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: OBJECTIVE To assess the efficacy and safety of aripiprazole versus placebo as adjunctive treatment to st and ard antidepressant therapy ( ADT ) in patients with major depressive disorder ( MDD ) who showed an incomplete response to 1 prospect i ve and 1 to 3 historical courses of ADT within the current episode . METHOD The study comprised a 7- to 28-day screening phase , an 8-week prospect i ve treatment phase , and a 6-week double-blind treatment phase . Patients with DSM-IV-TR-defined MDD were enrolled between June 16 , 2004 , and April 27 , 2006 . During prospect i ve treatment , patients received ADT : escitalopram , fluoxetine , paroxetine controlled-release , sertraline , or venlafaxine extended-release , each with single-blind , adjunctive placebo . Incomplete responders continued ADT and were r and omly assigned to double-blind , adjunctive placebo or adjunctive aripiprazole ( 2 - 15 mg/day with fluoxetine or paroxetine ; 2 - 20 mg/day with all others ) . The primary efficacy endpoint was the mean change from end of prospect i ve treatment to end of double-blind treatment ( week 14 , last observation carried forward ) in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score ( analysis of covariance ) . RESULTS A total of 178 patients were r and omly assigned to adjunctive placebo and 184 to adjunctive aripiprazole . Baseline demographics were similar between groups ( mean MADRS total score of 26.0 ) . Mean change in MADRS total score was significantly greater with adjunctive aripiprazole ( -8.8 ) than adjunctive placebo ( -5.8 ; p < .001 ) . Adverse events ( AEs ) that occurred in > or = 10 % of patients with adjunctive placebo or adjunctive aripiprazole were akathisia ( 4.5 % vs. 23.1 % ) , headache ( 10.8 % vs. 6.0 % ) , and restlessness ( 3.4 % vs. 14.3 % ) . Discontinuations due to AEs were low with adjunctive placebo ( 1.7 % ) and adjunctive aripiprazole ( 2.2 % ) ; only 1 adjunctive aripiprazole-treated patient discontinued due to akathisia . CONCLUSIONS In patients with MDD who showed an incomplete response to ADT , adjunctive aripiprazole was efficacious and well tolerated . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00095823 OBJECTIVE To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate ( quetiapine XR ) as monotherapy treatment for major depressive disorder ( MDD ) . METHOD This 8-week ( 6-week active-treatment , r and omized phase ; 2-week posttreatment drug-discontinuation/tapering phase ) , multicenter , double-blind , r and omized , parallel-group , placebo- and active-controlled , phase 3 study was conducted between April 2006 and May 2007 . In total , 612 patients with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition (DSM-IV)-defined MDD were r and omly assigned to quetiapine XR 150 mg/day or 300 mg/day , duloxetine 60 mg/day ( active control ) , or placebo . The primary endpoint was the change from baseline to week 6 in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score . RESULTS At week 6 , both doses of quetiapine XR ( p < .001 ) and duloxetine ( p < .01 ) significantly reduced mean MADRS total score versus placebo . A significant reduction was seen at week 1 with quetiapine XR 150 mg/day and 300 mg/day versus placebo ( p < .01 ) , but not with duloxetine . Response rates ( > or= 50 % reduction in MADRS total score ) at week 6 were significantly higher for both doses of quetiapine XR ( p < .01 ) and duloxetine ( p < .05 ) versus placebo . Remission rates ( MADRS score < or= 8) were significantly higher for quetiapine XR 300 mg/day and duloxetine versus placebo ( p < .05 ) , but not for quetiapine XR 150 mg/day . Hamilton Rating Scale for Depression , Hamilton Rating Scale for Anxiety , and Clinical Global Impressions-Severity of Illness total scores and the proportion of patients with Clinical Global Impressions-Improvement scores of 1 or 2 ( " much/very much improved " ) were significantly improved with both doses of quetiapine XR and duloxetine versus placebo . The most common adverse events reported were dry mouth , sedation , and somnolence for quetiapine XR and nausea , headache , dizziness , and dry mouth for duloxetine . CONCLUSION Quetiapine XR monotherapy ( 150 mg/day and 300 mg/day ) is effective , with safety and tolerability consistent with the known profile of quetiapine XR , in the treatment of patients with MDD , with onset of symptom improvement demonstrated at week 1 . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00321490 OBJECTIVE Patients ( 30 - 50 % ) with non-psychotic major depression will not respond despite an adequate trial of antidepressant medication . This study evaluated risperidone as an augmenting agent for patients who failed or only partially responded to an adequate trial of an antidepressant medication . METHOD Ninety-seven patients with unipolar non-psychotic major depression who were not responsive to antidepressant monotherapy were r and omized to risperidone ( 0.5 - 3mg/day ) or placebo augmentation in a four-week , double-blind , placebo controlled treatment trial . The primary outcome measure was remission defined by a score of < or = 10 on the Montgomery-Asberg Depression Rating Scale ( MADRS ) . Secondary outcomes measures were the Hamilton Rating Scale for Depression , the Clinician Global Impression of Severity scale and the overall satisfaction item of the Quality of Life and Enjoyment Question naire . RESULTS Subjects in both treatment groups improved significantly over time . The odds of remitting were significantly better for patients in the risperidone vs. placebo arm ( OR=3.33 , p=.011 ) . At the end of 4 weeks of treatment 52 % of the risperidone augmentation group remitted ( MADRS < or = 10 ) compared to 24 % of the placebo augmentation group ( CMH(1)=6.48 , p=.011 ) , but the two groups were converging . Patients in the risperidone group also reported significantly more improvement in quality -of-life than patients in the placebo group . There were no between-group differences in the number of adverse events reported , however , weight gain was significantly higher in the group receiving risperidone . CONCLUSION Augmentation of an antidepressant with risperidone for patients with difficult-to-treat depression leads to more rapid response and a higher remission rate and better quality -of-life Based on preliminary evidence of its usefulness in treatment-resistant depression ( TRD ) , an olanzapine/fluoxetine combination ( OFC ) was examined in comparison with olanzapine , fluoxetine , and venlafaxine in a TRD population . In this 12-week double-blind study , 483 subjects with unipolar , nonpsychotic TRD , with historic failure on a selective serotonin reuptake inhibitor ( SSRI ) and prospect i ve failure on open-label venlafaxine , were r and omized to an OFC or to an olanzapine , fluoxetine , or venlafaxine monotherapy group . Venlafaxine was continued r and omly in the double-blind acute phase to explore the benefits of continuation versus switching therapy . The Montgomery-Asberg Depression Rating Scale ( MADRS ) total change score at end point was the primary outcome measure . The OFC group had significantly greater improvement in depressive symptoms by week 1 of treatment ( MADRS mean change = -7.2 , baseline = 29.6 ) , in comparison to olanzapine ( -4.8 , P=.03 ) , fluoxetine ( -4.7 , P=.03 ) , or venlafaxine ( -3.7 , P=.002 ) groups and maintained its statistical separation from all three monotherapy groups through week 6 . At end point , the OFC group was significantly different only from the olanzapine group ( -14.1 vs. -7.7 , P<.001 ) . Analysis of a subgroup of subjects who had an SSRI failure in their current depressive episode ( n=334 ) revealed statistical separation from both olanzapine and fluoxetine ( but not venlafaxine ) at end point : OFC ( -14.6 ) versus olanzapine ( -9.4 , P<.001 ) versus fluoxetine ( -10.7 , P=.006 ) versus venlafaxine ( -14.7 , P=.98 ) . The OFC had a safety profile comparable to its component monotherapies ( i.e. , olanzapine and fluoxetine ) , showed a rapid onset of antidepressant effect , and was effective in this TRD sample . At the study end point , OFC , fluoxetine , venlafaxine , and low-dose OFC all appeared to be similarly effective BACKGROUND Evaluate the efficacy and tolerability of extended release quetiapine fumarate ( quetiapine XR ) once-daily monotherapy for patients with major depressive disorder ( MDD ) . METHODS In this 10-week , ( 8-week active treatment phase and 2-week drug-discontinuation/tapering phase ) , multicenter , parallel-group , placebo-controlled , double-blind , r and omized , Phase III study ( D1448C00003 : Opal ) , patients initially received quetiapine XR 150 mg/day or placebo . At Week 2 , inadequate responders ( < 20 % reduction in MADRS total score ) were up-titrated to 300 mg/day quetiapine XR or matching placebo for the final 6 weeks . Primary endpoint : change from r and omization to Week 8 in MADRS total score . Secondary endpoints included : MADRS response ( ≥50 % reduction in total score from r and omization ) and changes from r and omization to Week 8 in HAM-D and CGI-S. RESULTS 310 patients were r and omized . At Week 8 , quetiapine XR significantly reduced mean MADRS total score versus placebo ( -16.49 vs -13.10 , respectively ; p<0.01 ) . Mean MADRS score was significantly reduced by quetiapine XR versus placebo at Week 1 ( p<0.05 ) . MADRS response rates were significantly greater at Week 8 for quetiapine XR versus placebo ( 61.9 % vs 48.0 % , respectively ; p<0.05 ) . Significant changes in HAM-D total score and CGI-S were seen at Week 8 for quetiapine XR versus placebo . Withdrawal rates due to AEs were 9.9 % and 2.6 % for quetiapine XR and placebo , respectively . Common AEs ( > 10 % any group during the r and omized phase ) for quetiapine XR and placebo , respectively were dry mouth ( 32.9 % and 6.5 % ) , sedation ( 21.7 % and 1.9 % ) , somnolence ( 20.4 % and 5.2 % ) , and headache ( 10.5 % and 10.3 % ) . LIMITATIONS The study was not design ed to compare quetiapine XR 150 mg/day and 300 mg/day ; it was intended to reflect dose titration that might occur in clinical practice . CONCLUSIONS Quetiapine XR monotherapy is effective in patients with MDD , with symptom improvement seen as early as Week 1 , and tolerability results consistent with the known profile of quetiapine BACKGROUND Due to their favorable side-effect profile , atypical antipsychotic agents offer important therapeutic advantages in mood disorders .  