism of action of lithium augmentation is not fully understood. Our previous study reported that subchronic lithium treatment enhanced the anxiolytic-like effect of systemic mirtazapine. In the present study, we examined the effect of subchronic lithium in combination with acute local intracerebral injection of mirtazapine on fear-related behaviors in a contextual fear conditioning test in rats to clarify the target brain region of lithium augmentation of mirtazapine. After conditioning by footshock, diet (food pellets) containing Li2CO3 at a concentration of 0.2% was administered for 7 days. Ten min before testing and 7 days after conditioning, mirtazapine (3μg/site) in a volume of 0.5µl was acutely injected into the median raphe nucleus (MRN), hippocampus or amygdala. The combination of subchronic lithium and acute mirtazapine microinjection into the MRN but not the hippocampus or the amygdala reduced fear expression synergistically. These results suggest that intra-MRN mirtazapine treatment with subchronic lithium exerts the anxiolytic-like effect through the facilitation of the MRN-5HT pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

Predictors of Start of Different Antidepressants in Patient Charts among Patients with Depression

PubMed Central

Kim, Hyungjin Myra; Zivin, Kara; Choe, Hae Mi; Stano, Clare M.; Ganoczy, Dara; Walters, Heather; Valenstein, Marcia

2016-01-01

Background In usual psychiatric care, antidepressant treatments are selected based on physician and patient preferences rather than being randomly allocated, resulting in spurious associations between these treatments and outcome studies. Objectives To identify factors recorded in electronic medical chart progress notes predictive of antidepressant selection among patients who had received a depression diagnosis. Methods This retrospective study sample consisted of 556 randomly selected Veterans Health Administration (VHA) patients diagnosed with depression from April 1, 1999 to September 30, 2004, stratified by the antidepressant agent, geographic region, gender, and year of depression cohort entry. Predictors were obtained from administrative data, and additional variables were abstracted from electronic medical chart notes in the year prior to the start of the antidepressant in five categories: clinical symptoms and diagnoses, substance use, life stressors, behavioral/ideation measures (e.g., suicide attempts), and treatments received. Multinomial logistic regression analysis was used to assess the predictors associated with different antidepressant prescribing, and adjusted relative risk ratios (RRR) are reported. Results Of the administrative data-based variables, gender, age, illicit drug abuse or dependence, and number of psychiatric medications in prior year were significantly associated with antidepressant selection. After adjusting for administrative data-based variables, sleep problems (RRR = 2.47) or marital issues (RRR = 2.64) identified in the charts were significantly associated with prescribing mirtazapine rather than sertraline; however, no other chart-based variables showed a significant association or an association with a large magnitude. Conclusion Some chart data-based variables were predictive of antidepressant selection, but we neither found many nor found them highly predictive of antidepressant selection in patients treated for depression

The hippocampus and dorsal raphe nucleus are key brain areas associated with the antidepressant effects of lithium augmentation of desipramine.

PubMed

Cussotto, Sofia; Cryan, John F; O'Leary, Olivia F

2017-05-01

Approximately 50% of depressed individuals fail to achieve remission with first-line antidepressant drugs and a third remain treatment-resistant. When first-line antidepressant treatment is unsuccessful, second-line strategies include dose optimisation, switching to another antidepressant, combination with another antidepressant, or augmentation with a non-antidepressant medication. Much of the evidence for the efficacy of augmentation strategies comes from studies using lithium to augment the effects of tricyclic antidepressants. The neural circuitry underlying the therapeutic effects of lithium augmentation is not yet fully understood. Recently, we reported that chronic treatment with a combination of lithium and the antidepressant desipramine, exerted antidepressant-like behavioural effects in a mouse strain (BALB/cOLaHsd) that did not exhibit an antidepressant-like behavioural response to either drug alone. In the present study, we used this model in combination with ΔFosB/FosB immunohistochemistry to identify brain regions chronically affected by lithium augmentation of desipramine when compared to either treatment alone. The data suggest that the dorsal raphe nucleus and the CA3 regions of the dorsal hippocampus are key nodes in the neural circuitry underlying antidepressant action of lithium augmentation of desipramine. These data give new insight into the neurobiology underlying the mechanism of lithium augmentation in the context of treatment-resistant depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Antidepressants for depression in patients with dementia: a review of the literature.

PubMed

Leong, Christine

2014-04-01

To evaluate the literature investigating the efficacy and safety of antidepressants for treating depression in individuals with dementia. A literature search was conducted using MEDLINE, PUBMED, EMBASE, and Cochrane databases from inception to May 2013 for studies in English that evaluated the treatment of depression in patients with dementia. All relevant randomized controlled trials (RCTs) and meta-analyses were identified using the search terms "dementia" or "Alzheimer's disease," and "depression" or "major depressive disorder." Reference lists from retrieved articles and practice guidelines were also searched for relevant literature. Only randomized, placebo-controlled trials and meta-analyses that compared an antidepressant with placebo for the treatment of depression in patients with dementia were included. In this systematic review, 10 RCTs and 3 meta-analyses were identified that examined the efficacy and safety of antidepressants compared with placebo in treating depression in patients with dementia. The majority of the RCTs consisted of a small sample size, and the antidepressants studied were not routinely used in practice. The evidence for antidepressants in the treatment of depression in patients with dementia is inconclusive. The accumulation of evidence suggests nonpharmacologic approaches and watchful waiting be attempted for the first 8 to 12 weeks in a patient who presents with both mild-to-moderate depression and dementia. In cases of severe depression, or depression not managed through nonpharmacologic means, a trial of an antidepressant may be initiated. However, further well-designed trials are needed to support these recommendations.

Augmenting Antidepressant Medication Treatment of Depressed Women with Emotionally Focused Therapy for Couples: A Randomized Pilot Study

ERIC Educational Resources Information Center

Denton, Wayne H.; Wittenborn, Andrea K.; Golden, Robert N.

2012-01-01

This is the first study to evaluate adding emotionally focused therapy for couples (EFT) to antidepressant medication in the treatment of women with major depressive disorder and comorbid relationship discord. Twenty-four women and their male partners were randomized to 6 months of medication management alone (MM) or MM augmented with EFT (MM +…

Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy

PubMed Central

Kopschina Feltes, Paula; Doorduin, Janine; Klein, Hans C; Juárez-Orozco, Luis Eduardo; Dierckx, Rudi AJO; Moriguchi-Jeckel, Cristina M; de Vries, Erik FJ

2017-01-01

Major depressive disorder (MDD) is a prevalent and disabling psychiatric disease with rates of non-responsiveness to antidepressants ranging from 30–50%. Historically, the monoamine depletion hypothesis has dominated the view on the pathophysiology of depression. However, the lack of responsiveness to antidepressants and treatment resistance suggests that additional mechanisms might play a role. Evidence has shown that a subgroup of depressive patients may have an underlying immune deregulation that could explain the lack of therapeutic benefit from antidepressants. Stimuli like inflammation and infection can trigger the activation of microglia to release pro-inflammatory cytokines, acting on two main pathways: (1) activation of the hypothalamic–pituitary adrenal axis, generating an imbalance in the serotonergic and noradrenergic circuits; (2) increased activity of the enzyme indoleamine-2,3-dioxygenase, resulting in depletion of serotonin levels and the production of quinolinic acid. If this hypothesis is proven true, the subgroup of MDD patients with increased levels of pro-inflammatory cytokines, mainly IL-6, TNF-α and IL-1β, might benefit from an anti-inflammatory intervention. Here, we discuss the pre-clinical and clinical studies that have provided support for treatment with non-steroidal anti-inflammatory drugs in depressed patients with inflammatory comorbidities or an elevated immune profile, as well as evidences for anti-inflammatory properties of standard antidepressants. PMID:28653857

Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat.

PubMed

Zhang, Yang; Gu, Fenghua; Chen, Jia; Dong, Wenxin

2010-12-17

Stress activates the hypothalamo-pituitary-adrenal (HPA) axis, regulates the expression of brain-derived neurotrophic factor (BDNF) in the brain, and mediates mood. Antidepressants alleviate stress and up-regulate BDNF gene expression. In this study, we investigated the effect of chronic unpredictable mild stress (CUMS) and the different kinds of antidepressant treatments on the HPA axis and the BDNF expression in the rat brain. Adult Wistar male rats were exposed to a six-week CUMS procedure and received different antidepressant treatments including venlafaxine, mirtazapine, and fluoxetine. Immunohistochemistry and real-time PCR were used to measure BDNF expression levels in the rat brain, and ELISAs were used to investigate the plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels. CUMS significantly decreased the BDNF protein level in the DG, CA1, and CA3 of the hippocampus and increased plasma CORT level. Chronic antidepressant treatments all significantly increased BDNF protein levels in the hippocampus and the pre-frontal cortex. In addition, venlafaxine and mirtazapine inhibited the increase of plasma CORT level. These results suggested that an increase in the BDNF level in the brain could be a pivotal mechanism of various antidepressants to exert their therapeutic effects. Copyright © 2010 Elsevier B.V. All rights reserved.

Sildenafil citrate for the management of antidepressant-associated erectile dysfunction.

PubMed

Nurnberg, H George; Hensley, Paula L

2003-01-01

Sexual side effects of serotonin reuptake inhibitors, such as antidepressant-associated erectile dysfunction, are common and negatively impact treatment compliance. Current management approaches have important limitations, and most lack clear and meaningful efficacy in double-blind, placebo-controlled trials. A MEDLINE search (English language, 1966-2003) was performed using the terms antidepressive agents, erectile dysfunction, and sildenafil. Emphasis was placed on studies that used specific sexual function measurements and were placebo controlled. Sildenafil citrate, a selective and competitive inhibitor of phosphodiesterase type 5, enhances the cyclic guanosine monophosphate-mediated relaxation of cavernosal smooth muscles in response to sexual stimulation, permitting vascular engorgement and penile erection. The efficacy and tolerability of sildenafil in the treatment of antidepressant-associated erectile dysfunction have been confirmed in double-blind, placebo-controlled trials.

Antidepressants Accumulate in Lipid Rafts Independent of Monoamine Transporters to Modulate Redistribution of the G Protein, Gαs.

PubMed

Erb, Samuel J; Schappi, Jeffrey M; Rasenick, Mark M

2016-09-16

Depression is a significant public health problem for which currently available medications, if effective, require weeks to months of treatment before patients respond. Previous studies have shown that the G protein responsible for increasing cAMP (Gαs) is increasingly localized to lipid rafts in depressed subjects and that chronic antidepressant treatment translocates Gαs from lipid rafts. Translocation of Gαs, which shows delayed onset after chronic antidepressant treatment of rats or of C6 glioma cells, tracks with the delayed onset of therapeutic action of antidepressants. Because antidepressants appear to specifically modify Gαs localized to lipid rafts, we sought to determine whether structurally diverse antidepressants accumulate in lipid rafts. Sustained treatment of C6 glioma cells, which lack 5-hydroxytryptamine transporters, showed marked concentration of several antidepressants in raft fractions, as revealed by increased absorbance and by mass fingerprint. Closely related molecules without antidepressant activity did not concentrate in raft fractions. Thus, at least two classes of antidepressants accumulate in lipid rafts and effect translocation of Gαs to the non-raft membrane fraction, where it activates the cAMP-signaling cascade. Analysis of the structural determinants of raft localization may both help to explain the hysteresis of antidepressant action and lead to design and development of novel substrates for depression therapeutics. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Strategies to enhance the therapeutic efficacy of antidepressants: targeting residual symptoms

PubMed Central

Kurian, Benji T; Greer, Tracy L; Trivedi, Madhukar H

2009-01-01

Major depressive disorder (MDD) is an illness of great morbidity that affects many people across the world. The current goal for treatment of MDD is to achieve remission (i.e., no depressive symptoms). However, despite scientific advances in the treatment for MDD, antidepressants as first-line agents yield only modest remission rates. In fact, a recent study indicated that only one out of three subjects who received a standard, first-line antidepressant attained remission. Not achieving remission from depressive symptoms increases the risk of a more chronic and debilitating course of illness with frequent recurrences. Although a number of reasons contribute to these modest outcomes, the presence of residual symptoms is a major problem. Residual symptoms are defined as symptoms that linger despite an adequate dose and duration of an antidepressant medication. This article reviews the prevalence and clinical impact of common residual symptoms and discusses the utility of aggressively addressing residual symptoms to enhance the efficacy of antidepressant medications. PMID:19589048

Antidepressants induce autophagy dependent-NLRP3-inflammasome inhibition in Major depressive disorder.

PubMed

Alcocer-Gómez, Elísabet; Casas-Barquero, Nieves; Williams, Matthew R; Romero-Guillena, Samuel L; Cañadas-Lozano, Diego; Bullón, Pedro; Sánchez-Alcazar, José Antonio; Navarro-Pando, José M; Cordero, Mario D

2017-07-01

Major Depressive Disorder (MDD, ICD-10: F-33) is a prevalent illness in which the pathogenic mechanism remains elusive. Recently an important role has been attributed to neuro-inflammation, and specifically the NLRP3-inflammasome complex, in the pathogenesis of MDD. This suggests a key role for immunomodulation as a key pathway in the treatment of this disorder. This study evaluates the involvement of nine common antidepressants in the NLRP3-inflammasome complex (fluoxetine, paroxetine, mianserin, mirtazapine, venlafaxine, desvenlafaxine, amitriptyline, imipramine and agomelatine), both in in vitro THP-1 cells stimulated by ATP, and in a stress-induced depressive animal or MDD patients. Antidepressant treatment induced inflammasome inhibition was observed by decreased serum levels of IL-1β and IL-18 and decrease of NLRP3 and IL-1β (p17) protein expression. This was also observed under stress-induced depressive behaviour and inflammasome activation in C57Bl/6 mice in vivo. Deletion of key autophagy mediator Atg5 in embryonic fibroblasts (MEF cells) showed an autophagy dependent-NLRP3-inflammasome inhibition by antidepressant treatment. These results suggest the NLRP3-inflammasome could be a biomarker for antidepressant treatment response in MDD patients, and therefore the monitoring of NLRP3 expression levels and/or IL-1β/IL-18 release may have clinical value in drug selection. Existing evidence suggests an anti-inflammatory effect of some antidepressants shown by IL-1β, IL-6 and TNF-α. Our data have shown that antidepressant-mediated autophagy may have a role in restoration of certain metabolic and immunological pathways in MDD patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antidepressant-like effects of long-term sarcosine treatment in rats with or without chronic unpredictable stress.

PubMed

Chen, Kuang-Ti; Wu, Ching-Hsiang; Tsai, Mang-Hung; Wu, Ya-Chieh; Jou, Ming-Jia; Huang, Chih-Chia; Wei, I-Hua

2017-01-01

Sarcosine, an N-methyl-d-aspartate receptor enhancer, can improve depression-like behavior in rodent models and depression in humans. We found that a single dose of sarcosine exerted antidepressant-like effects with rapid concomitant increases in the mammalian target of rapamycin (mTOR) signaling pathway activation and enhancement of α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR) membrane insertion. Sarcosine may play a crucial role in developing novel therapy for depression. For a detailed understanding of sarcosine, this study examined the effects of long-term sarcosine treatment on the forced swim test (FST), mTOR signaling, and AMPAR membrane insertion in rats. The effects of long-term sarcosine treatment were examined in naive rats and rats exposed to chronic unpredictable stress (CUS). Long-term sarcosine treatment (560mg/kg/d for 21 d) significantly ameliorated the increased immobility induced by CUS in the FST, reaffirming the potential role of sarcosine as an antidepressant for depressed patients. The same long-term treatment exhibited no such effect in naive rats despite increased mTOR activation and AMPAR membrane insertion in both groups. Our findings clearly show CUS-exposed rats are sensitive to long-term sarcosine treatment in FST and the response at the same dose is absent in naïve rats. Nevertheless, the distinct sensitivity to long-term sarcosine treatment in rats with or without CUS is not associated with the activated mTOR signaling pathway or increased AMPAR membrane insertion. Additionally, understanding the behavioral and molecular basis of distinct responses is vital important for developing personalized treatment programs to increase the probability of success when treating depression. Copyright © 2016. Published by Elsevier B.V.

ANTIDEPRESSANT ADHERENCE ACROSS DIVERSE POPULATIONS AND HEALTHCARE SETTINGS.

PubMed

Rossom, Rebecca C; Shortreed, Susan; Coleman, Karen J; Beck, Arne; Waitzfelder, Beth E; Stewart, Christine; Ahmedani, Brian K; Zeber, John E; Simon, Greg E

2016-08-01

Early adherence is key to successful depression treatment, but nearly 60% of patients discontinue antidepressants within 3 months. Our study aimed to determine factors associated with poor early adherence to antidepressants in a large diverse sample of patients. Six Mental Health Research Network healthcare systems contributed data for adults with depression and a new antidepressant start, defined by a washout period of at least 270 days, between January 1, 2010 and December 31, 2012. Pharmacy fill and self-reported race/ethnicity data were obtained from the electronic medical record. Patients had early adherence if they had a second antidepressant fill within 180 days of the first. We used logistic regression to investigate the relationship between early adherence and patient characteristics. A total of 177,469 adult patients had 184,967 new episodes of depression with a filled antidepressant prescription. Patients refilled their antidepressants within 180 days in 71% of episodes. Race/ethnicity was a strong predictor of early adherence, with patients from racial/ethnic minorities other than Native Americans/Alaskan Natives less likely (adjusted odd ratios 0.50-0.59) to refill their antidepressants than non-Hispanic whites. Age, neighborhood education, comorbidity burden, provider type and engagement in psychotherapy were also associated with adherence. Other apparent predictors of early adherence, including neighborhood income, gender, and prior mental health hospitalizations, were no longer significant in the fully adjusted model. Race/ethnicity was a robust predictor of early antidepressant adherence, with minority groups other than Native Americans/Alaskan Natives less likely to be adherent. Further research is needed to determine whether early nonadherence in specific minority populations is intentional, due to side effects or patient preference, or unintentional and appropriate for targeted interventions to improve adherence. © 2016 Wiley Periodicals, Inc.

Beliefs about medications predict adherence to antidepressants in older adults.

PubMed

Fawzi, Waleed; Abdel Mohsen, Mohamed Yousry; Hashem, Abdel Hamid; Moussa, Suaad; Coker, Elizabeth; Wilson, Kenneth C M

2012-01-01

Adherence to treatment is a complex and poorly understood phenomenon. This study investigates the relationship between older depressed patients' adherence to antidepressants and their beliefs about and knowledge of the medication. Assessment was undertaken of 108 outpatients over the age of 55 years diagnosed with depressive disorder and treated for at least four weeks with antidepressants. Adherence was assessed using two self-report measures: the Medication Adherence Rating Scale (MARS) and a Global Adherence Measure (GAM). Potential predictors of adherence investigated included sociodemographic, medication and illness variables. In addition, 33 carers were interviewed regarding general medication beliefs. 56% of patients reported 80% or higher adherence on the GAM. Sociodemographic variables were not associated with adherence on the MARS. Specific beliefs about medicines, such as "my health depends on antidepressants" (necessity) and being less worried about becoming dependant on antidepressants (concern) were highly correlated with adherence. General beliefs about medicines causing harm or being overprescribed, experiencing medication side-effects and severity of depression also correlated with poor adherence. Linear regression with the MARS as the dependent variable explained 44.3% of the variance and showed adherence to be higher in subjects with healthy specific beliefs who received more information about antidepressants and worse with depression severity and autonomic side-effects. Our findings strongly support a role for specific beliefs about medicines in adherence. Challenging patients' beliefs, providing information about treatment and discussing side-effects could improve adherence. Poor response to treatment and medication side-effects can indicate poor adherence and should be considered before switching medications.

Trajectories of change in depression severity during treatment with antidepressants.

