***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: & NA ; This was a 6‐week , double‐blind , r and omized trial of the efficacy and tolerability of venlafaxine and fluoxetine in 109 patients with major depression and melancholia . Hospitalized and day care patients with DSM‐IV major depression and melancholia and a baseline Montgomery‐Asberg Depression Rating Scale ( MADRS ) score of ≥ 25 were eligible . The doses were venlafaxine 75 mg/day or fluoxetine 20 mg/day from days 1‐4 , venlafaxine 150 mg/day or fluoxetine 40 mg/day from days 5‐10 , and venlafaxine 225 mg/day or fluoxetine 60 mg/day from days 11‐42 . The intention‐to‐treat analyses included 55 patients on venlafaxine and 54 on fluoxetine . At the final evaluation , 70 % of patients with venlafaxine and 66 % with fluoxetine had ≥ 50 % reduction in the MADRS score , and 70 % with venlafaxine and 62 % with fluoxetine had a Clinical Global Impression ( CGI ) score of 1 or 2.A CGI improvement score of 1 was observed in 51 % of patients with venlafaxine and 32 % with fluoxetine ( P = 0.018 ) . A final Hamilton Depression Rating Scale ( HAM‐D ) score < 7 was attained in 41 % of venlafaxine‐treated and 36 % of fluoxetine‐treated patients . Overall , 22 % of patients in each group discontinued therapy , but only 5 % on venlafaxine and 9 % on fluoxetine discontinued for adverse events . Nausea was reported in 5.5 % of venlafaxinetreated patients and 14.8 % of fluoxetine‐treated patients . Venlafaxine was effective and well tolerated for treating in patients with major depression and melancholia . Based on remission criteria ( HAM‐D < 7 or CGI of 1 ) , venlafaxine was superior to fluoxetine Mild depressive syndromes are highly prevalent among primary -care patients . Evidence -based treatment recommendations need to be derived directly from this diagnostically heterogeneous group . The primary aim was to assess the efficacy of sertraline and cognitive-behavioural group therapy for treatment of depressed primary -care patients , the secondary aim was to evaluate if receiving treatment according to free choice is associated with a better outcome than r and omization to a particular treatment . We conducted a r and omized , placebo-controlled , single-centre , 10-wk trial with five arms : sertraline ( flexible dosages up to 200 mg/d ) ( n = 83 ) ; placebo ( n = 83 ) ; manual-guided cognitive-behavioural group therapy ( one individual session and nine group sessions per 90 min ) ( n = 61 ) ; guided self-help group ( control condition , n = 59 ) ; and treatment with sertraline or cognitive-behavioural group therapy according to patients ' choice ( n = 82 ) . From 1099 consecutively screened adult patients , 368 formed the intent-to-treat population with milder forms of depression . Primary outcome was a global efficacy measure combining z-converted Hamilton Depression Rating Scale and clinician-rated Inventory for Depressive Symptomatology scores .  Sertraline was superior to  placebo  ( p = 0.03 ) . Outcome for guided self-help groups was worse compared to cognitive-behavioural group therapy ( p = 0.002 ) and compared to all other treatment arms including pill placebo ( secondary analyses ) . Outcome in the patients ' choice arm was similar to that in the sertraline and cognitive-behavioural group therapy . Overall , sertraline is efficacious in primary -care patients with milder forms of depression . The superiority of cognitive-behavioural group therapy over guided self-help groups might partly be explained by ' nocebo ' effects of the latter & 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 OBJECTIVE Duloxetine doses of 80 and 120 mg/day were assessed for efficacy and safety in the treatment of major depressive disorder ( MDD ) . METHODS In this r and omized , double-blind trial , patients age > or = 18 meeting DSM-IV criteria for MDD were r and omized to placebo ( N=99 ) , duloxetine 80 mg/day ( N=93 ) , duloxetine 120 mg/day ( N=103 ) , or paroxetine 20 mg/day ( N=97 ) . The primary outcome measure was mean change from baseline in the 17-item Hamilton rating scale for depression ( HAMD(17 ) ) total score after 8 weeks of treatment ; a number of secondary efficacy measures also were assessed . Safety and tolerability were assessed via collection and analysis of treatment-emergent adverse events ( TEAEs ) , vital signs , and weight . The Arizona sexual experiences scale was used to assess sexual functioning . Patients who had a > or = 30 % reduction from baseline in the HAMD(17 ) total score  at the end of the acute phase entered a 6-month continuation phase where they remained on the same treatment as they had taken during the acute phase ; efficacy and safety/tolerability outcomes were assessed during continuation treatment . RESULTS More than 87 % of patients completed the acute phase in each treatment group . Duloxetine-treated patients ( both doses ) showed significantly greater improvement ( P<0.05 ) in the HAMD(17 ) total score at week 8 compared with placebo . Paroxetine was not significantly different from placebo ( P=0.089 ) on mean change on the HAMD(17 ) .  