human
***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: The current study sought to test the efficacy and safety of the novel selective norepinephrine reuptake inhibitor LY2216684 compared to placebo in patients with major depressive disorder ( MDD ) .  Escitalopram was used as a control for assay sensitivity . Adult out patients with MDD , confirmed at screening by the Mini International Neuropsychiatric Interview , a Self-Rated Quick Inventory of Depressive Symptomatology ( QIDS-SR ) score of at least 12 and a Clinical Global Impression-Severity Score of at least 4 , were r and omly assigned to LY2216684 ( N=269 ) , placebo ( N=138 ) , or escitalopram ( N=62 ) .  Efficacy , safety , and tolerability outcomes were compared during 8 weeks of double-blind treatment . LY2216684 plasma concentrations were measured . LY2216684 did not show statistically significant improvement from baseline compared to placebo in the primary analysis of the Hamilton depression rating scale ( HAM-D(17 ) ) total score . Escitalopram demonstrated significant improvement compared to placebo on the HAM-D(17 ) total score , suggesting adequate assay sensitivity . Both LY2216684 and escitalopram showed statistically significant improvement from baseline on the patient-rated QIDS-SR total score compared to placebo .  Headache , nausea , constipation , dry mouth , and insomnia were the most frequently reported adverse events in the LY2216684 group . A 3 - 6 beats per minute mean increase from baseline in pulse rate was observed in the LY2216684 group .  LY2216684 plasma concentrations increased as the dose increased from 3 mg to 12 mg . The results of this initial investigation of LY2216684 's efficacy suggest that it may have antidepressant potential . More definitive data to confirm this is necessary . Its safety profile does not preclude further clinical development Objectives To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate ( quetiapine XR ) monotherapy in patients with major depressive disorder ( MDD ) . Patients and methods This was a 10-week ( 8-week active treatment/2-week post-treatment ) r and omized , double-blind , placebo- and active-controlled study ( D1448C00004 ) . Patients received quetiapine XR 150 mg/day , escitalopram 10 mg/day , or placebo ; patients with an inadequate response ( < 20 % improvement in Montgomery – Åsberg Depression Rating Scale [ MADRS ] total score ) at week two received double-dose treatment . The primary end point was week eight change from r and omization in MADRS total score . Secondary end points included MADRS response ( ≥50 % improvement ) and remission ( score ≤8 ) ; Hamilton Rating Scale for Depression total and item 1 ; Hamilton Rating Scale for Anxiety total , psychic , and somatic ; Clinical Global Impressions – Severity of Illness total ; Pittsburgh Sleep Quality Index ( PSQI ) global ; and Quality of Life Enjoyment and Satisfaction Question naire – Short Form percentage maximum total scores . Tolerability was assessed throughout . Results A total of 471 patients was r and omized . No significant improvements in MADRS total score were observed at week eight ( last observation carried forward ) with either active treatment ( quetiapine XR , −17.21 [ P=0.174 ] ; escitalopram , −16.73 [ P=0.346 ] ) versus placebo ( −15.61 ) . There were no significant differences in secondary end points versus placebo , with the exception of week-eight change in PSQI global score  ( quetiapine XR , −4.96 [ P<0.01 ] versus placebo , −3.37 ) . Mixed-model repeated- measures analysis of observed-case data suggested that the primary analysis may not be robust . Most commonly reported adverse events included dry mouth , somnolence , and dizziness for quetiapine XR , and headache and nausea for escitalopram . Conclusion In this study , neither quetiapine XR ( 150/300 mg/day ) nor escitalopram ( 10/20 mg/day ) showed significant separation from placebo . Both compounds have been shown previously to be effective in the treatment of MDD ; possible reasons for this failed study are discussed . Quetiapine XR was generally well tolerated , with a profile similar to that reported previously This study was aim ed at resolving the time course of clinical action of antidepressants ( ADs ) and the type of early behavioral changes that precede recovery in treatment-responsive depressed patients . The first goal was to identify , during the first 2 weeks of treatment , the onset of clinical actions of the selective serotonin reuptake inhibitor ( SSRI ) , paroxetine , and the selective noradrenergic reuptake inhibitor , desipramine ( DMI ) . The second aim was to test the hypothesis that the two pharmacologic subtypes would induce different early behavioral changes in treatment-responsive patients . The design was a r and omized , parallel group , placebo-controlled , double-blind study for 6 weeks of treatment following a 1-week washout period . The study utilized measures of the major behavioral components of the depressive disorder as well as overall severity . The results indicated that the onset of clinical actions of DMI ranged from 3 to 13 days , averaged 13 days for paroxetine , and was 16–42 days for placebo . Furthermore , as hypothesized , the different types of ADs initially impacted different behavioral aspects of the disorder . After 1 week of treatment , DMI produced greater reductions in motor retardation and depressed mood than did paroxetine and placebo , and this difference persisted at the second week of treatment . Early improvement in depressed mood – motor retardation differentiated patients who responded to DMI after 