PubMed

Uher, R; Muthén, B; Souery, D; Mors, O; Jaracz, J; Placentino, A; Petrovic, A; Zobel, A; Henigsberg, N; Rietschel, M; Aitchison, K J; Farmer, A; McGuffin, P

2010-08-01

Response and remission defined by cut-off values on the last observed depression severity score are commonly used as outcome criteria in clinical trials, but ignore the time course of symptomatic change and may lead to inefficient analyses. We explore alternative categorization of outcome by naturally occurring trajectories of symptom change. Growth mixture models were applied to repeated measurements of depression severity in 807 participants with major depression treated for 12 weeks with escitalopram or nortriptyline in the part-randomized Genome-based Therapeutic Drugs for Depression study. Latent trajectory classes were validated as outcomes in drug efficacy comparison and pharmacogenetic analyses. The final two-piece growth mixture model categorized participants into a majority (75%) following a gradual improvement trajectory and the remainder following a trajectory with rapid initial improvement. The rapid improvement trajectory was over-represented among nortriptyline-treated participants and showed an antidepressant-specific pattern of pharmacogenetic associations. In contrast, conventional response and remission favoured escitalopram and produced chance results in pharmacogenetic analyses. Controlling for drop-out reduced drug differences on response and remission but did not affect latent trajectory results. Latent trajectory mixture models capture heterogeneity in the development of clinical response after the initiation of antidepressants and provide an outcome that is distinct from traditional endpoint measures. It differentiates between antidepressants with different modes of action and is robust against bias due to differential discontinuation.

Attention-deficit hyperactivity disorder comorbidity and antidepressant resistance among patients with major depression: A nationwide longitudinal study.

PubMed

Chen, Mu-Hong; Pan, Tai-Long; Hsu, Ju-Wei; Huang, Kai-Lin; Su, Tung-Ping; Li, Cheng-Ta; Lin, Wei-Chen; Tsai, Shih-Jen; Chang, Wen-Han; Chen, Tzeng-Ji; Bai, Ya-Mei

2016-11-01

The comorbidity between attention deficit hyperactivity disorder (ADHD) and major depression is common. However, the influence of ADHD comorbidity in the response or resistance to antidepressants remains unknown among patients with major depression. 1891 patients with major depression and ADHD and 1891 age-/sex-matched patients with major depression only were enrolled and followed for 1 year in our study. Use of antidepressants and ADHD medications during 1-year follow-up period were assessed. Antidepressant resistance was defined as treatment failure in two or more than two different antidepressants for adequate treatment dose and duration. Patients with major depression and ADHD had an increased risk of treatment resistance to antidepressants (odds ratio [OR]: 2.32, 95% confidence interval [CI]: 1.63-3.32) compared with patients with major depression only after adjusting for demographic characteristics and other psychiatric comorbidities. Regular treatment for ADHD would reduce this risk (OR: 1.76, 95% CI: 0.72-4.27). Anxiety (OR: 3.15, 95% CI: 2.24-4.44) and substance use (OR: 2.45, 95% CI: 1.16-5.17) disorders were also associated with an elevated likelihood of resistance to antidepressants during the follow-up. Patients who had dual diagnoses of major depression and ADHD were more likely to have treatment resistance to antidepressants compared with patients with major depression only. Prompt and regular treatment for ADHD would reduce this risk. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

[Antidepressant drugs and breastfeeding].

PubMed

Bellantuono, Cesario; Migliarese, Giovanni; Maggioni, Francesca; Imperadore, Giuseppe

2007-01-01

The post-partum period, as well as pregnancy, is associated with an increased risk of anxiety and/or affective disorders. Postnatal depression, frequently in co-morbidity with anxiety symptoms, is recognised as the most frequent form of maternal morbidity after delivery, with a prevalence rate estimated between 5% to 15%. Among antidepressant drugs, the SSRIs are considered the drugs of choice in the treatment of post-partum affective disorders, particularly in the major depression. It is, thus, crucial from a clinical standpoint to establish, in the newborn whose mother needs to be treated with an SSRI, the safety profile of these drugs during breastfeeding. The benefits of breastfeeding, on the other hand, both for the nursing mother and the infant, are in fact very well documented. Unfortunately, all antidepressant drugs, including SSRIs, cross into breast milk and the milk-to-plasma ratio, a measure proposed to establish the amount of drug transferred to maternal milk, does not seem to be a reliable parameter to predict the safety of these drugs. From the available literature, however, it seems that among SSRIs, paroxetina and sertralina offer the best safety profile, as these drugs has never been associated with unsafe reports in suckling infants. Despite these reassuring but preliminary data, more studies are needed to better assess the safety of the antidepressant drugs in the infants exposed during breastfeeding. As general rule, it is important to recommend if the mother wishes to breastfeed her infant while taking an antidepressant, that the baby should be closely monitored in order to detect, as soon as possible, any unwanted drug-related side effect.

Two Phase III randomised double-blind studies of fixed-dose TC-5214 (dexmecamylamine) adjunct to ongoing antidepressant therapy in patients with major depressive disorder and an inadequate response to prior antidepressant therapy.

PubMed

Möller, Hans-Jürgen; Demyttenaere, Koen; Olausson, Bengt; Szamosi, Johan; Wilson, Ellis; Hosford, David; Dunbar, Geoffrey; Tummala, Raj; Eriksson, Hans

2015-10-01

To evaluate the neuronal nicotinic channel modulator TC-5214 (dexmecamylamine) as adjunct therapy in patients with major depressive disorder (MDD) and inadequate response to prior antidepressant treatment. Study 004 (D4130C00004) and Study 005 (D4130C00005) comprised an 8-week open-label antidepressant (SSRI/SNRI) treatment period followed by an 8-week randomised, active treatment with twice-daily TC-5214 (0.5, 2 or 4 mg in Study 004; 0.1, 1 or 4 mg in Study 005) or placebo, adjunct to ongoing SSRI/SNRI. Primary efficacy endpoint was change in MADRS total score from randomisation (Week 8) to treatment end (Week 16). Secondary endpoints included MADRS response and remission, and changes in SDS and HAM-D-17-item scores. Safety and tolerability were monitored throughout. Studies 004 and 005 randomised 640 and 696 patients, respectively, to TC-5214 or placebo. No statistically significant improvements in MADRS total score or any secondary endpoints were seen with TC-5214 versus placebo in either study at treatment end. The most commonly reported adverse events (> 10%) with TC-5214 were constipation, dizziness and dry mouth. TC-5214 adjunct to antidepressant was generally well tolerated. However, the studies were not supportive of an antidepressant effect for TC-5214 in patients with MDD and inadequate response to prior antidepressant therapy.

Physicians' decisions to prescribe antidepressant therapy in older patients with depression in a US managed care plan.

PubMed

Ivanova, Jasmina I; Bienfait-Beuzon, Catherine; Birnbaum, Howard G; Connolly, Cristina; Emani, Srinivas; Sheehy, Michael

2011-01-01

Published studies indicate that depression in older adults is severely under-recognized and under-treated. To characterize primary-care physicians' decisions to prescribe antidepressants to older patients with depression. Electronic medical record (EMR) notes from office visits of older patients (aged ≥65 years), treated in a central Massachusetts multi-specialty medical group practice, were screened every 2 weeks between August 2007 and July 2008 for mention of depression. Electronic surveys containing questions about depression severity and onset, and antidepressant treatment, were sent to physicians whose EMR notes indicated that they had treated an older patient with depression, until approximately 400 responses had been received. Physicians were asked about whether they prescribed antidepressants or made changes to antidepressant treatment and were asked about the extent to which they agreed with a set of pre-specified reasons for treatment recommendations. Physicians were also allowed to document any other reasons that influenced their decision. Patient characteristics and treatment were identified from administrative claims. Univariate analyses were used to describe patient characteristics and physician survey responses. Physicians responded to the survey and confirmed a depression diagnosis for 396 patients, for whom the average age was 77.1 years and 76.5% were female. Most patients had physician-reported depression onset after age 60 years (72.2%) and moderately severe depression (58.8%). Physicians reported that 62.9% of patients were already being treated with antidepressants prior to their visit, 28.5% were recommended antidepressant initiation and 8.6% were not prescribed antidepressants. Selective serotonin reuptake inhibitors were most frequently prescribed. Maintaining prior therapy was recommended for 81.1% of treated patients and treatment modification for 18.9%. Almost all physicians (>92%) agreed that experience in use of prescription drugs

Antidepressants and Alcohol

MedlinePlus

... the concern? Why is it bad to mix antidepressants and alcohol? Answers from Daniel K. Hall-Flavin, M.D. It's best to avoid combining antidepressants and alcohol. It may worsen your symptoms, and ...

Antidepressants May Mitigate the Effects of Prenatal Maternal Anxiety on Infant Auditory Sensory Gating

PubMed Central

Hunter, Sharon K.; Mendoza, Jordan H.; D’Anna, Kimberly; Zerbe, Gary O; McCarthy, LizBeth; Hoffman, Camille; Freedman, Robert; Ross, Randal G.

2013-01-01

Objective Prenatal maternal anxiety has detrimental effects on the resulting offspring’s neurocognitive development, including impaired attentional function. Antidepressants are commonly utilized during pregnancy, yet their impact on offspring attention and their interaction with maternal anxiety has not been assessed. Using P50 auditory sensory gating, a putative marker of early attentional processes measurable in young infants, the impact of maternal anxiety and antidepressant use are explored. Method Two hundred forty-two mother-infant dyads were classified relative to maternal history of anxiety and maternal prenatal antidepressant use. Infant P50 auditory sensory gating was recorded during active sleep at a mean± standard deviation of 76 ± 38 days of age. Results In the absence of prenatal antidepressant exposure, infants with mothers with a history of anxiety diagnoses had diminished P50 sensory gating (p<.001). Prenatal antidepressants mitigated the effect of anxiety (uncorrected p=.041). The effect of maternal anxiety was limited to amplitude of response to the second stimulus while antidepressants impacted the amplitude or response to both the first and second stimulus. Conclusion Maternal anxiety disorders are associated less inhibition during infant sensory gating, a performance deficit mitigated by prenatal antidepressant use. This effect may be important in considering the risks and benefits of prenatal antidepressant treatment. Cholinergic mechanisms are hypothesized for both anxiety and antidepressant effects; however the cholinergic receptors involved are likely different for anxiety and antidepressant effects. Additional work focused on understanding how treatment impacts the relationship between maternal prenatal illness and offspring neurocognitive development is indicated. PMID:22581104

Treating depression with antidepressants: drug-placebo efficacy debates limit broader considerations.

PubMed

Yapko, Michael D

2013-01-01

The core issue regarding antidepressants for many clinicians is whether they perform significantly better than placebos. However, this article suggests eight additional concerns beyond drug efficacy alone to consider regarding antidepressants including: (1) formulating only a one-dimensional, biological view of depression; (2) defining the client's role as passive in treatment; (3) economic corruption of the research and reporting; (4) false or misleading consumer advertising; (5) conflicting data that confuse practitioners and consumers alike; (6) over- and under-prescription of medications; (7) drug side-effects; and (8) harm to the environment. The enhanced effects of psychotherapy utilizing hypnosis offer a means of avoiding most, if not all, of the problems associated with the use of antidepressants as a primary form of treatment.

FKBP5/FKBP51 enhances autophagy to synergize with antidepressant action

PubMed Central

Gassen, Nils C; Hartmann, Jakob; Schmidt, Mathias V; Rein, Theo

2015-01-01

Levels of autophagy markers rise upon treatment of cells with antidepressants. However, it was not known whether this phenomenon might be linked to other antidepressant pathways or to any physiological effect. In this punctum, we summarize and discuss our recent findings that provide evidence for a role of the cochaperone FKBP5/FKBP51 (FK506 binding protein 5) in autophagy as a prerequisite for antidepressant action in cells, mice, and humans. FKBP5 associates with BECN1, changes its phosphorylation and protein levels and enhances markers of autophagy and autophagic flux. The effects of antidepressants on autophagy as well as their physiological effects in mice and human depend on FKBP5. PMID:25714272

Trajectories of depressive symptoms in the acute phase of psychosis: Implications for treatment.

PubMed

Kjelby, E; Gjestad, R; Sinkeviciute, I; Kroken, R A; Løberg, E-M; Jørgensen, H A; Johnsen, E

2018-06-02

Depression is common in schizophrenia and associated with negative outcomes. Previous studies have identified heterogeneity in treatment response in schizophrenia. We aimed to investigate different trajectories of depression in patients suffering from psychosis and predictors of change in depressive symptoms during antipsychotic treatment. Two hundred and twenty-six patients >18 years acutely admitted due to psychosis were consecutively included and the follow-up was 27 weeks. The Calgary Depression Scale for Schizophrenia (CDSS) sum score was the primary outcome. Latent growth curve (LGCM) and Growth Mixture Models (GMM) were conducted. Predictors were the Positive sum score of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), Schizophrenia spectrum/non-spectrum psychoses, gender and being antipsychotic naive at inclusion. We found support for three depression-trajectories, including a high- (14.7%), a low depression-level (69.6%) class and a third depressed class quickly decreasing to a low level (15.7%). Change in CDSS was associated with change in PANSS positive score in all time intervals (4 weeks: b = 0.18, p < 0.001, 3 months: 0.21, p < 0.023, 6 months: 0.43, p < 0.001) and with a diagnosis within schizophrenia spectrum but not with antipsychotic naivety or gender. The schizophrenia-spectrum patients had less depressive symptoms at inclusion (-2.63, p < 0.001). In conclusion, an early responding and a treatment refractory group were identified. The treatment-refractory patients are candidates for enhanced anti-depressive treatment, for which current evidence is limited. The post-psychotic depression group was characterized by depressive symptoms in the acute phase as well. We could not identify differentiating characteristics of the depression trajectories. Copyright © 2018 Elsevier Ltd. All rights reserved.

Study design features affecting outcome in antidepressant trials.

PubMed

Henkel, Verena; Casaulta, Flurina; Seemüller, Florian; Krähenbühl, Stephan; Obermeier, Michael; Hüsler, Jürg; Möller, Hans-Jürgen

2012-12-10

A key issue in the approval process of antidepressants is the inconsistency of results between antidepressant clinical phase III trials. Identifying factors influencing efficacy data is needed to facilitate interpretation of the results. We reviewed data packages submitted as new drug applications to Swissmedic focusing on pivotal, short-term antidepressant trials. Included studies used HAMD-17 or HAMD-21 as primary measures and enrolled patients aged 18-65 years with a diagnosis of major depression. Due to the hierarchical structure of the data a mixed-effect regression model has been applied with responder rates as primary outcome criterion. Random intercepts were estimated for the different trials, while study design factors were assigned as explanatory fixed effects. The final dataset was based upon 35 study reports with a total of N=10,835 patients. Significant results were found for study arm (placebo vs. active compound, p<0.001), sample size (p=0.002), duration of treatment (p=0.024), two or more active treatment arms (p=0.022) and the individual drug (p=0.029). Furthermore, a tendency to an association with the outcome was observed for baseline disease severity (p=0.077) and possibility of dosing adaptation (p=0.076). Due to strict confidentiality agreements, individual drugs are not reported here. Further research should consider additional variables that might have an impact on the results of antidepressant trials. Efficacy data in antidepressant trials is significantly affected by various factors. These factors and their potentially confounding role have to be considered in the interpretation of the results. Copyright © 2012 Elsevier B.V. All rights reserved.

Drug-drug interactions involving antidepressants: focus on desvenlafaxine.

PubMed

Low, Yvette; Setia, Sajita; Lima, Graca

2018-01-01

Psychiatric and physical conditions often coexist, and there is robust evidence that associates the frequency of depression with single and multiple physical conditions. More than half of patients with depression may have at least one chronic physical condition. Therefore, antidepressants are often used in cotherapy with other medications for the management of both psychiatric and chronic physical illnesses. The risk of drug-drug interactions (DDIs) is augmented by complex polypharmacy regimens and extended periods of treatment required, of which possible outcomes range from tolerability issues to lack of efficacy and serious adverse events. Optimal patient outcomes may be achieved through drug selection with minimal potential for DDIs. Desvenlafaxine is a serotonin-norepinephrine reuptake inhibitor approved for the treatment of adults with major depressive disorder. Pharmacokinetic studies of desvenlafaxine have shown a simple metabolic profile unique among antidepressants. This review examines the DDI profiles of antidepressants, particularly desvenlafaxine, in relation to drugs of different therapeutic areas. The summary and comparison of information available is meant to help clinicians in making informed decisions when using desvenlafaxine in patients with depression and comorbid chronic conditions.

Decisional conflict among women considering antidepressant medication use in pregnancy.

PubMed

Walton, Georgia D; Ross, Lori E; Stewart, Donna E; Grigoriadis, Sophie; Dennis, Cindy-Lee; Vigod, Simone

2014-12-01

The purpose of this study was to examine decision-making among women considering antidepressant medication use in pregnancy. Decisional conflict was assessed using the Decisional Conflict Scale (DCS) among pregnant women considering antidepressant medication treatment (N = 40). Overall DCS and subscale scores were compared between women who were antidepressant users and non-users. Semi-structured interviews (N = 10) explored barriers and facilitators of decision-making. Twenty-one women (52 %) had moderate or high decisional conflict (DCS ≥ 25). Overall DCS scores did not differ between groups, but antidepressant use was associated with feeling more adequately informed (subscale mean 17.5, SD 17.9 vs. 42.1, SD 23.8, p = 0.001) and clear about values (subscale mean 16.7, SD 15.1 vs. 29.8, SD 24.0, p = 0.043). Barriers to decision-making were (1) difficulty weighing maternal versus infant health, (2) lack of high quality information, (3) negative external influences, and (4) emotional reactions to decision-making. Facilitators were (1) interpersonal supports, (2) accessible subspecialty care, and (3) severe depressive symptoms. Many pregnant women facing decisions regarding antidepressant medication use experience decisional conflict. Interventions that provide accurate information, assistance with weighing risks and benefits of treatment, management of problematic external influences, and emotional support may reduce decisional conflict and facilitate the decision-making process.

The prevalence and use of antidepressant medication in pediatric cancer patients.

PubMed

Portteus, Andrew; Ahmad, Naveed; Tobey, Daniel; Leavey, Patrick

2006-08-01

During the period of cancer diagnosis and active treatment, several small case series have revealed high rates of psychiatric difficulty in pediatric patients. However, due to the methodological limitations in these studies, it remains impossible to determine accurately the true prevalence of mood disorders in pediatric cancer patients receiving cancer treatment. To date, no study has reported rates of antidepressant treatment in this population. The aims of this study were: (1) To determine the prevalence of the use of antidepressant medication (ADM) in children with cancer; (2) to identify a group of children being treated for cancer, that are likely to receive ADM, and who therefore may be eligible for a prospective observational or interventional clinical trial of depression during cancer therapy. We reviewed the medical records of 224 pediatric patients suspected for cancer in 2003 at the Children's Medical Center of Dallas. Of these, 6 proved non-oncologic and 2 were lost to follow up, leaving 216 charts for review. Within 1 year of diagnosis, 29 patients (13%) had received a psychiatric consultation. Twenty-two patients (10.2%) received ADM within 1 year of cancer diagnosis. Children >/= 12 years, children with acute lymphoblastic leukemia, and children receiving radiotherapy or opiate analgesics were more likely to receive ADM by multivariate analysis. Race, sex, bone marrow transplant, and surgery were not significantly associated with ADM use. The prevalence of ADM use in pediatric cancer patients (10.2%) was higher than the reported rates of depression (4-8%) and ADM treatment (1%) in the general pediatric population. Teenagers and those who received opiate analgesic medications during their cancer therapy represent a subgroup of children in whom further study of depression and cancer therapy may be valuable.

Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis.

PubMed

Ross, Lori E; Grigoriadis, Sophie; Mamisashvili, Lana; Vonderporten, Emily H; Roerecke, Michael; Rehm, Jürgen; Dennis, Cindy-Lee; Koren, Gideon; Steiner, Meir; Mousmanis, Patricia; Cheung, Amy

2013-04-01

Untreated depression during pregnancy has been associated with increased morbidity and mortality for both mother and child and, as such, optimal treatment strategies are required for this population. There are conflicting data regarding potential risks of prenatal antidepressant treatment. To determine whether prenatal antidepressant exposure is associated with risk for selected adverse pregnancy or delivery outcomes. DATA SOURCES MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and the Cochrane Library were searched from their start dates to June 30, 2010. STUDY SELECTION English-language studies reporting outcomes associated with pharmacologic treatment during pregnancy were included. We reviewed 3074 abstracts, retrieved 735 articles, and included 23 studies in this meta-analysis. Study design, antidepressant exposure, adjustment for confounders, and study quality were extracted by 2 independent reviewers. There was no significant association between antidepressant medication exposure and spontaneous abortion (odds ratio [OR], 1.47; 95% CI, 0.99 to 2.17; P = .055). Gestational age and preterm delivery were statistically significantly associated with antidepressant exposure (mean difference [MD] [weeks], -0.45; 95% CI, -0.64 to -0.25; P < .001; and OR, 1.55; 95% CI, 1.38 to 1.74; P < .001, respectively), regardless of whether the comparison group consisted of all unexposed mothers or only depressed mothers without antidepressant exposure. Antidepressant exposure during pregnancy was significantly associated with lower birth weight (MD [grams], -74; 95% CI, -117 to -31; P = .001); when this comparison group was limited to depressed mothers without antidepressant exposure, there was no longer a significant association. Antidepressant exposure was significantly associated with lower Apgar scores at 1 and 5 minutes, regardless of whether the comparison group was all mothers or only those who were depressed during pregnancy but not

Acute treatment of migraine headaches.

