Science.gov

Sample records for sertraline

  1. Sertraline

    MedlinePlus

    ... to abnormally excited) or mania (frenzied, abnormally excited mood) or has thought about or attempted suicide. Talk to your doctor about your condition, symptoms, and personal and family medical history. You and your doctor will decide what type of treatment is right for you.

  2. 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

  3. 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

  4. 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

  5. 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

  6. Sertraline Induces Toxicity and Behavioral Alterations in Planarians.

    PubMed

    Thumé, Isabela Salvador; Frizzo, Marcos Emílio

    2017-01-01

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the number of asynchronous paroxysms; both effects were significantly maintained even 24 h after the sertraline was withdrawn.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concentrations suggest that sertraline might have residual biological consequences for planarians, even after it is withdrawn.

  7. In vivo investigation on the chronic hepatotoxicity induced by sertraline.

    PubMed

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

    2018-05-30

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2008-12-25

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

  10. Treatment of ballism and pseudobulbar affect with sertraline.

    PubMed

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

    2001-10-01

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

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

    PubMed

    Kummen, Ingvild; Jensen, Thomas Giver

    2016-12-12

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

  12. Clinical Subtypes of Premenstrual Syndrome and Responses to Sertraline Treatment

    PubMed Central

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

    2011-01-01

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

  13. Myxedema coma associated with combination aripiprazole and sertraline therapy.

    PubMed

    Church, Chelsea O; Callen, Erin C

    2009-12-01

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

  14. Sertraline-induced periorbital purpura: a case report.

    PubMed

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

    2015-08-01

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

  15. Sertraline inhibits formalin-induced nociception and cardiovascular responses

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2010-04-15

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

  17. Changes in personality traits during treatment with sertraline or citalopram.

    PubMed

    Ekselius, L; Von Knorring, L

    1999-05-01

    Recent studies indicate that selective serotonin re-uptake inhibitors (SSRIs) reduce the symptoms accompanying personality disorders and modulate a normal personality. To examine the effect of two SSRIs, sertraline and citalopram, on personality traits in major depressed patients. Personality traits were evaluated at baseline and after six months using the Karolinska Scales of Personality (KSP). After treatment, significant changes in the direction of normalisation were seen in all scales. To determine whether the observed changes could be explained by improved depressive symptoms, multiple stepwise regressions with the separate KSP as dependent variables were performed. Improvements in depressive symptoms only accounted for 0-8.4% of the observed variance. In depressed patients treated with SSRIs significant effects are seen on personality traits measured by the KSP.

  18. Dynamic potential and surface morphology study of sertraline membrane sensors

    PubMed Central

    Khater, M.M.; Issa, Y.M.; Hassib, H.B.; Mohammed, S.H.

    2014-01-01

    New rapid, sensitive and simple electrometric method was developed to determine sertraline hydrochloride (Ser-Cl) in its pure raw material and pharmaceutical formulations. Membrane sensors based on heteropolyacids as ion associating material were prepared. Silicomolybdic acid (SMA), silicotungstic acid (STA) and phosphomolybdic acid (PMA) were used. The slope and limit of detection are 50.00, 60.00 and 53.24 mV/decade and 2.51, 5.62 and 4.85 μmol L−1 for Ser-ST, Ser-PM and Ser-SM membrane sensors, respectively. Linear range is 0.01–10.00 for the three sensors. These new sensors were used for the potentiometric titration of Ser-Cl using sodium tetraphenylborate as titrant. The surface morphologies of the prepared membranes with and without the modifier (ion-associate) were studied using scanning and atomic force microscopes. PMID:26257944

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-10-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2014-11-01

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

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

    PubMed

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

    2012-06-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2018-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2013-02-01

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

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

    PubMed

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

    2016-11-08

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

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

    PubMed Central

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

    2016-01-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    PubMed Central

    Eugene, Andy R.; Masiak, Jolanta

    2016-01-01

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

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

    PubMed

    Eugene, Andy R; Masiak, Jolanta

    2016-06-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    DTIC Science & Technology

    2012-11-01

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

  16. Sertraline, paroxetine, and venlafaxine in refugee posttraumatic stress disorder with depression symptoms.

    PubMed

    Smajkic, A; Weine, S; Djuric-Bijedic, Z; Boskailo, E; Lewis, J; Pavkovic, I

    2001-07-01

    Three new antidepressants were used in treating posttraumatic stress disorder (PTSD) and symptoms of depression in Bosnian refugees. Thirty-two Bosnian refugees seeking treatment at a mental health clinic participated in a case series study. All received open trials of Sertraline (n = 15), Paroxetine (n = 12), or Venlafaxine (n = 5), with standard clinical doses. Overall, Sertraline and Paroxetine produced statistically significant improvement at 6 weeks in PTSD symptom severity in depression, and in Global Assessment of Functioning. Venlafaxine produced improvement in PTSD symptom severity and in Global Assessment of Functioning, did not yield improvement in symptoms of major depressive disorder; and had a high rate of side effects. Notwithstanding improvement of symptoms, all 32 refugees remained PTSD positive at the diagnostic level at the 6-week follow-up.

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

    PubMed

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

    1994-03-01

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

  18. Intraperitoneal sertraline and fluvoxamine increase contextual fear conditioning but are without effect on overshadowing between cues

    PubMed Central

    Cassaday, H.J.; Thur, K.E.

    2015-01-01

    Treatment with selective serotonin reuptake inhibitors (SSRIs) can reduce contextual conditioning. Since contexts comprise a variety of potentially competing cues, impaired overshadowing may provide an account of such effects. The present study therefore compared the effects of two SSRIs on overshadowing and contextual conditioning, testing suppression of an ongoing behavioral response (licking) by cues previously paired with foot shock. Conditioning to a 5 s light stimulus was reduced when it was presented in compound with a 5 s noise, thus overshadowing was demonstrated. In two experiments, this overshadowing was unaffected by treatment with either sertraline or fluvoxamine. However, unconditioned suppression to the noise (tested in a control group previously conditioned to the light alone) was reduced after sertraline (10 mg/kg, i.p.). The successful demonstration of overshadowing required the use of a second conditioning session or an additional conditioning trial within the same conditioning session. Neither weak nor strong overshadowing (of the light by the tone) was affected by any drug treatment. Moreover, counter to prediction, conditioning to contextual cues was increased rather than impaired by treatment with sertraline (10 mg/kg, i.p.) and fluvoxamine (30 mg/kg, i.p.). PMID:25532461

  19. Intraperitoneal sertraline and fluvoxamine increase contextual fear conditioning but are without effect on overshadowing between cues.

    PubMed

    Cassaday, H J; Thur, K E

    2015-02-01

    Treatment with selective serotonin reuptake inhibitors (SSRIs) can reduce contextual conditioning. Since contexts comprise a variety of potentially competing cues, impaired overshadowing may provide an account of such effects. The present study therefore compared the effects of two SSRIs on overshadowing and contextual conditioning, testing suppression of an ongoing behavioral response (licking) by cues previously paired with foot shock. Conditioning to a 5 s light stimulus was reduced when it was presented in compound with a 5 s noise, thus overshadowing was demonstrated. In two experiments, this overshadowing was unaffected by treatment with either sertraline or fluvoxamine. However, unconditioned suppression to the noise (tested in a control group previously conditioned to the light alone) was reduced after sertraline (10 mg/kg, i.p.). The successful demonstration of overshadowing required the use of a second conditioning session or an additional conditioning trial within the same conditioning session. Neither weak nor strong overshadowing (of the light by the tone) was affected by any drug treatment. Moreover, counter to prediction, conditioning to contextual cues was increased rather than impaired by treatment with sertraline (10 mg/kg, i.p.) and fluvoxamine (30 mg/kg, i.p.). Copyright © 2015. Published by Elsevier Inc.

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

    PubMed

    Halbreich, Uriel; Kahn, Linda S

    2003-11-01

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

  1. A comparative review of escitalopram, paroxetine, and sertraline: are they all alike?

    PubMed Central

    Reines, Elin H.; Montgomery, Stuart A.

    2014-01-01

    It is known that newer antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), provide advantages in tolerability over antidepressants such as the tricyclics. However, even within the SSRI class, differences in efficacy or tolerability exist between the individual drugs. Among the three most widely prescribed SSRIs are paroxetine, sertraline, and escitalopram. Escitalopram is commonly referred to as an SSRI, but also has well-documented allosteric properties, and thus can be further classed as an allosteric serotonin reuptake inhibitor. All three antidepressants are efficacious compared with placebo, but there is evidence that escitalopram is more effective than a range of other antidepressants. There are no direct data to regard either paroxetine or sertraline as a superior antidepressant. Escitalopram is superior compared with paroxetine, which has a less favorable tolerability profile. Paroxetine is associated with cholinergic muscarinic antagonism and potent inhibition of CYP2D6, and sertraline has moderate drug interaction issues in comparison with escitalopram. Overall, as an allosteric serotonin reuptake inhibitor that is somewhat different from classical SSRIs, escitalopram is the first choice judged by combined efficacy and tolerability, and nonclinical data have offered possible mechanisms through which escitalopram could be more efficacious, based on its interaction with orthosteric and allosteric binding sites at the serotonin transporter. PMID:24424469

  2. A comparative review of escitalopram, paroxetine, and sertraline: Are they all alike?

    PubMed

    Sanchez, Connie; Reines, Elin H; Montgomery, Stuart A

    2014-07-01

    It is known that newer antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), provide advantages in tolerability over antidepressants such as the tricyclics. However, even within the SSRI class, differences in efficacy or tolerability exist between the individual drugs. Among the three most widely prescribed SSRIs are paroxetine, sertraline, and escitalopram. Escitalopram is commonly referred to as an SSRI, but also has well-documented allosteric properties, and thus can be further classed as an allosteric serotonin reuptake inhibitor. All three antidepressants are efficacious compared with placebo, but there is evidence that escitalopram is more effective than a range of other antidepressants. There are no direct data to regard either paroxetine or sertraline as a superior antidepressant. Escitalopram is superior compared with paroxetine, which has a less favorable tolerability profile. Paroxetine is associated with cholinergic muscarinic antagonism and potent inhibition of CYP2D6, and sertraline has moderate drug interaction issues in comparison with escitalopram. Overall, as an allosteric serotonin reuptake inhibitor that is somewhat different from classical SSRIs, escitalopram is the first choice judged by combined efficacy and tolerability, and nonclinical data have offered possible mechanisms through which escitalopram could be more efficacious, based on its interaction with orthosteric and allosteric binding sites at the serotonin transporter.

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

    PubMed

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

    2000-03-01

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

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

    PubMed

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

    2006-01-01

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

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

    PubMed

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

    2017-02-07

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

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

    PubMed

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

    2011-01-01

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

  7. Antidepressants and ejaculation: a double-blind, randomized, placebo-controlled, fixed-dose study with paroxetine, sertraline, and nefazodone.

    PubMed

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

    2001-06-01

    Antidepressant medication is often associated with sexual side effects. A double-blind, placebo-controlled study in men with lifelong rapid ejaculation was performed to assess the effects of two selective serotonin (5-HT) reuptake inhibitors--paroxetine and sertraline--and the 5-HT2 antagonist and 5-HT/noradrenaline reuptake inhibitor nefazodone on the latency to ejaculate. Forty-eight men with an intravaginal ejaculation latency time (IELT) of a maximum of 1 minute were randomly assigned to receive paroxetine (20 mg/day), sertraline (50 mg/day), nefazodone (400 mg/day), or placebo for 6 weeks. During the 1-month baseline and 6-week treatment period, IELTs were measured at home with a stopwatch. The trial was completed by 40 men. During the 6-week treatment period, the geometric mean IELT in the placebo group was stable at approximately 20 seconds. Analysis of variance revealed a between-group difference in the evolution of IELT delay over time (p = 0.002); the IELT after paroxetine and sertraline gradually increased to approximately 146 and 58 seconds, respectively, compared with 28 seconds in the nefazodone group. The paroxetine and sertraline groups differed significantly (p < 0.001 and p = 0.024, respectively) from placebo, but the nefazodone group did not (p = 0.85). Compared with baseline, paroxetine exerted the strongest delay in ejaculation, whereas sertraline delayed it only moderately. There was no clinically relevant delay in ejaculation with nefazodone.

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

    PubMed

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

    2008-02-01

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

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

    PubMed

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

    2010-12-01

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

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

    PubMed

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

    2017-06-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2007-11-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  14. Sertraline for the treatment of depression in Alzheimer disease: genetic influences.

    PubMed

    Peters, Matthew E; Vaidya, Vijay; Drye, Lea T; Rosenberg, Paul B; Martin, Barbara K; Porsteinsson, Anton P; Frangakis, Constantine E; Mintzer, Jacobo; Weintraub, Daniel; Schneider, Lon S; Rabins, Peter V; Munro, Cynthia A; Meinert, Curtis L; Lyketsos, Constantine G; Avramopoulos, Dimitri; Dimitri, Avramopoulos

    2011-12-01

    To assess the potential for genetic influences on sertraline treatment efficacy for depression of Alzheimer disease (dAD). Four functional genetic variants were studied: 2 serotonin receptors (HTR2A-T102C and HTR2C-Cys23Ser), the serotonin transporter (5HTT-LPR), and brain-derived neurotrophic factor (BDNF-Val66Met). Treatment response by genotype was measured by (1) the modified Alzheimer's Disease Cooperative Study Clinical Global Impression of Change, (2) the Cornell scale for Depression in Dementia, and (3) remission of depression. We utilized data from the Depression in Alzheimer's Disease Study 2 (DIADS-2), a 24-week, randomized, multicenter trial showing no significant treatment effect of sertraline on dAD. Proportional odds logistic regression and mixed effects models were used to examine the above mentioned outcome measures. No significant interactions were seen between any of the genetic polymorphisms and the selected outcomes above at 12 or 24 weeks. Treatment outcomes in the DIADS-2 trial were not significantly influenced by genetic variation at the loci that were assessed. Future studies should continue to examine the interaction of depression-related genetic variants with antidepressant treatment in Alzheimer disease patients with depression.

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

    PubMed

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

    2007-01-01

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

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

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

    PubMed

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

    2008-01-01

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

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

    PubMed

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

    2009-06-01

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

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

    PubMed

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

    2002-04-01

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

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

    PubMed

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

    2015-02-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2018-05-01

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

  3. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression.

    PubMed

    Rush, A John; Trivedi, Madhukar H; Wisniewski, Stephen R; Stewart, Jonathan W; Nierenberg, Andrew A; Thase, Michael E; Ritz, Louise; Biggs, Melanie M; Warden, Diane; Luther, James F; Shores-Wilson, Kathy; Niederehe, George; Fava, Maurizio

    2006-03-23

    After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor (SSRI), it is not known whether switching to one antidepressant is more effective than switching to another. We randomly assigned 727 adult outpatients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram to receive one of the following drugs for up to 14 weeks: sustained-release bupropion (239 patients) at a maximal daily dose of 400 mg, sertraline (238 patients) at a maximal daily dose of 200 mg, or extended-release venlafaxine (250 patients) at a maximal daily dose of 375 mg. The study was conducted in 18 primary and 23 psychiatric care settings. The primary outcome was symptom remission, defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of the study. Scores on the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR-16), obtained at treatment visits, determined secondary outcomes, including remission (a score of 5 or less at exit) and response (a reduction of 50 percent or more on baseline scores). Remission rates as assessed by the HRSD-17 and the QIDS-SR-16, respectively, were 21.3 percent and 25.5 percent for sustained-release bupropion, 17.6 percent and 26.6 percent for sertraline, and 24.8 percent and 25.0 percent for extended-release venlafaxine. QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion, 26.7 percent for sertraline, and 28.2 percent for extended-release venlafaxine. These treatments did not differ significantly with respect to outcomes, tolerability, or adverse events. After unsuccessful treatment with an SSRI, approximately one in four patients had a remission of symptoms after switching to another antidepressant. Any one of the medications in the study provided a reasonable second-step choice for patients with depression. (ClinicalTrials.gov number, NCT00021528.). Copyright 2006

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

    PubMed

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

    2017-01-01

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

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

    PubMed

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

    2013-12-01

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

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

    PubMed

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

    2017-12-01

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

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

    PubMed

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

    2017-03-01

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

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

    PubMed

    Rogóz, Zofia; Skuza, Grazyna

    2006-01-01

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

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

    PubMed

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

    2006-03-01

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

  10. Adverse effects of the SSRI antidepressant sertraline on early life stages of marine invertebrates.

    PubMed

    Estévez-Calvar, Noelia; Canesi, Laura; Montagna, Michele; Faimali, Marco; Piazza, Veronica; Garaventa, Francesca

    2017-07-01

    Widespread contamination of coastal environments by emerging compounds includes low concentrations of pharmaceuticals. These pollutants are not currently incorporated in monitoring programs despite their effects on non-target organisms are very little documented. Among the selective serotonin reuptake inhibitor (SSRI) antidepressants, sertraline (SRT) is one of the most prescribed globally. In this work, earlier life stages of Amphibalanus amphitrite, Brachionus plicatilis and Mytilus galloprovincialis were exposed to environmental concentrations of SRT in order to study both sub-lethal and lethal responses in 24/48 h-tests. Low concentrations of SRT altered significantly swimming behavior in A. amphitrite and B. plicatilis giving 48 h-EC 50 (μg/L) of 113.88 and 282.23, respectively whereas higher values were observed for mortality and immobilization. EC 50 embryotoxicity with M. galloprovincialis was 206.80 μg/L. This work add new data about SRT ecotoxicity on marine invertebrates and confirms the applicability of behavioral endpoints to evaluate the environmental impact of antidepressants in marine organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. What would you choose? Sertraline or prolonged exposure in community and PTSD treatment seeking women.

    PubMed

    Feeny, Norah C; Zoellner, Lori A; Mavissakalian, Matig R; Roy-Byrne, Peter P

    2009-01-01

    Both sertraline (SER) and prolonged exposure (PE) are empirically supported treatments for chronic posttraumatic stress disorder (PTSD). While efficacious, these treatments are quite different in approach, and such differences may influence both treatment choice and treatment outcome. To date, we know very little about the relative efficacy of pharmacological and psychological treatments for chronic PTSD. In Study 1, we compared rates of treatment choice (SER or PE) in 74 trauma-exposed women. In Study 2, we extended this work to an open-choice treatment trial, in which 31 female assault survivors with chronic PTSD received their choice of SER or PE for ten weeks and were followed over time. In Study 1 (82%) and Study 2 (74.2%), the majority of women chose PE. In Study 2, both SER and PE evidenced moderate to large unadjusted effect sizes, with evidence of an advantage for PE in propensity adjusted analyses at posttreatment. Women with co-occurring major depressive disorder (MDD) were more likely to choose SER than those without MDD. However, among those with MDD, the advantage of PE was particularly evident. Our results highlight the presence of clear treatment preferences for PTSD and their potential impact on outcome. This study underscores the importance of systematic study of patient preferences and encourages a rethinking of one-size fits all approaches to treatment for mental disorders. (c) 2009 Wiley-Liss, Inc.

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

    PubMed

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

    2010-08-01

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

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

    PubMed Central

    Lee, Seung Hyun; Hyun, Jae Seog

    2010-01-01

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

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

    PubMed

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

    2007-09-01

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

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

    PubMed

    Li, Jian-xin; Lu, Qing-ge

    2015-05-01

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

  16. Effective use of sertraline for pathological laughing after severe vasospasm due to aneurysmal subarachnoid hemorrhage: case report.

    PubMed

    Takeuchi, Hayato; Iwamoto, Kazuhide; Mukai, Mao; Fujita, Tomoaki; Tsujino, Hitoshi; Iwamoto, Yoshihiro

    2014-01-01

    Pathological laughing, one subgroup of psuedobulbar affect, is known as laughter inappropriate to the patient's external circumstances and unrelated to the patient's internal emotional state. The authors present the case of a 76-year-old woman with no significant medical history who experienced pathological laughing after subarachnoid hemorrhage (SAH) due to rupture of an aneurysm, which was successfully treated with craniotomy for aneurysm clipping. In the acute stage after the operation she suffered from severe vasospasm and resulting middle cerebral artery territory infarction and conscious disturbance. As she regained consciousness she was afflicted by pathological laughing 6 months after the onset of SAH. Her involuntary laughter was inappropriate to the situation and was incongruent with the emotional state, and she could not control by herself. Finally the diagnosis of pathological laughing was made and treatment with sertraline, a selective serotonin reuptake inhibitor (SSRI), effectively cured the symptoms. Her pathological laughing was estimated to be consequence of infarction in the right prefrontal cortex and/or corona radiata, resulting from vasospasm. To the authors' knowledge, this is the first report of pathological laughing after aneurysmal SAH. The authors offer insight into the pathophysiology of this rare phenomenon. Effectiveness of sertraline would widen the treatment modality against pathological laughing.

  17. Effective Use of Sertraline for Pathological Laughing after Severe Vasospasm Due to Aneurysmal Subarachnoid Hemorrhage: Case Report

    PubMed Central

    TAKEUCHI, Hayato; IWAMOTO, Kazuhide; MUKAI, Mao; FUJITA, Tomoaki; TSUJINO, Hitoshi; IWAMOTO, Yoshihiro

    2014-01-01

    Pathological laughing, one subgroup of psuedobulbar affect, is known as laughter inappropriate to the patient's external circumstances and unrelated to the patient's internal emotional state. The authors present the case of a 76-year-old woman with no significant medical history who experienced pathological laughing after subarachnoid hemorrhage (SAH) due to rupture of an aneurysm, which was successfully treated with craniotomy for aneurysm clipping. In the acute stage after the operation she suffered from severe vasospasm and resulting middle cerebral artery territory infarction and conscious disturbance. As she regained consciousness she was afflicted by pathological laughing 6 months after the onset of SAH. Her involuntary laughter was inappropriate to the situation and was incongruent with the emotional state, and she could not control by herself. Finally the diagnosis of pathological laughing was made and treatment with sertraline, a selective serotonin reuptake inhibitor (SSRI), effectively cured the symptoms. Her pathological laughing was estimated to be consequence of infarction in the right prefrontal cortex and/or corona radiata, resulting from vasospasm. To the authors' knowledge, this is the first report of pathological laughing after aneurysmal SAH. The authors offer insight into the pathophysiology of this rare phenomenon. Effectiveness of sertraline would widen the treatment modality against pathological laughing. PMID:24201096

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

    PubMed

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

    2017-09-01

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

  19. Possible prenatal impact of sertraline on human placental glutathione S-transferase-π.

    PubMed

    Dalmizrak, O; Kulaksiz-Erkmen, G; Ozer, N

    2012-05-01

    Sertraline (SER), a tricyclic antidepressant, is considered to belong to the group of selective amine reuptake inhibitors. Its ability to cross the blood-brain barrier and transplacental transport has been reported previously. It is widely distributed in the brain and is bound to human glutathione S-transferase-π (GST-π). If SER is taken during pregnancy, it gets accumulated in the embryo and fetus, and some studies have suggested it may cause congenital malformations, thus the study of the interaction of GST-π with antidepressants is crucial. In this study, the interaction of human placental GST-π with SER in the presence of the natural ligand, reduced glutathione (GSH) and a xenobiotic ligand, 1-chloro-2,4-dinitrobenzene (CDNB) was investigated. The V(m) values obtained at variable [CDNB] and variable [GSH] were 61.3 ± 2.3 and 46.4 ± 1.7 U/mg protein, respectively. The k(cat) and k(cat)/K(m) values for GSH and CDNB were 3.63 × 10(6) s(-1), 2.59 × 10(10) M(-1) s(-1) and 4.79 × 10(6) s(-1), 1.29 × 10(10) M(-1) s(-1), respectively. The half maximal inhibitory concentration value for SER was 4.60 mM. At constant [CDNB] and variable [GSH] the inhibition type was linear mixed-type, with K(s), α, and K(i) values of 0.14 ± 0.02, 2.90 ± 1.64, and 2.18 ± 0.80 mM, respectively. On the other hand, at fixed [GSH] and at variable [CDNB], the inhibition type was competitive, with K(i) value of 0.96 ± 0.10 mM. Thus, these findings weaken the importance of the protective role of GST against toxic electrophiles in vivo in adults, but due to its immature enterohepatic system SER may accumulate in the fetus and cause congenital malformations.

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

    PubMed

    Heydari, Azhdar; Davoudi, Shima

    2017-02-01

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

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

    PubMed Central

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

    2009-01-01

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

  2. “How Will It Help Me?”: Reasons Underlying Treatment Preferences Between Sertraline and Prolonged Exposure in PTSD

    PubMed Central

    Chen, Jessica A.; Keller, Stephanie M.; Zoellner, Lori A.; Feeny, Norah C.

    2014-01-01

    Individuals with posttraumatic stress disorder (PTSD) often wait years before seeking treatment. Improving treatment initiation and adherence requires a better understanding patient beliefs that lead to treatment preferences. Using a treatment-seeking sample (N = 200) with chronic PTSD, qualitative reasons underlying treatment preferences for either prolonged exposure (PE) or sertraline (SER) were examined. Reasons for treatment preference primarily focused on how the treatment was perceived to reduce PTSD symptoms rather than practical ones. Patients were more positive about PE than SER. Individual differences did not reliably predict underlying preference reasons, suggesting that what makes a treatment desirable is not strongly determined by current functioning, treatment, or trauma history. Taken together, this information is critical for treatment providers, arguing for enhancing psychoeducation about how treatment works and acknowledging pre-existing biases against pharmacotherapy for PTSD that should be addressed. This knowledge has the potential to optimize and better personalize PTSD patient care. PMID:23896851

  3. Treatment of traumatized refugees with sertraline versus venlafaxine in combination with psychotherapy - study protocol for a randomized clinical trial.

    PubMed

    Sonne, Charlotte; Carlsson, Jessica; Elklit, Ask; Mortensen, Erik Lykke; Ekstrøm, Morten

    2013-05-11

    Sufficient evidence is lacking to draw final conclusions on the efficiency of medical and psychological treatments of traumatized refugees with PTSD. The pharmacological treatments of choice today for post-traumatic stress disorder are antidepressants from the subgroup selective serotonin reuptake inhibitors, especially sertraline. The evidence for the use of selective serotonin reuptake inhibitors in the treatment of complex post-traumatic stress disorder in traumatized refugees is very limited. Venlafaxine is a dual-action antidepressant that works on several pathways in the brain. It influences areas in the brain which are responsible for the enhanced anxiety and hyper-arousal experienced by traumatized refugees and which some studies have found to be enlarged among patients suffering from post-traumatic stress disorder. This study will include approximately 150 patients, randomized into two different groups treated with either sertraline or venlafaxine. Patients in both groups will receive the same manual-based cognitive behavioral therapy, which has been especially adapted to this group of patients. The treatment period will be 6 to 7 months. The trial endpoints will be post-traumatic stress disorder and depressive symptoms and social functioning, all measured on validated ratings scales. Furthermore the study will examine the relation between a psycho-social resources and treatment outcome based on 15 different possible outcome predictors. This study is expected to bring forward new knowledge on treatment and clinical evaluation of traumatized refugees and the results are expected to be used in reference programs and clinical guidelines. ClinicalTrials.gov NCT01569685.

  4. Treatment of traumatized refugees with Sertraline versus Venlafaxine in combination with psychotherapy – study protocol for a randomized clinical trial

    PubMed Central

    2013-01-01

    Background Sufficient evidence is lacking to draw final conclusions on the efficiency of medical and psychological treatments of traumatized refugees with PTSD. The pharmacological treatments of choice today for post-traumatic stress disorder are antidepressants from the subgroup selective serotonin reuptake inhibitors, especially Sertraline. The evidence for the use of selective serotonin reuptake inhibitors in the treatment of complex post-traumatic stress disorder in traumatized refugees is very limited. Venlafaxine is a dual-action antidepressant that works on several pathways in the brain. It influences areas in the brain which are responsible for the enhanced anxiety and hyper-arousal experienced by traumatized refugees and which some studies have found to be enlarged among patients suffering from post-traumatic stress disorder. Design This study will include approximately 150 patients, randomized into two different groups treated with either Sertraline or Venlafaxine. Patients in both groups will receive the same manual-based cognitive behavioral therapy, which has been especially adapted to this group of patients. The treatment period will be 6 to 7 months. The trial endpoints will be post-traumatic stress disorder and depressive symptoms and social functioning, all measured on validated ratings scales. Furthermore the study will examine the relation between a psycho-social resources and treatment outcome based on 15 different possible outcome predictors. Discussion This study is expected to bring forward new knowledge on treatment and clinical evaluation of traumatized refugees and the results are expected to be used in reference programs and clinical guidelines. Trial registration ClinicalTrials.gov NCT01569685 PMID:23663588

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

    NASA Astrophysics Data System (ADS)

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

    2007-02-01

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2017-04-01

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

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

    PubMed

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

    2017-11-01

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

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

    PubMed Central

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

    2014-01-01

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

  10. Severe Hypernatremic Dehydration and Lower Limb Gangrene in an Infant Exposed to Lamotrigine, Aripiprazole, and Sertraline in Breast Milk.

    PubMed

    Morin, Caroline; Chevalier, Isabelle

    Hypernatremic dehydration is well described in exclusively breastfed neonates, although life-threatening complications are rarely reported. The present article describes a case of severe hypernatremic dehydration in a previously healthy term neonate. Other published cases of severe complications of hypernatremic dehydration are discussed. The exclusively breastfed neonate described had severe hypernatremic dehydration because of inadequate milk intake, with disseminated intravascular coagulation and right lower limb gangrene that required amputation of all five toes and surgical debridement of the metatarsals. The usual etiology of hypernatremic dehydration in this age group is insufficient breast milk intake. Here, the infant's mother was treated for bipolar disorder with lamotrigine 250 mg orally once daily, aripiprazole 15 mg orally once daily, and sertraline 100 mg orally once daily. Awareness of these complications should prompt close follow-up of the infant with poor weight gain. The role of maternal medication as a risk factor for hypernatremic dehydration among exclusively breastfed infants needs to be further explored.

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

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    2013-10-01

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

  13. Danish physicians' preferences for prescribing escitalopram over citalopram and sertraline to treatment-naïve patients: a national, register-based study.

    PubMed

    Poulsen, Karen Killerup; Glintborg, Dorte; Moreno, Søren Ilsøe; Thirstrup, Steffen; Aagaard, Lise; Andersen, Stig Ejdrup

    2013-05-01

    To investigate whether general practitioners, hospital physicians and specialized practitioners in psychiatry have similar preferences for initiating treatment with expensive serotonin-specific reuptake inhibitors (SSRIs). All first-time prescriptions for the SSRIs escitalopram, citalopram and sertraline reported to the Danish National Register of Medicinal Product Statistics from April 1, 2009 until March 31, 2010 were analysed with regard to treatment naivety and type of prescriber. A prescription was considered as first time if the patient had not received a prescription for the same drug within the last 2 years. Patients who had not received a prescription for an antidepressant within 6 months prior to the date of redemption were classified as treatment-naïve. We included 82,702 first-time prescriptions, 65,313 (79 %) of which were for treatment-naïve patients. Of the treatment-naïve patients, 19 % were initially prescribed escitalopram. Hospital physicians prescribed escitalopram to 34 % of their treatment-naïve patients, while practitioners specialized in psychiatry prescribed it to 25 %, and general practitioners prescribed it to 17 %. General practitioners, however, were responsible for initiating 87 % of all treatment-naïve patients. The most expensive SSRI, escitalopram, is prescribed as first choice to one in five patients receiving their first antidepressant of escitalopram, citalopram or sertraline. General practitioners made the bulk of all first-time SSRI prescriptions to treatment-naïve patients.

  14. Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline.

    PubMed

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

    1998-08-01

    Depression is a common cause of sexual dysfunction, but also antidepressant medication is often associated with sexual side effects. This article includes two related studies. The first double-blind, placebo-controlled study was conducted in men with lifelong rapid ejaculation and aimed to assess putative differences between the major selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, fluvoxamine, paroxetine, and sertraline) with regard to their ejaculation-delaying effect. Sixty men with an intravaginal ejaculation latency time (IELT) of 1 minute or less were randomly assigned to receive fluoxetine 20 mg/day, fluvoxamine 100 mg/day, paroxetine 20 mg/day, sertraline 50 mg/day, or placebo for 6 weeks. During the 1-month baseline and 6-week treatment periods, the men measured their IELT at home using a stopwatch. The trial was completed by 51 men. During the 6-week treatment period, the geometric mean IELT in the placebo group was constant at approximately 20 seconds. Analysis of variance revealed a between-groups difference in the evolution of IELT delay (p = 0.0004); in the paroxetine, fluoxetine, and sertraline groups there was a gradual increase to about 110 seconds, whereas in the fluvoxamine group, IELT was increased to only approximately 40 seconds. The paroxetine, fluoxetine, and sertraline groups differed significantly (p < 0.001, p < 0.001, p = 0.017, respectively) from placebo but the fluvoxamine group did not (p = 0.38). Compared with baseline, paroxetine exerted the strongest delay in ejaculation, followed by fluoxetine and sertraline. There was no clinically relevant delay in ejaculation with fluvoxamine. In men with lifelong rapid ejaculation, paroxetine delayed ejaculation most strongly, whereas fluvoxamine delayed ejaculation the least. The second double-blind, placebo-controlled study was carried out in men with lifelong rapid ejaculation (IELT < or = 1 minute) and in men with lifelong less-rapid ejaculation (IELT > 1 minute) to

  15. Sertraline-induced potentiation of the CYP3A4-dependent neurotoxicity of carbamazepine: an in vitro study.

    PubMed

    Ghosh, Chaitali; Hossain, Mohammad; Spriggs, Addison; Ghosh, Arnab; Grant, Gerald A; Marchi, Nicola; Perucca, Emilio; Janigro, Damir

    2015-03-01

    Drug toxicity is a hurdle to drug development and to clinical translation of basic research. Antiepileptic drugs such as carbamazepine (CBZ) and selective serotonin reuptake inhibitors such as sertraline (SRT) are commonly co-prescribed to patients with epilepsy and comorbid depression. Because SRT may interfere with cytochrome P450 (CYP) enzyme activity and CYPs have been implicated in the conversion of CBZ to reactive cytotoxic metabolites, we investigated in vitro models to determine whether SRT affects the neurotoxic potential of CBZ and the mechanisms involved. Human fetal brain-derived dopaminergic neurons, human brain microvascular endothelial cells (HBMECs), and embryonic kidney (HEK) cells were used to evaluate cytotoxicity of CBZ and SRT individually and in combination. Nitrite and glutathione (GSH) levels were measured with drug exposure. To validate the role of CYP3A4 in causing neurotoxicity, drug metabolism was compared to cell death in HEK CYP3A4 overexpressed and cells pretreated with the CYP3A4 inhibitor ketoconazole. In all cellular systems tested, exposure to CBZ (127 μM) or SRT (5 μM) alone caused negligible cytotoxicity. By contrast CBZ, tested at a much lower concentration (17 μM) in combination with SRT (5 μM), produced prominent cytotoxicity within 15 min exposure. In neurons and HBMECs, cytotoxicity was associated with increased nitrite levels, suggesting involvement of free radicals as a pathogenetic mechanism. Pretreatment of HBMECs with reduced GSH or with the GSH precursor N-acetyl-L-cysteine prevented cytotoxic response. In HEK cells, the cytotoxic response to the CBZ + SRT combination correlated with the rate of CBZ biotransformation and production of 2-hydroxy CBZ, further suggesting a causative role of reactive metabolites. In the same system, cytotoxicity was potentiated by overexpression of CYP3A4, and prevented by CYP3A4 inhibitor. These results demonstrate an unexpected neurotoxic interaction between CBZ and SRT, apparently

  16. Sertraline (Zoloft) and Pregnancy

    MedlinePlus

    ... or motor skills compared to other children. Another study evaluated behaviors in children ages 4-5 years old. This study found no difference in behavior between children whose mothers took an SSRI and those children ...

  17. Rationale and design of A Trial of Sertraline vs. Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression (ASCEND).

    PubMed

    Hedayati, S Susan; Daniel, Divya M; Cohen, Scott; Comstock, Bryan; Cukor, Daniel; Diaz-Linhart, Yaminette; Dember, Laura M; Dubovsky, Amelia; Greene, Tom; Grote, Nancy; Heagerty, Patrick; Katon, Wayne; Kimmel, Paul L; Kutner, Nancy; Linke, Lori; Quinn, Davin; Rue, Tessa; Trivedi, Madhukar H; Unruh, Mark; Weisbord, Steven; Young, Bessie A; Mehrotra, Rajnish

    2016-03-01

    Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes. Published by Elsevier Inc.

  18. Rationale and Design of A Trial of Sertraline vs. Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression (ASCEND)

    PubMed Central

    Hedayati, S. Susan; Daniel, Divya M.; Cohen, Scott; Comstock, Bryan; Cukor, Daniel; Diaz-Linhart, Yaminette; Dember, Laura M.; Dubovsky, Amelia; Greene, Tom; Grote, Nancy; Heagerty, Patrick; Katon, Wayne; Kimmel, Paul L.; Kutner, Nancy; Linke, Lori; Quinn, Davin; Rue, Tessa; Trivedi, Madhukar H.; Unruh, Mark; Weisbord, Steven; Young, Bessie A.; Mehrotra, Rajnish

    2015-01-01

    Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes. PMID:26621218

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

    PubMed

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

    2011-10-01

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

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

    PubMed

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

    2016-11-29

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

  1. A study of sertraline in dialysis (ASSertID): a protocol for a pilot randomised controlled trial of drug treatment for depression in patients undergoing haemodialysis.

    PubMed

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

    2015-10-26

    The prevalence of depression in people receiving haemodialysis is high with estimates varying between 20 and 40 %. There is little research on the effectiveness of antidepressants in dialysis patients with the few clinical trials suffering significant methodological issues. We plan to carry out a study to evaluate the feasibility of conducting a randomised controlled trial in patients on haemodialysis who have diagnosed Major Depressive Disorder. The study has two phases, a screening phase and the randomised controlled trial. Patients will be screened initially with the Beck Depression Inventory to estimate the number of patients who score 16 or above. These patients will be invited to an interview with a psychiatrist who will invite those with a diagnosis of Major Depressive Disorder to take part in the trial. Consenting patients will be randomised to either Sertraline or placebo. Patients will be followed-up for 6 months. Demographic and clinical data will be collected at screening interview, baseline interview and 2 weeks, and every month (up to 6 months) after baseline. The primary outcome is to evaluate the feasibility of conducting a randomised, double blind, placebo pilot trial in haemodialysis patients with depression. Secondary outcomes include estimation of the variability in the outcome measures for the treatment and placebo arms, which will allow for a future adequately powered definitive trial. Analysis will primarily be descriptive, including the number of patients eligible for the trial, drug exposure of Sertraline in haemodialysis patients and the patient experience of participating in this trial. There is an urgent need for this research in the dialysis population because of the dearth of good quality and adequately powered studies. Research with renal patients is particularly difficult as they often have complex medical needs. This research will therefore not only assess the outcome of anti-depressants in haemodialysis patients with depression but

  2. SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients.

    PubMed

    Montejo-González, A L; Llorca, G; Izquierdo, J A; Ledesma, A; Bousoño, M; Calcedo, A; Carrasco, J L; Ciudad, J; Daniel, E; De la Gandara, J; Derecho, J; Franco, M; Gomez, M J; Macias, J A; Martin, T; Perez, V; Sanchez, J M; Sanchez, S; Vicens, E

    1997-01-01

    The authors analyzed the incidence of sexual dysfunction (SD) with different selective serotonin reuptake inhibitors (SSRIs; fluoxetine, fluvoxamine, paroxetine, and sertraline) and hence the qualitative and quantitative changes in SD throughout time in a prospective and multicenter study. Outpatients (192 women and 152 men; age = 39.6 +/- 11.4 years) under treatment with SSRIs were interviewed with an SD questionnaire designed for this purpose by the authors and that included questions about the following: decreased libido, delayed orgasm or anorgasmia, delayed ejaculation, inability to ejaculate, impotence, and general sexual satisfaction. Patients with the following criteria were included: normal sexual function before SSRI intake, exclusive treatment with SSRIs or treatment associated with benzodiazepines, previous heterosexual or self-erotic current sexual practices. Excluded were patients with previous sexual dysfunction, association of SSRIs with neuroleptics, recent hormone intake, and significant medical illnesses. There was a significant increase in the incidence of SD when physicians asked the patients direct questions (58%) versus when SD was spontaneously reported (14%). There were some significant differences among different SSRIs: paroxetine provoked more delay of orgasm or ejaculation and more impotence than fluvoxamine, fluoxetine and sertraline (chi 2, p < .05). Only 24.5% of the patients had a good tolerance of their sexual dysfunction. Twelve male patients who suffered from premature ejaculation before the treatment preferred to maintain delayed ejaculation, and their sexual satisfaction, and that of their partners, clearly improved. Sexual dysfunction was positively correlated with dose. Patients experienced substantial improvement in sexual function when the dose was diminished or the drug was withdrawn. Men showed more incidence of sexual dysfunction than women, but women's sexual dysfunction was more intense than men's. In only 5.8% of

  3. CUSP9* treatment protocol for recurrent glioblastoma: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, sertraline augmenting continuous low dose temozolomide

    PubMed Central

    Kast, Richard E.; Karpel-Massler, Georg; Halatsch, Marc-Eric

    2014-01-01

    CUSP9 treatment protocol for recurrent glioblastoma was published one year ago. We now present a slight modification, designated CUSP9*. CUSP9* drugs- aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, sertraline, ritonavir, are all widely approved by regulatory authorities, marketed for non-cancer indications. Each drug inhibits one or more important growth-enhancing pathways used by glioblastoma. By blocking survival paths, the aim is to render temozolomide, the current standard cytotoxic drug used in primary glioblastoma treatment, more effective. Although esthetically unpleasing to use so many drugs at once, the closely similar drugs of the original CUSP9 used together have been well-tolerated when given on a compassionate-use basis in the cases that have come to our attention so far. We expect similarly good tolerability for CUSP9*. The combined action of this suite of drugs blocks signaling at, or the activity of, AKT phosphorylation, aldehyde dehydrogenase, angiotensin converting enzyme, carbonic anhydrase -2,- 9, -12, cyclooxygenase-1 and -2, cathepsin B, Hedgehog, interleukin-6, 5-lipoxygenase, matrix metalloproteinase -2 and -9, mammalian target of rapamycin, neurokinin-1, p-gp efflux pump, thioredoxin reductase, tissue factor, 20 kDa translationally controlled tumor protein, and vascular endothelial growth factor. We believe that given the current prognosis after a glioblastoma has recurred, a trial of CUSP9* is warranted. PMID:25211298

  4. CUSP9* treatment protocol for recurrent glioblastoma: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, sertraline augmenting continuous low dose temozolomide.

    PubMed

    Kast, Richard E; Karpel-Massler, Georg; Halatsch, Marc-Eric

    2014-09-30

    CUSP9 treatment protocol for recurrent glioblastoma was published one year ago. We now present a slight modification, designated CUSP9*. CUSP9* drugs--aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, sertraline, ritonavir, are all widely approved by regulatory authorities, marketed for non-cancer indications. Each drug inhibits one or more important growth-enhancing pathways used by glioblastoma. By blocking survival paths, the aim is to render temozolomide, the current standard cytotoxic drug used in primary glioblastoma treatment, more effective. Although esthetically unpleasing to use so many drugs at once, the closely similar drugs of the original CUSP9 used together have been well-tolerated when given on a compassionate-use basis in the cases that have come to our attention so far. We expect similarly good tolerability for CUSP9*. The combined action of this suite of drugs blocks signaling at, or the activity of, AKT phosphorylation, aldehyde dehydrogenase, angiotensin converting enzyme, carbonic anhydrase -2,- 9, -12, cyclooxygenase-1 and -2, cathepsin B, Hedgehog, interleukin-6, 5-lipoxygenase, matrix metalloproteinase -2 and -9, mammalian target of rapamycin, neurokinin-1, p-gp efflux pump, thioredoxin reductase, tissue factor, 20 kDa translationally controlled tumor protein, and vascular endothelial growth factor. We believe that given the current prognosis after a glioblastoma has recurred, a trial of CUSP9* is warranted.

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

    PubMed

    Hosseini, Seyed Hamzeh; Rafiei, Alireza; Gaemian, Ali; Tirgari, Abdolhakim; Zakavi, Aliasghar; Yazdani, Jamshid; Bolhari, Jafar; Golzari, Mahmood; Esmaeili Douki, Zahra; Vaezzadeh, Nazanin

    2017-07-01

    Objective: The present study aimed at comparing the effects of Religious Cognitive Behavioral Therapy (RCBT), Cognitive Behavioral Therapy (CBT), and sertraline on depression, anxiety, biomarker levels, and quality of life in patients after coronary artery bypass graft (CABG) surgery. Method: This was a randomized controlled trial with parallel groups. A total of 160 patients after CABG surgery will be screened for anxiety and depression according to clinical interviews based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria and Hospital Anxiety Depression Scale (HADS) scores (≥ 8). To assess religious attitude, Golriz and Baraheni's Religious Attitude questionnaire will be used. Participants will be randomly allocated to 4 groups of 40 including 3 intervention groups (RCBT, CBT, and sertraline) and 1 control group (usual care). RCBT and CBT programs will consist of 12 one-hour weekly sessions. The participants in the pharmacological intervention group will receive 25-200 mg/d of sertraline for 3 months. The Short Form-36 Health Survey (SF-36) will be administered to assess the patients' quality of life. Blood samples will be taken and biomarker levels will be determined using the enzyme-linked immunosorbent assay (ELISA). The primary outcome will be reduction in anxiety and depression scores after the interventions. The secondary outcomes will be increase in quality of life scores and normalized biomarker levels after the interventions. Discussion: If RCBT is found to be more effective than the other methods; it can be used to improve patients' health status after CABG surgery. Irct ID: IRCT201404122898N5.

  6. The effects of sertraline administration from adolescence to adulthood on physiological and emotional development in prenatally stressed rats of both sexes

    PubMed Central

    Pereira-Figueiredo, Inês; Sancho, Consuelo; Carro, Juan; Castellano, Orlando; López, Dolores E.

    2014-01-01

    Sertraline (SERT) is a clinically effective Selective Serotonin Reuptake Inhibitor (SSRI) known to increase and stabilize serotonin levels. This neurotransmitter plays an important role in adolescent brain development in both rodents and humans, and its dysregulation has been correlated with deficits in behavior and emotional regulation. Since prenatal stress may disturb serotoninergic homeostasis, the aim of this study was to examine the long-lasting effects of exposure to SERT throughout adolescence on behavioral and physiological developmental parameters in prenatally stressed Wistar rats. SERT was administered (5 mg/kg/day p.o.) from the age of 1–3 months to half of the progeny, of both sexes, of gestating dams stressed by use of a restraint (PS) or not stressed. Our data reveal that long-term SERT treatment slightly reduced weight gain in both sexes, but reversed the developmental disturbed “catch-up” growth found in PS females. Neither prenatal stress nor SERT treatment induced remarkable alterations in behavior and had no effects on mean startle reflex values. However, a sex-dependent effects of PS was found: in males the PS paradigm slightly increased anxiety-like behavior in the open field, while in females, it impaired startle habituation. In both cases, SERT treatment reversed the phenomena. Additionally, the PS animals exhibited a disturbed leukocyte profile in both sexes, which was reversed by SERT. The present findings are evidence that continuous SERT administration from adolescence through adulthood is safe in rodents and lessens the impact of prenatal stress in rats. PMID:25147514

  7. Preliminary evidence that a functional polymorphism in type 1 deiodinase is associated with enhanced potentiation of the antidepressant effect of sertraline by triiodothyronine.

    PubMed

    Cooper-Kazaz, Rena; van der Deure, Wendy M; Medici, Marco; Visser, Theo J; Alkelai, Ana; Glaser, Benjamin; Peeters, Robin P; Lerer, Bernard

    2009-07-01

    Triiodothyronine (T3) is used to potentiate the clinical effect of antidepressant drugs. Inter-individual differences in efficacy may be related to genetically-based variability in thyroid function. DNA was obtained from 64 patients treated with sertraline plus T3 (SERT-T3, N=35) or plus placebo (SERT-PLB, N=29), for 8 weeks. Antidepressant efficacy was rated with the 21 item Hamilton Rating Scale for Depression (HRSD-21). Functional polymorphisms in type 1 (DIO1-C785T, DIO1-A1814G) and type 2 deiodinase (DIO2-Thr92Ala and DIO2-ORFa-Gly3Asp) were genotyped. DIO1-C785T was associated with efficacy of T3 but not placebo supplementation, as indicated by the interaction of treatment, DIO1-C758T genotype and time (p=0.04) and a stronger effect of SERT-T3 among DIO1-758T allele carriers (p=0.01). HRSD-21 scores of DIO1-758T allele carriers declined by 68.7+26.6% (mean+SD) over 8 weeks compared to 42.9+37.8% among non-carriers (p=0.02). DIO1 plays a key-role in T4 to T3 conversion and in clearance of the inactive metabolite, rT3. Previous data associate the DIO1-785T allele with lower DIO1 activity. This is consistent with our observation that responders to T3 supplementation had lower baseline serum T3 levels than non-responders. Depressed patients, who have a genetically determined lower T4 to T3 conversion, may be more likely to benefit from T3 supplementation.

  8. Stability of Allopurinol, Amitriptyline Hydrochloride, Carbamazepine, Domperidone, Isoniazid, Ketoconazole, Lisinopril, Naproxen, Paracetamol (Acetaminophen), and Sertraline Hydrochloride in SyrSpend SF PH4 Oral Suspensions.

