title: Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events? A randomized, double‐blind, 24‐week study comparing the efficacy and tolerability of mirtazapine and paroxetine in depressed patients in primary care Escitalopram versus sertraline in the treatment of major depressive disorder: a randomized clinical trial* A multicentre, double-blind, amitriptyline-controlled study of mirtazapine in patients with major depression Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline Efficacy and tolerability of hypericum extract STW3 in long-term treatment with a once-daily dosage in comparison with sertraline. Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients. A National Survey of Cardiovascular Physicians' Beliefs and Clinical Care Practices When Diagnosing and Treating Depression in Patients With Cardiovascular Disease Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial. Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles. Nefazodone versus sertraline in outpatients with major depression: focus on efficacy, tolerability, and effects on sexual function and satisfaction. A 12-week study comparing moclobemide and sertraline in the treatment of outpatients with atypical depression Response to phenelzine and imipramine in placebo nonresponders with atypical depression A randomized, double-blind, active-control study of sertraline versus venlafaxine XR in major depressive disorder. Effects of the serotonin transporter gene promoter polymorphism on mirtazapine and paroxetine efficacy and adverse events in geriatric major depression. Randomized trial of sertraline versus venlafaxine XR in major depression: efficacy and discontinuation symptoms. Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study. Trait anxiety and the effect of a single high dose of diazepam in unipolar depression. Acute Efficacy of Fluoxetine Versus Sertraline and Paroxetine in Major Depressive Disorder Including Effects of Baseline Insomnia Comparison of mirtazapine and fluoxetine in the treatment of major depressive disorder: a double-blind, randomized trial. Mirtazapine Orally Disintegrating Tablets Versus Venlafaxine Extended Release: A Double-blind, Randomized Multicenter Trial Comparing the Onset of Antidepressant Response in Patients With Major Depressive Disorder Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients. Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry. A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: a STAR*D report. A double‐blind study of the efficacy and safety of sertraline and clomipramine in outpatients with severe major depression A double-blind comparison of sertraline and fluoxetine in depressed elderly outpatients. A comparative, randomized, double-blind study of trazodone prolonged-release and sertraline in the treatment of major depressive disorder Mirtazapine Versus Venlafaxine in Hospitalized Severely Depressed Patients With Melancholic Features A double‐blind multicentre comparison of mirtazapine and amitriptyline in elderly depressed patients Double‐blind study of the efficacy and safety of sertraline versus fluoxetine in major depression A double-blind study comparing the efficacy and tolerability of mirtazapine and doxepin in patients with major depression Association between industry funding and statistically significant pro-industry findings in medical and surgical randomized trials. Moclobemide and sertraline in the treatment of depressive disorders: a comparative study. Venlafaxine and mirtazapine treatment lowers serum concentrations of dehydroepiandrosterone-sulfate in depressed patients remitting during the course of treatment. Sertraline versus paroxetine in major depression: clinical outcome after six months of continuous therapy. The impact of reboxetine and mirtazapine on driving simulator performance and psychomotor function in depressed patients. Comparison of sertraline and nortriptyline in the treatment of major depressive disorder in late life. Double-blind comparison of bupropion sustained release and sertraline in depressed outpatients. Mirtazapine compared with paroxetine in major depression. Treatment of mood-congruent psychotic depression with imipramine. Comparison of the Effects of Mirtazapine and Fluoxetine in Severely Depressed Patients [Comparison of reboxetine and sertraline in terms of efficacy and safety in major depressive disorder]. The Norwegian naturalistic treatment study of depression in general practice (NORDEP)—I: randomised double blind study A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression. Prevalence of sexual dysfunction among newer antidepressants. A double‐blind multicenter trial comparing sertraline and citalopram in patients with major depression treated in general practice Reboxetine, the first selective noradrenaline reuptake inhibitor antidepressant: Efficacy and tolerability in 2613 patients Fluoxetine versus sertraline and paroxetine in major depression: tolerability and efficacy in anxious depression. Efficacy and tolerability of mirtazapine in treating major depressive disorder with anxiety symptoms: an 8-week open-label randomised paroxetine-controlled trial. A double-blind, randomized, group-comparative study of the tolerability and efficacy of 6 weeks' treatment with mirtazapine or fluoxetine in depressed Chinese patients. Comparison of 2 treatment strategies for depressed inpatients: imipramine and lithium addition or mirtazapine and lithium addition. [Efficacy and acceptability of tianeptine and sertraline in the acute treatment phase of depression]. Sertraline is more effective than imipramine in the treatment of non-melancholic depression:: Results from a multicentre, randomized study Mirtazapine is more effective than trazodone: a double‐blind controlled study in hospitalized patients with major depression Pharmacogenetics of antidepressant medication intolerance. Antidepressant efficacy and safety of low-dose sertraline and standard-dose imipramine for the treatment of depression in older adults: results from a double-blind, randomized, controlled clinical trial. Pharmacoeconomic analysis of sertraline treatment of depression in patients with unstable angina or a recent myocardial infarction. Mirtazapine Orally Disintegrating Tablet Versus Sertraline: A Prospective Onset of Action Study Mirtazapine: efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. Mirtazapine-Fluoxetine Study Group. Cardiovascular variability in major depressive disorder and effects of imipramine or mirtazapine (Org 3770). Double-blind controlled trial of sertraline versus paroxetine in the treatment of delusional depression. Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression. Effects of serotonergic and noradrenergic antidepressants on auditory startle response in patients with major depression Sertraline versus fluoxetine in the treatment of major depression: a combined analysis of five double‐blind comparator studies Comparative effects of mirtazapine and fluoxetine on sleep physiology measures in patients with major depression and insomnia. A preliminary study on the efficacy of sertraline and imipramine on anger attacks in atypical depression and dysthymia. A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients. A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline. Efficacy and tolerability of mirtazapine versus citalopram: a double-blind, randomized study in patients with major depressive disorder. Nordic Antidepressant Study Group. St John's wort or sertraline? Randomized controlled trial in primary care. Comparisons of the Efficacy and Tolerability of Extended-Release Venlafaxine, Mirtazapine, and Paroxetine in Treatment-Resistant Depression: A Double-Blind, Randomized Pilot Study in a Chinese Population Antidepressant treatment with mirtazapine, but not venlafaxine, lowers cortisol concentrations in saliva: A randomised open trial Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder. Mirtazapine and paroxetine in major depression: A comparison of monotherapy versus their combination from treatment initiation A double-blind comparison of sertraline and clomipramine in the treatment of major depressive disorder and associated anxiety in general practice Probing the safety of medications in the frail elderly: evidence from a randomized clinical trial of sertraline and venlafaxine in depressed nursing home residents. Efficacy and response time to sertraline versus fluoxetine in the treatment of unipolar major depressive disorder. Depressed in-patients respond differently to imipramine and mirtazapine. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials FKBP5 polymorphisms and antidepressant response in geriatric depression
abstract: CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P<.001 ; chi2 test ) . Logistic regression analyses indicated that funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data & NA ; Primary care patients with a major depressive disorder and 17‐item Hamilton Rating Scale for Depression ( 17‐HAM‐D ) score > 18 were r and omized to 24 weeks of treatment with mirtazapine  30‐45 mg/day ( n= 99 ) or paroxetine 20‐30 mg/day ( n=98 ) . Both treatments were efficacious in improving depressive symptomatology , as assessed by group mean 17‐HAM‐D scores , percentages of HAM‐D responders and remitters and Clinical Global Improvement responders . The mirtazapine group showed statistically significantly larger decreases from baseline in group mean 17‐HAM‐D scores at weeks 1 , 2 and 4 , and the difference with the paroxetine group reached the level of clinical relevance at weeks 2 and 4 . Antidepressant efficacy was maintained throughout both the acute and continuation phase of treatment . Both treatments were well tolerated . The only adverse event with a statistically significantly higher incidence in the mirtazapine group was fatigue . Statistically significantly more paroxetine‐treated patients complained of increased sweating , headache and nausea . The results demonstrate that both mirtazapine and paroxetine were efficacious and well tolerated when used for 24 weeks in depressed patients treated in primary care . An observed difference in efficacy favouring mirtazapine between weeks 1 and 4 indicates that mirtazapine patients had improved earlier compared to those on paroxetine , and corroborates similar findings in other comparisons of mirtazapine versus selective serotonin reuptake inhibitors ABSTRACT Objective : This trial was conducted to compare the efficacy and tolerability of a fixed dose of escitalopram 10 mg/day with sertraline optimally dosed within its recommended dose range ( 50–200 mg/day ) for the treatment of major depressive disorder . Methods : In this multicenter trial , depressed patients ( DSM‑IV defined ; baseline Montgomery – Asberg Depression Rating Scale [ MADRS ] ≥ 22 ) aged 18–80 years were r and omly assigned to 8 weeks of double-blind treatment with escitalopram ( 10 mg/day ) or sertraline ( 50–200 mg/day ) following a 1‑week single-blind placebo lead-in period . There was no placebo comparison arm . Sertraline was initiated at 50 mg/day , and could be increased by 50 mg/day at weekly intervals based on clinical need and tolerability at the lower dose level . The blind was maintained with matching double-blind placebo capsules for the escitalopram group . Change from baseline to endpoint in MADRS total score ( last observation carried forward ) was the primary efficacy measure . Results : A total of 212 patients received double-blind medication . At week 8 , the mean sertraline dosage was 144 mg/day ( median = 150 mg/day ) . Mean changes from baseline to endpoint in MADRS scores were –19.1 and –18.4 for the escitalopram and sertraline groups , respectively . At endpoint , 75 % and 70 % of escitalopram- and sertraline-treated patients , respectively , were responders ( ≥ 50 % improvement from baseline in mean MADRS scores ) . Both treatments were generally well tolerated ; only 2 % and 4 % of patients prematurely discontinued escitalopram and sertraline treatment , respectively , due to adverse events . Conclusion : No differences in efficacy were observed for fixed-dose escitalopram 10 mg/day and sertraline flexibly dosed from 50–200 mg/day . At these doses , both escitalopram and sertraline were generally well tolerated Background : the efficacy and tolerability of the new antidepressant mirtazapine were evaluated in a multicentre , r and omized , double-blind , amitriptyline-controlled , 5 week clinical study . Method : 156 patients with a DSM-III diagnosis of major depressive episode and 21-item Hamilton Psychiatric Rating Scale for Depression ( HPRSD ) score ≥ 18 , were r and omized to treatment with either mirtazapine  20 - 60 mg/day or amitriptyline  75 - 225 mg/day . Results : mirtazapine and amitriptyline were equally effective in reducing depressive symptoms , as assessed by the 17-item HPRSD and MADRS scales . Mirtazapine was better tolerated than amitriptyline , with fewer drop-outs due to adverse events and lower incidences of adverse events both at the beginning and at the end of the trial . Conclusion : this study shows that mirtazapine is as effective as amitriptyline in treating major depression , while at the same time better tolerated BACKGROUND Previous comparative studies of the selective serotonin reuptake inhibitors ( SSRIs ) have rarely included a placebo control group and have rarely demonstrated significant between-group differences . The study reported on here was a placebo-controlled comparison of the antidepressant effects of two SSRIs , citalopram and sertraline . METHODS Three hundred twenty-three patients with DSM-IV-defined major depressive disorder were r and omized to 24 weeks of double-blind treatment with citalopram ( 20 - 60 mg/day ) , sertraline ( 50 - 150 mg/day ) , or a placebo . The primary efficacy measure was the Hamilton Depression Rating Scale ( HAMD ) and the primary statistical analysis was an analysis of variance comparing the change from baseline to the last observation carried forward in each treatment group . RESULTS Both citalopram and sertraline produced significantly greater improvement than placebo on the HAMD , the Montgomery-Asberg Depression Rating Scale , and the Clinical Global Impression Scale . Significant improvement was observed at earlier timepoints in the citalopram group than the sertraline group ; however , sertraline treatment was associated with increased gastrointestinal side effects and a tendency toward early discontinuation , and analyses that excluded early dropouts revealed similar acute efficacy for the two active treatments . The Hamilton Anxiety Scale demonstrated a significant anxiolytic effect of citalopram , but not sertraline , relative to placebo . CONCLUSIONS This study confirms the antidepressant efficacy of two SSRIs , citalopram and sertraline . It is hypothesized that the more consistent evidence of antidepressant activity that was observed early in treatment in the citalopram group was related to more pronounced antianxiety effects and better tolerability upon initiation of therapy OBJECTIVE The objective of this double-blind , multi-center clinical study was to demonstrate the non-inferiority of hypericum extract versus sertraline in the treatment of moderate depression . METHODS A total of 241 patients with a diagnosis of moderate depressive disorder ( according to ICD-10 criteria ) were r and omized with either 50 mg sertraline or 612 mg hypericum extract ( hypericum group n = 123 ; sertraline group n = 118 ) . According to the study protocol , 200 patients were treated for at least 12 weeks ( n = 102 hypericum extract ; n = 98 sertraline )  ; 81 patients in the hypericum group and 80 in the sertraline group were treated after week 12 for an additional 12 weeks . Thus , most patients were treated for a period of 6 months . The primary efficacy variable was the 17-item HAMD total score at the end of the first 12-week double-blind treatment period . RESULTS After the first 12-week treatment period , the HAMD score decreased from almost identical initial values ( 22.0 + /- 1.1 for hypericum and 22.1 + /- 1.1 points for sertraline ) to 8.3 + /- 5.5 points ( hypericum ) and 8.1 + /- 5.6 points ( sertraline ) ( mean + /- SD ) in the patients treated per- protocol ( PP ) population . The statistical test for non-inferiority ( boundary delta = 3 ) revealed that hypericum extract is not inferior to sertraline ( P < 0.0001 ) . The mean difference between the treatments was 0.1995 points , with a corresponding one-sided 97.5 % confidence interval ( -infinity , 1.3772 ) . In patients who continued treatment in the follow-up phase , the HAMD score at the end of the study was 5.7 + /- 4.8 points ( hypericum group ) and 7.1 + /- 6.3 points ( sertraline group ) . Comparable improvement was also found for the von Zerssen 's Adjective Mood Scale ( BfS ) and CGI during the first and second 12-week treatment period in both treatment groups . With 68.6 % of patients in the hypericum group and 70.4 % in the sertraline group , the percentage of patients rated as responders did not differ significantly between treatment groups ( 12 weeks ) . The adverse events of 12 patients in the hypericum group ( 9.8 % ) and of 16 patients in the sertraline group ( 13.6 % ) were possibly related to study medication . No basic differences in the treatment groups were observed and no interaction with concomitant medication was documented . In most cases , the investigators assessed the tolerability of hypericum extract and sertraline as " good " or " very good . " CONCLUSIONS The results indicate that hypericum extract STW 3 is not inferior to sertraline and that it is a well-tolerated drug for the treatment of moderate depression . These favorable effects were achieved with a once-daily dose of 612 mg of hypericum extract given for up to 24 weeks OBJECTIVE Authors studied the efficacy and tolerability of mirtazapine and paroxetine in elderly patients with major depression during an acute phase ( 8 weeks ) and an extension phase ( 16 weeks ) . METHODS Patients with major depression and without dementia , at least 65 years old , were eligible ; they were r and omized to mirtazapine or paroxetine once daily , with doses increasing over 42 days . Efficacy was assessed with the Ham-D and Clinical Global Impressions Scale , and tolerability was assessed from adverse events . RESULTS Of 255 patients r and omized , 126 on mirtazapine and 120 on paroxetine were included in the efficacy analysis . Differences favoring mirtazapine were observed for the mean change from baseline in Ham-D-17 score . Other significant differences were in the proportion of patients classified as responders ( 50 % decrease from baseline Ham-D-17 scores ) at Day 14 and in remission ( Ham-D-17 score of 7 or less ) at Day 42 . The median time to response was 26 days in the mirtazapine group and 40 days in the paroxetine group . The mirtazapine group also showed more reduction in Ham-D Factor I ( Anxiety/Somatization ) and Factor VI ( Sleep Disturbance ) scores . Efficacy of both drugs was maintained during the extension phase . Patients on paroxetine were more likely to discontinue therapy in