Duloxetine 120 mg/day also showed significant improvement on most secondary efficacy measures ( six of nine ) compared with placebo while duloxetine 80 mg/day ( three of nine ) and paroxetine ( three of nine ) were significantly superior to placebo on fewer secondary measures . HAMD(17 ) mean change data from this study and an identical sister study were pooled as defined a priori for the purpose s of performing a non-inferiority test versus paroxetine . Both duloxetine doses met statistical criteria for non-inferiority to paroxetine .  TEAE reporting rates were low in all treatment groups and no deaths occurred in the acute or continuation phases . CONCLUSIONS The efficacy of duloxetine at doses of 80 and 120 mg/day in the treatment of MDD was demonstrated . Tolerability , as measured by TEAEs , and safety were similar to paroxetine 20 mg/day and consistent with previous published data on duloxetine in the treatment of MDD Pramipexole , a dopamine D2 receptor agonist , was tested in 174 patients with major depression , with or without melancholia and without psychotic features . Three daily dose levels ( 0.375 mg , 1.0 mg , and 5.0 mg ) were compared to fluoxetine ( Prozac ) at 20 mg and placebo in a r and omized , double-blind , parallel-group study . After a 1 week placebo run-in period , patients were treated for 8 weeks , had a post- study follow-up ( week 9 ) , and were evaluated primarily with the Hamilton Psychiatric Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the Clinician 's Global Impressions-Severity of Illness scale ( CGI-SI ) .  All patients who received one dose of study medication were included in the observed-case analysis ( no missing data were replaced ) . Results indicated that by endpoint ( week 8) , patients receiving pramipexole at the 1.0 mg per day dose had significant improvement over baseline compared to the placebo group by measure of the HAM-D , MADRS , and CGI-SI . Significant improvement in this dose group was seen at other timepoints as well . The most obvious improvement was seen in the pramipexole 5.0 mg group , although a substantial dropout rate for this group precluded statistical tests vs. placebo late in the study . Patients taking fluoxetine also showed significant improvements at endpoint on the MADRS and earlier in the study on the HAM-D. No new or unusual safety concerns were generated during this study . Pramipexole helped safely alleviate the symptoms of depression at 1.0 mg per day and especially in those patients who could tolerate the escalation to 5 mg per day A placebo-controlled , double-blind study of 63 in patients with major affective disorder was performed to compare the safety and efficacy of fluvoxamine and imipramine . Results indicate that fluvoxamine and imipramine are superior to placebo and demonstrate a trend toward superiority of fluvoxamine over imipramine . Fluvoxamine was generally well tolerated in most patients Fluoxetine , a selective serotonin reuptake inhibitor , was compared with mianserin and placebo in a double‐blind study . In total , 81 depressed patients were included . Patients were rated weekly on the Hamilton Depression Rating Scale ( HDRS ) and the Montgomery & Asberg Depression Rating Scale ( MADRS ) . The duration was 6 weeks , and 52 patients completed the study . Significantly more patients on fluoxetine improved than patients on placebo . For mianserin no significant differences were found with either fluoxetine or placebo . Mean HDRS at the end of the study was also statistically significantly lower for fluoxetine , but not for mianserin , than placebo . Subscores of the MADRS showed improved sleep on mianserin at weeks 2 and 3 . Suicidal feelings were reduced to a greater degree on fluoxetine than on mianserin and placebo at weeks 6 and 7 . Fluoxetine  induced weight loss , while patients on mi 
    Output:
    
Overall , our analyses indicate that IR and extended-release formulations do not differ substantially with respect to efficacy and risk of harms .
The evidence is mixed with respect to differences in adherence , indicating lower adherence for IR formulations .
Conclusion Available evidence currently shows no clear differences between the two formulations and therefore we can not recommend a first choice .