    PubMed

    Polonini, Hudson C; Loures, Sharlene; de Araujo, Edson Peter; Brandão, Marcos Antônio F; Ferreira, Anderson O

    2016-01-01

    Oral liquids are safe alternatives to solid dosage forms, notably for elderly and pediatric patients that present dysphagia. The use of ready-to-use suspending vehicles such as SyrSpend SF PH4 is a suitable resource for pharmacists as they constitute a safe and timesaving option that has been studied often. The objective of this study was to evaluate the stability of 10 commonly used active pharmaceutical ingredients (allopurinol 20 mg/mL; amitriptyline hydrochloride 10 mg/mL; carbamazepine 25 mg/mL; domperidone 5 mg/mL; isoniazid 10 mg/mL; ketoconazole 20 mg/mL; lisinopril 1 mg/mL; naproxen 25 mg/mL; paracetamol [acetaminophen] 50 mg/mL; and sertraline hydrochloride 10 mg/mL) compounded in oral suspensions using SyrSpend SF PH4 as the vehicle throughout the study period and stored both at controlled refrigerated (2°C to 8°C) and room temperature (20°C to 25°C). Stability was assessed by means of measuring the percent recovery at varying time points throughout a 90-day period. The quantification of the active pharmaceutical ingredients was performed by high-performance liquid chromatography through a stability-indicating method. Methods were adequately validated. Forced-degradation studies showed that at least one parameter influenced the stability of the active pharmaceutical ingredients. All suspensions were assayed and showed active pharmaceutical ingredient contents between 90% and 110% during the 90-day study period. Although the forced-degradation experiments led to visible fluctuations in the chromatographic responses, the final preparations were stable in the storage conditions. The beyond-use dates of the preparations were found to be at least 90 days for all suspensions, both for controlled refrigerated temperature and room temperature. This confirms that SyrSpend SF PH4 is a stable suspending vehicle for compounding with a broad range of different active pharmaceutical ingredients for different medical usages. Copyright© by International Journal of

  9. Effects of Passion Flower Extract, as an Add-On Treatment to Sertraline, on Reaction Time in Patients ‎with Generalized Anxiety Disorder: A Double-Blind Placebo-Controlled Study

    PubMed Central

    Nojoumi, Mandana; Ghaeli, Padideh; Salimi, Samrand; Sharifi, Ali; Raisi, Firoozeh

    2016-01-01

    Objective: Because of functional impairment caused by generalized anxiety disorder and due to cognitive side ‎effects of many anti-anxiety agents, in this study we aimed to evaluate the influence of Passion ‎flower standardized extract on reaction time in patients with generalized anxiety disorder.‎ Method: Thirty patients aged 18 to 50 years of age, who were diagnosed with generalized anxiety disorder and ‎fulfilled the study criteria, entered this double-blind placebo-controlled study. Reaction time was ‎measured at baseline and after one month of treatment using computerized software. Correct ‎responses, omission and substitution errors and the mean time of correct responses (reaction time) in ‎both visual and auditory tests were collected. The analysis was performed between the two groups ‎and within each group utilizing SPSS PASW- statics, Version 18. P-value less than 0.05 was ‎considered statistically significant.‎ Results: All the participants were initiated on Sertraline 50 mg/day, and the dosage was increased to 100 ‎mg / day after two weeks. Fourteen patients received Pasipy (Passion Flower) 15 drops three times ‎daily and 16 received placebo concurrently. Inter-group comparison proved no significant difference ‎in any of the test items between assortments while a significant decline was observed in auditory ‎omission errors in passion flower group after on month of treatment using intra-group analysis.‎‎ Conclusion: This study noted that passion flower might be suitable as an add-on in the treatment of generalized ‎anxiety disorder with low side effects. Further studies with longer duration are recommended to ‎confirm the results of this study.‎ PMID:27928252

  10. Effects of Passion Flower Extract, as an Add-On Treatment to Sertraline, on Reaction Time in Patients ‎with Generalized Anxiety Disorder: A Double-Blind Placebo-Controlled Study.

    PubMed

    Nojoumi, Mandana; Ghaeli, Padideh; Salimi, Samrand; Sharifi, Ali; Raisi, Firoozeh

    2016-07-01

    Objective: Because of functional impairment caused by generalized anxiety disorder and due to cognitive side ‎effects of many anti-anxiety agents, in this study we aimed to evaluate the influence of Passion ‎flower standardized extract on reaction time in patients with generalized anxiety disorder.‎ Method: Thirty patients aged 18 to 50 years of age, who were diagnosed with generalized anxiety disorder and ‎fulfilled the study criteria, entered this double-blind placebo-controlled study. Reaction time was ‎measured at baseline and after one month of treatment using computerized software. Correct ‎responses, omission and substitution errors and the mean time of correct responses (reaction time) in ‎both visual and auditory tests were collected. The analysis was performed between the two groups ‎and within each group utilizing SPSS PASW- statics, Version 18. P-value less than 0.05 was ‎considered statistically significant.‎ Results: All the participants were initiated on Sertraline 50 mg/day, and the dosage was increased to 100 ‎mg / day after two weeks. Fourteen patients received Pasipy (Passion Flower) 15 drops three times ‎daily and 16 received placebo concurrently. Inter-group comparison proved no significant difference ‎in any of the test items between assortments while a significant decline was observed in auditory ‎omission errors in passion flower group after on month of treatment using intra-group analysis.‎‎ Conclusion: This study noted that passion flower might be suitable as an add-on in the treatment of generalized ‎anxiety disorder with low side effects. Further studies with longer duration are recommended to ‎confirm the results of this study.‎.

  11. Pilot of a randomised controlled trial of the selective serotonin reuptake inhibitor sertraline versus cognitive behavioural therapy for anxiety symptoms in people with generalised anxiety disorder who have failed to respond to low-intensity psychological treatments as defined by the National Institute for Health and Care Excellence guidelines.

    PubMed

    Buszewicz, Marta; Cape, John; Serfaty, Marc; Shafran, Roz; Kabir, Thomas; Tyrer, Peter; Clarke, Caroline S; Nazareth, Irwin

    2017-08-01

    Generalised anxiety disorder (GAD) is common, causing unpleasant symptoms and impaired functioning. The National Institute for Health and Care Excellence (NICE) guidelines have established good evidence for low-intensity psychological interventions, but a significant number of patients will not respond and require more intensive step 3 interventions, recommended as either high-intensity cognitive behavioural therapy (CBT) or a pharmacological treatment such as sertraline. However, there are no head-to-head comparisons evaluating which is more clinically effective and cost-effective, and current guidelines suggest that treatment choice at step 3 is based mainly on patient preference. To assess clinical effectiveness and cost-effectiveness at 12 months of treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline compared with CBT for patients with persistent GAD not improved with NICE-defined low-intensity psychological interventions. Participant randomised trial comparing treatment with sertraline with high-intensity CBT for patients with GAD who had not responded to low-intensity psychological interventions. Community-based recruitment from local Improving Access to Psychological Therapies (IAPT) services. Four pilot services located in urban, suburban and semirural settings. People considered likely to have GAD and not responding to low-intensity psychological interventions identified at review by IAPT psychological well-being practitioners (PWPs). Those scoring ≥ 10 on the Generalised Anxiety Disorder-7 (GAD-7) anxiety measure were asked to consider involvement in the trial. Aged ≥ 18 years, a score of ≥ 10 on the GAD-7, a primary diagnosis of GAD diagnosed on the Mini International Neuropsychiatric Interview questionnaire and failure to respond to NICE-defined low-intensity interventions. Inability to participate because of insufficient English or cognitive impairment, current major depression, comorbid anxiety disorder(s) causing

  12. Study protocol of the Diabetes and Depression Study (DAD): a multi-center randomized controlled trial to compare the efficacy of a diabetes-specific cognitive behavioral group therapy versus sertraline in patients with major depression and poorly controlled diabetes mellitus.

    PubMed

    Petrak, Frank; Herpertz, Stephan; Albus, Christian; Hermanns, Norbert; Hiemke, Christoph; Hiller, Wolfgang; Kronfeld, Kai; Kruse, Johannes; Kulzer, Bernd; Ruckes, Christian; Müller, Matthias J

    2013-08-06

    Depression is common in diabetes and associated with hyperglycemia, diabetes related complications and mortality. No single intervention has been identified that consistently leads to simultaneous improvement of depression and glycemic control. Our aim is to analyze the efficacy of a diabetes-specific cognitive behavioral group therapy (CBT) compared to sertraline (SER) in adults with depression and poorly controlled diabetes. This study is a multi-center parallel arm randomized controlled trial currently in its data analysis phase. We included 251 patients in 70 secondary care centers across Germany. Key inclusion criteria were: type 1 or 2 diabetes, major depression (diagnosed with the Structured Clinical Interview for DSM-IV, SCID) and hemoglobin A1C >7.5% despite current insulin therapy. During the initial phase, patients received either 50-200 mg/d sertraline or 10 CBT sessions aiming at the remission of depression and enhanced adherence to diabetes treatment and coping with diabetes. Both groups received diabetes treatment as usual. After 12 weeks of this initial open-label therapy, only the treatment-responders (50% depression symptoms reduction, Hamilton Depression Rating Scale, 17-item version [HAMD]) were included in the subsequent one year study phase and represented the primary analysis population. CBT-responders received no further treatment, while SER-responders obtained a continuous, flexible-dose SER regimen as relapse prevention. Adherence to treatment was analyzed using therapeutic drug monitoring (measurement of sertraline and N-desmethylsertraline concentrations in blood serum) and by counting the numbers of CBT sessions received. Outcome assessments were conducted by trained psychologists blinded to group assignment. Group differences in HbA1c (primary outcome) and depression (HAMD, secondary outcome) between 1-year follow-up and baseline will be analyzed by ANCOVA controlling for baseline values. As primary hypothesis we expect that CBT

  13. Study protocol of the Diabetes and Depression Study (DAD): a multi-center randomized controlled trial to compare the efficacy of a diabetes-specific cognitive behavioral group therapy versus sertraline in patients with major depression and poorly controlled diabetes mellitus

    PubMed Central

    2013-01-01

    Background Depression is common in diabetes and associated with hyperglycemia, diabetes related complications and mortality. No single intervention has been identified that consistently leads to simultaneous improvement of depression and glycemic control. Our aim is to analyze the efficacy of a diabetes-specific cognitive behavioral group therapy (CBT) compared to sertraline (SER) in adults with depression and poorly controlled diabetes. Methods/Design This study is a multi-center parallel arm randomized controlled trial currently in its data analysis phase. We included 251 patients in 70 secondary care centers across Germany. Key inclusion criteria were: type 1 or 2 diabetes, major depression (diagnosed with the Structured Clinical Interview for DSM-IV, SCID) and hemoglobin A1C >7.5% despite current insulin therapy. During the initial phase, patients received either 50–200 mg/d sertraline or 10 CBT sessions aiming at the remission of depression and enhanced adherence to diabetes treatment and coping with diabetes. Both groups received diabetes treatment as usual. After 12 weeks of this initial open-label therapy, only the treatment-responders (50% depression symptoms reduction, Hamilton Depression Rating Scale, 17-item version [HAMD]) were included in the subsequent one year study phase and represented the primary analysis population. CBT-responders received no further treatment, while SER-responders obtained a continuous, flexible-dose SER regimen as relapse prevention. Adherence to treatment was analyzed using therapeutic drug monitoring (measurement of sertraline and N-desmethylsertraline concentrations in blood serum) and by counting the numbers of CBT sessions received. Outcome assessments were conducted by trained psychologists blinded to group assignment. Group differences in HbA1c (primary outcome) and depression (HAMD, secondary outcome) between 1-year follow-up and baseline will be analyzed by ANCOVA controlling for baseline values. As primary

  14. The Influence of the Menstrual Cycle on Lithium and Sertraline Blood Levels

    ClinicalTrials.gov

    2017-02-17

    Bipolar Affective Disorders; Cyclothymic Disorder; Schizoaffective Disorder; Major Depressive Disorder; Dysthymic Disorder; Obsessive-Compulsive Disorder; Panic Disorder; Posttraumatic Stress Disorder; Premenstrual Dysphoric Disorder; Social Anxiety Disorder

  15. A Comparison of Cognitive-Behavioral Therapy, Sertraline, and Their Combination for Adolescent Depression

    ERIC Educational Resources Information Center

    Melvin, Glenn A.; Tonge, Bruce J.; King, Neville J.; Heyne, David; Gordon, Michael S.; Klimkeit, Ester

    2006-01-01

    Objective: To evaluate cognitive-behavioral therapy, antidepressant medication alone, and combined CBT and antidepressant medication in the treatment of depressive disorders in adolescents. Method: Seventy-three adolescents (ages 12-18 years) with a primary diagnosis of DSM-IV major depressive disorder, dysthymic disorder, or depressive disorder…

  16. Randomized Controlled Trial of Sertraline, Prolonged Exposure Therapy and Their Combination in OEF/OIF with PTSD

    DTIC Science & Technology

    2015-12-01

    et al., Association of posttraumatic stress disorder with somatic symptoms, health care visits, and absenteeism among Iraq War veterans. The...American Journal of Psychiatry, 2007. 164(1): p. 150-153. 8. Marciniak, M., et al. Medical and productivity costs of anxiety disorders: Case control study

  17. Inflammation Markers and Major Depressive Disorder in Patients With Chronic Heart Failure: Results From the Sertraline Against Depression and Heart Disease in Chronic Heart Failure Study.

    PubMed

    Xiong, Glen L; Prybol, Kevin; Boyle, Stephen H; Hall, Russell; Streilein, Robert D; Steffens, David C; Krishnan, Ranga; Rogers, Joseph G; O'Connor, Christopher M; Jiang, Wei

    2015-09-01

    Major depressive disorder (MDD) and chronic heart failure (CHF) have in common heightening states of inflammation, manifested by elevated inflammation markers such as C-reactive protein. This study compared inflammatory biomarker profiles in patients with CHF and MDD to those without MDD. The study recruited patients admitted to inpatient care for acute heart failure exacerbations, after psychiatric diagnostic interview. Patients with Beck Depression Inventory (BDI) scores lower than 10 and with no history of depression served as the nondepressed reference group (n = 25). MDD severity was defined as follows: mild (BDI 10-15; n = 48), moderate (BDI 16-23; n = 51), and severe (BDI ≥ 24; n = 33). A Bio-Plex assay measured 18 inflammation markers. Ordinal logistic models were used to examine the association of MDD severity and biomarker levels. Adjusting for age, sex, statin use, body mass index, left ventricular ejection fraction, tobacco use, and New York Heart Association class, the MDD overall group variable was significantly associated with elevated interleukin (IL)-2 (p = .019), IL-4 (p = .020), IL-6 (p = .026), interferon-γ (p = .010), monocyte chemoattractant protein 1 (p = .002), macrophage inflammatory protein 1β (p = .003), and tumor necrosis factor α (p = .004). MDD severity subgroups had a greater probability of elevated IL-6, IL-8, interferon-γ, monocyte chemoattractant protein 1, macrophage inflammatory protein 1β, and tumor necrosis factor α compared with nondepressed group. The nondepressed group had greater probability of elevated IL-17 (p < .001) and IL-1β (p < .01). MDD in patients with CHF was associated with altered inflammation marker levels compared with patients with CHF who had no depression. Whether effective depression treatment will normalize the altered inflammation marker levels requires further study. ClinicalTrials.gov NCT00078286.

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

    PubMed

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

    2016-09-01

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  20. Neuroprotective Effects of Psychotropic Drugs in Huntington’s Disease

    PubMed Central

    Lauterbach, Edward C.

    2013-01-01

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

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

    PubMed

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

    2017-01-01

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

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

    PubMed

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

    2005-06-01

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

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

    PubMed Central

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

    2017-01-01

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

  4. When Medication Is Prescribed

    MedlinePlus

    ... or combination of medications for the patient. Selective serotonin reuptake inhibitors (SSRIs): citalopram (brand name: Celexa) escitalopram ( ... brand names: Paxil, Pexeva) sertraline (brand name: Zoloft) Serotonin and norepinephrine reuptake inhibitors (SNRIs): venlafaxine (brand name: ...

  5. St. John's Wort

    MedlinePlus

    ... Berner MM, Kriston L. St. John’s wort for major depression. Cochrane Database of Systematic Reviews. 2008;(4):CD000448 [ ... Hypericum perforatum) versus sertraline and placebo in major depressive disorder: continuation data from a 26-week RCT . Pharmacopsychiatry. ...

  6. Presidential Green Chemistry Challenge: 2002 Greener Synthetic Pathways Award

    EPA Pesticide Factsheets

    Presidential Green Chemistry Challenge 2002 award winner, Pfizer, improved its synthesis of sertraline, the active ingredient in its drug, Zoloft, to double the yield and reduce the use of raw materials, energy, and water.

  7. Antidepressant-selective gynecomastia.

    PubMed

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

    2013-01-01

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

  8. Segmental hair testing to disclose chronic exposure to psychoactive drugs.

    PubMed

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

    2016-06-15

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

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

    PubMed

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

    2005-12-01

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

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

    PubMed

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

    2018-03-29

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

  11. Generic penetration in the retail antidepressant market.

    PubMed

    Ventimiglia, Jeffrey; Kalali, Amir H

    2010-06-01

    In this article, we explore the accelerated penetration of generic antidepressants in the United States market following the availability of generic citalopram and sertraline. Analysis suggests that overall, generic penetration into the antidepressant market has grown from approximately 41 percent in January 2004 to over 73 percent in January 2010. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty.

  12. Unreported Medications Used in Incapacitating Medical Conditions Found in Fatal Civil Aviation Accidents

    DTIC Science & Technology

    1994-08-01

    Carbamazepine 62 = Verapamil 21 = Diazepam 13 = Lidocaine 96 = Fluoxetine 72 = Propranolol 113 = Trazodone 30 = Metoprolol 116 = Sertraline 41 = Procainamid...examined by an aviation medi- Lopressor ( Metoprolol ) for the treatment of high cal examiner, the majority of the cardiovascular drugs blood pressure. In

  13. Treatment Preferences Affect the Therapeutic Alliance: Implications for Randomized Controlled Trials

    ERIC Educational Resources Information Center

    Iacoviello, Brian M.; McCarthy, Kevin Scott; Barrett, Marna S.; Rynn, Moira; Gallop, Robert; Barber, Jacques P.

    2007-01-01

    The influence of treatment preferences on the development of the therapeutic alliance was investigated. Seventy-five patients were followed while participating in a randomized controlled trial comparing supportive-expressive psychotherapy with sertraline or pill placebo in the treatment of major depressive disorder. Therapeutic alliance was…

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

    PubMed

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

    2015-09-01

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

  15. Pharmacological Management of Treatment-Resistant Pediatric Depression

    ERIC Educational Resources Information Center

    Kratochvil, Christopher J.; Wagner, Karen Dineen; Emslie, Graham; March, John

    2005-01-01

    A 13-year-old boy presents with treatment-resistant symptoms of major depression. This is his first episode of depression, initially treated with 200 mg sertraline for 12 weeks with no significant benefit. The severe depression has shown a partial response to weekly cognitive-behavioral therapy (CBT) and fluoxetine, which was titrated up to 60 mg…

  16. Recent NIMH Clinical Trials and Implications for Practice

    ERIC Educational Resources Information Center

    Vitiello, Benedetto; Kratochvil, Christopher J.

    2008-01-01

    Optimal treatment of adolescent depression requires the use of antidepressants such as fluoxetine, and the addition of cognitive-behavioral therapy (CBT) offers better potential. Second-step pharmacological treatment of the disorder offers a success rate of around 50%. Clinical trial for the use of sertraline and CBT in treating…

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

    PubMed

    Zidan, Ahmed S; Aldawsari, Hibah

    2015-01-01

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

  18. Dynamical Systems in Neuropharmacology

    DTIC Science & Technology

    1992-04-15

    induced hyperactivity with the selective serotonin uptake blockers fluoxetine , sertraline, or zimelidine or with the serotonin synthesis inhibitor PCPA. By...Conversely, the catecholamine synthesis inhibitor AMPT, which blocks the effects of amphetamine, did not affect the response to MDMA. We applied our scaling

  19. 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.

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

    PubMed Central

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

    2012-01-01

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

  1. Sertralilne, paroxetine and venlafaxine in refugee post traumatic stress disorder with depression symptoms.

    PubMed

    Smajkić, A; Weine, S; Durić-Bijedić, Z; Boskailo, E; Lewis, J; Pavković, I

    2001-01-01

    The authors describe the use of three new antidepressants: Sertralilne, Paroxetine and Venlafaxine in treating Posttraumatic Stress Disorder and symptoms of Depression in adult Bosnian refugees victims of ethnic cleansing. 32 Bosnian refugees with PTSD and symptoms of Depression presenting for treatment of the mental health consequences of surviving ethnic cleansing, participated in a case series study. All subjects completed open trials of Sertraline (15), Paroxetine (12) or Venlafaxine (5), with standard clinical doses. Overall, Sertraline and Paroxetine yielded statistically significant improvement at 6 weeks in the total PTSD symptom severity, in each symptom cluster, in Beck Depression Inventory and in Global Assessment of Functioning. Venlafaxine produced statistically significant improvement at 6 weeks in the total PTSD symptom severity, in each symptom cluster and in Global Assessment of Functioning but did not yield significant improvement in symptoms of depression and had a high rate of side effects.

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

    PubMed Central

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

    2015-01-01

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

  3. The STRONG STAR Multidisciplinary PTSD Research Consortium

    DTIC Science & Technology

    2011-09-01

    NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b . ABSTRACT U c. THIS PAGE U UU 24 19b. TELEPHONE NUMBER...measures are made. 4. To determine the effects of treatments with the SSRI sertraline in adults exposed to early life stress. B . BODY: During the last...Program no. 190.06. Bingham B , Kaddapakam S, Strong R, Morilak DA (2011) Potential role of corticosterone in the long-lasting effects of prenatal stress

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

    PubMed

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

    2018-04-01

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

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

    PubMed

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

    2014-10-01

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

  6. Generic Penetration in the Retail Antidepressant Market

    PubMed Central

    Kalali, Amir H.

    2010-01-01

    In this article, we explore the accelerated penetration of generic antidepressants in the United States market following the availability of generic citalopram and sertraline. Analysis suggests that overall, generic penetration into the antidepressant market has grown from approximately 41 percent in January 2004 to over 73 percent in January 2010. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty. PMID:20622940

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

    PubMed

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

    2015-05-01

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

  8. Quantitative Prediction of Drug–Drug Interactions Involving Inhibitory Metabolites in Drug Development: How Can Physiologically Based Pharmacokinetic Modeling Help?

    PubMed Central

    Chen, Y; Mao, J; Lin, J; Yu, H; Peters, S; Shebley, M

    2016-01-01

    This subteam under the Drug Metabolism Leadership Group (Innovation and Quality Consortium) investigated the quantitative role of circulating inhibitory metabolites in drug–drug interactions using physiologically based pharmacokinetic (PBPK) modeling. Three drugs with major circulating inhibitory metabolites (amiodarone, gemfibrozil, and sertraline) were systematically evaluated in addition to the literature review of recent examples. The application of PBPK modeling in drug interactions by inhibitory parent–metabolite pairs is described and guidance on strategic application is provided. PMID:27642087

  9. Psychotropic drugs in mixture alter swimming behaviour of Japanese medaka (Oryzias latipes) larvae above environmental concentrations.

    PubMed

    Chiffre, Axelle; Clérandeau, Christelle; Dwoinikoff, Charline; Le Bihanic, Florane; Budzinski, Hélène; Geret, Florence; Cachot, Jérôme

    2016-03-01

    Psychiatric pharmaceuticals, such as anxiolytics, sedatives, hypnotics and antidepressors, are among the most prescribed active substances in the world. The occurrence of these compounds in the environment, as well as the adverse effects they can have on non-target organisms, justifies the growing concern about these emerging environmental pollutants. This study aims to analyse the effects of six psychotropic drugs, valproate, cyamemazine, citalopram, sertraline, fluoxetine and oxazepam, on the survival and locomotion of Japanese medaka Oryzias latipes larvae. Newly hatched Japanese medaka were exposed to individual compounds for 72 h, at concentrations ranging from 10 μg L(-1) to 10 mg L(-1). Lethal concentrations 50 % (LC50) were estimated at 840, 841 and 9,136 μg L(-1) for fluoxetine, sertraline and citalopram, respectively, while other compounds did not induce any significant increase in mortality. Analysis of the swimming behaviour of larvae, including total distance moved, mobility and location, provided an estimated lowest observed effect concentration (LOEC) of 10 μg L(-1) for citalopram and oxazepam, 12.2 μg L(-1) for cyamemazine, 100 μg L(-1) for fluoxetine, 1,000 μg L(-1) for sertraline and >10,000 μg L(-1) for valproate. Realistic environmental mixture of the six psychotropic compounds induced disruption of larval locomotor behaviour at concentrations about 10- to 100-fold greater than environmental concentrations.

  10. Cognitive outcomes after sertaline treatment in patients with depression of Alzheimer disease.

    PubMed

    Munro, Cynthia A; Longmire, Crystal Flynn; Drye, Lea T; Martin, Barbara K; Frangakis, Constantine E; Meinert, Curtis L; Mintzer, Jacobo E; Porsteinsson, Anton P; Rabins, Peter V; Rosenberg, Paul B; Schneider, Lon S; Weintraub, Daniel; Lyketsos, Constantine G

    2012-12-01

    Although many depressed patients with Alzheimer disease (AD) are treated with antidepressants, the effect of such treatment on cognitive performance in these patients is not known. The authors report cognitive outcomes in patients with depression of AD (dAD) after a 24-week trial of sertraline or placebo. Placebo-controlled, randomized, double-blind trial. Outpatient memory clinics at five academic medical centers in the United States. A total of 131 patients with dAD (60 men) and Mini-Mental State Examination scores of 10-26. Sertraline (n = 67), target dose of 100 mg daily or matching placebo (n = 64). Caregivers received standardized psychosocial intervention throughout the trial. Mini-Mental State Examination, cognitive subscale of the Alzheimer's Disease Assessment Scale, letter fluency, backward digit span, Symbol Digit Modalities Test, and Finger Tapping Test, administered at baseline, and 8, 16, and 24 weeks following baseline. A series of linear models indicated no effect of treatment or of depression remission on cognitive test performance at 24 weeks. Regardless of treatment condition, very little change in cognitive test performance was noted in general. Treatment with sertraline in patients with dAD is not associated with greater improvement in cognition at week 24 than treatment with placebo.

  11. Development of resistance to serotonin-induced itch in bile duct ligated mice.

    PubMed

    Ostadhadi, Sattar; Haddadi, Nazgol-Sadat; Foroutan, Arash; Azimi, Ehsan; Elmariah, Sarina; Dehpour, Ahmad-Reza

    2017-06-01

    Cholestatic itch can be severe and significantly impair the quality of life of patients. The serotonin system is implicated in cholestatic itch; however, the pruritogenic properties of serotonin have not been evaluated in cholestatic mice. Here, we investigated the serotonin-induced itch in cholestatic mice which was induced by bile duct ligation (BDL). Serotonin, sertraline or saline were administered intradermally to the rostral back area in BDL and sham operated (SHAM) mice, and the scratching behaviour was videotaped for 1 hour. Bile duct ligated mice had significantly increased scratching responses to saline injection on the seventh day after surgery. Additionally, serotonin or sertraline significantly induced scratching behaviour in BDL mice compared to saline at day 7 after surgery, while it did not induce itch at day 5. The scratching behaviour induced by serotonin or sertraline was significantly less in BDL mice compared to SHAM mice. Likewise, the locomotor activity of BDL or SHAM mice was not significantly different from unoperated (UNOP) mice on the fifth and seventh day, suggesting that the scratching behaviour was not affected by motor dysfunctions. Our data suggest that despite the potentiation of evoked itch, a resistance to serotonin-induced itch is developed in cholestatic mice. © 2017 John Wiley & Sons Australia, Ltd.

  12. Presence of pharmaceuticals in benthic fauna living in a small stream affected by effluent from a municipal sewage treatment plant.

    PubMed

    Grabicova, Katerina; Grabic, Roman; Blaha, Martin; Kumar, Vimal; Cerveny, Daniel; Fedorova, Ganna; Randak, Tomas

    2015-04-01

    Aquatic organisms can be affected not only via polluted water but also via their food. In the present study, we examined bioaccumulation of seventy pharmaceuticals in two benthic organisms, Hydropsyche sp. and Erpobdella octoculata in a small stream affected by the effluent from a sewage treatment plant (STP) in Prachatice (South Bohemia region, Czech Republic). Furthermore, water samples from similar locations were analyzed for all seventy pharmaceuticals. In water samples from a control locality situated upstream of the STP, ten of the seventy pharmaceuticals were found with average total concentrations of 200 ng L(-1). In water samples collected at STP-affected sites (downstream the STP's effluent), twenty-nine, twenty-seven and twenty-nine pharmaceuticals were determined at average total concentrations of 2000, 2100 and 1700 ng L(-1), respectively. Six of the seventy pharmaceuticals (azithromycin, citalopram, clarithromycin, clotrimazole, sertraline, and verapamil) were found in Hydropsyche. Four pharmaceuticals (clotrimazole, diclofenac, sertraline, and valsartan) were detected in Erpobdella. Using evaluation criterion bioconcentration factor (BCF) is higher than 2000 we can assign azithromycin and sertraline as bioaccumulative pharmaceuticals. Even pharmaceuticals present at low levels in water were found in benthic organisms at relatively high concentrations (up to 85 ng g(-1) w.w. for azithromycin). Consequently, the uptake of pharmaceuticals via the food web could be an important exposure pathway for the wild fish population. Copyright © 2014. Published by Elsevier Ltd.

  13. Interface between authorship, industry and science in the domain of therapeutics.

    PubMed

    Healy, David; Cattell, Dinah

    2003-07-01

    Changes in the character of medical authorship. Aims To compare the impact of industry-linked and non-industry linked articles. We compared articles on sertraline being coordinated by a medical writing agency with articles not coordinated in this way. We calculated numbers of Medline-listed articles per author, journal impact factors, literature profiles and citation rates of both sets of articles. Non-agency-linked articles on sertraline had an average of 2.95 authors per article, a mean length of 3.4 pages, a mean Medline listing of 37 articles per author (95% CI 27-47) and a mean literature profile of 283 per article (95% CI 130-435). Agency-linked articles on sertraline had an average of 6.6 authors per article, a mean length of 10.7 pages, a mean Medline listing of 70 articles per author (95% CI 62-79) and a mean literature profile of 1839 per article (95% CI 1076-2602). The citation rate for agency articles was 20.2 (95% CI 13.4-27.0) and for non-agency articles it was 3.7 (95% CI 3.3-8.1). The literature profiles and citation rates of industry-linked and non-industry-linked articles differ. The emerging style of authorship in industry-linked articles can deliver good-quality articles, but it raises concerns for the scientific base of therapeutics.

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

    PubMed

    Mastroianni, Patrícia de Carvalho; Forgerini, Marcela

    2018-01-01

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

  15. Serotonin reuptake inhibitors and breastfeeding: a systematic review.

    PubMed

    Orsolini, Laura; Bellantuono, Cesario

    2015-01-01

    The postnatal period represents a critical phase for mothers because of physiological hormonal changes, the increase of emotional reactions and a greater susceptibility for the onset/recrudescence of psychiatric disorders. Despite the evidence of an increasing utilization of antidepressant drugs during breastfeeding, there is still few reliable information on the neonatal safety of the selective serotonin reuptake inhibitors (SSRIs) and selective noradrenergic reuptake inhibitors (SNRIs) [serotonin reuptake inhibitors (SRIs)] in nursing mothers. The aim of this study is to provide a systematic review on the neonatal safety profile of these drugs during breastfeeding, also assessing the limits of available tools. MEDLINE and PubMed databases were searched without any language restrictions by using the following set of keywords: ((SSRIs OR selective serotonin inhibitor reuptake OR SNRIs OR selective serotonin noradrenaline inhibitor reuptake) AND (breastfeeding OR lactation OR breast milk)). A separate search was also performed for each SSRIs (paroxetine, fluvoxamine, fluoxetine, sertraline, citalopram and escitalopram) and SNRIs (venlafaxine and duloxetine). Sertraline and paroxetine show a better neonatal safety profile during breastfeeding as compared with other SRIs. Less data are available for fluvoxamine, escitalopram and duloxetine. Few studies followed up infants breastfeed for assessing the neurodevelopmental outcomes. Literature review clearly indicates paroxetine and sertraline as the drugs that should be preferred as first line choice in nursing women who need an antidepressant treatment. Copyright © 2014 John Wiley & Sons, Ltd.

  16. A population-based study of the use of selective serotonin reuptake inhibitors before and after introduction of generic equivalents.

    PubMed

    Bolton, James M; Dahl, Matthew; Sareen, Jitender; Enns, Murray W; Leslie, William D; Collins, David M; Alessi-Severini, Silvia

    2012-04-01

    Generic drugs are less expensive than their branded equivalents, but receive limited promotion. This study sought to examine how user rates of individual selective serotonin reuptake inhibitors (SSRIs) changed after the introduction of their generic equivalents. Administrative health and census data were used to examine the rates of use of all 6 SSRIs from 1996 to 2009 in the province of Manitoba (population of 1.2 million). The primary outcome measure was a comparison of the rates of use in the pre- and post-generic periods, using generalized estimating equations. Secondary analyses were stratified by specialty of physician prescriber. Escalating rates of use of branded SSRIs in the pre-generic period significantly decreased after generic versions became available (all Ps < 0.001). Incident use of sertraline and paroxetine continued to decrease throughout the post-generic period (1.5% and 1.9% quarterly decreasing rates, respectively). During the years when generic sertraline, fluoxetine, and fluvoxamine were available, their use declined while branded paroxetine and citalopram use continued to increase. Use of branded citalopram, sertraline, and paroxetine prescribed by general practitioners (GPs) increased at rates significantly higher than when prescribed by psychiatrists (all Ps < 0.001). The introduction of cheaper generic alternatives of SSRIs paradoxically resulted in their use diminishing rather than increasing. With the exception of escitalopram, branded SSRIs tended to be preferentially used, compared with available less expensive generic SSRIs. These patterns were more pronounced for prescriptions by GPs.

  17. Racial differences in adherence and response to combined treatment for full and subthreshold post-traumatic stress disorder and alcohol use disorders: A secondary analysis.

    PubMed

    Ruglass, Lesia M; Pedersen, Annelisa; Cheref, Soumia; Hu, Mei-Chen; Hien, Denise A

    2016-01-01

    We conducted a secondary data analysis to examine whether there were racial differences in adherence and treatment outcomes for participants with co-occurring full and subthreshold post-traumatic stress disorder (PTSD) and alcohol/substance use disorders (A/SUD) who were treated with Seeking Safety (a cognitive-behavioral therapy) and sertraline or Seeking Safety and placebo as part of a clinical trial. Bivarate analyses examined the association between race and adherence, and generalized estimating equations assessed whether race moderated the effect of combination treatment on PTSD and alcohol use outcomes. Except for education, there were no statistically significant racial differences in baseline demographic and psychiatric characteristics. African Americans and Caucasians were equally adherent in number of psychotherapy and medication sessions attended and medication compliance. After controlling for baseline demographics and psychiatric symptoms, however, a race by treatment condition interaction emerged suggesting that African Americans who received the Seeking Safety and sertraline treatment had significantly lower PTSD symptom severity posttreatment and at six months follow-up compared to their counterparts who received Seeking Safety and placebo. No differential effect of treatment condition was found for Caucasians. Moreover, results indicated that a diagnosis of major depressive disorder negatively impacted PTSD symptom recovery for African American participants but not for Caucasians. In conclusion, no differences emerged between African Americans and Caucasians in adherence to combination treatments for PTSD and A/SUD. Findings also suggest assessment and treatment of MDD among African Americans may improve treatment outcomes. More research is needed to determine whether the differential response to Seeking Safety and sertraline among African Americans compared to Caucasians can be replicated.

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2016-09-01

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

  20. Pharmacologic management of comorbid post-traumatic stress disorder and addictions.

    PubMed

    Shorter, Daryl; Hsieh, John; Kosten, Thomas R

    2015-12-01

    Post-traumatic Stress Disorder (PTSD) and substance use disorders (SUD) frequently co-occur, and their combination can increase poor health outcomes as well as mortality. Using PUBMED and the list of references from key publications, this review article covered the epidemiology, neurobiology and pharmacotherapy of PTSD with comorbid alcohol, opiate, and cannabis use disorders. These SUD represent two with and one without FDA approved pharmacotherapies. SUD is two to three times more likely among individuals with lifetime PTSD, and suicide, which is made more likely by both of these disorders, appears to be additively increased by having this comorbidity of SUD and PTSD. The shared neurobiological features of these two illnesses include amygdalar hyperactivity with hippocampal, medial prefrontal and anterior cingulate cortex dysfunction. Medications for comorbid PTSD and SUD include the PTSD treatment sertraline, often used in combination with anticonvulsants, antipsychotics, and adrenergic blockers. When PTSD is comorbid with alcohol use disorder (AUD), naltrexone, acamprosate or disulfiram may be combined with PTSD treatments. Disulfiram alone may treat both PTSD and AUD. For PTSD combined with opiate use disorder methadone or buprenorphine are most commonly used with sertraline. Marijuana use has been considered by some to be a treatment for PTSD, but no FDA treatment for this addiction is approved. Pregabalin and D-cycloserine are two innovations in pharmacotherapy for PTSD and SUD. Comorbid PTSD and SUD amplifies their lethality and treatment complexity. Although they share important neurobiology, these patients uncommonly respond to a single pharmacotherapy such as sertraline or disulfiram and more typically require medication combinations and consideration of the specific type of SUD. © American Academy of Addiction Psychiatry.

  1. Environmental risk assessment of three selective serotonin reuptake inhibitors in the aquatic environment: a case study including a cocktail scenario.

    PubMed

    Styrishave, Bjarne; Halling-Sørensen, Bent; Ingerslev, Flemming

    2011-01-01

    We present an environmental risk assessment of three selective serotonin reuptake inhibitors (SSRIs; citalopram, sertraline, and fluoxetine) in the aquatic environment based on two case scenarios. Abiotic and biotic degradation experiments and sorption estimates were used to predict environmental concentrations of three SSRIs from the wastewater of two psychiatric hospitals, the primary sector, and wastewater entering and leaving wastewater treatment plants (WWTPs). Assuming a sewage treatment retention time of 8 h, abiotic degradation was low, for all three SSRIs inhibitors, ranging between 0 and 2% for hydrolysis and 0 and 6% for photolysis. The biodegradation was also slow, ranging from 0 to 3% within an 8-h period. In untreated sewage, citalopram (CIT) and sertraline (SER) concentrations may be high enough to exert effects on the aquatic biota (CIT: 0.19-10.3 µg/L; SER: 0.14-17.1 µg/L). Removal of the pharmaceuticals is due primarily to sorption in the WWTP. Sertraline was estimated to have the highest concentrations in the sewage effluents, 4.4 and 19.9 ng/L for the two cases, respectively. In treated wastewater, individual SSRI concentrations are probably too low to exert effects on biota. By using concentration addition, a cocktail exposure scenario was estimated. The predicted concentration in the biota calculated from the cocktail effect was 0.05 and 0.16 nmol/g for the two cases, respectively, and SER was found to give the highest contribution to this cocktail effect. The results indicate that the concentrations in the wastewater effluents are one to two orders of magnitude lower than the concentrations likely to cause an effect in the aquatic biota. © 2010 SETAC.

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

    PubMed

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

    2017-02-01

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

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

    PubMed Central

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

    2018-01-01

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

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

    USGS Publications Warehouse

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

    2010-01-01

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

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

    PubMed

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

    2014-04-01

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

  6. Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis.

    PubMed

    Greenberg, Gian D; Laman-Maharg, Abigail; Campi, Katharine L; Voigt, Heather; Orr, Veronica N; Schaal, Leslie; Trainor, Brian C

    2013-01-01

    Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males. We examined the effects of social defeat in monogamous California mice (Peromyscus californicus), a species in which both males and females defend territories. We demonstrate that defeat stress increases mature brain-derived neurotrophic factor (BDNF) protein but not mRNA in the bed nucleus of the stria terminalis (BNST) in females but not males. Changes in BDNF protein were limited to anterior subregions of the BNST, and there were no changes in the adjacent nucleus accumbens (NAc). The effects of defeat on social withdrawal behavior and BDNF were reversed by chronic, low doses of the antidepressant sertraline. However, higher doses of sertraline restored social withdrawal and elevated BDNF levels. Acute treatment with a low dose of sertraline failed to reverse the effects of defeat. Infusions of the selective tyrosine-related kinase B receptor (TrkB) antagonist ANA-12 into the anterior BNST specifically increased social interaction in stressed females but had no effect on behavior in females naïve to defeat. These results suggest that stress-induced increases in BDNF in the anterior BNST contribute to the exaggerated social withdrawal phenotype observed in females.

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

    PubMed Central

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

    2014-01-01

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

  8. Pilot pharmacologic randomized controlled trial for psychogenic nonepileptic seizures(e–Pub ahead of print)(LOE Classification)

    PubMed Central

    LaFrance, W.C.; Keitner, G.I.; Papandonatos, G.D.; Blum, A.S.; Machan, J.T.; Ryan, C.E.; Miller, I.W.

    2010-01-01

    Objective: There have been few treatment trials for psychogenic nonepileptic seizures (PNES). Some psychotherapies have been shown to improve PNES and comorbid symptom outcomes. We evaluated a pharmacologic intervention to test the hypothesis that sertraline would reduce PNES. Methods: We conducted a pilot, double-blind, randomized, placebo-controlled trial in an academic medical hospital with epilepsy center outpatients. Subjects aged 18 to 65 years diagnosed with video-EEG–confirmed PNES were treated with flexible-dose sertraline or placebo over 12 weeks. Seizure calendars and symptom scales were charted prospectively. Secondary outcome measures included psychiatric symptom scales and psychosocial variables. Results: Thirty-eight subjects enrolled, and 26 (68%) completed the trial. Thirty-three subjects with nonzero nonepileptic seizure rates at baseline were included in intent-to-treat analysis of the primary outcome. Subjects assigned to the sertraline arm experienced a 45% reduction in seizure rates from baseline to final visit (p = 0.03) vs an 8% increase in placebo (p = 0.78). Secondary outcome scales revealed no significant between-group differences in change scores from baseline to final visit, after adjustment for differences at baseline. Conclusions: PNES were reduced in patients treated with a serotonin selective reuptake inhibitor, whereas those treated with placebo slightly increased. This study provides feasibility data for a larger-scale study. Level of evidence: This study provides Class II evidence that flexible-dose sertraline up to a maximum dose of 200 mg is associated with a nonsignificant reduction in PNES rate compared with a placebo control arm (risk ratio 0.51, 95% confidence interval 0.25–1.05, p = 0.29), adjusting for differences at baseline. GLOSSARY AED = antiepileptic drug; CI = confidence interval; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; ES = epileptic seizures; ITT = intent to treat; PNES

  9. Emerging Hyperprolactinemic Galactorrhea in Obsessive Compulsive Disorder with a Stable Dose of Fluoxetine.

    PubMed

    Chatterjee, Seshadri Sekhar; Mitra, Sayantanava; Mallik, Nitu

    2015-12-31

    While fluoxetine (FXT) is a frequently prescribed selective serotonin reuptake inhibitor (SSRI), with few major side-effects; altered serotonergic transmissions in hypothalamic pathways might lead to a distressing, and often embarrassing, manifestation of galactorrhea by altering prolactin release in those on FXT. We report here a case of FXT-induced hyperprolactinemic galactorrhea developing late into treatment on a stable regimen, who responded well to subsequent replacement with sertraline. Based on present finding, we suggest that while SSRIs may share similar mechanisms of action, there exist individual differences in their effects on prolactin secretion pathways.

  10. Psychopharmacologic interventions for repetitive behaviors in autism spectrum disorders.

    PubMed

    Soorya, Latha; Kiarashi, Jessica; Hollander, Eric

    2008-10-01

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

  11. Ondansetron reduces naturalistic drinking in non-treatment seeking alcohol dependent individuals with the LL 5′-HTTLPR genotype: a laboratory study

    PubMed Central

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

    2014-01-01

    Background One hypothesis suggests that the differential response to ondansetron and serotonin specific re-uptake inhibitors (SSRIs) may be due to a functional polymorphism of the 5′-HTTLPR promoter region in SLC6A4, the gene that codes for the serotonin transporter (5-HTT). The LL 5′-HTTLPR genotype is postulated to be specifically sensitive to the effects of ondansetron with SS/SL 5′-HTTLPR genotypes sensitive to SSRIs. This study tests this hypothesis by matching non-treatment seeking alcohol dependent (AD) individuals with LL genotype to ondansetron and SS/SL genotypes to the SSRI sertraline, and mis-matching them assessing naturalistic and bar-laboratory alcohol drinking. Methods Seventy-seven AD individuals were randomized to one of two counterbalanced arms to receive sertraline 200mg/day or ondansetron 0.5 mg/day for three weeks followed by an alcohol self-administration experiment (ASAE), then received placebo for three weeks followed by a second ASAE. Individuals then received the alternate drug for three weeks followed by a third ASAE. Drinks per drinking day (DDD with drinks in SDUs) for 7 days prior to each ASAE and milliliters consumed during each ASAE were the primary outcomes. Results Fifty-five participants completed the study. The genotype x order interaction was significant [F(1,47) = 8.42, p = .006] for DDD. Three ANCOVAs were conducted for DDD during the week before each ASAE. Ondansetron compared to sertraline resulted in a significant reduction in DDD during the week before the first [F(1,47) = 7.64, p = .008] but not the third ASAE. There was no difference in milliliters consumed during each ASAE. Conclusion This study modestly supports the hypothesis that ondansetron may reduce DDD in AD individuals with the LL genotype as measured naturalistically. By contrast there was no support that ondansetron reduces drinking during the ASAEs or that sertraline reduces alcohol use in individuals who have SS/SL genotypes. We provide limited

  12. Down Syndrome and Fragile X Syndrome in a Colombian Woman: Case Report.

    PubMed

    Saldarriaga, Wilmar; Ruiz, Fabian Andres; Tassone, Flora; Hagerman, Randi

    2017-09-01

    Down syndrome (DS) and Fragile X syndrome (FXS) are the major genetic causes of intellectual disabilities. Here, we present a case of a 32-year-old woman with the diagnosis of both FXS and DS. She is the daughter of a 47-year-old pre-mutation woman who also has three sons with FXS. Cytogenetic testing detected the presence of a complete trisomy 21. A combination of PCR and Southern blot analysis was utilized to document the presence of the FMR1 full mutation. The patient has physical characteristics and behavioural disturbances typical of both FXS and DS, which were confirmed by molecular testing. Her treatment plan included a trial of sertraline because of the severity of her shyness and lack of language. She had an excellent response to sertraline with improvement in shyness and social interactions, particularly with family members. In this study, we report the case of a woman with both FXS and DS, which is the fifth case of FXS and DS in the world's literature. The patient is from Ricaurte, a small town in Colombia, South America, where there is the world's highest prevalence for FXS. © 2016 John Wiley & Sons Ltd.

  13. Antidepressants in paediatric depression: do not look back in anger but around in awareness.

    PubMed

    Brent, David A; Gibbons, Robert D; Wilkinson, Paul; Dubicka, Bernadka

    2018-02-01

    In this paper, we summarise and critique a network meta-analysis (NMA) of antidepressant efficacy and tolerability for paediatric depression and an accompanying editorial. Although we agree that many of the extant studies are flawed, this meta-analysis showed clear efficacy of fluoxetine in the NMA, and for sertraline and escitalopram in pairwise analyses. Consequently, these papers underestimate the benefits of antidepressants for paediatric depression, and provide support for current practice guideline, which recommends the use of an antidepressant if the patient does not respond to psychotherapy. In these circumstances, fluoxetine should be the first choice, with escitalopram and sertraline as alternatives. Declaration of interest D.A.B. receives royalties from Guilford Press, has or will receive royalties from the electronic self-rated version of the C-SSRS from eResearch Technology, Inc., is on the editorial board of UpToDate, and is a reviewer for Healthwise. R.D.G. serves as an expert witness for the US Department of Justice, Pfizer, Wyeth and GSK; and is the founder of Adaptive Testing Technologies. P.W. receives personal fees from Lundbeck and Takeda. B.D. reports a licensing agreement with Lundbeck for a psychosocial treatment manual for depression. No other disclosures were reported.

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

    PubMed

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

    2017-09-01

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

  15. The Effects of Positive Patient Testimonials on PTSD Treatment Choice

    PubMed Central

    Pruitt, Larry D.; Zoellner, Lori A.; Feeny, Norah C.; Caldwell, Daniel; Hanson, Robert

    2012-01-01

    Despite the existence of effective treatment options for PTSD, these treatments are failing to reach those that stand to benefit from PTSD treatment. Understanding the processes underlying an individual’s treatment seeking behavior holds the potential for reducing treatment-seeking barriers. The current study investigates the effects that positive treatment testimonials have on decisions regarding PTSD treatment. An undergraduate (N = 439) and a trauma-exposed community (N = 203) sample were provided with videotaped treatment rationales for prolonged exposure (PE) and sertraline treatments of PTSD. Half of each sample also viewed testimonials, detailing a fictional patient’s treatment experience. All participants then chose among treatment options and rated the credibility of- and personal reactions toward- those options. Among treatment naïve undergraduates, testimonials increased the proportion choosing PE alone; and among treatment naïve members of the trauma-exposed community sample, testimonials increased the proportion choosing a combined PE plus sertraline treatment. These effects were not observed for those with prior history of either psychotherapeutic or pharmacological treatment. Major barriers exist that prevent individuals with PTSD from seeking treatment. For a critical unreached treatment sample, those who are treatment naïve, positive patient testimonials offer a mechanism in which to make effective treatments more appealing and accessible. PMID:23103234

  16. 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.

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

    PubMed

    Rogóż, Zofia; Kabziński, Marcin

    2011-01-01

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

  18. Intranasal Cotinine Plus Krill Oil Facilitates Fear Extinction, Decreases Depressive-Like Behavior, and Increases Hippocampal Calcineurin A Levels in Mice.

    PubMed

    Alvarez-Ricartes, Nathalie; Oliveros-Matus, Patricia; Mendoza, Cristhian; Perez-Urrutia, Nelson; Echeverria, Florencia; Iarkov, Alexandre; Barreto, George E; Echeverria, Valentina

    2018-02-27

    Failure in fear extinction is one of the more troublesome characteristics of posttraumatic stress disorder (PTSD). Cotinine facilitates fear memory extinction and reduces depressive-like behavior when administered 24 h after fear conditioning in mice. In this study, it was investigated the behavioral and molecular effects of cotinine, and other antidepressant preparations infused intranasally. Intranasal (IN) cotinine, IN krill oil, IN cotinine plus krill oil, and oral sertraline were evaluated on depressive-like behavior and fear retention and extinction after fear conditioning in C57BL/6 mice. Since calcineurin A has been involved in facilitating fear extinction in rodents, we also investigated changes of calcineurin in the hippocampus, a region key on contextual fear extinction. Short-term treatment with cotinine formulations was superior to krill oil and oral sertraline in reducing depressive-like behavior and fear consolidation and enhancing contextual fear memory extinction in mice. IN krill oil slowed the extinction of fear. IN cotinine preparations increased the levels of calcineurin A in the hippocampus of conditioned mice. In the light of the results, the future investigation of the use of IN cotinine preparations for the extinction of contextual fear memory and treatment of treatment-resistant depression (TRD) in PTSD is discussed.

  19. Multivariate therapeutic approach to binge-eating disorder: combined nutritional, psychological and pharmacological treatment.