the acute phase because of adverse events . CONCLUSION During the first weeks of treatment , antidepressant effects were more pronounced in the mirtazapine group , suggesting that mirtazapine has an earlier onset of action . Mirtazapine also demonstrated a better tolerability profile and represents a valuable option for the treatment of depression in elderly patients A national survey was administered to determine 1 ) cardiovascular physicians ' beliefs about the association between depression and cardiovascular disease ( CVD ) , 2 ) the methods used to diagnose depression , 3 ) referral patterns for treatment of depression , and 4 ) frequency of use and preferred choice of antidepressant . A national survey of 50 % of r and omly selected U.S. cardiovascular physicians belonging to the American College of Cardiology was conducted ; 796 of 8854 physicians who received the question naires responded . Cardiovascular physicians were aware of indirect associations between depression and coronary artery disease ( CAD ) . However , 49.9 % were unaware of depression as an independent cardiac risk factor ; 71.2 % asked less than half their patients with CAD about depression ; 79 % used no st and ard screening method to diagnose depression . Among cardiovascular physicians , 84.8 % reported that between 1 % and 50 % of their patients have depression , and 49.2 % indicated that they treat the symptoms of depression in their patients with CAD . Cardiovascular physicians often refer depressed patients with CAD to mental health professionals and recommend exercise , relaxation training , stress management , psychotherapy , and diaries for their patients . Among cardiovascular physicians , 55.5 % treat depression/CAD with antidepressant medication : sertraline ( 28 % ) , paroxetine ( 16.1 % ) , fluoxetine ( 10.8 % ) , escitalopram ( 8.7 % ) , citalopram ( 7.9 % ) , bupropion ( 4.4 % ) , tricyclic antidepressants ( 3.8 % ) , and venlafaxine 2.9 % CONTEXT Extracts of Hypericum perforatum ( St John 's wort ) are widely used for the treatment of depression of varying severity . Their efficacy in major depressive disorder , however , has not been conclusively demonstrated . OBJECTIVE To test the efficacy and safety of a well-characterized H perforatum extract ( LI-160 ) in major depressive disorder . DESIGN AND SETTING Double-blind , r and omized , placebo-controlled trial conducted in 12 academic and community psychiatric research clinics in the United States . PARTICIPANTS Adult out patients ( n = 340 ) recruited between December 1998 and June 2000 with major depression and a baseline total score on the Hamilton Depression Scale ( HAM-D ) of at least 20 . INTERVENTIONS Patients were r and omly assigned to receive H perforatum , placebo , or sertraline ( as an active comparator ) for 8 weeks . Based on clinical response , the daily dose of H perforatum could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg . Responders at week 8 could continue blinded treatment for another 18 weeks . MAIN OUTCOME MEASURES Change in the HAM-D total score from baseline to 8 weeks ; rates of full response , determined by the HAM-D and Clinical Global Impressions ( CGI ) scores . RESULTS On the 2 primary outcome measures , neither sertraline nor H perforatum was significantly different from placebo . The r and om regression parameter estimate for mean ( SE ) change in HAM-D total score from baseline to week 8 ( with a greater decline indicating more improvement ) was -9.20 ( 0.67 ) ( 95 % confidence interval [ CI ] , -10.51 to -7.89 ) for placebo vs -8.68 ( 0.68 ) ( 95 % CI , -10.01 to -7.35 ) for H perforatum ( P = .59 ) and -10.53 ( 0.72 ) ( 95 % CI , -11.94 to -9.12 ) for sertraline ( P = .18 ) . Full response occurred in 31.9 % of the placebo-treated patients vs 23.9 % of the H perforatum-treated patients ( P = .21 ) and 24.8 % of sertraline-treated patients ( P = .26 ) . Sertraline was better than placebo on the CGI improvement scale ( P = .02 ) , which was a secondary measure in this study . Adverse-effect profiles for H perforatum and sertraline differed relative to placebo . CONCLUSION This study fails to support the efficacy of H perforatum in moderately severe major depression . The result may be due to low assay sensitivity of the trial , but the complete absence of trends suggestive of efficacy for H perforatum is noteworthy CONTEXT Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected , but direct evidence of such bias is currently limited to case reports . OBJECTIVE To study empirically the extent and nature of outcome reporting bias in a cohort of r and omized trials . DESIGN Cohort study using protocol s and published reports of r and omized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg , Denmark , in 1994 - 1995 . The number and characteristics of reported and unreported trial outcomes were recorded from protocol s , journal articles , and a survey of trialists . An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta- analysis . Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias . Protocol s and published articles were also compared to identify discrepancies in primary outcomes . MAIN OUTCOME MEASURES Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes ; consistency between primary outcomes defined in the most recent protocol s and those defined in published articles . RESULTS One hundred two trials with 122 published journal articles and 3736 outcomes were identified . Overall , 50 % of efficacy and 65 % of harm outcomes per trial were incompletely reported . Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy ( pooled odds ratio , 2.4 ; 95 % confidence interval [ CI ] , 1.4 - 4.0 ) and harm ( pooled odds ratio , 4.7 ; 95 % CI , 1.8 - 12.0 ) data . In comparing published articles with protocol s , 62 % of trials had at least 1 primary outcome that was changed , introduced , or omitted . Eighty-six percent of survey responders ( 42/49 ) denied the existence of unreported outcomes despite clear evidence to the contrary . CONCLUSIONS The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocol s. Published articles , as well as review s that incorporate them , may therefore be unreliable and overestimate the benefits of an intervention . To ensure transparency , planned trials should be registered and protocol s should be made publicly available prior to trial completion BACKGROUND The efficacy , tolerability , and effects on sexual function and satisfaction of nefazodone and sertraline were compared in a multicenter , r and omized , double-blind , parallel-group study in out patients with major depression . METHOD One hundred sixty patients , 18 years of age or older , who met DSM-III-R criteria for single or recurrent nonpsychotic major depressive episodes were r and omly assigned to 6 weeks of treatment with either nefazodone ( 100 - 600 mg/day ) or sertraline ( 50 - 200 mg/day ) . Symptoms were assessed before and during treatment using the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) , Clinical Global Impressions ( CGI ) Improvement scale , the CGI Severity of Illness scale , and a sexual function question naire . RESULTS Of 143 patients evaluable for efficacy , 72 received sertraline and 71 received nefazodone . The mean modal daily dose at endpoint was 148 mg for sertraline and 456 mg for nefazodone . Analysis of efficacy measures ( HAM-D-17 and CGI ) showed consistent and comparable improvement in symptoms of depression for both treatment groups . Sertraline had negative effects on sexual function and satisfaction in both men and women , and nefazodone had no adverse effect on sexual well-being . Safety assessment s based on adverse events , vital sign measurements , electrocardiographs , physical examinations , and clinical laboratory tests revealed no serious adverse events or organ toxicity associated with nefazodone or sertraline administration . CONCLUSION Nefazodone and sertraline are well tolerated , and there was no statistically significant difference in their antidepressant activity .  Sertraline treatment has negative effects on sexual function and performance in both sexes , while nefazodone has none . These findings may have clinical implication s when choosing antidepressant therapy One hundred and ninety-seven out patients with atypical depression [ Atypical Depression Diagnostic Scale ( ADDS ) score=4 ] were r and omized to 12 weeks of double-blind treatment with sertraline or moclobemide  in a multicentre , parallel-group clinical trial . Patients were started on either 50 mg/day sertraline or 300 mg/day moclobemide . If the therapeutic response was not satisfactoryafter 4 weeks , the dose could be increased to either 100 mg/day sertraline or 450 mg/day moclobemide . Primary effcacy evaluations were the 29-item Hamilton Psychiatric Rating Scale for Depression ( HAM-D ) and the Clinical Global Impression of Improvement ( CGI I ) response rate ( much or very much improved ) at study endpoint . Secondary effcacy evaluations included the ADDS , the Hamilton Anxiety Scale ( HAMA ) , the Leeds Sleep Scale , and the Battelle Quality of Life Battery ( BQOLB ) . In the analysis of the 172 patient effcacy-evaluable population , there was significant baseline to endpoint improvement in all primary and secondary effcacy assessment s after treatment with either sertraline or moclobemide . At the endpoint , the proportion of responders on CGI-I , was 77.5 % in the sertraline group and 67.5 % in the moclobemide group ( p=0.052 ) . The baseline to endpoint mean 29-item HAM-D score decreased from 35.9 to 14.5 in the sertraline group and from 36.3 to 16.1 in the moclobemide group . Sertraline also result ed in a significantly ( p50.05 ) greater degree of improvement at the endpoint , compared with moclobemide , in the proportion of remitters on the HAMA ( total score47 ) , ADDS Category IID ( Rejection Sensitivity ) , Leeds Sleep Factor 4 ( Integrity of Behaviour Following Awakening ) , and on three dimensions of the BQOLB ( Energy/Vitality , Social Interaction and Life Satisfaction ) . There were no other significant differences between treatment groups . Overall , both medications were well tolerated . In this study , both sertraline and moclobemide improved the symptoms of atypical depression We employed a study design that permitted a double-blind 12-week contrast of imipramine hydrochloride and phenelzine sulfate therapies in patients who met Columbia University criteria for atypical depression and were unresponsive to 7 weeks of treatment with placebo .  These patients were found to benefit selectively from therapy with monoamine oxidase inhibitors compared with tricyclic drug therapy . This supports our observation about treatment response in depressed patients with reversed vegetative features . The design we utilized in this study has not previously been reported , to our knowledge . It was hypothesized that it would offer the advantage of the removal of a portion of placebo responders and serve to replicate our original findings . Treatment response to therapy with both  imipramine and pheneizine  in placebo nonresponders was uniformly lower ( roughly 20 % less than corresponding rates for patients who did not participate in the initial 6-week placebo trial ) . This is consistent with the view that the lower response rates were a result of the removal of some " placebo " responders in the drug groups . We think this is a useful design that should be considered in all studies of placebo and two active treatment regimens OBJECTIVE Sertraline may produce dual neurotransmitter effects similar to the serotonin-norepinephrine reuptake inhibitors ( SNRIs ) ; however , it has been tested against an SNRI in only 1 previous study , and never at an optimal dose . The objective of the current multisite study was to compare relatively higher doses of sertraline ( i.e. , 150 mg/day ) and venlafaxine extended release ( XR ) ( 225 mg/day ) in out patients with major depressive disorder . METHOD Subjects with DSM-IV major depressive disorder were r and omly assigned to 8 weeks of double-blind treatment with sertraline ( N = 82 ) or venlafaxine XR ( N = 78 ) . The study ran from January 2002 through January 2003 . The primary outcome measure was the Quality of Life Enjoyment and Satisfaction Question naire ; secondary outcome variables included the 17-item Hamilton Rating Scale for Depression . RESULTS Both treatments led to significant improvement in depressive symptoms and quality -of-life measures . No significant differences were noted between treatment groups for final scores on the primary or secondary measures . The treatment groups did not differ significantly in the percentage of responders  ( sertraline = 55 % , venlafaxine XR = 65 % ; intent-to-treat [ ITT ] sample ) or remitters ( sertra-line = 38 % , venlafaxine XR = 49 % ; ITT sample ) , although the proportions are similar to those found in earlier selective serotonin reuptake inhibitor ( SSRI ) vs. venlafaxine meta-analyses . In patients who achieved the maximum dose of drug and maintained it for 3 weeks , response rates were similar to those found at lower doses ( sertraline = 59 % , venlafaxine XR = 70 % ) ; however , remission rates for this sample were comparable for both drug groups ( sertraline = 48 % , venlafaxine XR = 50 % ) . CONCLUSIONS The efficacies of sertraline and venlafaxine XR were comparable . Although response and remission rates did not differ statistically , the rates were analogous to those reported in previous meta-analyses . However , at clinical ly relevant higher doses , the remission rates were very similar . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00179283 BACKGROUND The " long/short"polymorphism ( 5HTTLPR ) in the promoter of the serotonin transporter gene ( SLC6A4 ) has been proposed as a pharmacogenetic marker for antidepressant efficacy . Some but not all studies have found that the short form of 5HTTLPR ( S allele ) results in decreased efficacy of selective serotonin reuptake inhibitors . OBJECTIVE To determine if the 5HTTLPR polymorphism influences the efficacy and tolerability of mirtazapine and paroxetine hydrochloride , 2 frequently prescribed antidepressants with differing pharmacologic profiles , in geriatric depression . DESIGN Double-blind , r and omized 8-week study . SETTING Eighteen academic and private outpatient clinics . PATIENTS We evaluated 246 cognitively intact patients 65 years or older with major depression . INTERVENTIONS Antidepressant therapy with 15 to 45 mg/d of mirtazapine ( n = 124 ) or 20 to 40 mg/d of paroxetine ( n = 122 ) . MAIN OUTCOME MEASURES The Hamilton Depression Rating Scale-17 and Geriatric Depression Scale , severity of adverse events and dosing compliance indexes , and discontinuations due to adverse events . Outcome measures were stratified according to 5HTTLPR genotypes . RESULTS Geriatric Depression Scale scores indicated that S allele carriers treated with paroxetine showed a small impairment in antidepressant response . Among mirtazapine-treated patients , there was little indication that the 5HTTLPR genotype affected antidepressant efficacy . However , the 5HTTLPR polymorphism had a dramatic effect on adverse events . Among paroxetine-treated subjects , S allele carriers experienced more severe adverse events during the course of the study , achieved significantly lower final daily doses , and had more discontinuations at days 14 , 21 , 28 , 42 , and 49 . Surprisingly , among mirtazapine-treated subjects , S allele carriers had fewer discontinuations due to adverse events , experienced less severe adverse events , and achieved higher final daily doses . CONCLUSIONS These results support the hypothesis that the S allele of 5HTTLPR at the SLC6A4 locus is associated with a poor outcome after treatment with selective serotonin reuptake inhibitors . However , the major effect was on the tolerability of these drugs rather than efficacy . Results from mirtazapine-treated patients indicate that the effect of this polymorphism on outcome may depend on the mechanism of antidepressant action BACKGROUND The comparative efficacy of selective serotonin reuptake inhibitors ( SSRIs ) and serotonin-norepinephrine reuptake inhibitors ( SNRIs ) was recently debated . Meta-analyses , based mainly on fluoxetine comparator data , suggest that the SNRI venlafaxine has superior efficacy to SSRIs in treatment of major depression . OBJECTIVE To compare quality of life ( QOL ) , efficacy , safety , and tolerability associated with sertraline and venlafaxine extended release ( XR ) for treatment of DSM-IV major depression . METHOD This was an 8-week , double-blind , r and omized study of sertraline ( 50 - 150 mg/day ) versus venlafaxine XR ( 75 - 225 mg/day ) , followed by a 2-week taper period . Subjects were recruited from 7 sites in Turkey and 6 sites in Australia between October 2002 and July 2003 . The primary outcome measure was the Quality of Life Enjoyment and Satisfaction Question naire . Secondary outcome measures included measures of depression ( including response and remission ) , anxiety , pain , safety ( e.g. , blood pressure ) , and tolerability ( e.g. , discontinuation symptoms ) . RESULTS A total of 163 subjects received study treatment ( women , 69 % ; mean age , 37.0 [ SD = 12.9 ] years ) . No significant differences in QOL or efficacy were noted between treatments on the primary or secondary endpoints for the total study population or the anxious depression and severe depression subgroups . A priori analyses of symptoms associated with treatment discontinuation demonstrated no difference between treatment groups . However , in post hoc analyses , sertraline was associated with less burden of moderate to severe discontinuation symptoms . Venlafaxine XR was associated with a relative increase in mean blood pressure ( supine diastolic blood pressure , -4.4 mm Hg difference at week 8/last observation carried forward ) . CONCLUSION Sertraline and venlafaxine XR demonstrated comparable effects on QOL and efficacy in treatment of major depression , although sertraline may be associated with a lower symptom burden during treatment discontinuation and a reduced risk of blood pressure increase CONTEXT Few r and omized controlled trials have evaluated the efficacy of treatments for major depression in patients with coronary artery disease ( CAD ) . None have simultaneously evaluated an antidepressant and short-term psychotherapy . OBJECTIVE To document the short-term efficacy of a selective serotonin reuptake inhibitor ( citalopram ) and interpersonal psychotherapy ( IPT ) in reducing depressive symptoms in patients with CAD and major depression . DESIGN , SETTING , AND PARTICIPANTS The Canadian Cardiac R and omized Evaluation of Antidepressant and Psychotherapy Efficacy , a r and omized , controlled , 12-week , parallel-group , 2 x 2 factorial trial conducted May 1 , 2002 , to March 20 , 2006 , among 284 patients with CAD from 9 Canadian academic centers . All patients met Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria for diagnosis of major depression of 4 weeks ' duration or longer and had baseline 24-item Hamilton Depression Rating Scale ( HAM-D ) scores of 20 or higher . INTERVENTIONS Participants underwent 2 separate r and omizations : ( 1 ) to receive 12 weekly sessions of IPT plus clinical management ( n = 142 ) or clinical management only ( n = 142 ) and ( 2 ) to receive 12 weeks of citalopram , 20 to 40 mg/d ( n = 142 ) , or matching placebo ( n = 142 ) . MAIN OUTCOME MEASURES The primary outcome measure was change between baseline and 12 weeks on the 24-item HAM-D , administered blindly during central ized telephone interviews ( tested at alpha = .033 ) ; the secondary outcome measure was self-reported Beck Depression Inventory II ( BDI-II ) score ( tested at alpha = .017 ) . RESULTS Citalopram was superior to placebo in reducing 12-week HAM-D scores ( mean difference , 3.3 points ; 96.7 % confidence interval [ CI ] , 0.80 - 5.85 ; P = .005 ) , with a small to medium effect size of 0.33 . Mean HAM-D response ( 52.8 % vs 40.1 % ; P = .03 ) and remission rates ( 35.9 % vs 22.5 % ; P = .01 ) and the reduction in BDI-II scores ( difference , 3.6 points ; 98.3 % CI , 0.58 - 6.64 ; P = .005 ; effect size = 0.33 ) also favored citalopram . There was no evidence of a benefit of IPT over clinical management , with the mean HAM-D difference favoring clinical management ( -2.26 points ; 96.7 % CI , -4.78 to 0.27 ; P = .06 ; effect size , 0.23 ) . The difference on the BDI-II did not favor clinical management ( 1.13 points ; 98.3 % CI , -1.90 to 4.16 ; P = .37 ; effect size = 0.11 ) . CONCLUSIONS This trial documents the efficacy of citalopram administered in conjunction with weekly clinical management for major depression among patients with CAD and found no evidence of added value of IPT over clinical management . Based on these results and those of previous trials , citalopram or sertraline plus clinical management should be considered as a first-step treatment for patients with CAD and major depression . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N15858091 OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are widely used to treat depression , but the rates , timing , and baseline predictors of remission in " real world " patients are not established . The authors ' primary objectives in this study were to evaluate the effectiveness of citalopram , an SSRI , using measurement-based care in actual practice , and to identify predictors of symptom remission in out patients with major depressive disorder . METHOD This clinical study included out patients with major depressive disorder who were treated in 23 psychiatric and 18 primary care " real world " setting s. The patients received flexible doses of citalopram prescribed by clinicians for up to 14 weeks . The clinicians were assisted by a clinical research coordinator in the application of measurement-based care , which included the routine measurement of symptoms and side effects at each treatment visit and the use of a treatment manual that described when and how to modify medication doses based on these measures . Remission was defined as an exit score of < or=7 on the 17-item Hamilton Depression Rating Scale ( HAM-D ) ( primary outcome ) or a score of < or=5 on the 16-item Quick Inventory of Depressive Symptomatology , Self-Report ( QIDS-SR ) ( secondary outcome ) . Response was defined as a reduction of > or=50 % in baseline QIDS-SR score . RESULTS Nearly 80 % of the 2,876 out patients in the analyzed sample had chronic or recurrent major depression ; most also had a number of comorbid general medical and psychiatric conditions . The mean exit citalopram dose was 41.8 mg/day . Remission rates were 28 % ( HAM-D ) and 33 % ( QIDS-SR ) . The response rate was 47 % ( QIDS-SR ) . Patients in primary and psychiatric care setting s did not differ in remission or response rates . A substantial portion of participants who achieved either response or remission at study exit did so at or after 8 weeks of treatment . Participants who were Caucasian , female , employed , or had higher levels of education or income had higher HAM-D remission rates ; longer index episodes , more concurrent psychiatric disorders ( especially anxiety disorders or drug abuse ) , more general medical disorders , and lower baseline function and quality of life were associated with lower HAM-D remission rates . CONCLUSIONS The response and remission rates in this highly generalizable sample with substantial axis I and axis III comorbidity closely resemble those seen in 8-week efficacy trials . The systematic use of easily implemented measurement-based care procedures may have assisted in achieving these results BACKGROUND Hypericum ( St. John 's wort ) has been shown to be as efficacious and well tolerated as st and ard antidepressants in the treatment of depression but has not been compared with selective serotonin reuptake inhibitors ( SSRIs ) . OBJECTIVE This study compared hypericum and the SSRI sertraline in the treatment of depression . METHODS In a double-blind , r and omized study conducted in a community hospital , 30 male and female out patients ( 19 women , 11 men ; mean age , 45.5 years ) with mild to moderate depression received 600 mg/d of a st and ardized extract of hypericum ( LI 160 ) or 50 mg/d sertraline for I week , followed by hypericum 900 mg/d or sertraline 75 mg/d for 6 weeks . RESULTS The severity of symptoms , as assessed by scores on the Hamilton Rating Scale for Depression ( HAM-D ) and the Clinical Global Impression scale , was significantly reduced in both treatment groups ( P < 0.01 ) . Clinical response ( defined as a > or = 50 % reduction in HAM-D scores ) was noted in 47 % of patients receiving hypericum and 40 % of those receiving sertraline . The difference was not statistically significant . Both agents were well tolerated . A post hoc power analysis indicated that failure to reach statistical significance between treatments result ed primarily from an absence of clinical differences rather than the small sample size . CONCLUSION The hypericum extract was at least as effective as sertraline in the treatment of mild to moderate depression in a small group of out patients In this cross-sectional study we explored in 101 depressive in- patients ( DSM III-R ) the association between level of trait anxiety and variables that have been investigated previously to discern primary and secondary depression , respectively . Besides , we explored the influence of trait anxiety level on difference in treatment response to either imipramine or mirtazapine .  Trait anxiety was measured interviewing a close relative of the patient using a question naire related to aspects of psychic anxiety and to aspects of somatic anxiety . The interviewer focussed on fluctuating anxiety symptoms without persistent mood disturbance during the patient 's normal lifelong functioning before developing a depressed mood . We found no relation between trait anxiety level and treatment response to either imipramine or mirtazapine . The most important finding of this study is the significant differential response to the diazepam test : depressive patients with high trait anxiety showed , predominantly , a disappearance of depressive symptoms without sedation and depressive patients with low trait anxiety showed , predominantly , sedation without disappearance of depressive symptoms . The opposite response to the diazepam test in patients with a different history of trait anxiety in spite of similar depressive symptomatology suggests differences in underlying pathophysiologic mechanisms This study assessed whether fluoxetine , sertraline , and paroxetine differ in efficacy and tolerability in depressed patients and the impact of baseline insomnia on outcomes . Patients ( N = 284 ) with DSM-IV major depressive disorder were r and omly assigned in a double-blind fashion to fluoxetine , paroxetine , or sertraline for 10 to 16 weeks of treatment . Using the Hamilton Rating Scale for Depression ( HAM-D ) sleep disturbance factor score , patients were categorized into low ( < 4 ) or high ( ≥4 ) baseline insomnia subgroups . Changes in depression and insomnia were assessed . Safety assessment s included treatment-emergent adverse events ( AEs ) , reasons for discontinuation , and AEs leading to discontinuation . In addition , AEs were evaluated within insomnia subgroups to determine emergence of activation or sedation . Depression improvement , assessed with the HAM-D-17 total score , was similar among treatments in all patients ( p = 0.365 ) and the high ( p = 0.853 ) and low insomnia ( p = 0.415 ) subgroups . Insomnia improvement , assessed with the HAM-D sleep disturbance factor score , was similar among treatments in all patients ( p = 0.868 ) and in the high ( p = 0.852 ) and low insomnia ( p = 0.982 ) subgroups . Analyses revealed no significant differences between treatments in the percentages of patients with substantial worsening , any worsening , worsening at endpoint , or improvement at endpoint in the HAM-D sleep disturbance factor in either insomnia subgroup . Treatments were well tolerated in most patients . No significant differences between treatments in the incidence of AEs suggestive of activation or sedation were seen in the insomnia subgroups . These data show no significant differences in acute treatment efficacy and tolerability across fluoxetine , sertraline , and paroxetine in major depressive disorder patients . Improvement in overall depression and in associated insomnia was achieved by most patients regardless of baseline insomnia BACKGROUND Depression is an international public health problem . The aim of this study was to compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Iranian patients suffering major depressive disorder . METHODS Thirty-six in patients and out patients with a diagnosis of major depressive disorder ( Diagnostic and Statistical Manual of Mental Disorders-IV ) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) were r and omly assigned to 6 weeks of treatment with mirtazapine ( 30 mg/day ) or fluoxetine ( 20 mg/day ) . Efficacy was assessed by HAM-D-17 . Information about adverse events was obtained by question ing of participants and /or their examination . Assessment s were performed at weeks 0 , 1 , 2 , 3 , 4 and 6 . RESULTS Sixteen of mirtazapine-treated patients and fifteen of fluoxetine-treated patients completed the 6-week study period . Both treatment groups were well matched at baseline with respect to demographic and disease characteristics . Both drugs showed a significant improvement over the 6 weeks of treatment ( P < 0.001 ) . There was no statistically significant difference between the mean + /- SEM HAM-D scores of two groups at weeks 1 , 2 , 3 , 4 , and at the end point . There were no significant differences between two groups in terms of response to treatment ( > or = 50 % decrease from baseline in HAM-D-17 total score ) and remission ( HAM-D-17 score of < or = 7 ) . None of the differences in reported adverse events was statistically significant . CONCLUSION In this study , mirtazapine and fluoxetine were equally effective and well tolerated after 6 weeks of treatment in patients with major depressive disorder This r and omized , multicenter , double-blind study was design ed to compare specifically the onset of antidepressant action of mirtazapine orally disintegrating tablets ( ODT ) with venlafaxine extended-release ( XR ) formulation in out patients with major depression . Both treatments were administered in a rapidly escalating dosing regimen . Target doses ( mirtazapine ODT , 45 mg OD ; venlafaxine XR , 225 mg OD ) were reached by day 6 of treatment . On the primary efficacy parameter [ the average of the change in HAM-D ( 17-item ) total score on days 5 , 8 , 11 , and 15 ] , mirtazapine ODT was significantly superior to venlafaxine XR ( P = 0.008 ) . In addition , calculating the HAM-D score without the sleep items result ed in significant reductions in favor of mirtazapine ODT on days 8 ( P = 0.006 ) and 11 ( P = 0.037 ) . The proportion of responders ( HAM-D decrease of ≥50 % from baseline ) was higher in the mirtazapine ODT group on all assessment days , being significant on days 8 ( P = 0.002 ) , 11 ( P = 0.004 ) , and 22 ( P = 0.027 ) . More patients in the mirtazapine ODT group achieved remission ( HAM-D total score of ≤7 ) up to day 29 , and the difference was statistically significant on day 15 ( P = 0.016 ) . Significant differences in favor of mirtazapine ODT were evident in the CGI of change on days 8 ( P = 0.019 ) , 11 ( P = 0.004 ) , and 15 ( P = 0.031 ) , and the CGI of severity on days 8 ( P = 0.014 ) and 11 ( P = 0.033 ) . Both treatments were well tolerated . These results indicate that mirtazapine ODT has a faster onset of antidepressant efficacy  than venlafaxine XR in patients with major depressive disorder , and that this effect is independent of its sleep-improving properties Two hundred forty-one elderly depressed patients entered the 8-week , double-blind phase of this parallel-group , multicenter study ; 161 patients were r and omized to receive sertraline ( 50 - 200 mg/day ) and 80 were r and omized to receive amitriptyline  ( 50 - 150 mg/day ) . Among evaluable patients , there were no statistically significant differences between treatments in any of the primary efficacy variables : change in total Hamilton Rating Scale for Depression ( HAM-D ) score ( 17 items ) , percentage change in HAM-D score , change in HAM-D Item 1 , change in Clinical Global Impressions ( CGI ) Severity score , change in the Depression Factor of the 56-item Hopkins Symptom Checklist , and the CGI Improvement score at the last visit . Similar results were obtained using data from all patients ( intention-to-treat analysis ) , except that amitriptyline was superior in HAM-D Total score ( p = .044 ) . The two drugs produced a similar degree of response : on the basis of the HAM-D criterion , 69.4 % of sertraline patients and 62.5 % of amitriptyline patients responded , and , on the basis of CGI criterion , 79.5 % of sertraline and 73.4 % of amitriptyline patients responded . Twenty-eight percent of the sertraline patients withdrew from the study because of a treatment-related side effect and 2.5 % ( 4 ) because of a laboratory abnormality . In comparison , 35 % of the amitriptyline patients withdrew because of treatment-related side effects . Sertraline was associated with a statistically lower frequency of somnolence , dry mouth , constipation , ataxia , and pain and a higher frequency of nausea , anorexia , diarrhea/loose stools , and insomnia ; thus , anticholinergic effects were less common and gastrointestinal effects were more common with sertraline than with amitriptyline . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE Financial conflict of interest has been reported to be prevalent in clinical trials in general medicine and associated with a greater likelihood of reporting results favorable to the intervention being studied . The extent and implication s of industry sponsorship and financial conflict of interest in psychiatric clinical trials have not been investigated , to the authors ' knowledge . METHOD The authors examined funding source and author financial conflict of interest in all clinical trials published in the American Journal of Psychiatry , the Archives of General Psychiatry , the Journal of Clinical Psychopharmacology , and the Journal of Clinical Psychiatry between 2001 and 2003 . RESULTS Among 397 clinical trials identified , 239 ( 60 % ) reported receiving funding from a pharmaceutical company or other interested party , and 187 studies ( 47 % ) included at least one author with a reported financial conflict of interest . Among the 162 r and omized , double-blind , placebo-controlled studies examined , those that reported conflict of interest were 4.9 times more likely to report positive results ; this association was significant only among the subset of pharmaceutical industry-funded studies . CONCLUSIONS Author conflict of interest appears to be prevalent among psychiatric clinical trials and to be associated with a greater likelihood of reporting a drug to be superior to placebo OBJECTIVE Few controlled studies have addressed the issue of which antidepressant medications should be recommended for out patients who have not responded to multiple treatment trials . This study compared the efficacy of switching to mirtazapine to that of switching to a tricyclic antidepressant ( nortriptyline ) following two prospect i ve , consecutive , unsuccessful medication treatments for nonpsychotic major depressive disorder . METHOD Following lack of remission or an inability to tolerate an initial trial of citalopram for up to 12 weeks ( first step ) and a second trial with either monotherapy involving another antidepressant or augmentation of citalopram with bupropion or buspirone ( second step ) , adult out patients ( N=235 ) with nonpsychotic major depressive disorder were r and omly assigned to 14 weeks of treatment with mirtazapine ( up to 60 mg/day ) ( N=114 ) or nortriptyline ( up to 200 mg/day ) ( N=121 ) . The primary outcome , symptom remission , was defined a priori as a total exit score of < /=7 on the 17-item Hamilton Rating Scale for Depression . The 16-item Quick Inventory of Depressive Symptomatology-Self-Report ( QIDS-SR(16 ) ) , obtained at treatment visits , provided secondary outcomes of remission ( score < /=5 at exit ) and response ( > /=50 % reduction in score from baseline ) . RESULTS For mirtazapine , remission rates were 12.3 % and 8.0 % per the Hamilton and QIDS-SR(16 ) scores , respectively . For nortriptyline , remission rates were 19.8 % and 12.4 % , respectively . QIDS-SR(16 ) response rates were 13.4 % for mirtazapine and 16.5 % for nortriptyline . Neither response nor remission rates statistically differed by treatment , nor did these two treatments differ in tolerability or adverse events . CONCLUSIONS Switching to a third antidepressant monotherapy regimen after two consecutive unsuccessful antidepressant trials result ed in low remission rates ( < 20 % ) among patients with major depressive disorder & NA ; This study compared the efficacy and safety of the selective serotonin reuptake inhibitor sertraline with that of the tricyclic antidepressant clomipramine in patients with severe depression , as defined by a baseline 17‐item Hamilton Depression Rating Scale ( HAM‐D ) of at least 25 . The study included 166 out patients , r and omized to double‐blind treatment with sertraline ( 50‐200 mg ) or clomipramine ( 50‐150 mg ) for 8 weeks .  