PubMed

Taylor, Frederick R

2010-04-01

Optimum acute treatment of migraine requires prevention of headache as a top priority. Recognition of the multitude of migraine presentations, the frequency of total headache attacks, and number of days of headache disability are critical. Successful treatment requires excellent patient-clinician communication enhancing confidence and mutual trust based on patient needs and preferences. Optimum management of acute migraine nearly always requires pharmacologic treatment for rapid resolution. Migraine-specific triptans, dihydroergotamine, and several antiinflammatories have substantial empirical clinical efficacy. Older nonspecific drugs, particularly butalbital and opioids, contribute to medication overuse headache and are to be avoided. Clinicians should utilize evidence-based acute migraine-specific therapy stressing the imperative acute treatment goal of early intervention, but not too often with the correct drug, formulation, and dose. This therapy needs to provide cost-effective fast results, meaningful to the patient while minimizing the need for additional drugs. Migraine-ACT evaluates 2-hour pain freedom with return to normal function, comfort with treatment, and consistency of response. Employ a thoroughly educated patient, formulary, testimonials, stratification, and rational cotherapy against the race to central sensitization for optimum outcomes. Thieme Medical Publishers.

Factors associated with switching and combination use of antidepressants in young Swedish adults

PubMed Central

Andersson Sundell, K; Petzold, M G; Wallerstedt, S M

2013-01-01

Aims Little is known on factors associated with switching and combination use of antidepressants. Our aim was to describe such use and to analyse the association with socioeconomic factors and level of care in Swedish adults aged 20–34 years. Methods Individuals, aged 20–34 years, who purchased an antidepressant in January–June 2006, and who had not purchased any antidepressant in the preceding 6 months (n = 24,897) were followed from 6 up to 12 months. Among those who purchased ≥ 2 antidepressant substances, switchers were defined as those who did not fulfil the requirements for combination use. Data on purchased antidepressants and socioeconomic characteristics were obtained from the Swedish Prescribed Drug Register and Statistics Sweden. The association between (i) ≥ 2 antidepressants or (ii) switching, respectively, and socioeconomic factors as well as level of care was analysed with multiple logistic regression. Results A total of 4254 individuals (17%) purchased ≥ 2 antidepressant substances, and the remaining 20,643 (83%) purchased one antidepressant. The adjusted odds ratio (OR) for purchase of ≥ 2 antidepressants (vs. purchase of one antidepressant only) was higher among those who started on mirtazapine compared with selective serotonin re-uptake inhibitors: 2.23 (95% confidence interval: 1.93–2.57), and lower in individuals with high education: 0.64 (0.54–0.75), and shorter length of follow-up: 0.73 (0.62–0.85). Among those with ≥ 2 antidepressants, 71.6% were classified as switchers. The adjusted OR for switching (vs. combination use) were higher among divorced/widows/widowers: 1.61 (1.05–2.49), and lower among individuals with short university education: 0.58 (0.43–0.78), those starting on mirtazapine: 0.78 (0.62–0.97), and when treatment was initiated in psychiatric care: 0.75 (0.63–0.88). Conclusions One of six new users purchased at least two antidepressants, the majority were classified as switchers. Purchase

Agmatine enhances antidepressant potency of MK-801 and conventional antidepressants in mice.

PubMed

Neis, Vivian Binder; Moretti, Morgana; Manosso, Luana Meller; Lopes, Mark W; Leal, Rodrigo Bainy; Rodrigues, Ana Lúcia S

2015-03-01

Agmatine, an endogenous guanidine amine, has been shown to produce antidepressant-like effects in animal studies. This study investigated the effects of the combined administration of agmatine with either conventional monoaminergic antidepressants or the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 in the tail suspension test (TST) in mice. The aim was to evaluate the extent of the antidepressant synergism by examining the ability of a fixed dose of agmatine to shift the antidepressant potency of fluoxetine, imipramine, bupropion and MK-801. A sub-effective dose of agmatine (0.0001 mg/kg, p.o.) significantly increased the potency by which fluoxetine, imipramine, bupropion and MK-801 decreased immobility time in the TST by 2-fold (fluoxetine), 10-fold (imipramine and bupropion) and 100-fold (MK-801). Combined with previous evidence indicating a role of monoaminergic systems in the effect of agmatine, the current data suggest that agmatine may modulate monoaminergic neurotransmission and augment the activity of conventional antidepressants. Moreover, this study found that agmatine substantially augmented the antidepressant-like effect of MK-801, reinforcing the notion that this compound modulates NMDA receptor activation. These preclinical data may stimulate future clinical studies testing the effects of augmentation therapy with agmatine for the management of depressive disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Involvement of PI3K/Akt Signaling Pathway and Its Downstream Intracellular Targets in the Antidepressant-Like Effect of Creatine.

PubMed

Cunha, Mauricio P; Budni, Josiane; Ludka, Fabiana K; Pazini, Francis L; Rosa, Julia Macedo; Oliveira, Ágatha; Lopes, Mark W; Tasca, Carla I; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

2016-07-01

Creatine has been proposed to exert beneficial effects in the management of depression, but the cell signaling pathways implicated in its antidepressant effects are not well established. This study investigated the involvement of PI3K/Akt signaling pathway and its downstream intracellular targets in the antidepressant-like effect of creatine. The acute treatment of mice with creatine (1 mg/kg, po) increased the Akt and P70S6K phosphorylation, and HO-1, GPx and PSD95 immunocontents. The pretreatment of mice with LY294002 (10 nmol/mouse, icv, PI3K inhibitor), wortmannin (0.1 μg/mouse, icv, PI3K inhibitor), ZnPP (10 μg/mouse, icv, HO-1 inhibitor), or rapamycin (0.2 nmol/mouse, icv, mTOR inhibitor) prevented the antidepressant-like effect of creatine (1 mg/kg, po) in the TST. In addition, the administration of subeffective dose of either the selective GSK3 inhibitor AR-A014418 (0.01 μg/mouse, icv), the nonselective GSK3 inhibitor lithium chloride (10 mg/kg, po), or the HO-1 inductor CoPP (0.01 μg/mouse, icv), in combination with a subeffective dose of creatine (0.01 mg/kg, po) reduced the immobility time in the TST as compared with either drug alone. No treatment caused significant changes in the locomotor activity of mice. These results indicate that the antidepressant-like effect of creatine in the TST depends on the activation of Akt, Nrf2/HO-1, GPx, and mTOR, and GSK3 inhibition.

Two standardized fractions of Gardenia jasminoides Ellis with rapid antidepressant effects are differentially associated with BDNF up-regulation in the hippocampus.

PubMed

Ren, Li; Tao, Weiwei; Zhang, Hailou; Xue, Wenda; Tang, Juanjuan; Wu, Ruyan; Xia, Baomei; Wu, Haoxing; Chen, Gang

2016-07-01

Gardenia jasminoides Ellis (GJ) is one of the five constituents of Yueju pill, a Traditional Chinese Medicine for treatment of syndromes associated with mood disorders. Recently, preclinical and clinical studies suggest that Yueju pill confers rapid antidepressant effects. GJ is identified as the constituent primary for Yueju pill's rapid antidepressant effects. GJ's antidepressant action is temporally associated with up-regulated expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. The present study aimed to identify chemical fractions responsible for the rapid antidepressant efficacy of GJ and its association with BDNF signaling. Four fractions of GJ were extracted using standardized procedure. The four fractions were screened for rapid antidepressant potential, using the behavioral paradigm of forced swimming test (FST) and tail suspension test (TST) assessed at 24h post a single administration. A single dose of the putatively effective fractions was further tested in mice exposed to chronic mild stress (CMS), followed with a comprehensive behavioral testing including TST, FST, sucrose preference test (SPT), and novelty suppressed-feeding (NSF). To test the association of BDNF signaling with rapid antidepressant effects of effective factions, the expressions of BDNF and its receptor tropomyosin receptor kinase B (TrkB) in the hippocampus were assessed at different times post a single administration of effective fractions. Both petroleum ether (GJ-PE) and n-butyl alcohol fraction (GJ-BO) fractions of GJ displayed rapid antidepressant potential in the FST. In the TST, the antidepressant effects of GJ-PE lasted for a longer time than GJ-BO. Acute administration of either GJ-PE or GJ-BO significantly reversed the behavioral deficits in the tests of TST, FST, SPT and NSF in chronically stressed mice, confirming both fractions conferred rapid antidepressant efficacy. Interestingly, GJ-PE, but not GJ-BO, increased the expression of BDNF and Trk

Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

MedlinePlus

... Childhood ALL Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key ...

Treatment Options for Adult Acute Lymphoblastic Leukemia

MedlinePlus

... Childhood ALL Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key ...

Comparative efficacy, acceptability, and safety of medicinal, cognitive-behavioral therapy, and placebo treatments for acute major depressive disorder in children and adolescents: a multiple-treatments meta-analysis.

PubMed

Ma, Dongfeng; Zhang, Zhijun; Zhang, Xiangrong; Li, Lingjiang

2014-06-01

New generation antidepressant therapies, including serotonin-norepinephrine reuptake inhibitor (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) were introduced in the late 1980s; however, few comprehensive studies compared the benefits and risks of various contemporary treatments for major depressive disorder (MDD) in pediatric patients. Multiple-treatments meta-analysis (MTM) was conducted to assess efficacy, acceptability, and safety of contemporary interventions in children and adolescents with MDD. Cochrane Library, AMED, CINAHL, EMBASE, LiLACS, MEDLINE, PSYCINFO, PSYNDEX, and Journal of Medicine and Pharmacy databases were searched for randomized controlled trials (RCTs) comparing medicinal interventions (citalopram, escitalopram, fluoxetine, mirtazapine, paroxetine, sertraline, venlafaxine), cognitive behavioral therapy (CBT), combined fluoxetine with CBT, and placebo treatment for acute MDD from January 1988 to March 2013. Treatment success, dropout rate, and suicidal ideation/attempt outcomes were measured. Bayesian methods were used to conduct a MTM including age and funding subgroups. A total of 21 RCTs (4969 participants) were identified. Combined fluoxetine/CBT exhibited the highest efficacy, with fluoxetine alone superior to CBT, paroxetine, sertraline, citalopram, escitalopram, and placebo treatment. Sertraline, paroxetine, escitalopram, and venlafaxine showed superior acceptability to fluoxetine and combined fluoxetine/CBT. Combined fluoxetine/CBT combination was less safe, though CBT was safer than fluoxetine alone. Combined fluoxetine/CBT, fluoxetine, and mirtazapine exhibited the highest efficacy; sertraline, escitalopram, venlafaxine, and paroxetine were the best tolerated; and mirtazapine and venlafaxine were the safest. Sertraline and mirtazapine exhibited optimally balanced efficacy, acceptability, and safety for first-line acute treatment of child and adolescent MDD.

Risk of manic switch associated with antidepressant therapy in pediatric bipolar depression.

PubMed

Bhowmik, Debajyoti; Aparasu, Rajender R; Rajan, Suja S; Sherer, Jeffrey T; Ochoa-Perez, Melissa; Chen, Hua

2014-12-01

The purpose of this study was to assess the risk of manic switch associated with antidepressants in Medicaid-enrolled pediatric patients with bipolar depression. This retrospective cohort study involved 2003-2007 Medicaid Analytic eXtract (MAX) data from four geographically diverse states. The study sample included children and adolescents (ages 6-18 years) who had received a diagnosis of bipolar disorder on two or more separate occasions or during a hospital discharge, followed by a diagnosis of depression. According to the pharmacotherapy received by these patients in the 30 days around the index bipolar depression diagnosis, patients were categorized into five mutually exclusive groups. Manic switch was defined as having received a diagnosis of mania within 6 weeks after the initiation of bipolar depression treatment. Relative risks of manic switch between antidepressant monotherapy/polytherapy and their alternatives were assessed using Cox proportional hazards model. The robustness of the conventional Cox proportional hazards model toward possible bias caused by unobserved confounders was tested using instrumental variable analysis, and the uncertainty regarding manic switch definition was tested by altering the duration of follow-up. After applying all the selection criteria, 179 antidepressant monotherapy, 1047 second-generation antipsychotic (SGA) monotherapy, 570 mood stabilizer monotherapy, 445 antidepressant polytherapy, and 1906 SGA-mood stabilizer polytherapy users were identified. In Cox proportional hazard analyses, both antidepressant monotherapy and polytherapy exhibited higher risk of manic switch than their alternatives (antidepressant monotherapy vs. SGA monotherapy, hazard ratio [HR]=2.87 [95% CI: 1.10-7.49]; antidepressant monotherapy vs. mood stabilizer monotherapy, HR=1.41 [95% CI: 0.52-3.80); antidepressant polytherapy vs. SGA-mood stabilizer polytherapy, HR=1.61 [95% CI: 0.90-2.89]). However, only the comparison between antidepressant

Antidepressant medications and osteoporosis.

PubMed

Rizzoli, R; Cooper, C; Reginster, J-Y; Abrahamsen, B; Adachi, J D; Brandi, M L; Bruyère, O; Compston, J; Ducy, P; Ferrari, S; Harvey, N C; Kanis, J A; Karsenty, G; Laslop, A; Rabenda, V; Vestergaard, P

2012-09-01

Use of antidepressant medications that act on the serotonin system has been linked to detrimental impacts on bone mineral density (BMD), and to osteoporosis. This article reviews current evidence for such effects, and identifies themes for future research. Serotonin receptors are found in all major types of bone cell (osteoblasts, osteocytes, and osteoclasts), indicating an important role of the neuroendocrine system in bone. Observational studies indicate a complex relationship between depression, antidepressants, and fracture. First, the presence of depression itself increases fracture risk, in relation with decreased BMD and an increase in falls. A range of aspects of depression may operate, including behavioral factors (e.g., smoking and nutrition), biological changes, and confounders (e.g., comorbidities and concomitant medications). A substantial proportion of depressed patients receive antidepressants, mostly selective serotonin reuptake inhibitors (SSRIs). Some of these have been linked to decreased BMD (SSRIs) and increased fracture risk (SSRIs and tricyclic agents). Current use of SSRIs and tricyclics increases fracture risk by as much as twofold versus nonusers, even after adjustment for potential confounders. While there is a dose-response relationship for SSRIs, the effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. The increase in risk is the greatest in the early stages of treatment, with a dramatic increase after initiation, reaching a peak within 1 month for tricyclics and 8 months for SSRIs. Treatment-associated increased risk diminishes towards baseline in the year following discontinuation. The body of evidence suggests that SSRIs should be considered in the list of medications that are risk factors for osteoporotic fractures. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of antidepressants and psychological therapies, including hypnotherapy, in irritable bowel syndrome: systematic review and meta-analysis.

PubMed

Ford, Alexander C; Quigley, Eamonn M M; Lacy, Brian E; Lembo, Anthony J; Saito, Yuri A; Schiller, Lawrence R; Soffer, Edy E; Spiegel, Brennan M R; Moayyedi, Paul

2014-09-01

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. Evidence relating to the treatment of this condition with antidepressants and psychological therapies continues to accumulate. We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Trials recruiting adults with IBS, which compared antidepressants with placebo, or psychological therapies with control therapy or "usual management," were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). The search strategy identified 3,788 citations. Forty-eight RCTs were eligible for inclusion: thirty-one compared psychological therapies with control therapy or "usual management," sixteen compared antidepressants with placebo, and one compared both psychological therapy and antidepressants with placebo. Ten of the trials of psychological therapies, and four of the RCTs of antidepressants, had been published since our previous meta-analysis. The RR of IBS symptom not improving with antidepressants vs. placebo was 0.67 (95% CI=0.58-0.77), with similar treatment effects for both tricyclic antidepressants and selective serotonin reuptake inhibitors. The RR of symptoms not improving with psychological therapies was 0.68 (95% CI=0.61-0.76). Cognitive behavioral therapy, hypnotherapy, multicomponent psychological therapy, and dynamic psychotherapy were all beneficial. Antidepressants and some psychological therapies are effective treatments for IBS. Despite the considerable number of studies published in the intervening 5 years since we last examined this issue, the overall summary estimates of treatment effect have remained remarkably stable.

Housing conditions modulate escitalopram effects on antidepressive-like behaviour and brain neurochemistry.

PubMed

Bjørnebekk, Astrid; Mathé, Aleksander A; Gruber, Susanne H M; Brené, Stefan

2008-12-01

Despite limited understanding of the pathophysiology of depression and the underlying mechanisms mediating antidepressant effects, there are several efficient treatments. The anhedonia symptoms of depression are characterized by decreased motivation and drive and imply possible malfunctioning of the mesolimbic dopamine system, whereas cognitive deficits might reflect decreased plasticity in hippocampus. In female Flinders Sensitive Line (FSL) rats, a model of depression, we compared the effects of three long-term antidepressant treatments: voluntary running, escitalopram and the combination of both on antidepressant-like behaviour in the Porsolt swim test (PST), and on regulation of mRNA for dopamine and neuropeptides in striatal dopamine pathways and brain-derived neurotrophic factor (BDNF) in hippocampus. Escitalopram diet attenuated running behaviour in FSL rats but not in non-depressed controls rats. In the PST the running group had increased climbing activity (noradrenergic/dopaminergic response), whereas the combination of escitalopram and running-wheel access increased swimming (serotonergic response). Running elevated mRNA for dynorphin in caudate putamen and BDNF in hippocampus. The combined treatment down-regulated D1 receptor and enkephalin mRNA in accumbens. Escitalopram alone did not affect behaviour or mRNA levels. We demonstrate a novel behavioural effect of escitalopram, i.e. attenuation of running in 'depressed' rats. The antidepressant-like effect of escitalopram was dependent on the presence of a running wheel, but not actual running indicating that the environment influenced the antidepressant effect of escitalopram. Different patterns of mRNA changes in hippocampus and brain reward pathways and responses in the PST by running and escitalopram suggest that antidepressant-like responses by running and escitalopram are achieved by different mechanisms.

Mouse Strain Affects Behavioral and Neuroendocrine Stress Responses Following Administration of Probiotic Lactobacillus rhamnosus JB-1 or Traditional Antidepressant Fluoxetine.

PubMed

McVey Neufeld, Karen-Anne; Kay, Sebastian; Bienenstock, John

2018-01-01

Currently, there is keen interest in the development of alternative therapies in the treatment of depression. Given the explosion of research focused on the microbiota-gut-brain axis, consideration has turned to the potential of certain probiotics to improve patient outcomes for those suffering from mood disorders. Here we examine the abilities of a known antidepressant, fluoxetine, and the probiotic Lactobacillus rhamnosus JB-1™, to attenuate responses to two established criteria for depressive-like behavior in animal models, the tail suspension test (TST) and the corticosterone response to an acute restraint stressor. We examine two different strains of mice known to differ in the extent to which they express both anxiety-like behavior and measures of despair-BALB/c and Swiss Webster-with respectively high and normal behavioral phenotypes for each. While adult male BALB/c mice responded with increased antidepressive-like behavior to both fluoxetine and L. rhamnosus JB-1 in both the TST and the corticosterone stress response, SW mice did not respond to either treatment as compared to controls. These findings highlight the importance of investigating putative antidepressants in mouse strains known to express face validity for some markers of depression. Clinical studies examining the activity of L. rhamnosus JB-1 in patients suffering from mood disorders are warranted, as well as further pre-clinical work examining how interactions between host genotype and intestinal microbial alterations may impact behavioral responses. This study adds to the literature supporting the possibility that modifying the intestinal microbiota via probiotics represents a promising potential therapeutic breakthrough in the treatment of psychiatric disease.