Ziprasidone , an atypical antipsychotic agent with strong 5-HT(1A ) agonist activity , may be particularly useful when used in conjunction with st and ard antidepressants in treatment-resistant depression . The purpose of this study is to test this hypothesis in depressed out patients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor ( SSRI ) . METHOD Twenty patients with major depressive disorder ( MDD ) who had failed to experience a clinical response to an adequate trial of an SSRI were treated with open-label ziprasidone in addition to their SSRI for 6 weeks between February 2002 and December 2002 . MDD was diagnosed with the Structured Clinical Interview for DSM-IV Axis I disorders . Clinical response was defined as a 50 % or greater decrease in depressive symptoms during the course of the trial ( baseline to endpoint ) , as measured by the HAM-D-17 total score . RESULTS Thirteen of 20 patients ( 65.0 % ) completed the trial . Using a completer 
    Output:
    
agent
There were some beneficial effects compared to placebo or antidepressants but tolerability was worse .
Quetiapine was more effective than placebo treatment .
Aripiprazole and quetiapine and partly also olanzapine and risperidone augmentation showed beneficial effects compared to placebo .
Some evidence indicated beneficial effects of low-dose amisulpride for dysthymic people .
Most SGAs showed worse tolerability
***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: OBJECTIVE To assess the efficacy and safety of aripiprazole versus placebo as adjunctive treatment to st and ard antidepressant therapy ( ADT ) in patients with major depressive disorder ( MDD ) who showed an incomplete response to 1 prospect i ve and 1 to 3 historical courses of ADT within the current episode . METHOD The study comprised a 7- to 28-day screening phase , an 8-week prospect i ve treatment phase , and a 6-week double-blind treatment phase . Patients with DSM-IV-TR-defined MDD were enrolled between June 16 , 2004 , and April 27 , 2006 . During prospect i ve treatment , patients received ADT : escitalopram , fluoxetine , paroxetine controlled-release , sertraline , or venlafaxine extended-release , each with single-blind , adjunctive placebo . Incomplete responders continued ADT and were r and omly assigned to double-blind , adjunctive placebo or adjunctive aripiprazole ( 2 - 15 mg/day with fluoxetine or paroxetine ; 2 - 20 mg/day with all others ) . The primary efficacy endpoint was the mean change from end of prospect i ve treatment to end of double-blind treatment ( week 14 , last observation carried forward ) in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score ( analysis of covariance ) . RESULTS A total of 178 patients were r and omly assigned to adjunctive placebo and 184 to adjunctive aripiprazole . Baseline demographics were similar between groups ( mean MADRS total score of 26.0 ) . Mean change in MADRS total score was significantly greater with adjunctive aripiprazole ( -8.8 ) than adjunctive placebo ( -5.8 ; p < .001 ) . Adverse events ( AEs ) that occurred in > or = 10 % of patients with adjunctive placebo or adjunctive aripiprazole were akathisia ( 4.5 % vs. 23.1 % ) , headache ( 10.8 % vs. 6.0 % ) , and restlessness ( 3.4 % vs. 14.3 % ) . Discontinuations due to AEs were low with adjunctive placebo ( 1.7 % ) and adjunctive aripiprazole ( 2.2 % ) ; only 1 adjunctive aripiprazole-treated patient discontinued due to akathisia . CONCLUSIONS In patients with MDD who showed an incomplete response to ADT , adjunctive aripiprazole was efficacious and well tolerated . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00095823 OBJECTIVE To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate ( quetiapine XR ) as monotherapy treatment for major depressive disorder ( MDD ) . METHOD This 8-week ( 6-week active-treatment , r and omized phase ; 2-week posttreatment drug-discontinuation/tapering phase ) , multicenter , double-blind , r and omized , parallel-group , placebo- and active-controlled , phase 3 study was conducted between April 2006 and May 2007 . In total , 612 patients with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition (DSM-IV)-defined MDD were r and omly assigned to quetiapine XR 150 mg/day or 300 mg/day , duloxetine 60 mg/day ( active control ) , or placebo . The primary endpoint was the change from baseline to week 6 in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score . RESULTS At week 6 , both doses of quetiapine XR ( p < .001 ) and