6 weeks of treatment from those that did not . Paroxetine initially reduced anxiety more in responders than in nonresponders , and by the second week , significantly improved depressed mood and distressed expression in responders to a greater extent . Depressed patients who responded to placebo showed no consistent early pattern of behavior improvement . Early drug-specific behavioral changes were highly predictive of ultimate clinical response to the different ADs , results that could eventually be applied directly to clinical practice 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 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 mianserin gained weight . Side effects were present in most patients on the two active drugs ; those on fluoxetine experienced nausea and vomiting , and those on mianserin drowsiness Previous studies indicate that selective serotonin reuptake inhibitors ( SSRIs ) , including fluoxetine , fluvoxamine , citalopram and paroxetine , suppress rapid eye movement sleep , and increased nocturnal arousals . There has been no published report of the impact of sertraline on the sleep of depressed patients . This study examines such effects . Forty-seven patients with major depressive disorder , r and omized to double-blind treatment with sertraline or placebo , completed sleep studies before and after 12 weeks of pharmacotherapy . Groups were compared using multivariate analyses of covariance and /or analyses of covariance to examine 4 empirically defined sets of sleep measures . Compared to the placebo-treated group , patients who received sertraline experienced an increase in delta wave sleep in the first sleep cycle and prolonged rapid eye movement ( REM ) sleep latency . Although , sertraline therapy decreased the average number of REM periods ( from 3.86 to 2.40 ) , the activity of both REM period 1 and REM period 2 was significantly increased . Aside from an increase in sleep latency , sertraline therapy was not associated with a worsening of measures of sleep continuity . There was also no significant difference between the groups on a measure of subjective sleepiness . These findings are both similar and different from those observed in previous studies of other SSRIs . The increase in delta sleep ratio and consolidation of REM sleep may have some other clinical implication s. However , the generalizability of these findings is limited because of a number of reasons . Further studies are needed to examine the effects of SSRIs in acute treatment of depressed patients with severe insomnia , and the relationship of acute changes and relapse prevention of recurrent depression BACKGROUND Previous comparative studies of the selective serotonin 
    Output:
    
agent
SSRIs significantly increase the risk of both serious and non-serious adverse events .
The potential small beneficial effects seem to be outweighed by harmful effects .
***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: The current study sought to test the efficacy and safety of the novel selective norepinephrine reuptake inhibitor LY2216684 compared to placebo in patients with major depressive disorder ( MDD ) .  Escitalopram was used as a control for assay sensitivity . Adult out patients with MDD , confirmed at screening by the Mini International Neuropsychiatric Interview , a Self-Rated Quick Inventory of Depressive Symptomatology ( QIDS-SR ) score of at least 12 and a Clinical Global Impression-Severity Score of at least 4 , were r and omly assigned to LY2216684 ( N=269 ) , placebo ( N=138 ) , or escitalopram ( N=62 ) .  Efficacy , safety , and tolerability outcomes were compared during 8 weeks of double-blind treatment . LY2216684 plasma concentrations were measured . LY2216684 did not show statistically significant improvement from baseline compared to placebo in the primary analysis of the Hamilton depression rating scale ( HAM-D(17 ) ) total score . Escitalopram demonstrated significant improvement compared to placebo on the HAM-D(17 ) total score , suggesting adequate assay sensitivity . Both LY2216684 and escitalopram showed statistically significant improvement from baseline on the patient-rated QIDS-SR total score compared to placebo .  Headache , nausea , constipation , dry mouth , and insomnia were the most frequently reported adverse events in the LY2216684 group . A 3 - 6 beats per minute mean increase from baseline in pulse rate was observed in the LY2216684 group .  LY2216684 plasma concentrations increased as the dose increased from 3 mg to 12 mg . The results of this initial investigation of LY2216684 's efficacy suggest that it may have antidepressant potential . More definitive data to confirm this is necessary . Its safety profile does not preclude further clinical development Objectives To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate ( quetiapine XR ) monotherapy in patients with major depressive disorder ( MDD ) . Patients and methods This was a 10-week ( 8-week active treatment/2-week post-treatment ) r and omized , double-blind , placebo- and active-controlled study ( D1448C00004 ) . Patients received quetiapine XR 150 mg/day , escitalopram 10 mg/day , or placebo ; patients with an inadequate response ( < 20 % improvement in Montgomery – Åsberg Depression Rating Scale [ MADRS ] total score ) at week two received double-dose treatment . The primary end point was week eight change from r and omization in MADRS total score . Secondary end points included MADRS response ( ≥50 % improvement ) and remission ( score ≤8 ) ; Hamilton Rating Scale for Depression total and item 1 ; Hamilton Rating Scale for Anxiety