Mouse Strain Affects Behavioral and Neuroendocrine Stress Responses Following Administration of Probiotic Lactobacillus rhamnosus JB-1 or Traditional Antidepressant Fluoxetine

PubMed Central

McVey Neufeld, Karen-Anne; Kay, Sebastian; Bienenstock, John

2018-01-01

Currently, there is keen interest in the development of alternative therapies in the treatment of depression. Given the explosion of research focused on the microbiota-gut-brain axis, consideration has turned to the potential of certain probiotics to improve patient outcomes for those suffering from mood disorders. Here we examine the abilities of a known antidepressant, fluoxetine, and the probiotic Lactobacillus rhamnosus JB-1™, to attenuate responses to two established criteria for depressive-like behavior in animal models, the tail suspension test (TST) and the corticosterone response to an acute restraint stressor. We examine two different strains of mice known to differ in the extent to which they express both anxiety-like behavior and measures of despair—BALB/c and Swiss Webster—with respectively high and normal behavioral phenotypes for each. While adult male BALB/c mice responded with increased antidepressive-like behavior to both fluoxetine and L. rhamnosus JB-1 in both the TST and the corticosterone stress response, SW mice did not respond to either treatment as compared to controls. These findings highlight the importance of investigating putative antidepressants in mouse strains known to express face validity for some markers of depression. Clinical studies examining the activity of L. rhamnosus JB-1 in patients suffering from mood disorders are warranted, as well as further pre-clinical work examining how interactions between host genotype and intestinal microbial alterations may impact behavioral responses. This study adds to the literature supporting the possibility that modifying the intestinal microbiota via probiotics represents a promising potential therapeutic breakthrough in the treatment of psychiatric disease.

Antidepressant and Neurocognitive Effects of Isoflurane Anesthesia versus Electroconvulsive Therapy in Refractory Depression

PubMed Central

Weeks, Howard R.; Tadler, Scott C.; Smith, Kelly W.; Iacob, Eli; Saccoman, Mikala; White, Andrea T.; Landvatter, Joshua D.; Chelune, Gordon J.; Suchy, Yana; Clark, Elaine; Cahalan, Michael K.; Bushnell, Lowry; Sakata, Derek; Light, Alan R.; Light, Kathleen C.

2013-01-01

Background Many patients have serious depression that is nonresponsive to medications, but refuse electroconvulsive therapy (ECT). Early research suggested that isoflurane anesthesia may be an effective alternative to ECT. Subsequent studies altered drug, dose or number of treatments, and failed to replicate this success, halting research on isoflurane's antidepressant effects for a decade. Our aim was to re-examine whether isoflurane has antidepressant effects comparable to ECT, with less adverse effects on cognition. Method Patients with medication-refractory depression received an average of 10 treatments of bifrontal ECT (n = 20) or isoflurane (n = 8) over 3 weeks. Depression severity (Hamilton Rating Scale for Depression-24) and neurocognitive responses (anterograde and retrograde memory, processing speed and verbal fluency) were assessed at Pretreatment, Post all treatments and 4-week Follow-up. Results Both treatments produced significant reductions in depression scores at Post-treatment and 4-week Follow-up; however, ECT had modestly better antidepressant effect at follow-up in severity-matched patients. Immediately Post-treatment, ECT (but not isoflurane) patients showed declines in memory, fluency, and processing speed. At Follow-up, only autobiographical memory remained below Pretreatment level for ECT patients, but isoflurane patients had greater test-retest neurocognitive score improvement. Conclusions Our data reconfirm that isoflurane has an antidepressant effect approaching ECT with less adverse neurocognitive effects, and reinforce the need for a larger clinical trial. PMID:23922809

Drug–drug interactions involving antidepressants: focus on desvenlafaxine

PubMed Central

Low, Yvette; Setia, Sajita; Lima, Graca

2018-01-01

Psychiatric and physical conditions often coexist, and there is robust evidence that associates the frequency of depression with single and multiple physical conditions. More than half of patients with depression may have at least one chronic physical condition. Therefore, antidepressants are often used in cotherapy with other medications for the management of both psychiatric and chronic physical illnesses. The risk of drug–drug interactions (DDIs) is augmented by complex polypharmacy regimens and extended periods of treatment required, of which possible outcomes range from tolerability issues to lack of efficacy and serious adverse events. Optimal patient outcomes may be achieved through drug selection with minimal potential for DDIs. Desvenlafaxine is a serotonin–norepinephrine reuptake inhibitor approved for the treatment of adults with major depressive disorder. Pharmacokinetic studies of desvenlafaxine have shown a simple metabolic profile unique among antidepressants. This review examines the DDI profiles of antidepressants, particularly desvenlafaxine, in relation to drugs of different therapeutic areas. The summary and comparison of information available is meant to help clinicians in making informed decisions when using desvenlafaxine in patients with depression and comorbid chronic conditions. PMID:29497300

Platelet alpha 2-adrenergic receptors in major depressive disorder. Binding of tritiated clonidine before and after tricyclic antidepressant drug treatment

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

Garcia-Sevilla, J.A.; Zis, A.P.; Hollingsworth, P.J.

1981-12-01

The specific binding of tritiated (3H)-clonidine, an alpha 2-adrenergic receptor agonist, to platelet membranes was measured in normal subjects and in patients with major depressive disorder. The number of platelet alpha 2-adrenergic receptors from the depressed group was significantly higher than that found in platelets obtained from the control population. Treatment with tricyclic antidepressant drugs led to significant decreases in the number of platelet alpha 2-adrenergic receptors. These results support the hypothesis that the depressive syndrome is related to an alpha 2-adrenergic receptor supersensitivity and that the clinical effectiveness of tricyclic antidepressant drugs is associated with a decrease in themore » number of these receptors.« less

Possible involvement of neuropeptide Y Y1 receptors in antidepressant like effect of agmatine in rats.

PubMed

Kotagale, Nandkishor R; Paliwal, Nikhilesh P; Aglawe, Manish M; Umekar, Milind J; Taksande, Brijesh G

2013-09-01

Agmatine and neuropeptide Y (NPY) are widely distributed in central nervous system and critically involved in modulation of depressive behavior in experimental animals. However their mutual interaction, if any, in regulation of depression remain largely unexplored. In the present study we explored the possible interaction between agmatine and neuropeptide Y in regulation of depression like behavior in forced swim test. We found that acute intracerebroventricular (i.c.v.) administration of agmatine (20-40μg/rat), NPY (5 and 10μg/rat) and NPY Y1 receptor agonist, [Leu(31), Pro(34)]-NPY (0.4 and 0.8ng/rat) dose dependently decreased immobility time in forced swim test indicating their antidepressant like effects. In combination studies, the antidepressant like effect of agmatine (10μg/rat) was significantly potentiated by NPY (1 and 5μg/rat, icv) or [Leu(31), Pro(34)]-NPY (0.2 and 0.4ng/rat, icv) pretreatment. Conversely, pretreatment of animals with NPY Y1 receptor antagonist, BIBP3226 (0.1ng/rat, i.c.v.) completely blocked the antidepressant like effect of agmatine (20-40μg/rat) and its synergistic effect with NPY (1μg/rat, icv) or [Leu(31), Pro(34)]-NPY (0.2ng/rat, icv). The results of the present study showed that, agmatine exerts antidepressant like effects via NPYergic system possibly mediated by the NPY Y1 receptor subtypes and suggest that interaction between agmatine and neuropeptide Y may be relevant to generate the therapeutic strategies for the treatment of depression. Copyright © 2013 Elsevier Inc. All rights reserved.

Antidepressants and Youth: Healing or Harmful?

PubMed Central

Markowitz, Sara; Cuellar, Alison

2007-01-01

A series of drug innovations that began in 1987, including the introduction of several Selective Serotonin Reuptake Inhibitors (SSRIs) has led to a tremendous growth in the use of antidepressants in the United States. This growth, however, has been accompanied by a growing concern about the risks of prescribing antidepressants, particularly to children. Indeed, research linking the use of antidepressant drugs to an increased risk of suicidal behaviors in youth motivated the U.S. Food and Drug Administration to direct antidepressant drug manufacturers to include warning labels about the potential dangers. This paper examines the relationship between antidepressants and suicide among youth in the USA. Using state-level data on youth suicides and age-specific prescriptions for antidepressants, we find no relationships between suicides for adolescents ages 15 to 19 and prescriptions for Selective Serotonin Reuptake Inhibitors/Serotonin-Norepinephrine Reuptake Inhibitors or tricyclic and tetracyclic antidepressants. In contrast, we find that newer generation antidepressants are associated with lower numbers of suicides for this age group. For younger children, ages 10 to 14 we find no relationship with suicides for any type of antidepressant. PMID:17374550

Are studies of psychotherapies for depression more or less generalizable than studies of antidepressants?

PubMed

Lorenzo-Luaces, Lorenzo; Zimmerman, Mark; Cuijpers, Pim

2018-07-01

The generalizability of findings from studies exploring the efficacy of psychotherapy and antidepressants has been called into question in part because studies exclude many patients. Despite this, the frequency with which psychotherapy and antidepressant studies use specific inclusion and exclusion criteria has never been compared. We explored the exclusion criteria used in psychotherapy and pharmacotherapy studies from 1995 to 2014. Systematic literature searches were conducted in PubMed, Medline, PsycINFO, and Embase of published randomized controlled trials (RCTs) of the treatment of major depressive disorder (MDD) in adults with either antidepressants (vs. placebos) or psychotherapy (vs. placebos, treatments as usual, or other controls). Most psychotherapy (81%) and antidepressant (100%) trials excluded patients with milder symptoms as well as patients with elevated suicidal risk (56-75%), psychotic symptoms (84-88%), or substance misuse (75-81%). Psychotherapy studies were less likely to exclude patients on the basis of brief episode duration (0% vs. 48%) and co-morbid Axis I disorders (6% vs. 27%). However, psychotherapy studies excluded patients with more severe symptoms more frequently (38%) than antidepressant studies (8%). Overall, psychotherapy studies appear somewhat more inclusive than antidepressant studies. On average, antidepressant studies appear to target patients with more chronic and severe, as well as more purely depressive presentations. Copyright © 2018 Elsevier B.V. All rights reserved.

Appropriateness of antidepressant prescribing: an observational study in a Scottish primary-care setting.

PubMed

Cameron, Isobel M; Lawton, Kenneth; Reid, Ian C

2009-09-01

Since the 1990s, Scottish community-based antidepressant prescribing has increased substantially. To assess whether GPs prescribe antidepressants appropriately. Observational study of adults (aged >/=16 years) screened with the Hospital Anxiety and Depression Scale (HADS) attending a GP. Four practices in Grampian, Scotland. Patients (n = 898) completed the HADS, and GPs independently estimated depression status. Notes were scrutinised for evidence of antidepressant use, and the appropriateness of prescribing was assessed. A total of 237 (26%) participants had HADS scores indicating 'possible' (15%) or 'probable' (11%) depression. The proportion of participants rated as depressed by their GP differed significantly by HADS depression subscale scores. Odds ratio for 'possible' versus 'no' depression was 3.54 (95% confidence interval [CI] = 2.17 to 5.76, P<0.001); and for 'probable' versus 'possible' depression was 3.59 (95% CI = 2.06 to 6.26, P<0.001). Similarly, the proportion of participants receiving antidepressants differed significantly by HADS score. Odds ratio for 'possible' versus 'no' depression was 2.79 (95% CI = 1.70 to 4.58, P<0.001); and for 'probable' versus 'possible' was 2.12 (95% CI = 1.21 to 3.70, P = 0.009). In 101 participants with 'probable' depression, GPs recognised 53 (52%) participants as having a clinically significant depression. Inappropriate initiation of antidepressant treatment occurred very infrequently. Prescribing to participants who were not symptomatic was accounted for by the treatment of pain, anxiety, or relapse prevention, and for ongoing treatment of previously identified depression. There was little evidence of prescribing without relevant indication. Around half of patients with significant symptoms were not identified by their GP as suffering from a depressive disorder: this varied inversely with severity ratings. Rather than prescribing indiscriminately (as has been widely assumed), it is likely that GPs are initiating

Antidepressant sales and the risk for alcohol-related and non-alcohol-related suicide in Finland--an individual-level population study.

PubMed

Moustgaard, Heta; Joutsenniemi, Kaisla; Myrskylä, Mikko; Martikainen, Pekka

2014-01-01

A marked decline in suicide rates has co-occurred with increased antidepressant sales in several countries but the causal connection between the trends remains debated. Most previous studies have focused on overall suicide rates and neglected differential effects in population subgroups. Our objective was to investigate whether increasing sales of non-tricyclic antidepressants have reduced alcohol- and non-alcohol-related suicide risk in different population subgroups. We followed a nationally representative sample of 950,158 Finnish adults in 1995-2007 for alcohol-related (n = 2,859) and non-alcohol-related (n = 8,632) suicides. We assessed suicide risk by gender and social group according to regional sales of non-tricyclic antidepressants, measured by sold doses per capita, prevalence of antidepressant users, and proportion of antidepressant users with doses reflecting minimally adequate treatment. Fixed-effects Poisson regression models controlled for regional differences and time trends that may influence suicide risk irrespective of antidepressant sales. The number of sold antidepressant doses per capita and the prevalence of antidepressant users were unrelated to male suicide risk. However, one percentage point increase in the proportion of antidepressant users receiving minimally adequate treatment reduced non-alcohol-related male suicide risk by one percent (relative risk 0.987, 95% confidence interval 0.976-0.998). This beneficial effect only emerged among men with high education, high income, and employment, among men without a partner, and men not owning their home. Alcohol-related suicides and female suicides were unrelated to all measures of antidepressant sales. We found little evidence that increase in overall sales or in the prevalence of non-tricyclic antidepressant users would have caused the fall in suicide rates in Finland in 1995-2007. However, the rise in the proportion of antidepressant users receiving minimally adequate treatment, possibly

Acute working memory improvement after tDCS in antidepressant-free patients with major depressive disorder.

PubMed

Oliveira, Janaina F; Zanão, Tamires A; Valiengo, Leandro; Lotufo, Paulo A; Benseñor, Isabela M; Fregni, Felipe; Brunoni, André R

2013-03-14

Based on previous studies showing that transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique that employs weak, direct currents to induce cortical-excitability changes, might be useful for working memory (WM) enhancement in healthy subjects and also in treating depressive symptoms, our aim was to evaluate whether tDCS could acutely enhance WM in depressed patients. Twenty-eight age- and gender-matched, antidepressant-free depressed subjects received a single-session of active/sham tDCS in a randomized, double-blind, parallel design. The anode was positioned over the left and the cathode over the right dorsolateral prefrontal cortex. The n-back task was used for assessing WM and it was performed immediately before and 15min after tDCS onset. We found that active vs. sham tDCS led to an increase in the rate of correct responses. We also used signal detection theory analyses to show that active tDCS increased both discriminability, i.e., the ability to discriminate signal (correct responses) from noise (false alarms), and response criterion, indicating a lower threshold to yield responses. All effect sizes were large. In other words, one session of tDCS acutely enhanced WM in depressed subjects, suggesting that tDCS can improve "cold" (non affective-loaded) working memory processes in MDD. Based on these findings, we discuss the effects of tDCS on WM enhancement in depression. We also suggest that the n-back task could be used as a biomarker in future tDCS studies investigating prefrontal activity in healthy and depressed samples. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Evaluation of Antidepressant-like Effect of Citrus Maxima Leaves in Animal Models of Depression.

PubMed

Potdar, Vikram H; Kibile, Swati J

2011-09-01

This study planned to assess antidepressant like activity of aqueous extract from leaves of Citrus maxima Merr. (Rutaceae). Boiling was used for aqueous extraction. Acute toxicity study was performed in mice. Antidepressant activity was studied using locomotor activity test, modified forced swimming test (FST) and tail suspension test (TST). Three doses 100, 200 and 300 mg/kg of aqueous extract of leaves were selected for testing. Fluoxetine (20 mg/kg, i.p.) and imipramine (30 mg/kg, i.p.) were used as the standard drugs. Aqueous extract of Citrus maxima leaves significantly reduced immobility time in both TST and FST. In locomotor activity testing it showed psychostimulant effect. Extract increased the climbing behavior in FST, which is similar to effect observed with imipramine. The results of this study suggest that antidepressant like effect of Citrus maxima seems to be mediated by an increase in norepinephrine level in synapses.

[Headache Treatment].

PubMed

Diener, Hans Christoph; Holle-Lee, Dagny; Nägel, Steffen; Gaul, Charly

2017-03-01

A precondition for the successful treatment of headaches is the correct headache diagnosis. Triptans are effective for attack treatment of migraine and cluster headache. However, there are not effective for the treatment of tension-type headache. For the prevention of frequent episodic migraine betablockers, flunarizine, topiramate and amitriptyline are recommended. For the prevention of chronic migraine evidence is only available for onabotulinumtoxinA and topiramate. For prophylactic treatment of tension-type headaches tricyclic antidepressants are used. In cluster headache verapamil (in combination with steroids) is the most frequently used prophylactic agent. This article focusses on the current acute and prophylactic treatment of common headache syndromes. © Georg Thieme Verlag KG Stuttgart · New York.

Patterns and predictors of antidepressant use in ambulatory cancer patients with common solid tumors.

PubMed

Fisch, Michael J; Zhao, Fengmin; Manola, Judith; Miller, Andrew H; Pirl, William F; Wagner, Lynne I

2015-05-01

Depressive symptoms and antidepressant use are prevalent among cancer patients. We sought to identify determinants of prescribing commonly used antidepressants. This multi-institutional study enrolled 3106 ambulatory patients with cancer of the breast, prostate, colon/rectum, or lung. Five case-finding methods were used to identify patients with depressive symptoms. Logistic models were used to examine factors that impact antidepressant use. Approximately, 47% of patients were defined as having depressive symptoms. Clinicians rated being sad/depressed as one of the top three priority problems for 10.5% of patients. Antidepressants were prescribed in 19% of all patients, 25% with depressive symptoms and 14% nondepressed patients. After adjusting for other covariates, these variable categories were significantly associated with greater use of antidepressants: depressive symptoms, family history of depression, concurrent medication use, cancer treatment status, and certain other clinical and demographic variables. The strongest individual predictors were concurrent use of more than 10 medications (odds ratio [OR] = 3.3), a family history of depression (OR = 2.2), sedative use (OR = 2.1), non-Hispanic white race (OR = 2.0), and anxiolytics use (OR = 2.0). Depressive symptoms are found in nearly half of outpatients with cancer, and one-fourth of patients with depressive symptoms are taking an antidepressant. Patients receiving antidepressants are more often those taking multiple medications, those with a depression diathesis, and those with more extensive cancer treatment. Patients who were younger, white, and female were also more likely to be taking antidepressants. Copyright © 2014 John Wiley & Sons, Ltd.

Voluntary Exercise Produces Antidepressant and Anxiolytic Behavioral Effects in Mice

PubMed Central

Duman, Catharine H.; Schlesinger, Lee; Russell, David S.; Duman, Ronald S.

2008-01-01

Reports of beneficial effects of exercise on psychological health in humans are increasingly supported by basic research studies. Exercise is hypothesized to regulate antidepressant-related mechanisms and we therefore characterized the effects of chronic exercise in mouse behavioral paradigms relevant to antidepressant actions. Mice given free access to running wheels showed antidepressant-like behavior in learned helplessness, forced-swim (FST) and tail suspension paradigms. These responses were similar to responses of antidepressant drug-treated animals. When tested under conditions where locomotor activity was not altered, exercising mice also showed reduced anxiety compared to sedentary control mice. In situ hybridization analysis showed that BDNF mRNA was increased in specific subfields of hippocampus after wheel running. We chose one paradigm, the FST, in which to investigate a functional role for brain-derived neurotrophic factor (BDNF) in the behavioral response to exercise. We tested mice heterozygous for a deletion of the BDNF gene in the FST after wheel-running. Exercising wild-type mice showed the expected antidepressant-like behavioral response in the FST but exercise was ineffective in improving FST performance in heterozygous BDNF knockout mice. A possible functional contribution of a BDNF signaling pathway to FST performance in exercising mice was investigated using the specific MEK inhibitor PD184161 to block the MAPK signaling pathway. Subchronic administration of PD184161 to exercising mice blocked the antidepressant-like behavioral response seen in vehicle-treated exercising mice in the FST. In summary, chronic wheel-running exercise in mice results in antidepressant-like behavioral changes that may involve a BDNF related mechanism similar to that hypothesized for antidepressant drug treatment. PMID:18267317

Antidepressant use in Alzheimer's disease patients: results of the REAL.FR cohort.