    PubMed

    Brambilla, Francesca; Samek, Lorenzo; Company, Marta; Lovo, Francesca; Cioni, Luisa; Mellado, Carmen

    2009-11-01

    Treatment for binge-eating disorder (BED) is directed towards either the physical or psychopathological impairments, and often does not cover all the alterations characterizing the disease. In 30 BED patients, we monitored the effects of three types of 6-month treatment, randomly assigned to one of the three treatment groups, each consisting of 10 patients. Group 1 received a 1700-kcal diet (21% proteins, 27% lipids, 52% carbohydrate), cognitive-behavioural therapy (CBT), sertraline (50-150 mg/day) and topiramate (25-150 mg/day); group 2 received the same diet, CBT, sertraline; and group 3 received nutritional counselling and CBT. Binge frequency and weight were assessed every month. The Eating Disorder Inventory-2, the Symptoms Check List-90-Revised (SCL-90-R) and the Personality Diagnostic Questionnaire-4-Revised (PDQ-4-R) were administered before and after treatment. Binge frequency and excessive weight decreased significantly only in group 1 patients, in whom improvement was noted in total Eating Disorder Inventory-2 scores and the subitems 'bulimia', 'drive for thinness', 'maturity fear', 'ascetism', in total SCL-90-R scores and in the subitem 'somatization', in PDQ-4-R subitems 'schizotypic personality' and 'dependent personality'. Group 2 patients improved on the SCL-90-R subitems 'depression' and 'interpersonal relationship' and in the PDQ-4-R 'schizoid personality'. Combination therapy seems to be the only fully effective treatment in BED patients.

  20. Broken heart: depression in cardiovascular disease

    PubMed Central

    Krishnan, K. Ranga R.

    2003-01-01

    Heart disease and depression are among the most common diseases seen in developed countries. The relation-ship between heart disease and depression has been the subject of both popular interest and scientific research. Sadness is often portrayed as a feeling of heaviness in the chest or as a “broken heart.” Interestingly as we learn more about the expression of emotions, it appears that these perceptions may simply be the language representation of somatic feelings. Large, prospective, longitudinal studies that have examined the relationship between depression and development of coronary artery disease (CAD) have shown that depression is a risk factor for the development of CAD. Depression also increases mortality in patients with stable CAD or myocardial infarction compared with patients without depression. The recent Sertraline AntiDepressant HeARt attack Trial (SADHART) has shown that selective serotonin reuptake inhibitors like sertraline can be safely used in patients with depression following myocardial infarction. There is also intriguing evidence that treating depression with antidepressants may improve outcomes, including mortality. PMID:22034195

  1. Mediators of Change in the Child/Adolescent Anxiety Multimodal Treatment Study

    PubMed Central

    Kendall, Philip C.; Cummings, Colleen M.; Villabø, Marianne A.; Narayanan, Martina K.; Treadwell, Kimberli; Birmaher, Boris; Compton, Scott; Piacentini, John; Sherrill, Joel; Walkup, John; Gosch, Elizabeth; Keeton, Courtney; Ginsburg, Golda; Suveg, Cindy; Albano, Anne Marie

    2015-01-01

    Objective Test changes in (a) coping efficacy and (b) anxious self-talk as potential mediators of treatment gains at 3-month follow-up in the Child/Adolescent Anxiety Multimodal Treatment Study (CAMS). Method Participants were 488 youth (ages 7-17; 50.4% male) randomized to cognitive-behavioral therapy (CBT; Coping cat program), pharmacotherapy (sertraline), their combination, or pill placebo. Participants met DSM-IV criteria for generalized anxiety disorder, social phobia, and/or separation anxiety disorder. Coping efficacy (reported ability to manage anxiety provoking situations) was measured by youth and parent reports on the Coping Questionnaire, and anxious self-talk was measured by youth report on the Negative Affectivity Self-Statement Questionnaire. Outcome was measured using the Pediatric Anxiety Rating Scale (completed by Independent Evaluators blind to condition). For temporal precedence, residualized treatment gains were assessed at 3-month follow-up. Results Residualized gains in coping efficacy mediated gains in the CBT, sertraline, and combination conditions. In the combination condition, some unique effect of treatment remained. Treatment assignment was not associated with a reduction in anxious self-talk, nor did anxious self-talk predict changes in anxiety symptoms. Conclusions The findings suggest that improvements in coping efficacy are a mediator of treatment gains. Anxious self-talk did not emerge as a mediator. PMID:26460572

  2. Do early changes in the HAM-D-17 anxiety/somatization factor items affect treatment outcome among depressed outpatients? Comparison of two controlled trials of St John’s Wort (Hypericum Perforatum) versus an SSRI

    PubMed Central

    Bitran, Stella; Farabaugh, Amy H; Ameral, Victoria E; LaRocca, Rachel A; Clain, Alisabet J; Fava, Maurizio; Mischoulon, David

    2011-01-01

    Objective To assess whether early changes in HAM-D-17 anxiety/somatization items predict remission in two controlled studies of hypericum perforatum (St. John’s wort) versus an SSRI for major depressive disorder (MDD). Methods The Hypericum Depression Trial Study Group (NIMH) study randomized 340 subjects to hypericum, sertraline, or placebo for 8 weeks. The MGH study randomized 135 subjects to hypericum, fluoxetine, or placebo for 12 weeks. We examined whether remission was associated with early changes in anxiety/somatization symptoms. Results In the NIMH study, significant associations were observed between remission and early improvement in the anxiety-psychic item (sertraline arm), somatic-gastrointestinal item (hypericum arm), and somatic symptoms-general (placebo arm). None of the three treatment arms of the MGH study showed significant associations between anxiety/somatization symptoms and remission. When both study samples were pooled, we found associations for anxiety-psychic (SSRI arm), somatic-gastrointestinal and hypochondriasis (hypericum arm), and anxiety-psychic and somatic symptoms-general (placebo arm). In the entire sample, remission was associated with improvement in the anxiety-psychic, somatic-gastrointestinal, and somatic symptoms-general items. Conclusions The number and type of anxiety/somatization items associated with remission varied depending on the intervention. Early scrutiny of the HAM-D-17 anxiety/somatization items may help predict remission of MDD. PMID:21278577

  3. Do early changes in the HAM-D-17 anxiety/somatization factor items affect the treatment outcome among depressed outpatients? Comparison of two controlled trials of St John's wort (Hypericum perforatum) versus a SSRI.

    PubMed

    Bitran, Stella; Farabaugh, Amy H; Ameral, Victoria E; LaRocca, Rachel A; Clain, Alisabet J; Fava, Maurizio; Mischoulon, David

    2011-07-01

    To assess whether early changes in Hamilton Depression Rating Scale-17 anxiety/somatization items predict remission in two controlled studies of Hypericum perforatum (St John's wort) versus selective serotonin reuptake inhibitors for major depressive disorder. The Hypericum Depression Trial Study Group (National Institute of Mental Health) randomized 340 patients to Hypericum, sertraline, or placebo for 8 weeks, whereas the Massachusetts General Hospital study randomized 135 patients to Hypericum, fluoxetine, or placebo for 12 weeks. The investigators examined whether remission was associated with early changes in anxiety/somatization symptoms. In the National Institute of Mental Health study, significant associations were observed between remission and early improvement in the anxiety (psychic) item (sertraline arm), somatic (gastrointestinal item; Hypericum arm), and somatic (general) symptoms (placebo arm). None of the three treatment arms of the Massachusetts General Hospital study showed significant associations between anxiety/somatization symptoms and remission. When both study samples were pooled, we found associations for anxiety (psychic; selective serotonin reuptake inhibitors arm), somatic (gastrointestinal), and hypochondriasis (Hypericum arm), and anxiety (psychic) and somatic (general) symptoms (placebo arm). In the entire sample, remission was associated with the improvement in the anxiety (psychic), somatic (gastrointestinal), and somatic (general) items. The number and the type of anxiety/somatization items associated with remission varied depending on the intervention. Early scrutiny of the Hamilton Depression Rating Scale-17 anxiety/somatization items may help to predict remission of major depressive disorder.

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

    PubMed

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

    2017-06-01

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

  5. The Therapeutic Relationship in Cognitive-Behavioral Therapy and Pharmacotherapy for Anxious Youth

    PubMed Central

    Cummings, Colleen M.; Caporino, Nicole E.; Settipani, Cara A.; Read, Kendra L.; Compton, Scott N.; March, John; Sherrill, Joel; Piacentini, John; McCracken, James; Walkup, John; Ginsburg, Golda; Albano, Anne Marie; Rynn, Moira; Birmaher, Boris; Sakolsky, Dara; Gosch, Elizabeth; Keeton, Courtney; Kendall, Philip C.

    2014-01-01

    Objective Examine the therapeutic relationship with cognitive-behavioral therapists and with pharmacotherapists for youth from the Child/Adolescent Anxiety Multimodal Study (CAMS; Walkup et al., 2008). The therapeutic relationship was examined in relation to treatment outcomes. Method Participants were 488 youth (ages 7-17; 50% male) randomized to cognitive-behavioral therapy (CBT; Coping cat), pharmacotherapy (SRT; sertraline), their combination, or pill placebo. Participants met DSM-IV criteria for generalized anxiety disorder, social phobia, and/or separation anxiety disorder. The therapeutic relationship was assessed by youth-report at weeks 6 and 12 of treatment using the Child's Perception of Therapeutic Relationship scale. Outcome measures (Pediatric Anxiety Rating Scale; Clinical Global Impressions Scales) were completed by Independent Evaluators blind to condition. Results For youth who received CBT only, a stronger therapeutic relationship predicted positive treatment outcome. In contrast, the therapeutic relationship did not predict outcome for youth receiving sertraline, combined treatment, or placebo. Conclusions A therapeutic relationship may be important for anxious youth who receive CBT alone. PMID:23750468

  6. Antidepressant Specificity of Serotonin Transporter Suggested by Three LeuT-SSRI Structures

    SciTech Connect

    Zhou, Z.; Zhen, J; Karpowich, N

    2009-01-01

    Sertraline and fluoxetine are selective serotonin re-uptake inhibitors (SSRIs) that are widely prescribed to treat depression. They exert their effects by inhibiting the presynaptic plasma membrane serotonin transporter (SERT). All SSRIs possess halogen atoms at specific positions, which are key determinants for the drugs' specificity for SERT. For the SERT protein, however, the structural basis of its specificity for SSRIs is poorly understood. Here we report the crystal structures of LeuT, a bacterial SERT homolog, in complex with sertraline, R-fluoxetine or S-fluoxetine. The SSRI halogens all bind to exactly the same pocket within LeuT. Mutation at this halogen-binding pocket (HBP)more » in SERT markedly reduces the transporter's affinity for SSRIs but not for tricyclic antidepressants. Conversely, when the only nonconserved HBP residue in both norepinephrine and dopamine transporters is mutated into that found in SERT, their affinities for all the three SSRIs increase uniformly. Thus, the specificity of SERT for SSRIs is dependent largely on interaction of the drug halogens with the protein's HBP.« less

  7. Is Trauma Memory Special? Trauma Narrative Fragmentation in PTSD: Effects of Treatment and Response.

    PubMed

    Bedard-Gilligan, Michele; Zoellner, Lori A; Feeny, Norah C

    2017-03-01

    Seminal theories posit that fragmented trauma memories are critical to posttraumatic stress disorder (PTSD; van der Kolk & Fisler, 1995; Brewin, 2014) and that elaboration of the trauma narrative is necessary for recovery (e.g., Foa, Huppert, & Cahill, 2006). According to fragmentation theories, trauma narrative changes, particularly for those receiving trauma-focused treatment, should accompany symptom reduction. Trauma and control narratives in 77 men and women with chronic PTSD were examined pre- and post-treatment, comparing prolonged exposure (PE) and sertraline. Utilizing self-report, rater coding, and objective coding of narrative content, fragmentation was compared across narrative types (trauma, negative, positive) by treatment modality and response, controlling for potential confounds. Although sensory components increased with PE ( d = 0.23 - 0.44), there were no consistent differences in fragmentation from pre- to post-treatment between PE and sertraline or treatment responders and non-responders. Contrary to theories, changes in fragmentation may not be a crucial mechanism underlying PTSD therapeutic recovery.

  8. Clinical study of duloxetine hydrochloride combined with doxazosin for the treatment of pain disorder in chronic prostatitis/chronic pelvic pain syndrome: An observational study.

    PubMed

    Zhang, Mingxin; Li, Hanzhong; Ji, Zhigang; Dong, Dexin; Yan, Su

    2017-03-01

    To explore the safety and efficacy of the selective 5-serotonin and norepinephrine reuptake inhibitor duloxetine hydrochloride and alpha-adrenergic receptor blocker (alpha-blocker) doxazosin mesylate-controlled tablets in the treatment of pain disorder in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).In all, 150 patients were enrolled and 126 patients completed the study (41 patients in the doxazosin group, 41 patients in the sertraline group, and 44 patients in the duloxetine group). This was an open randomized 6-month study. CP/CPPS patients who met the diagnostic criteria were randomized into 3 groups. The patients in the duloxetine group received doxazosin 4 mg + duloxetine 30 mg once a day, and the dosage of duloxetine was increased to 60 mg after a week. The patients in the doxazosin group received doxazosin 4 mg once a day. The patients in the sertraline group received doxazosin 4 mg + sertraline 50 mg once a day. National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, the short-form McGill Pain questionnaire (SF-MPQ), and the hospital anxiety and depression scale (HAD) were applied for evaluations during follow-up of 1, 3, and 6 months after treatment.There were slight positive significant correlations between NIH-CPSI scores and HAD scores, moderate positive significant correlations between the quality of life (QOL) and SF-MPQ, and slight positive significant correlations between HAD and QOL. The effective rate in the doxazosin group was 4.88%, 19.51%, and 56.10% after 1, 3, and 6 months, respectively (P < 0.05). The SF-MPQ score in the doxazosin group decreased to 1.80 ± 1.29, 2.66 ± 1.57, and 3.24 ± 1.67 after 1, 3, and 6 months, respectively (P < 0.05). The HAD score in the doxazosin group decreased to 2.24 ± 2.17, 4 ± 2.11, and 4.90 ± 2.62 after 1, 3, and 6 months, respectively (P < 0.05). The effective rate in the sertraline group was 9.76%, 36.59%, and 63

  9. Plasma Methylphenidate Levels in Youths With Attention Deficit Hyperactivity Disorder Treated With OROS Formulation.

    PubMed

    Yorbik, Ozgur; Mutlu, Caner; Ozilhan, Selma; Eryilmaz, Gul; Isiten, Nuket; Alparslan, Serdar; Saglam, Esra

    2015-06-01

    There are limited studies investigating the relationship between oral release osmotic system-methylphenidate (OROS-MPH) doses and plasma methylphenidate (MPH) concentrations in children and adolescents. The aim of this study was to investigate the relationship between the doses of OROS-MPH and the plasma levels of the drug. We also examined the effects of the other drugs including aripiprazole, risperidone, fluoxetine, and sertraline on the levels of the MPH in the plasma. The files of 100 attention deficit hyperactivity disorder (ADHD) subjects (76 male, 24 female) who were diagnosed as ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria, were screened. The ages of subjects were between 6 and 18 years (mean = 11.5 ± 3.8 years). Plasma MPH levels were determined by high-performance liquid chromatography-tandem mass spectrometry assay. Daily mean OROS-MPH dose used in ADHD children was 0.7 ± 0.2 mg/kg (range: 0.3-1.3 mg/kg). The mean plasma OROS-MPH was 11.6 ± 7.3 ng/mL (range: 0.5-43.4 ng/mL). There was no group difference in the mean plasma MPH and dose-related MPH levels between the groups that used any additional drug including aripiprazole (n = 25), risperidone (n = 10), fluoxetine (n = 16), sertraline (n = 10), and did not use these drugs (P > 0.05). There was a positive correlation between the OROS-MPH doses (mg/kg) and the blood MPH levels (Pearson correlation = 0.40; P < 0.001). The plasma levels of MPH were found to be less than 13 ng/mL in 65% of the subjects. Our findings point to the fact that plasma levels of MPH show a wide range of changes at similar doses, correlate positively with the doses and, as expected, are not affected by using risperidone, sertraline, fluoxetine, and aripiprazole. Therapeutic drug monitoring may help to optimize MPH dose in patients not responding to treatment or in those experiencing serious side effects, but not in routine clinical practice. The presence of intermediate

  10. 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

  11. Effect of memantine combination therapy on symptoms in patients with moderate-to-severe depressive disorder: randomized, double-blind, placebo-controlled study.

    PubMed

    Amidfar, M; Khiabany, M; Kohi, A; Salardini, E; Arbabi, M; Roohi Azizi, M; Zarrindast, M-R; Mohammadinejad, P; Zeinoddini, A; Akhondzadeh, S

    2017-02-01

    Current treatments for depressive disorders are far from optimum. This study was planned to evaluate possible antidepressant effects and safety of memantine, a selective N-methyl-d-aspartate receptor antagonist, in humans. Sixty-six outpatients with the diagnosis of moderate-to-severe major depressive disorder, based on DSM-V diagnostic criteria, were recruited to participate in a parallel, randomized, controlled trial. Sixty-two participants completed 6 weeks of treatment with either memantine (20 mg/day) plus sertraline (200 mg/day) or placebo plus sertraline (200 mg/day). Patients were evaluated using the Hamilton Depression Rating Scale (HDRS) at baseline and at weeks 2, 4 and 6. Comparison of treatment efficacy in improving depressive symptoms between the two groups was the principal outcome measure. A repeated-measures analysis demonstrated significant time × treatment interaction on HDRS score [F (2·09, 125·67) = 5·09, P = 0·007]. Significantly greater improvement was seen at all three follow-up sessions as well as significantly greater response rates at weeks 4 and 6 (P = 0·018 and P < 0·001, respectively) in the memantine group. Significantly more early improvers and more rapid response to treatment were observed in the memantine group (P = 0·001 and P < 0·001, respectively). A significant reduction was observed in HDRS score from baseline to the study endpoint in both memantine (P < 0·001, Cohen's d = 12·71) and placebo groups (P < 0·001, Cohen's d = 5·13). No serious adverse event occurred. No significantly greater remission rate was seen in the adjunctive memantine therapy. A 6-week course of treatment with memantine as adjunct to sertraline showed a favourable safety and efficacy profile in patients with major depressive disorder. Nonetheless, larger controlled studies of longer duration are necessary to assess long-term safety, efficacy and optimal dosing. © 2016 John Wiley & Sons Ltd.

  12. Site-Selective Copper-Catalyzed Amination and Azidation of Arenes and Heteroarenes via Deprotonative Zincation.

    PubMed

    Hendrick, Charles E; Bitting, Katie J; Cho, Seoyoung; Wang, Qiu

    2017-08-23

    Arene amination is achieved by site-selective C-H zincation followed by copper-catalyzed coupling with O-benzoylhydroxylamines under mild conditions. Key to this success is ortho-zincation mediated by lithium amidodiethylzincate base that is effective for a wide range of arenes, including nonactivated arenes bearing simple functionalities such as fluoride, chloride, ester, amide, ether, nitrile, and trifluoromethyl groups as well as heteroarenes including indole, thiophene, pyridine, and isoquinoline. An analogous C-H azidation is also accomplished using azidoiodinane for direct introduction of a useful azide group onto a broad scope of arenes and heteroarenes. These new transformations offer rapid access to valuable and diverse chemical space of aminoarenes. Their broad applications in organic synthesis and drug discovery are demonstrated in the synthesis of novel analogues of natural product (-)-nicotine and antidepressant sertraline by late-stage amination and azidation reactions.

  13. Concentrations of prioritized pharmaceuticals in effluents from 50 large wastewater treatment plants in the US and implications for risk estimation.

    PubMed

    Kostich, Mitchell S; Batt, Angela L; Lazorchak, James M

    2014-01-01

    We measured concentrations of 56 active pharmaceutical ingredients (APIs) in effluent samples from 50 large wastewater treatment plants across the US. Hydrochlorothiazide was found in every sample. Metoprolol, atenolol, and carbamazepine were found in over 90% of the samples. Valsartan had the highest concentration (5300 ng/L), and also had the highest average concentration (1600 ng/L) across all 50 samples. Estimates of potential risks to healthy human adults were greatest for six anti-hypertensive APIs (lisinopril, hydrochlorothiazide, valsartan, atenolol, enalaprilat, and metoprolol), but nevertheless suggest risks of exposure to individual APIs as well as their mixtures are generally very low. Estimates of potential risks to aquatic life were also low for most APIs, but suggest more detailed study of potential ecological impacts from four analytes (sertraline, propranolol, desmethylsertraline, and valsartan). Published by Elsevier Ltd.

  14. Integrated treatment approach improves cognitive function in demented and clinically depressed patients.

    PubMed

    Bragin, Valentin; Chemodanova, Marina; Dzhafarova, Narmina; Bragin, Ilya; Czerniawski, Jennifer L; Aliev, Gjumrakch

    2005-01-01

    The purpose of this study was to evaluate the efficacy of an integrative treatment approach on cognitive performance. The study sample comprised 35 medically ill patients (20 male, 15 female) with an average age of 71.05, who were diagnosed with mild dementia and depression. These patients were evaluated at baseline and at six, 12, and 24 months of treatment, which included antidepressants (sertraline, citalopram, or venlafaxine XR, alone or in combination with bupropion XR), cholinesterase inhibitors (donepezil, rivastigmine or galantamine), as well as vitamins and supplements (multivitamins, vitamin E, alpha-lipoic acid, omega-3 and coenzyme Q-10). Patients were encouraged to modify their diet and lifestyle and perform mild physical exercises. Results show that the integrative treatment not only protracted cognitive decline for 24 months but even improved cognition, especially memory and frontal lobe functions.

  15. Acute Frontal Lobe Dysfunction Following Prefrontal Low-Frequency Repetitive Transcranial Magnetic Stimulation in a Patient with Treatment-Resistant Depression

    PubMed Central

    Carle, Guilhem; Touat, Mehdi; Bruno, Nicolas; Galanaud, Damien; Peretti, Charles-Siegfried; Valero-Cabré, Antoni; Levy, Richard; Azuar, Carole

    2017-01-01

    The potential of repetitive transcranial magnetic stimulation (rTMS) to treat numerous neurological and psychiatric disorders has been thoroughly studied for the last two decades. Here, we report for the first time, the case of a 65-year-old woman suffering from treatment-resistant depression who developed an acute frontal lobe syndrome following eight sessions of low-frequency rTMS (LF-rTMS) to the right dorsolateral prefrontal cortex while also treated with sertraline and mianserin. The pathophysiological mechanisms underlying such an unexpected acute frontal lobe dysfunction are discussed in relation to the therapeutic use of LF-rTMS in combination with pharmacotherapy in depressed patients. PMID:28611694

  16. Electrochemical Synthesis and Kinetic Evaluation of Electrooxidation of Acetaminophen in the Presence of Antidepressant Drugs

    PubMed Central

    Nematollahi, Davood; Feyzi Barnaji, Bahareh; Amani, Ameneh

    2015-01-01

    With the aim of obtaining information about drug-drug interaction (DDI) between acetaminophen and some of antidepressant drugs (fluoxetine, sertraline and nortriptyline), in the present work we studied the electrochemical oxidation of acetaminophen (paracetamol) in the presence of these drugs by means of cyclic voltammetry and Controlled-potential coulometry. The reaction between N-acetyl-p-benzoquinone-imine (NAPQI) produced from electrooxidation of acetaminophen and antidepressant drugs (see scheme 1) cause to reduce the concentration of NAPQI and decreases the effective concentration of antidepressants. The cyclic voltammetric data were analyzed by digital simulation to measure the homogeneous parameters for the suggesting electrode mechanism. The calculated observed homogeneous rate constants (kobs) for the reaction of electrochemically generated N-acetyl-para benzoquinn-imine with antidepressant drugs was found to vary in the order kobsnortriptyline > kobssertraline > kobsfluxetine at biological pH. PMID:26664378

  17. Navigating Undiagnosed Dissociative Identity Disorder in the Inpatient Setting: A Case Report.

    PubMed

    Urbina, Theresa M; May, Tania; Hastings, Michelle

    2017-05-01

    This case illustrates previously undiagnosed dissociative identity disorder (DID) in a middle-aged female with extensive childhood trauma, who was high functioning prior to a trigger that caused a reemergence of her symptoms. The trigger sparked a dissociative state, attempted suicide, and subsequent inpatient psychiatric hospitalization. Practitioners should include in their differential and screen for undiagnosed DID in patients with episodic psychiatric hospitalizations refractory to the standard treatments for previously diagnosed mental illnesses. Case study. During hospitalization, the diagnosis of DID became apparent and treatment included low-dose risperidone, mirtazapine, sertraline, unconditional positive regard, normalization of her dissociative states in an attempt to decrease her anxiety during treatment, and documentation for the patient via written notes following interviews. These methods helped her come to terms with the diagnosis and allowed the treatment team to teach her coping skills to lessen the impact of dissociative states following discharge.

  18. Clinical characteristics and treatment response to SSRI in a female pedophile.

    PubMed

    Chow, Eva W C; Choy, Alberto L

    2002-04-01

    Although much investigation has been done with male sex offenders, there have been few studies on female sex offenders. Female sex offenders have been reported as having a high incidence of psychiatric disorders, but female paraphilics were rarely described. The literature on the treatment of female sex offenders is also limited and treatment with a selective serotonin reuptake inhibitor (SSRI) has not been reported. This paper presents the case of a woman with DSM-IV pedophilia. Her clinical characteristics, her offense history, and her positive response to treatment with sertraline (a SSRI) are described. This case adds to the limited literature on female pedophiles and suggests that SSRIs may be an effective treatment for paraphilic disorders in female sex offenders.

  19. Pharmacological treatment of unipolar depression during pregnancy and breast-feeding--a clinical overview.

    PubMed

    Nielsen, René Ernst; Damkier, Per

    2012-06-01

    This overview is aimed at clinicians working with patients in the fertile age who suffer from depressive disorders. The study of adverse effects of antidepressants on the foetus is hampered by difficulty in distinguishing between the behavioural changes that are related to the disorder itself and changes that accompany its treatment with antidepressants. The current lack of solid scientific knowledge and the implications, mainly emotional, of treating pregnant or breast-feeding women often raise anxiety and cause concern among patients and clinicians. Currently available data are evaluated and clinical recommendations given. Citalopram and sertraline can be used during pregnancy, while some controversy remains over in utero exposure to paroxetine and fluoxetine, which might be associated with an increased risk of foetal cardiovascular malformation. Less data is available concerning fluvoxamine and escitalopram use but current data does not indicate a specific risk. Citalopram, paroxetine and sertraline can be used during breast-feeding, while fluoxetine probably should be avoided. Nortriptyline, amitriptyline and clomipramine can be used during pregnancy and lactation, although data are more abundant for SSRI treatment. Venlafaxine can be used during pregnancy, while caution is advised during breast-feeding. Other antidepressants should be avoided because of lack of data on their effect. A strongly indicated lithium therapy should be continued. Close monitoring of lithium levels throughout pregnancy is mandatory, as is detailed foetal echocardiography in weeks 18-22 of gestation. Lithium should not be used during breast-feeding. Electroconvulsive therapy (ECT) is a valid option if indicated, both during pregnancy and breast-feeding.

  20. Sequenced treatment alternatives to relieve depression (STAR*D): rationale and design.

    PubMed

    Rush, A John; Fava, Maurizio; Wisniewski, Stephen R; Lavori, Philip W; Trivedi, Madhukar H; Sackeim, Harold A; Thase, Michael E; Nierenberg, Andrew A; Quitkin, Frederic M; Kashner, T Michael; Kupfer, David J; Rosenbaum, Jerrold F; Alpert, Jonathan; Stewart, Jonathan W; McGrath, Patrick J; Biggs, Melanie M; Shores-Wilson, Kathy; Lebowitz, Barry D; Ritz, Louise; Niederehe, George

    2004-02-01

    STAR*D is a multisite, prospective, randomized, multistep clinical trial of outpatients with nonpsychotic major depressive disorder. The study compares various treatment options for those who do not attain a satisfactory response with citalopram, a selective serotonin reuptake inhibitor antidepressant. The study enrolls 4000 adults (ages 18-75) from both primary and specialty care practices who have not had either a prior inadequate response or clear-cut intolerance to a robust trial of protocol treatments during the current major depressive episode. After receiving citalopram (level 1), participants without sufficient symptomatic benefit are eligible for randomization to level 2 treatments, which entail four switch options (sertraline, bupropion, venlafaxine, cognitive therapy) and three citalopram augment options (bupropion, buspirone, cognitive therapy). Those who receive cognitive therapy (switch or augment options) at level 2 without sufficient improvement are eligible for randomization to one of two level 2A switch options (venlafaxine or bupropion). Level 2 and 2A participants are eligible for random assignment to two switch options (mirtazapine or nortriptyline) and to two augment options (lithium or thyroid hormone) added to the primary antidepressant (citalopram, bupropion, sertraline, or venlafaxine) (level 3). Those without sufficient improvement at level 3 are eligible for level 4 random assignment to one of two switch options (tranylcypromine or the combination of mirtazapine and venlafaxine). The primary outcome is the clinician-rated, 17-item Hamilton Rating Scale for Depression, administered at entry and exit from each treatment level through telephone interviews by assessors masked to treatment assignments. Secondary outcomes include self-reported depressive symptoms, physical and mental function, side-effect burden, client satisfaction, and health care utilization and cost. Participants with an adequate symptomatic response may enter the 12-month

  1. [Selective serotonin reuptake inhibitors in the therapy of various types of endogenous depressions].

    PubMed

    Panteleeva, G P; Abramova, L I; Korenev, A N

    2000-01-01

    In order to specify differential indications for the use of selective serotonin reuptake inhibitors (SSRI) their therapeutic effect was investigated in apathic-adynamic, melancholic and anxious depressions. Group of 151 patients received monotherapy with one of SSRI-drugs: citalopram--22 patients (mean daily dosage--27.4 mg), paroxetine--47 patients (23 mg), sertraline--19 patients (107 mg), fluvoxamine--28 patients (162 mg), fluoxetine--35 patients (20 mg). The state of the patients was estimated 5 times during 42 days of therapy by clinical estimations and according to Hamilton Depression Scale (HAM-D). Therapeutic effects of the drugs were determined according to the degree of reduction of the total HAM-D scores and they were considered as "significant" (a reduction of the scores by 50% and more), "moderate" (by 21-49%), and "insignificant" (by 1-20%). Positive antidepressive effect, including "significant" was obtained in the case of the use of all the drugs studied. Differential evaluation of the three components of antidepressive activity (thymoleptic, sedative-anxiolytic, and stimulative) according to the degrees and data of expression of drugs' therapeutic effect has allowed to determine indications for the therapy of endogenous depressions by each of SSRI: to recommend cytalopram for the treatment of various types of depressive states mainly, for anxious and apatho-adynamic types; paroxetin--for treatment of melancholic depressions as well as for anxious and apatho-dynamic ones; sertralin++--for depression with anxiety and fobic disorders; fluvoxamine--for melancholic and anxious depression; fluoxetine--for apatho-adynamic depressions.

  2. A case report of schizoaffective disorder with ritualistic behaviors and catatonic stupor: successful treatment by risperidone and modified electroconvulsive therapy.

    PubMed

    Bai, Yuanhan; Yang, Xi; Zeng, Zhiqiang; Yang, Haichen

    2018-03-13

    Ritualistic behaviors are common in obsessive compulsive disorder (OCD), while catatonic stupor occasionally occurs in psychotic or mood disorders. Schizoaffective disorder is a specific mental disorder involving both psychotic and affective symptoms. The syndrome usually represents a specific diagnosis, as in the case of the 10th edition of the International Classification of Diseases (ICD-10) or the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). However, symptom-based diagnosis can result in misdiagnosis and hinder effective treatment. Few cases of ritualistic behaviors and catatonic stupor associated with schizoaffective disorder have been reported. Risperidone and modified electroconvulsive therapy (MECT) were effective in our case. A 35-year-old man with schizoaffective disorder-depression was admitted to the hospital because of ritualistic behaviors, depression, and distrust. At the time of admission, prominent ritualistic behaviors and depression misled us to make the diagnosis of OCD. Sertraline add-on treatment exacerbated the psychotic symptoms, such as pressure of thoughts and delusion of control. In the presence of obvious psychotic symptoms and depression, schizoaffective disorder-depression was diagnosed according to ICD-10. Meanwhile, the patient unfortunately developed catatonic stupor and respiratory infection, which was identified by respiratory symptoms, blood tests, and a chest X-ray. To treat psychotic symptoms, catatonic stupor, and respiratory infection, risperidone, MECT, and ceftriaxone were administered. As a result, we successfully cured the patient with the abovementioned treatment strategies. Eventually, the patient was diagnosed with schizoaffective disorder-depression with ritualistic behaviors and catatonia. Risperidone and MECT therapies were dramatically effective. Making a differential diagnosis of mental disorders is a key step in treating disease. Sertraline was not recommended for treating

  3. Physical Exercise for Late-Life Depression: Customizing an Intervention for Primary Care.

    PubMed

    Zanetidou, Stamatula; Belvederi Murri, Martino; Menchetti, Marco; Toni, Giulio; Asioli, Fabrizio; Bagnoli, Luigi; Zocchi, Donato; Siena, Matteo; Assirelli, Barbara; Luciano, Claudia; Masotti, Mattia; Spezia, Carlo; Magagnoli, Monica; Neri, Mirco; Amore, Mario; Bertakis, Klea D

    2017-02-01

    To identify which individual- and context-related factors influence the translation into clinical practice of interventions based on physical exercise (PE) as an adjunct to antidepressants (AD) for the treatment of late-life major depression (LLMD). Secondary analysis of a randomized controlled trial. Primary care with psychiatric consultation-liaison programs (PCLPs)-organizational protocols that regulate the clinical management of individuals with psychiatric disorders. Individuals aged 65 and older with major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (N = 121). Participants with LLMD were randomized to AD (sertraline) or AD plus PE (AD + PE). Participant characteristics that were associated with greater effectiveness of AD + PE (moderators) were identified, and effect sizes were calculated from success rate differences. Whether the characteristics of the study setting influenced participant flow and attendance at exercise sessions was then explored, and primary care physicians (PCPs) were surveyed regarding their opinions on PE as a treatment for LLMD. The following participant characteristics were associated with greater likelihood of achieving remission from depression with AD + PE than with AD alone: aged 75 and older (effect size 0.32), polypharmacy (0.35), greater aerobic capacity (0.48), displaying psychomotor slowing (0.49), and less-severe anxiety (0.30). The longer the PCLP had been established at a particular center, the more individuals were recruited at that center. After participating in the study, PCPs expressed positive views on AD + PE as a treatment for LLMD and were more likely to use this as a therapeutic strategy. The combination of PE and sertraline could improve the management of LLMD, especially when customized for individuals with specific clinical features. Liaison programs might influence the implementation of similar interventions in primary care, and PCPs viewed them positively

  4. [Sexual dysfunction secondary to SSRIs. A comparative analysis in 308 patients].

    PubMed

    Montejo, A I; Llorca, G; Izquierdo, J A; Ledesma, A; Bousoño, M; Calcedo, A; Carrasco, J L; Daniel, E; de Dios, A; de la Gándara, J; Derecho, J; Franco, M; Gómez, M J; Macías, J A; Martín, T; Pérez, V; Sánchez, J M; Sánchez, S; Vicens, E

    1996-01-01

    The authors analyze the incidence of sexual dysfunction (SD) with different SSRIs (Fluoxetine, Fluvoxamine, Paroxetine and Sertraline) and hence the qualitative and quantitative changes in SD throughout time 308 outpatients (169 women, 139 men; mean +/- SD age = 41 +/- 7) under treatment with SSRIs were interviewed with an SD questionnaire designed for this purpose by the authors including questions about the following items decreased libido, delayed orgasm or anorgasmia, delayed ejaculation inability to ejaculation, impotence and general sexual satisfaction. Patients with the following criteria were included: normal sexual function before SSRIs intake, exclusive treatment with SSRIs or associated with benzodiazepines, previous heterosexual or self-orone current sexual practices. We excluded patients with previous sexual dysfunction, association of SSRIs with neuroleptics, recently hormone intake and significant medical illnesses. There is a significant increase in the incidence of SD when the physicians ask the patients direct questions (55.29%) versus spontaneous SD reported (14.2%). There are some significant differences among different SSRIs paroxetine provoked more delay of orgasm/ejaculation and more impotence than fluvoxamine, fluoxetine and sertraline (Chi square p < 0.05). Only 22.6% of the patients had a good tolerance about their sexual dysfunction. SD has positive correlation with the dose. The patients experienced substantial improvement in sexual function when the dose was diminished or the drug was withdrawn. Men showed more incidence of sexual dysfunction than women but women's sexual dysfunction was more intense than men. Seven of nine patients (77.7%) experienced total improvement when the treatment was changed to Moclobemide (450 mg/day) and two of four patients (50%) improved when treatment was changed to Amineptine.

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

    PubMed

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

    2015-01-01

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

  6. Rescue of IL-1β-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants.

    PubMed

    Borsini, Alessandra; Alboni, Silvia; Horowitz, Mark A; Tojo, Luis M; Cannazza, Giuseppe; Su, Kuan-Pin; Pariante, Carmine M; Zunszain, Patricia A

    2017-10-01

    Both increased inflammation and reduced neurogenesis have been associated with the pathophysiology of major depression. We have previously described how interleukin-1 (IL-1) β, a pro-inflammatory cytokine increased in depressed patients, decreases neurogenesis in human hippocampal progenitor cells. Here, using the same human in vitro model, we show how omega-3 (ω-3) polyunsaturated fatty acids and conventional antidepressants reverse this reduction in neurogenesis, while differentially affecting the kynurenine pathway. We allowed neural cells to proliferate for 3days and further differentiate for 7days in the presence of IL-1β (10ng/ml) and either the selective serotonin reuptake inhibitor sertraline (1µM), the serotonin and norepinephrine reuptake inhibitor venlafaxine (1µM), or the ω-3 fatty acids eicosapentaenoic acid (EPA, 10µM) or docosahexaenoic acid (DHA, 10µM). Co-incubation with each of these compounds reversed the IL-1β-induced reduction in neurogenesis (DCX- and MAP2-positive neurons), indicative of a protective effect. Moreover, EPA and DHA also reversed the IL-1β-induced increase in kynurenine, as well as mRNA levels of indolamine-2,3-dioxygenase (IDO); while DHA and sertraline reverted the IL-1β-induced increase in quinolinic acid and mRNA levels of kynurenine 3-monooxygenase (KMO). Our results show common effects of monoaminergic antidepressants and ω-3 fatty acids on the reduction of neurogenesis caused by IL-1β, but acting through both common and different kynurenine pathway-related mechanisms. Further characterization of their individual properties will be of benefit towards improving a future personalized medicine approach. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2004-06-01

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

  8. Cognitive effects of transcranial direct current stimulation in depression: Results from the SELECT-TDCS trial and insights for further clinical trials.

    PubMed

    Brunoni, André Russowsky; Tortella, Gabriel; Benseñor, Isabela Martins; Lotufo, Paulo Andrade; Carvalho, André Ferrer; Fregni, Felipe

    2016-09-15

    Cognitive dysfunction treatment remains an unmet clinical need in major depressive disorder (MDD). Transcranial direct current stimulation (tDCS) may improve cognitive symptoms in MDD. Our aim was to investigate the cognitive effects of tDCS in the Sertraline vs. Electric Current Therapy for Treating Depression Clinical Study (SELECT-TDCS). We also explored whether tDCS could have mood-independent cognitive effects. One hundred twenty MDD patients aged from 18 to 65 years received 12 sessions of active/sham tDCS (2mA for 30min) and real/placebo 50mg/d sertraline over 6 weeks in a factorial trial. We analyzed whether changes in performance of neuropsychological tests (Trail Making, Digit Span, Stroop Task, Mini-Mental Status Exam and Montreal Cognitive Assessment) occurred over time, according to treatment group and depression improvement. Exploratory analyses were carried out to verify the influence of clinical and demographic variables on the outcomes. Cognitive improvement was showed in most tests used, although they occurred regardless of intervention type and depression improvement. Further exploratory analyses revealed that clinical response and education level could have mediated pro-cognitive tDCS effects on some of the tests used. The neuropsychological battery used might not have been sensitive to detect tDCS-induced effects on cognition. Lack of simultaneous cognitive training during application may have also limited its cognitive effects. We found no evidence of beneficial or deleterious cognitive effects of tDCS as a treatment for depression. We discussed clinical trial design considerations for further tDCS studies assessing cognitive effects, including sample and outcomes considerations. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. A comparative study of QT prolongation with serotonin reuptake inhibitors.

    PubMed

    Ojero-Senard, Ana; Benevent, Justine; Bondon-Guitton, Emmanuelle; Durrieu, Geneviève; Chebane, Leila; Araujo, Melanie; Montastruc, Francois; Montastruc, Jean-Louis

    2017-10-01

    QT interval prolongations were described with citalopram and escitalopram. However, the effects of the other serotonin reuptake inhibitors (SRIs) remained discussed. In order to identify a putative signal with other SRIs, the present study investigates the reports of QT interval prolongation with SRIs in two pharmacovigilance databases (PVDB). Two kinds of investigations were performed: (1) a comparative study in VigiBase®, the WHO PVDB, where notifications of QT prolongation with six SRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) were selected. Cases with overdose or pregnancy were excluded. The relationship between the "suspected" SRI and occurrence of QT prolongation was assessed by calculating reporting odds ratio (ROR) in a case/non-case design. (2) A descriptive study of QT prolongation reports with citalopram and escitalopram in the French FPVD. In VigiBase®, 855 notifications were identified (mean age 56.2 years, mainly women 73%). Among them, 172 (20.1%) were associated to escitalopram; 299 (35.0%), to citalopram; 186 (21.8%), to fluoxetine; 94 (11.0%), to sertraline; 66 (7.7%), to paroxetine; and 38 (4.4%) to fluvoxamine. A significant ROR value (higher than 1) was only found for citalopram (3.35 CI95% [2.90-3.87]) or escitalopram (2.50 [2.11-2.95]). In the FPVD, eight reports of QT prolongation were found with citalopram and 27 with escitalopram, mainly in women (77.1%) with a mean age of 73.2 years. In 23 cases (66%), SRIs were associated with other suspected drugs, mainly cardiotropic or psychotropic ones. Hypokalemia was associated in six patients. This study, performed in real conditions of life, shows a clear signal of QT prolongation with only two SRIs, citalopram and escitalopram, indicating that QT prolongation is not a SRI class effect.

  10. Occurrence of pharmaceuticals and personal care products in fish: results of a national pilot study in the United States.

    PubMed

    Ramirez, Alejandro J; Brain, Richard A; Usenko, Sascha; Mottaleb, Mohammad A; O'Donnell, John G; Stahl, Leanne L; Wathen, John B; Snyder, Blaine D; Pitt, Jennifer L; Perez-Hurtado, Pilar; Dobbins, Laura L; Brooks, Bryan W; Chambliss, C Kevin

    2009-12-01

    Pharmaceuticals and personal care products are being increasingly reported in a variety of biological matrices, including fish tissue; however, screening studies have presently not encompassed broad geographical areas. A national pilot study was initiated in the United States to assess the accumulation of pharmaceuticals and personal care products in fish sampled from five effluent-dominated rivers that receive direct discharge from wastewater treatment facilities in Chicago, Illinois; Dallas, Texas; Orlando, Florida; Phoenix, Arizona; and West Chester, Pennsylvania, USA. Fish were also collected from the Gila River, New Mexico, USA, as a reference condition expected to be minimally impacted by anthropogenic influence. High performance liquid chromatography-tandem mass spectrometry analysis of pharmaceuticals revealed the presence of norfluoxetine, sertraline, diphenhydramine, diltiazem, and carbamazepine at nanogram-per-gram concentrations in fillet composites from effluent-dominated sampling locations; the additional presence of fluoxetine and gemfibrozil was confirmed in liver tissue. Sertraline was detected at concentrations as high as 19 and 545 ng/g in fillet and liver tissue, respectively. Gas chromatography-tandem mass spectrometry analysis of personal care products in fillet composites revealed the presence of galaxolide and tonalide at maximum concentrations of 2,100 and 290 ng/g, respectively, and trace levels of triclosan. In general, more pharmaceuticals were detected at higher concentrations and with greater frequency in liver than in fillet tissues. Higher lipid content in liver tissue could not account for this discrepancy as no significant positive correlations were found between accumulated pharmaceutical concentrations and lipid content for either tissue type from any sampling site. In contrast, accumulation of the personal care products galaxolide and tonalide was significantly related to lipid content. Results suggest that the detection of

  11. Kefir protective effects against nicotine cessation-induced anxiety and cognition impairments in rats

    PubMed Central

    Noori, Negin; Bangash, Mohammad Yasan; Motaghinejad, Majid; Hosseini, Pantea; Noudoost, Behshad

    2014-01-01

    Background: Nicotine as one of the potent psychostimulant drugs is characterized by its parasympathomimetic activity. Upon the abrupt discontinuation of nicotine intake, a number of symptoms such as anxiety, depression and cognition impairment develop. Kefir as a food supplement is rich in tryptophan. In this study, we have evaluated the effects of Kefir on nicotine cessation-induced anxiety, depression and cognition impairment. Materials and Methods: Forty adult male rats were divided into four groups. All the groups received 6 mg/kg/day of nicotine for 17 days and then the negative control groups got 5 mg/kg/day of normal saline. The positive control groups were given 40 mg/kg/day of Sertraline HCl for 7 days. The group treated with Cow Milk Kefir (CMK) and Soy Milk Kefir (SMK) received 5 mg/kg/day for 7 days. On the 25th day, Elevated Plus Maze (EPM), Open Field Test (OFT) and Forced Swim Test (FST) were used to investigate anxiety and depression. In addition, Moris Water Maze was applied to evaluate learning and memory in the animals between the 20th and 25th days. Results: The results showed that administration of CMK, SMK and Sertraline had higher anti-depression and anxiolytic effects on nicotine withdrawal-induced depression and anxiety in rats (P < 0.05). Moreover, CMK and SMK improved learning and memory impairment results in the nicotine withdrawal period (P < 0.05). Conclusion: This study revealed that Kefir had a potential effect on the treatment of nicotine cessation-induced depression, anxiety and cognition impairment in the animal model. Kefir may be useful for adjunct therapy for nicotine abandonment treatment protocols. PMID:25590029

  12. Kefir protective effects against nicotine cessation-induced anxiety and cognition impairments in rats.

    PubMed

    Noori, Negin; Bangash, Mohammad Yasan; Motaghinejad, Majid; Hosseini, Pantea; Noudoost, Behshad

    2014-01-01

    Nicotine as one of the potent psychostimulant drugs is characterized by its parasympathomimetic activity. Upon the abrupt discontinuation of nicotine intake, a number of symptoms such as anxiety, depression and cognition impairment develop. Kefir as a food supplement is rich in tryptophan. In this study, we have evaluated the effects of Kefir on nicotine cessation-induced anxiety, depression and cognition impairment. Forty adult male rats were divided into four groups. All the groups received 6 mg/kg/day of nicotine for 17 days and then the negative control groups got 5 mg/kg/day of normal saline. The positive control groups were given 40 mg/kg/day of Sertraline HCl for 7 days. The group treated with Cow Milk Kefir (CMK) and Soy Milk Kefir (SMK) received 5 mg/kg/day for 7 days. On the 25(th) day, Elevated Plus Maze (EPM), Open Field Test (OFT) and Forced Swim Test (FST) were used to investigate anxiety and depression. In addition, Moris Water Maze was applied to evaluate learning and memory in the animals between the 20(th) and 25(th) days. The results showed that administration of CMK, SMK and Sertraline had higher anti-depression and anxiolytic effects on nicotine withdrawal-induced depression and anxiety in rats (P < 0.05). Moreover, CMK and SMK improved learning and memory impairment results in the nicotine withdrawal period (P < 0.05). This study revealed that Kefir had a potential effect on the treatment of nicotine cessation-induced depression, anxiety and cognition impairment in the animal model. Kefir may be useful for adjunct therapy for nicotine abandonment treatment protocols.

  13. Predictors of response in generalized social phobia: effect of age of onset.

    PubMed

    Van Ameringen, Michael; Oakman, Jonathan; Mancini, Catherine; Pipe, Beth; Chung, Henry

    2004-02-01

    Selective serotonin reuptake inhibitors (SSRIs) are the gold standard for the pharmacological treatment of generalized social phobia (GSP). However, little is known about the predictors of response to treatment. Two hundred and four outpatients with GSP were randomized to sertraline (Zoloft) or placebo, for a 20-week double-blind study, with a flexible dose range of sertraline 50 to 200 mg/d. Response was defined as the percentage of patients with a Clinical Global Impression-Improvement scale (CGI-I) of 1 (very much improved) or 2 (much improved). Outcome analyses were conducted using regression models including treatment group as a categorical predictor and study visit as a repeated measure. Dependent measures included Marks Fear Questionnaire (MFQ), Brief Social Phobia Scale (BSPS), CGI-I, and Sheehan Disability Scale (SDS). We investigated several possible predictors of response to treatment including DSM-IV comorbidity, age, sex, age of onset of GSP, and duration of illness. Patients with later-onset (especially adult-onset) GSP tend to have a better response to treatment than those with earlier-onset GSP. This result generally appears in our analyses as a 2-way interaction, where the association with response is greatest for patients with adult-onset GSP (in contrast to those with child or adolescent onset). This finding is most robust for symptom measures, but is still apparent for the Sheehan measure of disability at work. This advantage for later-onset GSP can be accounted for neither by severity of illness nor by duration of illness. Superior treatment outcome for later-onset GSP may be mediated by the degree of social and family disability.

  14. Ultrasound-assisted low-density solvent dispersive liquid-liquid microextraction for the simultaneous determination of 12 new antidepressants and 2 antipsychotics in whole blood by gas chromatography-mass spectrometry.