total , psychic , and somatic ; Clinical Global Impressions – Severity of Illness total ; Pittsburgh Sleep Quality Index ( PSQI ) global ; and Quality of Life Enjoyment and Satisfaction Question naire – Short Form percentage maximum total scores . Tolerability was assessed throughout . Results A total of 471 patients was r and omized . No significant improvements in MADRS total score were observed at week eight ( last observation carried forward ) with either active treatment ( quetiapine XR , −17.21 [ P=0.174 ] ; escitalopram , −16.73 [ P=0.346 ] ) versus placebo ( −15.61 ) . There were no significant differences in secondary end points versus placebo , with the exception of week-eight change in PSQI global score  ( quetiapine XR , −4.96 [ P<0.01 ] versus placebo , −3.37 ) . Mixed-model repeated- measures analysis of observed-case data suggested that the primary analysis may not be robust . Most commonly reported adverse events included dry mouth , somnolence , and dizziness for quetiapine XR , and headache and nausea for escitalopram . Conclusion In this study , neither quetiapine XR ( 150/300 mg/day ) nor escitalopram ( 10/20 mg/day ) showed significant separation from placebo . Both compounds have been shown previously to be effective in the treatment of MDD ; possible reasons for this failed study are discussed . Quetiapine XR was generally well tolerated , with a profile similar to that reported previously This study was aim ed at resolving the time course of clinical action of antidepressants ( ADs ) and the type of early behavioral changes that precede recovery in treatment-responsive depressed patients . The first goal was to identify , during the first 2 weeks of treatment , the onset of clinical actions of the selective serotonin reuptake inhibitor ( SSRI ) , paroxetine , and the selective noradrenergic reuptake inhibitor , desipramine ( DMI ) . The second aim was to test the hypothesis that the two pharmacologic subtypes would induce different early behavioral changes in treatment-responsive patients . The design was a r and omized , parallel group , placebo-controlled , double-blind study for 6 weeks of treatment following a 1-week washout period . The study utilized measures of the major behavioral components of the depressive disorder as well as overall severity . The results indicated that the onset of clinical actions of DMI ranged from 3 to 13 days , averaged 13 days for paroxetine , and was 16–42 days for placebo . Furthermore , as hypothesized , the different types of ADs initially impacted different behavioral aspects of the disorder . After 1 week of treatment , DMI produced greater reductions in motor retardation and depressed mood than did paroxetine and placebo , and this difference persisted at the second week of treatment . Early improvement in depressed mood – motor retardation differentiated patients who responded to DMI after 6 weeks of treatment from those that did not . Paroxetine initially reduced anxiety more in responders than in nonresponders , and by the second week , significantly improved depressed mood and distressed expression in responders to a greater extent . Depressed patients who responded to placebo showed no consistent early pattern of behavior improvement . Early drug-specific behavioral changes were highly predictive of ultimate clinical response to the different ADs , results that could eventually be applied directly to clinical practice 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 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 mianserin gained weight . Side effects were present in most patients on the two active drugs ; those on fluoxetine experienced nausea and vomiting , and those on mianserin drowsiness Previous studies indicate that selective serotonin reuptake inhibitors ( SSRIs ) , including fluoxetine , fluvoxamine , citalopram and paroxetine , suppress rapid eye movement sleep , and increased nocturnal arousals . There has been no published report of the impact of sertraline on the sleep of depressed patients . This study examines such effects . Forty-seven patients with major depressive disorder , r and omized to double-blind treatment with sertraline or placebo , completed sleep studies before and after 12 weeks of pharmacotherapy . Groups were compared using multivariate analyses of covariance and /or analyses of covariance to examine 4 empirically defined sets of sleep measures . Compared to the placebo-treated group , patients who received sertraline experienced an increase in delta wave sleep in the first sleep cycle and prolonged rapid eye movement ( REM ) sleep latency . Although , sertraline therapy decreased the average number of REM periods ( from 3.86 to 2.40 ) , the activity of both REM period 1 and REM period 2 was significantly increased . Aside from an increase in sleep latency , sertraline therapy was not associated with a worsening of measures of sleep continuity . There was also no significant difference between the groups on a measure of subjective sleepiness . These findings are both similar and different from those observed in previous studies of other SSRIs . The increase in delta sleep ratio and consolidation of REM sleep may have some other clinical implication s. However , the generalizability of these findings is limited because of a number of reasons . Further studies are needed to examine the effects of SSRIs in acute treatment of depressed patients with severe insomnia , and the relationship of acute changes and relapse prevention of recurrent depression BACKGROUND Previous comparative studies of the selective serotonin 
    Output:
    