PubMed

Arbus, Christophe; Gardette, Virginie; Bui, Eric; Cantet, Christelle; Andrieu, Sandrine; Nourhashémi, Fati; Schmitt, Laurent; Vellas, Bruno

2010-02-01

Psychotropic medication is widely prescribed in clinical practice for the management of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). However, there have been few pharmaco-epidemiological studies or studies conducted in a natural setting on the real use of antidepressants in AD. The aim of this survey was to assess the prevalence of antidepressant use in AD and to identify the clinical factors associated with antidepressant prescription. REAL.FR is a four-year, prospective, multi-center study. Baseline data including demographic characteristics, clinical variables and drug intake were obtained. Depressive symptoms were determined using the Neuropsychiatric Inventory (NPI). A total of 686 AD patients were included. Antidepressant treatment was prescribed for 34.8% of patients. Clinically significant depressive symptoms (NPI >or= 4) were observed in 20.5% of the total population. Although depressed subjects were significantly more likely to be treated with antidepressants than non-depressed subjects (p<0.0001), only 60% of depressed subjects overall were prescribed an antidepressant. In multivariate analysis, clinically significant depressive symptoms were associated with antidepressant prescription although this result was only observed in subjects without a previous history of depression. The available data on antidepressant efficacy in BPSD other than depression (in particular, agitation, aggression and, occasionally, psychotic symptoms) do not influence prescription choices. Depressive symptoms may be taken more seriously in the absence of a previous history of depression, leading to increased antidepressant prescription rates in individuals presenting with depression for the first time.

Adaptation of a Motivational Interviewing Intervention to Improve Antidepressant Adherence among Latinos

PubMed Central

Interian, Alejandro; Martinez, Igda; Rios, Lisbeth Iglesias; Krejci, Jonathan; Guarnaccia, Peter J.

2009-01-01

Poor antidepressant adherence is a significant issue in depression treatment that adversely affects treatment outcomes. While being a common problem, it tends to be more common among Latinos. To address this problem, the current study adapted a Motivational Interviewing (MI) intervention to improve adherence among Latinos with depression. The adaptation process included six focus groups that elicited participants’ perspectives (N = 30), applying the intervention with test cases (N = 7) to fine tune the intervention, and eliciting feedback on the intervention (N = 5). The findings generated from these adaptation phases are described, along with a case example. Examples of adaptations to the MI included reframing antidepressant adherence as a way to luchar (struggle) against problems, focusing on motivation for improving depression and not just medication, refining methods for imparting antidepressant information, and inclusion of personalized visual feedback on dose-taking. The findings provide a description of the antidepressant issues experienced by a group of Latinos, as well as considerations for applying MI with this population. The intervention remained grounded in MI principles, but was contextualized for this Latino group. PMID:20438160

Prevalence and characteristics of antidepressant drug prescriptions in older Italian patients.

PubMed

Marengoni, A; Bianchi, G; Nobili, A; Tettamanti, M; Pasina, L; Corrao, S; Salerno, F; Iorio, A; Marcucci, M; Mannucci, P M

2012-04-01

During last few decades, the proportion of elderly persons prescribed with antidepressants for the treatment of depression and anxiety has increased. The aim of this study was to evaluate prevalence of antidepressant prescription and related factors in elderly in-patients, as well as the consistency between prescription of antidepressants and specific diagnoses requiring these medications. Thirty-four internal medicine and four geriatric wards in Italy participated in the Registro Politerapie SIMI-REPOSI study during 2008. In all, 1,155 in-patients, 65 years or older, were enrolled. Prevalence of the use of antidepressants was calculated at both admission and discharge. Logistic regression was used to evaluate the association between patients' characteristics (age, gender, Charlson Index, number of drugs, specific diseases, other psychotropic medications) and the prescription of antidepressants. The number of patients treated with antidepressant medication at hospital admission was 115 (9.9%) and at discharge 119 (10.3%). In a multivariate analysis, a higher number of drugs (OR = 1.2; 95% CI = 1.1-1.3), use of anxiolytic drugs (OR = 2.1; 95% CI = 1.2-3.6 and OR = 3.8; 95% CI = 2.1-6.8), and a diagnosis of dementia (OR = 6.1; 95% CI = 3.1-11.8 and OR = 5.8; 95% CI = 3.3-10.3, respectively, at admission and discharge) were independently associated with antidepressant prescription. A specific diagnosis requiring the use of antidepressants was present only in 66 (57.4%) patients at admission and 76 (66.1%) at discharge. Antidepressants are commonly prescribed in geriatric patients, especially in those receiving multiple drugs, other psychotropic drugs, and those affected by dementia. There is an inconsistency between the prescription of antidepressants and a specific diagnosis that the hospitalization only slightly improves.

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.

Alterations in leukocyte transcriptional control pathway activity associated with major depressive disorder and antidepressant treatment.

PubMed

Mellon, S H; Wolkowitz, O M; Schonemann, M D; Epel, E S; Rosser, R; Burke, H B; Mahan, L; Reus, V I; Stamatiou, D; Liew, C-C; Cole, S W

2016-05-24

Major depressive disorder (MDD) is associated with a significantly elevated risk of developing serious medical illnesses such as cardiovascular disease, immune impairments, infection, dementia and premature death. Previous work has demonstrated immune dysregulation in subjects with MDD. Using genome-wide transcriptional profiling and promoter-based bioinformatic strategies, we assessed leukocyte transcription factor (TF) activity in leukocytes from 20 unmedicated MDD subjects versus 20 age-, sex- and ethnicity-matched healthy controls, before initiation of antidepressant therapy, and in 17 of the MDD subjects after 8 weeks of sertraline treatment. In leukocytes from unmedicated MDD subjects, bioinformatic analysis of transcription control pathway activity indicated an increased transcriptional activity of cAMP response element-binding/activating TF (CREB/ATF) and increased activity of TFs associated with cellular responses to oxidative stress (nuclear factor erythroid-derived 2-like 2, NFE2l2 or NRF2). Eight weeks of antidepressant therapy was associated with significant reductions in Hamilton Depression Rating Scale scores and reduced activity of NRF2, but not in CREB/ATF activity. Several other transcriptional regulation pathways, including the glucocorticoid receptor (GR), nuclear factor kappa-B cells (NF-κB), early growth response proteins 1-4 (EGR1-4) and interferon-responsive TFs, showed either no significant differences as a function of disease or treatment, or activities that were opposite to those previously hypothesized to be involved in the etiology of MDD or effective treatment. Our results suggest that CREB/ATF and NRF2 signaling may contribute to MDD by activating immune cell transcriptome dynamics that ultimately influence central nervous system (CNS) motivational and affective processes via circulating mediators.

Antidepressant-like effects of erythropoietin: a focus on behavioural and hippocampal processes.

PubMed

Osborn, Meagan; Rustom, Nazneen; Clarke, Melanie; Litteljohn, Darcy; Rudyk, Chris; Anisman, Hymie; Hayley, Shawn

2013-01-01

Depression is a chronic and debilitating condition with a significant degree of relapse and treatment resistance that could stem, at least in part, from disturbances of neuroplasticity. This has led to an increased focus on treatment strategies that target brain derived neurotrophic factor (BDNF), synaptic plasticity and adult neurogenesis. In the current study we aimed to assess whether erythropoietin (EPO) would have antidepressant-like effects given its already established pro-trophic actions. In particular, we assessed whether EPO would diminish the deleterious effects of a social stressor in mice. Indeed, EPO induced anxiolytic and antidepressant-like responses in a forced swim test, open field, elevated-plus maze, and a novelty test, and appeared to blunt some of the negative behavioural effects of a social stressor. Furthermore, EPO promoted adult hippocampal neurogenesis, an important feature of effective antidepressants. Finally, a separate study using the mTOR inhibitor rapamycin revealed that antagonizing this pathway prevented the impact of EPO upon forced swim performance. These data are consistent with previous findings showing that the mTOR pathway and its neurogenic and synaptogenic effects might mediate the behavioral consequences of antidepressant agents. Our findings further highlight EPO as a possible adjunct treatment for affective disorders, as well as other stressor associated disorders of impaired neuroplasticity.

Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases.

PubMed

Healy, David; Le Noury, Joanna; Mangin, Derelie

2018-05-01

To investigate clinical reports of post-SSRI sexual dysfunction (PSSD), post-finasteride syndrome (PFS) and enduring sexual dysfunction following isotretinoin. Data from RxISK.org, a global adverse event reporting website, have been used to establish the clinical features, demographic details and clinical trajectories of syndromes of persistent sexual difficulties following three superficially different treatment modalities.RESULTSWe report on 300 cases of enduring sexual dysfunction from 37 countries following 14 different drugs comprised of serotonin reuptake inhibiting antidepressants, 5α-reductase inhibitors and isotretinoin. While reports of certain issues were unique to the antidepressants, such as the onset of premature ejaculation and persistent genital arousal disorder (PGAD), there was also a significant overlap in symptom profile between the drug groups, with common features including genital anaesthesia, pleasureless or weak orgasm, loss of libido and impotence. Secondary consequences included relationship breakdown and impaired quality of life.CONCLUSIONSThese data point to a legacy syndrome or syndromes comprising a range of disturbances to sexual function. More detailed studies will require developments in coding systems that recognise the condition(s). Further exploration of these tardive sexual syndromes may yield greater understanding of tardive syndromes in general.

Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases

PubMed Central

Healy, David; Le Noury, Joanna; Mangin, Derelie

2018-01-01

OBJECTIVE: To investigate clinical reports of post-SSRI sexual dysfunction (PSSD), post-finasteride syndrome (PFS) and enduring sexual dysfunction following isotretinoin. METHODS: Data from RxISK.org, a global adverse event reporting website, have been used to establish the clinical features, demographic details and clinical trajectories of syndromes of persistent sexual difficulties following three superficially different treatment modalities. RESULTS We report on 300 cases of enduring sexual dysfunction from 37 countries following 14 different drugs comprised of serotonin reuptake inhibiting antidepressants, 5α-reductase inhibitors and isotretinoin. While reports of certain issues were unique to the antidepressants, such as the onset of premature ejaculation and persistent genital arousal disorder (PGAD), there was also a significant overlap in symptom profile between the drug groups, with common features including genital anaesthesia, pleasureless or weak orgasm, loss of libido and impotence. Secondary consequences included relationship breakdown and impaired quality of life. CONCLUSIONS These data point to a legacy syndrome or syndromes comprising a range of disturbances to sexual function. More detailed studies will require developments in coding systems that recognise the condition(s). Further exploration of these tardive sexual syndromes may yield greater understanding of tardive syndromes in general. PMID:29733030

Repeated systemic administration of the cinnamon essential oil possesses anti-anxiety and anti-depressant activities in mice.

PubMed

Sohrabi, Reyhaneh; Pazgoohan, Nasim; Seresht, Hasan Rezaei; Amin, Bahareh

2017-06-01

The present study aimed to evaluate the putative antidepressant and anti-anxiety effects of the cinnamon essential oil when administered acute (for 3 doses) and sub-acute (for 14 days) to mice. In an acute experimental study, forced swim test (FST) was conducted to evaluate the antidepressant-like behavior of animals treated with the intraperitoneal (IP) essential oil of cinnamon in triple doses (0.5, 1, and 2 mg/kg). In a sub-acute study (14 days in 24-hr intervals) antidepressant-like effects of essential oil (0.5, 1, and 2 mg/kg) with the same route were assessed in FST and tail suspension test (TST). Anti-anxiety and motor activities were evaluated using elevated plus-maze (EPM) and open field tests, respectively. Determination of different constituents within the sample oil was via gas chromatography-mass spectrometry (GC-MS) analysis. Repetitive administration of cinnamon essential oil (0.5, 1, 2 mg/kg) during 14 days significantly decreased the time of immobility in both FST and TST as compared to the control group. Mice treated with oil at the dose of 2 mg/kg spent a longer time and had more entries into the open arms of EPM as compared with the vehicle-treated ones. According to GC-MS analysis, 46 chemical compounds were identified in the studied cinnamon essential oil with the main constituent being trans-cinnamaldehyde (87.32%). Cinnamon essential oil might be used as an adjunctive therapy in improving symptoms of depressive and anxiety disorders. However, dose-response effects need further evaluation. Trans-cinnamaldehyde might be responsible for the beneficial effect observed.

Preclinical Evidence of Rapid-Onset Antidepressant-Like Effect in Radix Polygalae Extract

PubMed Central

Park, Hyunwoo; Kim, Yoorim; Park, Sung Hyun; Swanberg, Kelley; Shin, Joo-Yeon; Ha, Sang-Kyu; Cho, Yoonju; Bang, Soo-Yong; Lew, Jae-Hwan; Cho, Seung-Hun; Maeng, Sungho

2014-01-01

Radix Polygalae (the root of Polygala tenuifolia) is a herb widely used in traditional Asian medicine that is thought to exert a variety of neuropsychiatric effects. Radix Polygalae extract can protect against N-methyl D-aspartate (NMDA) neurotoxicity and induce brain-derived neurotrophic factor (BDNF) expression, suggesting modulatory roles at glutamatergic synapses and possible antidepressant action. In accordance with this hypothesis, Radix Polygalae extract demonstrated antidepressant-like effects in 8-week-old male C57Bl/6 mice by decreasing behavioral despair in the forced swim and tail suspension tasks and increasing hedonic-like behavior in the female urine sniffing test 30 minutes after a single oral administration of 0.1 mg/kg. Reduced latency to acquire a food pellet in the novely suppressed feeding paradigm, without change in anxiety-like behaviors suggested a rapid-onset nature of the antidepressant-like effect. In addition, it decreased the number of failed escapes in the learned helplessness paradigm after two oral administrations 24 hours and 30 minutes before the first test. Finally, it reversed anhedonia as measured by saccharin preference in mice exposed to the chronic stress model after two administrations of 0.1 mg/kg, in contrast to the repeated administration generally needed for similar effect by monoamergic antidepressants. Immobility reduction in tail suspension task was blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist NBQX, a pattern previously demonstrated by ketamine and other ketamine-like rapid-onset antidepressants. Also similarly to ketamine, Radix Polygalae appeared to acutely decrease phosphorylation of GluR1 serine-845 in the hippocampus while leaving the phosphorylation of hippocampal mTOR serine 2448 unchanged. These findings serve as preclinical evidence that Radix Polygalae extract exerts rapid-onset antidepressant effects by modulating glutamatergic synapses in critical brain

Acute and long-term treatment of late-life major depressive disorder: duloxetine versus placebo.

PubMed

Robinson, Michael; Oakes, Tina Myers; Raskin, Joel; Liu, Peng; Shoemaker, Scarlett; Nelson, J Craig

2014-01-01

To compare the efficacy of duloxetine with placebo on depression in elderly patients with major depressive disorder. Multicenter, 24-week (12-week short-term and 12-week continuation), randomized, placebo-controlled, double-blind trial. United States, France, Mexico, Puerto Rico. Age 65 years or more with major depressive disorder diagnosis (one or more previous episode); Mini-Mental State Examination score ≥20; Montgomery-Asberg Depression Rating Scale total score ≥20. Duloxetine 60 or 120 mg/day or placebo; placebo rescue possible. Primary-Maier subscale of the 17-item Hamilton Depression Rating Scale (HAMD-17) at week 12. Secondary-Geriatric Depression Scale, HAMD-17 total score, cognitive measures, Brief Pain Inventory (BPI), Numeric Rating Scales (NRS) for pain, Clinical Global Impression-Severity scale, Patient Global Impression of Improvement in acute phase and acute plus continuation phase of treatment. Compared with placebo, duloxetine did not show significantly greater improvement from baseline on Maier subscale at 12 weeks, but did show significantly greater improvement at weeks 4, 8, 16, and 20. Similar patterns for Geriatric Depression Scale and Clinical Global Impression-Severity scale emerged, with significance also seen at week 24. There was a significant treatment effect for all BPI items and 4 of 6 NRS pain measures in the acute phase, most BPI items and half of the NRS measures in the continuation phase. More duloxetine-treated patients completed the study (63% versus 55%). A significantly higher percentage of duloxetine-treated patients versus placebo discontinued due to adverse event (15.3% versus 5.8%). Although the antidepressant efficacy of duloxetine was not confirmed by the primary outcome, several secondary measures at multiple time points suggested efficacy. Duloxetine had significant and meaningful beneficial effects on pain. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights

Fluoxetine potentiation of omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents.

PubMed

Laino, Carlos Horacio; Garcia, Pilar; Podestá, María Fernanda; Höcht, Christian; Slobodianik, Nora; Reinés, Analía

2014-10-01

We previously reported that combined fluoxetine administration at antidepressant doses renders additive antidepressant effects, whereas non-antidepressant doses potentiate the omega-3 fatty acid antidepressant effect. In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats. Coadministration of omega-3 fatty acids with a non-antidepressant dose of fluoxetine (1 mg/kg day) failed to affect both brain fluoxetine concentration and norfluoxetine plasma concentration profile. Fluoxetine plasma concentrations remained below the sensitivity limit of the detection method. Either antidepressant (10 mg/kg day) or non-antidepressant (1 mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels. Although individual treatments had no effects on DPA concentration, DPA increase was higher when omega-3 were combined with the non-antidepressant dose of fluoxetine. Chronic DPA administration exerted antidepressant-like effects in the forced swimming test while increasing hippocampal docosahexaenoic (22:6 omega-3) and DPA levels. Our results suggest no pharmacokinetic interaction and reveal specific hippocampal DPA changes after fluoxetine and omega-3 combined treatments in our experimental conditions. The DPA role in the synergistic effect of fluoxetine and omega-3 combined treatments will be for sure the focus of future studies. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3316-3325, 2014. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Preventive treatment of migraine.

PubMed

Silberstein, Steven D

2005-01-01

Migraine preventive therapy, even in the absence of a headache, is given in an attempt to reduce the frequency, duration, or severity of attacks. Circumstances that might warrant preventive treatment include disabling migraine attacks, the overuse of acute medications or failure of or contraindication to acute medications, troublesome side effects from medication, hemiplegic migraine, or very frequent headaches (more than 2 a week). The major medication groups for preventive treatment include anticonvulsants, antidepressants, b-adrenergic blockers, calcium channel antagonists, serotonin antagonists, neurotoxins, nonsteroidal anti-inflammatory drugs, and others. If preventive medication is indicated, the agent preferentially should be chosen from one of the first-line categories, based on the drug's side-effect profile and the patient's coexistent and comorbid conditions.

Antidepressant-Like Effect of Isorhynchophylline in Mice.

PubMed

Xian, Yan-Fang; Fan, Ding; Ip, Siu-Po; Mao, Qing-Qiu; Lin, Zhi-Xiu

2017-02-01

Isorhynchophylline (IRN), an oxindole alkaloid, has been identified as the main active ingredient responsible for the biological activities of Uncaria rhynchophylla (Miq) Miq ex Havil. (Rubiaceae). Previous studies in our laboratory have revealed that IRN possesses potent neuroprotective effects in different models of Alzheimer's disease. However, the antidepressant-like effects of IRN are remained unclear. The present study aims to evaluate the antidepressant-like effects of IRN. The antidepressant-like effects of IRN was determined by using animal models of depression including forced swimming and tail suspension tests. The acting mechanism was explored by determining the effect of IRN on the levels of monoamine neurotransmitters and the activities of monoamine oxidases. Intragastric administration of IRN at 10, 20 and 40 mg/kg for 7 days caused a significant reduction of immobility time in both forced swimming and tail suspension tests, while IRN did not stimulate locomotor activity in the open-field test. In addition, IRN treatment antagonized reserpine-induced ptosis and significantly enhanced the levels of monoamine neurotransmitters including norepinephrine (NE) and 5-hydroxytryptamine (5-HT), and the activity of monoamine oxidase A (MAO-A) in the hippocampus and frontal cortex of mice. These results suggest that the antidepressant-like effects of IRN are mediated, at least in part, by the inhibition of monoamine oxidases.