    PubMed

    Chen, Xiujuan; Zheng, Shuiqing; Le, Jian; Qian, Zheyuan; Zhang, Runsheng; Hong, Zhanying; Chai, Yifeng

    2017-08-05

    Antidepressant drugs are widely used in the treatment of different psychiatric disorders, as well as in conjunction with antipsychotics for the treatment of major depressive disorder. In this study, a simple and rapid ultrasound-assisted low-density solvent dispersive liquid-liquid microextraction (UA-LDS-DLLME) method was developed for the simultaneous determination of 12 new antidepressants (norfluoxetine, fluoxetine, fluvoxamine, agomelatine, mirtazapine, moclobemide, melitracen, N-desmethylmirtazapine, maprotiline, sertraline, citalopram, paroxetine) and 2 antipsychotics (clozapine and haloperidol) in human whole blood by gas chromatography-mass spectrometry (GC-MS). Different parameters affecting the UA-LDS-DLLME were optimized and the optimal conditions were as follows: 100μL of toluene as extraction solvent, extraction pH 12 and 3min of ultrasound stirring. Good linearity (R 2 ≥0.991) was obtained at the concentration range of 15-1500ng/mL for norfluoxetine, fluoxetine, fluvoxamine, melitracen, maprotiline and citalopram, and 5-500ng/mL for agomelatine, mirtazapine, moclobemide, N-desmethylmirtazapine, sertraline, paroxetine, clozapine and haloperidol. The intra-day and inter-day precision were all less than 10%, and accuracy of intra-day and inter-day were in the range of -12.7% to 7.9% and -13.9 to 11.8%, respectively. The extraction recoveries of most analytes were more than 60%. The UA-LDS-DLLME/GC-MS method was demonstrated with acceptable precision, accuracy and good specificity for the simultaneous determination of 12 antidepressants and 2 antipsychotics, and has been successfully applied in a real case. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn

    PubMed Central

    Gien, Jason; Roe, Gates; Isenberg, Nicole; Kailey, Jenai; Abman, Steven H.

    2013-01-01

    Although past studies demonstrate that altered serotonin (5-HT) signaling is present in adults with idiopathic pulmonary arterial hypertension, whether serotonin contributes to the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN) is unknown. We hypothesized that 5-HT contributes to increased pulmonary vascular resistance (PVR) in a sheep model of PPHN and that selective 5-HT reuptake inhibitor (SSRI) treatment increases PVR in this model. We studied the hemodynamic effects of 5-HT, ketanserin (5-HT2A receptor antagonist), and sertraline, an SSRI, on pulmonary hemodynamics of the late gestation fetal sheep with PPHN caused by prolonged constriction of the ductus arteriosis. Brief intrapulmonary infusions of 5-HT increased PVR from 1.0 ± 0.07 (baseline) to 1.4 ± 0.22 mmHg/ml per minute of treatment (P < 0.05). Ketanserin decreased PVR from 1.1 ± 0.15 (baseline) to 0.82 ± 0.09 mmHg/ml per minute of treatment (P < 0.05). Sertraline increased PVR from 1.1 ± 0.17 (baseline) to 1.4 ± 0.17 mmHg/ml per minute of treatment (P = 0.01). In addition, we studied 5-HT production and activity in vitro in experimental PPHN. Compared with controls, pulmonary artery endothelial cells from fetal sheep with PPHN exhibited increased expression of tryptophan hydroxylase 1 and 5-HT production by twofold and 56%, respectively. Compared with controls, 5-HT2A R expression was increased in lung homogenates and pulmonary artery smooth muscle cell lysates by 35% and 32%, respectively. We concluded that increased 5-HT contributes to high PVR in experimental PPHN through activation of the 5-HT2A receptor and that SSRI infusion further increases PVR in this model. PMID:23605003

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

    PubMed

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

    2017-04-01

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

  17. Pharmacogenetically driven treatments for alcoholism: are we there yet?

    PubMed

    Arias, Albert J; Sewell, R Andrew

    2012-06-01

    Pharmacogenetic analyses of treatments for alcohol dependence attempt to predict treatment response and side-effect risk for specific medications. We review the literature on pharmacogenetics relevant to alcohol dependence treatment, and describe state-of-the-art methods of pharmacogenetic research in this area. Two main pharmacogenetic study designs predominate: challenge studies and treatment-trial analyses. Medications studied include US FDA-approved naltrexone and acamprosate, both indicated for treating alcohol dependence, as well as several investigational (and off-label) treatments such as sertraline, olanzapine and ondansetron. The best-studied functional genetic variant relevant to alcoholism treatment is rs1799971, a single-nucleotide polymorphism in exon 1 of the OPRM1 gene that encodes the μ-opioid receptor. Evidence from clinical trials suggests that the presence of the variant G allele of rs1799971 may predict better treatment response to opioid receptor antagonists such as naltrexone. Evidence from clinical trials also suggests that several medications interact pharmacogenetically with variation in genes that encode proteins involved in dopaminergic and serotonergic neurotransmission. Variation in the DRD4 gene, which encodes the dopamine D(4) receptor, may predict better response to naltrexone and olanzapine. A polymorphism in the serotonin transporter gene SLC6A4 promoter region appears related to differential treatment response to sertraline depending on the subject's age of onset of alcoholism. Genetic variation in SLC6A4 may also be associated with better treatment response to ondansetron. Initial pharmacogenetic efforts in alcohol research have identified functional variants with potential clinical utility, but more research is needed to further elucidate the mechanism of these pharmacogenetic interactions and their moderators in order to translate them into clinical practice.

  18. Simultaneous quantification of selective serotonin reuptake inhibitors and metabolites in human plasma by liquid chromatography-electrospray mass spectrometry for therapeutic drug monitoring.

    PubMed

    Ansermot, Nicolas; Brawand-Amey, Marlyse; Eap, Chin B

    2012-02-15

    A simple and sensitive liquid chromatography-electrospray ionization mass spectrometry method was developed for the simultaneous quantification in human plasma of all selective serotonin reuptake inhibitors (citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) and their main active metabolites (desmethyl-citalopram and norfluoxetine). A stable isotope-labeled internal standard was used for each analyte to compensate for the global method variability, including extraction and ionization variations. After sample (250μl) pre-treatment with acetonitrile (500μl) to precipitate proteins, a fast solid-phase extraction procedure was performed using mixed mode Oasis MCX 96-well plate. Chromatographic separation was achieved in less than 9.0min on a XBridge C18 column (2.1×100mm; 3.5μm) using a gradient of ammonium acetate (pH 8.1; 50mM) and acetonitrile as mobile phase at a flow rate of 0.3ml/min. The method was fully validated according to Société Française des Sciences et Techniques Pharmaceutiques protocols and the latest Food and Drug Administration guidelines. Six point calibration curves were used to cover a large concentration range of 1-500ng/ml for citalopram, desmethyl-citalopram, paroxetine and sertraline, 1-1000ng/ml for fluoxetine and fluvoxamine, and 2-1000ng/ml for norfluoxetine. Good quantitative performances were achieved in terms of trueness (84.2-109.6%), repeatability (0.9-14.6%) and intermediate precision (1.8-18.0%) in the entire assay range including the lower limit of quantification. Internal standard-normalized matrix effects were lower than 13%. The accuracy profiles (total error) were mainly included in the acceptance limits of ±30% for biological samples. The method was successfully applied for routine therapeutic drug monitoring of more than 1600 patient plasma samples over 9 months. The β-expectation tolerance intervals determined during the validation phase were coherent with the results of quality control samples analyzed

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

    PubMed

    Zwink, Nadine; Jenetzky, Ekkehart

    2018-05-10

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

  20. Cost-effectiveness analysis of treatments for premenstrual dysphoric disorder.

    PubMed

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

    2010-01-01

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

  1. 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

  2. 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

  3. Pharmacological treatment of comorbid PTSD and substance use disorder: recent progress.

    PubMed

    Sofuoglu, Mehmet; Rosenheck, Robert; Petrakis, Ismene

    2014-02-01

    Previous research has identified a strong association between posttraumatic stress disorder (PTSD) and substance use disorder (SUD), necessitating the development of treatments that address both conditions. Some pharmacotherapies are effective for the treatment of PTSD and SUD alone, however; no medications have been proven to be effective for the combination of these conditions. We review the recent advances in pharmacological treatment of comorbid PTSD and SUD. A randomized clinical trial of sertraline, a serotonin reuptake inhibitor (SSRI), did not show overall efficacy for comorbid PTSD and alcohol dependence (AD), although it may have efficacy among light drinkers. Another clinical trial demonstrated the efficacy of both disulfiram and naltrexone for the treatment of AD in individuals with PTSD. A more recent clinical trial suggested that norepinephrine uptake inhibitors may also have efficacy for the treatment of comorbid PTSD and AD. In animal and preliminary human studies, brain norepinephrine and glutamate/GABA have emerged as potential treatment targets for comorbid PTSD and SUD. Noradrenergic medications that are promising for comorbid PTSD and SUD include prazosin, guanfacine, and atomoxetine. Promising glutamate/GABA medications include topiramate, memantine, acamprosate, N-acetylcysteine (NAC), and ketamine. The safety and efficacy of these medications for the treatment of PTSD and SUD need to be tested in controlled clinical trials. Published by Elsevier Ltd.

  4. Pharmacology for sleep disturbance in PTSD.

    PubMed

    Lipinska, Gosia; Baldwin, David S; Thomas, Kevin G F

    2016-03-01

    Symptoms of sleep disturbance, particularly nightmares and insomnia, are a central feature of post-traumatic stress disorder (PTSD). Emerging evidence suggests that specific treatment of PTSD-related sleep disturbance improves other symptoms of the disorder, which in turn suggests that such disturbance may be fundamental to development and maintenance of the disorder. This mini-review focuses on pharmacological treatment of sleep disturbance in adult PTSD (specifically, studies testing the efficacy of antidepressants, adrenergic inhibiting agents, antipsychotics and benzodiazepine and non-benzodiazepine hypnotics). We conclude that only prazosin, an adrenergic inhibiting agent, has had its efficacy established by multiple randomised controlled trials. There is also high-level evidence supporting use of eszopiclone, as well as risperidone and olanzapine as adjunct therapy. Antidepressants such as sertraline, venlafaxine and mirtazapine, benzodiazepines such as alprazolam and clonazepam and non-benzodiazepine hypnotics such as zolpidem appear ineffective in treating PTSD-related sleep disturbance. Most studies that report reduced frequency of nightmares and insomnia also report decreases in overall symptom severity. Such findings suggest that (i) sleep disruption is central to PTSD; (ii) treating sleep disruption may be an effective way to address other symptoms of the disorder and (iii) PTSD symptoms tend to cluster together in predictable ways. Copyright © 2016 John Wiley & Sons, Ltd.

  5. The Impact of PTSD Treatment on the Cortisol Awakening Response

    PubMed Central

    Pacella, Maria L.; Feeny, Norah; Zoellner, Lori; Delahanty, Douglas L.

    2015-01-01

    Background Posttraumatic stress disorder (PTSD) is associated with abnormal functioning of the hypothalamic-pituitary-adrenal (HPA) axis; however, limited research has examined whether cortisol levels change following successful PTSD treatment. The current study examined the impact of successful PTSD treatment on the cortisol awakening response (CAR). Method Twenty-nine adults participating in a treatment trial for chronic PTSD provided saliva samples (upon waking, and 30, 45, and 60-min post-waking) before and after receiving either prolonged exposure therapy or sertraline. PTSD responder status (i.e., loss or retention of a PTSD diagnosis) served as the predictor variable. Outcome measures included area under the curve with respect to ground and increase, reflecting total cortisol output and HPA axis reactivity, respectively. Results A series of hierarchical regressions revealed no significant main effects of PTSD responder status for either CAR outcome. However, a significant gender by treatment response interaction for cortisol reactivity revealed that female treatment non-responders displayed higher cortisol reactivity following treatment than female responders, whereas cortisol reactivity did not change pre- to post-treatment for male responders. Findings remained after controlling for age, trauma history, baseline medication status, baseline PTSD, and baseline depressive symptoms. Conclusion Loss of a PTSD diagnosis may contribute to decreased cortisol reactivity in females. Neuroendocrine changes following treatment may emerge only for specific subgroups, highlighting the importance of exploring treatment moderators. PMID:25327949

  6. Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson's Disease

    PubMed Central

    Wang, Bing; Chen, Li-Hua

    2016-01-01

    In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE) precursor droxidopa (L-DOPS) or α2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA) or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain. PMID:27747105

  7. Non-compliance with pharmacotherapy of depression is associated with a sensation seeking personality.

    PubMed

    Ekselius, L; Bengtsson, F; von Knorring, L

    2000-09-01

    Inadequate compliance of drug intake is an important cause of ineffective pharmacotherapy and has been associated with therapeutic failure. We hypothesized that sensation seeking personality traits would affect compliance with long-term antidepressant medication. Three hundred and eight depressed patients participating in a randomized double-blind study of sertraline and citalopram were included. Personality traits were assessed using the Karolinska Scales of Personality. Compliance to medication was determined in two ways, by means of tablet counting and by measurement concentration of drug in serum. Tablet non-compliance was defined as less than 80% or more than 100% intake of the prescribed drug during weeks 20-24. Serum drug non-compliance was defined as undetectable amounts of either drug and main metabolite in the serum samples at week 24. Two virtually not overlapping groups of non-compliant patients were identified, where those regarded as non-compliant due to the interpretation of the serum drug levels were in majority. The group of serum drug non-compliant patients were recognized by significantly higher scores on the Monotony Avoidance scale and the Impulsive Sensation Seeking Psychopathy factor. The need for better methods than tablet counting and patient questioning to ascertain compliance is emphasized.

  8. Bioaccumulation and trophic dilution of human pharmaceuticals across trophic positions of an effluent-dependent wadeable stream

    PubMed Central

    Du, Bowen; Haddad, Samuel P.; Luek, Andreas; Scott, W. Casan; Saari, Gavin N.; Kristofco, Lauren A.; Connors, Kristin A.; Rash, Christopher; Rasmussen, Joseph B.; Chambliss, C. Kevin; Brooks, Bryan W.

    2014-01-01

    Though pharmaceuticals are increasingly observed in a variety of organisms from coastal and inland aquatic systems, trophic transfer of pharmaceuticals in aquatic food webs have not been reported. In this study, bioaccumulation of select pharmaceuticals was investigated in a lower order effluent-dependent stream in central Texas, USA, using isotope dilution liquid chromatography–tandem mass spectrometry (MS). A fish plasma model, initially developed from laboratory studies, was tested to examine observed versus predicted internal dose of select pharmaceuticals. Pharmaceuticals accumulated to higher concentrations in invertebrates relative to fish; elevated concentrations of the antidepressant sertraline and its primary metabolite desmethylsertraline were observed in the Asian clam, Corbicula fluminea, and two unionid mussel species. Trophic positions were determined from stable isotopes (δ15N and δ13C) collected by isotope ratio-MS; a Bayesian mixing model was then used to estimate diet contributions towards top fish predators. Because diphenhydramine and carbamazepine were the only target compounds detected in all species examined, trophic magnification factors (TMFs) were derived to evaluate potential trophic transfer of both compounds. TMFs for diphenhydramine (0.38) and carbamazepine (1.17) indicated neither compound experienced trophic magnification, which suggests that inhalational and not dietary exposure represented the primary route of uptake by fish in this effluent-dependent stream. PMID:25313153

  9. Investigating the role of nisoldipine in foot-shock-induced post-traumatic stress disorder in mice.

    PubMed

    Verma, Meenu; Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar S

    2016-04-01

    This study was designed to investigate the effectiveness of nisoldipine, an L-type voltage-sensitive calcium channel blocker, to ameliorate anxiety and fear response in a mouse model of post-traumatic stress disorder (PTSD). Acute trauma was induced in Swiss albino mice in a 2-day electric foot-shock paradigm consisting of 15 intermittent foot-shocks of 0.8 mA intensity, 10-s duration and 10-s intershock interval, during 5 min, followed by 3 weekly situational reminders, that is, once per week in the same context on three successive weeks. PTSD-induced behavioral changes were assessed using actophotometer, open-field, social interaction test, and freezing behavior. Biochemically, the serum corticosterone levels were estimated. Electric foot-shock and situational reminders produced behavioral alterations and decreased corticosterone levels, assessed on the 21st day following the traumatic event. Administration of sertraline (Ser 15 mg/kg), a selective serotonin reuptake inhibitor (SSRI) and nisoldipine (20 and 40 mg/kg), significantly attenuated the foot-shock-trauma-induced behavioral changes along with normalization of the corticosterone levels. It may be concluded that nisoldipine produces beneficial effects in re-establishing behavioral alterations, which may be due to normalization of reduced corticosterone levels in PTSD in mice. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  10. Inhibitors of alprazolam metabolism in vitro: effect of serotonin-reuptake-inhibitor antidepressants, ketoconazole and quinidine.

    PubMed Central

    von Moltke, L L; Greenblatt, D J; Cotreau-Bibbo, M M; Harmatz, J S; Shader, R I

    1994-01-01

    1. The biotransformation of the triazolobenzodiazepine alprazolam (ALP) to its hydroxylated metabolites (4-OH-ALP and alpha-OH-ALP) was evaluated in human, monkey, rat, and mouse liver microsomes. 2. In all species 4-OH-ALP was the principal metabolite, accounting for 84% of clearance in human microsomes compared with 16% for alpha-OH-ALP. 3. Among the serotonin-specific reuptake inhibitors fluoxetine (FLU) and sertraline (SERT), and their respective demethylated metabolites norfluoxetine (NOR) and desmethylsertraline (DES), NOR was the most potent inhibitor (mean Ki for 4-OH-ALP formation in humans: 11 microM), FLU the weakest (Ki = 83 microM), with SERT and DES falling in between (Ki = 24 and 20 microM). 4. The in vitro data predict 29% inhibition of ALP clearance at mean FLU and NOR plasma concentrations of 77 ng ml-1 and 72 ng ml-1, respectively, after correction for liver:water partition ratios in the range of 12-14. The observed mean degree of inhibition in a previous in vivo study was 21%. 5. Ketoconazole was a potent inhibitor of ALP metabolism in vitro (Ki = 0.046 microM), suggesting that ALP hydroxylation is mediated by the cytochrome P450-3A sub-family. Quinidine was a weak inhibitor (Ki = 626 microM). PMID:7946933

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

    PubMed

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

    2016-09-05

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

  12. A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care

    PubMed Central

    Kast, Richard E.; Boockvar, John A.; Brüning, Ansgar; Cappello, Francesco; Chang, Wen-Wei; Cvek, Boris; Dou, Q. Ping; Duenas-Gonzalez, Alfonso; Efferth, Thomas; Focosi, Daniele; Ghaffari, Seyed H.; Karpel-Massler, Georg; Ketola, Kirsi; Khoshnevisan, Alireza; Keizman, Daniel; Magné, Nicolas; Marosi, Christine; McDonald, Kerrie; Muñoz, Miguel; Paranjpe, Ameya; Pourgholami, Mohammad H.; Sardi, Iacopo; Sella, Avishay; Srivenugopal, Kalkunte S.; Tuccori, Marco; Wang, Weiguang; Wirtz, Christian R.; Halatsch, Marc-Eric

    2013-01-01

    To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma's compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed. PMID:23594434

  13. Contaminants of emerging concern in a large temperate estuary.

    PubMed

    Meador, James P; Yeh, Andrew; Young, Graham; Gallagher, Evan P

    2016-06-01

    This study was designed to assess the occurrence and concentrations of a broad range of contaminants of emerging concern (CECs) from three local estuaries within a large estuarine ecosystem. In addition to effluent from two wastewater treatment plants (WWTP), we sampled water and whole-body juvenile Chinook salmon (Oncorhynchus tshawytscha) and Pacific staghorn sculpin (Leptocottus armatus) in estuaries receiving effluent. We analyzed these matrices for 150 compounds, which included pharmaceuticals, personal care products (PPCPs), and several industrial compounds. Collectively, we detected 81 analytes in effluent, 25 analytes in estuary water, and 42 analytes in fish tissue. A number of compounds, including sertraline, triclosan, estrone, fluoxetine, metformin, and nonylphenol were detected in water and tissue at concentrations that may cause adverse effects in fish. Interestingly, 29 CEC analytes were detected in effluent and fish tissue, but not in estuarine waters, indicating a high potential for bioaccumulation for these compounds. Although concentrations of most detected analytes were present at relatively low concentrations, our analysis revealed that overall CEC inputs to each estuary amount to several kilograms of these compounds per day. This study is unique because we report on CEC concentrations in estuarine waters and whole-body fish, which are both uncommon in the literature. A noteworthy finding was the preferential bioaccumulation of CECs in free-ranging juvenile Chinook salmon relative to staghorn sculpin, a benthic species with relatively high site fidelity. Published by Elsevier Ltd.

  14. A case of serotonin syndrome associated with methadone overdose.

    PubMed

    Martinez, Terry T; Martinez, Daniel N

    2008-01-01

    A chronic pain patient prescribed 20 mg of methadone per day was seen at the Emergency Department within one hour following a witnessed intentional 200 mg ingestion. In addition, he was taking the serotonin re-uptake inhibitor antidepressant drugs, sertraline and venlafaxine as prescribed. Methadone is also a serotonin re-uptake inhibitor which has been involved in serotonin toxicity reactions. Initially, no symptoms of narcotic overdose (depressed central nervous system, respiration, or blood pressure) could be distinguished, and the standard narcotic urine screen was negative. No decontamination or antagonist therapy was given, and the patient was discharged to a psychiatric unit for observation. At 5 hours post-ingestion he presented in a panic with hallucinations and elevated blood pressure, pulse, and respiration. These symptoms are characteristic of serotonin syndrome which is often described as mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. At 10 hours post-ingestion the patient was found unconscious. He had aspirated stomach contents into his lungs. His respiration, blood pressure, and pulse were all severely depressed. He never regained conciousness, and he died 5 days later. The medical examiner's finding was probable acute methadone intoxication. In this case serotonin syndrome appears to have opposed and delayed typical narcotic symptoms. Methadone has additional pharmacologic and toxicologic properties which may complicate the assessment and treatment in overdose situations.

  15. Selective Serotonin Reuptake Inhibitors for Treating Neurocognitive and Neuropsychiatric Disorders Following Traumatic Brain Injury: An Evaluation of Current Evidence

    PubMed Central

    Yue, John K.; Burke, John F.; Upadhyayula, Pavan S.; Winkler, Ethan A.; Deng, Hansen; Robinson, Caitlin K.; Pirracchio, Romain; Suen, Catherine G.; Sharma, Sourabh; Ferguson, Adam R.; Ngwenya, Laura B.; Stein, Murray B.; Manley, Geoffrey T.; Tarapore, Phiroz E.

    2017-01-01

    The prevalence of neuropsychiatric disorders following traumatic brain injury (TBI) is 20%–50%, and disorders of mood and cognition may remain even after recovery of neurologic function is achieved. Selective serotonin reuptake inhibitors (SSRI) block the reuptake of serotonin in presynaptic cells to lead to increased serotonergic activity in the synaptic cleft, constituting first-line treatment for a variety of neurocognitive and neuropsychiatric disorders. This review investigates the utility of SSRIs in treating post-TBI disorders. In total, 37 unique reports were consolidated from the Cochrane Central Register and PubMed (eight randomized-controlled trials (RCTs), nine open-label studies, 11 case reports, nine review articles). SSRIs are associated with improvement of depressive but not cognitive symptoms. Pooled analysis using the Hamilton Depression Rating Scale demonstrate a significant mean decrease of depression severity following sertraline compared to placebo—a result supported by several other RCTs with similar endpoints. Evidence from smaller studies demonstrates mood improvement following SSRI administration with absent or negative effects on cognitive and functional recovery. Notably, studies on SSRI treatment effects for post-traumatic stress disorder after TBI remain absent, and this represents an important direction of future research. Furthermore, placebo-controlled studies with extended follow-up periods and concurrent biomarker, neuroimaging and behavioral data are necessary to delineate the attributable pharmacological effects of SSRIs in the TBI population. PMID:28757598

  16. Selective Serotonin Reuptake Inhibitors for Treating Neurocognitive and Neuropsychiatric Disorders Following Traumatic Brain Injury: An Evaluation of Current Evidence.

    PubMed

    Yue, John K; Burke, John F; Upadhyayula, Pavan S; Winkler, Ethan A; Deng, Hansen; Robinson, Caitlin K; Pirracchio, Romain; Suen, Catherine G; Sharma, Sourabh; Ferguson, Adam R; Ngwenya, Laura B; Stein, Murray B; Manley, Geoffrey T; Tarapore, Phiroz E

    2017-07-25

    The prevalence of neuropsychiatric disorders following traumatic brain injury (TBI) is 20%-50%, and disorders of mood and cognition may remain even after recovery of neurologic function is achieved. Selective serotonin reuptake inhibitors (SSRI) block the reuptake of serotonin in presynaptic cells to lead to increased serotonergic activity in the synaptic cleft, constituting first-line treatment for a variety of neurocognitive and neuropsychiatric disorders. This review investigates the utility of SSRIs in treating post-TBI disorders. In total, 37 unique reports were consolidated from the Cochrane Central Register and PubMed (eight randomized-controlled trials (RCTs), nine open-label studies, 11 case reports, nine review articles). SSRIs are associated with improvement of depressive but not cognitive symptoms. Pooled analysis using the Hamilton Depression Rating Scale demonstrate a significant mean decrease of depression severity following sertraline compared to placebo-a result supported by several other RCTs with similar endpoints. Evidence from smaller studies demonstrates mood improvement following SSRI administration with absent or negative effects on cognitive and functional recovery. Notably, studies on SSRI treatment effects for post-traumatic stress disorder after TBI remain absent, and this represents an important direction of future research. Furthermore, placebo-controlled studies with extended follow-up periods and concurrent biomarker, neuroimaging and behavioral data are necessary to delineate the attributable pharmacological effects of SSRIs in the TBI population.

  17. [Child protection network and the intersector implementation of the circle of security as alternatives to medication].

    PubMed

    Becker, Ana Laura Martins M M; de Souza, Paulo Haddad; de Oliveira, Mônica Martins; Paraguay, Nestor Luiz Bruzzi B

    2014-09-01

    To describe the clinical history of a child with aggressive behavior and recurring death-theme speech, and report the experience of the team of authors, who proposed an alternative to medication through the establishment of a protection network and the inter-sector implementation of the circle of security concept. A 5-year-old child has a violent and aggressive behavior at the day-care. The child was diagnosed by the healthcare center with depressive disorder and behavioral disorder, and was medicated with sertraline and risperidone. Side effects were observed, and the medications were discontinued. Despite several actions, such as talks, teamwork, psychological and psychiatric follow-up, the child's behavior remained unchanged. A unique therapeutic project was developed by Universidade Estadual de Campinas' Medical School students in order to establish a connection between the entities responsible for the child's care (daycare center, healthcare center, and family). Thus, the team was able to develop a basic care protection network. The implementation of the inter-sector circle of security, as well as the communication and cooperation among the teams, produced very favorable results in this case. This initiative was shown to be a feasible and effective alternative to the use of medication for this child. Copyright © 2014 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  18. Increased expression of BDNF transcript with exon VI in hippocampi of patients with pharmaco-resistant temporal lobe epilepsy.

    PubMed

    Martínez-Levy, G A; Rocha, L; Lubin, F D; Alonso-Vanegas, M A; Nani, A; Buentello-García, R M; Pérez-Molina, R; Briones-Velasco, M; Recillas-Targa, F; Pérez-Molina, A; San-Juan, D; Cienfuegos, J; Cruz-Fuentes, C S

    2016-02-09

    A putative role of the brain-derived neurotrophic factor (BDNF) in epilepsy has emerged from in vitro and animal models, but few studies have analyzed human samples. We assessed the BDNF expression of transcripts with exons I (BDNFI), II (BDNFII), IV (BDNFIV) and VI (BDNFVI) and methylation levels of promoters 4 and 6 in the hippocampi of patients with pharmaco-resistant temporal lobe epilepsy (TLE) (n=24). Hippocampal sclerosis (HS) and pre-surgical pharmacological treatment were considered as clinical independent variables. A statistical significant increase for the BDNFVI (p<0.05) was observed in TLE patients compared to the autopsy control group (n=8). BDNFVI was also increased in anxiety/depression TLE (N=4) when compared to autopsies or to the remaining group of patients (p<0.05). In contrast, the use of the antiepileptic drug Topiramate (TPM) (N=3) was associated to a decrease in BDNFVI expression (p<0.05) when compared to the remaining group of patients. Methylation levels at the BDNF promoters 4 and 6 were similar between TLE and autopsies and in relation to the use of either Sertraline (SRT) or TPM. These results suggest an up-regulated expression of a specific BDNF transcript in patients with TLE, an effect that seems to be dependent on the use of specific drugs. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Trajectories of Change in Youth Anxiety during Cognitive Behavior Therapy

    PubMed Central

    Peris, Tara S.; Compton, Scott N.; Kendall, Philip C.; Birmaher, Boris; Sherill, Joel; March, John; Gosch, Elizabeth; Ginsburg, Golda; Rynn, Moira; McCracken, James T.; Keeton, Courtney P.; Sakolsky, Dara; Suveg, Cynthia; Aschenbrand, Sasha; Almirall, Daniel; Iyengar, Satish; Walkup, John T.; Albano, Anne Marie; Piacentini, John

    2015-01-01

    Objective To evaluate changes in the trajectory of youth anxiety following the introduction of specific cognitive behavior therapy (CBT) components: relaxation training, cognitive restructuring, and exposure tasks. Methods 488 youths ages 7–17 years (50% female; 74% ≤ 12 years) were randomly assigned to receive either CBT, sertraline (SRT), their combination (COMB), or pill placebo (PBO) as part of their participation in the Child/Adolescent Anxiety Multimodal Study (CAMS). Youths in the CBT conditions were evaluated weekly by therapists using the Clinical Global Impression Scale-Severity (CGI-S; Guy, 1976) and the Children’s Global Assessment Scale (CGAS; Schaffer et al., 1983) and every four weeks by blind independent evaluators (IEs) using the Pediatric Anxiety Ratings Scale (PARS; Rupp Study Group, 2002). Youths in SRT and PBO were included as controls. Results Longitudinal discontinuity analyses indicated that the introduction of both cognitive restructuring (e.g., changing self-talk) and exposure tasks significantly accelerated the rate of progress on measures of symptom severity and global functioning moving forward in treatment; the introduction of relaxation training had limited impact. Counter to expectations, no strategy altered the rate of progress in the specific domain of anxiety that it was intended to target (i.e., somatic symptoms, anxious self-talk, avoidance behavior). Conclusions Findings support CBT theory and suggest that cognitive restructuring and exposure tasks each make substantial contributions to improvement in youth anxiety. Implications for future research are discussed. PMID:25486372

  20. Two-phase electromembrane extraction followed by gas chromatography-mass spectrometry analysis.

    PubMed

    Davarani, Saied Saeed Hosseiny; Morteza-Najarian, Amin; Nojavan, Saeed; Pourahadi, Ahmad; Abbassi, Mojtaba Beigzadeh

    2013-02-01

    A two-phase electromembrane extraction (EME) was developed and directly coupled with gas chromatography mass spectrometry (GC-MS) analysis. The proposed method was successfully applied to the simultaneous determination of imipramine, desipramine, citalopram and sertraline. The model compounds were extracted from neutral aqueous sample solutions into the organic phase filled in the lumen of the hollow fiber. This method was accomplished with 1-heptanol as organic phase, by means of 60 V applied voltage and with the extraction time of 15 min. Experiments reported recoveries in the range of 69-87% from 1.2 mL neutral sample solution. The compounds were quantified by GC-MS instrument, with acceptable linearity ranging from 1 to 500 ng mL(-1) (R(2) in the range of 0.989 to 0.998), and repeatability (RSD) ranging between 7.5 and 11.5% (n = 5). The estimated detection limits (S/N ratio of 3:1) were less than 0.25 ng mL(-1). This novel approach based on two-phase EME brought advantages such as simplicity, low-costing, low detection limit and fast extraction with a total analysis time less than 25 min. These experimental findings were highly interesting and demonstrated the possibility of solving ionic species in the organic phase at the presence of electrical potential. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Swift onset of central nervous system depression and asystole followingan overdose of Guaifenesin.

    PubMed

    Okic, Merisa; Johnson, Tom; Crifasi, Joseph A; Long, Christopher; Mitchell, Erik K

    2013-06-01

    Guaifenesin is an over-the-counter expectorant used for chest congestion and is available both in single-ingredient formulations and in combination with antihistamines, cough suppressants and decongestants. The documented side-effects of guaifenesin are generally mild. We present the case of a 23-year-old female who committed suicide by ingestion of guaifenesin along with small amounts of cetirizine, ethanol and sertraline. Approximately 2 h after ingestion, the patient experienced central nervous system depression followed by asystole. No anatomic cause of death could be determined at autopsy. The initial toxicology detected only ethanol, which was found at a concentration insufficient to cause death. Upon further analysis, guaifenesin was detected in femoral blood at 25.0 μg/mL, urine at >50.0 μg/mL, vitreous fluid at 9.2 μg/mL, brain at 17.0 μg/g and liver at 25.0 μg/g. This is the first reported human case that can be considered a death to which guaifenesin was the significant pharmacologic contributor. Guaifenesin is not detected by the primary screening methods employed by some labs and may be missed in toxicological analyses of overdoses unless specifically suspected.

  2. Determination of pharmaceuticals in groundwater collected in five cemeteries' areas (Portugal).

    PubMed

    Paíga, P; Delerue-Matos, C

    2016-11-01

    There are growing public attention and concern about the possibility of ecosystem and human health effects from pharmaceuticals in environment. Several types of environmental samples were target of studies by the scientific community, namely drinking water, groundwater, surface water (river, ocean), treated water (influent and effluent), soils, and sediments near to Wastewater Treatment Plants or near to others potential sources of contaminations. Normally, studies in the cemeteries areas are for historical and architectural research and questions of the potential risk for adverse impact of cemeteries in environment have never received enough attention. However, this risk may exist when cemeteries are placed in areas that are vulnerable to contamination. The objective of the present work was the determination of pharmaceuticals (nonsteroidal anti-inflammatory/analgesics, antibiotics and psychiatric drugs) in groundwater samples collected inside of the cemeteries areas. Acetaminophen, salicylic acid, ibuprofen, ketoprofen, nimesulide, carbamazepine, fluoxetine, and sertraline were the pharmaceuticals achieved in the analysed samples. None of the studied antibiotics were detected. The highest concentration was obtained for salicylic acid (in the range of 33.7 to 71.0ng/L) and carbamazepine (between 20.0 and 22.3ng/L), respectively. By the cluster analysis similarity between carbamazepine and fluoxetine was achieved. Copyright © 2016. Published by Elsevier B.V.

  3. Comparison of a rational vs. high throughput approach for rapid salt screening and selection.

    PubMed

    Collman, Benjamin M; Miller, Jonathan M; Seadeek, Christopher; Stambek, Julie A; Blackburn, Anthony C

    2013-01-01

    In recent years, high throughput (HT) screening has become the most widely used approach for early phase salt screening and selection in a drug discovery/development setting. The purpose of this study was to compare a rational approach for salt screening and selection to those results previously generated using a HT approach. The rational approach involved a much smaller number of initial trials (one salt synthesis attempt per counterion) that were selected based on a few strategic solubility determinations of the free form combined with a theoretical analysis of the ideal solvent solubility conditions for salt formation. Salt screening results for sertraline, tamoxifen, and trazodone using the rational approach were compared to those previously generated by HT screening. The rational approach produced similar results to HT screening, including identification of the commercially chosen salt forms, but with a fraction of the crystallization attempts. Moreover, the rational approach provided enough solid from the very initial crystallization of a salt for more thorough and reliable solid-state characterization and thus rapid decision-making. The crystallization techniques used in the rational approach mimic larger-scale process crystallization, allowing smoother technical transfer of the selected salt to the process chemist.

  4. Jaundice associated pruritis: a review of pathophysiology and treatment.

    PubMed

    Bassari, Ramez; Koea, Jonathan B

    2015-02-07

    To review the underlying pathophysiology and currently available treatments for pruritis associated with jaundice. English language literature was reviewed using MEDLINE, PubMed, EMBASE and clinicaltrials.gov for papers and trails addressing the pathophysiology and potential treatments for pruritis associated with jaundice. Recent advances in the understanding of the peripheral anatomy of itch transmission have defined a histamine stimulated pathway and a cowhage stimulated pathway with sensation conveyed centrally via the contralateral spinothalamic tract. Centrally, cowhage and histamine stimulated neurons terminate widely within the thalamus and sensorimotor cortex. The causative factors for itch in jaundice have not been clarified although endogenous opioids, serotonin, steroid and lysophosphatidic acid all play a role. Current guidelines for the treatment of itching in jaundice recommend initial management with biliary drainage where possible and medical management with ursodeoxycholic acid, followed by cholestyramine, rifampicin, naltrexone and sertraline. Other than biliary drainage no single treatment has proved universally effective. Pruritis associated with jaundice is a common but poorly understood condition for which biliary drainage is the most effective therapy. Pharmacological therapy has advanced but remains variably effective.

  5. Jaundice associated pruritis: A review of pathophysiology and treatment

    PubMed Central

    Bassari, Ramez; Koea, Jonathan B

    2015-01-01

    To review the underlying pathophysiology and currently available treatments for pruritis associated with jaundice. English language literature was reviewed using MEDLINE, PubMed, EMBASE and clinicaltrials.gov for papers and trails addressing the pathophysiology and potential treatments for pruritis associated with jaundice. Recent advances in the understanding of the peripheral anatomy of itch transmission have defined a histamine stimulated pathway and a cowhage stimulated pathway with sensation conveyed centrally via the contralateral spinothalamic tract. Centrally, cowhage and histamine stimulated neurons terminate widely within the thalamus and sensorimotor cortex. The causative factors for itch in jaundice have not been clarified although endogenous opioids, serotonin, steroid and lysophosphatidic acid all play a role. Current guidelines for the treatment of itching in jaundice recommend initial management with biliary drainage where possible and medical management with ursodeoxycholic acid, followed by cholestyramine, rifampicin, naltrexone and sertraline. Other than biliary drainage no single treatment has proved universally effective. Pruritis associated with jaundice is a common but poorly understood condition for which biliary drainage is the most effective therapy. Pharmacological therapy has advanced but remains variably effective. PMID:25663760

  6. Biomarkers of anhedonic-like behavior, antidepressant drug refraction, and stress resilience in a rat model of depression.

    PubMed

    Christensen, T; Bisgaard, C F; Wiborg, O

    2011-11-24

    The aim of the present study was to identify potential biomarkers for depression in the search for novel disease targets and treatment regimens. Furthermore, the study includes a search for biomarkers involved in treatment resistance and stress resilience in order to investigate mechanisms underlying antidepressant drug refraction and stress-coping strategies. Depression-related transcriptomic changes in gene expression profiles were investigated in laser-captured microdissected (LCM) rat hippocampal granular cell layers (GCL) using the chronic mild stress (CMS) rat model of depression and chronic administration of two selective serotonin reuptake inhibitors (SSRIs), escitalopram and sertraline. CMS rats were segregated into diverging groups according to behavioral readouts, and under stringent constraints, the associated differential gene regulations were analyzed. Accordingly, we identified four genes associated with recovery, two genes implicated in treatment resistance, and three genes involved in stress resilience. The identified genes associated with mechanisms of cellular plasticity, including signal transduction, cell proliferation, cell differentiation, and synaptic release. Hierarchical clustering analysis confirmed the subgroup segregation pattern in the CMS model. Thus antidepressant treatment refractors cluster with anhedonic-like rats, and, interestingly, stress-resilient rats cluster with rats undergoing antidepressant-mediated recovery from anhedonia, suggesting antidepressant mechanisms of action to emulate endogenous stress-coping strategies. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Antidepressants at environmentally relevant concentrations affect predator avoidance behavior of larval fathead minnows (Pimephales promelas).

    USGS Publications Warehouse

    Furlong, Edward T.; Barber, Larry B.; Meghan R. McGee,; Megan A. Buerkley,; Matthew L. Julius,; Vajda, Alan M.; Heiko L. Schoenfuss,; Schultz, Melissa M.; Norris, David O.

    2009-01-01

    The effects of embryonic and larval exposure to environmentally relevant (ng/L) concentrations of common antidepressants, fluoxetine, sertraline, venlafaxine, and bupropion (singularly and in mixture) on C-start escape behavior were evaluated in fathead minnows (Pimephales promelas). Embryos (postfertilization until hatching) were exposed for 5 d and, after hatching, were allowed to grow in control well water until 12 d old. Similarly, posthatch fathead minnows were exposed for 12 d to these compounds. High-speed (1,000 frames/s) video recordings of escape behavior were collected and transferred to National Institutes of Health Image for frame-by- frame analysis of latency periods, escape velocities, and total escape response (combination of latency period and escape velocity). When tested 12 d posthatch, fluoxetine and venlafaxine adversely affected C-start performance of larvae exposed as embryos. Conversely, larvae exposed for 12 d posthatch did not exhibit altered escape responses when exposed to fluoxetine but were affected by venlafaxine and bupropion exposure. Mixtures of these four antidepressant pharmaceuticals slowed predator avoidance behaviors in larval fathead minnows regardless of the exposure window. The direct impact of reduced C-start performance on survival and, ultimately, reproductive fitness provides an avenue to assess the ecological relevance of exposure in an assay of relatively short duration.

  8. Antidepressants at environmentally relevant concentrations affect predator avoidance behavior of larval fathead minnows (Pimephales promelas)

    USGS Publications Warehouse

    Painter, M.M.; Buerkley, M.A.; Julius, M.L.; Vajda, A.M.; Norris, D.O.; Barber, L.B.; Furlong, E.T.; Schultz, M.M.; Schoenfuss, H.L.

    2009-01-01

    The effects of embryonic and larval exposure to environmentally relevant (ng/L) concentrations of common antidepressants, fluoxetine, sertraline, venlafaxine, and bupropion (singularly and in mixture) on C-start escape behavior were evaluated in fathead minnows (Pimephales promelas). Embryos (postfertilization until hatching) were exposed for 5 d and, after hatching, were allowed to grow in control well water until 12 d old. Similarly, posthatch fathead minnows were exposed for 12 d to these compounds. High-speed (1,000 frames/s) video recordings of escape behavior were collected and transferred to National Institutes of Health Image for frame-by-frame analysis of latency periods, escape velocities, and total escape response (combination of latency period and escape velocity). When tested 12 d posthatch, fluoxetine and venlafaxine adversely affected C-start performance of larvae exposed as embryos. Conversely, larvae exposed for 12 d posthatch did not exhibit altered escape responses when exposed to fluoxetine but were affected by venlafaxine and bupropion exposure. Mixtures of these four antidepressant pharmaceuticals slowed predator avoidance behaviors in larval fathead minnows regardless of the exposure window. The direct impact of reduced C-start performance on survival and, ultimately, reproductive fitness provides an avenue to assess the ecological relevance of exposure in an assay of relatively short duration. ?? 2009 SETAC.

  9. Prescribing Pattern of Antidepressants in Children and Adolescents: Findings from the Research on Asia Psychotropic Prescription Pattern.

    PubMed

    Chee, K Y; Tripathi, A; Avasthi, A; Chong, M Y; Xiang, Y T; Sim, K; Kanba, S; He, Y L; Lee, M S; Chiu, H F K; Yang, S Y; Kuga, H; Udomratn, P; Tanra, A J; Maramis, M M; Grover, S; Mahendran, R; Kallivayalil, R A; Shen, W W; Shinfuku, N; Tan, C H; Sartorius, N

    2016-03-01

    Pharmacotherapy of depression in children and adolescents is complex. In the absence of research into the efficacy and safety of antidepressants in this group of patients, their off-label prescription is common. This paper aimed to illustrate the prescription pattern of antidepressants in children and adolescents from major psychiatric centres in Asia. The Research on Asia Psychotropic Prescription Pattern on Antidepressants worked collaboratively in 2013 to study the prescription pattern of antidepressants in Asia using a unified research protocol and questionnaire. Forty psychiatric centres from 10 Asian countries / regions participated and 2321 antidepressant prescriptions were analysed. A total of 4.7% antidepressant prescriptions were for children and adolescents. Fluoxetine, sertraline, and escitalopram were the most common antidepressants prescribed for children and adolescents. Almost one-third (30.3%) of prescriptions were for diagnoses other than depressive and anxiety disorders. There was less antidepressant polypharmacy and concomitant use of benzodiazepine, but more concomitant use of antipsychotics in children and adolescents compared with adults. Off-label use of antidepressants in children and adolescents was reported by 40 Asian psychiatric institutions that participated in the study. In-service education and regulatory mechanisms should be reinforced to ensure efficacy and safety of antidepressants in children and adolescents.

  10. Pharmacotherapy for the treatment of depression in patients with alzheimer's disease: a treatment-resistant depressive disorder.

    PubMed

    Lozupone, Madia; La Montagna, Maddalena; D'Urso, Francesca; Piccininni, Carla; Sardone, Rodolfo; Dibello, Vittorio; Giannelli, Gianluigi; Solfrizzi, Vincenzo; Greco, Antonio; Daniele, Antonio; Quaranta, Nicola; Seripa, Davide; Bellomo, Antonello; Logroscino, Giancarlo; Panza, Francesco

    2018-06-01

    Pharmacotherapy for the treatment of depressive disorders in Alzheimer's Disease (AD) represents a clinical challenge. pharmacological options are often attempted after a period of watchful waiting (8-12 weeks). monoaminergic antidepressant drugs have shown only modest or null clinical benefits, maybe because the etiology of depressive symptoms in ad patients is fundamentally different from that of nondemented subjects. Areas covered: The following article looks at the selective serotonin reuptake inhibitor sertraline, which is one of the most frequently studied antidepressant medications in randomized controlled trials (RCTs). It also discusses many other pharmacological approaches that have proven to be inadequate (antipsychotics, acetylcholinesterase inhibitors, anticonvulsants, hormone replacement therapy) and new drug classes (mainly affecting glutamate transmission) that are being studied for treating depression in AD. It also gives discussion to the phase II RCT on the alternative drug S47445 and the potential effect on cognition of the multimodal antidepressant vortioxetine in older depressed patients. Finally, it discusses the N-methyl-D-aspartate antagonist ketamine. Expert opinion: The present RCT methodologies are too disparate to draw firm conclusions. Future studies are required to identify effective and multimodal pharmacological treatments that efficiently treat depression in AD. Genotyping may boost antidepressant treatment success.

  11. Fragile X Syndrome

    PubMed Central

    Tassone, Flora; González-Teshima, Laura Yuriko; Forero-Forero, Jose Vicente; Ayala-Zapata, Sebastián; Hagerman, Randi

    2014-01-01

    Fragile X Syndrome (FXS) is a genetic disease due to a CGG trinucleotide expansion, named full mutation (greater than 200 CGG repeats), in the fragile X mental retardation 1 gene locus Xq27.3; which leads to an hypermethylated region in the gene promoter therefore silencing it and lowering the expression levels of the fragile X mental retardation 1, a protein involved in synaptic plasticity and maturation. Individuals with FXS present with intellectual disability, autism, hyperactivity, long face, large or prominent ears and macroorchidism at puberty and thereafter. Most of the young children with FXS will present with language delay, sensory hyper arousal and anxiety. Girls are less affected than boys, only 25% have intellectual disability. Given the genomic features of the syndrome, there are patients with a number of triplet repeats between 55 and 200, known as premutation carriers. Most carriers have a normal IQ but some have developmental problems. The diagnosis of FXS has evolved from karyotype with special culture medium, to molecular techniques that are more sensitive and specific including PCR and Southern Blot. During the last decade, the advances in the knowledge of FXS, has led to the development of investigations on pharmaceutical management or targeted treatments for FXS. Minocycline and sertraline have shown efficacy in children. PMID:25767309

  12. The Effects of Antidepressants and Quetiapine on Heart Rate Variability.

    PubMed

    Huang, W-L; Liao, S-C; Kuo, T B J; Chang, L-R; Chen, T-T; Chen, I-M; Yang, C C H

    2016-09-01

    Introduction: The autonomic effects of antidepressants and quetiapine on heart rate variability (HRV) are inconsistent based on past studies. The aim of this study was to explore their influence on the HRV of psychiatric patients without psychotic symptoms. Methods: A total of 94 patients with depression, anxiety, or somatic symptoms, were recruited into this study. Based on their medication, 4 groups were identified: the no antidepressant group (n=19), the SSRI group (using sertraline or escitalopram, n=53), the other antidepressants group (using venlafaxine or mirtazapine, n=9), and the augmentation group (AG, using an antidepressant+quetiapine, n=13). The HRV of the 4 groups were compared. The correlations between HRV and the medication(s) used were clarified. Results: Among the 4 groups, the AG had the lowest HRV with its total power (TP), very low frequency power (VLF) and low frequency power (LF) of HRV being significantly different from those of the other groups. Age and using quetiapine were found to be negatively correlated with TP, VLF and LF. With this study group, the autonomic effects of antidepressants were found not to be significant. Discussion: Among psychiatric patients without psychotic symptoms, quetiapine causes an overt decrease in HRV. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Reasons Underlying Treatment Preference

    PubMed Central

    Cochran, Bryan N.; Pruitt, Larry; Fukuda, Seiya; Zoellner, Lori A.; Feeny, Norah C

    2008-01-01

    Very little is known about what factors influence women’s treatment preferences after a sexual assault. To learn more about these factors, data were collected from 273 women who read a standard “if this happened to you, what would you do” scenario describing a sexual assault and subsequent trauma-related psychiatric symptoms. After reading standardized treatment options for a pharmacotherapy (sertraline) and a psychotherapy (cognitive behavioral treatment), participants made a hypothetical treatment choice and reported the main reasons for their choice. Women often cited reasons surrounding the effectiveness of a treatment as the primary reason for their treatment preference, suggesting potential masking of symptoms with the medication and more logical, long-lasting effects with the psychotherapy. Other common reasons underlying treatment preference were wariness of the medication and positive feelings about talking in psychotherapy. Better understanding factors that influence treatment preference may aid in refining psychoeducation materials regarding the psychological consequences of sexual assault and their treatment for the lay public and in helping clinicians further tailor their discussion of treatment alternatives for these women. PMID:18162641

  14. Determination of antidepressants in human urine extracted by magnetic multiwalled carbon nanotube poly(styrene-co-divinylbenzene) composites and separation by capillary electrophoresis.

    PubMed

    Murtada, Khaled; de Andrés, Fernando; Ríos, Angel; Zougagh, Mohammed

    2018-04-20

    Poly(styrene-co-divinylbenzene)-coated magnetic multiwalled carbon nanotube composite synthesized by in-situ high temperature combination and precipitation polymerization of styrene-co-divinylbenzene has been employed as a magnetic sorbent for the solid phase extraction of antidepressants in human urine samples. Fluoxetine, venlafaxine, citalopram and sertraline were, afterwards, separated and determined by capillary electrophoresis with diode array detection. The presence of magnetic multiwalled carbon nanotubes in native poly(styrene-co-divinylbenzene) not only simplified sample treatment but also enhanced the adsorption efficiencies, obtaining extraction recoveries higher than 89.5% for all analytes. Moreover, this composite can be re-used at least 10 times without loss of efficiency and limits of detection ranging from 0.014 to 0.041 μg mL -1 were calculated. Additionally, precision values ranging from 0.08 to 7.50% and from 0.21 to 3.05% were obtained for the responses and for the migration times of the analytes, respectively. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Quantitative determination of antidepressants and their select degradates by liquid chromatography/electrospray ionization tandem mass spectrometry in biosolids destined for land application.