The efficacy of both treatments was similar , 74 % of patients in the sertraline group and 71 % of clomipramine patients being classified as responders at the end‐point , as defined by a Clinical Global Impression‐Improvement ( CGI‐I ) score of 1 or 2 . Mean HAM‐D scores fell from 29.8 at baseline to 12.3 at endpoint in the sertraline group , and from 29.6‐12.7 in the clomipramine group . There were more withdrawals due to adverse events in the clomipramine group than in the sertraline group ( 17 % versus 12 % ) . Dry mouth , tremor , dizziness and constipation were all substantially more common in the clomipramine group , whereas diarrhoea / loose stools was more common in the sertraline group . Overall , sertraline was as effective as clomipramine in this group of severely depressed out patients , and showed better tolerability BACKGROUND There has been a paucity of well- design ed studies comparing selective serotonin reuptake inhibitor ( SSRI ) medications in the treatment of depression in the elderly . This multicenter study was design ed to examine the efficacy and safety of sertraline and fluoxetine in depressed elderly out patients . A secondary objective was to examine the effects of SSRI treatment on quality of life and cognitive function . METHOD Two hundred thirty-six out patients 60 years of age and older who met DSM-III-R criteria for major depressive disorder received 1 week of single-blind placebo before being r and omly assigned to 12 weeks of double-blind , parallel-group treatment with flexible daily doses of either sertraline ( range , 50 - 100 mg ) or fluoxetine ( range , 20 - 40 mg ) . Primary efficacy measures consisted of the 24-item Hamilton Rating Scale for Depression and Clinical Global Impressions scale ratings . Secondary outcome assessment s included clinician- and patient-rated measures of depression symptoms and factors , cognitive functioning , and quality of life , as well as plasma drug concentrations , which were correlated with clinical response . RESULTS Both drugs produced a similarly positive response on the primary efficacy measures , with 12-week responder rates of 73 % for sertraline and 71 % for fluoxetine . Sertraline-treated patients showed statistically greater cognitive improvement on several measures . Both drugs were safe and well tolerated . CONCLUSION Data indicate that both drugs are effective antidepressants for the treatment of depressed elderly out patients . Differences in cognitive performance effects deserve further investigation ABSTRACT Objectives : To evaluate the efficacy and safety of trazodone prolonged-release compared with sertraline in the treatment of patients with major depression . Research design and methods : A total of 122 patients aged 19–64 years were enrolled in this multicenter , double-blind , double-dummy , r and omized , comparator-controlled study . Patients received 7 days of single-blind placebo treatment followed by 6 weeks of double-blind treatment with trazodone prolonged-release 150–450 mg/day ( n = 62 ) or sertraline 50–100 mg/day ( n = 60 ) . Outcome measures : Efficacy was evaluated by mean changes from baseline in the Hamilton Depression Rating scale ( HAM‐D ) , Montgomery Asberg Depression Rating Scale , Hamilton Anxiety Rating scale , and the Clinical Global Impression-Global Improvement/Severity scores ; and by the rates of patients responding to treatment and considered to be in remission . Time to onset of efficacy and safety were assessed . Results : Trazodone and sertraline were equally effective in reducing depressive symptoms and promoting remission , and had similar onset times . In the Intent-to-Treat population , there were no significant differences in favor of trazodone at study endpoint in all efficacy measures , while a statistically significant difference was detected in the Per- Protocol population on HAM‐D and in the percentage of responders . Analysis of HAM‐D factors ( anxiety/somatization , cognitive disturbance , retardation , and sleep disturbance ) indicated that sleep disturbances were significantly less evident for patients taking trazodone at study endpoint . Adverse drug reactions , mostly of mild intensity , were reported in 42 % of trazodone-treated patients ( mainly of the nervous system ) and 43 % of sertraline-treated patients ( mainly gastrointestinal ) . One event was considered to be serious : a patient treated with trazodone 450 mg/day showed moderate anxiety/tremor/insomnia and was hospitalized . Treatment was discontinued ; the patient made a full recovery . Conclusions : This study showed that after 6 weeks , trazodone and sertraline were not different in reducing symptoms of depression and in producing disease remission . Tolerability profiles reflected the differing pharmacological properties of these antidepressants . Trazodone may be a therapeutic option in the treatment of patients with major depression showing prevalent sleep disturbances The aim of this multicenter , r and omized , double-blind , 8-week study was to compare the antidepressant efficacy and tolerability of mirtazapine and venlafaxine in the treatment of hospitalized patients with DSM-IV diagnosis of severe depressive episode with melancholic features . Patients with a baseline score of ≥ 25 on the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) were r and omly assigned to receive treatment with either mirtazapine ( N = 78 , 15–60 mg/day ) or venlafaxine ( N = 79 , 75–375 mg/day , twice a day ) in a rapid up-titration schedule . Efficacy was assessed with the Montgomery-Åsberg Depression Rating Scale ( MADRS ) , HAM-D-17 , and Clinical Global Impression scale , and quality of life was assessed with the Quality of Life , Enjoyment , and Satisfaction Question naire and Quality of Life in Depression Scale . Tolerability was assessed with the Utvalg for Kliniske Undersogelser ( UKU ) side effect scale and by reporting adverse events . Both drugs were effective in reducing overall symptoms of depression , showing substantial reductions in group mean MADRS scores ( −20.1 for mirtazapine and −17.5 for venlafaxine ) and HAM-D-17 scores ( −17.1 for mirtazapine and −14.6 for venlafaxine ) at the end of the treatment . Although not statistically significant , at all assessment times higher percentages of patients treated with mirtazapine were classified as responders ( ≥50 % reduction ) on the HAM-D ( at endpoint , 62 % vs. 52 % ) and MADRS ( at endpoint : 64 % vs. 58 % ) . Likewise were the percentages of remitters ( HAM-D score ≤7 ; MADRS score ≤12 ) also higher in the mirtazapine group . A statistically significant difference favoring mirtazapine was found on the HAM-D Sleep Disturbance factor at all assessment points ( p ≤ 0.03 ) . Both treatments were well tolerated . Although slightly more subjects treated with mirtazapine reported at least one adverse event , a statistically significantly higher percentage of patients treated with venlafaxine ( 15.3 % ) than mirtazapine ( 5.1 % ) dropped out because of adverse events ( p = 0.037 ) . Quality of life improved in both treatment groups . In this study , treatment with mirtazapine result ed in a trend toward more responders and remitters than treatment with venlafaxine and in significantly fewer dropouts as a result of adverse events Hnyberg OJ , Maragakis B , Mullin J , Norum D , Stordall E , Ekdahl P , Ose E , Moksnes KM , Sennef C. A double‐blind multicentre comparison of mirtazapine and amitriptyline in elderly depressed patients . Acta Psychiatr Sc and 1996 : 93 : 184–190 . © Munksgaard 1996 An eight-week double-blind , multicentre study was performed to evaluate the efficacy and safety of sertraline vs. fluoxetine in the treatment of major depression ( DSM-III-R ) . There were 108 out- patients , from nine Italian centres , entered into the study , of whom 88 were evaluable ( 48 sertraline , 40 fluoxetine ) . The final mean daily dose of sertraline was 72 mg and for fluoxetine it was 28 mg . Both treatment groups showed a statistically significant improvement from baseline at one week , and this was maintained until the end of treatment for all of the following measures : Hamilton Rating Scales for Depression and Anxiety , the Montgomery Asberg Depression Rating Scale , Clinical Global Impressions Scale , Zung Self-Rating Scale for Anxiety and the Leeds Sleep Evaluation Question naire . Although there was a numerical advantage for sertraline on several efficacy measures , there was no statistically significant difference found between the treatment groups . The incidence of adverse events was similar for both treatments ; 40.4 % for sertraline and 39.3 % for fluoxetine . However , adverse events were generally rated by patients as of lower severity in the sertraline group . In addition , for the fluoxetine group , there was a higher incidence of agitation , anxiety and insomnia than for sertraline . Sertraline was considered to be better tolerated than fluoxetine overall , since only 9.6 % of sertraline-treated patients discontinued treatment due to therapy failure whereas in the fluoxetine-treated group this figure was 19.6 % . By contrast , 13.5 % of sertraline-treated patients discontinued prematurely because of clinical improvement , compared with 10.7 % of fluoxetine-treated patients One hundred and sixty-three patients with major depression were r and omly assigned to treatment with mirtazapine or doxepin for 6 weeks in a double-blind clinical trial . Initially , patients received mirtazapine 20 mg/day or doxepin 75 mg/day ; dosages were then titrated up to a maximum of 60 mg/day and 300 mg/day , respectively . Both drugs produced considerable improvement in depressive symptoms with no statistically significant differences between the two patient groups . In the mirtazapine group only two patients prematurely terminated the study due to adverse drug experiences , as compared to six in the doxepin-treated group . Moreover , doxepin-treated patients complained more frequently of dry mouth and movement disorders . In conclusion , mirtazapine is an effective treatment for major depression and appears to offer advantages in tolerability over doxepin BACKGROUND Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings . In this study , we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials . METHODS We examined a consecutive series of 332 r and omized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals . Each eligible study was independently review ed for method ological quality using a 21-point index with 5 domains : r and omization , outcomes , eligibility criteria , interventions and statistical issues . Our primary analysis included studies that explicitly identified the primary outcome and reported it as statistically significant . For studies that did not explicitly identify a primary outcome , we defined a " positive " study as one with at least 1 statistically significant outcome measure . We used multivariable regression analysis to determine whether there was an association between reported industry funding and trial results , while controlling for study quality and sample size . RESULTS Among the 332 r and omized trials , there were 158 drug trials , 87 surgical trials and 87 trials of other therapies . In 122 ( 37 % ) of the trials , authors declared industry funding . An unadjusted analysis of this sample of trials revealed that industry funding was associated with a statistically significant result in favour of the new industry product ( odds ratio [ OR ] 1.9 , 95 % confidence interval [ CI ] 1.3 - 3.5 ) . The association remained significant after adjustment for study quality and sample size ( adjusted OR 1.8 , 95 % CI 1.1 - 3.0 ) . There was a nonsignificant difference between surgical trials ( OR 8.0 , 95 % CI 1.1 - 53.2 ) and drug trials ( OR 1.6 , 95 % CI 1.1 - 2.8 ) , both of which were likely to have a pro-industry result ( relative OR 5.0 , 95 % CI 0.7 - 37.5 , p = 0.14 ) . INTERPRETATION Industry-funded trials are more likely to be associated with statistically significant pro-industry findings , both in medical trials and surgical interventions The efficacy and tolerability of moclobemide and sertraline were compared in a 13 week trial on 55 depressive patients . Patients were diagnosed according to DSM-III-R criteria using SCID ( Structured Clinical Interview for DSM-III-R ) . The study group was composed of 48 patients with major depression and 7 with minor depression . Patients were r and omized in two drug groups and raters were blind to the drugs patients used . HDRS and CGI were used to assess the change in depressive symptoms . Twenty seven patients received moclobemide and 28 patients received sertraline . The dose of moclobemide used was 300 - 600 mg/day and that of sertraline was 50 - 200 mg/day . At the end of 13 weeks mean drop in HDRS for the overall group was 14.78 and the response rate calculated as percentage of patients showing a 50 % drop in HDRS score was 77.8 . The response rate was 76.5 % for moclobemide and 78.5 % for sertraline . The difference was not significant . The side effects were assessed by using UKU Side Effects Rating Scale . The most three observed side effects were dry mouth , headache and insomnia OBJECTIVES The adrenal and rogen dehydroepi and rosterone-sulfate ( DHEA-S ) seems to be involved in the pathophysiology of depression , although its precise role in the etiology and remission of depression remains unclear . In the present study we intended to examine possible differential effects of venlafaxine and mirtazapine in a r and omised open trial with regard to DHEA-S serum concentrations in patients suffering from major depressive episode compared to healthy controls . METHODS We assessed DHEA-S concentrations both at baseline and after a 4-week treatment period in 70 depressed patients ( n=33 for venlafaxine and n=37 for mirtazapine ) and 33 matched healthy controls . RESULTS We describe the decrease of DHEA-S levels in depressive patients who remitted after treatment with both venlafaxine or mirtazapine .  Patients without remission of depression did not show a significant decline in DHEA-S concentrations . CONCLUSIONS Our results suggest an effect of treatment outcome upon DHEA-S concentrations rather than a direct drug effect . The change of plasma DHEA-S levels as a marker of treatment-response of depression warrant further investigation reuptake inhibitors ( SSRIs ) during continuation therapy . This investigation reports the differential effect of 6 months of treatment with sertraline versus paroxetine for symptoms of depression , quality of life , and personality outcomes .  Out patients with unipolar major depression ( DSM-III-R ) were r and omly assigned to receive 24 weeks of double-blind treatment with flexible doses of paroxetine ( 20 - 40 mg ) or sertraline ( 50 - 150 mg ) . Assessment s included the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Clinical Global Impression Scale , the Battelle Quality of Life Question naire , and the Structured Clinical Interview for DSM-III-R Personality Disorders screen question naire . One hundred seventy-six patients ( mean age , 43 years ; 64 % female ; baseline MADRS , 30.3 ) were treated with sertraline and 177 patients ( mean age , 42 years ; 71 % female ; MADRS , 30.7 ) with paroxetine .  Antidepressant efficacy during continuation therapy was sustained , with only 2 % of patients receiving sertraline and 9 % of patients receiving paroxetine suffering a relapse . Continuation therapy result ed in a substantial conversion of responders during short-term treatment to full remission : remitter rates increased from 52 % to 80 % for sertraline and from 57 % to 74 % for paroxetine . The improvements in quality of life were related to a reduced depression score .  SSRI treatment had significant beneficial effects on both categorical and dimensional measures of personality . A logistic regression analysis identified early response ( 25 % reduction in MADRS scores at week 2 ) as the most important predictor of treatment response , whereas high severity , chronicity , and poor baseline quality of life had no effect . Both treatments were well-tolerated , with sertraline having a somewhat lower side effect profile .  Sertraline and paroxetine demonstrated comparable efficacy during short-term and continuation therapy . Treatment was associated with significant improvement in quality of life and with reductions in axis II personality psychopathology OBJECTIVE The aim of the present study was to examine the influence of reboxetine and mirtazapine on psychomotor functions related to driving skills and on driving simulator performance in depressed in patients . METHOD Forty depressed in patients diagnosed according to DSM-IV-TR criteria were r and omly assigned to treatment with either reboxetine ( N = 20 ) or mirtazapine ( N = 20 ) . To control for retest effects in psychomotor measures , a group of 10 healthy controls was examined on the same time schedule . Participants were tested once before pharmacologic treatment and twice after initiation of treatment ( days 7 and 14 ) with computerized tests related to car-driving skills .  