Non-monoaminergic targets for the development of antidepressants: focus on neuropeptides.

PubMed

Catena-Dell'Osso, Mario; Fagiolini, Andrea; Marazziti, Donatella; Baroni, Stefano; Bellantuono, Cesario

2013-01-01

In the last decades, no significant paradigm shifts in the psychopharmacology of major depressive disorder (MDD) have occurred. In fact, after the serendipitous discovery of the first antidepressant, the poor understanding of the pathophysiology of the illness has deeply limited the development of novel antidepressant agents. Although the discovery of the selective serotonin reuptake inhibitors and the dual-acting serotonin/norepinephrine reuptake inhibitors allowed to improve the treatment of MDD, there are still important unmet clinical needs, as the long latency of antidepressant action, the presence of relevant side effects and the lack of efficacy. In fact, even though the available antidepressants have consistently improved the prognosis of the disorder, the pharmacological treatment of MDD is far from being satisfactory and the disorder remains one of the major causes of morbidity and disability worldwide. Recently, besides the classical research involving the monoamines, other non-monoaminergic molecular mechanisms have been explored in search of new antidepressants. Amongst them, the investigation of the central neuropeptides, including substance P, corticotropin-releasing factor, neuropeptide Y, vasopressin and oxytocin, galanin and melanin-concentrating hormone, is increasingly attracting the attention of researchers worldwide. A number of novel compounds acting on neuropeptide receptors have been developed and tested in both animals and humans with different results. In this review, we provided a synthetic overview of the main neuropeptides, going through biochemical and molecular aspects up to preclinical and clinical evidence which link these molecules to the presence of MDD.

A Randomized, Placebo-Controlled Pilot Study of Quetiapine-XR Monotherapy or Adjunctive Therapy to Antidepressant in Acute Major Depressive Disorder with Current Generalized Anxiety Disorder

PubMed Central

Li, Ranran; Wu, Renrong; Chen, Jun; Kemp, David E.; Ren, Ming; Conroy, Carla; Chan, Philip; Serrano, Mary Beth; Ganocy, Stephen J.; Calabrese, Joseph R.; Gao, Keming

2016-01-01

Objectives To pilot efficacy and safety data of quetiapine-XR monotherapy or adjunctive therapy to antidepressant(s) in the acute treatment of MDD with current generalized anxiety disorder (GAD). Methods The Mini International Neuropsychiatric Interview was used to ascertain the diagnosis of DSM-IV Axis I disorders. Eligible patients were randomly assigned to quetiapine-XR or placebo for up to 8 weeks. Changes from baseline to endpoint in Hamilton Depression Rating Scale-17 items (HAMD-17), Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impression-Severity (CGI-S), Quick Inventory of Depression Symptomatology-16 items Self-Report (QIDS-16-SR) total scores, and other outcome measures were analyzed with the last observation carried forward strategy and/or mixed-effects modeling for repeated measures. Results Of the 34 patients screened, 23 patients were randomized to receive quetiapine-XR (n = 11) or placebo (n = 12), with 5 and 4 completing the study, respectively. The mean dose of quetiapine-XR was 154 ± 91 mg/d. The change from baseline to endpoint in the total scores of HAMD-17, HAM-A, QIDS-16-SR, and CGI-S were significant in the quetiapine-XR group, but only the change in HAM-A total score was significant in the placebo group. The differences in these changes between the two groups were only significant in CGI-S scores, with the rest of numerical larger in the quetiapine-XR group. The most common side effects from quetiapine-XR were dry mouth, somnolence/sedation, and fatigue. Conclusions In this pilot study, quetiapine-XR was numerically superior to placebo in reducing depressive and anxiety symptoms in patients with MDD and current GAD. Large sample studies are warranted to support or refute these preliminary findings. PMID:27738370

A Randomized, Placebo-Controlled Pilot Study of Quetiapine-XR Monotherapy or Adjunctive Therapy to Antidepressant in Acute Major Depressive Disorder with Current Generalized Anxiety Disorder.

PubMed

Li, Ranran; Wu, Renrong; Chen, Jun; Kemp, David E; Ren, Ming; Conroy, Carla; Chan, Philip; Serrano, Mary Beth; Ganocy, Stephen J; Calabrese, Joseph R; Gao, Keming

2016-03-01

To pilot efficacy and safety data of quetiapine-XR monotherapy or adjunctive therapy to antidepressant(s) in the acute treatment of MDD with current generalized anxiety disorder (GAD). The Mini International Neuropsychiatric Interview was used to ascertain the diagnosis of DSM-IV Axis I disorders. Eligible patients were randomly assigned to quetiapine-XR or placebo for up to 8 weeks. Changes from baseline to endpoint in Hamilton Depression Rating Scale-17 items (HAMD-17), Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impression-Severity (CGI-S), Quick Inventory of Depression Symptomatology-16 items Self-Report (QIDS-16-SR) total scores, and other outcome measures were analyzed with the last observation carried forward strategy and/or mixed-effects modeling for repeated measures. Of the 34 patients screened, 23 patients were randomized to receive quetiapine-XR (n = 11) or placebo (n = 12), with 5 and 4 completing the study, respectively. The mean dose of quetiapine-XR was 154 ± 91 mg/d. The change from baseline to endpoint in the total scores of HAMD-17, HAM-A, QIDS-16-SR, and CGI-S were significant in the quetiapine-XR group, but only the change in HAM-A total score was significant in the placebo group. The differences in these changes between the two groups were only significant in CGI-S scores, with the rest of numerical larger in the quetiapine-XR group. The most common side effects from quetiapine-XR were dry mouth, somnolence/sedation, and fatigue. In this pilot study, quetiapine-XR was numerically superior to placebo in reducing depressive and anxiety symptoms in patients with MDD and current GAD. Large sample studies are warranted to support or refute these preliminary findings.

Cost effectiveness analysis comparing repetitive transcranial magnetic stimulation to antidepressant medications after a first treatment failure for major depressive disorder in newly diagnosed patients - A lifetime analysis.

PubMed

Voigt, Jeffrey; Carpenter, Linda; Leuchter, Andrew

2017-01-01

Repetitive Transcranial Magnetic Stimulation (rTMS) commonly is used for the treatment of Major Depressive Disorder (MDD) after patients have failed to benefit from trials of multiple antidepressant medications. No analysis to date has examined the cost-effectiveness of rTMS used earlier in the course of treatment and over a patients' lifetime. We used lifetime Markov simulation modeling to compare the direct costs and quality adjusted life years (QALYs) of rTMS and medication therapy in patients with newly diagnosed MDD (ages 20-59) who had failed to benefit from one pharmacotherapy trial. Patients' life expectancies, rates of response and remission, and quality of life outcomes were derived from the literature, and treatment costs were based upon published Medicare reimbursement data. Baseline costs, aggregate per year quality of life assessments (QALYs), Monte Carlo simulation, tornado analysis, assessment of dominance, and one way sensitivity analysis were also performed. The discount rate applied was 3%. Lifetime direct treatment costs, and QALYs identified rTMS as the dominant therapy compared to antidepressant medications (i.e., lower costs with better outcomes) in all age ranges, with costs/improved QALYs ranging from $2,952/0.32 (older patients) to $11,140/0.43 (younger patients). One-way sensitivity analysis demonstrated that the model was most sensitive to the input variables of cost per rTMS session, monthly prescription drug cost, and the number of rTMS sessions per year. rTMS was identified as the dominant therapy compared to antidepressant medication trials over the life of the patient across the lifespan of adults with MDD, given current costs of treatment. These models support the use of rTMS after a single failed antidepressant medication trial versus further attempts at medication treatment in adults with MDD.

A Systematic Review of the Effectiveness of Antianxiety and Antidepressive Agents for Functional Dyspepsia.

PubMed

Hojo, Mariko; Nagahara, Akihito; Asaoka, Daisuke; Shimada, Yuji; Sasaki, Hitoshi; Matsumoto, Kohei; Takeda, Tsutomu; Ueyama, Hiroya; Matsumoto, Kenshi; Watanabe, Sumio

2017-12-01

Objective Functional dyspepsia (FD) is defined as persistent or recurrent pain or discomfort centered in the upper abdomen without organic disease. Psychosocial factors have been proposed as an important element in the pathophysiology of FD. Therefore, psychotropic agents having antianxiety or antidepressive action are expected to alleviate FD. We previously reported on the treatment of FD using such agents in a systematic review, wherein the effectiveness of the agents on FD was suggested, although there were several limitations. We searched for articles on this subject after our systematic review and re-reviewed them systematically. Methods Articles were searched for in MEDLINE from 2003 to 2014 using terms related to antianxiety or antidepressive agents. Clinical studies in which the effectiveness of such agents was clearly stated were selected from the retrieved articles. The newly selected and previously selected studies were combined, and statistical analyses were carried out. Results Nine studies were selected. Five of the studies indicated a significant symptomatic improvement using psychotropic drugs. A statistical analysis suggested a significant treatment effect of psychotropic agents having antianxiety or antidepressive action [pooled relative risk (PRR), 0.72; 95% confidence interval (95% CI), 0.52-0.99; p=0.0406] but did not show a significant benefit of treatment with agents having an antidepressive action alone (PRR, 0.63; 95% CI, 0.38-1.03; p=0.0665). Conclusion Our systematic review suggested that psychotropic drugs having antianxiety and antidepressive actions as a whole might be effective in alleviating FD symptoms, whereas those having only antidepressive action were not effective.

A Systematic Review of the Effectiveness of Antianxiety and Antidepressive Agents for Functional Dyspepsia

PubMed Central

Hojo, Mariko; Nagahara, Akihito; Asaoka, Daisuke; Shimada, Yuji; Sasaki, Hitoshi; Matsumoto, Kohei; Takeda, Tsutomu; Ueyama, Hiroya; Matsumoto, Kenshi; Watanabe, Sumio

2017-01-01

Objective Functional dyspepsia (FD) is defined as persistent or recurrent pain or discomfort centered in the upper abdomen without organic disease. Psychosocial factors have been proposed as an important element in the pathophysiology of FD. Therefore, psychotropic agents having antianxiety or antidepressive action are expected to alleviate FD. We previously reported on the treatment of FD using such agents in a systematic review, wherein the effectiveness of the agents on FD was suggested, although there were several limitations. We searched for articles on this subject after our systematic review and re-reviewed them systematically. Methods Articles were searched for in MEDLINE from 2003 to 2014 using terms related to antianxiety or antidepressive agents. Clinical studies in which the effectiveness of such agents was clearly stated were selected from the retrieved articles. The newly selected and previously selected studies were combined, and statistical analyses were carried out. Results Nine studies were selected. Five of the studies indicated a significant symptomatic improvement using psychotropic drugs. A statistical analysis suggested a significant treatment effect of psychotropic agents having antianxiety or antidepressive action [pooled relative risk (PRR), 0.72; 95% confidence interval (95% CI), 0.52-0.99; p=0.0406] but did not show a significant benefit of treatment with agents having an antidepressive action alone (PRR, 0.63; 95% CI, 0.38-1.03; p=0.0665). Conclusion Our systematic review suggested that psychotropic drugs having antianxiety and antidepressive actions as a whole might be effective in alleviating FD symptoms, whereas those having only antidepressive action were not effective. PMID:29021437

Treatment of Acute Pelvic Inflammatory Disease

PubMed Central

Sweet, Richard L.

2011-01-01

Pelvic inflammatory disease (PID), one of the most common infections in nonpregnant women of reproductive age, remains an important public health problem. It is associated with major long-term sequelae, including tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. In addition, treatment of acute PID and its complications incurs substantial health care costs. Prevention of these long-term sequelae is dependent upon development of treatment strategies based on knowledge of the microbiologic etiology of acute PID. It is well accepted that acute PID is a polymicrobic infection. The sexually transmitted organisms, Neisseria gonorrhoeae and Chlamydia trachomatis, are present in many cases, and microorganisms comprising the endogenous vaginal and cervical flora are frequently associated with PID. This includes anaerobic and facultative bacteria, similar to those associated with bacterial vaginosis. Genital tract mycoplasmas, most importantly Mycoplasma genitalium, have recently also been implicated as a cause of acute PID. As a consequence, treatment regimens for acute PID should provide broad spectrum coverage that is effective against these microorganisms. PMID:22228985

Cost-effectiveness of linaclotide compared to antidepressants in the treatment of irritable bowel syndrome with constipation in Scotland.

PubMed

Fisher, Mark; Walker, Andrew; Falqués, Meritxell; Moya, Miguel; Rance, Mark; Taylor, Douglas; Lindner, Leandro

2016-12-01

Presently, linaclotide is the only EMA-approved therapy indicated for the treatment of irritable bowel syndrome with constipation (IBS-C). This study sought to determine the cost-effectiveness of linaclotide compared to antidepressants for the treatment of adults with moderate to severe IBS-C who have previously received antispasmodics and/or laxatives. A Markov model was created to estimate costs and QALYs over a 5-year time horizon from the perspective of NHS Scotland. Health states were based on treatment satisfaction (satisfied, moderately satisfied, not satisfied) and mortality. Transition probabilities were based on satisfaction data from the linaclotide pivotal studies and Scottish general all-cause mortality statistics. Treatment costs were calculated from the British National Formulary. NHS resource use and disease-related costs for each health state were estimated from Scottish clinician interviews in combination with NHS Reference costs. Quality of life was based on EQ-5D data collected from the pivotal studies. Costs and QALYs were discounted at 3.5 % per annum. Uncertainty was explored through extensive deterministic and probabilistic sensitivity analyses. Over a 5-year time horizon, the additional costs and QALYs generated with linaclotide were £659 and 0.089, resulting in an incremental cost-effectiveness ratio of £7370 per QALY versus antidepressants. Based on the probabilistic sensitivity analysis, the likelihood that linaclotide was cost-effective at a willingness to pay of £20,000 per QALY was 73 %. Linaclotide can be a cost-effective treatment for adults with moderate-to-severe IBS-C who have previously received antispasmodics and/or laxatives in Scotland.

Long-term treatment effect of trauma-affected refugees with flexible cognitive behavioural therapy and antidepressants.

PubMed

Buhmann, Caecilie Böck; Nordentoft, Merete; Ekstroem, Morten; Carlsson, Jessica; Mortensen, Erik Lykke

2018-04-04

Few studies exist on the long-term effect of treatment of trauma-affected refugees. The purpose of this study was to estimate the long-term treatment effects of cognitive behavioural therapy and antidepressants (sertraline and mianserin) in trauma-affected refugees. Follow-ups were conducted 6 and 18 months after a randomised controlled clinical trial. The included patients were refugees with war-related traumatic experiences, PTSD and without psychotic disorders. We found a small improvement over time in PTSD, depression and anxiety symptoms and level of functioning, but the improvement was not associated with any specific treatment. Personality change after catastrophic experiences and life events influenced the symptom level at all follow-ups while depression at completion of treatment was associated with a steeper decline in symptom load at the follow-ups. In spite of the limited decline in symptom scores and treatment effects immediately after treatment, the condition of the treated trauma-affected refugees was significantly improved 6 and 18 months after treatment although the improvement was small. Copyright © 2018 Elsevier B.V. All rights reserved.

The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders

PubMed Central

Pacchiarotti, Isabella; Bond, David J.; Baldessarini, Ross J.; Nolen, Willem A.; Grunze, Heinz; Licht, Rasmus W.; Post, Robert M.; Berk, Michael; Goodwin, Guy M.; Sachs, Gary S.; Tondo, Leonardo; Findling, Robert L.; Youngstrom, Eric A.; Tohen, Mauricio; Undurraga, Juan; González-Pinto, Ana; Goldberg, Joseph F.; Yildiz, Ayşegül; Altshuler, Lori L.; Calabrese, Joseph R.; Mitchell, Philip B.; Thase, Michael E.; Koukopoulos, Athanasios; Colom, Francesc; Frye, Mark A.; Malhi, Gin S.; Fountoulakis, Konstantinos N.; Vázquez, Gustavo; Perlis, Roy H.; Ketter, Terence A.; Cassidy, Frederick; Akiskal, Hagop; Azorin, Jean-Michel; Valentí, Marc; Mazzei, Diego Hidalgo; Lafer, Beny; Kato, Tadafumi; Mazzarini, Lorenzo; Martínez-Aran, Anabel; Parker, Gordon; Souery, Daniel; Özerdem, Ayşegül; McElroy, Susan L.; Girardi, Paolo; Bauer, Michael; Yatham, Lakshmi N.; Zarate, Carlos A.; Nierenberg, Andrew A.; Birmaher, Boris; Kanba, Shigenobu; El-Mallakh, Rif S.; Serretti, Alessandro; Rihmer, Zoltan; Young, Allan H.; Kotzalidis, Georgios D.; MacQueen, Glenda M.; Bowden, Charles L.; Ghaemi, S. Nassir; Lopez-Jaramillo, Carlos; Rybakowski, Janusz; Ha, Kyooseob; Perugi, Giulio; Kasper, Siegfried; Amsterdam, Jay D.; Hirschfeld, Robert M.; Kapczinski, Flávio; Vieta, Eduard

2014-01-01

Objective The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. Method An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. Results There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. Conclusions Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications

Study on the treatment of acute thallium poisoning.

PubMed

Zhang, Hong-Tao; Qiao, Bao-Ping; Liu, Bao-Ping; Zhao, Xian-Guo

2014-05-01

Acute thallium poisoning rarely occurs but is a serious and even fatal medical condition. Currently, patients with acute thallium poisoning are usually treated with Prussian blue and blood purification therapy. However, there are few studies about these treatments for acute thallium poisoning. Nine patients with acute thallium poisoning from 1 family were treated successfully with Prussian blue and different types of blood purification therapies and analyzed. Prussian blue combined with sequential hemodialysis, hemoperfusion and/or continuous veno-venous hemofiltration were effective for the treatment of patients with acute thallium poisoning, even after delayed diagnosis. Blood purification therapies help in the clearance of thallium in those with acute thallium poisoning. Prussian blue treatment may do the benefit during this process.

Antidepressive effects of targeting ELK-1 signal transduction.

PubMed

Apazoglou, Kallia; Farley, Séverine; Gorgievski, Victor; Belzeaux, Raoul; Lopez, Juan Pablo; Grenier, Julien; Ibrahim, El Chérif; El Khoury, Marie-Anne; Tse, Yiu C; Mongredien, Raphaele; Barbé, Alexandre; de Macedo, Carlos E A; Jaworski, Wojciech; Bochereau, Ariane; Orrico, Alejandro; Isingrini, Elsa; Guinaudie, Chloé; Mikasova, Lenka; Louis, Franck; Gautron, Sophie; Groc, Laurent; Massaad, Charbel; Yildirim, Ferah; Vialou, Vincent; Dumas, Sylvie; Marti, Fabio; Mechawar, Naguib; Morice, Elise; Wong, Tak P; Caboche, Jocelyne; Turecki, Gustavo; Giros, Bruno; Tzavara, Eleni T

2018-05-07

Depression, a devastating psychiatric disorder, is a leading cause of disability worldwide. Current antidepressants address specific symptoms of the disease, but there is vast room for improvement 1 . In this respect, new compounds that act beyond classical antidepressants to target signal transduction pathways governing synaptic plasticity and cellular resilience are highly warranted 2-4 . The extracellular signal-regulated kinase (ERK) pathway is implicated in mood regulation 5-7 , but its pleiotropic functions and lack of target specificity prohibit optimal drug development. Here, we identified the transcription factor ELK-1, an ERK downstream partner 8 , as a specific signaling module in the pathophysiology and treatment of depression that can be targeted independently of ERK. ELK1 mRNA was upregulated in postmortem hippocampal tissues from depressed suicides; in blood samples from depressed individuals, failure to reduce ELK1 expression was associated with resistance to treatment. In mice, hippocampal ELK-1 overexpression per se produced depressive behaviors; conversely, the selective inhibition of ELK-1 activation prevented depression-like molecular, plasticity and behavioral states induced by stress. Our work stresses the importance of target selectivity for a successful approach for signal-transduction-based antidepressants, singles out ELK-1 as a depression-relevant transducer downstream of ERK and brings proof-of-concept evidence for the druggability of ELK-1.