    PubMed

    Niemi, Lydia M; Stencel, Katherine A; Murphy, Madigan J; Schultz, Melissa M

    2013-08-06

    Antidepressants are one of the most widely dispensed classes of pharmaceuticals in the United States. As wastewater treatment plants are a primary source of pharmaceuticals in the environment, the use of biosolids as fertilizer is a potential route for antidepressants to enter the terrestrial environment. A microsolvent extraction method, utilizing green chemistry, was developed for extraction of the target antidepressants and degradation products from biosolids, or more specifically lagoon biosolids. Liquid chromatography/tandem mass spectrometry was used for quantitative determination of antidepressants in the lagoon biosolid extracts. Recoveries from matrix spiking experiments for the individual antidepressants had an average of 96%. The limits of detection for antidepressant pharmaceuticals and degradates ranged from 0.36 to 8.0 ng/kg wet weight. The method was applied to biosolids destined for land application. A suite of antidepressants was consistently detected in the lagoon biosolid samples, and thus antidepressants are being introduced to terrestrial environments through the land application of these biosolids. Sertraline and norsertraline were the most abundant antidepressant and degradation product detected in the biosolid samples. Detected, individual antidepressant concentrations ranged from 8.5 ng/kg (norfluoxetine) to 420 ng/kg wet weight (norsertraline).

  16. Obsessive-Compulsive Disorder with Suicide Obsessions in a First Responder without Previous Diagnosis of OCD or History of Suicide Attempts.

    PubMed

    Rachamallu, Vivekananda; Song, Michael M; Liu, Haiying; Giles, Charles L; McMahon, Terry

    2017-01-01

    Obsessive-compulsive disorder (OCD) is a distressing and often debilitating disorder characterized by obsessions, compulsions, or both that are time-consuming and cause impairment in social, occupational, or other areas of functioning. There are many published studies reporting higher risk of suicidality in OCD patients, as well as studies describing increased risk of suicidality in OCD patients with other comorbid psychiatric conditions such as major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). Existing case reports on OCD with suicide as the obsessive component describe patients with long standing diagnosis of OCD with suicidal ideations or previous suicide attempts. This report describes the case of a 28-year-old male, who works as a first responder, who presented with new onset symptoms characteristic of MDD and PTSD, with no past history of OCD or suicidality who developed OCD with suicidal obsessions. Differentiating between suicidal ideation in the context of other psychiatric illnesses and suicidal obsessions in OCD is critical to ensuring accurate diagnosis and timely provision of most appropriate treatment. The combination of exposure and response prevention therapy and pharmacotherapy with sertraline and olanzapine was effective in helping the patient manage the anxiety and distress stemming from the patient's OCD with suicidal obsession.

  17. Obsessive-Compulsive Disorder with Suicide Obsessions in a First Responder without Previous Diagnosis of OCD or History of Suicide Attempts

    PubMed Central

    Song, Michael M.; Liu, Haiying; Giles, Charles L.; McMahon, Terry

    2017-01-01

    Obsessive-compulsive disorder (OCD) is a distressing and often debilitating disorder characterized by obsessions, compulsions, or both that are time-consuming and cause impairment in social, occupational, or other areas of functioning. There are many published studies reporting higher risk of suicidality in OCD patients, as well as studies describing increased risk of suicidality in OCD patients with other comorbid psychiatric conditions such as major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). Existing case reports on OCD with suicide as the obsessive component describe patients with long standing diagnosis of OCD with suicidal ideations or previous suicide attempts. This report describes the case of a 28-year-old male, who works as a first responder, who presented with new onset symptoms characteristic of MDD and PTSD, with no past history of OCD or suicidality who developed OCD with suicidal obsessions. Differentiating between suicidal ideation in the context of other psychiatric illnesses and suicidal obsessions in OCD is critical to ensuring accurate diagnosis and timely provision of most appropriate treatment. The combination of exposure and response prevention therapy and pharmacotherapy with sertraline and olanzapine was effective in helping the patient manage the anxiety and distress stemming from the patient's OCD with suicidal obsession. PMID:29098105

  18. Rhodiola rosea therapy for major depressive disorder: a study protocol for a randomized, double-blind, placebo- controlled trial

    PubMed Central

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

    2014-01-01

    Background Rhodiola rosea (R. rosea), a botanical of both western and traditional Chinese medicine, has been used as a folk remedy for improving stamina and reducing stress. However, few controlled clinical trials have examined the safety and efficacy of R. rosea for the treatment of major depressive disorder (MDD). This study seeks to evaluate the safety and efficacy of R. rosea in a 12-week, randomized, double-blind, placebo-controlled, parallel group study design. Methods / Design Subjects with MDD not receiving antidepressant therapy will be randomized to either R. rosea extract 340–1,360 mg daily; sertraline 50–200 mg daily, or placebo for 12 weeks. The primary outcome measure will be change over time in the mean 17-item Hamilton Depression Rating score. Secondary outcome measures will include safety and quality of life ratings. Statistical procedures will include mixed-effects models to assess efficacy for primary and secondary outcomes. Discussion This study will provide valuable preliminary information on the safety and efficacy data of R. rosea versus conventional antidepressant therapy of MDD. It will also inform additional hypotheses and study design of future, fully powered, phase III clinical trials with R. rosea to determine its safety and efficacy in MDD. PMID:25610752

  19. 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.

  20. 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.

  1. Occurrence and fate of select psychoactive pharmaceuticals and antihypertensives in two wastewater treatment plants in New York State, USA.

    PubMed

    Subedi, Bikram; Kannan, Kurunthachalam

    2015-05-01

    The fates of psychoactive pharmaceuticals, including two antischizophrenics, six sedative-hypnotic-anxiolytics, four antidepressants, four antihypertensives, and their select metabolites, were determined in two wastewater treatment plants (WWTPs) in the Albany area of New York. All target psychoactive pharmaceuticals and their metabolites were found at a mean concentration that ranged from 0.98 (quetiapine) to 1220 ng/L (atenolol) in wastewater and from 0.26 (lorazepam) to 1490 ng/g dry weight (sertraline) in sludge. In this study, the fraction of psychoactive pharmaceuticals that was sorbed to suspended particulate matter (SPM) was calculated for the first time. Over 50% of the total mass of aripiprazole, norquetiapine, norsertraline, citalopram, desmethyl citalopram, propranolol, verapamil, and norverapamil was found sorbed to SPM in the influent. The mass loadings, i.e., influx, of target psychoactive pharmaceuticals in WWTPs ranged from 0.91 (diazepam) to 347 mg/d/1000 inhabitants (atenolol), whereas the environmental emissions ranged from 0.01 (dehydro-aripiprazole) to 316 mg/d/1000 inhabitants (atenolol). The highest calculated removal efficiencies were found for antischizophrenics (quetiapine=88%; aripiprazole=71%). However, the removal of some psychoactive pharmaceuticals through adsorption onto sludge was minimal (<1% of the initial mass load), which suggests that bio-degradation and/or chemical-transformation are the dominant mechanisms of removal of these pharmaceuticals in WWTPs. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed

    Fuller, R W

    1995-01-01

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

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

    PubMed

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

    2005-07-01

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

  4. 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.

  5. Online Sales of Unscheduled Pharmaceutical Agents: A Case Report of Tianeptine Use in the United States.

    PubMed

    Gupta, Swapnil; Wallace, Ryan; Sloshower, Jordan

    : Tianeptine is a tricyclic antidepressant that stimulates mu-opioid receptors at high doses. It is marketed and used across Europe and Latin America as an antidepressant, but is not approved by the Food and Drug Administration for use in the United States. In the United States, tianeptine is sold through online health stores as a cognition enhancer, dietary supplement, or as research chemical. We report the case of a 36-year-old man with a history of major depressive disorder, responsive to sertraline, who turned to the unmonitored use of tianeptine purchased online to treat residual feelings of apathy and boredom. His use of tianeptine was marked by rapidly escalating doses and a significant withdrawal syndrome that made discontinuation of this substance difficult. This case serves as a reminder that unscheduled pharmaceutical agents are available for misuse by the general population and have the potential to cause significant harm. Therefore, medical providers must be aware of and screen for the use of such products amongst their patients.

  6. Serotonergic system antagonists target breast tumor initiating cells and synergize with chemotherapy to shrink human breast tumor xenografts.

    PubMed

    Gwynne, William D; Hallett, Robin M; Girgis-Gabardo, Adele; Bojovic, Bojana; Dvorkin-Gheva, Anna; Aarts, Craig; Dias, Kay; Bane, Anita; Hassell, John A

    2017-05-09

    Breast tumors comprise an infrequent tumor cell population, termed breast tumor initiating cells (BTIC), which sustain tumor growth, seed metastases and resist cytotoxic therapies. Hence therapies are needed to target BTIC to provide more durable breast cancer remissions than are currently achieved. We previously reported that serotonergic system antagonists abrogated the activity of mouse BTIC resident in the mammary tumors of a HER2-overexpressing model of breast cancer. Here we report that antagonists of serotonin (5-hydroxytryptamine; 5-HT) biosynthesis and activity, including US Federal Food and Drug Administration (FDA)-approved antidepressants, targeted BTIC resident in numerous breast tumor cell lines regardless of their clinical or molecular subtype. Notably, inhibitors of tryptophan hydroxylase 1 (TPH1), required for 5-HT biosynthesis in select non-neuronal cells, the serotonin reuptake transporter (SERT) and several 5-HT receptors compromised BTIC activity as assessed by functional sphere-forming assays. Consistent with these findings, human breast tumor cells express TPH1, 5-HT and SERT independent of their molecular or clinical subtype. Exposure of breast tumor cells ex vivo to sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI), reduced BTIC frequency as determined by transplanting drug-treated tumor cells into immune-compromised mice. Moreover, another SSRI (vilazodone; Viibryd) synergized with chemotherapy to shrink breast tumor xenografts in immune-compromised mice by inhibiting tumor cell proliferation and inducing their apoptosis. Collectively our data suggest that antidepressants in combination with cytotoxic anticancer therapies may be an appropriate treatment regimen for testing in clinical trials.

  7. Depression in dementia patients: issues and challenges for a physician.

    PubMed

    Pattanayak, Raman Deep; Sagar, Rajesh

    2011-10-01

    Depression and dementia share a complex and interesting relationship, with a possibility of biological linkages between the two disorders. Research has shown consistently increased prevalence of depression in patients suffering from dementia. As many as one fourth to half of dementia patients are likely to experience clinical depression during the course of illness. However, the onset of depressive symptoms is often misinterpreted as worsening of cognitive decline and hence, it remains under-diagnosed. The lack of a coherent account from patient, frequent overlap of symptoms, inadequate sensitization of physicians may enhance the diagnostic difficulty. Undetected depression adds to patient disability and caregiver burden. Early recognition and proper intervention will improve the patient outcomes including quality of life. Selective serotonin reuptake inhibitors, especially Sertraline and Citalopram, with a very gradual dose titration are likely to benefit. Certain behavioral interventions e.g involvement of patient in physical activity and pleasant activities has been found to be useful. All dementia cases should be routinely screened for depression and managed accordingly.

  8. Docking studies of antidepressants against single crystal structure of tryptophan 2, 3-dioxygenase using Molegro Virtual Docker software.

    PubMed

    Dawood, Shazia; Zarina, Shamshad; Bano, Samina

    2014-09-01

    Tryptophan 2, 3-dioxygenase (TDO) a heme containing enzyme found in mammalian liver is responsible for tryptophan (Trp) catabolism. Trp is an essential amino acid that is degraded in to N-formylkynurenine by the action of TDO. The protein ligand interaction plays a significant role in structural based drug designing. The current study illustrates the binding of established antidepressants (ADs) against TDO enzyme using in-silico docking studies. For this purpose, Fluoxetine, Paroxetine, Sertraline, Fluvoxamine, Seproxetine, Citalopram, Moclobamide, Hyperforin and Amoxepine were selected. In-silico docking studies were carried out using Molegro Virtual Docker (MVD) software. Docking results show that all ADs fit well in the active site of TDO moreover Hyperforin and Paroxetine exhibited high docking scores of -152.484k cal/mol and -139.706k cal/mol, respectively. It is concluded that Hyperforin and Paroxetine are possible lead molecules because of their high docking scores as compared to other ADs examined. Therefore, these two ADs stand as potent inhibitors of TDO enzyme.

  9. Exploring evidence of a dissociative subtype in PTSD: Baseline symptom structure, etiology, and treatment efficacy for those who dissociate.

    PubMed

    Burton, Mark S; Feeny, Norah C; Connell, Arin M; Zoellner, Lori A

    2018-05-01

    With the inclusion of a dissociative subtype, recent changes to the DSM-5 diagnosis of posttraumatic stress disorder (PTSD) have emphasized the role of dissociation in the experience and treatment of the disorder. However, there is a lack of research exploring the clinical impact for highly dissociative groups receiving treatment for PTSD. The current study examined the presence and clinical impact of a dissociative subtype in a sample of individuals receiving treatment for chronic PTSD. This study used latent transition analyses (LTA), an expanded form of latent profile analyses (LPA), to examine latent profiles of PTSD and dissociation symptoms before and after treatment for individuals (N = 200) receiving prolonged exposure (PE) or sertraline treatment for chronic PTSD. The best fitting LTA model was one with a 4-class solution at both pretreatment and posttreatment. There was a latent class at pretreatment with higher levels of dissociative symptoms. However, this class was also marked by higher reexperiencing symptoms, and membership was not predicted by chronic child abuse. Further, although those in the class were less likely to transition to the responder class overall, this was not the case for exposure-based treatment specifically. These findings are not in line with the dissociative-subtype theoretical literature that proposes those who dissociate represent a clinically distinct group that may respond worse to exposure-based treatments for PTSD. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  10. Physiogenomic analysis of CYP450 drug metabolism correlates dyslipidemia with pharmacogenetic functional status in psychiatric patients

    PubMed Central

    Ruaño, Gualberto; Villagra, David; Szarek, Bonnie; Windemuth, Andreas; Kocherla, Mohan; Gorowski, Krystyna; Berrezueta, Christopher; Schwartz, Harold I; Goethe, John

    2011-01-01

    Aims To investigate associations between novel human cytochrome P450 (CYP450) combinatory (multigene) and substrate-specific drug metabolism indices, and elements of metabolic syndrome, such as low density lipoprotein cholesterol (LDLc), high density lipoprotein cholesterol (HDLc), triglycerides and BMI, using physiogenomic analysis. Methods CYP2C9, CYP2C19 and CYP2D6 genotypes and clinical data were obtained for 150 consecutive, consenting hospital admissions with a diagnosis of major depressive disorder and who were treated with psychotropic medications. Data analysis compared clinical measures of LDLc, HDLc, triglyceride and BMI with novel combinatory and substrate-specific CYP450 drug metabolism indices. Results We found that a greater metabolic reserve index score is related to lower LDLc and higher HDLc, and that a greater metabolic alteration index score corresponds with higher LDLc and lower HLDc values. We also discovered that the sertraline drug-specific indices correlated with cholesterol and triglyceride values. Conclusions Overall, we demonstrated how a multigene approach to CYP450 genotype analysis yields more accurate and significant results than single-gene analyses. Ranking the individual with respect to the population represents a potential tool for assessing risk of dyslipidemia in major depressive disorder patients who are being treated with psychotropics. In addition, the drug-specific indices appear useful for modeling a variable of potential relevance to an individual’s risk of drug-related dyslipidemia. PMID:21861666

  11. Physiogenomic analysis of CYP450 drug metabolism correlates dyslipidemia with pharmacogenetic functional status in psychiatric patients.

    PubMed

    Ruaño, Gualberto; Villagra, David; Szarek, Bonnie; Windemuth, Andreas; Kocherla, Mohan; Gorowski, Krystyna; Berrezueta, Christopher; Schwartz, Harold I; Goethe, John

    2011-08-01

    To investigate associations between novel human cytochrome P450 (CYP450) combinatory (multigene) and substrate-specific drug metabolism indices, and elements of metabolic syndrome, such as low density lipoprotein cholesterol (LDLc), high density lipoprotein cholesterol (HDLc), triglycerides and BMI, using physiogenomic analysis. CYP2C9, CYP2C19 and CYP2D6 genotypes and clinical data were obtained for 150 consecutive, consenting hospital admissions with a diagnosis of major depressive disorder and who were treated with psychotropic medications. Data analysis compared clinical measures of LDLc, HDLc, triglyceride and BMI with novel combinatory and substrate-specific CYP450 drug metabolism indices. We found that a greater metabolic reserve index score is related to lower LDLc and higher HDLc, and that a greater metabolic alteration index score corresponds with higher LDLc and lower HLDc values. We also discovered that the sertraline drug-specific indices correlated with cholesterol and triglyceride values. Overall, we demonstrated how a multigene approach to CYP450 genotype analysis yields more accurate and significant results than single-gene analyses. Ranking the individual with respect to the population represents a potential tool for assessing risk of dyslipidemia in major depressive disorder patients who are being treated with psychotropics. In addition, the drug-specific indices appear useful for modeling a variable of potential relevance to an individual's risk of drug-related dyslipidemia.

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

    PubMed

    Freeman, Ellen W

    2004-01-01

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

  13. Aripiprazole-induced sleep-related eating disorder: a case report.

    PubMed

    Kobayashi, Nobuyuki; Takano, Masahiro

    2018-04-05

    Sleep-related eating disorder is characterized by parasomnia with recurrent episodes of nocturnal eating or drinking during the main sleep period. Several drugs, including atypical antipsychotics, induce sleep-related eating disorder. However, aripiprazole has not previously been associated with sleep-related eating disorder. A 41-year-old Japanese man visited our clinic complaining of depression. The patient was treated with sertraline, which was titrated up to 100 mg for 4 weeks. A sleep inducer and an anxiolytic were coadministered. His depressive mood slightly improved, but it continued for an additional 4 months. Subsequently, aripiprazole (3 mg) was added as an adjunctive therapy. After 3 weeks, the patient's mother found that the patient woke up and ate food at night. The next morning, the patient was amnesic for this event, felt full, and wondered why the bags of food were empty. This episode lasted for 2 days. The patient gained 5 kg during these 3 weeks. After the aripiprazole dose was reduced to 1.5 mg, the patient's nocturnal eating episodes rapidly and completely disappeared. To the best of our knowledge, this is first report of sleep-related eating disorder induced by aripiprazole, and it indicates that this disorder should be considered a possible side effect of aripiprazole. Although aripiprazole is used mainly in patients with schizophrenia, its recently documented use as an adjunctive therapy in patients with depression might induce hitherto unknown side effects.

  14. Trypophobia: What Do We Know So Far? A Case Report and Comprehensive Review of the Literature

    PubMed Central

    Martínez-Aguayo, Juan Carlos; Lanfranco, Renzo C.; Arancibia, Marcelo; Sepúlveda, Elisa; Madrid, Eva

    2018-01-01

    In this article, we describe the case of a girl who suffers from a phobia to repetitive patterns, known as trypophobia. This condition has not yet been recognised by diagnostic taxonomies such as the Diagnostic and Statistical Manual of Mental Disorders. Trypophobia usually involves an intense and disproportionate fear towards holes, repetitive patterns, protrusions, etc., and, in general, images that present high-contrast energy at low and midrange spatial frequencies. It is commonly accompanied by neurovegetative symptoms. In the case we present here, the patient also suffered from generalised anxiety disorder and was treated with sertraline. After she was diagnosed, she showed symptoms of both fear and disgust towards trypophobic images. After some time following treatment, she only showed disgust towards said images. We finish this case report presenting a comprehensive literature review of the peer reviewed articles we retrieved after an exhaustive search about trypophobia, we discuss how this case report contributes to the understanding of this anxiety disorder, and what questions future studies should address in order to achieve a better understanding of trypophobia. PMID:29479321

  15. SSRI effects on pyschomotor performance: assessment of citalopram and escitalopram on normal subjects.

    PubMed

    Paul, Michel A; Gray, Gary W; Love, Ryan J; Lange, Marvin

    2007-07-01

    Standard aeromedical doctrine dictates that aircrew receiving treatment for depression are grounded during treatment and follow-up observation, generally amounting to at least 1 yr. The Canadian Forces has initiated a program to return selected aircrew being treated for depression to restricted flying duties once stabilized on an approved antidepressant with resolution of depression. The currently approved medications are sertraline (a selective serotonin reuptake inhibitor) and bupropion (noradrenaline and dopamine reuptake inhibitor). This study was undertaken to determine whether or not citalopram or escitalopram affect psychomotor performance. In a double-blind crossover protocol with counter-balanced treatment order, 24 normal volunteer subjects (14 men and 10 women) were assessed for psychomotor performance during placebo, citalopram (40 mg), and escitalopram (20 mg) treatment. Each treatment arm lasted 2 wk, involving a daily morning ingestion of one capsule. There was a 1-wk washout period between medication courses. Subjects completed a drug side-effect questionnaire and were tested on three psychomotor test batteries once per week. Neither citalopram nor escitalopram affected serial reaction time, logical reasoning, serial subtraction, multitask, or MacWorth clock task performance. While we found some of the expected side effects due to citalopram and escitalopram, there was no impact on psychomotor performance. These findings support the possibility of using citalopram and escitalopram for returning aircrew to restricted flight duties (non-tactical flying) under close observation as a maintenance treatment after full resolution of depression.

  16. Changing tides: Adaptive monitoring, assessment, and management of pharmaceutical hazards in the environment through time.

    PubMed

    Gaw, Sally; Brooks, Bryan W

    2016-04-01

    Pharmaceuticals are ubiquitous contaminants in aquatic ecosystems. Adaptive monitoring, assessment, and management programs will be required to reduce the environmental hazards of pharmaceuticals of concern. Potentially underappreciated factors that drive the environmental dose of pharmaceuticals include regulatory approvals, marketing campaigns, pharmaceutical subsidies and reimbursement schemes, and societal acceptance. Sales data for 5 common antidepressants (duloxetine [Cymbalta], escitalopram [Lexapro], venlafaxine [Effexor], bupropion [Wellbutrin], and sertraline [Zoloft]) in the United States from 2004 to 2008 were modeled to explore how environmental hazards in aquatic ecosystems changed after patents were obtained or expired. Therapeutic hazard ratios for Effexor and Lexapro did not exceed 1; however, the therapeutic hazard ratio for Zoloft declined whereas the therapeutic hazard ratio for Cymbalta increased as a function of patent protection and sale patterns. These changes in therapeutic hazard ratios highlight the importance of considering current and future drivers of pharmaceutical use when prioritizing pharmaceuticals for water quality monitoring programs. When urban systems receiving discharges of environmental contaminants are examined, water quality efforts should identify, prioritize, and select target analytes presently in commerce for effluent monitoring and surveillance. © 2015 SETAC.

  17. Rational-emotive and cognitive-behavior therapy (REBT/CBT) versus pharmacotherapy versus REBT/CBT plus pharmacotherapy in the treatment of major depressive disorder in youth; a randomized clinical trial.

    PubMed

    Iftene, Felicia; Predescu, Elena; Stefan, Simona; David, Daniel

    2015-02-28

    Major depressive disorder is a highly prevalent and debilitating condition in youth, so developing efficient treatments is a priority for mental health professionals. Psychotherapy (i.e., cognitive behavioral therapy/CBT), pharmacotherapy (i.e., SSRI medication), and their combination have been shown to be effective in treating youth depression; however, the results are still mixed and there are few studies engaging multi-level analyses (i.e., subjective, cognitive, and biological). Therefore, the aims of this randomized control study (RCT) were both theoretical - integrating psychological and biological markers of depression in a multi-level outcome analysis - and practical - testing the generalizability of previous results on depressed Romanian youth population. Eighty-eight (N=88) depressed Romanian youths were randomly allocated to one of the three treatment arms: group Rational Emotive Behavior Therapy (REBT)/CBT (i.e., a form of CBT), pharmacotherapy (i.e., sertraline), and group REBT/CBT plus pharmacotherapy. The results showed that all outcomes (i.e., subjective, cognitive, and biological) significantly change from pre to post-treatment under all treatment conditions at a similar rate and there were no significant differences among conditions at post-test. In case of categorical analysis of the clinical response rate, we found a non-significant trend favoring group REBT/CBT therapy. Results of analyses concerning outcome interrelations are discussed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. 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.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2004-08-13

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

  1. Post-traumatic stress disorder.

    PubMed

    Bisson, Jonathan I

    2010-02-03

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

  2. Post-traumatic stress disorder.

    PubMed

    Bisson, Jonathan I

    2007-08-01

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

  3. The efficacy of group metacognitive therapy on self-esteem and mental health of patients suffering from major depressive disorder.

    PubMed

    Farahmand, Vahid; Hassanzadeh, Ramezan; Mirzaian, Bahram; Fayyazi Bordbar, Mohammad Reza; Feizi, Jaleh

    2014-01-01

    The present research aims to analyze the efficacy of group metacognitive therapy (MCT) on self-esteem and mental Health of those who suffer from major depressive disorder. The research was a randomized clinical controlled trial, using pretest and posttest with 2 months of follow-up. Twenty-two patients with major depressive disorder based on DSM-IV-TR criteria were selected through available sampling from patients of two psychiatric hospitals of Mashhad, Iran, in 2011. They were allocated randomly into two groups of trial (n = 11) and control (n = 11). Citalopram and sertraline were prescribed as antidepressant to both groups. The experimental group also attended nine 90-minute sessions of MCT (a 5-week program). Eysenck self-esteem scale (ESES) and Mental Health Checklist (MHC) were used in pretest, posttest, and follow-up as the study instrument. The data were analyzed by analysis of covariance (ANCOVA) using SPSS. ANCOVA revealed that the patients receiving group MCT had significantly increased (p < 0.001) self-esteem in posttest, which remained significant in the follow up (p < 0.001). Moreover, mental health scores had increased in the MCT group (posttest, p < 0.001; follow up, p < 0.001). Group MCT has beneficial therapeutic roles in improving the self-steam and recuperation of mental health in MDD patients.

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

    PubMed

    Morishita, Shigeru

    2009-04-01

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

  5. A cross-sectional observation of the factors associated with deliberate self-poisoning with acetaminophen: impact of gender differences and psychiatric intervention.

    PubMed

    Zyoud, Sa'ed H; Awang, Rahmat; Sulaiman, Syed Azhar Syed; Al-Jabi, Samah W

    2010-08-01

    The objectives of this study were to determine the risk factors and life stressors that are prevalent among the acetaminophen deliberate self-poisoning (DSP) cases, to identify gender differences in the associated factors, and to determine the prevalence of psychiatric diagnosis and the patterns and types of psychotherapeutic interventions provided by psychiatrists. This is a cross-sectional study, a retrospective descriptive case review of hospital admissions for acetaminophen DSP. There were 177 incidences of DSP during the study period. The mean age of the cases was 23.1 +/- 7.3 years and 84.1% of them were females. The risk factors were more significantly associated with males: chronic ethanol intake (p = 0.04), higher reported dose ingested (p = 0.01), higher latency time (p = 0.04) and longer hospital stay (p = 0.03). The most commonly reported psychotherapeutic interventions used by psychiatrists were psychoeducation of the patient, followed by referral to a psychiatric clinic, family psychoeducation and psychotropic medication. Sertraline (SSRI) was the most frequently prescribed antidepressant. Males have been shown to use more toxic doses and to delay treatment due to high latency time. Most DSP patients have different life stressors and psychiatric diagnoses that may be associated with varying degrees of suicidal intent. All patients presenting following DSP need to be carefully screened for psychiatric illness. Randomized controlled studies need to be conducted on DSP patients with psychiatric illness to determine which treatments are effective. Copyright 2010 John Wiley & Sons, Ltd.

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

    PubMed

    Bellantuono, Cesario; Migliarese, Giovanni; Gentile, Salvatore

    2007-04-01

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

  7. [Pharmacologic therapy of depression during pregnancy].

    PubMed

    Bellantuono, Cesario; Migliarese, Giovanni; Imperadore, Giuseppe

    2006-02-01

    The pregnancy is considered to be relatively high risk period for depressive episodes in women, particularly for those with pre-existing affective disorders. Epidemiological studies indicate that between 10% to 16% of pregnant women fulfil the diagnostic criteria for major depression and on average 20% is affected by an anxiety disorder. Pharmacological treatment of depression during pregnancy, however, brings with it certainties and dilemmas. It has been reported that untreated depression is associated with impaired feto-placental function, premature delivery, miscarriage, low fetal growth and perinatal unwanted effects. On the other hand, the use of antidepressant drugs in pregnancy might be at risk of major malformations (teratogenesis), neonatal toxicity, especially withdrawal symptoms and neuropsychological-behavioural impairment. In addition, the abrupt discontinuation of antidepressants, because of fear for adverse fetal effects, exposes women to serious clinical problems, in particular the disease relapse. A number of reviews indicates that among antidepressant drugs, the older SSRIs (in particular fluoxetine, sertraline, citalopram) seem to be avoided of teratogenic risks; for these reasons such drugs are nowadays considered of choice for the treatment of depression during pregnancy. Less information is available for other drugs, including triciclycs, venlafaxine, mirtazapine, bupropion, escitalopram and duloxetine. Withdrawal symptoms have been reported for all antidepressants; these symptoms, however, were self-limiting in majority of cases and had a favourable outcome. Inconclusive findings emerge, so far, from the few longitudinal studies focusing on the long-term neurodevelopment outcome in children.

  8. Fatigue: an overview.

    PubMed

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

    2008-11-15

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

  9. 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.

  10. PHARMACOLOGICAL TREATMENTS FOR TINNITUS: NEW AND OLD

    PubMed Central

    Salvi, R.; Lobarinas, E.; Sun, W.

    2011-01-01

    Subjective tinnitus, the phantom ringing or buzzing sensation that occurs in the absence of sound, affects 12–14% of adults; in some cases the tinnitus is so severe or disabling that patients seek medical treatment. However, although the economic and emotional impact of tinnitus is large, there are currently no FDA-approved drugs to treat this condition. Clinical trials are now underway to evaluate the efficacy of N-methyl-d-aspartate (NMDA) and dopamine D2 antagonists, selective serotonin reuptake inhibitors (SSRIs), γ-aminobutyric acid (GABA) agonists and zinc dietary supplements. Previous off-label clinical studies, while not definitive, suggest that patients with severe depression may experience improvement in their tinnitus after treatment with antidepressants such as nortriptyline or sertraline. A small subpopulation of patients with what has been described as “typewriter tinnitus” have been shown to gain significant relief from the anticonvulsant carbamazepine. Preliminary studies with misoprostol, a synthetic prostaglandin E1 analogue, and sulpiride, a dopamine D2 antagonist, have shown promise. Animal behavioral studies suggest that GABA transaminase inhibitors and potassium channel modulators can suppress tinnitus. Additionally, improvements in tinnitus have also been noted in patients taking melatonin for significant sleep disturbances. Like other complex neurological disorders, one drug is unlikely to resolve tinnitus in all patients; therapies targeting specific subgroups are likely to yield the greatest success. PMID:21765586

  11. Gateways to Clinical Trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-09-01

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

  12. Treatment of the psychiatric problems associated with fragile X syndrome.

    PubMed

    Hagerman, Randi J; Polussa, Jonathan

    2015-03-01

    This work reviews recent research regarding treatment of fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism spectrum disorder. The phenotype includes anxiety linked to sensory hyperarousal, hyperactivity, and attentional problems consistent with attention deficit hyperactivity disorder and social deficits leading to autism spectrum disorder in 60% of boys and 25% of girls with FXS. Multiple targeted treatments for FXS have rescued the phenotype of the fmr1 knockout mouse, but few have been beneficial to patients with FXS. The failure of the metabotropic glutamate receptor 5 antagonists falls on the heels of the failure of Arbaclofen's efficacy in children and adults with autism or FXS. In contrast, efficacy has been demonstrated in a controlled trial of minocycline in children with FXS. Minocycline lowers the abnormally elevated levels of matrix metalloproteinase 9 in FXS. Acamprosate and lovastatin have been beneficial in open-label trials in FXS. The first 5 years of life may be the most efficacious time for intervention when combined with behavioral and/or educational interventions. Minocycline, acamprosate, lovastatin, and sertraline are treatments that can be currently prescribed and have shown benefit in children with FXS. Use of combined medical and behavioral interventions will likely be most efficacious for the treatment of FXS.

  13. 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

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

    PubMed

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

    2015-09-01

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

  15. 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.

  16. Predictors and Moderators of Treatment Response in Childhood Anxiety Disorders: Results from the CAMS Trial

    PubMed Central

    Compton, Scott N.; Peris, Tara S.; Almirall, Daniel; Birmaher, Boris; Sherrill, Joel; Kendall, Phillip C.; March, John S.; Gosch, Elizabeth A.; Ginsburg, Golda S.; Rynn, Moira A.; Piacentini, John C.; McCracken, James T.; Keeton, Courtney P.; Suveg, Cynthia M.; Aschenbrand, Sasha G.; Sakolsky, Dara; Iyengar, Satish; Walkup, John T.; Albano, Anne Marie

    2014-01-01

    Objective To examine predictors and moderators of treatment outcomes among 488 youth ages 7-17 years (50% female; 74% ≤ 12 years) with DSM-IV diagnoses of separation anxiety disorder, social phobia, or generalized anxiety disorder who were randomly assigned to receive either cognitive behavior therapy (CBT), sertraline (SRT), their combination (COMB), or medication management with pill placebo (PBO) in the Child/Adolescent Anxiety Multimodal Study (CAMS). Method Six classes of predictor and moderator variables (22 variables) were identified from the literature and examined using continuous (Pediatric Anxiety Ratings Scale; PARS) and categorical (Clinical Global Impression Scale-Improvement; CGI-I) outcome measures. Results Three baseline variables predicted better outcomes (independent of treatment condition) on the PARS, including low anxiety severity (as measured by parents and independent evaluators) and caregiver strain. No baseline variables were found to predict week 12 responder status (CGI-I). Participant's principal diagnosis moderated treatment outcomes, but only on the PARS. No baseline variables were found to moderate treatment outcomes on week 12 responder status (CGI-I). Discussion Overall, anxious children responded favorably to CAMS treatments. However, having more severe and impairing anxiety, greater caregiver strain, and a principal diagnosis of social phobia were associated with less favorable outcomes. Clinical implications of these findings are discussed. PMID:24417601

  17. Epidemiological risk factors in microscopic colitis: a prospective case-control study.

    PubMed

    Fernández-Bañares, Fernando; de Sousa, Monia R; Salas, Antonio; Beltrán, Belén; Piqueras, Marta; Iglesias, Eva; Gisbert, Javier P; Lobo, Beatriz; Puig-Diví, Valentí; García-Planella, Esther; Ordás, Ingrid; Andreu, Montserrat; Calvo, Marta; Montoro, Miguel; Esteve, Maria; Viver, Josep M

    2013-02-01

    The cause of collagenous colitis (CC) and lymphocytic colitis (LC) is unknown and epidemiological risk factors for CC and LC are not well studied. The aim was to evaluate in a case-control study epidemiological risk factors for CC and LC. In all, 120 patients with CC, 70 with CL, and 128 controls were included. For all cases and controls information was prospectively recorded. A binary logistic regression analysis was performed separately for CC and LC. Independent associations observed with the diagnosis of CC were: current smoking (odds ratio [OR], 2.4), history of polyarthritis (OR, 20.8), and consumption of lansoprazole (OR, 6.4), low-dose aspirin (OR, 3.8), beta-blockers (OR, 3.6), and angiotensin II receptor antagonists (OR 0.20). In the case of LC they were: current smoking (OR, 3.8), associated autoimmune diseases (OR, 8), and consumption of sertraline (OR, 17.5), omeprazole (OR 2.7), low-dose aspirin (OR, 4.7), and oral antidiabetic drugs (OR, 0.14). The consumption of drugs, current smoking, and associated autoimmune diseases were independently associated with the risk of microscopic colitis.

  18. Changing epidemiology of intentional antidepressant drug overdose in Victoria, Australia.

    PubMed

    Wong, Anselm; Taylor, David McD; Ashby, Karen; Robinson, Jeff

    2010-08-01

    To determine the epidemiology of intentional antidepressant drug overdose (OD), over an extended time period, in Victoria, Australia. Retrospective epidemiological study of all cases reported to the Victorian Emergency Minimum Dataset (VEMD) January 1998 to December 2007 and calls to the Victorian Poisons Information Centre (VPIC) June 2005 to September 2008. 5467 VEMD cases were analysed. 3169 (57.9%) cases involved selective serotonin reuptake inhibitors (SSRIs) and 1149 (21%) involved tricyclic antidepressants (TCAs). Sertraline (1252, 22.9% cases) was the most common drug. During 2001, the peak year of OD, there were 8.8 OD/100 000 population in the SSRI group and 3.8 OD/100 000 population in the TCA group. Trends over the study period showed increasing SSRI and 'other' newer antidepressant prescription rates and decreases for TCA and monoamine oxidase inhibitors (MAOI). However, the risks of OD in all drug classes were similar and OD/100 000 prescriptions trended downwards for all drug classes over time. 1833 VPIC calls were analysed. Calls relating to SSRIs were the most common yet SSRI OD was associated with significantly fewer symptoms (p < 0.001) and fewer patients with Poisoning Severity Score classifications of moderate or severe (p < 0.01). Antidepressant OD patterns are changing. Antidepressant OD incidence is following prescribing trends. The risk of OD is similar for all drug classes. Absolute numbers of OD and OD/100 000 prescriptions are decreasing for all drug classes.

  19. A Clinician’s Guide to PTSD Treatments for Returning Veterans

    PubMed Central

    Sharpless, Brian A.; Barber, Jacques P.

    2011-01-01

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

  20. A short-term swimming speed alteration test with nauplii of Artemia franciscana.

    PubMed

    Morgana, Silvia; Estévez-Calvar, Noelia; Gambardella, Chiara; Faimali, Marco; Garaventa, Francesca

    2018-01-01

    The presence of toxicant needs to be assessed within short time in order to effectively protect the aquatic environment from serious threat. Based on the observation that at high temperatures aquatic organisms become more vulnerable to stressors than those maintained at room temperature, a new test was developed. The proposed bioassay consisted in the evaluation of the swimming speed alteration (SSA) of nauplii of Artemia franciscana incubated at 39°C (± 1) for 6h, using a Swimming Behavior Recorder system (SBR). A comparative ecotoxicological study between the 6h SSA test and the 24h mortality test was carried out in order to validate the new method in terms of sensitivity by means of EC 50 values. The bioassay was applied to screen different toxicants: K 2 Cr 2 O 7 , Cu(SO 4 ) 2 , NaClO, SDS and Sertraline hydrochloride. The EC 50s calculated for the short-term SSA test and those of the mortality test showed comparable values. For all toxicants, the 6h SSA test was proved to be as sensitive as the 24h mortality test. The method developed in this study is the first temperature-based toxicity test with nauplii of Artemia franciscana and it represents an attractive assay in ecotoxicology because of its convenience in terms of time and costs, feasibility and sensitivity. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Jogging Therapy for Hikikomori Social Withdrawal and Increased Cerebral Hemodynamics: A Case Report.

    PubMed

    Nishida, Masaki; Kikuchi, Senichiro; Fukuda, Kazuhito; Kato, Satoshi

    2016-01-01

    Severe social withdrawal, called hikikomori, has drawn increased public attention. However, an optimal clinical approach and strategy of treatment has not been well established. Here, we report a case of hikikomori for which an exercise intervention using jogging therapy was effective, showing cerebral hemodynamic improvement. The patient was a 20 year old Japanese male who was hospitalized in order to evaluate and treat severe social withdrawal. Although depressive and anxiety symptoms partially subsided with sertraline alone, social withdrawal persisted due to a lack of self confidence. With his consent, we implemented exercise therapy with 30 minutes of jogging three times a week for three months. We did not change the pharmacotherapy, and his social withdrawal remarkably improved with continuous jogging exercise. Using near infrared spectroscopy to evaluate hemodynamic alteration, bilateral temporal hemodynamics considerably increased after the three-month jogging therapy. Regarding exercise therapy for mental illness, numerous studies have reported the effectiveness of exercise therapy for major depression. This case implied, however, that the applicability of exercise therapy is not limited to major depressive disorder. Jogging therapy may contribute to reinforcing self confidence associated with "resilience" in conjunction with neurophysiological modulation of neural networks.

  2. Use of psychotropic drugs during pregnancy and breast-feeding.

    PubMed

    Larsen, E R; Damkier, P; Pedersen, L H; Fenger-Gron, J; Mikkelsen, R L; Nielsen, R E; Linde, V J; Knudsen, H E D; Skaarup, L; Videbech, P

    2015-01-01

    To write clinical guidelines for the use of psychotropic drugs during pregnancy and breast-feeding for daily practice in psychiatry, obstetrics and paediatrics. As we wanted a guideline with a high degree of consensus among health professionals treating pregnant women with a psychiatric disease, we asked the Danish Psychiatric Society, the Danish Society of Obstetrics and Gynecology, the Danish Paediatric Society and the Danish Society of Clinical Pharmacology to appoint members for the working group. A comprehensive review of the literature was hereafter conducted. Sertraline and citalopram are first-line treatment among selective serotonin reuptake inhibitor for depression. It is recommended to use lithium for bipolar disorders if an overall assessment finds an indication for mood-stabilizing treatment during pregnancy. Lamotrigine can be used. Valproate and carbamazepin are contraindicated. Olanzapine, risperidone, quetiapine and clozapine can be used for bipolar disorders and schizophrenia. It is important that health professionals treating fertile women with a psychiatric disease discuss whether psychotropic drugs are needed during pregnancy and how it has to be administered. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

    Gelsleichter, James; Szabo, Nancy J

    2013-07-01

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

  5. The Clinical and Cost Effectiveness of Vortioxetine for the Treatment of a Major Depressive Episode in Patients With Failed Prior Antidepressant Therapy: A Critique of the Evidence.

    PubMed

    Lomas, James; Llewellyn, Alexis; Soares, Marta; Simmonds, Mark; Wright, Kath; Eastwood, Alison; Palmer, Stephen

    2016-09-01

    The National Institute for Health and Care Excellence (NICE) invited the manufacturer of vortioxetine (Lundbeck) to submit clinical and cost-effectiveness evidence for vortioxetine for the treatment of major depressive episodes (MDEs), as part of the Institute's Single Technology Appraisal (STA) process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and the resulting NICE guidance TA367 issued in November 2015. The ERG critically reviewed the evidence presented in the manufacturer's submission and identified areas requiring clarification, for which the manufacturer provided additional evidence. Two phase III randomised controlled trials for a second-line population involving vortioxetine were identified-REVIVE and TAK318. These two trials represent only 972 of over 7000 patients included in trials of vortioxetine. In REVIVE, there was a statistically significant difference in depression scores favouring vortioxetine compared with agomelatine [mean Montgomery-Åsberg Depression Rating Scale (MADRS) score difference of 2.16 points; 95 % confidence interval 0.81-3.51]. The ERG concluded that, based on all the evidence, rather than the substantially restricted subset of evidence originally considered by the manufacturer, vortioxetine is likely to be similar in efficacy to other analysed antidepressants [citalopram, sertraline, escitalopram and venlafaxine extended release (XR)], and may be more efficacious than agomelatine and inferior to duloxetine. The ERG concluded that vortioxetine may be more tolerable than other analysed antidepressants (sertraline, venlafaxine XR and bupropion), although the limited data prevent firm conclusions. The base-case incremental cost-effectiveness ratio (ICER) of vortioxetine reported by the manufacturer was £378 per quality

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

    PubMed

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

    2006-01-01

    One method to reduce drug costs is to promote dose form optimization strategies that take advantage of the flat pricing of some drugs, i.e., the same or nearly the same price for a 100 mg tablet and a 50 mg tablet of the same drug. Dose form optimization includes tablet splitting; taking half of a higher-strength tablet; and dose form consolidation, using 1 higher-strength tablet instead of 2 lower-strength tablets. Dose form optimization can reduce the direct cost of therapy by up to 50% while continuing the same daily dose of the same drug molecule. To determine if voluntary prescription change forms for antidepressant drugs could induce dosing changes and reduce the cost of antidepressant therapy in a Medicaid population. Specific regimens of 4 selective serotonin reuptake inhibitors (SSRIs)- citalopram, escitalopram, paroxetine, and sertraline- were identified for conversion to half tablets or dose optimization. Change forms, which served as valid prescriptions, were faxed to Oregon prescribers in October 2004. The results from both the returned forms and subsequent drug claims data were evaluated using a segmented linear regression. Citalopram claims were excluded from the cost analysis because the drug became available in generic form in October 2004. A total of 1,582 change forms were sent to 556 unique prescribers; 9.2% of the change forms were for dose consolidation and 90.8% were for tablet splitting. Of the 1,118 change forms (70.7%) that were returned, 956 (60.4% of those sent and 85.5% of those returned) authorized a prescription change to a lower-cost dose regimen. The average drug cost per day declined by 14.2%, from Dollars 2.26 to Dollars 1.94 in the intervention group, versus a 1.6% increase, from Dollars 2.52 to Dollars 2.56, in the group without dose consolidation or tablet splitting of the 3 SSRIs (sertraline, escitalopram, and immediate-release paroxetine). Total drug cost for the 3 SSRIs declined by 35.6%, from Dollars 333,567 to Dollars 214

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

    PubMed

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

    2011-02-01

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

  8. Treatment of alcohol use disorder and co-occurring PTSD.

    PubMed

    Taylor, Mandrill; Petrakis, Ismene; Ralevski, Elizabeth

    2017-07-01

    Alcohol use disorder (AUD) is a serious psychiatric disorder with medical, psychiatric, and social consequences. In individuals with comorbid post-traumatic stress disorder (PTSD), treatment outcomes are notably worse in comparison with treatment outcomes associated with either disorder occurring alone. There is a growing literature evaluating treatments, both pharmacotherapy and psychotherapy focused, in individuals with co-occurring AUD and PTSD. The main objective of this review was to evaluate pharmacotherapy and psychotherapy studies that were specifically designed to evaluate the treatment of individuals with comorbid AUD and PTSD. MEDLINE and PUBMED databases were searched with no specific time period. Studies focusing on SUD treatments were excluded. Because the number of random clinical trial (RCT) studies was small, all publications (including open label, single case, and secondary analyses) were included. Sixteen studies met criteria and were organized based on whether they evaluated the efficacy of pharmacotherapy, psychotherapy, or both. Pharmacological interventions with either AUD or PTSD agents were mainly effective in reducing drinking outcomes; only one study using sertraline found that the active study medication was superior to placebo in reducing PTSD symptoms. Psychotherapies were not superior to a comparative treatment in reducing drinking outcomes. Only 1 study showed reduction in PTSD symptoms in a small sample of completers. The single RCT that evaluated the efficacy of naltrexone in combination with psychotherapies (prolonged exposure or supportive counseling) found that naltrexone in combination with prolonged exposure was better for drinking outcomes at follow-up. Although these studies represent a good start in terms of research in treatment interventions of co-occurring AUD and PTSD, the studies are very limited, most lack adequate power, and the majority suffer from inadequate control groups. In particular, there is a strong need to

  9. 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

  10. Prefrontal Reactivity to Social Signals of Threat as a Predictor of Treatment Response in Anxious Youth

    PubMed Central

    Kujawa, Autumn; Swain, James E; Hanna, Gregory L; Koschmann, Elizabeth; Simpson, David; Connolly, Sucheta; Fitzgerald, Kate D; Monk, Christopher S; Phan, K Luan

    2016-01-01

    Neuroimaging has shown promise as a tool to predict likelihood of treatment response in adult anxiety disorders, with potential implications for clinical decision-making. Despite the relatively high prevalence and emergence of anxiety disorders in youth, very little work has evaluated neural predictors of response to treatment. The goal of the current study was to examine brain function during emotional face processing as a predictor of response to treatment in children and adolescents (age 7–19 years; N=41) with generalized, social, and/or separation anxiety disorder. Prior to beginning treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline or cognitive behavior therapy (CBT), participants completed an emotional faces matching task during functional magnetic resonance imaging (fMRI). Whole brain responses to threatening (ie, angry and fearful) and happy faces were examined as predictors of change in anxiety severity following treatment. Greater activation in inferior and superior frontal gyri, including dorsolateral prefrontal cortex and ventrolateral prefrontal cortex, as well as precentral/postcentral gyri during processing of threatening faces predicted greater response to CBT and SSRI treatment. For processing of happy faces, activation in postcentral gyrus was a significant predictor of treatment response. Post-hoc analyses indicated that effects were not significantly moderated by type of treatment. Findings suggest that greater activation in prefrontal regions involved in appraising and regulating responses to social signals of threat predict better response to SSRI and CBT treatment in anxious youth and that neuroimaging may be a useful tool for predicting how youth will respond to treatment. PMID:26708107

  11. Differential impact of anxiety symptoms and anxiety disorders on treatment outcome for psychotic depression in the STOP-PD study

    PubMed Central

    Davies, Simon J.C.; Mulsant, Benoit H.; Flint, Alastair J.; Rothschild, Anthony J.; Whyte, Ellen M.; Meyers, Barnett S.