Data were collected with the Act and React Testsystem ART-90 and the Wiener Testsystem , measuring visual perception , reactivity , stress tolerance , concentration , and vigilance . In addition , patients went through various risk simulations on a static driving simulator . Data were analyzed with nonparametric statistics and repeated- measures analysis of variance . The study was conducted from June 2004 through June 2006 . RESULTS Before onset of treatment with antidepressants , about 65 % of patients did not reach the threshold criterion according to the German guidelines for road and traffic safety . After 14 days of treatment with reboxetine or mirtazapine , patients improved in driving ability skills . Controlling for retest effects in psychomotor measures , data indicate that both patient groups significantly improved in tests measuring selective attention and reactivity ( all p < .01 ) . Furthermore , the frequency of accidents in the risk simulations markedly decreased in patients receiving mirtazapine and reboxetine ( all p < .05 ) . Statistically significant differences between treatment groups could not be shown . CONCLUSION Our results indicate that partially remitted depressed in patients treated with reboxetine or mirtazapine show a better performance on tasks related to driving skills than do untreated depressives OBJECTIVE This study was design ed to evaluate the comparative efficacy and safety of sertraline and nortriptyline for the treatment of major depressive disorder in older adults . METHOD A double-blind , parallel group design was used to compare 210 out patients , 60 years of age and older , who met DSM-III-R criteria for major depressive episode and had a minimum Hamilton Depression Rating Scale score of 18 . The patients were r and omly assigned to 12 weeks of treatment with either sertraline ( 50 - 150 mg/day ) or nortriptyline ( 25 - 100 mg/day ) . RESULTS The safety profiles of the two treatments were similar except that nortriptyline treatment was associated with a significant increase in pulse rate , whereas sertraline was associated with a nonsignificant decrease . Efficacy of both drugs was similar for both treatments at all time points , with 71.6 % ( N=53 of 74 ) of the sertraline-treated patients and 61.4 % ( N=43 of 70 ) of the nortriptyline-treated patients achieving responder status by week 12 . Time to response was also similar , with more than 75 % of the improvement in scores on the Hamilton depression scale having occurred by week 6 . Secondary efficacy measures ( posttreatment measures of cognitive function , memory , and quality of life ) revealed a significant advantage for sertraline treatment . CONCLUSIONS Primary efficacy measures showed sertraline and nortriptyline to be similarly effective . With secondary outcome measures there was consistent evidence of an advantage for the sertraline-treated group . The clinical impact of these measures on the long-term well-being of elderly depressed patients should be examined in a study of maintenance treatment BACKGROUND A sustained-release formulation of bupropion ( bupropion SR ) , developed with an improved pharmacokinetic profile to permit less frequent dosing than the immediate-release form , has not been evaluated in active comparator trials . This r and omized , double-blind , parallel-group trial was conducted to compare the efficacy and safety of bupropion SR and sertraline . METHOD Out patients with moderate to severe major depressive disorder ( DSM-IV ) received bupropion SR ( 100 - 300 mg/day ) or sertraline ( 50 - 200 mg/day ) for 16 weeks . Psychiatric evaluations , including the Hamilton Rating Scale for Depression ( HAM-D ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , the Clinical Global Impressions scale for Severity of Illness ( CGI-S ) , and for Improvement ( CGI-I ) were completed , and adverse events were assessed in the clinic periodically throughout treatment . Patients ' orgasm function was also assessed . RESULTS Mean HAM-D , HAM-A , CGI-I , and CGI-S scores improved over the course of treatment in both the bupropion SR group and the sertraline group ; no between-group differences were observed on any of the scales . Orgasm dysfunction was significantly ( p < .001 ) more common in  sertraline-treated patients compared with bupropion SR-treated patients . The adverse events of nausea , diarrhea , somnolence , and sweating were also experienced more frequently ( p < .05 ) in sertraline-treated patients . No differences were noted between the two treatments for vital signs and weight . CONCLUSION This double-blind comparison of bupropion SR and sertraline demonstrates that bupropion and sertraline are similarly effective for the treatment of depression . Both compounds were relatively well tolerated , and orgasm dysfunction , nausea , diarrhea , somnolence , and sweating were reported more frequently in sertraline-treated patients BACKGROUND The aim was to compare the efficacy and tolerability of mirtazapine with those of paroxetine . METHOD 275 out patients with a diagnosis of major depressive episode ( DSM-IV ) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) were r and omly assigned to 6 weeks of treatment with mirtazapine ( 15 - 45 mg/day ) or paroxetine ( 20 - 40 mg/day ) . Efficacy was assessed by the HAM-D-17 , Hamilton Rating Scale for Anxiety ( HAM-A ) , and Clinical Global Impressions scales ( Severity and Improvement ) , and analyses were performed on the intent-to-treat sample ( 127 mirtazapine-treated patients and 123 paroxetine-treated patients ) . RESULTS Mean daily doses were 32.7 mg of mirtazapine and 22.9 mg of paroxetine . Thirty patients in the mirtazapine group and 33 in the paroxetine group dropped out . Both drugs were equally effective in reducing symptoms of depression . At week 1 , the mean HAM-D-17 total score was significantly lower in mirtazapine- than paroxetine-treated patients ( 16.5 vs. 18.8 , p = .0032 ) . Similarly , significantly more mirtazapine-treated patients were HAM-D-17 responders ( > or = 50 % decrease from baseline ) at weeks 1 ( 23.2 % vs. 8.9 % , p = .002 ) and 4 ( 58.3 % vs. 44.5 % , p = .04 ) . Both treatments were equally effective in reducing anxiety . However , the reduction in mean HAM-A total score was significantly greater with mirtazapine than with paroxetine at week 1 ( -5.1 vs. -3.5 , p = .0435 ) . Tolerability of both treatments was good , with more nausea , vomiting , tremor , and sweating in the paroxetine group and more weight increase and influenza-like symptoms in the mirtazapine group . CONCLUSION Mirtazapine and paroxetine were equally effective after 6 weeks of therapy and were both well tolerated . A potentially faster onset of overall therapeutic efficacy of mirtazapine was suggested by significant differences between treatments after 1 week of therapy that were due to slightly larger improvements of several core symptoms of depression as well as distinct prevention of treatment-emergent worsening of anxiety and physical components of depression BACKGROUND Most studies report a poor response of psychotic depressed patients to treatment with a tricyclic antidepressant alone compared to combined treatment with an antipsychotic preparation and compared to non-psychotic depressed patients . However , the issue of optimal treatment of psychotic depressed patients has not been resolved as yet . Previously , we reported a significant difference in response to mirtazapine compared to imipramine in a r and omised , double-blind , fixed-blood-level study with in- patients with major depression . In the current study we focus on the treatment response to imipramine in a group of patients with psychotic depression and compare this to patients who manifest no psychotic features . Our aim in presenting these findings was to contribute to the discussion on the optimal treatment of psychotic depressed patients . METHODS Fifty-two patients with a unipolar major depression ( DSM-IIIR ) , comprising 15 patients with mood-congruent psychotic features and 37 patients with no psychotic features , were commenced on treatment with imipramine after a drug-free and placebo-washout period of 7 days . The dose of imipramine was adjusted for all patients to a predetermined blood level . The Hamilton ( HRSD ) and Montgomery-Asberg ( MADRS ) Depression Rating Scales were used to evaluate treatment response . RESULTS Of the 45 patients who completed the study , nine of the 13 psychotic patients ( 69.2 % ) and 14 of the 32 non-psychotic patients ( 43.8 % ) responded to treatment . The patients with psychotic features demonstrated a lower mean final HRSD score , together with a greater fall in MADRS score over time , compared to the non-psychotic group . Both these findings remained statistically significant after controlling for a number of possible confounding factors . CONCLUSIONS These results demonstrate that , in this group of patients with mood-congruent psychotic depression , imipramine used on its own together with strict control of serum drug levels produced a high treatment response rate of 70 % . CLINICAL IMPLICATION S If replicated , these findings suggest that imipramine with control of blood levels of medication may be a useful first-line treatment for depressed patients with mood-congruent psychotic features . LIMITATIONS Our sample size was modest . This fact may caution against generalisation of the results Abstract Introduction : Depression is a major global problem associated with large medical , sociological and economic burdens . Mirtazapine ( Remeron ® , Organon NV , The Netherl and s ) is an antidepressant with a unique mechanism of action that has similar or superior efficacy to TCAs and SSRIs in moderate-to-severe depression . However , this agent has not yet been tested in patients with severe depression alone . Objective : To compare the antidepressant efficacy and tolerability of mirtazapine and fluoxetine and their effects on anxiety and quality of life in patients with severe depression ( ≥25 points on the first 17 items of the Hamilton Depression Rating Scale [ HDRS-17 ] ) . Methods : In this double-blind study , 297 severely depressed patients were r and omised to receive mirtazapine 15–60 mg/day ( n = 147 ) or fluoxetine 20–40 mg/day ( n = 152 ) for 8 weeks . 294 subjects were actually treated and 292 included in the intent-to-treat population . Symptom severity was measured by the HDRS-17 , Montgomery-Asberg Depression Rating Scale ( MADRS ) and Clinical Global Impression ( CGI ) rating scale . Quality of life was self-assessed by patients using the Leeds Sleep Evaluation Question naire and the Quality of Life , Enjoyment and Satisfaction Question naire . Adverse events were recorded throughout the study . Results : No statistically significant differences were noted between the two groups in change from baseline HDRS-17 score at any time point ; both treatments were associated with large ( ∼15 points ) decreases by study end . However , more mirtazapine-treated patients tended to exhibit a ≥50 % decrease in HDRS score ( significant at day 7 ; 9.0 % vs 0.7 % , p = 0.002 ) . Significant differences in favour of mirtazapine were also observed at day 14 for changes in MADRS scores ( −10.9 vs −8.5 , p = 0.006 ) and the proportion of patients with ≥50 % decrease in MADRS score ( 21.4 % vs 10.9 % , p = 0.031 ) . On the CGI , the proportion of ‘ much/very much improved ’ patients tended to be greater with mirtazapine ( significant at day 7 ; 9.7 % vs 3.4 % , p = 0.032 ) . No significant between-group differences were observed for the majority of quality -of-life measures . However , mirtazapine produced significantly better improvements on ‘ sleeping assessment 1 ’ ( 14.9 ± 5.2 vs 13.7 ± 5.4 , p = 0.028 ) and ‘ sleeping assessment 2 ’ ( p = 0.013 ) than fluoxetine . Both agents were generally well tolerated  but mirtazapine-treated patients experienced a mean weight gain of 0.8 ± 2.7 kg compared with a mean decrease in weight of 0.4 ± 2.1 kg for fluoxetine-treated patients ( p < 0.001 ) . Conclusions : Mirtazapine is as effective and well tolerated as fluoxetine in the treatment of patients with severe depression OBJECTIVE To compare the efficacy , safety and tolerability of reboxetine and sertraline in major depressive disorder ( MDD ) . METHOD The study subjects consisted of 41 patients who met the DSM-IV MDD diagnostic criteria . Patients were r and omly assigned to receive either reboxetine or sertraline . During the study the patients were assessed 6 times ( baseline visit = day 0 , visit 1=day 8 , visit 2=day 22 , visit 3=day 36 , visit 4=day 57 and visit 5=day 78 ) over 11 weeks . Antidepressant response was measured by the Hamilton Depression Rating Scale ( HDRS ) , Clinical Global Impressions-Severity of Illness ( CGI-SI ) and Global Impressions-Global Improvement ( CGI-GI ) . RESULTS Comparing the two groups in terms of response and remission ( HAM-D < or = 10 ) measures , the results were in favour of the reboxetine group at visits 2 , 3 and 4 . At visit 5 , the scores were similar and no statistically significant difference was found between the two groups . However , when remission was evaluated as HAM-D < or = 7 , a significant statistical difference was found in favour of the reboxetine group . Evaluating the side effects , dry mouth , sweating , palpitation , headache , hot flushing and sedation were more frequent in the reboxetine group . Only one patient , in the reboxetine group , dropped out due to a side effect ( constipation ) . CONCLUSION Higher rates of full remission achievement , which is the main target of MDD treatment , in the reboxetine group compared with the sertraline group may be due to the suppression of anxiety symptoms by the noradrenergic feature of the drug . In order to underst and the role of the noradrenergic system in treating MDD , larger patient sample s are needed . Both reboxetine and sertraline were well tolerated and effective in treating MDD Abstract Objective : To evaluate the efficacy of emotional support and counselling combined with placebo or antidepressants with single or dual mechanism of action in the treatment of depression in primary care . Design : R and omised double blind study . Setting : Several locations in Norway . Subjects : 372 patients with depression . Main outcome measures : Improvement ( clinical remission ) reported both by the patient ( Montgomery Åsberg depression rating scale ) and the physician ( clinical global improvement and impression scales ) . Results : Intention to treat analyses showed 47 % remission in patients r and omised to placebo compared with 61 % remission in patients r and omised to sertraline ( odds ratio 0.56 , 95 % confidence interval 0.33 to 0.96 ) and 54 % in patients r and omised to mianserin ( 0.75 , 0.44 to 1.27 ) . Women responded  better than men ( 1.86 , 1.17 to 2.96 ) . Subgroup analyses showed that subjects with recurrent depression ( n=273 ) responded more frequently to sertraline than to placebo ( 0.43 , 0.23 to 0.82 ) than those having their first episode of depression ( 1.18 , 0.39 to 3.61 ) . Statistically significant interactions between type of drug treatment and history of depression were not shown by logistic regression . Conclusion : The combination of active drug and simple psychological treatment ( counselling , emotional support , and close follow up over a 24 week period ) was more effective than simple psychological treatment alone , in particular for those with recurrent depression . Overall , women may benefit more than men . If confirmed in future studies , the findings should lead to more differentiated treatment guidelines for depression in primary care BACKGROUND This study was design ed to compare the efficacy , safety , tolerability profiles , and effects on quality of life of the serotonin selective reuptake inhibitor antidepressant sertraline versus the nonselective tricyclic antidepressant amitriptyline and placebo in patients with major depression . METHOD Out patients with DSM-III-R major depression were r and omly assigned to double-blind treatment for 8 weeks with sertraline ( 50 - 200 mg daily ) , amitriptyline ( 50 - 150 mg daily ) , or matching placebo . Assessment s included the Hamilton Rating Scale for Depression , Montgomery-Asberg Depression Rating Scale , Clinical Global Impressions-Severity of Illness scale , Clinical Global Impressions-Improvement scale , Global Assessment Scale , Profile of Mood States , Beck Depression Inventory , Quality of Life Enjoyment and Satisfaction Question naire , and Health-Related Quality of Life battery . RESULTS All treatment groups demonstrated statistically significant improvement from baseline in depression ratings by Week 1 and thereafter . The antidepressant effects of amitriptyline and sertraline were significantly ( p < .05 ) greater than placebo and did not differ significantly from each other . Sertraline was associated with significantly ( p < .05 ) greater subjective ( i.e. , patient-rated ) improvement in mood than amitriptyline or placebo . Both active drugs were associated with greater improvements than placebo on most quality of life measurements . On several items , sertraline , but not amitriptyline , was superior to placebo . There was a discernible effect of sertraline earlier than amitriptyline on most quality of life scales .  Amitriptyline therapy was associated with significantly more treatment-related adverse events , and discontinuations due to treatment-related adverse events , in comparison to both sertraline and placebo therapy . CONCLUSION Sertraline and amitriptyline each were effective treatments for major depression as assessed by both physician- and patient-rated scales . These results show that sertraline therapy is better tolerated than amitriptyline therapy . Quality of life was also improved by effective antidepressant treatment , with sertraline showing a tendency to produce greater improvements on quality of life measures BACKGROUND Sexual dysfunction commonly occurs during  antidepressant treatment .  However , the reported rates of sexual dysfunction vary across antidepressants and are typically underreported in product literature . The objectives of this study were ( 1 ) to estimate the prevalence of  sexual dysfunction among patients taking newer antidepressants ( bupropion immediate release [ IR ] , bupropion sustained release [ SR ] , citalopram , fluoxetine , mirtazapine , nefazodone , paroxetine , sertraline , venlafaxine , and venlafaxine extended release [ XR ] )  and ( 2 ) to compare physician-perceived with patient-reported prevalence rates of antidepressant-associated sexual dysfunction . METHOD This cross-sectional , observational study was conducted in 1101 U.S. primary care clinics . Adult out patients ( 4534 women and 1763 men ) receiving antidepressant monotherapy were enrolled . The prevalence of sexual dysfunction was measured using the Changes in Sexual Functioning Question naire . RESULTS In the overall population , bupropion IR ( 22 % ) and SR ( 25 % ) and nefazodone ( 28 % ) were associated with the lowest risk for sexual dysfunction , whereas selective serotonin reuptake inhibitor ( SSRI ) antidepressants , mirtazapine , and venlafaxine XR were associated with higher rates ( 36%-43 % ) . In a prospect ively defined sub population unlikely to have predisposing factors for sexual dysfunction , the prevalence of sexual dysfunction ranged from 7 % to 30 % , with the odds of having sexual dysfunction 4 to 6 times greater with SSRIs or venlafaxine XR than with bupropion SR . Physicians consistently underestimated the prevalence of antidepressant-associated sexual dysfunction . CONCLUSION Ours is the first study to assess sexual dysfunction across the newer antidepressants using consistent methodology and a vali date d rating scale . Overall , SSRIs and venlafaxine XR were associated with higher rates of sexual dysfunction than bupropion or nefazodone . Because antidepressant-associated sexual dysfunction is considerably underestimated by physicians , greater recognition and education are imperative when prescribing antidepressant treatment The purpose of this double-blind , multicenter trial was to compare the efficacy and safety of sertraline ( 50–150 ing/day ) with those of citalopram ( 20–60 mg/day ) in patients with major depression in general practice during 24 weeks of treatment . The patients were assessed using the Montgomery-Åsberg Depression Rating Scale and the Clinical Global Impressions of severity and improvement scales . Observed and spontaneously reported adverse events were recorded and side-effects were assessed by means of the UKU Side-Effect Scale .  