Antidepressant Sales and the Risk for Alcohol-Related and Non-Alcohol-Related Suicide in Finland—An Individual-Level Population Study

PubMed Central

Moustgaard, Heta; Joutsenniemi, Kaisla; Myrskylä, Mikko; Martikainen, Pekka

2014-01-01

Objectives A marked decline in suicide rates has co-occurred with increased antidepressant sales in several countries but the causal connection between the trends remains debated. Most previous studies have focused on overall suicide rates and neglected differential effects in population subgroups. Our objective was to investigate whether increasing sales of non-tricyclic antidepressants have reduced alcohol- and non-alcohol-related suicide risk in different population subgroups. Methods We followed a nationally representative sample of 950,158 Finnish adults in 1995–2007 for alcohol-related (n = 2,859) and non-alcohol-related (n = 8,632) suicides. We assessed suicide risk by gender and social group according to regional sales of non-tricyclic antidepressants, measured by sold doses per capita, prevalence of antidepressant users, and proportion of antidepressant users with doses reflecting minimally adequate treatment. Fixed-effects Poisson regression models controlled for regional differences and time trends that may influence suicide risk irrespective of antidepressant sales. Results The number of sold antidepressant doses per capita and the prevalence of antidepressant users were unrelated to male suicide risk. However, one percentage point increase in the proportion of antidepressant users receiving minimally adequate treatment reduced non-alcohol-related male suicide risk by one percent (relative risk 0.987, 95% confidence interval 0.976–0.998). This beneficial effect only emerged among men with high education, high income, and employment, among men without a partner, and men not owning their home. Alcohol-related suicides and female suicides were unrelated to all measures of antidepressant sales. Conclusion We found little evidence that increase in overall sales or in the prevalence of non-tricyclic antidepressant users would have caused the fall in suicide rates in Finland in 1995–2007. However, the rise in the proportion of antidepressant

Clinical application of antidepressant pharmacogenetics: considerations for the design of future studies.

PubMed

Fabbri, Chiara; Serretti, Alessandro

2018-06-12

A frustrating inertia has affected the development of clinical applications of antidepressant pharmacogenetics and personalized treatments of depression are still lacking 20 years after the first findings. Candidate gene studies provided replicated findings for some polymorphisms, but each of them shows at best a small effect on antidepressant efficacy and the cumulative effect of different polymorphisms is unclear. Further, no candidate was immune by at least some negative studies. These considerations give rise to some concerns about the clinical benefits of currently available pharmacogenetic tests since they are based on the results of candidate gene studies. Clinical guidelines in fact suggest that only polymorphisms that alter cytochrome 2D6 or 2C19 enzymatic activity probably provide useful clinical indications, while variants in genes involved in antidepressant pharmacodynamics have no recommended clinical applications. The present review discusses possible strategies to facilitate the identification of genetic biomarkers with clinical usefulness in guiding antidepressant treatments. These include analysis methods for the study of the polygenic/omnigenic nature of antidepressant response, the prioritization of polymorphisms on the basis of functional considerations, the incorporation of clinical-demographic predictors in pharmacogenetic studies (e.g. mixed polygenic and clinical risk scores), the application of methodological improvements to the design of future studies in order to maximize the comparability of results and improve power. Copyright © 2018. Published by Elsevier B.V.

Interplay between the key proteins of serotonin system in SSRI antidepressants efficacy.

PubMed

Kulikov, Alexander V; Gainetdinov, Raul R; Ponimaskin, Evgeni; Kalueff, Allan V; Naumenko, Vladimir S; Popova, Nina K

2018-04-01

Selective serotonin reuptake inhibitors (SSRIs) are the most effective and most used antidepressant drugs. Acting by inhibiting serotonin (5-HT) transporter, SSRIs display a typical 3-4-week delay in their therapeutic effects, with nearly 40% of depressed patients remaining treatment-resistant. Recent evidence suggests complex interplay between 5-HT receptors and key proteins of 5-HT metabolism in molecular mechanisms of such delay and resistance to SSRIs. Area covered: This paper concentrates on the interplay between 5-HT receptors in the delay of therapeutic effect of SSRIs, and the interaction between tryptophan hydroxylase 2 and 5-HT transporter in the SSRI resistance. Specifically, it discusses: (1) the data on the association between antidepressant drug efficacy and genetically defined characteristics of key proteins in the 5-HT signaling (TPH2, MAOA, SERT and 5-HT 1A receptor), (2) the effect of dimerization of 5-HT 7 and 5-HT 1A receptors on the internalization and functioning of 5-HT 1A presynaptic receptors, (3) the role of Tph2 deficiency in the resistance to SSRIs treatment. We shift the emphasis from individual proteins to their interactions in explaining antidepressant action of SSRI. Expert opinion: These interactions should be considered when developing more effective antidepressant drugs as well as for predicting and improving the efficacy of antidepressant therapies.

Increased use of antidepressants in Wuhan, China: a retrospective study from 2006 to 2012.

PubMed

Gao, Ping; Zhang, Huanian; Xu, Hua; Zhang, Chengliang; Liu, Dong

2013-01-01

The aim of this study was to investigate the trend of antidepressant use and analyze the daily cost of antidepressants in Wuhan, China. The data on the expenditure of antidepressants in Wuhan from 2006 to 2012 were retrospectively analyzed based on the defined daily dose (DDD) method recommended by the World Health Organization. In addition, the daily cost of antidepressants was calculated for the pharmacoeconomic evaluation. The overall sales of antidepressants increased by 566.7% over the 7-year period. The utilization of antidepressants increased annually from 1.067 DDDs per 1000 inhabitants per day in 2006 to 4.144 in 2012. This upward trend was mainly driven by an increase in the use of selective serotonin reuptake inhibitors (SSRIs), which accounted for about 60% of antidepressant use. Notably, the use of traditional Chinese patent medicines (TCMs) approved to treat depression in China in 2010 increased from 0.158 DDDs per 1000 inhabitants per day in 2010 to 0.305 in 2012. The daily drug cost analysis indicated that selective serotonin and norepinephrine reuptake inhibitors (SNRIs) and other new antidepressants were more expensive while tricyclic and tetracyclic antidepressants (TCAs) had a low-cost advantage. Antidepressants were increasingly used over the study period. Among them, SSRIs followed by SNRIs were the most commonly used. After the approval for the treatment of depression, TCMs were generally accepted by physicians and patients. The low-cost advantage allowed TCAs to be used in the antidepressant therapy.

A comparison of cognitive-behavioral therapy, antidepressants, their combination and standard treatment for Chinese patients with moderate-severe major depressive disorders.

PubMed

Zu, Si; Xiang, Yu-Tao; Liu, Jing; Zhang, Ling; Wang, Gang; Ma, Xin; Kilbourne, Amy M; Ungvari, Gabor S; Chiu, Helen F K; Lai, Kelly Y C; Wong, Samuel Y S; Yu, Doris S F; Li, Zhan-Jiang

2014-01-01

No study has examined the effect of cognitive-behavioral therapy (CBT) on moderate-severe major depressive disorders (MDD) in China. The objective of this study was to evaluate the effect of CBT, antidepressants alone (MED), combined CBT and antidepressants (COMB) and standard treatment (ST; i.e., receiving psycho-educational intervention and/or medication treatment determined by treating psychiatrists) on depressive symptoms and social functioning in Chinese patients with moderate-severe MDD. A total of 180 patients diagnosed with MDD according to ICD-10 were randomly allocated to one of the four treatment regimens for a period of 6 months. Depressive symptoms were measured using the Hamilton Rating Scale for Depression (HAMD) and the Quick Inventory of Depressive Symptomatology-Self-Report (C-QIDS-SR). Remission threshold was defined as a C-QIDS-SR total score of <5. Social functioning was evaluated with the Work and Social Adjustment Scale (WSAS). All outcome measures were evaluated at entry, and at 3- and 6-months follow-up. At the 6-months assessment, the remission rates in the whole sample (n=96), the MED, the CBT, the COMB and the ST groups were 54.2%, 48%, 75%, 53.5% and 50%, respectively. Following the treatment periods, there was no significant difference in any of the study outcomes between the four groups. However, the CBT showed the greatest effect in the HAMD total score with the effect size=0.94, whereas the ST has only a moderate effect size in the WSAS total score (effect size=0.47). The findings support the feasibility and effectiveness of CBT as a psychosocial intervention for Chinese patients with moderate-severe MDD. We also found that single treatment using MED or CBT performed equally well as the combined CBT-antidepressant treatment in controlling the remission. The study provided important knowledge to inform the mental health care planning in China. © 2013 Elsevier B.V. All rights reserved.

[Cappuccino coffee treatment of xerostomia in patients taking tricyclic antidepressants: preliminary report].

PubMed

Chodorowski, Zygmunt

2002-01-01

10 patients underwent a trial treatment with Cappuccino coffee. All of them (8 university lecturers and 2 clerks) aged from 60 to 69 (average 63) years old, used tricyclic antidepressant because of insomnia as a monosymptomatic type of depression or insomnia as a dominant symptom in the course of depression. One, evening dose of doxepine was from 150 to 250 (average 225) mg, causing xerostomia next day usually between 9-15 o'clock. The five-minute--chewing of 15.0 g of Cappuccino coffee increased the amount of saliva, decreased xerostomia and improved the ability of speech. Beneficial effect of coffee lasted from 0.5 to 4 (average about 2) hours. To the best of our knowledge there are no publications dealing with the positive effect of coffee in xerostomia.

Comparative efficacy and acceptability of antidepressants, psychological interventions, and their combination for depressive disorder in children and adolescents: protocol for a network meta-analysis

PubMed Central

Zhou, Xinyu; Cipriani, Andrea; Zhang, Yuqing; Cuijpers, Pim; Hetrick, Sarah E; Weisz, John R; Pu, Juncai; Giovane, Cinzia Del; Furukawa, Toshiaki A; Barth, Jürgen; Coghill, David; Leucht, Stefan; Yang, Lining; Ravindran, Arun V; Xie, Peng

2017-01-01

Introduction Depressive disorder is common in children and adolescents, with important consequences and serious impairments in terms of personal and social functioning. While both pharmacological and psychological interventions have been shown to be effective, there is still uncertainty about the balance between these and what treatment strategy should be preferred in clinical practice. Therefore, we aim to compare and rank in a network meta-analysis (NMA) the commonly used psychological, pharmacological and combined interventions for depressive disorder in children and adolescents. Methods and analysis We will update the literature search of two previous NMAs for the identification of trials of antidepressant and psychotherapy alone for depressive disorder in children and adolescents. For identification of trials of combination interventions, seven databases (PubMed, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science, PsycINFO, CINAHL, LiLACS) will be searched from date of inception. We will also search ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform and check relevant reports on the US Food and Drug Administration website for unpublished data. Building on our previous findings in the field, we will include any commonly prescribed oral antidepressants and any manualised or structured psychotherapies, as well as their combinations. Randomised controlled trials assessing any active intervention against active comparator or pill placebo/psychological controls in acute treatment for depressive disorder in children and adolescents will be included. The primary outcomes will be efficacy (mean change in depressive symptoms), and acceptability of treatment (dropout rate due to any cause). The secondary outcomes will be remission rate, tolerability of treatment (dropouts for adverse events), as well as suicide-related outcomes (suicidal behaviour or ideation). We will perform Bayesian NMAs for all relative outcome

Parallel-group placebo-controlled trial of testosterone gel in men with major depressive disorder displaying an incomplete response to standard antidepressant treatment.

PubMed

Pope, Harrison G; Amiaz, Revital; Brennan, Brian P; Orr, Guy; Weiser, Mark; Kelly, John F; Kanayama, Gen; Siegel, Arthur; Hudson, James I; Seidman, Stuart N

2010-04-01

Exogenous testosterone therapy has psychotropic effects and has been proposed as an antidepressant augmentation strategy for depressed men. We sought to assess the antidepressant effects of testosterone augmentation of a serotonergic antidepressant in depressed, hypogonadal men. For this study, we recruited 100 medically healthy adult men with major depressive disorder showing partial response or no response to an adequate serotonergic antidepressant trial during the current episode and a screening total testosterone level of 350 ng/dL or lower. We randomized these men to receive testosterone gel or placebo gel in addition to their existing antidepressant regimen. The primary outcome measure was the Hamilton Depression Rating Scale (HDRS) score. Secondary measures included the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression Scale, and the Quality of Life Scale. Our primary analysis, using a mixed effects linear regression model to compare rate of change of scores between groups on the outcome measures, failed to show a significant difference between groups (mean [95% confidence interval] 6-week change in HDRS for testosterone vs placebo, -0.4 [-2.6 to 1.8]). However, in one exploratory analysis of treatment responders, we found a possible trend in favor of testosterone on the HDRS. Our findings, combined with the conflicting data from earlier smaller studies, suggest that testosterone is not generally effective for depressed men. The possibility remains that testosterone might benefit a particular subgroup of depressed men, but if so, the characteristics of this subgroup would still need to be established.

Acute Treatment of Migraine

PubMed Central

ÖZTÜRK, Vesile

2013-01-01

Migraine is one of the most frequent disabling neurological conditions with a major impact on the patient’s quality of life. Migraine has been described as a chronic disorder that characterized with attacks. Attacks are characterized by moderate–severe, often unilateral, pulsating headache attacks, typically lasting 4 to 72 hours. Migraine remains underdiagnosed and undertreated despite advances in the understanding of its pathophysiology. This article reviews management of migraine acute pharmacological treatment. Currently, for the acute treatment of migraine attacks, non-steroidal anti-inflammatory drugs (NSAIDs) and triptans (serotonin 5HT1B/1D receptor agonists) are recommended. Before intake of NSAID and triptans, metoclopramide or domperidone is useful. In very severe attacks, subcutaneous sumatriptan is first choice. The patient should be treated early in the attack, use an adequate dose and formulation of a medication. Ideally, acute therapy should be restricted to no more than 2 to 3 days per week to avoid medication overuse. PMID:28360580

Antidepressant-induced Dopamine Receptor Dysregulation: A Valid Animal Model of Manic-Depressive Illness

PubMed Central

Demontis, Francesca; Serra, Francesca; Serra, Gino

2017-01-01

Background: Mania seems to be associated with an increased dopamine (DA) transmission. Antidepressant treatments can induce mania in humans and potentiated DA transmission in animals, by sensitizing DA D2 receptors in the mesolimbic system. We have suggested that the sensitization of D2 receptors may be responsible of antidepressant-induced mania. This review aims to report the experimental evidence that led to the hypothesis that antidepressant-induced DA receptors dysregulation can be considered an animal model of bipolar disorder. Methods: We reviewed papers reporting preclinical and clinical studies on the role of DA in the mechanism of action of antidepressant treatments and in the patho-physiology of mood disorders. Results: A number of preclinical and clinical evidence suggests that mania could be associated with an increased DA activity, while a reduced function of this neurotransmission might underlie depression. Chronic treatment with imipramine induces a sensitization of DA D2 receptors in the mesolimbic system, followed, after drug discontinuation, by a reduced sensitivity associated with an increased immobility time in forced swimming test of depression (FST). Blockade of glutamate NMDA receptors by memantine administration prevents the imipramine effect on DA receptors sensitivity and on the FST. Conclusion: We suggest that chronic treatment with antidepressants induces a behavioural syndrome that mimics mania (the sensitization of DA receptors), followed by depression (desensitization of DA receptors and increased immobility time in the FST), i.e. an animal model of bipolar disorder. Moreover the observation that memantine prevents the “bipolar-like” behavior, suggests that the drug may have an antimanic and mood stabilizing effect. Preliminary clinical observations support this hypothesis. PMID:28503114

Age-Related Response to Redeemed Antidepressants Measured by Completed Suicide in Older Adults: A Nationwide Cohort Study

PubMed Central

Erlangsen, Annette; Conwell, Yeates

2013-01-01

Objective To examine if the suicide rate of older adults prescribed antidepressants varies with age and to assess the proportion of older adults who died by suicide that had recently been prescribed antidepressants. Methods A population-based cohort study using a nationwide linkage of individual-level records was conducted on all persons aged 50+ living in Denmark during 1996–2006 (1,215,524 men and 1,343,568 women). Suicide rates by treatment status were calculated using data on all antidepressant prescriptions redeemed at pharmacies. Results Individual-level data covered 9,354,620 and 10,720,639 person-years for men and women, respectively. Men aged 50–59 who received antidepressants had a mean suicide rate of 185 (95% confidence interval [CI]: 160–211) per 100,000, whereas for those aged 80+ the rate was 119 (95% CI: 91–146). For women, the corresponding values were 82 (95% CI: 70–94) and 28 (95% CI: 20–35). Logistic regression showed a 2% and 3% decline in the rate for men and women, respectively, considered in treatment with antidepressants, with each additional year of age. An opposite trend was found for persons not in treatment. Fewer persons aged 80+ dying by suicide had received antidepressant prescriptions during the last months of life than younger persons. Conclusion An age-dependent decline in suicide rate for antidepressant recipients was identified. One reason could be that older adults respond better to antidepressants than younger age groups. Still, the increasing gap with age between estimated prevalence of depression and antidepressant prescription rate in persons dying by suicide underscores the need for assessment of depression in the oldest old. PMID:23567434

Influence of acute bupropion pre-treatment on the effects of intranasal cocaine.

PubMed

Stoops, William W; Lile, Joshua A; Glaser, Paul E A; Hays, Lon R; Rush, Craig R

2012-06-01

The aim of this experiment was to determine the influence of acute bupropion pre-treatment on subject-rated effects and choice of intranasal cocaine versus money. A randomized, within-subject, placebo-controlled, double-blind experiment. An out-patient research unit. Eight cocaine-using adults. Subjects completed nine experimental sessions in which they were pre-treated with 0, 100 or 200 mg oral immediate release bupropion. Ninety minutes later they sampled an intranasal cocaine dose [4 (placebo), 15 or 45 mg] and made six choices between that dose and an alternative reinforcer (US$0.25), available on independent, concurrent progressive ratio schedules. Subjects also completed a battery of subject-rated, performance and physiological measures following the sample doses of cocaine. After 0 mg bupropion, the high dose of cocaine (45 mg) was chosen five of six times on average compared to 2.25 of six choices for placebo cocaine (4 mg) (P < 0.05). Active bupropion reduced choice of 45 mg cocaine to 3.13 (100 mg) or 4.00 (200 mg) out of six drug choices on average. Bupropion also consistently enhanced positive subject-rated effects of cocaine (e.g. good effects; willing to take again) while having no effects of its own. The atypical antidepressant, bupropion, acutely appears to reduce preference for intranasal cocaine versus a small amount of money but to increase reported positive experiences of the drug. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Omega-3 fatty acids have antidepressant activity in forced swimming test in Wistar rats.

PubMed

Lakhwani, Lalit; Tongia, Sudheer K; Pal, Veerendra S; Agrawal, Rajendra P; Nyati, Prem; Phadnis, Pradeep

2007-01-01

Forced swimming test is used to induce a characteristic behavior of immobility in rats, which resembles depression in humans to some extent. We evaluated the effect of omega-3 fatty acids alone as well as compared it with the standard antidepressant therapy with fluoxetine in both acute and chronic studies. In both the studies, rats were divided into 4 groups and subjected to the following drug interventions - Group 1- control: Group 2- fluoxetine in dose of 10 mg/kg subcutaneously 23.5, 5 and 1 h before the test: Group 3- omega-3 fatty acids in dose of 500 mg/kg orally; Group 4- fluoxetine plus omega-3 fatty acids both. In acute study, omega-3 fatty acids were given in single dose 2 h prior to the test while in chronic study omega-3 fatty acids were given daily for a period of 28 days. All animals were subjected to a 15-min pretest followed 24 h later by a 5-min test. A time sampling method was used to score the behavioral activity in each group. The results revealed that in acute study, omega-3 fatty acids do not have any significant effect in forced swimming test. However, in chronic study, omega-3 fatty acids affect the immobility and swimming behavior significantly when compared with control (p < 0.01) without any significant effect on climbing behavior and the efficacy of combination of omega-3 fatty acids and fluoxetine is significantly more than that of fluoxetine alone in changing the behavioral activity of rats in forced swimming test. It leads to the conclusion that omega-3 fatty acids have antidepressant activity per se, and the combination of fluoxetine and omega-3 fatty acids has more antidepressant efficacy than fluoxetine alone in forced swimming test in Wistar rats.

Gemfibrozil has antidepressant effects in mice: Involvement of the hippocampal brain-derived neurotrophic factor system.