    2014-01-01

    Background There are conflicting results on the impact of anxiety on depression outcomes. The impact of anxiety has not been studied in major depression with psychotic features (“psychotic depression”). Aims We assessed the impact of specific anxiety symptoms and disorders on the outcomes of psychotic depression. Methods We analyzed data from the Study of Pharmacotherapy for Psychotic Depression that randomized 259 younger and older participants to either olanzapine plus placebo or olanzapine plus sertraline. We assessed the impact of specific anxiety symptoms from the Brief Psychiatric Rating Scale (“tension”, “anxiety” and “somatic concerns” and a composite anxiety score) and diagnoses (panic disorder and GAD) on psychotic depression outcomes using linear or logistic regression. Age, gender, education and benzodiazepine use (at baseline and end) were included as covariates. Results Anxiety symptoms at baseline and anxiety disorder diagnoses differentially impacted outcomes. On adjusted linear regression there was an association between improvement in depressive symptoms and both baseline “tension” (coefficient = 0.784; 95% CI: 0.169–1.400; p = 0.013) and the composite anxiety score (regression coefficient = 0.348; 95% CI: 0.064–0.632; p = 0.017). There was an interaction between “tension” and treatment group, with better responses in those randomized to combination treatment if they had high baseline anxiety scores (coefficient = 1.309; 95% CI: 0.105–2.514; p = 0.033). In contrast, panic disorder was associated with worse clinical outcomes (coefficient = −3.858; 95% CI: –7.281 to −0.434; p = 0.027) regardless of treatment. Conclusions Our results suggest that analysis of the impact of anxiety on depression outcome needs to differentiate psychic and somatic symptoms. PMID:24656524

  12. Treatment patterns of schizophrenia based on the data from seven Central and Eastern European Countries.

    PubMed

    Szkultecka-Dębek, Monika; Miernik, Katarzyna; Stelmachowski, Jarosław; Jakovljević, Miro; Jukić, Vlado; Aadamsoo, Kaire; Janno, Sven; Bitter, István; Tolna, Judit; Jarema, Marek; Jankovic, Slobodan; Pecenak, Jan; Vavrusova, Livia; Tavčar, Rok; Walczak, Jacek; Talbot, Darren; Augustyńska, Joanna

    2016-09-01

    The aim is to analyze how schizophrenia is pharmacologically treated in seven CEE countries: Croatia, Estonia, Hungary, Poland, Serbia, Slovakia and Slovenia. Psychiatrists from selected centers in each of participating countries were asked to complete a pre-defined questionnaire on their current clinical practice. Information on protocols and resource utilization in schizophrenia treatment was included and derived from randomly selected patient medical records. Expert opinions on country-wide treatment patterns were additionally sought. This sub-analysis focuses on pharmacological treatment patterns in the last six months and over the course of the disease. 961 patients' data show that during last six months the most commonly prescribed medications were oral atypical antipsychotics: olanzapine (n=268), clozapine (n=234) and risperidone (n=160). The most frequently prescribed atypical antipsychotics over course of disease were: risperidone (54.5%), olanzapine (52.4%) and clozapine (35.1%), along with haloperidol (39.3%). Experts reported risperidone (four countries) and olanzapine (three countries) as first-line treatment, with the same two medications prescribed as second-line treatment. Clozapine was the most reported medication for refractory patients. Approximately 22% of patients received polypharmacy with antipsychotics in at least one period over the disease course. Mean time since diagnosis was 13.1 years and on average 4.8 treatment courses received during that period. Anxiolytics (70%), antidepressants (42%), mood-stabilizers (27%) were also prescribed, with diazepam (35.4%), sertraline (10.5%), valproic acid (17.5%) the most commonly reported, respectively, in each group. The most frequently reported treatment change was switch from one oral atypical antipsychotic to another (51%). Oral atypical antipsychotics, mostly older drugs (risperidone, olanzapine, clozapine), were most commonly prescribed for schizophrenia treatment in participating countries

  13. Lost human capital from early-onset chronic depression.

    PubMed

    Berndt, E R; Koran, L M; Finkelstein, S N; Gelenberg, A J; Kornstein, S G; Miller, I M; Thase, M E; Trapp, G A; Keller, M B

    2000-06-01

    Chronic depression starts at an early age for many individuals and could affect their accumulation of "human capital" (i.e., education, higher amounts of which can broaden occupational choice and increase earnings potential). The authors examined the impact, by gender, of early- (before age 22) versus late-onset major depressive disorder on educational attainment. They also determined whether the efficacy and sustainability of antidepressant treatments and psychosocial outcomes vary by age at onset and quantified the impact of early- versus late-onset, as well as never-occurring, major depressive disorder on expected lifetime earnings. The authors used logistic and multivariate regression methods to analyze data from a three-phase, multicenter, double-blind, randomized trial that compared sertraline and imipramine treatment of 531 patients with chronic depression aged 30 years and older. These data were integrated with U.S. Census Bureau data on 1995 earnings by age, educational attainment, and gender. Early-onset major depressive disorder adversely affected the educational attainment of women but not of men. No significant difference in treatment responsiveness by age at onset was observed after 12 weeks of acute treatment or, for subjects rated as having responded, after 76 weeks of maintenance treatment. A randomly selected 21-year-old woman with early-onset major depressive disorder in 1995 could expect future annual earnings that were 12%-18% lower than those of a randomly selected 21-year-old woman whose onset of major depressive disorder occurred after age 21 or not at all. Early-onset major depressive disorder causes substantial human capital loss, particularly for women. Detection and effective treatment of early-onset major depressive disorder may have substantial economic benefits.

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

    PubMed

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

    2017-01-01

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

  15. 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

  16. Concentration and risk of pharmaceuticals in freshwater systems are related to the population density and the livestock units in Iberian Rivers.

    PubMed

    Osorio, Victoria; Larrañaga, Aitor; Aceña, Jaume; Pérez, Sandra; Barceló, Damià

    2016-01-01

    Considerable amounts of pharmaceuticals are used in human and veterinary medicine, which are not efficiently removed during wastewater and slurries treatment and subsequently entering continuously into freshwater systems. The intrinsic biological activity of these non-regulated pollutants turns their presence in the aquatic environment into an ecological matter of concern. We present the first quantitative study relating the presence of pharmaceuticals and their predicted ecotoxicological effects with human population and livestock units. Four representative Iberian River basins (Spain) were studied: Llobregat, Ebro, Júcar and Guadalquivir. The levels of pharmaceuticals were determined in surface water and sediment samples collected from 77 locations along their stream networks. Predicted total toxic units to algae, Daphnia and fish were estimated for pharmaceuticals detected in surface waters. The use of chemometrics enabled the study of pharmaceuticals for: their spatial distribution along the rivers in two consecutive years; their potential ecotoxicological risk to aquatic organisms; and the relationships among their occurrence and predicted ecotoxicity with human population and animal farming pressure. The Llobregat and the Ebro River basins were characterized as the most polluted and at highest ecotoxicological risk, followed by Júcar and Guadalquivir. No significant acute risks of pharmaceuticals to aquatic organisms were observed. However potential chronic ecotoxicological effects on algae could be expected at two hot spots of pharmaceuticals pollution identified in the Llobregat and Ebro basins. Analgesics/antiinflammatories, antibiotics and diuretics were the most relevant therapeutic groups across the four river basins. Among them, hydrochlorothiazide and gemfibrozil, as well as azithromycin and ibuprofen were widely spread and concentrated pharmaceuticals in surface waters and sediments, respectively. Regarding their predicted ecotoxicity, sertraline

  17. Oral health impacts of medications used to treat mental illness.

    PubMed

    Cockburn, N; Pradhan, A; Taing, M W; Kisely, S; Ford, P J

    2017-12-01

    Many psychotropic medications affect oral health. This review identified oral side effects for antidepressant, antipsychotic, anticonvulsant, antianxiety and sedative drugs that are recommended in Australia for the management of common mental illnesses and provides recommendations to manage these side-effects. The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat common mental health conditions. For each medication, the generic name, class, and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (eMIMs) and UpToDate databases. Meyler's Side Effect of Drugs Encyclopaedia was used to identify additional oral adverse reactions to these medications. Fifty-seven drugs were identified: 23 antidepressants, 22 antipsychotics or mood stabilisers, and 12 anxiolytic or sedative medications. Xerostomia (91%) the most commonly reported side effect among all classes of medications of the 28 identified symptoms. Other commonly reported adverse effects included dysguesia (65%) for antidepressants, and tardive dyskinesia (94%) or increased salivation (78%) for antipsychotic medications. While xerostomia has often been reported as a common adverse effect of psychotropic drugs, this review has identified additional side effects including dysguesia from antidepressants and tardive dyskinesia and increased salivation from antipsychotics. Clinicians should consider oral consequences of psychotropic medication in addition to other side-effects when prescribing. For antidepressants, this would mean choosing duloxetine, agomelatine and any of the serotonin re-uptake inhibitors except sertraline. In the case of antipsychotics and mood stabilisers, atypical agents have less oral side effects than older alternatives. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Next-Step Strategies for Panic Disorder Refractory to Initial Pharmacotherapy

    PubMed Central

    Simon, NM; Otto, MW; Worthington, JJ; Hoge, EA; Thompson, EH; LeBeau, RT; Moshier, SJ; Zalta, AK; Pollack, MH

    2010-01-01

    Background More data is needed to guide next step interventions for panic disorder refractory to initial intervention. Method This 24-week randomized clinical trial (RCT) consisted of three phases. Phase 1 is a 6-week lead-in with open-label sertraline flexibly dosed to 100mg (or escitalopram equivalent) to prospectively define treatment refractoriness (lack of remission). Phase 2 is a six-week double blind RCT of (1) increased dose serotonin selective reuptake inhibitor (SSRI) versus (2) continued SSRI plus placebo. Phase 3 is a 12-week RCT of added cognitive-behavioral therapy (CBT) compared to “medication-optimization” (MO) with SSRI plus clonazepam. Primary endpoints were remission and change in Panic Disorder Severity Scale (PDSS) score in the intent to treat sample in each phase. Results In Phase 1, 20.5% (8/39) achieved remission, and only baseline severity predicted endpoint PDSS (β (SE)= 1.04(0.15), t=6.76, p<0.000). In Phase 2, increasing the SSRI dose did not result in greater improvement or remission rates (placebo 15% [n=2] vs. increased dose 9%[n=1]: FET p=n.s.). In Phase 3, remission was minimal (MO = 11%; CBT =10%), with a lack of group difference in PDSS reduction (t(df)=0.51(17), p>0.60) consistent with a small effect size (d=0.24). Conclusion Although power was limited and larger studies are needed, we failed to find evidence for greater benefit of increased SSRI dose versus continuation of current dose for panic disorder symptomatic after 6 weeks at moderate dose. Further, augmentation with CBT or medication optimization with clonazepam augmentation in non-remitted panic after 12 weeks of an SSRI did not differ, suggesting both are reasonable next-step options. However, low overall remission rates in this comorbid refractory population suggest better predictors of response to specific treatments over time and additional interventions are needed. PMID:19814948

  19. Correlates of incident bipolar disorder in children and adolescents diagnosed with attention-deficit/hyperactivity disorder.

    PubMed

    Jerrell, Jeanette M; McIntyre, Roger S; Park, Yong-Moon Mark

    2014-11-01

    The greater severity and chronicity of illness in youths with co-occurring attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder deserve further investigation as to the risk imparted by comorbid conditions and the pharmacotherapies employed. A retrospective cohort design was employed, using South Carolina's Medicaid claims dataset covering outpatient and inpatient medical and psychiatric service claims with International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses and medication prescriptions between January 1996 and December 2006 for patients ≤ 17 years of age. The cohort included 22,797 cases diagnosed with ADHD at a mean age of 7.8 years; 1,604 (7.0%) were diagnosed with bipolar disorder at a mean age of 12.2 years. The bipolar disorder group developed conduct disorder (CD)/oppositional defiant disorder (ODD), anxiety disorder, and a substance use disorder later than the ADHD-only group. The odds of a child with ADHD developing bipolar disorder were significantly and positively associated with a comorbid diagnosis of CD/ODD (adjusted odds ratio [aOR] = 4.01), anxiety disorder (aOR = 2.39), or substance use disorder (aOR = 1.88); longer treatment with methylphenidate, mixed amphetamine salts, or atomoxetine (aOR = 1.01); not being African American (aOR = 1.61); and being treated with certain antidepressant medications, most notably fluoxetine (aOR = 2.00), sertraline (aOR = 2.29), bupropion (aOR = 2.22), trazodone (aOR = 2.15), or venlafaxine (aOR = 2.37) prior to the first diagnosis of mania. Controlling for pharmacotherapy differences, incident bipolar disorder was more likely in individuals clustering specific patterns of comorbid psychiatric disorders, suggesting that there are different pathways to bipolarity and providing a clinical impetus for prioritizing prevention and preemptive strategies to reduce their hazardous influence. © Copyright 2014 Physicians Postgraduate Press, Inc.

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

    PubMed

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

    2011-04-01

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

  1. Assessment of Lemna minor (duckweed) and Corbicula fluminea (freshwater clam) as potential indicators of contaminated aquatic ecosystems: responses to presence of psychoactive drug mixtures.

    PubMed

    Bourioug, Mohamed; Mazzitelli, Jean-Yves; Marty, Pierre; Budzinsky, Hélène; Aleya, Lotfi; Bonnafé, Elsa; Geret, Florence

    2018-04-01

    The pharmaceutical products are emerging pollutants continuously released into the environment, because they cannot be effectively removed by the wastewater treatment plants. In recent years, questions have been raised concerning the environmental risks related to these pollutants. The goal of this research was to evaluate the responses in Lemna minor after 7 days and in Corbicula fluminea after differing durations (1, 3, 7, and 19 days) of exposure to the psychoactive drug mixture (valproic acid, citalopram, carbamazepine, cyamemazine, hydroxyzine, oxazepam, norfluoxetine, lorazepam, fluoxetine, and sertraline) in different concentrations (0, 0 + ethanol, drug concentration (DC) 1 = river water concentration, DC2 = effluent concentration, and DC3 = 10× effluent concentration). In this aim, growth parameters of L. minor, gluthathione S-transferase (GSTs), catalase (CAT), ethoxyresorufin-O-deethylase (EROD) and/or gene expressions (pi-gst, cat, cytochrome P450 4 (cyp4), multidrug resistant 1 (mdr1), and superoxide dismutase (sod)) were measured. GST activities increased significantly in L. minor exposed to DC3, but no changes were found in CAT activity. In C. fluminea, EROD activity was induced significantly in both gill and digestive gland tissues after 3 days' exposure to DC3, while a GST increase was observed only in digestive gland tissues, suggesting that these pharmaceuticals induced an oxidative effect. Gene expression analysis revealed transient transcriptomic responses of cyp4, sod, and mdr1 under drug concentrations 2 or 3 and no change of expression for the other genes (cat and pi-gst) or condition (environmental drug concentration) tested. Finally, the data reported in this study represent important ecotoxicological information, confirming that this enzyme family (cyp4, sod, and mdr1) may be considered as a sensible and early indicator of exposure to drugs and emphasizing the involvement of selected genes in detoxification pathways.

  2. 24- and 36-week outcomes for the Child/Adolescent Anxiety Multimodal Study (CAMS).

    PubMed

    Piacentini, John; Bennett, Shannon; Compton, Scott N; Kendall, Phillip C; Birmaher, Boris; Albano, Anne Marie; March, John; Sherrill, Joel; Sakolsky, Dara; Ginsburg, Golda; Rynn, Moira; Bergman, R Lindsey; Gosch, Elizabeth; Waslick, Bruce; Iyengar, Satish; McCracken, James; Walkup, John

    2014-03-01

    We report active treatment group differences on response and remission rates and changes in anxiety severity at weeks 24 and 36 for the Child/Adolescent Anxiety Multimodal Study (CAMS). CAMS youth (N = 488; 74% ≤ 12 years of age) with DSM-IV separation, generalized, or social anxiety disorder were randomized to 12 weeks of cognitive-behavioral therapy (CBT), sertraline (SRT), CBT+SRT (COMB), or medication management/pill placebo (PBO). Responders attended 6 monthly booster sessions in their assigned treatment arm; youth in COMB and SRT continued on their medication throughout this period. Efficacy of COMB, SRT, and CBT (n = 412) was assessed at 24 and 36 weeks postrandomization. Youth randomized to PBO (n = 76) were offered active CAMS treatment if nonresponsive at week 12 or over follow-up and were not included here. Independent evaluators blind to study condition assessed anxiety severity, functioning, and treatment response. Concomitant treatments were allowed but monitored over follow-up. The majority (>80%) of acute responders maintained positive response at both weeks 24 and 36. Consistent with acute outcomes, COMB maintained advantage over CBT and SRT, which did not differ, on dimensional outcomes; the 3 treatments did not differ on most categorical outcomes over follow-up. Compared to COMB and CBT, youth in SRT obtained more concomitant psychosocial treatments, whereas those in SRT and CBT obtained more concomitant combined (medication plus psychosocial) treatment. COMB maintained advantage over CBT and SRT on some measures over follow-up, whereas the 2 monotherapies remained indistinguishable. The observed convergence of COMB and monotherapy may be related to greater use of concomitant treatment during follow-up among youth receiving the monotherapies, although other explanations are possible. Although outcomes were variable, most CAMS-treated youth experienced sustained treatment benefit. Clinical trial registration information-Child and Adolescent

  3. Benefits of Child-Focused Anxiety Treatments for Parents and Family Functioning

    PubMed Central

    Keeton, Courtney P.; Ginsburg, Golda S.; Drake, Kelly L.; Sakolsky, Dara; Kendall, Philip C.; Birmaher, Boris; Albano, Anne Marie; March, John S.; Rynn, Moira; Piacentini, John; Walkup, John T.

    2014-01-01

    Background To examine (1) changes in parent (global psychological distress, trait anxiety) and family (dysfunction, burden) functioning following 12 weeks of child-focused anxiety treatment, and (2) whether changes in these parent and family factors were associated with child's treatment condition and response. Methods Participants were 488 youth ages 7–17 years (50% female; mean age 10.7 years) who met DSM-IV-TR criteria for social phobia, separation anxiety, and/or generalized anxiety disorder, and their parents. Youth were randomly assigned to 12 weeks of “Coping Cat” individual cognitive-behavioral therapy (CBT), medication management with sertraline (SRT), their combination (COMB), or medication management with pill placebo (PBO) within the multisite Child/Adolescent Anxiety Multimodal Study (CAMS). At pre- and posttreatment, parents completed measures of trait anxiety, psychological distress, family functioning, and burden of child illness; children completed a measure of family functioning. Blinded independent evaluators rated child's response to treatment using the Clinical Global Impression-Improvement Scale at posttreatment. Results Analyses of covariance revealed that parental psychological distress and trait anxiety, and parent-reported family dysfunction improved only for parents of children who were rated as treatment responders, and these changes were unrelated to treatment condition. Family burden and child-reported family dysfunction improved significantly from pre- to posttreatment regardless of treatment condition or response. Conclusions Findings suggest that child-focused anxiety treatments, regardless of intervention condition, can result in improvements in nontargeted parent symptoms and family functioning particularly when children respond successfully to the treatment. PMID:23390005

  4. Treatment of depression in patients with epilepsy.

    PubMed

    Noe, Katherine H; Locke, Dona E C; Sirven, Joseph I

    2011-08-01

    In this article, we review the current best evidence for the treatment of depression in patients with epilepsy. Depression is a common epilepsy comorbidity, but it is often unrecognized. The most important step in appropriately managing mood disorders in this population is making the diagnosis. Clinical vigilance and routine use of a validated screening tool can improve detection and quality of care. As is increasingly the case for the general population, persons with epilepsy are often interested in exploring alternative therapies for chronic conditions, including depression. Unfortunately, the benefit of complementary and alternative therapies for depression currently is largely unproven for persons with a seizure history, although an early study of exercise for mild depression has shown some benefit. Concerns about drug interactions, side effects, and expense may be barriers to the prescription of antidepressant medications for people requiring chronic antiepileptic drug (AED) therapy. For this reason, use of an AED with mood-stabilizing properties has appeal and may be appropriate for selected individuals with mild depressive symptoms. Undue fear of lowering seizure threshold should not preclude the prescription of an antidepressant medication, as the perceived risks are often overestimated and rarely outweigh the risk of leaving depression untreated. At present, the best evidence for efficacy and safety support the use of citalopram, sertraline, or mirtazapine as initial pharmacotherapy, whereas bupropion should be avoided. Start low, go slow, and use the lowest effective dose. Cognitive behavioral therapy is a valuable adjunct to antidepressant therapy in this population. For people with refractory partial epilepsy and refractory depression, vagus nerve stimulation has some appeal, in that it may be beneficial for both conditions, but the efficacy of vagus nerve stimulation in improving mood in patients with epilepsy remains unclear.

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

    PubMed

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

    2015-08-01

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

  6. Effects of methiothepin on changes in brain serotonin release induced by repeated administration of high doses of anorectic serotoninergic drugs

    NASA Technical Reports Server (NTRS)

    Gardier, A. M.; Kaakkola, S.; Erfurth, A.; Wurtman, R. J.

    1992-01-01

    We previously observed, using in vivo microdialysis, that the potassium-evoked release of frontocortical serotonin (5-HT) is suppressed after rats receive high doses (30 mg/kg, i.p., daily for 3 days) of fluoxetine, a selective blocker of 5-HT reuptake. We now describe similar impairments in 5-HT release after repeated administration of two other 5-HT uptake blockers, zimelidine and sertraline (both at 20 mg/kg, i.p. for 3 days) as well as after dexfenfluramine (7.5 mg/kg, i.p. daily for 3 days), a drug which both releases 5-HT and blocks its reuptake. Doses of these indirect serotonin agonists were about 4-6 times the drug's ED50 in producing anorexia, a serotonin-related behavior. In addition, methiothepin (20 microM), a non-selective receptor antagonist, locally perfused through the dialysis probe 24 h after the last drug injection, enhanced K(+)-evoked release of 5-HT at serotoninergic nerve terminals markedly in control rats and slightly in rats treated with high doses of dexfenfluramine or fluoxetine. On the other hand, pretreatment with methiothepin (10 mg/kg, i.p.) one hour before each of the daily doses of fluoxetine or dexfenfluramine given for 3 days, totally prevented the decrease in basal and K(+)-evoked release of 5-HT. Finally, when methiothepin was injected systemically the day before the first of 3 daily injections of dexfenfluramine, it partially attenuated the long-term depletion of brain 5-HT and 5-HIAA levels induced by repeated administration of high doses of dexfenfluramine. These data suggest that drugs which bring about the prolonged blockade of 5-HT reuptake - such as dexfenfluramine and fluoxetine - can, by causing prolonged increases in intrasynaptic 5-HT levels as measured by in vivo microdialysis, produce receptor-mediated long-term changes in the processes controlling serotonin levels and dynamics.

  7. Increase in work productivity of depressed individuals with improvement in depressive symptom severity.

    PubMed

    Trivedi, Madhukar H; Morris, David W; Wisniewski, Stephen R; Lesser, Ira; Nierenberg, Andrew A; Daly, Ella; Kurian, Benji T; Gaynes, Bradley N; Balasubramani, G K; Rush, A John

    2013-06-01

    The authors sought to identify baseline clinical and sociodemographic characteristics associated with work productivity in depressed outpatients and to assess the effect of treatment on work productivity. Employed depressed outpatients 18-75 years old who completed the Work Productivity and Activity Impairment scale (N=1,928) were treated with citalopram (20-40 mg/day) in the Sequenced Treatment Alternatives to Relieve Depression study. For patients who did not remit after an initial adequate antidepressant trial (level 1), either a switch to sertraline, sustained-release bupropion, or extended-release venlafaxine or an augmentation with sustained-release bupropion or buspirone was provided (level 2). Participants' clinical and demographic characteristics and treatment outcomes were analyzed for associations with baseline work productivity and change in productivity over time. Education, baseline depression severity, and melancholic, atypical, and recurrent depression subtypes were all independently associated with lower benefit to work productivity domains. During level 1 treatment, work productivity in several domains improved with reductions in depressive symptom severity. However, these findings did not hold true for level 2 outcomes; there was no significant association between treatment response and reduction in work impairment. Results were largely confirmed when multiple imputations were employed to address missing data. During this additional analysis, an association was also observed between greater impairment in work productivity and higher levels of anxious depression. Patients with clinically significant reductions in symptom severity during initial treatment were more likely than nonresponders to experience significant improvements in work productivity. In contrast, patients who achieved symptom remission in second-step treatment continued to have impairment at work. Patients who have demonstrated some degree of treatment resistance are more prone to

  8. Contamination profiles, mass loadings, and sewage epidemiology of neuropsychiatric and illicit drugs in wastewater and river waters from a community in the Midwestern United States.

    PubMed

    Skees, Allie J; Foppe, Katelyn S; Loganathan, Bommanna; Subedi, Bikram

    2018-08-01

    In this study, residues of the neuropsychiatric and illicit drugs including stimulants, opioids, hallucinogens, antischizophrenics, sedatives, and antidepressants were determined in influent and effluent samples from a small wastewater treatment plant, a receiving creek, and river waters in the Four Rivers region of the Midwestern United States. Nineteen neuropsychiatric drugs, eight illicit drugs, and three metabolites of illicit drugs were detected and quantitated in the water samples using HPLC-MS/MS. Residual concentrations of the drugs varied from below the detection limit to sub-μg/L levels. The source of residual cocaine and benzoylecgonine in wastewater is primarily from human consumption of cocaine rather than direct disposal. Wastewater based epidemiology is utilized to estimate the community usage of drugs based on the concentration of drug residues in wastewater, wastewater inflow, and the population served by the centralized wastewater treatment plant. The per-capita consumption rate of methamphetamine (1740 mg/d/1000 people) and amphetamine (970 mg/d/1000 people) found in this study were the highest reported per-capita consumption rates in the USA. Antidepressant venlafaxine found to have the highest environmental emission from the WWTP (333 ± 160 mg/d/1000 people) followed by citalopram (132 ± 60.2 mg/d/1000 people), methamphetamine (111 ± 43.6 mg/d/1000 people), and hydrocodone (108 ± 90.1 mg/d/1000 people). Bee Creek, an immediate receiving water body, is found to be a source of several neuropsychiatric and illicit drugs including methamphetamine, methadone, alprazolam, oxazepam, temazepam, carbamazepine, venlafaxine, citalopram, sertraline, oxycodone, and hydrocodone (p < 0.036) in the Clarks River. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. 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.

  10. Bereavement dream? Successful antidepressant treatment for bereavement-related distressing dreams in patients with major depression.

    PubMed

    Ishida, Mayumi; Onishi, Hideki; Wada, Mei; Wada, Tomomi; Wada, Makoto; Uchitomi, Yosuke; Nomura, Shinobu

    2010-03-01

    The death of a person is a stressful event. Such stress affects the physical and psychological well-being of the bereaved. As an associated mental disorder, major depressive disorder (MDD) is common. Some dream of the deceased, and these dreams are called bereavement dreams. Some MDD patients also experience dreams. These two types of dreams are sometimes difficult to differentiate. The dream of the bereaved might be only a bereavement-related dream, yet it might be a symptom of MDD. Herein, we report one patient who had distressing dreams after the death of her mother. A 63-year-old woman was referred for psychiatric consultation because of generalized fatigue and insomnia. Questioning her about recent events, she said that her mother had died of colonic carcinoma 5 months previously. Two months after the death, she suddenly started dreaming of her mother, getting angry with her almost every night. Generalized fatigue, insomnia, and distressing dreams appeared simultaneously. The dream caused much distress, making her afraid to fall asleep. Her psychiatric features fulfilled the DSM-IV-TR criteria for MDD, single episode. The death of her mother was considered to be one of the causes of MDD. She was administered 25 mg/day of sertraline hydrochloride. After that, her symptoms gradually disappeared, and the frequency of distressing dreams was reduced. Five months later, physical and psychiatric symptoms of MDD were completely resolved. Subsequently, she has not suffered from any distressing dreams of her mother. This case indicates that dreams experienced after the death of a loved one should not be regarded simply as bereavement dreams. Some of the dreams may be symptoms of MDD. If the dreams are the symptoms of MDD, antidepressant treatment as well as psychotherapy may be useful. Therefore, we should avoid regarding symptoms of MDD as reactions to bereavement.

  11. [Sleep disorders and impaired sleep as adverse drug reactions of psychotropic drugs: an evaluation of data of summaries of product characteristics].

    PubMed

    Gahr, Maximilian; Connemann, Bernhard J; Zeiss, René; Fröhlich, Albrecht

    2018-03-02

     Psychopharmacotherapy is essential in the treatment of many mental disorders. Adverse drug reactions (ADR) have impact on compliance and tolerability. Sleep disorders or impaired sleep may occur as ADRs of psychopharmacotherapy. Sleep disorders are associated with an increased risk for physical and mental illness and may impair cognition, impulse control, emotion regulation and mood. Objective of the following study was the systematic presentation of type and risk of sleep disorders/impairments of sleep of frequently prescribed psychotropic drugs.  Psychotropic agents that are most frequently prescribed in Germany were identified by using the Arzneiverordnungs-Report 2016. Summaries of product characteristics (SmPC) of corresponding original products were analyzed regarding presence and frequency of sleep disorders/impairments of sleep according to the International Classification of Sleep Disorders 3 (ICSD-3).  N = 64 SmPCs were analyzed. In most of the analyzed SmPCs, at least one sleep disorder (50/64; 78 %) was listed. At least one SmPC with a corresponding ADR was found in the categories insomnia (52 %), parasomnias (33 %), and sleep-related movement disorders (20 %); sleep-related breathing disorders (6 %) and central disorders of hypersomnolence (5 %) were rarely listed; circadian rhythm sleep-wake disorder was not found. The SmPCs of the four most frequently prescribed agents (citalopram > venlafaxine > mirtazapine > sertraline) listed insomnia as an ADR. Nearly all analysed hypnotics (except chloral hydrate) were associated with nightmares.  Most of the psychotropic agents frequently prescribed in Germany may induce sleep disorders/impairments of sleep. The four most frequently prescribed agents were antidepressants and all of the corresponding SmPCs listed insomnia as a possible ADR. Sleep disorders should be taken seriously as possible ADRs of psychopharmacotherapy. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Practical application of cure mixture model for long-term censored survivor data from a withdrawal clinical trial of patients with major depressive disorder.

    PubMed

    Arano, Ichiro; Sugimoto, Tomoyuki; Hamasaki, Toshimitsu; Ohno, Yuko

    2010-04-23

    Survival analysis methods such as the Kaplan-Meier method, log-rank test, and Cox proportional hazards regression (Cox regression) are commonly used to analyze data from randomized withdrawal studies in patients with major depressive disorder. However, unfortunately, such common methods may be inappropriate when a long-term censored relapse-free time appears in data as the methods assume that if complete follow-up were possible for all individuals, each would eventually experience the event of interest. In this paper, to analyse data including such a long-term censored relapse-free time, we discuss a semi-parametric cure regression (Cox cure regression), which combines a logistic formulation for the probability of occurrence of an event with a Cox proportional hazards specification for the time of occurrence of the event. In specifying the treatment's effect on disease-free survival, we consider the fraction of long-term survivors and the risks associated with a relapse of the disease. In addition, we develop a tree-based method for the time to event data to identify groups of patients with differing prognoses (cure survival CART). Although analysis methods typically adapt the log-rank statistic for recursive partitioning procedures, the method applied here used a likelihood ratio (LR) test statistic from a fitting of cure survival regression assuming exponential and Weibull distributions for the latency time of relapse. The method is illustrated using data from a sertraline randomized withdrawal study in patients with major depressive disorder. We concluded that Cox cure regression reveals facts on who may be cured, and how the treatment and other factors effect on the cured incidence and on the relapse time of uncured patients, and that cure survival CART output provides easily understandable and interpretable information, useful both in identifying groups of patients with differing prognoses and in utilizing Cox cure regression models leading to meaningful

  13. The Pathophysiology of Repetitive Concussive Traumatic Brain Injury in Experimental Models; New Developments and Open Questions

    PubMed Central

    Brody, David L; Benetatos, Joseph; Bennett, Rachel E; Klemenhagen, Kristen C; Donald, Christine L Mac

    2015-01-01

    In recent years, there has been an increasing interest in the pathophysiology of repetitive concussive traumatic brain injury (rcTBI) in large part due to the association with dramatic cases of progressive neurological deterioration in professional athletes, military personnel, and others. However, our understanding of the pathophysiology of rcTBI is less advanced than for more severe brain injuries. Most prominently, the mechanisms underlying traumatic axonal injury, microglial activation, amyloid-beta accumulation, and progressive tau pathology are not yet known. In addition, the role of injury to dendritic spine cytoskeletal structures, vascular reactivity impairments, and microthrombi are intriguing and subjects of ongoing inquiry. Methods for quantitative analysis of axonal injury, dendritic injury, and synaptic loss need to be refined for the field to move forward in a rigorous fashion. We and others are attempting to develop translational approaches to assess these specific pathophysiological events in both animals and humans to facilitate clinically relevant pharmacodynamic assessments of candidate therapeutics. In this article, we review and discuss several of the recent experimental results from our lab and others. We include new initial data describing the difficulty in modeling progressive tau pathology in experimental rcTBI, and results demonstrating that sertraline can alleviate social interaction deficits and depressive-like behaviors following experimental rcTBI plus foot shock stress. Furthermore, we propose a discrete set of open, experimentally tractable questions that may serve as a framework for future investigations. In addition, we also raise several important questions that are less experimentally tractable at this time, in hopes that they may stimulate future methodological developments to address them. PMID:25684677

  14. Kynurenine 3-monooxygenase is implicated in antidepressants-responsive depressive-like behaviors and monoaminergic dysfunctions.

    PubMed

    Tashiro, Tomoyuki; Murakami, Yuki; Mouri, Akihiro; Imamura, Yukio; Nabeshima, Toshitaka; Yamamoto, Yasuko; Saito, Kuniaki

    2017-01-15

    l-Tryptophan (TRP) is metabolized via serotonin and kynurenine pathways (KP). Several studies have demonstrated that abnormality of both pathways is involved in the pathogenesis of major depressive disorder (MDD). Kynurenine 3-monooxygenase (KMO), a pivotal enzyme in the KP, has been suggested to play major roles in physiological and pathological events mediated by bioactive kynurenine metabolites. In this study, we investigated the role of KMO in the emotional and cognitive functions by using KMO knockout (KO) mice. We measured contents of TRP and monoamines and their metabolites in the serum and hippocampus of KMO KO mice. Further, we investigated whether antidepressants improved the depressive-like behaviors in KMO KO mice. KMO KO mice showed depressive-like behaviors such as decreased sucrose preference and increased immobility in the forced swimming test and high anxiety by decreased time spent in the center area of open field. But, there was no difference in spontaneous alternation in Y-maze test, counts of rearing or locomotor activity. Higher contents of TRP metabolites such as kynurenine (KYN), kynurenic acid (KA), anthranilic acid (AA), and 3-hydroxykynurenine (3-HK) in the serum and hippocampus and decreased serotonin turnover and higher content of normetanephrine (NM) in the hippocampus were observed in the KMO KO mice. Although both antidepressant attenuated increase of immobility, sertraline but not imipramine improved decrease of sucrose preference in the KMO KO mice. These findings suggested that KMO KO mice show antidepressants-responsive depressive-like behaviors and monoaminergic dysfunctions via abnormality of kynurenine metabolism with good validities as MDD model. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2010-06-01

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

  16. 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

  17. [Psychocardiology: clinically relevant recommendations regarding selected cardiovascular diseases].

    PubMed

    Albus, C; Ladwig, K-H; Herrmann-Lingen, C

    2014-03-01

    Psychosocial risk factors (work stress, low socioeconomic status, impaired social support, anger, anxiety and depression), certain personality traits (e.g. hostility) and post-traumatic stress disorders may negatively influence the incidence and course of multiple cardiovascular disease conditions. Systematic screening for these factors may help to adequately assess the psychosocial risk pattern of a given patient and may also contribute to the treatment of these patients. Recommendations for treatment are based on current guidelines. The physician-patient interaction should basically follow the principle of a patient centered communication and should gender and age specific aspects into consideration. Integrated biopsychosocial care is an effective, low threshold option to treat psycho-social risk factors and should be offered on a regular basis. Patients with high blood pressure may profit from relaxation programs and biofeedback procedures (however with moderate success). An individually adjusted multimodal treatment strategy should be offered to patients with coronary heart disease, heart failure and after heart surgery. It may incorporate educational tools, exercise therapy, motivational modules, relaxation and stress management programs. In case of affective comorbidity, psychotherapy may be indicated. Anti-depressant pharmacotherapy with selective serotonin reuptake inhibitors (SSRIs) in the first line should only be offered to patients with at least moderate severe depressive episodes. Psychotherapy and SSRIs, particularly sertraline, have been proven to be safe and effective with regard to improvements of the patient's quality of life. A prognostic benefit has not been clearly proven so far. Patients with an implanted cardioverter/defibrillator (ICD) should receive psychosocial support on a regular basis. Concomitant psychotherapy and/or psychopharmacotherapy (SSRIs) should be offered in case of a severe mental comorbidity. Generally, tricyclic

  18. Effects of selective serotonin reuptake inhibitors on thought-action fusion, metacognitions, and thought suppression in obsessive-compulsive disorder.

    PubMed

    Besiroglu, Lutfullah; Çetinkaya, Nuralay; Selvi, Yavuz; Atli, Abdullah

    2011-01-01

    We aimed to assess whether cognitive processes change over time in patients with obsessive-compulsive disorder (OCD) receiving selective serotonin reuptake inhibitors without cognitive behavioral therapy and to investigate the factors associated with probable cognitive changes. During the 16 weeks of the study, 55 patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for OCD received open-label treatment with sertraline (100-200 mg/d) or fluoxetine (40-80 mg/d) and were assessed using the Yale-Brown Obsessive-Compulsive Scale, Beck Depression Inventory (BDI), Thought-Action Fusion Scale (TAFS), Metacognitions Questionnaire (MCQ-30), and White Bear Suppression Inventory (WBSI). The Yale-Brown Obsessive-Compulsive Scale (P < .001), BDI (P < .001), TAFS morality (P < .005), MCQ-30 (P < .01), and WBSI (P < .005) scores at follow-up were significantly lower than baseline scores. When we excluded OCD patients with depressive disorder (n = 12), statistical significance in paired comparisons for MCQ and WBSI disappeared. Similarly, when OCD patients with religious obsessions (n = 16) were excluded, paired comparisons for MCQ and TAF morality were not statistically significant. Changes in BDI, TAFS morality, MCQ-30, and WBSI (P < .005) were significantly correlated with changes in severity of obsessions, but not that of compulsions. After controlling for the change in depression severity, significant correlations between changes in obsessive and cognitive scales did not continue to have statistical significance. The BDI changes (P < .05) significantly explained the changes in symptom severity in a linear regression model. Our findings suggest that selective serotonin reuptake inhibitors can change appraisals of obsessive intrusions via their effects on negative emotions. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Concentrating mixtures of neuroactive pharmaceuticals and altered neurotransmitter levels in the brain of fish exposed to a wastewater effluent.

    PubMed

    David, Arthur; Lange, Anke; Tyler, Charles R; Hill, Elizabeth M

    2018-04-15

    Fish can be exposed to a variety of neuroactive pharmaceuticals via the effluent discharges from wastewater treatment plants and concerns have arisen regarding their potential impacts on fish behaviour and ecology. In this study, we investigated the uptake of 14 neuroactive pharmaceuticals from a treated wastewater effluent into blood plasma and brain regions of roach (Rutilus rutilus) after exposure for 15days. We show that a complex mixture of pharmaceuticals including, 6 selective serotonin reuptake inhibitors, a serotonin-noradrenaline reuptake inhibitor, 3 atypical antipsychotics, 2 tricyclic antidepressants and a benzodiazepine, concentrate in different regions of the brain including the telencephalon, hypothalamus, optic tectum and hindbrain of effluent-exposed fish. Pharmaceuticals, with the exception of nordiazepam, were between 3-40 fold higher in brain compared with blood plasma, showing these neuroactive drugs are readily uptaken, into brain tissues in fish. To assess for the potential for any adverse ecotoxicological effects, the effect ratio was calculated from human therapeutic plasma concentrations (HtPCs) and the measured or predicted fish plasma concentrations of pharmaceuticals. After accounting for a safety factor of 1000, the effect ratios indicated that fluoxetine, norfluoxetine, sertraline, and amitriptyline warrant prioritisation for risk assessment studies. Furthermore, although plasma concentrations of all the pharmaceuticals were between 33 and 5714-fold below HtPCs, alterations in serotonin, glutamate, acetylcholine and tryptophan concentrations were observed in different brain regions of effluent-exposed fish. This study highlights the importance of determining the potential health effects arising from the concentration of complex environmental mixtures in risk assessment studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Sensitivity to changes during antidepressant treatment: a comparison of unidimensional subscales of the Inventory of Depressive Symptomatology (IDS-C) and the Hamilton Depression Rating Scale (HAMD) in patients with mild major, minor or subsyndromal depression.

    PubMed

    Helmreich, Isabella; Wagner, Stefanie; Mergl, Roland; Allgaier, Antje-Kathrin; Hautzinger, Martin; Henkel, Verena; Hegerl, Ulrich; Tadić, André

    2012-06-01

    In the efficacy evaluation of antidepressant treatments, the total score of the Hamilton Depression Rating Scale (HAMD) is still regarded as the 'gold standard'. We previously had shown that the Inventory of Depressive Symptomatology (IDS) was more sensitive to detect depressive symptom changes than the HAMD17 (Helmreich et al. 2011). Furthermore, studies suggest that the unidimensional subscales of the HAMD, which capture the core depressive symptoms, outperform the full HAMD regarding the detection of antidepressant treatment effects. The aim of the present study was to compare several unidimensional subscales of the HAMD and the IDS regarding their sensitivity to changes in depression symptoms in a sample of patients with mild major, minor or subsyndromal depression (MIND). Biweekly IDS-C28 and HAMD17 data from 287 patients of a 10-week randomised, placebo-controlled trial comparing the effectiveness of sertraline and cognitive-behavioural group therapy in patients with MIND were converted to subscale scores and analysed during the antidepressant treatment course. We investigated sensitivity to depressive change for all scales from assessment-to-assessment, in relation to depression severity level and placebo-verum differences. The subscales performed similarly during the treatment course, with slight advantages for some subscales in detecting treatment effects depending on the treatment modality and on the items included. Most changes in depressive symptomatology were detected by the IDS short scale, but regarding the effect sizes, it performed worse than most subscales. Unidimensional subscales are a time- and cost-saving option in judging drug therapy outcomes, especially in antidepressant treatment efficacy studies. However, subscales do not cover all facets of depression (e.g. atypical symptoms, sleep disturbances), which might be important for comprehensively understanding the nature of the disease depression. Therefore, the cost-to-benefit ratio must be

  1. Parental psychopathology and treatment outcome for anxious youth: Roles of family functioning and caregiver strain

    PubMed Central

    Schleider, Jessica L.; Ginsburg, Golda S.; Keeton, Courtney P.; Weisz, John R.; Birmaher, Boris; Kendall, Phillip C.; Piacentini, John; Sherrill, Joel; Walkup, John T.

    2014-01-01

    Objective Research has examined the effects of parental psychopathology, family functioning, and caregiver strain on treatment response in anxious youths. Although these variables have shown individual links to youth treatment response, theoretical models for their combined effects remain unexplored. This study tested the hypothesis that improvements in family functioning and reductions in caregiver strain explained the effects of parental psychopathology on youth treatment outcome in an anxiety treatment trial. Method A multiple mediation technique was used to test the proposed model across independent evaluator (IE), parent, and youth informants in 488 youths, aged 7–17 years (50% female; mean age 10.7) meeting DSM-IV-TR criteria for social phobia, separation anxiety, and/or generalized anxiety disorder. Youths were randomized to receive 12 weeks of cognitive-behavioral treatment (Coping Cat), medication (sertraline), their combination, or a pill placebo. At pre- and post-treatment, parents completed self-report measures of global psychopathology symptoms, family functioning, and caregiver strain; parents, youths, and IEs rated youths’ anxiety symptom severity. Results Changes in family functioning and caregiver strain jointly explained relations between parental psychopathology and reductions in youth anxiety. Specifically, across IE and parent informants, families with higher pre-treatment parental psychopathology showed more improvement in family functioning and caregiver strain, which in turn predicted greater youth anxiety reductions. Further, higher pre-treatment parental psychopathology predicted greater caregiver strain reductions, and in turn, greater youth anxiety reductions, based on youths’ reports of their own anxiety. Conclusions Findings suggest that improvements in family functioning and reductions in caregiver strain can influence treatment outcomes for anxious youths, especially among youths with more distressed parents. Public health

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

    PubMed

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

    2017-12-19

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

  3. 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

  4. Hyponatraemia: an audit of aged psychiatry patients taking SSRIs and SNRIs.

    PubMed

    Giorlando, Francesco; Teister, Julia; Dodd, Seetal; Udina, Marc; Berk, Michael

    2013-07-01

    Hyponatraemia is a serious adverse event commonly reported in elderly people treated with serotonergic antidepressants. The mechanism, incidence and risk factors for antidepressant induced hyponatraemia are not fully understood. In a retrospective chart analysis, depressed patients aged >63 years were investigated for change in serum sodium levels between two time points, separated by a median period of 45.5 days, with the first specimen taken prior to treatment. Patients were grouped into three cohorts; treated with an SSRI or SNRI (n=77), treated with an antidepressant other than an SSRI or SNRI (n=54) and not treated with an antidepressant (n=128). For change in sodium level between measurements and total number of patients with hyponatraemia, there was no significant difference between cohorts. However, the rate of reduction of serum sodium levels between time points was significantly greater for SSRI and SNRI treated patients (p<0.001) and patients treated with other antidepressants (p=0.03) compared to patients not treated with antidepressants. Moreover, the distribution of values of change in serum sodium was skewed towards reduced serum sodium in patients treated with SSRI or SNRIs (skew -0.43) and patients treated with other antidepressants (skew -0.09) but not for patients without antidepressants (skew 0.25). These data suggest that antidepressant treatment is associated with hyponatraemia affecting a subgroup of individuals only. Generalised linear modelling showed that the risk of hyponatraemia increases with increased age, female gender, and particularly the antidepressant agents sertraline and escitalopram. The findings are of clinical significance as they demonstrate that hyponatraemia can occur rapidly with antidepressants, and SSRI/SNRI medications induce more rapid changes. They support the use of electrolyte monitoring early in antidepressant treatment in patients receiving antidepressants.

  5. International Study to Predict Optimized Treatment for Depression (iSPOT-D), a randomized clinical trial: rationale and protocol.

    PubMed

    Williams, Leanne M; Rush, A John; Koslow, Stephen H; Wisniewski, Stephen R; Cooper, Nicholas J; Nemeroff, Charles B; Schatzberg, Alan F; Gordon, Evian

    2011-01-05

    Clinically useful treatment moderators of Major Depressive Disorder (MDD) have not yet been identified, though some baseline predictors of treatment outcome have been proposed. The aim of iSPOT-D is to identify pretreatment measures that predict or moderate MDD treatment response or remission to escitalopram, sertraline or venlafaxine; and develop a model that incorporates multiple predictors and moderators. The International Study to Predict Optimized Treatment - in Depression (iSPOT-D) is a multi-centre, international, randomized, prospective, open-label trial. It is enrolling 2016 MDD outpatients (ages 18-65) from primary or specialty care practices (672 per treatment arm; 672 age-, sex- and education-matched healthy controls). Study-eligible patients are antidepressant medication (ADM) naïve or willing to undergo a one-week wash-out of any non-protocol ADM, and cannot have had an inadequate response to protocol ADM. Baseline assessments include symptoms; distress; daily function; cognitive performance; electroencephalogram and event-related potentials; heart rate and genetic measures. A subset of these baseline assessments are repeated after eight weeks of treatment. Outcomes include the 17-item Hamilton Rating Scale for Depression (primary) and self-reported depressive symptoms, social functioning, quality of life, emotional regulation, and side-effect burden (secondary). Participants may then enter a naturalistic telephone follow-up at weeks 12, 16, 24 and 52. The first half of the sample will be used to identify potential predictors and moderators, and the second half to replicate and confirm. First enrolment was in December 2008, and is ongoing. iSPOT-D evaluates clinical and biological predictors of treatment response in the largest known sample of MDD collected worldwide. International Study to Predict Optimised Treatment - in Depression (iSPOT-D) ClinicalTrials.gov Identifier: NCT00693849. URL: http://clinicaltrials.gov/ct2/show/NCT00693849?term

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Rosenblat, Joshua D; Kakar, Ron

    2016-01-01

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

  8. Serotonergic system antagonists target breast tumor initiating cells and synergize with chemotherapy to shrink human breast tumor xenografts

    PubMed Central

    Gwynne, William D; Hallett, Robin M; Girgis-Gabardo, Adele; Bojovic, Bojana; Dvorkin-Gheva, Anna; Aarts, Craig; Dias, Kay; Bane, Anita; Hassell, John A

    2017-01-01

    Breast tumors comprise an infrequent tumor cell population, termed breast tumor initiating cells (BTIC), which sustain tumor growth, seed metastases and resist cytotoxic therapies. Hence therapies are needed to target BTIC to provide more durable breast cancer remissions than are currently achieved. We previously reported that serotonergic system antagonists abrogated the activity of mouse BTIC resident in the mammary tumors of a HER2-overexpressing model of breast cancer. Here we report that antagonists of serotonin (5-hydroxytryptamine; 5-HT) biosynthesis and activity, including US Federal Food and Drug Administration (FDA)-approved antidepressants, targeted BTIC resident in numerous breast tumor cell lines regardless of their clinical or molecular subtype. Notably, inhibitors of tryptophan hydroxylase 1 (TPH1), required for 5-HT biosynthesis in select non-neuronal cells, the serotonin reuptake transporter (SERT) and several 5-HT receptors compromised BTIC activity as assessed by functional sphere-forming assays. Consistent with these findings, human breast tumor cells express TPH1, 5-HT and SERT independent of their molecular or clinical subtype. Exposure of breast tumor cells ex vivo to sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI), reduced BTIC frequency as determined by transplanting drug-treated tumor cells into immune-compromised mice. Moreover, another SSRI (vilazodone; Viibryd) synergized with chemotherapy to shrink breast tumor xenografts in immune-compromised mice by inhibiting tumor cell proliferation and inducing their apoptosis. Collectively our data suggest that antidepressants in combination with cytotoxic anticancer therapies may be an appropriate treatment regimen for testing in clinical trials. PMID:28404880

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

    PubMed

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

    2016-08-01

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

  10. Management strategies for premenstrual syndrome/premenstrual dysphoric disorder.

    PubMed

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

    2008-07-01

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

  11. 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.

  12. Exogenous daytime melatonin modulates response of adolescent mice in a repeated unpredictable stress paradigm.

    PubMed

    Onaolapo, Adejoke Yetunde; Adebayo, Ajibola Nurudeen; Onaolapo, Olakunle James

    2017-02-01

    The immediate and short-term behavioural and physiological implications of exposure to stressful scenarios in the adolescent period are largely unknown; however, increases in occurrence of stress-related physiological and psychological disorders during puberty highlight the need to study substances that may modulate stress reactivity during a crucial stage of maturation. Seven groups of mice (12-15 g each) were administered distilled water (DW) (non-stressed and stressed controls), sertraline (10 mg/kg), diazepam (2 mg/kg) or one of three doses of melatonin (5, 10 and 15 mg/kg). Mice were exposed to 30 min of chronic mild stress (25 min of cage shaking, cage tilting, handling and 5 min of forced swimming in tepid warm water at 25 °C, in a random order) after administration of DW or drugs, daily for 21 days. Behavioural assessments were conducted on day 1 and day 21 (after which mice were sacrificed, blood taken for estimation of corticosterone levels and brain homogenates used for estimation of antioxidant activities). Administration of melatonin resulted in an increase in horizontal locomotion and self-grooming, while rearing showed a time-dependent increase, compared to non-stress and stress controls. Working memory improved with increasing doses of melatonin (compared to controls and diazepam); in comparison to setraline however, working memory decreased. A dose-related anxiolytic effect is seen when melatonin is compared to non-stressed and stressed controls. Melatonin administration reduced the systemic/oxidant response to repeated stress. Administration of melatonin in repeatedly stressed adolescent mice was associated with improved central excitation, enhancement of working memory, anxiolysis and reduced systemic response to stress.