Altogether 400 patients were r and omized into the study . A total of 308 patients completed the 24-week study in accordance with the protocol . A significant reduction in the total Montgomery-Åsberg Depression Rating Scale scores was observed in both treatment groups as early as 2 weeks , with no statistically significant differences between the drugs . In the intention to treat-lust observation carried forward analysis 76 % responded to treatment in the sertraline and 81 % in the citalopram group . The final mean doses were 82 mg/day ( 64 % higher than baseline ) in the sertraline group and 34 mg/day ( 70 % higher than baseline ) in the citalopram group . The response rate in completers in accordance with protocol was 90 % in the sertraline group and 93 % in the citalopram group . The side-effects were those usually seen , and both sertraline and citalopram were considered to be well tolerated . It was concluded that patients with major depression in general practice  respond well to 24 weeks of treatment with sertraline or citalopram . With regard to efficacy , no statistically significant differences were found between the drugs INTRODUCTION : Reboxetine is the first available selective noradrenaline re-uptake inhibitor ( selective NRI ) . This paper gives an overview of its antidepressant efficacy and tolerability in eight r and omized double-blind , multicentre clinical trials . The clinical profile of reboxetine is also compared with that of the tricyclic antidepressants ( TCAs ) desipramine and imipramine and the selective serotonin re-uptake inhibitor ( SSRI ) fluoxetine . METHODS : Pooled data were analysed from seven short-term ( 4 - 8 weeks ) and one long-term ( up to 1 year ) trials comparing reboxetine with placebo , imipramine , desipramine or fluoxetine . The tolerability of reboxetine was evaluated in 2613 patients with major depression or dysthymia . Data from 1959 patients with major depressive disorder were included to assess drug efficacy . Efficacy was principally assessed using the Hamilton Depression Rating Scale ( HAM-D ) . RESULTS : Reboxetine was more effective than placebo in three of four short-term trials , and it was as effective as fluoxetine , imipramine and desipramine . In long-term treatment , reboxetine was more effective than placebo in preventing relapse ( S 50 % increase in HAM-D ) and recurrence ( HAM-D total score h 10 ) . In a subset of severely depressed patients , reboxetine was as effective as imipramine and significantly more effective than fluoxetine . Reboxetine was as effective as imipramine in the elderly , but better tolerated . The most common adverse events among the 1503 patients ( adults and elderly ) who received reboxetine were dry mouth ( 22 % ) , constipation ( 15 % ) , sweating ( 12 % ) and insomnia ( 11 % ) . Overall , reboxetine was well tolerated , as well as the SSRI fluoxetine and better than the TCAs imipramine and desipramine . CONCLUSIONS : Reboxetine is effective and well tolerated in the short and long-term treatment of depression . It is as well tolerated as fluoxetine and better than imipramine and desipramine . ( Int J Psych Clin Pract 2000 ; 4 : 201 - 208 BACKGROUND Major depression with high levels of anxiety ( anxious depression ) is a common subtype of depression associated with greater psychosocial impairment and poorer response to antidepressant treatment . It is unclear whether in this population there are differences in efficacy or tolerability across selective serotonin reuptake inhibitors . For this reason , using head-to-head acute treatment comparison , we compared efficacy and tolerability of fluoxetine , sertraline , and paroxetine among depressed patients with high levels of anxiety . METHODS Patients ( N = 108 ) with DSM-IV major depression and high levels of anxiety ( a HAM-D-Anxiety/Somatization Factor score > or = 7 ) were r and omized to fluoxetine , sertraline , or paroxetine treatment in a double-blind fashion . Changes in overall depression and anxiety were assessed . RESULTS Patients demonstrated similar baseline-to-endpoint improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores . Patients also demonstrated similar change-over-time improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores , except at week one where fluoxetine- and sertraline-treated patients had statistically significantly greater improvement than paroxetine-treated patients in the HAM-D-Anxiety/Somatization Factor score . There were no significant differences across treatments in percentages of patients with substantial emergence , any worsening , or improvement at endpoint in individual HAM-D Items 9 ( agitation ) , 10 ( psychic anxiety ) , and 11 ( somatic anxiety ) . Overall , all treatments were well tolerated . CONCLUSION These data showed no significant differences in efficacy and tolerability of fluoxetine , sertraline , and paroxetine in patients with high levels of baseline anxiety symptoms during the acute treatment of major depression . Each treatment was similarly effective in improving depression in this subtype of patients with anxious depression AIMS Prominent anxiety symptoms are related to poor clinical course and outcome in major depressive disorder ( MDD ) . The aim of this r and omised , open-label , controlled study is to compare the efficacy and tolerability of mirtazapine in the form of orally disintegrating tablets against paroxetine in treating MDD patients with anxiety symptoms . METHODS A total of 60 MDD patients with a score above 18 on the Hamilton Anxiety Rating Scale ( HARS ) were r and omly assigned to 8 weeks of fixed dosing treatment with mirtazapine ( 15 - 30 mg/day ) and paroxetine ( 10 - 20 mg/day ) . Efficacy was primarily assessed with the HARS and with the 17-item Hamilton Depression Rating Scale ( HDRS ) at weeks 1 , 2 , 4 and 8 after treatment . Tolerability was assessed from adverse events . RESULTS The generalised estimating equations ( GEE ) models showed that the rates of improvement in HDRS scores from baseline to week 8 were similar between mirtazapine and paroxetine groups . However , patients with mirtazapine exhibited earlier improvement in HARS scores at weeks 1 and 2 . Week-by-week GEE models showed that these significant differences in improvement of HARS scores between the two treatment groups were detectable from the first evaluation after the treatment ( week 1 ) and maintained through week 2 . There was no difference in the overall frequency of adverse events experienced between the two treatment groups . The most common adverse event in the mirtazapine group was somnolence ( n = 8) , whereas that in the paroxetine group was gastrointestinal discomfort ( n = 9 ) . CONCLUSIONS Mirtazapine and paroxetine were equally effective and well tolerated for the depressive symptoms in MDD patients with the high level of anxiety symptoms .  Mirtazapine was , however , more effective in reducing the anxiety symptoms than paroxetine in the early weeks of treatment , suggesting that mirtazapine may have an earlier-onset action for the anxiety symptoms in MDD patients AIM To compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Chinese patients suffering moderate-to-severe depression . METHOD 133 patients with a diagnosis of major depressive episode ( DSM-IV ) and scoring 15 or more on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) were r and omly assigned to receive 6 weeks of treatment with either mirtazapine ( 15 - 45 mg/day ) or fluoxetine ( 20 - 40 mg/day ) . Efficacy was assessed using the HAM-D and Clinical Global Impressions scale , with analyses performed on the intent-to-treat sample using the last-observation-carried-forward method . Safety analysis was based on the all-subjects-treated group . RESULTS Mean daily doses were 34.1 mg for mirtazapine ( N = 66 ) and 30.7 mg for fluoxetine ( N = 66 ) . Thirty patients in the mirtazapine group and 22 in the fluoxetine group dropped out . Both drugs proved equally effective for reduction of the overall symptoms of depression throughout the treatment period . At day 42 , the mean reductions in HAM-D total score ( compared with baseline ) were 11.8 and 10.6 for the mirtazapine and fluoxetine groups , respectively ; however , the changes were not statistically significant . Both treatments were well tolerated , with more nausea and influenza-like symptoms observed for the fluoxetine group , and greater weight increase and somnolence for the mirtazapine analog . CONCLUSION Both mirtazapine and fluoxetine were indistinguishable in effectiveness for treatment of depressive symptoms , and both were well tolerated by our population of depressed Chinese patients . In line with analogous Western reports , the safety of mirtazapine and fluoxetine was comparable for our depressed Chinese patients ; however , slightly different side effect profiles were noted for the 2 drugs in our study BACKGROUND The purpose of this study was to compare the overall effectiveness of 2 treatment strategies for in patients with severe major depressive episode ( DSM-III-R ) : ( 1 ) mirtazapine ( phase 1 ) and subsequent lithium addition ( phase 2 ) or ( 2 ) imipramine ( phase 1 ) and subsequent lithium addition ( phase 2 ) . We previously reported the results of phase 1 . METHOD In phase 1 , patients were r and omly assigned to treatment with either mirtazapine or imipramine , and doses were adjusted to obtain predefined blood drug levels . Nonresponders had lithium added to the double-blind mirtazapine or imipramine medication . The dose was adjusted to obtain a blood lithium level of 0.5 - 1.0 mmol/L. Treatment effects were evaluated weekly by the Montgomery-Asberg Depression Rating Scale for up to 2 weeks on this blood lithium level . RESULTS Data for 100 patients were available for comparison of the 2 treatment strategies . 80 patients received no comedication . By the end of phase 2 , 24 ( 48 % ) of 50 had responded to mirtazapine and 32 ( 64 % ) of 50 had responded to imipramine ( intent-to-treat analysis ) . A survival analysis of the total patient group intent-to-treat showed a significant difference in favor of the treatment strategy with imipramine and subsequent lithium addition . CONCLUSION Efficacy of imipramine and subsequent lithium addition for nonresponders is superior to the same treatment strategy with mirtazapine . This applies to the patient sample studied , which consisted of 100 severely depressed in patients , 29 of whom were psychotically depressed . More serious side effects of imipramine , however , led to discontinuation of imipramine in 5 patients . No serious side effects were observed during the phase of lithium addition to either imipramine or mirtazapine . We , therefore , prefer to start treatment with imipramine and test for fixed blood drug levels , and , if necessary , add lithium . In the case of prohibitive side effects , patients are switched to a modern antidepressant such as mirtazapine , and , if necessary , lithium is added to this antidepressant Efficacy and acceptability of tianeptine were investigated in a multicenter , r and omized , double blind , and sertraline-controlled study . As a total , 212 in- or out patients with DSM IV major depression single episode , recurrent and bipolar depression , were treated for 42 days either with tianeptine ( 37.5 mg ) or with sertraline ( 50 mg ) . At inclusion , sociodemographic , physical and psychological parameters showed no significant intergroup differences . MADRS responders ( 50 % reduction of baseline score ) were 66 % and 67 % with tianeptine and sertraline , respectively . No statistical interdrug differences were observed either in the number of withdrawals or in the efficacy and acceptability parameters The acute treatment efficacy , tolerability , and effects on health-related quality of life of sertraline ( 50 - 200 mg/day ) versus imipramine ( 75 - 225 mg/day ) were compared in out patients with non-melancholic depression . The study employed an open-label , parallel-group design . One hundred and sixteen patients were r and omized to receive sertraline and 123 to receive imipramine for 8 weeks . In the intent-to-treat ( ITT ) , last-observation-carried-forward ( LOCF ) analysis , sertraline produced statistically significantly greater improvements in depressive ( 21-item Hamilton Depression Rating Scale [ HAM-D(21 ) ] scores of 24.9 and 24.4 were reduced to 10.3 and 13.1 at endpoint , P<.005 ) and anxiety symptoms ( Hamilton Anxiety Rating Scale [ HAM-A ] scores of 21.8 and 21.9 were reduced to 9.5 and 13.9 , P<.01 ) , as well as in response ( 69.0 % versus 53.7 % at endpoint , P=.016 ) and remission rates ( 51.3 % versus 38.0 % at endpoint , P=.041 ) from week 4 onwards compared with imipramine . The proportion of patients who were ' very much improved ' or ' much improved ' ( Clinical Global Impressions Scale of Improvement [ CGI-I ] score of 1 or 2 ) was significantly higher at endpoint in the sertraline group ( 76.1 % ) than in the imipramine group ( 62.8 % ) ( P=.028 ) . At week 8 , patients in both treatment groups showed clear improvements in quality of life , although nonstatistically significant differences were evident in the quality of life of sertraline- versus imipramine-treated patients . Sertraline was significantly superior in tolerability with less discontinuations due to adverse events ( 10.3 % ) compared with the imipramine group ( 24.4 % ) ( P=.004 ) . It was concluded that sertraline is more effective than imipramine in the acute treatment of depressive and anxiety symptoms in patients with non-melancholic depression Two hundred hospitalized patients with DSM-III diagnosis of moderate to severe major depressive episode were r and omized to receive mirtazapine or trazodone for 6 weeks in a double-blind trial . The dosages were 24–72 mg/day for mirtazapine and 150–450 mg/day for trazodone . The improvement on all depression rating scales used was generally greater for mirtazapine , wish statistically significant differences over trazodone in the Hamilton Psychiatric Rating Scale for Depression total score and two subscores ( the Bech melancholia factor and retardation factor ) , the Brief Psychiatric Rating Scale total score , the General Psychiatric Impression Global Assessment Scale , the Beck score and responder rates . Mirtazapine was well tolerated , while the trazodone-treated patients experienced somnolence more frequently , particularly during the first 2 weeks of treatment . Furthermore , postural symptoms were a clinical problem in > ' 6 % of the trazodone-treated patients . In this trial , mirtazapine showed significant clinical advantages over trazodone in terms of overall efficacy and tolerability OBJECTIVE The authors sought to identify genetic markers for antidepressant medication intolerance . Genetic variation in drug metabolizing enzymes such as cytochrome P450 2D6 ( CYP2D6 ) has been postulated to underlie antidepressant intolerance ( pharmacokinetic effect ) . However , variation in genes encoding serotonin receptors could also explain antidepressant side effects ( pharmacodynamic effect ) . METHOD An 8-week , double-blind , r and omized pharmacogenetic study compared the widely prescribed antidepressants paroxetine ( a selective serotonin reuptake inhibitor [ SSRI ] ) and mirtazapine ( not an SSRI ) in 246 elderly patients with major depression . Genotypes were determined for the 102 T/C single nucleotide polymorphism ( SNP ) in the serotonin 2A ( 5-HT(2A ) ) locus ( HTR2A ) , previously associated with psychotropic medication treatment outcome . Oligonucleotide microarrays were used to extensively characterize variation in the CYP2D6 gene . Clinical outcomes included treatment discontinuations , adverse events , medication compliance , and change in mood . RESULTS Survival analysis showed discontinuations due to paroxetine-induced side effects were strongly associated with the HTR2A C/C genotype . There was a significant linear relationship between the number of C alleles and the probability of discontinuation . Side effect severity in paroxetine-treated patients with the C/C genotype was also greater . In contrast , HTR2A 102 T/C genotype had no effect on mirtazapine side effects . CYP2D6 genotype did not predict treatment outcome for either medication . CONCLUSIONS Pharmacodynamic differences among patients due to variant 5-HT(2A ) receptors appear to be more important than pharmacokinetic variation in determining paroxetine intolerance . Pharmacogenetic markers may be useful in predicting antidepressant treatment outcome This study compared the efficacy and tolerability of 150 mg/day imipramine and 50 mg/day sertraline for the treatment of a major depressive episode ( DSM-IV ) in older adults ( N = 55 ) in an 8-week , r and omized , double-blind , controlled clinical trial . Intention-to-treat analysis ( last observation carried forwards ) showed a reduction of 50 % or more on the baseline scores of the Montgomery-Asberg Rating Scale ( MADRS ) in 60.7 % and 55.6 % of patients receiving imipramine and sertraline , respectively ( p = .698 ) . Full remission of symptoms ( MADRS < 9 ) was observed in 50.0 % and 51.8 % of patients , respectively ( p = .891 ) . Side effects were more frequent among patients treated with imipramine ( 86.7 % ) than among patients treated with sertraline ( 42.1 % ) ( p = .008 ) . Dropout rates were high in both groups ( 46.4 % and 29.6 % respectively , p = .200 ) . These results indicate that imipramine and sertraline are equally effective for the treatment of major depression in later life , although adverse reactions are more frequent among subjects treated with imipramine than with sertraline BACKGROUND The prevalence of major depressive disorder in patients with acute coronary syndromes ( ACSs ) is high and associated with worse cardiovascular outcomes and higher health care costs .  