PubMed

Ni, Yu-Fei; Wang, Hao; Gu, Qiu-Yan; Wang, Fei-Ying; Wang, Ying-Jie; Wang, Jin-Liang; Jiang, Bo

2018-04-01

Major depressive disorder has become one of the most serious neuropsychiatric disorders worldwide. However, currently available antidepressants used in clinical practice are ineffective for a substantial proportion of patients and always have side effects. Besides being a lipid-regulating agent, gemfibrozil is an agonist of peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the antidepressant effects of gemfibrozil on C57BL/6J mice using the forced swim test (FST) and tail suspension test (TST), as well as the chronic unpredictable mild stress (CUMS) model of depression. The changes in brain-derived neurotrophic factor (BDNF) signaling cascade in the brain after CUMS and gemfibrozil treatment were further assessed. Pharmacological inhibitors and lentivirus-expressed short hairpin RNA (shRNA) were also used to clarify the antidepressant mechanisms of gemfibrozil. Gemfibrozil exhibited significant antidepressant actions in the FST and TST without affecting the locomotor activity of mice. Chronic gemfibrozil administration fully reversed CUMS-induced depressive-like behaviors in the FST, TST and sucrose preference test. Gemfibrozil treatment also restored CUMS-induced inhibition of the hippocampal BDNF signaling pathway. Blocking PPAR-α and BDNF but not the serotonergic system abolished the antidepressant effects of gemfibrozil on mice. Gemfibrozil produced antidepressant effects in mice by promoting the hippocampal BDNF system.

Neural Correlates of Antidepressant Treatment Response in Adolescents with Major Depressive Disorder

PubMed Central

Klimes-Dougan, Bonnie; Vu, Dung Pham; Westlund Schreiner, Melinda; Mueller, Bryon A.; Eberly, Lynn E.; Camchong, Jazmin; Westervelt, Ana; Lim, Kelvin O.

2016-01-01

Abstract Objective: The neural changes underlying response to antidepressant treatment in adolescents are unknown. Identification of neural change correlates of treatment response could (1) aid in understanding mechanisms of depression and its treatment and (2) serve as target biomarkers for future research. Method: Using functional magnetic resonance imaging, we examined changes in brain activation and functional connectivity in 13 unmedicated adolescents with major depressive disorder (MDD) before and after receiving treatment with a selective serotonin reuptake inhibitor medication for 8 weeks. Specifically, we examined brain activation during a negative emotion task and resting-state functional connectivity (RSFC), focusing on the amygdala to capture networks relevant to negative emotion. We conducted whole-brain analyses to identify how symptom improvement was related to change in brain activation during a negative emotion task or amygdala RSFC. Results: After treatment, clinical improvement was associated with decreased task activation in rostral and subgenual anterior cingulate cortex and increased activation in bilateral insula, bilateral middle frontal cortices, right parahippocampus, and left cerebellum. Analysis of change in amygdala RSFC showed that treatment response was associated with increased amygdala RSFC with right frontal cortex, but decreased amygdala RSFC with right precuneus and right posterior cingulate cortex. Conclusion: The findings represent a foothold for advancing understanding of pathophysiology of MDD in adolescents by revealing the critical neural circuitry changes that underlie a positive response to a standard treatment. Although preliminary, the present study provides a research platform for future work needed to confirm these biomarkers at a larger scale before using them in future target engagement studies of novel treatments. PMID:27159204

Antidepressants and seizure-interactions at the GABA-receptor chloride-ionophore complex

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

Malatynska, E.; Knapp, R.J.; Ikeda, M.

1988-01-01

Convulsive seizures are a potential side effect of antidepressant drug treatment and can be produced by all classes of antidepressants. It is also know that some convulsant and anticonvulsant drug actions are mediated by the GABA-receptor chloride-ionophore complex. Drugs acting at this complex appear to induce convulsions by inhibiting chloride conductance through the associated chloride channel. Using the method of GABA-stimulated /sup 36/Cl-uptake by rat cerebral cortical vesicles, we show that some antidepressant drugs can inhibit the GABA-receptor chloride uptake, and that the degree of chloride channel inhibition by these drugs correlates with the frequency of convulsive seizures induced bymore » them.« less

Phytochemistry and pharmacology of anti-depressant medicinal plants: A review.

PubMed

Martins, Jeanette; S, Brijesh

2018-05-16

Stress renders an individual to experience mental pressure and exhaustion which brings about feelings of anxiety, depression, anger and/or other negative emotions. Depression affects a person's state of mind, behaviour, health and is often associated with suicide. The use of anti-depressant drugs as therapeutic agents is associated with symptoms such as, delayed onset of action, side-effects, drug-drug and dietary interactions, sexual dysfunction, cardiac toxicity, etc. Thus, there is need to target these issues and improve current treatment options. Medicinal plants have long been used in discovering novel treatment strategies and compounds with promising roles in treating various disease conditions. There has been an increase, worldwide, in the use of medicinal plants and herbs for developing nutraceuticals for treatment of depression and other psychiatric disorders. Medicinal plants in their natural forms are valuable as they are rich in various phytochemical compounds. These phytochemical compounds have pharmacological roles in treating various diseases conditions; apart from being widely available in nature and commercially beneficial. The phytochemical compounds in plants are constantly being explored through various experimental studies to determine the molecular basis of how medicinal plants work in relation to drugs and diseases and to develop neutraceuticals for improving conditions. This review summarizes 110 medicinal plants and their phytochemical constituents that have been shown to possess anti-depressant activity. This review also highlights the various mechanisms of anti-depressant action of some of these plants and their plant parts like roots, stem, leaves, flowers, fruit or whole plant; phytochemical compounds showing anti-depressant activity such flavanoids, steroids, saponins, sugars, lectins, alkaloids, etc.; and various anti-depressant screening models used such as tail suspension test, forced swim test, chronic unpredictable stress test

Antidepressant-Induced Female Sexual Dysfunction.

PubMed

Lorenz, Tierney; Rullo, Jordan; Faubion, Stephanie

2016-09-01

Because 1 in 6 women in the United States takes antidepressants and a substantial proportion of patients report some disturbance of sexual function while taking these medications, it is a near certainty that the practicing clinician will need to know how to assess and manage antidepressant-related female sexual dysfunction. Adverse sexual effects can be complex because there are several potentially overlapping etiologies, including sexual dysfunction associated with the underlying mood disorder. As such, careful assessment of sexual function at the premedication visit followed by monitoring at subsequent visits is critical. Treatment of adverse sexual effects can be pharmacological (dose reduction, drug discontinuation or switching, augmentation, or using medications with lower adverse effect profiles), behavioral (exercising before sexual activity, scheduling sexual activity, vibratory stimulation, psychotherapy), complementary and integrative (acupuncture, nutraceuticals), or some combination of these modalities. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Association of Antidepressant Medications With Incident Type 2 Diabetes Among Medicaid-Insured Youths.

PubMed

Burcu, Mehmet; Zito, Julie M; Safer, Daniel J; Magder, Laurence S; dosReis, Susan; Shaya, Fadia T; Rosenthal, Geoffrey L

2017-12-01

Antidepressants are one of the most commonly prescribed classes of psychotropic medications among US youths. For adults, there is emerging evidence on the increased risk of type 2 diabetes in association with antidepressant use. However, little is known about the antidepressant treatment-emergent risk of type 2 diabetes among youths. To assess the association between antidepressant use and the risk of incident type 2 diabetes in youths by antidepressant subclass and according to duration of use, cumulative dose, and average daily dose. A retrospective cohort study was conducted using Medicaid claims data from 4 geographically diverse, large states of youths 5 to 20 years of age who initiated antidepressant treatment from January 1, 2005, to December 31, 2009. Antidepressant use (selective serotonin reuptake inhibitors [SSRIs] or serotonin-norepinephrine reuptake inhibitors [SNRIs], tricyclic or other cyclic antidepressants, and other antidepressants) was assessed using the following 4 time-varying measures: current or former use, duration of use, cumulative dose, and average daily dose. Incident type 2 diabetes was assessed using discrete-time failure models, adjusting for disease risk score estimated using more than 125 baseline and time-dependent covariates. In this cohort of 119 608 youths aged 5 to 20 years who initiated antidepressant treatment (59 087 female youths and 60 521 male youths; 54.7% between 5 and 14 years of age) with a mean follow-up of 22.8 months, 79 285 [66.3%] had SSRI or SNRI exposure. The risk of type 2 diabetes was significantly greater during current use than former use of SSRIs or SNRIs (absolute risk, 1.29 per 10 000 person-months vs 0.64 per 10 000 person-months; adjusted relative risk [RR], 1.88; 95% CI, 1.34-2.64) and tricyclic or other cyclic antidepressants (absolute risk, 0.89 per 10 000 person-months vs 0.48 per 10 000 person-months; RR, 2.15; 95% CI, 1.06-4.36), but not of other antidepressants (absolute risk, 1

Cost effectiveness analysis comparing repetitive transcranial magnetic stimulation to antidepressant medications after a first treatment failure for major depressive disorder in newly diagnosed patients – A lifetime analysis

PubMed Central

2017-01-01

Objective Repetitive Transcranial Magnetic Stimulation (rTMS) commonly is used for the treatment of Major Depressive Disorder (MDD) after patients have failed to benefit from trials of multiple antidepressant medications. No analysis to date has examined the cost-effectiveness of rTMS used earlier in the course of treatment and over a patients’ lifetime. Methods We used lifetime Markov simulation modeling to compare the direct costs and quality adjusted life years (QALYs) of rTMS and medication therapy in patients with newly diagnosed MDD (ages 20–59) who had failed to benefit from one pharmacotherapy trial. Patients’ life expectancies, rates of response and remission, and quality of life outcomes were derived from the literature, and treatment costs were based upon published Medicare reimbursement data. Baseline costs, aggregate per year quality of life assessments (QALYs), Monte Carlo simulation, tornado analysis, assessment of dominance, and one way sensitivity analysis were also performed. The discount rate applied was 3%. Results Lifetime direct treatment costs, and QALYs identified rTMS as the dominant therapy compared to antidepressant medications (i.e., lower costs with better outcomes) in all age ranges, with costs/improved QALYs ranging from $2,952/0.32 (older patients) to $11,140/0.43 (younger patients). One-way sensitivity analysis demonstrated that the model was most sensitive to the input variables of cost per rTMS session, monthly prescription drug cost, and the number of rTMS sessions per year. Conclusion rTMS was identified as the dominant therapy compared to antidepressant medication trials over the life of the patient across the lifespan of adults with MDD, given current costs of treatment. These models support the use of rTMS after a single failed antidepressant medication trial versus further attempts at medication treatment in adults with MDD. PMID:29073256

Antidepressant activity of the adenosine A2A receptor antagonist, istradefylline (KW-6002) on learned helplessness in rats.

PubMed

Yamada, Koji; Kobayashi, Minoru; Shiozaki, Shizuo; Ohta, Teruko; Mori, Akihisa; Jenner, Peter; Kanda, Tomoyuki

2014-07-01

Istradefylline, an adenosine A2A receptor antagonist, improves motor function in animal models of Parkinson's disease (PD) and in patients with PD. In addition, some A2A antagonists exert antidepressant-like activity in rodent models of depression, such as the forced swim and the tail suspension tests. We have investigated the effect of istradefylline on depression-like behaviors using the rat learned helplessness (LH) model. Acute, as well as chronic, oral administration of istradefylline significantly improved the inescapable shock (IES)-induced escape deficit with a degree of efficacy comparable to chronic treatment with the tricyclic antidepressant desipramine and the selective serotonin (5-HT) reuptake inhibitor, fluoxetine. Both the A1/A2A receptor nonspecific antagonist theophylline and the moderately selective antagonist CGS15943, but not the A1 selective antagonist DPCPX, ameliorated the IES-induced escape deficit. The enhancement of escape response by istradefylline was reversed by a local injection of the A2A specific agonist CGS21680 either into the nucleus accumbens, the caudate-putamen, or the paraventricular nucleus of the hypothalamus, but not by the A1 specific agonist R-PIA into the nucleus accumbens. Moreover, neither the 5-HT2A/2C receptor antagonist methysergide or the adrenergic α 2 antagonist yohimbine, nor the β-adrenergic antagonist propranolol, affected the improvement of escape response induced by istradefylline. Istradefylline exerts antidepressant-like effects via modulation of A2A receptor activity which is independent of monoaminergic transmission in the brain. Istradefylline may represent a novel treatment option for depression in PD as well as for the motor symptoms.

The antidepressant-like effect of trans-astaxanthin involves the serotonergic system.

PubMed

Jiang, Xi; Zhu, Keqi; Xu, Quanyi; Wang, Guokang; Zhang, Jiajia; Cao, Rongrong; Ye, Jiang; Yu, Xuefeng

2017-04-11

The antidepressant-like effect of trans-astaxanthin, a compound present rich in algae, was evaluated through behavioral and neurochemical methods. Results showed that trans-astaxanthin treatment significantly decreased the immobility time in force swim test and tail suspension test, but did not influence locomotor activity. Trans-astaxanthin treatment did not effectively antagonize hypothermia and ptosis induced by reserpine. However, pre-treatment with para-chlorophenylalanine abolished the anti-immobility effect of trans-astaxanthin in force swim and tail suspension test. These results suggested that the mechanism of antidepressant-like effect of trans-astaxanthin may involve the serotonergic system, but not noradrenaline system. This hypothesis was confirmed by neurochemical assays which showed that trans-astaxanthin increased serotonin levels in the hippocampus, frontal cortex, striatum and hypothalamus. Furthermore, our data suggested that trans-astaxanthin decreased indoleamine 2, 3-dioxygenase activity in the hippocampus, frontal cortex and hypothalamus. Inhibition of indoleamine 2,3-dioxygenase activity subsequently decreased the kynurenine/tryptophan ratio and increased the serotonin/tryptophan ratio in these brain regions. Taken together, these findings indicate that the antidepressant-like effect of trans-astaxanthin involves the serotonergic system.

The antidepressant-like effect of trans-astaxanthin involves the serotonergic system

PubMed Central

Jiang, Xi; Zhu, Keqi; Xu, Quanyi; Wang, Guokang; Zhang, Jiajia; Cao, Rongrong; Ye, Jiang; Yu, Xuefeng

2017-01-01

The antidepressant-like effect of trans-astaxanthin, a compound present rich in algae, was evaluated through behavioral and neurochemical methods. Results showed that trans-astaxanthin treatment significantly decreased the immobility time in force swim test and tail suspension test, but did not influence locomotor activity. Trans-astaxanthin treatment did not effectively antagonize hypothermia and ptosis induced by reserpine. However, pre-treatment with para-chlorophenylalanine abolished the anti-immobility effect of trans-astaxanthin in force swim and tail suspension test. These results suggested that the mechanism of antidepressant-like effect of trans-astaxanthin may involve the serotonergic system, but not noradrenaline system. This hypothesis was confirmed by neurochemical assays which showed that trans-astaxanthin increased serotonin levels in the hippocampus, frontal cortex, striatum and hypothalamus. Furthermore, our data suggested that trans-astaxanthin decreased indoleamine 2, 3-dioxygenase activity in the hippocampus, frontal cortex and hypothalamus. Inhibition of indoleamine 2,3-dioxygenase activity subsequently decreased the kynurenine/tryptophan ratio and increased the serotonin/tryptophan ratio in these brain regions. Taken together, these findings indicate that the antidepressant-like effect of trans-astaxanthin involves the serotonergic system. PMID:28424423

Oxidative/nitrosative stress and antidepressants: targets for novel antidepressants.

PubMed

Lee, Seung-Yup; Lee, Soo-Jung; Han, Changsu; Patkar, Ashwin A; Masand, Prakash S; Pae, Chi-Un

2013-10-01

The brain is an organ predisposed to oxidative/nitrosative stress. This is especially true in the case of aging as well as several neurodegenerative diseases. Under such circumstances, a decline in the normal antioxidant defense mechanisms leads to an increase in the vulnerability of the brain to the deleterious effects of oxidative damage. Highly reactive oxygen/nitrogen species damage lipids, proteins, and mitochondrial and neuronal genes. Unless antioxidant defenses react appropriately to damage inflicted by radicals, neurons may experience microalteration, microdysfunction, and degeneration. We reviewed how oxidative and nitrosative stresses contribute to the pathogenesis of depressive disorders and reviewed the clinical implications of various antioxidants as future targets for antidepressant treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

Agomelatine, the first melatonergic antidepressant: discovery, characterization and development.

PubMed

de Bodinat, Christian; Guardiola-Lemaitre, Béatrice; Mocaër, Elisabeth; Renard, Pierre; Muñoz, Carmen; Millan, Mark J

2010-08-01

Current management of major depression, a common and debilitating disorder with a high social and personal cost, is far from satisfactory. All available antidepressants act through monoaminergic mechanisms, so there is considerable interest in novel non-monoaminergic approaches for potentially improved treatment. One such strategy involves targeting melatonergic receptors, as melatonin has a key role in synchronizing circadian rhythms, which are known to be perturbed in depressed states. This article describes the discovery and development of agomelatine, which possesses both melatonergic agonist and complementary 5-hydroxytryptamine 2C (5-HT2C) antagonist properties. Following comprehensive pharmacological evaluation and extensive clinical trials, agomelatine (Valdoxan/Thymanax; Servier) was granted marketing authorization in 2009 for the treatment of major depression in Europe, thereby becoming the first approved antidepressant to incorporate a non-monoaminergic mechanism of action.

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.

Mesoporous hydroxyapatite as a carrier of olanzapine for long-acting antidepression treatment in rats with induced depression.

PubMed

Shyong, Yan-Jye; Wang, Mao-Hsien; Kuo, Li-Wei; Su, Chang-Fu; Kuo, Wei-Ting; Chang, Kuo-Chi; Lin, Feng-Huei

2017-06-10

An antidepressant carrier, mesoporous hydroxyapatite olanzapine (mesoHAP-OLZ), was designed to maintain 3weeks of constant medication release. The carrier was intramuscularly (IM) injected, where cellular activity played a role in achieving the goal of constant release. The efficiency of the treatment was evaluated from 3 perspectives in in vivo studies: locomotor activities, biomarkers, and learning and memory ability. MesoHAP-OLZ can increase the locomotor activity in rats with induced depression determined by open field test (OFT) and forced swim test (FST). Serotonin (5-HT), one of the most important biomarker in depression can also be increased by mesoHAP-OLZ, leading to increased hippocampus activity as measured by functional magnetic resonance imaging (fMRI). MesoHAP-OLZ can also improve learning and memory ability in rats with induced depression during Morris water maze (MWM) test. Our findings further show that mesoHAP-OLZ can provide long-term drug release with a single IM injection, helping to solve the problem of non-adherent medication intake that often occurs in antidepressant therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Identifying genetic loci affecting antidepressant drug response in depression using drug–gene interaction models

PubMed Central

Noordam, Raymond; Avery, Christy L; Visser, Loes E; Stricker, Bruno H

2016-01-01

Antidepressants are often only moderately successful in decreasing the severity of depressive symptoms. In part, antidepressant treatment response in patients with depression is genetically determined. However, although a large number of studies have been conducted aiming to identify genetic variants associated with antidepressant drug response in depression, only a few variants have been repeatedly identified. Within the present review, we will discuss the methodological challenges and limitations of the studies that have been conducted on this topic to date (e.g., ‘treated-only design’, statistical power) and we will discuss how specifically drug–gene interaction models can be used to be better able to identify genetic variants associated with antidepressant drug response in depression. PMID:27248517

Duloxetine, an antidepressant with analgesic properties – a preliminary analysis

PubMed Central

Onuţu, Adela Hilda

2015-01-01

Serotonin and norepinephrine reuptake inhibitors are second-line antidepressants largely used because of their good tolerance and their reduced side effects. Two of these drugs, duloxetine and venlafaxine, are used also in chronic pain management. In this review we present recent data regarding duloxetine’s effects on the central nervous system, linked to acute pain management, and their efficiency in reducing postoperative chronic pain. The drug’s efficacy results from its modulating effect on the descending inhibitory pain pathways and the inhibition of the nociceptive input. There are already several studies in favor of the analgesic properties of duloxetine. However, further and larger randomized studies are necessary in order to clarify duloxetine efficiency in acute postoperative settings, and thereafter on persistent chronic postoperative pain. PMID:28913467