  13. [Clinical observation on the therapeutic effect of electroacupuncture combined with cupping on post-stroke fatigue].

    PubMed

    Zhou, Yuan; Zhou, Guo-Ying; Li, Shao-Kun; Jin, Jian-Hong

    2010-10-01

    To observe the therapeutic effect of electroacupuncture (EA) combined with cupping at the lumbo-back on post-stroke fatigue. A total of 128 cases of post-stroke fatigue patients were randomly divided into EA + cupping group and medication group, with 64 cases in each group. EA (20 Hz, 2 mA) was applied to Baihui (GV 20), Yintang (EX-HN 3), Shuigou (GV 26), Hegu (LI 4), Zusanli (ST 36), Sanyinjiao (SP 6), and Taichong (LR 3) for 30 min, once daily for 30 times, and cupping was applied at the patient's lumbo-back region once every two days, and continuously for 5 weeks. Patients of medication group were ordered to take compound aminobutyric acid vitamin E capsule (20 mg, t. i.d, po), magnesium gluconate solution (10 mL, t. i. d, po), sertraline hydrochloridetablet (50 mg, qd, po) for 5 weeks. The Stroke Specific Quality of Life Scale (SS-QOL) was used to evaluate the patients' energy state. After the treatment, the energy scores of SS-QOL of both EA + cupping and medication groups were increased significantly in comparison with the pre-treatment in each group (P < 0.05), and that of the EA+ cupping group was significantly higher than the score of the medication group (P < 0.05). Of the two 64 cases in EA + cupping group and medication group, 42 and 23 were recovered basically, 13 and 13 experienced marked improvement, 7 and 18 were effective, 2 and 10 failed in the treatment, with the effective rates being 96.87% and 84.37% respectively. The effective rate of EA + cupping group was obviously higher than that of medication group (P < 0.01). EA+ cupping at the lumbo-back can effectively relieve fatigue of post-stroke patients, and its therapeutic effect is superior to medication.

  14. Decreased functional connectivity to posterior cingulate cortex in major depressive disorder.

    PubMed

    Yang, Rui; Gao, Chengge; Wu, Xiaoping; Yang, Junle; Li, Shengbin; Cheng, Hu

    2016-09-30

    The default mode network (DMN) and its interaction with other key networks such as the salience network and executive network are keys to understand psychiatric and neurological disorders including major depressive disorder (MDD). In this study, we combined independent component analysis and seed based connectivity analysis to study the posterior default mode network between 20 patients with MDD and 25 normal controls, as well as pre-treatment and post-treatment conditions of the patients. Both correlated and anti-correlated networks centered at the posterior cingulate cortex (PCC) were examined (PCC+ and PCC-). Our results showed aberrant functional connectivity of the PCC+ and PCC- networks between patients and normal controls. Specifically, normal controls exhibited significantly higher connectivity between the PCC and frontal/temporal regions for the PCC+ network and stronger connectivity strength between the PCC and the insula/middle frontal cortex for the PCC- network. The overall connectivity strength of the PCC+ and PCC- networks was also significantly lower in MDD. Because the PCC is a hub in the DMN that interacts with other networks, our result suggested a stronger interaction between the DMN and the salience network but a weak interaction between the DMN and the executive network in MDD. The treatment using sertraline did increase the functional connectivity strength, especially in the PCC+ network. Despite a large inter-subject variability in the overall connectivity strengths and change of the PCC network in response to the treatment, a high correlation between change of connectivity strength and the Hamilton depression score was observed for both the PCC+ and PCC- network. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  17. Unusual way of suicide by carbon monoxide. Case Report.

    PubMed

    Zelený, Michal; Pivnička, Jan; Šindler, Martin; Kukleta, Pavel

    2015-01-01

    Authors discuss the case of a suicide of a 29-year-old man caused by carbon monoxide (CO) intoxication. What the authors found interesting was the unusual way of committing suicide that required good technical skills and expert knowledge. The level of carboxyhemoglobin (COHb) in the blood of the deceased man was routinely determined by the modified method by Blackmoore (1970), using gas chromatography/thermal conductivity detection. The level of saturation of the hemoglobin by CO in the collected blood sample is determined relatively to the same sample saturated to 100%. In the blood sample of the deceased man the lethal concentration of COHb of 76.5% was determined. Within the following examinations the blood alcohol concentration of 0.05 g.kg(-1) was determined. Further analysis revealed traces of sertraline, its metabolite N-desmethylsertraline, omeprazole and caffeine in the liver tissue, traces of N-desmethylsertraline, ibuprofen and caffeine in urine sample, and only traces of caffeine in the stomach content and blood samples were proved. To commit suicide the man used a sophisticated double container-system equipped with a timer for controlled generation of CO based on the chemical reaction of concentrated sulphuric acid and formic acid. The used timer was set by an electromechanical timer switch that triggered the fatal reaction of the acids while the man was sleeping. The authors discuss an unusual case of suicide by CO intoxication rarely seen in the area of forensic medicine and toxicology that is specific due to its sophisticated way of execution.

  18. Results of the Inclusion of New Medications in the Obligatory Health System Plan in Colombia, 2012-2013.

    PubMed

    Machado-Alba, Jorge Enrique; Torres, Daniel; Portilla, Alfredo; Felipe Ruiz, Andrés

    2015-12-01

    The Colombian health care system has had a plan with limited benefits, but since 2012, 57 drugs have been added to this plan. The objective of this article was to describe the trends of utilization and costs of medications covered by the Agreement 029/2011 and compare them with those that were contained in the benefits plan. This descriptive study involved a group of 3.8 million people affiliated with the Colombian health care system, in 110 cities from July 2011 until June 2013. The variables were new medications that were included, comparing them with homologous medications that were already in the plan, age, sex, dispensed quantities, and monthly billing. The study established the defined daily dosage per thousand inhabitants per day, cost per thousand inhabitants per day, cost per capita, and the rate of adoption or replacement medicines. The growth in the consumption of new medications was 830.0%. The defined daily dosage per thousand inhabitants per day grew from 4.3 to 42.9, with an increase of 905.5%. Medications with the highest growth were losartan/hydrochlorothiazide (15,723%), esomeprazole (4193%), atorvastatin (1402%), and sertraline (298%). There was an increase of US $16.40 in the cost per thousand inhabitants per day, which is equivalent to an increase of 61.7% and represents a rise of US $0.49 in cost per capita per month. The consumption behavior of new medications and the economic implications for Colombia can be demonstrated. In particular, the growth in the consumption of medications for chronic diseases can be seen, which would represent an increase of US $22.6 million per month to the entire population of the country. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  19. Post-traumatic stress disorder

    PubMed Central

    2010-01-01

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

  20. Variability in P-Glycoprotein Inhibitory Potency (IC50) Using Various in Vitro Experimental Systems: Implications for Universal Digoxin Drug-Drug Interaction Risk Assessment Decision Criteria

    PubMed Central

    Bentz, Joe; O’Connor, Michael P.; Bednarczyk, Dallas; Coleman, JoAnn; Lee, Caroline; Palm, Johan; Pak, Y. Anne; Perloff, Elke S.; Reyner, Eric; Balimane, Praveen; Brännström, Marie; Chu, Xiaoyan; Funk, Christoph; Guo, Ailan; Hanna, Imad; Herédi-Szabó, Krisztina; Hillgren, Kate; Li, Libin; Hollnack-Pusch, Evelyn; Jamei, Masoud; Lin, Xuena; Mason, Andrew K.; Neuhoff, Sibylle; Patel, Aarti; Podila, Lalitha; Plise, Emile; Rajaraman, Ganesh; Salphati, Laurent; Sands, Eric; Taub, Mitchell E.; Taur, Jan-Shiang; Weitz, Dietmar; Wortelboer, Heleen M.; Xia, Cindy Q.; Xiao, Guangqing; Yabut, Jocelyn; Yamagata, Tetsuo; Zhang, Lei

    2013-01-01

    A P-glycoprotein (P-gp) IC50 working group was established with 23 participating pharmaceutical and contract research laboratories and one academic institution to assess interlaboratory variability in P-gp IC50 determinations. Each laboratory followed its in-house protocol to determine in vitro IC50 values for 16 inhibitors using four different test systems: human colon adenocarcinoma cells (Caco-2; eleven laboratories), Madin-Darby canine kidney cells transfected with MDR1 cDNA (MDCKII-MDR1; six laboratories), and Lilly Laboratories Cells—Porcine Kidney Nr. 1 cells transfected with MDR1 cDNA (LLC-PK1-MDR1; four laboratories), and membrane vesicles containing human P-glycoprotein (P-gp; five laboratories). For cell models, various equations to calculate remaining transport activity (e.g., efflux ratio, unidirectional flux, net-secretory-flux) were also evaluated. The difference in IC50 values for each of the inhibitors across all test systems and equations ranged from a minimum of 20- and 24-fold between lowest and highest IC50 values for sertraline and isradipine, to a maximum of 407- and 796-fold for telmisartan and verapamil, respectively. For telmisartan and verapamil, variability was greatly influenced by data from one laboratory in each case. Excluding these two data sets brings the range in IC50 values for telmisartan and verapamil down to 69- and 159-fold. The efflux ratio-based equation generally resulted in severalfold lower IC50 values compared with unidirectional or net-secretory-flux equations. Statistical analysis indicated that variability in IC50 values was mainly due to interlaboratory variability, rather than an implicit systematic difference between test systems. Potential reasons for variability are discussed and the simplest, most robust experimental design for P-gp IC50 determination proposed. The impact of these findings on drug-drug interaction risk assessment is discussed in the companion article (Ellens et al., 2013) and recommendations

  1. 29 Year Old Man with Multiple Sclerosis and Schizophrenia: A Case Report.

    PubMed

    Noorani, Nahid; Hadi, Fateme; Ahmadkhaniha, Hamid Reza

    2016-12-01

    Multiple sclerosis (MS) is the most common debilitating neurological disease that affects adults, whether young adults or middle-aged. Although, most attention is toward the neurological signs of the disease, the neuropsychiatric signs are not uncommon. This case report presents a 29 year old male with a record of obsessive-compulsive disorder (OCD) without psychotic disorder, which coincides with the diagnosis MS, has been stricken to auditory hallucinations and reference delusion. The patient received some antipsychotic drugs such as Haloperidol and Perphenazine irregularly, but any psychotic signs of the patient were never in control. During this period he had several active episodes of MS disease, wherein the symptoms had subsided due to hospitalization and received corticosteroids pulse. The first time the patient was submitted to the emergency unit of Rasoul Akram Hospital, there was the possibility of schizophrenia which was confirmed in subsequent visits. The signs of the patient were not controllable for a long time and finally fully controlled by a combination of Aripiprazole (abilizol), Risperidone and Sertraline, and currently, for almost 3 years, both psychotic symptoms and MS disease have been under control. Our patient seems to catch the MS disease and schizophrenia simultaneously. There was no relation between MS and psychosis episodes and the MS attacks. Since the onset the patient had several acute MS attacks of MS, and hospitalization several times. These findings and characteristics regarding our patient made him completely different from other reported cases of MS along with neuropsychiatric signs which may help doctors in diagnosis and managment of similar cases.

  2. Cost-utility evaluation of vortioxetine in patients with Major Depressive Disorder experiencing inadequate response to alternative antidepressants in the United Kingdom.

    PubMed

    Young, A H; Evitt, L; Brignone, M; Diamand, F; Atsou, K; Campbell, R; Cure, S; Danchenko, N

    2017-08-15

    Patients frequently require several lines of therapy for treatment of major depressive episodes. This economic analysis details the management of patients who responded inadequately due to lack of efficacy or intolerability to two previous antidepressants in the UK. The model included a decision tree and a Markov component. Health states considered in the decision tree were remission, response, no response, withdrawal due to adverse events, relapse, recovery, and recurrence. The time horizon was 24 months. Patients were on third-line treatment for up to a 3-month acute phase and a 6-month maintenance phase. As third-line efficacy data were not available, inputs were calculated by adjusting original second-line data to third-line based on proportionate reductions observed in STAR*D. Equivalent efficacy was assumed for all comparators. Healthcare resource use and utilities were based on UK estimates. Vortioxetine was a cost-effective treatment option at a threshold of £20,000/QALY vs. escitalopram, citalopram, sertraline, and was associated with more health benefits, less costs (was dominant) versus relevant third-line comparators venlafaxine and duloxetine. Agomelatine was found not to be a cost-effective option. The 22-month maintenance phase treatment scenario results were similar to the 6-month base case. Third-line efficacy data were not available. This highlights the need for studies in patients receiving third-line treatment. This model provides an overview for the management of patients receiving third-line treatment where limited evidence currently exists. Vortioxetine, with its novel mechanism of action, is expected to be a dominant treatment option versus relevant comparators in the UK. Copyright © 2017. Published by Elsevier B.V.

  3. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows

    USGS Publications Warehouse

    Schultz, Melissa M.; Painter, Meghan M.; Bartell, Stephen E.; Logue, Amanda; Furlong, Edward T.; Werner, Stephen L.; Schoenfuss, Heiko L.

    2011-01-01

    Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimeplwles promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305 ng/L and 1104 ng/L) and SER (5.2 ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28 ng/L induced vitellogenin in male fish—a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies.

  4. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows

    USGS Publications Warehouse

    Schultz, M.M.; Painter, M.M.; Bartell, S.E.; Logue, A.; Furlong, E.T.; Werner, S.L.; Schoenfuss, H.L.

    2011-01-01

    Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimephales promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305. ng/L and 1104. ng/L) and SER (5.2. ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28. ng/L induced vitellogenin in male fish-a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies. ?? 2011 Elsevier B.V.

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

    PubMed

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

    2014-09-01

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

  6. Development of a flat membrane based device for electromembrane extraction: a new approach for exhaustive extraction of basic drugs from human plasma.

    PubMed

    Huang, Chuixiu; Eibak, Lars Erik Eng; Gjelstad, Astrid; Shen, Xiantao; Trones, Roger; Jensen, Henrik; Pedersen-Bjergaard, Stig

    2014-01-24

    In this work, a single-well electromembrane extraction (EME) device was developed based on a thin (100μm) and flat porous membrane of polypropylene supporting a liquid membrane. The new EME device was operated with a relatively large acceptor solution volume to promote a high recovery. Using this EME device, exhaustive extraction of the basic drugs quetiapine, citalopram, amitriptyline, methadone and sertraline was investigated from both acidified water samples and human plasma. The volume of acceptor solution, extraction time, and extraction voltage were found to be important factors for obtaining exhaustive extraction. 2-Nitrophenyl octyl ether was selected as the optimal organic solvent for the supported liquid membrane. From spiked acidified water samples (600μl), EME was carried out with 600μl of 20mM HCOOH as acceptor solution for 15min and with an extraction voltage of 250V. Under these conditions, extraction recoveries were in the range 89-112%. From human plasma samples (600μl), EME was carried out with 600μl of 20mM HCOOH as acceptor solution for 30min and with an extraction voltage of 300V. Under these conditions, extraction recoveries were in the range of 83-105%. When combined with LC-MS, the new EME device provided linearity in the range 10-1000ng/ml for all analytes (R(2)>0.990). The repeatability at low (10ng/ml), medium (100ng/ml), and high (1000ng/ml) concentration level for all five analytes were less than 10% (RSD). The limits of quantification (S/N=10) were found to be in the range 0.7-6.4ng/ml. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. PRIORITIZING FUTURE RESEACH ON OFF-LABEL PRESCRIBING: RESULTS OF A QUANTITATIVE EVALUATION

    PubMed Central

    Walton, Surrey M.; Schumock, Glen T.; Lee, Ky-Van; Alexander, G. Caleb; Meltzer, David; Stafford, Randall S.

    2015-01-01

    Background Drug use for indications not approved by the Food and Drug Administration exceeds 20% of prescribing. Available compendia indicate that a minority of off-label uses are well supported by evidence. Policy makers, however, lack information to identify where systematic reviews of the evidence or other research would be most valuable. Methods We developed a quantitative model for prioritizing individual drugs for future research on off-label uses. The base model incorporated three key factors, 1) the volume of off-label use with inadequate evidence, 2) safety, and 3) cost and market considerations. Nationally representative prescribing data were used to estimate the number of off-label drug uses by indication from 1/2005 through 6/2007 in the United States, and these indications were then categorized according to the adequacy of scientific support. Black box warnings and safety alerts were used to quantify drug safety. Drug cost, date of market entry, and marketing expenditures were used to quantify cost and market considerations. Each drug was assigned a relative value for each factor, and the factors were then weighted in the final model to produce a priority score. Sensitivity analyses were conducted by varying the weightings and model parameters. Results Drugs that were consistently ranked highly in both our base model and sensitivity analyses included quetiapine, warfarin, escitalopram, risperidone, montelukast, bupropion, sertraline, venlafaxine, celecoxib, lisinopril, duloxetine, trazodone, olanzapine, and epoetin alfa. Conclusion Future research into off-label drug use should focus on drugs used frequently with inadequate supporting evidence, particularly if further concerns are raised by known safety issues, high drug cost, recent market entry, and extensive marketing. Based on quantitative measures of these factors, we have prioritized drugs where targeted research and policy activities have high potential value. PMID:19025425

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

    SciTech Connect

    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

  9. 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.

  10. Assessment of full-scale biological nutrient removal systems upgraded with physico-chemical processes for the removal of emerging pollutants present in wastewaters from Mexico.

    PubMed

    Estrada-Arriaga, Edson Baltazar; Cortés-Muñoz, Juana Enriqueta; González-Herrera, Arturo; Calderón-Mólgora, César Guillermo; de Lourdes Rivera-Huerta, Ma; Ramírez-Camperos, Esperanza; Montellano-Palacios, Leticia; Gelover-Santiago, Silvia Lucila; Pérez-Castrejón, Sara; Cardoso-Vigueros, Lina; Martín-Domínguez, Alejandra; García-Sánchez, Liliana

    2016-11-15

    Two full-scale biological nutrient removal systems upgraded with three physico-chemical processes (coagulation, chemical precipitation, and neutral Fenton) were evaluated in order to determine the removal of emerging pollutants (EPs) present in municipal wastewater from Mexico. Between 41 and 55 EPs were detected in the influents of two wastewater treatment plants (WWTPs), including personal care products (PPCPs), antibiotics, analgesics, antiepileptics, antilipidemics, antihypertensives, antiseptics, stimulants, and hormones. Emerging pollutants were detected at concentrations ranging from 0.69ng/L to 94,600ng/L. High concentrations of emerging pollutants were found during dry season. WWTP 1, integrated by oxidation ditches and UV light lamps, showed removal efficiencies of EPs between 20% and 22%. On the other hand, WWTP 2 consisted of anaerobic/anoxic/aerobic tanks coupled with two disinfection processes; chlorine dioxide and UV light lamps, for which the removal of EPs was significant (up to 80%). The concentrations of emerging pollutants in WWTP 1 effluent was found within a rangesertraline, propranolol, propoxyphene, norverapamil, diazepam, alprazolam, sulfamethoxazole, metoprolol, ofloxacin, norfloxacin, fluoxetine, erythromycin-H2O, diphenhydramine, dehydronifedipine, clarithromycin, hydrochlorothiazide, and albuterol. The application of neutral Fenton reaction as post-treatment for the two effluents from the WWTPs is promising for the removal of emerging pollutants (up to 100

  11. Resveratrol ameliorated the behavioral deficits in a mouse model of post-traumatic stress disorder.

    PubMed

    Zhang, Ze-Shun; Qiu, Zhi-Kun; He, Jia-Li; Liu, Xu; Chen, Ji-Sheng; Wang, Yu-Lu

    2017-10-01

    Post-traumatic stress disorder (PTSD) has become a major psychiatric and neurological issue. Resveratrol is shown to be effective on depression and anxiety. However, the mechanism of anti-PTSD-like effects of resveratrol remains unknown. The present study aimed to explore the possible molecular and cellular mechanisms underlying the anti-PTSD-like effects of resveratrol. Following a 2-day exposure to inescapable electric foot shocks, animals were administered resveratrol (10, 20, and 40mg/kg, i.g.) during the behavioral tests, which included contextual freezing measurement, elevated plus maze test, staircase test, and open field test. Similar to the positive control drug sertraline (15mg/kg, i.g.), the behavioral deficits of stressed mice were blocked by resveratrol (20 and 40mg/kg, i.g.), which reversed the increased freezing time in contextual freezing measurement and the number of rears in the staircase test and blocked the decrease in time and number of entries in open arms in the elevated plus maze test without affecting the locomotor activity in the open field test. In addition, resveratrol (20 and 40mg/kg, i.g.) antagonized the decrease in the levels of progesterone and allopregnanolone in the prefrontal cortex and hippocampus. Furthermore, long-term resveratrol attenuated the dysfunctions of hypothalamic-pituitary-adrenal axis simultaneously. Collectively, the evidence indicated that the anti-PTSD-like effects of resveratrol were associated with the normalization of biosynthesis of neurosteroids in the brain and prevention of the hypothalamic-pituitary-adrenal axis dysfunction. Copyright © 2017. Published by Elsevier Inc.

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

    PubMed

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

    2017-02-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  16. A high throughput screening for TLR3-IRF3 signaling pathway modulators identifies several antipsychotic drugs as TLR inhibitors1

    PubMed Central

    Zhu, Jianzhong; Smith, Kevin; Hsieh, Paishiun N.; Mburu, Yvonne K.; Chattopadhyay, Saurabh; Sen, Ganes C.; Sarkar, Saumendra N.

    2010-01-01

    Toll-like Receptor 3 (TLR3) is one of the major innate immune sensors of double stranded RNA (dsRNA). The signal transduction pathway activated by TLR3, upon binding to dsRNA, leads to the activation of two major transcription factors: NF-κB and IRF3. In an effort to identify specific chemical modulators of TLR3-IRF3 signal transduction pathway we developed a cell-based read out system. Using the interferon stimulated gene 56 (ISG56) promoter driven firefly luciferase gene stably integrated in a TLR3 expressing HEK293 cell line, we were able to generate a cell line where treatment with dsRNA resulted in a dose dependent induction of luciferase activity. A screen of two pharmacologically active compound libraries using this system, identified a number of TLR3-IRF3 signaling pathway modulators. Among them we focused on a subset of inhibitors and characterized their mode of action. Several antipsychotic drugs, such as Sertraline, Trifluoperazine and Fluphenazine were found to be direct inhibitors of the innate immune signaling pathway. These inhibitors also showed the ability to inhibit ISG56 induction mediated by TLR4 and TLR7/8 pathways. Interestingly, they did not show significant effect on TLR3, TLR7 and TLR8 mediated NF-κB activation. Detailed analysis of the signaling pathway indicated that these drugs may be exerting their inhibitory effects on IRF3 via PI3K signaling pathway. The data presented here provides mechanistic explanation of possible anti-inflammatory roles of some antipsychotic drugs. PMID:20382888

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

    PubMed

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

    2017-06-01

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

  18. Impact of materials used in lab and field experiments on the recovery of organic micropollutants

    NASA Astrophysics Data System (ADS)

    Hebig, Klaus; Nödler, Karsten; Licha, Tobias; Scheytt, Traugott

    2015-04-01

    Organic micropollutants are frequently detected in the aquatic environment. There-fore, a large number of field and laboratory studies have been conducted in order to study their fate in the environment. Due to the diversity of chemical properties among these compounds some of them may interact with materials commonly used in field and laboratory studies like tubes, filters, or sample bottles. The aim of our experiment was to study the interaction between those materials and an aqueous solution of 43 widely detected basic, neutral, and acidic organic micropollutants hereby covering a broad range of polarities. Experiments with materials were conducted as a batch study using spiked tap water and for different syringe filters by filtration with subsequent fraction collection. The best recoveries over a wide range of organic compounds were observed for batches in contact with the following materials (in descending order) acryl glass, PTFE, HDPE, and PP. The use of Pharmed©, silicone, NBR70, Tygon©, and LDPE should be avoided. Flexible tubing materials especially influence many of the investigated compounds here. Filtration with most of the tested filter types leads to no significant loss of almost all of the investigated micropollutants. Nonetheless, significant mass losses of some compounds (loratadine, fluoxetine, sertraline, and diuron) were observed during the first mL of the filtration process. No systematic correlation between compound properties, tested materials, and ob-served mass losses could be identified in this study. The behavior of each compound is specific and thus, not predictable. It is therefore suggested to study the interaction of compounds with filters and material prior to the actual experiment or include blank studies.

  19. Pharmacotherapy for anxiety and comorbid alcohol use disorders.

    PubMed

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

    2015-01-20

    anxiety disorders with comorbid alcohol use disorders. Trials assessing drugs administered for the treatment of drinking behaviour, such as naltrexone, disulfiram and acomprosate were not eligible for inclusion in this systematic review. A systematic review is a standardised evaluation of all research studies that address a particular clinical issue.Two review authors independently assessed RCTs for inclusion in the review, collated trial data and assessed trial quality. We contacted investigators to obtain missing data. We calculated categorical and continuous treatment effect estimates and their 95% confidence intervals (CI) for treatment using a random-effects model with effect-size variability expressed using Chi(2) and I(2) heterogeneity statistics. We included five placebo-controlled pharmacotherapy RCTs (with 290 participants) in the review. Most of the trials provided little information on how randomization was performed or on whether both participants and study personnel were blinded to the intervention. Two of the three trials reporting superiority of medication compared with placebo on anxiety symptom outcomes were industry funded. We regarded one trial as being at high risk of bias due to selective reporting.Study participants had Diagnostic and Statistical Manual (DSM) III- and DSM IV-diagnosed alcohol use disorders and post-traumatic stress disorder (two studies), social anxiety disorder (SAD; two studies) or generalized anxiety disorder (GAD; one study). Four trials assessed the efficacy of the selective serotonin re-uptake inhibitors (SSRIs: sertraline, paroxetine); one RCT investigated the efficacy of buspirone, a 5-hydroxytryptamine (5-HT) partial agonist. Treatment duration lasted between eight and 24 weeks. Overall, 70% of participants included in the review were male.There was very low quality evidence for an effect of paroxetine on global clinical response to treatment, as assessed by the Clinical Global Impressions - Improvement scale (CGI

  20. Effect of interventions for major depressive disorder and significant depressive symptoms in patients with diabetes mellitus: a systematic review and meta-analysis.

    PubMed

    van der Feltz-Cornelis, Christina M; Nuyen, Jasper; Stoop, Corinne; Chan, Juliana; Jacobson, Alan M; Katon, Wayne; Snoek, Frank; Sartorius, Norman

    2010-01-01

    Comorbid depression in diabetes is highly prevalent, negatively impacting well-being and diabetes control. How depression in diabetes is best treated is unknown. This systematic review and meta-analysis aims to establish the effectiveness of existing anti-depressant therapies in diabetes. PubMed, Psycinfo, Embase and Cochrane library. Study eligibility criteria, participants, interventions: randomized controlled trials (RCTs) evaluating the outcome of treatment by psychotherapy, pharmacotherapy or collaborative care of depression in persons with Type 1 and Type 2 diabetes mellitus. risk of bias assessment; data extraction. Synthesis methods: data synthesis, random model meta analysis and publication bias analysis. Meta analysis of 14 RCTs with a total of 1724 patients show that treatment is effective in terms of reduction of depressive symptoms: -0.512; 95% CI -0.633 to -0.390. The combined effect of all interventions on clinical impact is moderate, -0.370; 95% CI -0.470 to -0.271; it is large for psychotherapeutic interventions that are often combined with diabetes self management: -0.581; 95% CI -0.770 to -0.391, n=310 and moderate for pharmacological treatment: -0.467; 95% CI -0.665 to -0.270, n=281. Delivery of collaborative care, which provided a stepped care intervention with a choice of starting with psychotherapy or pharmacotherapy, to a primary care population, yielded an effect size of -0.292; 95% CI -0.429 to -0.155, n=1133; indicating the effect size that can be attained on a population scale. Pharmacotherapy and collaborative care aimed at and succeeded in the reduction of depressive symptoms but, apart from sertraline, had no effect on glycemic control. amongst others, the number of RCTs is small. The treatment of depression in people with diabetes is a necessary step, but improvement of the general medical condition including glycemic control is likely to require simultaneous attention to both conditions. Further research is needed. Copyright 2010

  1. A preview of the efficiency of systemic family therapy in treatment of children with posttraumatic stress disorder developed after car accident.

    PubMed

    Stanković, Miodrag; Grbesa, Grozdanko; Kostić, Jelena; Simonović, Maja; Milenković, Tatjana; Visnjić, Aleksandar

    2013-02-01

    Traumatic stress refers to physical and emotional reactions caused by events which represent a life threat or a disturbance of physical and phychological integrity of a child, as well as their parents or gaerdians. Car accidents are the main cause of posttraumatic stress disorder (PTSD) in children. The aim of this study was to preview clinical efficiency of systemic family therapy (SFT) as therapy intervention in treatment of children with posttraumatic stress disorder (PTSD) traumatized in car accident under identical circumstances of exposure. We pointed out the importance of specific family factors (family cohesion and adaptability, emotional reaction of the parents) on PTSD clinical outcome. The sample of this clinical observational study included 7-sixth grade pupiles--5 boys and 2 girls, aged 13. All of the pupils were involved in car accident with one death. Two groups were formed--one group included three children who were involved in 8 SFT sessions together with their families. The second group included 4 children who received an antidepressant sertraline in the period of three months. Two months after the car accident, before the beginning of the therapy, all of the children were the members of rigidly enmeshed family systems, considering the high average cohesion scores and the low average adaptability scores on the FACES III. Three months after the received therapy, having evaluated the results of the therapeutic approaches, we established that the adaptability scores of the families included in the SFT were higher than the scores of the families of the children who received pharmacotherapy with one boy still meeting the criteria for PTSD. Systemic family therapy was efficient in the treatment of children with PTSD, traumatized in car accident. Therapy efficiency was higher when both parents and children were included in SFT than in the case when they were not included in the family therapy. The change in the functioning of the family systems was not

  2. Cauda equina syndrome following an uneventful spinal anesthesia in a patient undergoing drainage of the Bartholin abscess: A case report.

    PubMed

    Merino-Urrutia, Waldo; Villagrán-Schmidt, Milca; Ulloa-Vásquez, Priscilla; Carrasco-Moyano, Rubén; Uribe, Alberto; Stoicea, Nicoleta; Bergese, Sergio D

    2018-05-01

    a prescription for sertraline, clonazepam, pregabalin, paracetamol, and prednisone. The early detection and treatment of complications after neuraxial anesthesia is essential to minimize the risk of permanent damage.

  3. Effect of Vortioxetine vs. Escitalopram on Sexual Functioning in Adults with Well-Treated Major Depressive Disorder Experiencing SSRI-Induced Sexual Dysfunction.

    PubMed

    Jacobsen, Paula L; Mahableshwarkar, Atul R; Chen, Yinzhong; Chrones, Lambros; Clayton, Anita H

    2015-10-01

    Sexual dysfunction is common with serotonergic antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), and does not resolve in most patients. Vortioxetine, an antidepressant with a multimodal mechanism of action, has shown low rates of sexual dysfunction in previous major depressive disorder (MDD) trials. This study compared the effects of vortioxetine and escitalopram on sexual functioning in adults with well-treated MDD experiencing treatment-emergent sexual dysfunction (TESD). Participants treated with, and responding to, citalopram, paroxetine, or sertraline were randomized to switch to either vortioxetine (10/20 mg; n = 225) or escitalopram (10/20 mg; n = 222) for 8 weeks. Sexual function was assessed using the Changes in Sexual Functioning Questionnaire Short Form (CSFQ-14), and antidepressant efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impressions (CGI) scale, and Profile of Mood States brief form (POMS-brief). Safety and tolerability were also assessed. The primary endpoint was change from baseline in the CSFQ-14 total score after 8 weeks of treatment. The MADRS, CGI, and POMS-brief were used to assess antidepressant efficacy. Safety was assessed via adverse events, vital signs, electrocardiograms, laboratory values, weight, and physical examination findings. Vortioxetine showed significantly greater improvements in CSFQ-14 total score (8.8 ± 0.64, mean ± standard error) vs. escitalopram (6.6 ± 0.64; P = 0.013). Benefits vs. escitalopram were significant on four of five dimensions and all three phases of sexual functioning assessed by the CSFQ-14 (P < 0.05). Antidepressant efficacy continued in both groups, with similar, but slight, improvements in MADRS and CGI scores. Vortioxetine and escitalopram had similar clinical efficacy profiles in this study, with safety profiles similar to previous

  4. Persistent Encopresis, Enuresis, and Anxiety in a 7-Year-Old Girl.

    PubMed

    Nelson, Theodora; Chae, Heekyung; Anbar, Ran D; Stein, Martin T

    2017-10-01

    Sonia is a 7-year-old old girl who was referred to the Developmental-Behavioral Pediatrics Clinic by the Pediatric Urology Clinic because of persistent wetting and soiling behaviors. Since age 3 years, she has had a history of encopresis (and wetting) for which she has seen gastroenterology and urology specialists. The mother reports that Sonia has accidents almost daily, and she is not upset when sitting in her urine or feces. She dislikes going into the bathroom or sitting on the toilet by herself. She participated in a behavior modification program associated with the pediatric urology clinic, which helps children learn healthy voiding habits and achieve continence.Sonia also has anxious behaviors. She bites her nails and chews on her hair or shirt. She is afraid of small spaces such as those between the bed and the wall and needs to have stuffed animals cover them. Other instances that trigger her anxious behaviors include loud noises, having a substitute teacher, being separated from her mother, and going to certain bathrooms or new places. She also has severe tantrums, which involve throwing and breaking objects, kicking, and hitting her head against doors.A cognitive behavioral therapy program was recommended to target anxiety symptoms, in addition to timed toileting after meals and polyethylene glycol. At a clinic visit several months later, symptoms of anxiety, encopresis, and enuresis persisted. Cognitive behavior therapy was continued and sertraline 25 mg was prescribed for anxiety. In addition, she was referred to a pediatrician who specializes in relaxation techniques and hypnotherapy.Sonia showed modest improvement with these interventions. There were fewer episodes of angry outbursts and a decrease in soiling and wetting, but at times, but she continued to have intermittent periods of wetting and soiling and fear of going to the bathroom by herself persisted.(This Challenging Case extends observations reviewed in a previous Challenging Case: J Dev

  5. Prediction of Treatment Outcome in Patients with Obsessive-Compulsive Disorder with Low-Resolution Brain Electromagnetic Tomography: A Prospective EEG Study.

    PubMed

    Krause, Daniela; Folkerts, Malte; Karch, Susanne; Keeser, Daniel; Chrobok, Agnieszka I; Zaudig, Michael; Hegerl, Ulrich; Juckel, Georg; Pogarell, Oliver

    2015-01-01

    The issue of predicting treatment response and identifying, in advance, which patient will profit from treating obsessive-compulsive disorder (OCD) seems to be an elusive goal. This prospective study investigated brain electric activity [using Low-Resolution Brain Electromagnetic Tomography (LORETA)] for the purpose of predicting response to treatment. Forty-one unmedicated patients with a DSM-IV diagnosis of OCD were included. A resting 32-channel EEG was obtained from each participant before and after 10 weeks of standardized treatment with sertraline and behavioral therapy. LORETA was used to localize the sources of brain electrical activity. At week 10, patients were divided into responders and non-responders (according to a reduction of symptom severity >50% on the Y-BOCS). LORETA analysis revealed that at baseline responders showed compared to non-responders a significantly lower brain electric activity within the beta 1 (t = 2.86, p < 0.05), 2 (t = 2.81, p < 0.05), and 3 (t = 2.76, p < 0.05) frequency bands and ROI analysis confirmed a reduced activity in alpha 2 (t = 2.06, p < 0.05) in the anterior cingulate cortex (ACC). When baseline LORETA data were compared to follow-up data, the analysis showed in the responder group a significantly lower brain electrical resting activity in the beta 1 (t = 3.17. p < 0.05) and beta 3 (t = 3.11. p < 0.05) frequency bands and equally for the ROI analysis of the orbitofrontal cortex (OFC) in the alpha 2 (t = 2.15. p < 0.05) frequency band. In the group of non-responders the opposite results were found. In addition, a positive correlation between frequency alpha 2 (rho = 0.40, p = 0.010), beta 3 (rho = 0.42, p = 0.006), delta (rho = 0.33, p = 0.038), theta (rho = 0.34, p = 0.031), alpha 1 (rho = 0.38, p = 0.015), and beta1 (rho = 0.34, p = 0.028) of the OFC and the bands delta (rho = 0.33, p = 0.035), alpha 1 (rho = 0.36, p = 0.019), alpha 2 (rho = 0.34, p = 0.031), and beta 3 (rho = 0.38, p = 0.015) of the ACC with a

  6. Prediction of Treatment Outcome in Patients with Obsessive-Compulsive Disorder with Low-Resolution Brain Electromagnetic Tomography: A Prospective EEG Study

    PubMed Central

    Krause, Daniela; Folkerts, Malte; Karch, Susanne; Keeser, Daniel; Chrobok, Agnieszka I.; Zaudig, Michael; Hegerl, Ulrich; Juckel, Georg; Pogarell, Oliver

    2016-01-01

    The issue of predicting treatment response and identifying, in advance, which patient will profit from treating obsessive-compulsive disorder (OCD) seems to be an elusive goal. This prospective study investigated brain electric activity [using Low-Resolution Brain Electromagnetic Tomography (LORETA)] for the purpose of predicting response to treatment. Forty-one unmedicated patients with a DSM-IV diagnosis of OCD were included. A resting 32-channel EEG was obtained from each participant before and after 10 weeks of standardized treatment with sertraline and behavioral therapy. LORETA was used to localize the sources of brain electrical activity. At week 10, patients were divided into responders and non-responders (according to a reduction of symptom severity >50% on the Y-BOCS). LORETA analysis revealed that at baseline responders showed compared to non-responders a significantly lower brain electric activity within the beta 1 (t = 2.86, p < 0.05), 2 (t = 2.81, p < 0.05), and 3 (t = 2.76, p < 0.05) frequency bands and ROI analysis confirmed a reduced activity in alpha 2 (t = 2.06, p < 0.05) in the anterior cingulate cortex (ACC). When baseline LORETA data were compared to follow-up data, the analysis showed in the responder group a significantly lower brain electrical resting activity in the beta 1 (t = 3.17. p < 0.05) and beta 3 (t = 3.11. p < 0.05) frequency bands and equally for the ROI analysis of the orbitofrontal cortex (OFC) in the alpha 2 (t = 2.15. p < 0.05) frequency band. In the group of non-responders the opposite results were found. In addition, a positive correlation between frequency alpha 2 (rho = 0.40, p = 0.010), beta 3 (rho = 0.42, p = 0.006), delta (rho = 0.33, p = 0.038), theta (rho = 0.34, p = 0.031), alpha 1 (rho = 0.38, p = 0.015), and beta1 (rho = 0.34, p = 0.028) of the OFC and the bands delta (rho = 0.33, p = 0.035), alpha 1 (rho = 0.36, p = 0.019), alpha 2 (rho = 0.34, p = 0.031), and beta 3 (rho = 0.38, p = 0.015) of the ACC with a

  7. Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports.

    PubMed

    Sharma, Tarang; Guski, Louise Schow; Freund, Nanna; Gøtzsche, Peter C

    2016-01-27

    To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.Design Systematic review and meta-analysis. Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia. Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly's website. Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms. Two researchers extracted data independently; the outcomes were meta-analysed by Peto's exact method (fixed effect model). We included 70 trials (64,381 pages of clinical study reports) with 18,526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly's website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was incomplete. Because of the shortcomings identified and having only partial access to appendices with no access to case report forms, the harms

  8. Rapid analysis of pharmaceuticals and personal care products in fish plasma micro-aliquots using liquid chromatography tandem mass spectrometry.

    PubMed

    Chen, Fangfang; Gong, Zhiyuan; Kelly, Barry C

    2015-02-27

    A sensitive analytical method based on liquid-liquid extraction (LLE) and liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed for rapid analysis of 11 pharmaceuticals and personal care products (PPCPs) in fish plasma micro-aliquots (∼20μL). Target PPCPs included, bisphenol A, carbamazepine, diclofenac, fluoxetine, gemfibrozil, ibuprofen, naproxen, risperidone, sertraline, simvastatin and triclosan. A relatively quicker and cheaper LLE procedure exhibited comparable analyte recoveries with solid-phase extraction. Rapid separation and analysis of target compounds in fish plasma extracts was achieved by employing a high efficiency C-18 HPLC column (Agilent Poroshell 120 SB-C18, 2.1mm×50mm, 2.7μm) and fast polarity switching, enabling effective monitoring of positive and negative ions in a single 9min run. With the exception of bisphenol A, which exhibited relatively high background contamination, method detection limits of individual PPCPs ranged between 0.15 and 0.69pg/μL, while method quantification limits were between 0.05 and 2.3pg/μL. Mean matrix effect (ME) values ranged between 65 and 156% for the various target analytes. Isotope dilution quantification using isotopically labelled internal surrogates was utilized to correct for signal suppression or enhancement and analyte losses during sample preparation. The method was evaluated by analysis of 20μL plasma micro-aliquots collected from zebrafish (Danio rerio) from a laboratory bioaccumulation study, which included control group fish (no exposure), as well as fish exposed to environmentally relevant concentrations of PPCPs. Using the developed LC-MS/MS based method, concentrations of the studied PPCPs were consistently detected in the low pg/μL (ppb) range. The method may be useful for investigations requiring fast, reliable concentration measurements of PPCPs in fish plasma. In particular, the method may be applicable for in situ contaminant biomonitoring, as well as

  9. 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

  10. A 12-Month Open-Label Extension Study of the Safety and Tolerability of Lisdexamfetamine Dimesylate for Major Depressive Disorder in Adults.

    PubMed

    Richards, Cynthia; Iosifescu, Dan V; Mago, Rajnish; Sarkis, Elias; Geibel, Brooke; Dauphin, Matthew; McIntyre, Roger S; Weisler, Richard; Brawman-Mintzer, Olga; Gu, Joan; Madhoo, Manisha

    2018-06-16

    Psychostimulant augmentation is considered a potential treatment strategy for individuals with major depressive disorder who do not adequately respond to antidepressant monotherapy. The primary objective of this 12-month open-label extension study was to evaluate the safety and tolerability of lisdexamfetamine dimesylate (LDX) as augmentation therapy to an antidepressant in adults with major depressive disorder. Eligible adults who completed 1 of 3 short-term antecedent LDX augmentation of antidepressant monotherapy studies were treated with dose-optimized LDX (20-70 mg) for up to 52 weeks while continuing on the index antidepressant (escitalopram, sertraline, venlafaxine extended-release, or duloxetine) assigned during the antecedent short-term studies. Safety and tolerability assessments included the occurrence of treatment-emergent adverse events and vital sign changes. All 3 antecedent studies failed to meet the prespecified primary efficacy endpoint, so this open-label study was terminated early. Headache (15.5% [241/1559]), dry mouth (13.6% [212/1559]), insomnia (13.1% [204/1559]), and decreased appetite (12.1% [189/1559]) were the most frequently reported treatment-emergent adverse events. The greatest mean ± SD increases observed for systolic and diastolic blood pressure and for pulse were 2.6 ± 10.85 and 1.7 ± 7.94 mm Hg and 6.9 ± 10.27 bpm, respectively. Monitoring determined that less than 1% of participants experienced potentially clinically important changes in systolic blood pressure (10 [0.6%]), diastolic blood pressure (8 [0.5%]), or pulse (6 [0.4%]). The overall safety and tolerability of long-term LDX augmentation of antidepressant monotherapy was consistent with the profiles of the short-term antecedent studies, with no evidence of new safety signals.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and

  11. Magnetic Resonance Imaging Measures of Brain Structure to Predict Antidepressant Treatment Outcome in Major Depressive Disorder.

    PubMed

    Korgaonkar, Mayuresh S; Rekshan, William; Gordon, Evian; Rush, A John; Williams, Leanne M; Blasey, Christine; Grieve, Stuart M

    2015-01-01

    Less than 50% of patients with Major Depressive Disorder (MDD) reach symptomatic remission with their initial antidepressant medication (ADM). There are currently no objective measures with which to reliably predict which individuals will achieve remission to ADMs. 157 participants with MDD from the International Study to Predict Optimized Treatment in Depression (iSPOT-D) underwent baseline MRIs and completed eight weeks of treatment with escitalopram, sertraline or venlafaxine-ER. A score at week 8 of 7 or less on the 17 item Hamilton Rating Scale for Depression defined remission. Receiver Operator Characteristics (ROC) analysis using the first 50% participants was performed to define decision trees of baseline MRI volumetric and connectivity (fractional anisotropy) measures that differentiated non-remitters from remitters with maximal sensitivity and specificity. These decision trees were tested for replication in the remaining participants. Overall, 35% of all participants achieved remission. ROC analyses identified two decision trees that predicted a high probability of non-remission and that were replicated: 1. Left middle frontal volume < 14 · 8 mL & right angular gyrus volume > 6 · 3 mL identified 55% of non-remitters with 85% accuracy; and 2. Fractional anisotropy values in the left cingulum bundle < 0 · 63, right superior fronto-occipital fasciculus < 0 · 54 and right superior longitudinal fasciculus < 0 · 50 identified 15% of the non-remitters with 84% accuracy. All participants who met criteria for both decision trees were correctly identified as non-remitters. Pretreatment MRI measures seem to reliably identify a subset of patients who do not remit with a first step medication that includes one of these commonly used medications. Findings are consistent with a neuroanatomical basis for non-remission in depressed patients. Brain Resource Ltd is the sponsor for the iSPOT-D study (NCT00693849).

  12. Effect of mirtazapine versus selective serotonin reuptake inhibitors on benzodiazepine use in patients with major depressive disorder: a pragmatic, multicenter, open-label, randomized, active-controlled, 24-week trial.

    PubMed

    Hashimoto, Tasuku; Shiina, Akihiro; Hasegawa, Tadashi; Kimura, Hiroshi; Oda, Yasunori; Niitsu, Tomihisa; Ishikawa, Masatomo; Tachibana, Masumi; Muneoka, Katsumasa; Matsuki, Satoshi; Nakazato, Michiko; Iyo, Masaomi

    2016-01-01

    This study aimed to evaluate whether selecting mirtazapine as the first choice for current depressive episode instead of selective serotonin reuptake inhibitors (SSRIs) reduces benzodiazepine use in patients with major depressive disorder (MDD). We concurrently examined the relationship between clinical responses and serum mature brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF. We conducted an open-label randomized trial in routine psychiatric practice settings. Seventy-seven MDD outpatients were randomly assigned to the mirtazapine or predetermined SSRIs groups, and investigators arbitrarily selected sertraline or paroxetine. The primary outcome was the proportion of benzodiazepine users at weeks 6, 12, and 24 between the groups. We defined patients showing a ≥50 % reduction in Hamilton depression rating scale (HDRS) scores from baseline as responders. Blood samples were collected at baseline, weeks 6, 12, and 24. Sixty-five patients prescribed benzodiazepines from prescription day 1 were analyzed for the primary outcome. The percentage of benzodiazepine users was significantly lower in the mirtazapine than in the SSRIs group at weeks 6, 12, and 24 (21.4 vs. 81.8 %; 11.1 vs. 85.7 %, both P  < 0.001; and 12.5 vs. 81.8 %, P  = 0.0011, respectively). No between-group difference was observed in HDRS score changes. Serum proBDNF levels were significantly decreased ( χ 2  = 8.5, df  = 3, P  = 0.036) and serum mature BDNF levels were temporarily significantly decreased ( F  = 3.5, df  = 2.4, P  = 0.027) in the responders of both groups at week 24. This study demonstrated mirtazapine as the first-choice antidepressant for current depressive episodes may reduce benzodiazepine use in patients with MDD. Trial registration UMIN000004144. Registered 2nd September 2010. The date of enrolment of the first participant to the trial was 24th August 2010. This study was retrospectively registered 9 days after the first participant was

  13. Differences in rates of switchbacks after switching from branded to authorized generic and branded to generic drug products: cohort study

    PubMed Central

    Sarpatwari, Ameet; Dejene, Sara; Khan, Nazleen F; Lii, Joyce; Rogers, James R; Dutcher, Sarah K; Raofi, Saeid; Bohn, Justin; Connolly, John; Fischer, Michael A; Kesselheim, Aaron S; Gagne, Joshua J

    2018-01-01

    Abstract Objectives To compare rates of switchbacks to branded drug products for patients switched from branded to authorized generic drug products, which have the same active ingredients, appearance, and excipients as the branded product, with patients switched from branded to generic drug products, which have the same active ingredients as the branded product but may differ in appearance and excipients. Design Observational cohort study. Setting Private (a large commercial health plan) and public (Medicaid) insurance programs in the US. Participants Beneficiaries of a large US commercial health insurer between 2004 and 2013 (primary cohort) and Medicaid beneficiaries between 2000 and 2010 (replication cohort). Main outcome measures Patients taking branded products for one of the study drugs (alendronate tablets, amlodipine tablets, amlodipine-benazepril capsules, calcitonin salmon nasal spray, escitalopram tablets, glipizide extended release tablets, quinapril tablets, and sertraline tablets) were identified when they switched to an authorized generic or a generic drug product after the date of market entry of generic drug products. These patients were followed for switchbacks to the branded drug product in the year after their switch to an authorized generic or a generic drug product. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals after adjusting for demographics, including age, sex, and calendar year. Inverse variance meta-analysis was used to pool adjusted hazard ratios across all drug products. Results A total of 94 909 patients switched from branded to authorized generic drug products and 116 017 patients switched from branded to generic drug products and contributed to the switchback analysis. Unadjusted incidence rates of switchback varied across drug products, ranging from a low of 3.8 per 100 person years (for alendronate tablets) to a high of 17.8 per 100 person years (for amlodipine

  14. Brain imaging predictors and the international study to predict optimized treatment for depression: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Approximately 50% of patients with major depressive disorder (MDD) do not respond optimally to antidepressant treatments. Given this is a large proportion of the patient population, pretreatment tests that predict which patients will respond to which types of treatment could save time, money and patient burden. Brain imaging offers a means to identify treatment predictors that are grounded in the neurobiology of the treatment and the pathophysiology of MDD. Methods/Design The international Study to Predict Optimized Treatment in Depression is a multi-center, parallel model, randomized clinical trial with an embedded imaging sub-study to identify such predictors. We focus on brain circuits implicated in major depressive disorder and its treatment. In the full trial, depressed participants are randomized to receive escitalopram, sertraline or venlafaxine-XR (open-label). They are assessed using standardized multiple clinical, cognitive-emotional behavioral, electroencephalographic and genetic measures at baseline and at eight weeks post-treatment. Overall, 2,016 depressed participants (18 to 65 years old) will enter the study, of whom a target of 10% will be recruited into the brain imaging sub-study (approximately 67 participants in each treatment arm) and 67 controls. The imaging sub-study is conducted at the University of Sydney and at Stanford University. Structural studies include high-resolution three-dimensional T1-weighted, diffusion tensor and T2/Proton Density scans. Functional studies include standardized functional magnetic resonance imaging (MRI) with three cognitive tasks (auditory oddball, a continuous performance task, and Go-NoGo) and two emotion tasks (unmasked conscious and masked non-conscious emotion processing tasks). After eight weeks of treatment, the functional MRI is repeated with the above tasks. We will establish the methods in the first 30 patients. Then we will identify predictors in the first half (n = 102), test the

  15. Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants.