Sertraline is the only treatment for major depressive disorder studied in a placebo-controlled trial of patients with ACS and found to be safe and effective . The cost implication s of providing antidepressant treatment in this population have not yet been examined . The objective was to evaluate from a payer perspective the potential reduction in costs and psychiatric and cardiovascular events and procedures following sertraline versus placebo treatment of major depressive disorder in patients hospitalized for ACS . METHOD Data were analyzed from a r and omized , double-blind , placebo-controlled 24-week trial ( Sertraline Antidepressant Heart Attack R and omized Trial ) of sertraline treatment for major depressive disorder in patients hospitalized for ACS . Main outcome measures included frequency and costs ( derived from Medicare diagnosis-related group fee schedules ) of psychiatric and cardiovascular events occurring during the treatment period . RESULTS There was a trend toward significantly fewer psychiatric or cardiovascular hospitalizations in the sertraline compared with the placebo group ( 55/186 vs. 76/183 ; p = .054 ) . The mean per patient cost associated with psychiatric and medical events over the course of treatment was 2733 US dollars for sertraline and 3326 US dollars for placebo , but the difference was not statistically significant ( p = .32 ) . After including the costs of the sertra-line ( 360 US dollars over 24 weeks ) , there was no increase in treatment costs for sertraline compared with placebo . CONCLUSION Sertraline treatment of major depressive disorder following hospitalization for a recent myocardial infa rct ion or unstable angina appears to be a cost-effective strategy This multinational , r and omized , double-blind study was specifically design ed to prospect ively compare the onset of antidepressant efficacy of mirtazapine orally disintegrating tablets and sertraline at dosages commonly used in clinical practice . A total of 345 patients with major depressive episode ( DSM-IV ) received mirtazapine ( 30–45 mg/d ) or sertraline ( 50–150 mg/d ) for 8 weeks . Mirtazapine was administered in the newly developed fast dissolving , orally disintegrating tablet formulation . Assessment s were performed at baseline and on days 4 , 7 , 10 , 14 , 28 , 42 , and 56 . The primary efficacy variable ( mean absolute change from baseline in the Hamilton Depression Rating Scale [ HAMD ] total score [ 17 items ] ) showed that mirtazapine was significantly ( P < 0.05 ) more effective than sertraline at all assessment s during the first 2 weeks of the study . After this time , HAMD total scores were similar in both groups . These findings were supported by analysis of the HAMD response rate ( ie , ≥50 % reduction in HAMD total score from baseline ) , HAMD remission rate ( HAMD total score of ≤7 ) , and the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . Both treatments were well tolerated . In addition , mirtazapine had a greater effect  than sertraline  on sexual functioning . In conclusion , this first prospect i ve onset of action study using the orally disintegrating tablet indicates that mirtazapine has a faster onset of therapeutic effect  than sertraline . The orally disintegrating tablet formulation of mirtazapine used in this study is known to enhance the convenience and compliance by the patient OBJECTIVE To compare the efficacy and tolerability of mirtazapine and fluoxetine in depressed in patients and out patients . METHOD Patients with a major depressive episode ( DSM-III-R ) , a baseline score of > or=21 on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) , and > or=2 on HAM-D Item 1 ( depressed mood ) were r and omly assigned to a 6-week treatment with either mirtazapine ( N=66 , 15 - 60 mg/day ) or fluoxetine ( N=67 , 20 - 40 mg/day ) . The upper limit of the mirtazapine dose range was above the dose range approved in the United States ( 15 - 45 mg/day ) . Efficacy was evaluated by the HAM-D , Clinical Global Impressions , the Visual Analogue Mood Rating Scale ( VAMRS ) , and the Quality of Life Enjoyment and Satisfaction Question naire ( QLESQ ) . The efficacy analyses were performed on the intent-to-treat group using the last-observation-carried-forward method . RESULTS Mean total 17-item HAM-D scores at baseline were 26.0 for the mirtazapine- and 26.1 for the fluoxetine-treated group . The decrease from baseline on the HAM-D was larger in the mirtazapine than in the fluoxetine group throughout the treatment period , reaching statistical significance at days 21 and 28 . At assessment s from day 21 and onward , the absolute difference between the 2 study groups favoring mirtazapine ranged from 3.7 to 4.2 points , the magnitude of difference usually seen between an efficacious antidepressant drug and placebo . Mean dosages at weeks 1 - 4 were 36.5 mg/day for mirtazapine and 19.6 mg/day for fluoxetine ; the respective dosages at weeks 5 - 6 were 56.3 mg and 35.8 mg . Similar numbers of patients dropped out due to adverse events ; tolerability profiles were comparable except for changes in body weight from baseline which were statistically significantly more pronounced in the mirtazapine group compared to the fluoxetine group . CONCLUSION We found that mirtazapine was as well tolerated as fluoxetine and significantly more effective after 3 and 4 weeks of therapy Spectral analysis of fluctuations in heart rate ( HR ) and blood pressure ( BP ) was applied to assess sympathetic and parasympathetic cardiovascular control mechanisms in patients with unipolar affective disorder before and after treatment with imipramine ( IMI ) or mirtazapine ( MIR ) .  In a double-blind r and omized study , 10 patients received treatment with IMI and 10 patients received treatment with MIR .  Cardiovascular parameters were studied before and after 4 weeks of treatment :  HR and BP ( Finapres ) were recorded continuously during supine rest ( SR ) and orthostatic challenge ( OC ; 60-degrees head-up tilting ) . During SR and OC , power spectra were calculated for HR and systolic BP . Spectral density was assessed for three frequency b and s : low ( 0.02 - 0.06 Hz ) , mid ( 0.07 - 0.14 Hz ) , and high ( 0.15 - 0.50 Hz ) . Before treatment , the depressed patients ( N = 20 ) differed from age-matched controls ( N = 20 ) only in their response to OC : the depressed patients showed more suppression of HR variability ( both mid- and high-frequency b and fluctuations ) , indicating stronger vagal inhibition , and a reduced increase of BP variability ( mid-frequency b and fluctuations ) , indicating reduced sympathetic activation . After 4 weeks of treatment , patients treated with either antidepressant drug showed significant changes of HR ( increase ) and HR variability ( decrease ) during SR and OC ; the suppression of mid- and high-frequency fluctuations of HR was larger for IMI than for MIR . The increase in HR and decrease in HR variability may be attributed to the anticholinergic properties of IMI ( strong ) and MIR ( weak ) , result ing in cardiac vagal inhibition . Whereas MIR had no effect on BP or BP variability , IMI specifically reduced mid-frequency b and fluctuations of BP as the result of a suppression of central sympathetic activity . Our data confirm and extend previous observations on the presence of autonomic dysfunctions in unmedicated depressed patients : spectral analysis of HR and BP fluctuations suggested that both parasympathetic and sympathetic mechanisms are involved , specifically during OC . The preexisting autonomic cardiovascular dysfunctions were not normalized by antidepressant drugs . In fact , some of the components of the cardiovascular autonomic dysfunction were further aggravated , depending on the pharmacologic profile of the drug under investigation OBJECTIVE In this study the authors evaluated the efficacy and the tolerability of sertraline and paroxetine in the treatment of delusional depression . METHOD Under double-blind conditions , 46 hospitalized patients who met the DSM-III-R criteria for major depression with psychotic features were treated with sertraline or paroxetine for 6 weeks . RESULTS The response rates were 75 % and 46 % for sertraline and paroxetine , respectively . The dropout rate was substantial ( 41 % ) in the paroxetine group and was attributable to side effects . CONCLUSIONS Selective serotonin reuptake inhibitors administered alone are useful in the treatment of delusional depression A double-blind , placebo- and amitriptyline-controlled comparison study was performed to evaluate the antidepressant efficacy of sertraline , a specific serotonin uptake inhibitor . Patients with DSM-III-defined major depression r and omly received either sertraline  ( N = 149 ) , amitriptyline ( N = 149 ) , or placebo ( N = 150 ) once daily for the 8-week study period . The mean final daily medication dose for the all- patients group was 145 mg and 104 mg for the sertraline- and amitriptyline-treatment groups , respectively . As measured by the Hamilton Rating Scale for Depression and the Clinical Global Impressions Scale , both the sertraline and amitriptyline treatment groups showed a significantly greater improvement from baseline ( p less than or equal to .001 ) than the placebo group . The sertraline group had a higher proportion of gastrointestinal complaints and male sexual dysfunction than either the amitriptyline or the placebo group . The amitriptyline group showed a higher proportion of anticholinergic and sedative side effects and dizziness compared with patients who received either sertraline or placebo Rationale Amplitude , habituation and prepulse inhibition ( PPI ) of the acoustic startle response ( ASR ) in rodents and humans are sensitive to psychotropic drugs . Studies with rodents suggest that an increase or decrease in serotonin level in the brain alters several modalities of the ASR . So far , little is known about serotonergic and noradrenergic startle modulation in humans . Objective This study was design ed to investigate the effects of the selective serotonin uptake inhibitor sertraline versus the selective noradrenalin uptake inhibitor reboxetine on magnitude , habituation and PPI of ASR in patients with major depression . Methods We studied ASR in 23 patients with the diagnosis of major depression according to DSM-IV who were r and omly treated either with sertraline or with reboxetine .  Initially , ASR assessment was carried out when patients were drug-free for at least 2 weeks and again after 14 days of treatment . Results The habituation of ASR was strongly attenuated by sertraline and not significantly altered by reboxetine . None of the substances altered the startle reactivity . In addition , PPI was not altered by sertraline , but reboxetine tended to decrease PPI . The startle reactivity at baseline was correlated with improvement of depressive symptoms at the end of the study . Conclusion These results provide the first evidence for different effects of noradrenergic and serotonergic antidepressants on the startle response in depressed patients & NA ; The aim of this study was to examine response and remission rates in out patients treated with sertraline or fluoxetine who were suffering from two depression subtypes : anxious‐depression and severe depression . Data were pooled from five double‐blind studies comparing fluoxetine versus sertraline for the treatment of DSM‐III‐R or IV major depression . Clinical outcome was assessed using the Hamilton Depression Rating Scale ( HAM‐D ) and the Clinical Global Impression‐Improvement scale ( CGI‐I ) . One thous and and eighty‐eight patients were r and omized , with 654 ( 60 % ) meeting criteria for anxious depression and 212 ( 19 % ) meeting criteria for high severity depression . For the total sample , treatment response was similar for both sertraline and fluoxetine . In the high severity subgroup , the mean ( ±SD ) HAM‐D score at week 12 was 8.9±5.7 for sertraline and 10.8±6.9 for fluoxetine ( P=0.07 ) , and the mean ( ±SD ) CGI‐I score was 1.5±0.7 for sertraline and 2.0±1.1 for fluoxetine  ( P=0.005 ) . CGI‐I responder rates were 88 % versus 71 % ( P=0.03 ) in the high severity subgroup , and 84 % versus 79 % ( P=0.16 ) in the anxious‐depression subgroup . Overall , sertraline and fluoxetine showed comparable antidepressant efficacy , although sertraline may offer an advantage in those patients with severe depression BACKGROUND Sleep complaints are common in patients with major depressive disorder ( MDD ) . Both MDD and antidepressant drugs characteristically alter objective sleep measures . This study compares the effects of mirtazapine and fluoxetine on sleep continuity measures in DSM-IV MDD patients with insomnia . METHOD Patients ( N = 19 ) received initial baseline polysomnography evaluations over 2 consecutive nights . Subjects were r and omly assigned to either fluoxetine ( 20 - 40 mg/day ) or mirtazapine ( 15 - 45 mg/day ) treatment for an 8-week , double-blind , double-dummy treatment trial . Single-night polysomnograms were conducted at weeks 1 , 2 , and 8 , with depression ratings assessed at baseline and weeks 1 , 2 , 3 , 4 , 6 , and 8 . Statistical analysis was performed by repeated- measures analysis of variance followed by Dunnet 's post hoc analyses . RESULTS Patients receiving mirtazapine ( N = 8) had significant improvement in objective sleep physiology measures at 8 weeks . Improvements in sleep latency , sleep efficiency , and wake after sleep onset were significant after only 2 weeks of mirtazapine treatment . No significant changes in sleep continuity measures were observed in the fluoxetine group ( N = 11 ) . Both groups improved clinical ly in mood and subjective sleep measures from baseline , with no differences between groups . CONCLUSION These data demonstrate the differential effects of mirtazapine and fluoxetine , with significant improvement in favor of mirtazapine , on objective sleep parameters in MDD patients with insomnia There is clinical and biological evidence suggesting that patients with anger attacks , sudden spells of anger accompanied by intense autonomic activation , may represent a distinct psychopathological subgroup of patients with depressive disorders . We compared the prevalence of anger attacks in 168 out patients with atypical depression or primary dysthymia with 38 normal subjects and tested the effect of treatment on anger attacks in a double-blind , placebo-controlled trial of sertraline versus imipramine .  Patients were r and omly assigned to sertraline ( n = 56 ) , imipramine ( n = 52 ) , or placebo ( n = 60 ) and were administered the Anger Attacks Question naire before and after treatment . Depressed out patients were significantly more likely to report anger attacks than controls . Anger attacks ceased in 53 percent of the patients receiving sertraline , 57 percent of those receiving imipramine , and 37 percent of those in the placebo group . Our findings support previous studies indicating that anger attacks are more prevalent among depressed out patients than normals . Our results also suggest that sertraline and imipramine may be more effective than placebo in reducing the number of anger attacks following treatment although the differences were not statistically significant . Larger studies are needed to confirm our findings Depression is associated with considerable morbidity and mortality . As depressive disorders carry a high risk of relapse , treatment strategies include the use of a 6-month continuation period after resolution of the acute episode . Tolerability is of major importance when determining compliance and outcome during long-term therapy . Due to the superior tolerability profile of the selective serotonin reuptake inhibitors ( SSRIs ) over the older tricyclic antidepressants ( TCAs ) , the former may be more suitable for extended therapy . Comparative studies have not shown differences between the SSRIs in terms of efficacy , but side-effect profiles may vary . A multicenter , double-blind , comparative study of sertraline and fluoxetine was carried out in out patients fulfilling DSM-III-R criteria for major depressive disorder . Patients were r and omised to receive sertraline ( 50 - 150 mg , n = 118 ) or fluoxetine ( 20 - 60 mg , n = 120 ) for 24 weeks . Assessment s for depression ( HAM-D , HAD , CGI-I , CGI-S ) , anxiety ( Covi ) , sleep ( Leeds Sleep Evaluation scale ) and quality of life ( SIP ) were made at study entry and at weeks 2 , 4 , 8 , 12 , 18 and 24 . All adverse events were recorded to allow evaluation of tolerability . In total , 88 patients in the sertraline group completed the study compared with 79 in the fluoxetine group .  Side effects were responsible for the premature treatment withdrawal of seven ( 6 % ) sertraline patients and 12 ( 10 % ) fluoxetine patients . Two-hundred and thirty-four patients were included in an ITT analysis up to last visit ( 116 sertraline , 118 fluoxetine ) . At study endpoint , both treatments produced a significant improvement over baseline on all efficacy variables ( P < 0.001 ) . Although the magnitude of global changes in depression , anxiety , and quality of life was larger with sertraline than fluoxetine , none of the between-group differences reached statistical significance . However , significant differences in favour of sertraline were observed for individual HAM-D items including item 4 ( insomnia onset ) ( P = 0.04 ) , item 9 ( agitation ) ( P = 0.02 ) , and item 13 ( general somatic symptoms ) ( P = 0.008 ) . In addition , sertraline was associated with significantly superior performance on the Leeds Sleep Evaluation scale and on SIP items relating to sleep and rest , emotional behaviour and ambulation . Both sertraline and fluoxetine were well tolerated with no significant differences between treatments Sexual dysfunction , a frequently reported side effect of many antidepressants , may result in patient dissatisfaction and noncompliance with treatment regimens . This paper describes the results of the first placebo-controlled comparison of the efficacy , safety , and effects on sexual functioning of sustained-release bupropion ( bupropion SR ) and the selective serotonin reuptake inhibitor sertraline . This r and omized , double-masked , double-dummy , parallel-group , multicenter trial enrolled 360 patients with moderate-to-severe recurrent major depression . Patients were treated with bupropion SR 150 to 400 mg/d , sertraline 50 to 200 mg/d , or placebo for up to 8 weeks . Patients ' depression and sexual functioning were assessed at weekly or biweekly clinic visits ; safety was assessed by regular monitoring of adverse events , vital signs , and body weight . Treatment groups were similar at baseline in terms of age , sex , and race , and most patients had a diagnosis of moderate uncomplicated depression . Patients treated with bupropion SR or sertraline showed similar improvements on all efficacy measures ; both active treatments were superior to placebo in improving scores on all rating scales for depression at various time points . Significantly more patients treated with sertraline experienced orgasmic dysfunction throughout the study than did patients treated with bupropion SR or placebo ( P < 0.001 ) . Headache was the most frequently reported adverse event in all 3 treatment groups and occurred with similar frequency in each group ( 30 % to 40 % ) . Nausea ( 31 % ) , diarrhea ( 26 % ) , insomnia ( 18 % ) , and somnolence ( 17 % ) occurred in significantly more patients in the sertraline group than in the bupropion SR group ( 18 % , 7 % , 13 % , and 3 % , respectively ) and the placebo group ( 10 % , 11 % , 4 % , and 6 % , respectively ) . Dry mouth occurred more frequently with bupropion SR ( 19 % ) than with sertraline ( 14 % ) or placebo ( 12 % ) , although the differences were not significant . Changes in vital signs were similar in all groups . Similar ( small , but not statistically significant ) decreases in mean body weight were seen in both the bupropion SR ( -1.06 kg ) and sertraline ( -0.79 kg ) groups , whereas the placebo group experienced a minor increase ( 0.21 kg ) . Although bupropion SR and sertraline were similarly well tolerated and effective in the treatment of depression , sertraline treatment was more often associated with sexual dysfunction and certain other adverse events compared with bupropion SR and placebo . Therefore , bupropion SR may be an appropriate choice as an antidepressant for the treatment of sexually active patients We aim ed to compare the antidepressant and anxiolytic effects , tolerability and effects on quality of life of mirtazapine and citalopram in a r and omized , double-blind , multicentre , 8-week study . Patients with a Major Depressive Episode ( DSM-IV ) and a baseline score of > or = 22 on the Montgomery-Asberg Depression Rating Scale ( MADRS ) were r and omized to 8 weeks treatment with either mirtazapine  ( n = 137 , 15 - 60 mg/day ) or citalopram ( n = 133 , 20 - 60 mg/day ) . Efficacy was evaluated by the MADRS , Hamilton Anxiety Scale ( HAM-A ) , Clinical Global Impression scales ( CGI ) , the Leeds Sleep Evaluation Question naire ( LSEQ ) and Quality of Life Enjoyment and Satisfaction Question naire ( QLESQ ) . The efficacy analyses were performed on the Intent-To-Treat Group using the Last Observation Carried Forward method . Vital signs and laboratory variables are measured and adverse events recorded at each weekly visit . The magnitude of reduction from baseline in group mean MADRS scores was large in both groups , reaching after 8 weeks of treatment mean scores of 9.1 in the mirtazapine group and 8.9 in the citalopram group . Both treatments also result ed in a substantial improvement in anxiety symptoms , sleep disturbances and quality of life , and high percentage of responders . However , at day 14 , statistically significantly larger magnitudes of change favouring mirtazapine were present in the group mean MADRS , HAM-A and CGI-Severity of illness and Quality of life scores . A difference of 2.3 points on MADRS favouring mirtazapine is considered indicative for a clinical ly relevant superiority between two proven antidepressants . Mirtazapine treatment was also related to faster improvement of sleep , quality of sleep and improved alertness following awakening , as shown by statistically significant differences on the self-rating LSEQ at various time points . There were no differences between two treatment groups on self-rating QLSEQ . Both drugs were well tolerated , with a low number of patients in either group prematurely terminating the study due to adverse events  ( mirtazapine : 3.6 % , citalopram , 3.0 % ) . Sweating and nausea were statistically significantly more frequent in the citalopram group and increased appetite and complaints of weight increase in the mirtazapine group . There were no clinical ly relevant changes in laboratory parameters and vital sign variables with either treatment , except for clinical ly relevant increase in body weight , occurring more frequently in mirtazapine patients . In this study , mirtazapine and citalopram were equally effective in reducing symptoms of depression and anxiety , and well tolerated . However , mirtazapine was significantly more effective than citalopram after 2 weeks of treatment on the MADRS , HAM-A and CGI Severity of illness and Quality of life scales . This finding , consistently present at all major efficacy variables , suggests potentially faster onset of efficacy of mirtazapine over citalopram OBJECTIVE To compare the change in severity of depressive symptoms and occurrence of side effects in primary care patients treated with St John 's wort ( SJW ) and sertraline .  