    PubMed

    Mischoulon, David; Hylek, Lindsay; Yeung, Albert S; Clain, Alisabet J; Baer, Lee; Cusin, Cristina; Ionescu, Dawn Flosnik; Alpert, Jonathan E; Fava, Maurizio; Soskin, David P

    2017-01-15

    Given the proposed dopaminergic mechanism of low-dose naltrexone (LDN), we examined its efficacy as augmentation for depressive breakthrough on pro-dopaminergic antidepressant regimens. 12 adults (67% female, mean age = 45±12) with recurrent DSM-IV major depressive disorder (MDD) on dopaminergic antidepressant regimens (stimulants, dopamine agonists, bupropion [≥300mg/day], aripiprazole [≤2.5mg/day], or sertraline [≥150mg/day]) were randomized to naltrexone 1mg b.i.d. (n=6) or placebo (n=6) augmentation for 3 weeks. All subjects completed the trial. Hamilton Depression Rating Scale (HAM-D-17) scores (primary outcome measure) decreased from 21.2±2.0 to 11.7±7.7 for LDN, from 23.7±2.3 to 17.8±5.9 for placebo (Cohen's d=0.62; p=0.3 between treatment groups). HAM-D-28 scores decreased from 26.2±4.0 to 12.0±9.8 for LDN, from 26.3±2.6 to 19.8±6.6 for placebo (d=1.15; p=0.097). Montgomery-Asberg Depression Rating Scale (MADRS-10 item) scores decreased from 30.4±4.9 to 12.2±8.4 for LDN, from 30.7±4.3 to 22.8±8.5) for placebo (d=1.45; p=0.035). MADRS-15 item scores decreased from 36.6±6.2 to 13.2±8.8 for LDN, from 36.7±4.2 to 26.0±10.0 for placebo (d=1.49; p=0.035). Clinical Global Improvement Scale-Severity (CGI-S) scores decreased from 4.3±0.5 to 3.0±1.1 for LDN, from 4.3±0.5 to 4.0±0.6 for placebo (d=1.22; p=0.064). Small study; restrictions on allowed antidepressants. LDN augmentation showed some benefit for MDD relapse on dopaminergic agents. Confirmation in larger studies is needed. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. 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

  17. 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

  18. Putative role of glycogen as a peripheral biomarker of GSK3β activity.

    PubMed

    Frizzo, Marcos Emilio

    2013-09-01

    GSK3β expression were upregulated by continuous treatment with sertraline. Here, we hypothesized that the quantification of glycogen in platelets might be used as a peripheral biomarker of GSK3β activity. Since it has been recently demonstrated that the modulation of GSK3β activity causes changes in glycogen stores, the glycogen levels in platelets could be used to assay the effects of drugs that have this kinase as a target, or diseases where its activity is affected. In conclusion, we hypothesized that the determination of glycogen peripherally may be useful to indicate a change in the activity of this enzyme, providing a faster and non-invasive approach to guide the therapeutic procedures for the patient. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Diagnosis and Treatment of Depression in Patients With Congestive Heart Failure: A Review of the Literature

    PubMed Central

    Stern, Theodore A.; Hebert, Kathy A.; Musselman, Dominique L.

    2013-01-01

    failure, particularly in those patients with coronary artery disease , and is associated with a poorer quality of life, increased use of health care resources, more frequent adverse clinical events and hospitalizations, and twice the risk of mortality. Conclusions: At present, limited empirical data exist with regard to treatment of depression in the increasingly large population of patients with congestive heart failure. Evidence reveals that both psychotherapeutic treatment (eg, cognitive-behavioral therapy) and pharmacologic treatment (eg, use of the selective serotonin reuptake inhibitor sertraline) are safe and effective in reducing depression severity in patients with cardiovascular disease. Collaborative care programs featuring interventions that work to improve adherence to medical and psychiatric treatments improve both cardiovascular disease and depression outcomes. Depression rating scales such as the 9-item Patient Health Questionnaire should be used to monitor therapeutic efficacy. PMID:24392265

  20. Occurrence of antidepressant residues in the sewage-impacted Vistula and Utrata rivers and in tap water in Warsaw (Poland).

    PubMed

    Giebułtowicz, Joanna; Nałęcz-Jawecki, Grzegorz

    2014-06-01

    Antidepressants, even at low concentrations, can reveal some adverse effects on aquatic life due to disturbing homeostasis throughout the central and peripheral nervous system both in vertebrates and invertebrates. To date there have not been any reports regarding the presence of these pharmaceuticals in surface and tap waters in Eastern Europe. Therefore the aim of this study was to determine the presence of 21 antidepressant pharmaceuticals at specific points of the main Polish river - the Vistula, a smaller river of the Warsaw region - the Utrata, as well as in tap water samples of Warsaw. Samples were collected twice at one month intervals and analysed using solid-phase extraction (SPE) technique coupled with the liquid chromatography-electrospray ionisation-tandem mass spectrometer (LC-MS/MS) method operated under the multiple reaction monitoring mode (MRM). This is the first study where active compounds such as moclobemid or trazodone in the environment have been investigated. Environmental risk assessment of antidepressants in Poland was estimated on the basis of annuals sale data extracted from the NFZ (Narodowy Fundusz Zdrowia-National Health Service) base of reimbursed pharmaceuticals(1). Predicted environmental concentration (PEC) of target pharmaceuticals were compared with their measured concentration (MEC). Moreover, the application of the EMEA/CHMP guideline for environmental risk assessment of the antidepressants was discussed. The highest concentration of antidepressants was observed in the small river Utrata. In tap water only trace amounts of antidepressants including citalopram (up to 1.5ng/l), mianserin (up to 0.9ng/l), sertraline (<3.1ng/l), moclobemid (up to 0.3ng/l) and venlafaxine (up to 1.9ng/l) were detected. However this highlights their inadequate elimination in the drinking waste treatment facility. The presence of antidepressants in drinking water and the aquatic environment could have long-term effects even at low exposure level

  1. Systematic assessment of different solvents for the extraction of drugs of abuse and pharmaceuticals from an authentic hair pool.

    PubMed

    Madry, Milena M; Kraemer, Thomas; Baumgartner, Markus R

    2018-01-01

    Hair analysis has been established as a prevalent tool for retrospective drug monitoring. In this study, different extraction solvents for the determination of drugs of abuse and pharmaceuticals in hair were evaluated for their efficiency. A pool of authentic hair from drug users was used for extraction experiments. Hair was pulverized and extracted in triplicate with seven different solvents in a one- or two-step extraction. Three one- (methanol, acetonitrile, and acetonitrile/water) and four two-step extractions (methanol two-fold, methanol and methanol/acetonitrile/formate buffer, methanol and methanol/formate buffer, and methanol and methanol/hydrochloric acid) were tested under accurately equal experimental conditions. The extracts were directly analyzed by liquid chromatography-tandem mass spectrometry for opiates/opioids, stimulants, ketamine, selected benzodiazepines, antidepressants, antipsychotics, and antihistamines using deuterated internal standards. For most analytes, a two-step extraction with methanol did not significantly improve the yield compared to a one-step extraction with methanol. Extraction with acetonitrile alone was least efficient for most analytes. Extraction yields of acetonitrile/water, methanol and methanol/acetonitrile/formate buffer, and methanol and methanol/formate buffer were significantly higher compared to methanol. Highest efficiencies were obtained by a two-step extraction with methanol and methanol/hydrochloric acid, particularly for morphine, 6-monoacetylmorphine, codeine, 6-acetylcodeine, MDMA, zopiclone, zolpidem, amitriptyline, nortriptyline, citalopram, and doxylamine. For some analytes (e.g., tramadol, fluoxetine, sertraline), all extraction solvents, except for acetonitrile, were comparably efficient. There was no significant correlation between extraction efficiency with an acidic solvent and the pka or log P of the analyte. However, there was a significant trend for the extraction efficiency with acetonitrile to

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

    PubMed

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

    2004-02-01

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

  3. A Gender Analysis of the Study of the Pharmacotherapy of Psychotic Depression (STOP-PD): gender and age as predictors of response and treatment-associated changes in body mass index and metabolic measures

    PubMed Central

    Deligiannidis, Kristina M.; Rothschild, Anthony J.; Barton, Bruce A.; Kroll-Desrosiers, Aimee R.; Meyers, Barnett S.; Flint, Alastair J.; Whyte, Ellen M.; Mulsant, Benoit H.

    2014-01-01

    Background: Gender differences exist in psychiatric disorders; however gender has not been well studied in psychotic depression. This analysis of the largest clinical trial in psychotic depression examined the effects of age and gender on clinical characteristics and predictors of treatment outcome and treatment-associated changes in body mass index (BMI) and metabolic measures. Methods: Analyses were performed on data from 259 subjects aged 18-93 in the double-blind randomized controlled trial of olanzapine plus sertraline (OLZ/SERT) vs. olanzapine plus placebo (OLZ/PBO) for psychotic depression (STOP-PD). Sociodemographic factors, clinical characteristics, treatment outcome and treatment-associated changes in BMI and metabolic measures were analyzed by gender and age. Results: Female gender was associated with divorced (χ2=5.3, d.f.=1, p=0.03) or widowed (χ2=8.1, d.f.=1, p=<0.01) marital status. Co-morbid anxiety disorders were more common in females than males (χ2=4.9, d.f.=1, p=0.03). Hallucinations(χ2=7.8, d.f.=1, p=0.005) and delusions with disorganization (t-test= −2.10, d.f. =257, p=0.04) were significantly associated with female gender as were higher cholesterol measures( χ2=7.15, d.f.=1, p=0.008).There were no significant interactions between treatment and gender in terms of change in BMI. Gender was not associated with treatment response. Discussion: This is the first analysis of gender and age as predictors of treatment outcome and treatment-associated changes in BMI and metabolic adverse effects in psychotic depression. Gender differences exist in patients with psychotic depression, most notably the presence of hallucinations. Female gender was associated with metabolic measures. Future studies with larger sample sizes may detect small gender differences in treatment outcome and treatment-associated changes in BMI and metabolic measures in psychotic depression. PMID:24229753

  4. Child/Adolescent Anxiety Multimodal Study (CAMS): rationale, design, and methods

    PubMed Central

    2010-01-01

    Objective To present the design, methods, and rationale of the Child/Adolescent Anxiety Multimodal Study (CAMS), a recently completed federally-funded, multi-site, randomized placebo-controlled trial that examined the relative efficacy of cognitive-behavior therapy (CBT), sertraline (SRT), and their combination (COMB) against pill placebo (PBO) for the treatment of separation anxiety disorder (SAD), generalized anxiety disorder (GAD) and social phobia (SoP) in children and adolescents. Methods Following a brief review of the acute outcomes of the CAMS trial, as well as the psychosocial and pharmacologic treatment literature for pediatric anxiety disorders, the design and methods of the CAMS trial are described. Results CAMS was a six-year, six-site, randomized controlled trial. Four hundred eighty-eight (N = 488) children and adolescents (ages 7-17 years) with DSM-IV-TR diagnoses of SAD, GAD, or SoP were randomly assigned to one of four treatment conditions: CBT, SRT, COMB, or PBO. Assessments of anxiety symptoms, safety, and functional outcomes, as well as putative mediators and moderators of treatment response were completed in a multi-measure, multi-informant fashion. Manual-based therapies, trained clinicians and independent evaluators were used to ensure treatment and assessment fidelity. A multi-layered administrative structure with representation from all sites facilitated cross-site coordination of the entire trial, study protocols and quality assurance. Conclusions CAMS offers a model for clinical trials methods applicable to psychosocial and psychopharmacological comparative treatment trials by using state-of-the-art methods and rigorous cross-site quality controls. CAMS also provided a large-scale examination of the relative and combined efficacy and safety of the best evidenced-based psychosocial (CBT) and pharmacologic (SSRI) treatments to date for the most commonly occurring pediatric anxiety disorders. Primary and secondary results of CAMS will hold

  5. A distinct pattern of memory and attention deficiency in patients with depression.

    PubMed

    Luo, Lan-Lan; Chen, Xin; Chai, Yan; Li, Jin-Hong; Zhang, Mian; Zhang, Jian-Ning

    2013-03-01

    Depression related cognitive deficits are frequently considered as simple epiphenomena of the disorder. However, whether or not the depression might directly bring about cognitive deficits is still under investigation. This study was to investigate the distinct pattern of cognitive deficits in patients with depression by comparing the cognitive function before and after anti-depressive drug therapy. Sixty cases of patients, first-time diagnosed with depression, were assessed by 17-item Hamilton Rating Scale for Depression (HAMD17scale). The memory ability was tested by quantitatively clinical memory scale, while the attention ability by modified Ruff 2&7 Selective Attention Test. Forty-two healthy volunteers were recruited as controls. The depressive patients were treated with Venlafaxine (75 - 300 mg/d), Fluoxetine (20 - 40 mg/d), Paroxetine (20 - 40 mg/d), and Sertraline (50 - 150 mg/d). After 12 weeks treatment, patients were tested again by HAMD17scale, quantitatively clinical memory scale, and modified Ruff 2&7 selective attention test to assess the effect of anti-depressive drugs on cognitive deficits. The memory quotient (MQ) was significantly lowered in depressive patients. The selection speed was also significantly decreased and the number of missing and error hits increased in the depression group as compared to control. However, there was no significant difference in clinical memory scale and Ruff 2&7 selective attention test between mild-to-moderate and severe depression group. Importantly, after anti-depressive drug therapy, the HAMD17 scale scores in depressive patients were significantly decreased, but the MQ, directional memory (DM), free recall (FR), associative learning (AL), and face recognition were comparable with those before the treatment. Furthermore, the selection speed and the number of missing and error hits were also not significantly different after anti-depressive drugs treatment. Depressive patients suffer from short-term memory

  6. Brain imaging predictors and the international study to predict optimized treatment for depression: study protocol for a randomized controlled trial.

    PubMed

    Grieve, Stuart M; Korgaonkar, Mayuresh S; Etkin, Amit; Harris, Anthony; Koslow, Stephen H; Wisniewski, Stephen; Schatzberg, Alan F; Nemeroff, Charles B; Gordon, Evian; Williams, Leanne M

    2013-07-18

    Approximately 50% of patients with major depressive disorder (MDD) do not respond optimally to antidepressant treatments. Given this is a large proportion of the patient population, pretreatment tests that predict which patients will respond to which types of treatment could save time, money and patient burden. Brain imaging offers a means to identify treatment predictors that are grounded in the neurobiology of the treatment and the pathophysiology of MDD. The international Study to Predict Optimized Treatment in Depression is a multi-center, parallel model, randomized clinical trial with an embedded imaging sub-study to identify such predictors. We focus on brain circuits implicated in major depressive disorder and its treatment. In the full trial, depressed participants are randomized to receive escitalopram, sertraline or venlafaxine-XR (open-label). They are assessed using standardized multiple clinical, cognitive-emotional behavioral, electroencephalographic and genetic measures at baseline and at eight weeks post-treatment. Overall, 2,016 depressed participants (18 to 65 years old) will enter the study, of whom a target of 10% will be recruited into the brain imaging sub-study (approximately 67 participants in each treatment arm) and 67 controls. The imaging sub-study is conducted at the University of Sydney and at Stanford University. Structural studies include high-resolution three-dimensional T1-weighted, diffusion tensor and T2/Proton Density scans. Functional studies include standardized functional magnetic resonance imaging (MRI) with three cognitive tasks (auditory oddball, a continuous performance task, and Go-NoGo) and two emotion tasks (unmasked conscious and masked non-conscious emotion processing tasks). After eight weeks of treatment, the functional MRI is repeated with the above tasks. We will establish the methods in the first 30 patients. Then we will identify predictors in the first half (n=102), test the findings in the second half, and

  7. Quantification of suvorexant in blood using liquid chromatography-quadrupole/time of flight (LC-Q/TOF) mass spectrometry.

    PubMed

    Skillman, Britni; Kerrigan, Sarah

    2018-08-01

    of 5, 50, and 160 ng/mL. Matrix effects were 16% (9% CV) and 15% (8% CV) for 20 ng/mL and 100 ng/mL (n = 20), respectively. No qualitative interferences or carryover were observed; however, a quantitative interference with the internal standard (estazolam-D5) could be attributed to sertraline when present at a 10-fold higher concentration. In the absence of a commercially available deuterated internal standard, the potential for quantitative interferences using LC-based methods are discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2015-05-01

    review included six studies on tension-type headache. We now include eight studies with a total of 412 participants with chronic forms of tension-type headache. These studies evaluated five SSRIs (citalopram, sertraline, fluoxetine, paroxetine, fluvoxamine) and one SNRI (venlafaxine). The two new studies included in this update are placebo controlled trials, one evaluated sertraline and one venlafaxine. Six studies, already included in the previous version of this review, compared SSRIs to other antidepressants (amitriptyline, desipramine, sulpiride, mianserin). Most of the included studies had methodological and/or reporting shortcomings and lacked adequate power. Follow-up ranged between two and four months.Six studies explored the effect of SSRIs or SNRIs on tension-type headache frequency, the primary endpoint. At eight weeks of follow-up, we found no difference when compared to placebo (two studies, N = 127; mean difference (MD) -0.96, 95% confidence interval (CI) -3.95 to 2.03; I(2)= 0%) or amitriptyline (two studies, N = 152; MD 0.76, 95% CI -2.05 to 3.57; I(2)= 44%).When considering secondary outcomes, SSRIs reduce the symptomatic/analgesic medication use for acute headache attacks compared to placebo (two studies, N = 118; MD -1.87, 95% CI -2.09 to -1.65; I(2)= 0%). However, amitriptyline appeared to reduce the intake of analgesic more efficiently than SSRIs (MD 4.98, 95% CI 1.12 to 8.84; I(2)= 0%). The studies supporting these findings were considered at unclear risk of bias. We found no differences compared to placebo or other antidepressants in headache duration and intensity.SSRIs or SNRI were generally more tolerable than tricyclics. However, the two groups did not differ in terms of number of participants who withdrew due to adverse events or for other reasons (four studies, N = 257; odds ratio (OR) 1.04; 95% CI 0.41 to 2.60; I(2)= 25% and OR 1.55, 95% CI 0.71 to 3.38; I(2)= 0%).We did not find any study comparing SSRIs or SNRIs with pharmacological

  9. 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

    other antidepressive agent. Two review authors independently extracted data and a double-entry procedure was employed. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability. A total of 13 studies (4495 participants) were included in this review. Agomelatine was compared to selective serotonin reuptake inhibitors (SSRIs), namely paroxetine, fluoxetine, sertraline, escitalopram, and to the serotonin-norepinephrine reuptake inhibitor (SNRI), venlafaxine. Participants were followed up for six to 12 weeks. Agomelatine did not show any advantage or disadvantage over the other antidepressants for our primary outcome, response to treatment (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.95 to 1.08, P value 0.75 compared to SSRIs, and RR 1.06; 95% CI 0.98 to 1.16, P value 0.16 compared to venlafaxine). Also, agomelatine showed no advantage or disadvantage over other antidepressants for remission (RR 0.83; 95% CI 0.68 to 1.01, P value 0.07 compared to SSRIs, and RR 1.08; 95% CI 0.94 to 1.24, P value 0.73 compared to venlafaxine). Overall, agomelatine appeared to be better tolerated than venlafaxine in terms of lower rates of drop outs (RR 0.40; 95% CI 0.24 to 0.67, P value 0.0005), and showed the same level of tolerability as SSRIs (RR 0.95; 95% CI 0.83 to 1.09, P value 0.44). Agomelatine induced a lower rate of dizziness than venlafaxine (RR 0.19, 95% CI 0.06 to 0.64, P value 0.007).With regard to the quality of the body of evidence, there was a moderate risk of bias for all outcomes, due to the number of included unpublished studies. There was some heterogeneity, particularly between published and unpublished studies. The included studies were conducted in inpatient and outpatient settings, thus limiting the generalisability of the results to primary care settings. With regard to precision, the efficacy outcomes were precise, but the tolerability

  10. Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-wide Association Study

    PubMed Central

    Nicoletti, Paola; Aithal, Guruprasad P.; Bjornsson, Einar S.; Andrade, Raul J.; Sawle, Ashley; Arrese, Marco; Barnhart, Huiman X.; Bondon-Guitton, Emmanuelle; Hayashi, Paul H.; Bessone, Fernando; Carvajal, Alfonso; Cascorbi, Ingolf; Cirulli, Elizabeth T.; Chalasani, Naga; Conforti, Anita; Coulthard, Sally A.; Daly, Mark J.; Day, Christopher P.; Dillon, John F.; Fontana, Robert J.; Grove, Jane I.; Hallberg, Pär; Hernández, Nelia; Ibáñez, Luisa; Kullak-Ublick, Gerd A.; Laitinen, Tarja; Larrey, Dominique; Lucena, M. Isabel; Maitland-van der Zee, Anke H.; Martin, Jennifer H.; Molokhia, Mariam; Pirmohamed, Munir; Powell, Elizabeth E.; Qin, Shengying; Serrano, Jose; Stephens, Camilla; Stolz, Andrew; Wadelius, Mia; Watkins, Paul B.; Floratos, Aris; Shen, Yufeng; Nelson, Matthew R.; Urban, Thomas J.; Daly, Ann K.

    2017-01-01

    chromosome 18 (OR=5.4; 95% CI, 3.0–9.5; P=7.1×10−9). We validated the association between A*33:01 terbinafine- and sertraline-induced DILI. We could not validate the association between DILI and rs72631567, rs28521457, or rs116561224. CONCLUSIONS In a GWAS of persons of European descent with DILI, we associated HLA-A*33:01 with DILI due to terbinafine and possibly fenofibrate and ticlopidine. We identified polymorphisms that appear to be associated with DILI from statins, as well as 2 non–drug-specific risk factors. PMID:28043905

  11. Novel Augmentation Strategies in Major Depression.

    PubMed

    Martiny, Klaus

    2017-04-01

    Hypothesis The hypotheses of all the four included studies share the common idea that it is possible to augment the effect of antidepressant drug treatment by applying different interventions and with each intervention attain a clinically meaningful better effect compared to a control condition, and with minor side effects, thus improving the short- and medium-term outcome in major depression. Procedures Study design The basic study design has been the double blind randomised controlled trial (RCT). In the light therapy study, all patients were treated with sertraline for the whole of the study duration. In the first five weeks of the study, patients were randomised to treatment with either 60 minutes of bright white or 30 minutes of dim red light (sham condition). In the four weeks follow-up period, patients were treated with sertraline alone. In the Pindolol study, all patients were treated with venlafaxine and randomised to augmentation with either active or placebo matching pindolol tablets. In the PEMF study patients were continued on ongoing medication and randomised to augmentation with active or inactive (sham) 30 minutes daily PEMF treatment on weekdays. In the Chronos study all patients were treated with duloxetine and randomized to either a combination of three wake therapies with daily bright light treatment and sleep time stabilisation (wake group) or to daily exercise of minimum 30 minutes as an active control intervention (exercise group). The Chronos study was divided into: (1) a one-week run-in phase where duloxetine were started (and continued for the whole 29 week study period), (2) a one-week inpatient intervention phase where patient in the wake group did three wake therapies (sleep abstinence for the whole night and the following day until evening) in combination with daily light therapy and guidance on sleep time stabilisation and patients in the exercise group started a daily exercise program, (3) a seven week continuation phase where

  12. Context-Sensitive Spelling Correction of Consumer-Generated Content on Health Care.

    PubMed

    Zhou, Xiaofang; Zheng, An; Yin, Jiaheng; Chen, Rudan; Zhao, Xianyang; Xu, Wei; Cheng, Wenqing; Xia, Tian; Lin, Simon

    2015-07-31

    Consumer-generated content, such as postings on social media websites, can serve as an ideal source of information for studying health care from a consumer's perspective. However, consumer-generated content on health care topics often contains spelling errors, which, if not corrected, will be obstacles for downstream computer-based text analysis. In this study, we proposed a framework with a spelling correction system designed for consumer-generated content and a novel ontology-based evaluation system which was used to efficiently assess the correction quality. Additionally, we emphasized the importance of context sensitivity in the correction process, and demonstrated why correction methods designed for electronic medical records (EMRs) failed to perform well with consumer-generated content. First, we developed our spelling correction system based on Google Spell Checker. The system processed postings acquired from MedHelp, a biomedical bulletin board system (BBS), and saved misspelled words (eg, sertaline) and corresponding corrected words (eg, sertraline) into two separate sets. Second, to reduce the number of words needing manual examination in the evaluation process, we respectively matched the words in the two sets with terms in two biomedical ontologies: RxNorm and Systematized Nomenclature of Medicine -- Clinical Terms (SNOMED CT). The ratio of words which could be matched and appropriately corrected was used to evaluate the correction system's overall performance. Third, we categorized the misspelled words according to the types of spelling errors. Finally, we calculated the ratio of abbreviations in the postings, which remarkably differed between EMRs and consumer-generated content and could largely influence the overall performance of spelling checkers. An uncorrected word and the corresponding corrected word was called a spelling pair, and the two words in the spelling pair were its members. In our study, there were 271 spelling pairs detected, among

  13. Chromatography as Method for Analytical Confirmation of Paracetamol in Postmortem Material Together with Psychoactive Substances.

    PubMed

    Biscevic-Tokic, Jasmina; Tokic, Nedim; Ibrahimpasic, Elma

    2015-10-01

    substance. Used GC-MS instrument was an Agilent 7890A with helium as the carrier gas. The analysis of blood samples, urine, bile and stomach contents, obtained after the autopsy of deceased persons, by using gas chromatography with mass spectrometry, in analytical manner confirmed the fact that paracetamol is a very common component of psychoactive substances poisoning. In our assay of samples we detected psychoactive substances (heroin, codeine, morphine, sertraline, diazepam), and almost all were found in the combination with paracetamol, indicating the poor quality of illicit drugs sold on the market. Paracetamol (Acetaminophen) is a very common component in mixtures of street drugs. Such mixtures almost anyone can afford, but the very quality of these drugs has become extremely low, because it does not sell the pure substance, but is mixed with various medications. According to research Pantazia et al. the heroin mixture proportion of the heroin is very small so a lot of that mixture has only 3% of heroin, a large number of cases can be only 1% of pure heroin. Most of the time it replaces caffeine and paracetamol. According to the Risser et al. reason why acetaminophen component is present in these mixtures is because it can be purchased without a prescription, it is cheap, well tolerated by most people and shows no side effects. When we talk about illegal drugs, we must emphasize the fact that there is no quality control, or the composition of the drug. The composition of the drug purchased on the black market is still unknown to potential user. While reaching the final drug users it pass through many hands, and at each step something is added to increase earnings. Most often present additives or impurities in narcotic drugs that are added are caffeine, ephedrine, acetaminophen, acetylsalicylic acid (aspirin) and additives such as powders, cement and chalk.

  14. Co-occurring depressive symptoms in the older patient with schizophrenia.

    PubMed

    Kasckow, John W; Zisook, Sidney

    2008-01-01

    Clinicians treating older patients with schizophrenia are often challenged by patients presenting with both depressive and psychotic features. The presence of co-morbid depression impacts negatively on quality of life, functioning, overall psychopathology and the severity of co-morbid medical conditions. Depressive symptoms in patients with schizophrenia include major depressive episodes (MDEs) that do not meet criteria for schizoaffective disorder, MDEs that occur in the context of schizoaffective disorder and subthreshold depressive symptoms that do not meet criteria for MDE. Pharmacological treatment of patients with schizophrenia and depression involves augmenting antipsychotic medications with antidepressants. Recent surveys suggest that clinicians prescribe antidepressants to 30% of inpatients and 43% of outpatients with schizophrenia and depression at all ages. Recent trials addressing the efficacy of this practice have evaluated selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, sertraline, fluvoxamine and citalopram. These trials have included only a small number of subjects and few older subjects participated; furthermore, the efficacy results have been mixed. Although no published controlled psychotherapeutic studies have specifically targeted major depression or depressive symptoms in older patients with schizophrenia, psychosocial interventions likely play a role in any comprehensive management plan in this population of patients.Our recommendations for treating the older patient with schizophrenia and major depression involve a stepwise approach. First, a careful diagnostic assessment to rule out medical or medication causes is important as well as checking whether patients are adherent to treatments. Clinicians should also consider switching patients to an atypical antipsychotic if they are not taking one already. In addition, dose optimization needs to be targeted towards depressive as well as positive and negative psychotic

  15. Context-Sensitive Spelling Correction of Consumer-Generated Content on Health Care

    PubMed Central

    Chen, Rudan; Zhao, Xianyang; Xu, Wei; Cheng, Wenqing; Lin, Simon

    2015-01-01

    Background Consumer-generated content, such as postings on social media websites, can serve as an ideal source of information for studying health care from a consumer’s perspective. However, consumer-generated content on health care topics often contains spelling errors, which, if not corrected, will be obstacles for downstream computer-based text analysis. Objective In this study, we proposed a framework with a spelling correction system designed for consumer-generated content and a novel ontology-based evaluation system which was used to efficiently assess the correction quality. Additionally, we emphasized the importance of context sensitivity in the correction process, and demonstrated why correction methods designed for electronic medical records (EMRs) failed to perform well with consumer-generated content. Methods First, we developed our spelling correction system based on Google Spell Checker. The system processed postings acquired from MedHelp, a biomedical bulletin board system (BBS), and saved misspelled words (eg, sertaline) and corresponding corrected words (eg, sertraline) into two separate sets. Second, to reduce the number of words needing manual examination in the evaluation process, we respectively matched the words in the two sets with terms in two biomedical ontologies: RxNorm and Systematized Nomenclature of Medicine -- Clinical Terms (SNOMED CT). The ratio of words which could be matched and appropriately corrected was used to evaluate the correction system’s overall performance. Third, we categorized the misspelled words according to the types of spelling errors. Finally, we calculated the ratio of abbreviations in the postings, which remarkably differed between EMRs and consumer-generated content and could largely influence the overall performance of spelling checkers. Results An uncorrected word and the corresponding corrected word was called a spelling pair, and the two words in the spelling pair were its members. In our study, there

  16. Assessing the efficiency of an unplanted horizontal flow constructed wetland to reduce some emerging organic micropollutants. Preliminary results

    NASA Astrophysics Data System (ADS)

    Tapias, Josefina C.; Vila, Marta; Himi, Mahjoub; Salvadó, Victoria; Casas, Albert; Hidalgo, Manuela

    2017-04-01

    ), antidepressants (sertraline, paroxetine, fluoxetine and citalopram) and in addition carbamazepine and triclosan. For the analysis of water samples, a 200 mL volume was filtrated through 0.45µm nylon filters, acidified, and extracted with Oasis HLB cartridges. The analytes were recovered with 3mL methanol followed by 3 mL acetonitrile. The extract was evaporated under a gentle nitrogen stream, reconstituted with 500 µL MeOH:ACN (1:1) and analyzed by LC/MS/MS. Highest influent concentrations of studied EOCs in raw wastewater were for naproxene (ranging 2.1 - 24.76µg/L) and iboprufene (ranging 4.2 - 11.74 µg/L) and final effluent concentrations of these same compounds showed high but variable removal efficiencies depending on environmental temperature. Additionally to the reductions within the wetland beds attributed to sorption by particulate matter and biofilm, further reduction was completed at the waste water stabilization ponds by photodegradation.

  17. Factors Influencing Depression Endpoints Research (FINDER): baseline results of Italian patients with depression

    PubMed Central

    Grassi, Luigi; Rossi, Andrea; Barraco, Alessandra

    2009-01-01

    Background Factors Influencing Depression Endpoints Research (FINDER) is a 6-month, prospective, observational study carried out in 12 European countries aimed at investigating health-related quality of life (HRQoL) in outpatients receiving pharmacological treatment for a first or new depressive episode. Baseline characteristics of patients enrolled in Italy are presented. Methods All treatment decisions were at the discretion of the investigator. Data were collected at baseline and after 3 and 6 months of treatment. Baseline evaluations included demographics, medical and psychiatric history, and medications used in the last 24 months and prescribed at enrolment. The Hospital Anxiety and Depression Scale (HADS), was adopted to evaluate depressive symptoms, while somatic and painful physical symptoms were assessed by using the Somatic Symptom Inventory (SSI) and a 0 to 100 mm visual analogue scale (VAS), HRQoL via 36-item Short Form Health Survey (SF-36), and the European Quality of Life 5-Dimensions (EQ-5D) instrument. Results A total of 513 patients were recruited across 38 sites. The mean ± standard deviation (SD) age at first depressive episode was 38.7 ± 15.9 years, the mean duration of depression 10.6 ± 12.3 years. The most common psychiatric comorbidities in the previous 24 months were anxiety/panic (72.6%) and obsessive/compulsive disorders (13.4%), while 35.9% had functional somatic syndromes. Most patients (65.1%) reported pain from any cause. Monotherapy with selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) was prescribed at enrolment in 64.5% and 6.4% of the cases, respectively. The most commonly prescribed agents were sertraline (17.3%), escitalopram (16.2%), venlaflaxine (15.6%) and paroxetine (14.8%). The mean HADS subscores for depression and anxiety were 13.3 ± 4.2 and 12.2 ± 3.9, respectively; 76.4% of patients could be defined as being 'probable cases' for depression and 66.2% for anxiety. The mean total

  18. Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis.

    PubMed

    Cipriani, Andrea; Zhou, Xinyu; Del Giovane, Cinzia; Hetrick, Sarah E; Qin, Bin; Whittington, Craig; Coghill, David; Zhang, Yuqing; Hazell, Philip; Leucht, Stefan; Cuijpers, Pim; Pu, Juncai; Cohen, David; Ravindran, Arun V; Liu, Yiyun; Michael, Kurt D; Yang, Lining; Liu, Lanxiang; Xie, Peng

    2016-08-27

    Major depressive disorder is one of the most common mental disorders in children and adolescents. However, whether to use pharmacological interventions in this population and which drug should be preferred are still matters of controversy. Consequently, we aimed to compare and rank antidepressants and placebo for major depressive disorder in young people. We did a network meta-analysis to identify both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LiLACS, regulatory agencies' websites, and international registers for published and unpublished, double-blind randomised controlled trials up to May 31, 2015, for the acute treatment of major depressive disorder in children and adolescents. We included trials of amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine. Trials recruiting participants with treatment-resistant depression, treatment duration of less than 4 weeks, or an overall sample size of less than ten patients were excluded. We extracted the relevant information from the published reports with a predefined data extraction sheet, and assessed the risk of bias with the Cochrane risk of bias tool. The primary outcomes were efficacy (change in depressive symptoms) and tolerability (discontinuations due to adverse events). We did pair-wise meta-analyses using the random-effects model and then did a random-effects network meta-analysis within a Bayesian framework. We assessed the quality of evidence contributing to each network estimate using the GRADE framework. This study is registered with PROSPERO, number CRD42015016023. We deemed 34 trials eligible, including 5260 participants and 14 antidepressant treatments. The quality of evidence was rated as very low in most comparisons. For efficacy, only fluoxetine was statistically significantly more

  19. Study of kinetic desorption rate constant in fish muscle and agarose gel model using solid phase microextraction coupled with liquid chromatography with tandem mass spectrometry.

    PubMed

    Togunde, Oluranti Paul; Oakes, Ken; Servos, Mark; Pawliszyn, Janusz

    2012-09-12

    , viscosity of the gel will be reduced therefore allowing faster diffusion which invariably affect desorption time constant. Also, desorption time constant of model drugs in the fish muscle and 0.8-0.9% (w/v) gel model are similar based on free diffusion of studied compounds. In addition, in vitro and in vivo desorption time constant comparison shows that desorption time constant in an in vivo system (live fish muscle) is generally higher than an in vitro system (dead fish muscle) except for sertraline and nordiazepam. This study demonstrates SPME as a simple investigative tool to understand kinetics of desorption in an in vivo system with a goal to measure desorption rate of pharmaceuticals in fish. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Tablet splitting: is it worthwhile? Analysis of drug content and weight uniformity for half tablets of 16 commonly used medications in the outpatient setting.

    PubMed

    Helmy, Sally A

    2015-01-01

    Tablet splitting is a well-established medical practice in clinical settings for multiple reasons, including cost savings and ease of swallowing. However, it does not necessarily result in weight-uniform half tablets. To (a) investigate the effect of tablet characteristics on weight and content uniformity of half tablets, resulting from splitting 16 commonly used medications in the outpatient setting and (b) provide recommendations for safe tablet-splitting prescribing practices. Ten random tablets from each of the selected medications were weighed and split by 5 volunteers (2 men and 3 women aged 25-44 years) using a knife. The selected medications were mirtazapine 30 mg, bromazepam 3 mg, oxcarbazepin 150 mg, sertraline 50 mg, carvedilol 25 mg, bisoprolol fumarate 10 mg, losartan 50 mg, digoxin 0.25 mg, amiodarone HCl 200 mg, metformin HCl 1,000 mg, glimepiride 4 mg, montelukast 10 mg, ibuprofen 600 mg, celecoxib 200 mg, meloxicam 15 mg, and sildenafil citrate 50 mg. The resulting half tablets were evaluated for weight and drug content uniformity in accordance with proxy United States Pharmacopeia (USP) specification (95%-105% for digoxin and 90%-110% for the other 15 drugs). Weight and drug content uniformity were assessed by comparing weight or drug content of the half tablets with one-half of the mean weight or drug content for all whole tablets in the sample. The percentages by which the weight and drug content of each whole tablet or half tablet differed from sample mean values were calculated. Other relevant physical characteristics of the 16 products were measured. A total of 52 of 320 half tablets (16.2%) and 48 of 320 half tablets (15.0%) fell outside of the proxy USP specification for weight and drug content, respectively. Bromazepam, carvedilol, bisoprolol, losartan, digoxin, and meloxicam half tablets failed the weight and content uniformity test; however, the half tablets for the rest of the medications passed the test. Mean percent weight loss after

  1. Effect of antidepressant treatment on cognitive impairments associated with depression: a randomised longitudinal study.

    PubMed

    Shilyansky, Carrie; Williams, Leanne M; Gyurak, Anett; Harris, Anthony; Usherwood, Timothy; Etkin, Amit

    2016-05-01

    Antidepressant treatment failure is a common problem worldwide. In this study, we assess whether or not an important aspect of depression, cognitive impairment, is untreated by antidepressants by studying the effect of acute antidepressant treatment on a range of cognitive domains. In this randomised longitudinal study, which is part of the International Study to Predict Optimized Treatment in Depression (iSPOT-D) trial, we assessed the effects of acute antidepressant treatment in a large patient population, across clinical remission outcomes, on a range of cognitive domains: attention, response inhibition, executive function during visuospatial navigation, cognitive flexibility, verbal memory, working memory, decision speed, information processing speed, and psychomotor response speed. We enrolled patients from primary or specialty care clinics in a multicentre, international, open-label, randomised, prospective trial. Eligible patients (aged 18-65 years) were previously untreated or were willing to undergo a 1-week medication washout before the study start, and could not have had inadequate response to study medications in the past. We enrolled a large population of medication-free (ie, untreated) outpatients in a depressive episode and assessed them for cognitive function at enrolment (pre-treatment), and again after 8 weeks of treatment with one of three antidepressant drugs (escitalopram, sertraline, or venlafaxine extended-release). Patients were randomly assigned (1:1:1) to one of the three antidepressants using a blocked randomisation procedure (block size of 12). As a comparison group, we also simultaneously enrolled matched healthy participants. Healthy participants received no medication or intervention, but were assessed for change in cognitive and clinical measures during the same interval and testing protocol. Therefore, this group acts as a test-retest control for the primary outcome measure examined in this study, change in cognitive measures over 8

  2. Interventions to treat premature ejaculation: a systematic review short report.

    PubMed

    Cooper, Katy; Martyn-St James, Marrissa; Kaltenthaler, Eva; Dickinson, Kath; Cantrell, Anna

    2015-03-01

    Zeneca), topical eutectic mixture for PE (Plethora Solutions Ltd) spray; selective serotonin reuptake inhibitors (SSRIs) - citalopram (Cipramil(®), Lundbeck), escitalopram (Cipralex(®), Lundbeck), fluoxetine, paroxetine, sertraline, dapoxetine (Priligy(®), Menarini), 30 mg or 60 mg; serotonin-noradrenaline reuptake inhibitors - duloxetine (Cymbalta(®), Eli Lilly & Co Ltd); tricyclic antidepressants - inhaled clomipramine 4 mg; phosphodiesterase-5 (PDE5) inhibitors - vardenafil (Levitra(®), Bayer), tadalafil (Cialis(®), Eli Lilly & Co Ltd); opioid analgesics - tramadol (Zydol SR(®), Grünenthal). Improvements in sexual satisfaction and other outcomes compared with placebo were evident for SSRIs, PDE5 inhibitors and tramadol. Outcomes for interventions not compared with placebo were as follows: behavioural therapies - improvements over wait list control in IELT and other outcomes, behavioural therapy plus pharmacotherapy better than either therapy alone; alpha blockers - terazosin (Hytrin(®), AMCO) not significantly different to antidepressants in ejaculation control; acupuncture - improvements over sham acupuncture in IELT, conflicting results for comparisons with SSRIs; Chinese medicine - improvements over treatment as usual; delay device - improvements in IELT when added to stop-start technique; yoga - improved IELT over baseline, fluoxetine better than yoga. Treatment-related AEs were evident with most pharmacological interventions. Although data extraction from reviews was optimised when more than one review reported data for the same RCT, the reliability of the data extraction within these reviews cannot be guaranteed by this assessment report. Several interventions significantly improved IELT. Many interventions also improved sexual satisfaction and other outcomes. However, assessment of longer-term safety and effectiveness is required to evaluate whether or not initial treatment effects are maintained long term, whether or not dose escalation is required, how

  3. Fluoxetine versus other types of pharmacotherapy for depression.

    PubMed

    Magni, Laura R; Purgato, Marianna; Gastaldon, Chiara; Papola, Davide; Furukawa, Toshi A; Cipriani, Andrea; Barbui, Corrado

    2013-07-17

    dosulepin (OR 2.13, 95% CI 1.08 to 4.20; number needed to treat (NNT) =6, 95% CI 3 to 50, 2 RCTs, 144 participants), sertraline (OR 1.37, 95% CI 1.08 to 1.74; NNT = 13, 95% CI 7 to 58, 6 RCTs, 1188 participants), mirtazapine (OR 1.46, 95% CI 1.04 to 2.04; NNT = 12, 95% CI 6 to 134, 4 RCTs, 600 participants) and venlafaxine(OR 1.29, 95% CI 1.10 to 1.51; NNT = 11, 95% CI 8 to 16, 12 RCTs, 3387 participants). On a continuous outcome, fluoxetine was more effective than ABT-200 (SMD -1.85, 95% CI -2.25 to -1.45, 1 RCT, 141 participants) and milnacipran (SMD -0.36, 95% CI-0.63 to -0.08, 2 RCTs, 213 participants); conversely, it was less effective than venlafaxine (SMD 0.10, 95% CI 0 to 0.19, 13 RCTs,3097 participants). Fluoxetine was better tolerated than TCAs considered as a group (total dropout OR 0.79, 95% CI 0.65 to 0.96;NNT = 20, 95% CI 13 to 48, 49 RCTs, 4194 participants) and was better tolerated in comparison with individual ADs, in particular amitriptyline (total dropout OR 0.62, 95% CI 0.46 to 0.85; NNT = 13, 95% CI 8 to 39, 18 RCTs, 1089 participants), and among the newer ADs ABT-200 (total dropout OR 0.18, 95% CI 0.08 to 0.39; NNT = 3, 95% CI 2 to 5, 1 RCT, 144 participants), pramipexole(total dropout OR 0.12, 95% CI 0.03 to 0.42, NNT = 3, 95% CI 2 to 5, 1 RCT, 105 participants), and reboxetine (total dropout OR0.60, 95% CI 0.44 to 0.82, NNT = 9, 95% CI 6 to 24, 4 RCTs, 764 participants). The present study detected differences in terms of efficacy and tolerability between fluoxetine and certain ADs, but the clinical meaning of these differences is uncertain.Moreover, the assessment of quality with the risk of bias tool showed that the great majority of included studies failed to report details on methodological procedures. Of consequence, no definitive implications can be drawn from the studies' results. The better efficacy profile of sertraline and venlafaxine (and possibly other ADs) over fluoxetine may be clinically meaningful,as already suggested by other

  4. IMPACT OF SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) DURING PREGNANCY AND LACTATION: A FOCUS ON SHORT AND LONG-TERM VASCULAR EFFECTS.

    PubMed

    Zullino, S; Simoncini, T

    2018-05-24

    SSRIs are the first choice for the treatment of mood disorders during pregnancy and lactation. Despite the known side effects, the benefits/risks balance suggests their use. Hypertensive disorders of pregnancy (HDP) and Intrauterine growth restriction (IUGR) are the main vascular effects of these drugs, with mechanisms that involves endothelial dysfunction in feto-placental system. These data are supported by animal models, even if preliminary findings are not yet adequately supported by molecular and clinical data. SSRIs. applications and mode of action. Nowadays selective serotonin reuptake inhibitors (SSRIs) are among the most used antidepressants in the treatment of major depressive and anxiety disorders. This class of drugs is also widely prescribed for panic disorders, obsessive-compulsive disorder (OCD), eating disorders and post-traumatic stress disorder (PTSD). The exact mechanism of action of SSRIs is unknown. However SSRIs are believed to increase the extracellular levels of the neurotransmitterserotonin by limiting its reuptake into the presynaptic cell, increasing the levels in the synaptic cleft available to bind the postsynaptic receptor. They have varying degrees of selectivity for the other monoamine transporters, with pure SSRIs having only weak affinity for the norepinephrine and dopamine transporters [1]. SSRIs during pregnancy and lactation: use and benefits/risk balance. Approximately 10-20% of women experience depression and/or anxiety during the perinatal period. Moreover an increasing number of patients needs to continue a previous psychiatric treatment during and after pregnancy. Data from the Slone Epidemiology Center Birth Defect Study [2] underlines an increased use of antidepressants from 1 to 7% in the last thirty years. SSRIs, and in particular sertraline and fluoxetine, are considered the gold standard to manage maternal mood disorders during pregnancy and in the post-partum [3-7]. They have replaced tricyclic antidepressants as the

  5. Traumatized refugees: morbidity, treatment and predictors of outcome.

    PubMed

    Buhmann, Caecilie Böck

    2014-08-01

    Despite large numbers of traumatized refugees, little is known about effective treatment of war trauma in refugees and immigrants. Few studies evaluating treatment have been published and most studies are follow-up studies with methodological limitations and little comparability across studies. The purpose of the PhD is to characterize transcultural trauma patients in Denmark needing psychiatric treatment with regards to psychopathology and predictors of mental health and to evaluate the effects of the treatment. Two studies reported in 4 papers form the basis of the thesis. FORLOB (Paper 1-3) was a follow-up study that included all patients receiving treatment at the Competence Center for Transcultural Psychiatry in Copenhagen from April 2008 to February 2010. Patients completed self-ratings of symptoms of PTSD, depression and anxiety as well as level of functioning and quality of life (HTQ, HSCL-25, SDS & WHO-5) before treatment and after treatment. Associations of co-morbid diagnoses and predictors of the patients' health condition were examined with linear and logistic regression and Pearson's correlation coefficients. Treatment in FORLOB consisted of a combination of Sertraline, Mianserin, psycho-education and Trauma-Focused Cognitive Behavioral Therapy (TFCBT). The treatment administered to each patient was monitored in detail and changes in outcome and predictors of change were analyzed. PTF1 (Paper 4) was a randomized controlled clinical trial with 2x2 factorial design (antidepressants, TFCBT, antidepressants & TFCBT, waiting list). Potential participants were screened amongst adult patients referred to the Competence Center for Transcultural Psychiatry in the period June 2009-2011. Patients with PTSD, war trauma and without a psychotic disorder were included. The manualized treatment consisted of weekly sessions with a physician and/or psychologist over a period of 6 months. The treatment effect was evaluated with a combination of self-ratings and blinded

  6. Pharmacy and medical costs associated with switching between venlafaxine and SSRI antidepressant therapy for the treatment of major depressive disorder.

    PubMed

    Khandker, Rezaul K; Kruzikas, Denise T; McLaughlin, Trent P

    2008-06-01

    maximum gap in therapy. The SSRIs included fluoxetine, citalopram, sertraline, and paroxetine; the only SNRI on the market at the time was venlafaxine. Multivariate regression analyses determined predictors of switching and factors influencing overall and depression-related costs, while controlling for confounding factors. For the 12-month period following the index date (fixed length of follow-up), the study compared per-patient per-year (PPPY) costs for (1) patients who switched versus those who did not switch and (2) patients with single versus multiple trials of SSRI for the subgroup of patients who switched from an SSRI to venlafaxine. For the time periods before versus after the switch (variable lengths of follow-up), per-patient means and medians of monthly cost averages (with follow-up periods <1 month set to 1 month for 16.5% [n=272] of SSRI-to-venlafaxine switchers and 14.1% [n=103] of venlafaxine-to-SSRI switchers) were calculated for the subgroup of patients who made a switch. A total of 48,950 patients were included in the study, with 43,653 (89.2%) treated first with SSRIs and 5,297 (10.8%) treated first with venlafaxine. Of the initial SSRI users, 1,645 (3.8%) switched to venlafaxine, and of the initial venlafaxine users, 733 (13.8%) switched to an SSRI. Mean (standard deviation [SD]) 12-month total (medical plus pharmacy) depression-related costs in 2002-2003 dollars were 118.0% higher for SSRI switchers ($1,225 [$3,438] vs. $562 [$2,153], P<0.001) and 18.4% higher for venlafaxine switchers ($863 [$1,503] vs. $729 [$1,185], P=0.021) as compared with non-switchers. From the pre-switch to post-switch periods, depression-related mean monthly medical costs declined by 66.4% among switchers from SSRIs ($113 [$912] vs. $38 [$347], P=0.001) and by 61.1% among switchers from venlafaxine ($54 [$299] vs. $21 [$138], P=0.005). Monthly mean depression-related pharmacy costs increased by 62.2% following a switch from an SSRI to venlafaxine (from $45 [$38] to $73 [$62

  7. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major de