DESIGN Double-blind , r and omized 12-week trial . SETTING Community-based offices of 12 family physicians practising in greater Montreal , Que . PARTICIPANTS Eighty-seven men and women with major depression and an initial score of > or = 16 on the Hamilton Rating Scale for Depression ( Ham-D ) . INTERVENTIONS Patients were r and omized to treatment with either sertraline ( 50 to 100 mg/d ) or SJW ( 900 to 1800 mg/d ) in a double-blind fashion . Assessment of depression was done at entry and at 2 , 4 , 8 , and 12 weeks using the Ham-D , the Beck Depression Inventory ( BDI ) , and a question naire asking about compliance and side effects . MAIN OUTCOME MEASURES Changes from baseline in Ham-D and BDI scores and self-reported side effects . RESULTS There were no important differences in changes in mean Ham-D and BDI scores ( using intention-to-treat analysis ) , with and without adjustment for baseline demographic characteristics , between the two groups at 12 weeks . Significantly more side effects were reported in the sertraline group than in the SJW group at 2 and 4 weeks ' follow up . CONCLUSION The more benign side effects of SJW make it a good first choice for this patient population To compare the efficacy and tolerability of antidepressants switch with extended-release venlafaxine ( venlafaxine-XR ) , mirtazapine , and paroxetine in Chinese patients with major depressive disorder who had 2 consecutive unsuccessful antidepressant trials . One hundred fifty adult patients with treatment-resistant depression according to their medical records and /or response to current treatments were r and omly assigned to receive fixed-dosage treatment of venlafaxine-XR 225 mg/d ( n = 50 ) , mirtazapine 45 mg/d ( n = 55 ) , or paroxetine 20 mg/d ( n = 45 ) for 8 weeks . The primary outcome was the remission rates that were defined as a score 7 or lower on the 17-item Hamilton Rating Scale for Depression ( HRSD-17 ) . Secondary outcomes included the remission rate defined by the Self-Rating Depression Scale of 50 or lower and the response rate defined by a 50 % reduction or greater on the HRSD-17 total score , and the improvement of patients ' general health functions . The completion rates were 82 % for venlafaxine-XR , 81.8 % for mirtazapine , and 82.2 % for paroxetine . Only one patient in paroxetine arm discontinued the study owing to an adverse event . The remission rates based on the HRSD-17 were 42.0 % for venlafaxine-XR , 36.4 % for mirtazapine , and 46.7 % for paroxetine . There were no statistical significance s between treatment arms in remission rates . Similarly , there were also no significant differences between groups in secondary outcome measure .  Venlafaxine-XR , mirtazapine , and paroxetine were equally effective in the treatment of Chinese patients with major depressive disorder who failed at least 2 previous antidepressant treatments . Selecting any of these 3 antidepressants as a third-step antidepressant is a reasonable choice for this group of patients Lowering the concentrations of free cortisol in depressed patients may be an important prerequisite to prevent glucocorticoid-related sequelae of depression . We tested the hypothesis that the hypothalamus-pituitary-adrenal ( HPA ) system-dampening effects of venlafaxine and mirtazapine differ . We compared the course of morning ( 08.00h ) and afternoon saliva cortisol ( 16.00h ) in 42 mirtazapine- and 45 venlafaxine-treated depressed patients during a 1-week wash-out and a 4-week treatment period in a r and omised open trial . Mirtazapine lowered afternoon cortisol from week 1 to 4 . In contrast , during the course of the entire treatment period , venlafaxine did not attenuate saliva cortisol concentrations . Treatment effects of mirtazapine on cortisol concentrations did not differ in remitters and non-remitters to treatment . High baseline cortisol concentrations , on the other h and , were related to an unfavourable course during venlafaxine treatment and patients remitting during venlafaxine treatment had significantly lower afternoon cortisol concentrations in saliva , when compared to non-remitting patients . Thus , mirtazapine and venlafaxine show different effects on HPA system activity as measured by saliva cortisol . This may be of relevance with regard to physical sequelae of depression Patients ( n = 150 ) were r and omized to a 6-week , double-blind study to evaluate the relative efficacy and safety of mirtazapine , amitriptyline , and placebo in the treatment of major depressive disorder symptoms . Average daily modal doses were mirtazapine , 18 mg ; amitriptyline , 111 mg ; and placebo , 4.6 capsules . Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression ( HAM-D ) score reductions ( weekly visits 1 , 2 , 4 , and endpoint ) compared to placebo . These findings were supported by the Montgomery-Asberg Depression Rating Scale ( MADRS ) ; the Zung Self-rating Depression Scale ( SDS ) ; and the Clinical Global Impressions ( CGI ) scales . Somnolence and weight gain were the only adverse clinical experiences ( ACEs ) reported substantially more often by mirtazapine-treated patients than by those in the placebo group . However , more amitriptyline-treated patients reported decreased visual accommodation , dry mouth , dyspepsia , constipation , tachycardia , hypertension , hypotension , discoordination , dizziness , and tremor than mirtazapine- or placebo-treated patients . Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients , and superior to amitriptyline in respect to anticholinergic and cardiovascular effects This double-blind study compared initial combination therapy against monotherapy using two antidepressant drugs with complementary mechanisms of action on the serotonin ( 5-HT ) and norepinephrine ( NE ) systems . Sixty one adult patients with a DSM-IV diagnosis of unipolar depression were r and omized to receive mirtazapine ( 30 mg/day ) , paroxetine ( 20 mg/day ) , or the combination of both drugs for 6 weeks . Response at week 4 was defined as a 30 % reduction in the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and at week 6 as a 50 % reduction in the MADRS . Remission was defined as a reduction in the MADRS score to 10 points or less . After 4 weeks , non-responders in the monotherapy groups had their medication dose increased by 50 % . After 6 weeks , non-responders on monotherapy had the second trial drug added to their current regimen . Non-responders on combination therapy had the dosage of both drugs increased by 50 % . There was a significantly greater decrease in MADRS scores in the combination group compared to the monotherapy groups at days 28 , 35 and 42 , with a 10 point difference separating the combination from the monotherapies at day 42 . Remission rates at week 6 were 19 % on mirtazapine , 26 % on paroxetine , and 43 % on the combination . Fifteen patients in the mirtazapine arm and 10 in the paroxetine arm who did not respond had the other drug added to their current regimen , and 5 on the combination had an increase in dose of both drugs secondary to non-response . Of these 30 patients , approximately 50 % went on to achieve remission in the subsequent 2 weeks . These results indicate that the combined use of two antidepressants was well tolerated and produced a greater improvement than monotherapy In this double-blind study in primary care patients , the efficacy and safety of sertraline , an antidepressant which is a selective inhibitor of serotonin re-uptake , was compared with clomipramine .  Patients with DSM-III-defined major depression and with significant anxiety r and omly received 50 - 150 mg of either sertraline ( N=51 ) or clomipramine ( N=55 ) once daily for 6 weeks . The mean final daily dose was 63.5 mg sertraline and 60.6 mg clomipramine . Seventy five percent of sertraline-treated and 79 % of clomipramine-treated patients were maintained on the lowest dose of 50 mg once daily . The mean scores of all the rating scales ( HAM-D , HAM-A , HAD , CGI ) showed similar efficacy between the treatments in reducing the symptoms of depression and anxiety .  Clomipramine was less well tolerated than sertraline with a greater overall incidence of side effects , or significantly greater incidence of anticholinergic side effects and significantly more patient withdrawals due to side effects ; 18 % in the clomipramine group compared with 4 % in the sertraline group . The results indicate that sertraline is an effective agent to use in primary care patients with depression and associated symptoms of anxiety  and is better tolerated than the tricyclic comparator clomipramine BACKGROUND In nursing home residents and other frail elderly patients , old age and potential drug-drug and drug-disease interactions may affect the relative safety and efficacy of medications . The purpose of this study was to examine the efficacy and tolerability of venlafaxine and sertraline for the treatment of  depression among nursing home residents . METHOD The study was a 10-week r and omized , double-blind , controlled trial of venlafaxine ( doses up to 150 mg/day ) versus sertraline ( doses up to 100 mg/day ) among 52 elderly nursing home residents with a DSM-IV depressive disorder and , at most , moderate dementia . The primary measure of outcome was the Hamilton Rating Scale for Depression ( HAM-D ) . Adverse events were monitored and recorded systematic ally during the trial . RESULTS Twelve subjects were discontinued due to serious adverse events ( SAE ) , 5 were discontinued due to other significant side effects , and 2 withdrew consent . Tolerability estimated by the time to termination was lower for venlafaxine than sertraline for serious adverse events ( log rank statistic = 5.28 , p = .022 ) , for serious adverse events or side effects ( log rank statistic = 8.08 , p = .005 ) , or for serious adverse events , side effects , or withdrawal of consent ( log rank statistic = 10.04 , p = .002 ) . Mean ( SD ) HAM-D scores at baseline were 20.2 ( 3.4 ) for sertraline and 20.3 ( 3.7 ) for venlafaxine ; intent-to-treat endpoint HAM-D scores were 12.2 ( 5.1 ) and 15.7 ( 6.2 ) ( F = 3.45 ; p = .069 ) . There were no differences in categorical responses for the intent-to-treat sample or completers . CONCLUSION In this frail elderly population , venlafaxine was less well tolerated and , possibly , less safe than sertraline without evidence for an increase in efficacy . This unexpected finding demonstrates the need for systematic research on the safety of drugs in the frail elderly BACKGROUND Few studies have compared the treatment efficacy of the 2 selective serotonin reuptake inhibitors sertraline and fluoxetine . METHOD A r and omized , single-blind , parallel-group study of 10 weeks ' duration comparing the efficacy of sertraline , 50 mg/day ; sertraline , 100 mg/day ; and fluoxetine , 20 mg/day , was conducted in 44 psychiatric out patients with DSM-IV unipolar major depressive disorder . Antidepressant dosages were doubled at 6 weeks for subjects who had not achieved remission . Primary outcome measurements included the 21-item Hamilton Rating Scale for Depression ( HAM-D ) and the Clinical Global Impressions-Improvement scale ( CGI-I ) , with scores of < or = 7 on the HAM-D and < or = 2 on the CGI-I representing a positive treatment response , i.e. , remission . RESULTS At 4 weeks , significant differences in rate of positive treatment response were noted , with 0 % for sertraline , 50 mg ; 46 % for sertraline , 100 mg ; and 31 % for fluoxetine , 20 mg ( p = .023 ) . At 6 weeks , positive treatment response rates were 21 % , 43 % , and 31 % for subjects taking 50 mg of sertraline , those taking 100 mg of sertraline , and those taking 20 mg of fluoxetine , respectively , with treatment groups no longer differing significantly from each other . In subjects for whom antidepressant dose was doubled at week 6 , response rates at week 10 ( 4 weeks on increased dose ) were 40 % for sertraline , 100 mg ; 43 % for sertraline , 200 mg ; and 55 % for fluoxetine , 40 mg . CONCLUSION Subjects taking sertraline , 100 mg , and  fluoxetine , 20 mg , demonstrated an earlier treatment response compared with subjects taking sertraline , 50 mg . For patients without a positive response at 6 weeks , an increased antidepressant dose result ed in remission for a substantial proportion of patients when assessed 4 weeks later Tricyclic antidepressants and more recent antidepressants are generally considered to have equivalent efficacy in the treatment of depression . After a previous report of a marked difference in the response to mirtazapine compared to imipramine , we report here an analysis of different symptom clusters . One hundred seven consecutive in- patients with major depression ( Diagnostic and Statistical Manual III-R , DSM-III-R ) and a Hamilton Rating Scale for Depression ( HRS-D ) score of 18 points or more were r and omly assigned to double-blind treatment . Two and four weeks after predefined blood levels had been obtained , the severity of depression was assessed using the HRS-D. The mean dosages used were 235 mg/day of imipramine and 77 mg/day of mirtazapine , the latter being in excess of the 15 - 45 mg/day range currently advised . Total HRS-D scores and seven symptom clusters were analyzed in the 85 patients ( 79 % ) who were not receiving any co-medication .  Imipramine was more effective against the clusters related to core symptoms of depression : " depression and guilt " , " retardation " , and " melancholia " , respectively . Mirtazapine showed a biphasic response with regard to the clusters " sleep " and " anxiety/agitation " , respectively , which consisted of a marked response after two weeks of predefined blood level , but with a waning of this effect at four weeks . Imipramine produced a more gradual response on these clusters , which was more pronounced at four weeks than with mirtazapine . Two aspects of the present study could be related to this finding : blood level control result ed in optimal treatment with imipramine but not mirtazapine , and - most importantly - the patients were not receiving any anxiolytic or hypnotic co-medication . These findings suggest that mirtazapine may have anxiolytic and sedative properties and fewer antidepressant properties than imipramine in severely depressed in- patients The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials Genetic variation at the FKBP5 locus has been reported to affect clinical outcomes in patients treated with antidepressant medications  in several studies . However , other reports have not confirmed this association . FKBP5 may regulate the sensitivity of the hypothalamic – pituitary – adrenal axis . We tested two  FKBP5 single nucleotide polymorphisms ( rs1360780 and rs3800373 ) in a sample of 246 geriatric patients treated for 8 weeks in a double‐blind r and omized comparison trial of paroxetine and mirtazapine .  These two polymorphisms had previously been reported to predict efficacy in depressed patients treated with selective serotonin reuptake inhibitors such as paroxetine , and those treated with mirtazapine , an agent with both serotonergic and noradrenergic actions . However , we found no significant associations between these FKBP5 genetic variants and clinical outcomes . Neither mean Hamilton Depression Rating Scale scores nor time to remission or response were predicted by FKBP5 genetic variation . These results suggest that FKBP5 is unlikely to play a major role in determining antidepressant treatment outcomes in geriatric patients . © 2009 Wiley‐Liss ,
target: Mirtazapine was significantly more effective than a serotonin-noradrenaline reuptake inhibitor ( venlafaxine only , two trials , n = 415 ) at two weeks ( OR 2.29 , 95 % CI 1.45 to 3.59 ) and at the end of acute-phase treatment ( OR 1.53 , 95 % CI 1.03 to 2.25).In terms of dropouts , there was no robust evidence to detect a difference between mirtazapine and other antidepressants .
  Mirtazapine was more likely to cause weight gain or increased appetite and somnolence than SSRIs but less likely to cause nausea or vomiting and sexual dysfunction .
  AUTHORS ' CONCLUSIONS Some statistically significant and possibly clinical ly meaningful differences between mirtazapine and other antidepressive agents were found for the acute-phase treatment of major depression .
  Mirtazapine is likely to have a faster onset of action than SSRIs during the acute-phase treatment .
  Dropouts occur similarly in participants treated with mirtazapine and those treated with other antidepressants , although the adverse event profile of mirtazapine is unique
background: BACKGROUND Mirtazapine has a unique mechanism of antidepressive action and is one of the commonly used antidepressants in clinical practice .
  OBJECTIVES The aim of the present review was to assess the evidence on the efficacy and acceptability of mirtazapine compared with other antidepressive agents in the acute-phase treatment of major depression in adults .