duloxetine ( p < .01 ) significantly reduced mean MADRS total score versus placebo . A significant reduction was seen at week 1 with quetiapine XR 150 mg/day and 300 mg/day versus placebo ( p < .01 ) , but not with duloxetine . Response rates ( > or= 50 % reduction in MADRS total score ) at week 6 were significantly higher for both doses of quetiapine XR ( p < .01 ) and duloxetine ( p < .05 ) versus placebo . Remission rates ( MADRS score < or= 8) were significantly higher for quetiapine XR 300 mg/day and duloxetine versus placebo ( p < .05 ) , but not for quetiapine XR 150 mg/day . Hamilton Rating Scale for Depression , Hamilton Rating Scale for Anxiety , and Clinical Global Impressions-Severity of Illness total scores and the proportion of patients with Clinical Global Impressions-Improvement scores of 1 or 2 ( " much/very much improved " ) were significantly improved with both doses of quetiapine XR and duloxetine versus placebo . The most common adverse events reported were dry mouth , sedation , and somnolence for quetiapine XR and nausea , headache , dizziness , and dry mouth for duloxetine . CONCLUSION Quetiapine XR monotherapy ( 150 mg/day and 300 mg/day ) is effective , with safety and tolerability consistent with the known profile of quetiapine XR , in the treatment of patients with MDD , with onset of symptom improvement demonstrated at week 1 . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00321490 OBJECTIVE Patients ( 30 - 50 % ) with non-psychotic major depression will not respond despite an adequate trial of antidepressant medication . This study evaluated risperidone as an augmenting agent for patients who failed or only partially responded to an adequate trial of an antidepressant medication . METHOD Ninety-seven patients with unipolar non-psychotic major depression who were not responsive to antidepressant monotherapy were r and omized to risperidone ( 0.5 - 3mg/day ) or placebo augmentation in a four-week , double-blind , placebo controlled treatment trial . The primary outcome measure was remission defined by a score of < or = 10 on the Montgomery-Asberg Depression Rating Scale ( MADRS ) . Secondary outcomes measures were the Hamilton Rating Scale for Depression , the Clinician Global Impression of Severity scale and the overall satisfaction item of the Quality of Life and Enjoyment Question naire . RESULTS Subjects in both treatment groups improved significantly over time . The odds of remitting were significantly better for patients in the risperidone vs. placebo arm ( OR=3.33 , p=.011 ) . At the end of 4 weeks of treatment 52 % of the risperidone augmentation group remitted ( MADRS < or = 10 ) compared to 24 % of the placebo augmentation group ( CMH(1)=6.48 , p=.011 ) , but the two groups were converging . Patients in the risperidone group also reported significantly more improvement in quality -of-life than patients in the placebo group . There were no between-group differences in the number of adverse events reported , however , weight gain was significantly higher in the group receiving risperidone . CONCLUSION Augmentation of an antidepressant with risperidone for patients with difficult-to-treat depression leads to more rapid response and a higher remission rate and better quality -of-life Based on preliminary evidence of its usefulness in treatment-resistant depression ( TRD ) , an olanzapine/fluoxetine combination ( OFC ) was examined in comparison with olanzapine , fluoxetine , and venlafaxine in a TRD population . In this 12-week double-blind study , 483 subjects with unipolar , nonpsychotic TRD , with historic failure on a selective serotonin reuptake inhibitor ( SSRI ) and prospect i ve failure on open-label venlafaxine , were r and omized to an OFC or to an olanzapine , fluoxetine , or venlafaxine monotherapy group . Venlafaxine was continued r and omly in the double-blind acute phase to explore the benefits of continuation versus switching therapy . The Montgomery-Asberg Depression Rating Scale ( MADRS ) total change score at end point was the primary outcome measure . The OFC group had significantly greater improvement in depressive symptoms by week 1 of treatment ( MADRS mean change = -7.2 , baseline = 29.6 ) , in comparison to olanzapine ( -4.8 , P=.03 ) , fluoxetine ( -4.7 , P=.03 ) , or venlafaxine ( -3.7 , P=.002 ) groups and maintained its statistical separation from all three monotherapy groups through week 6 . At end point , the OFC group was significantly different only from the olanzapine group ( -14.1 vs. -7.7 , P<.001 ) . Analysis of a subgroup of subjects who had an SSRI failure in their current depressive episode ( n=334 ) revealed statistical separation from both olanzapine and fluoxetine ( but not venlafaxine ) at end point : OFC ( -14.6 ) versus olanzapine ( -9.4 , P<.001 ) versus fluoxetine ( -10.7 , P=.006 ) versus venlafaxine ( -14.7 , P=.98 ) . The OFC had a safety profile comparable to its component monotherapies ( i.e. , olanzapine and fluoxetine ) , showed a rapid onset of antidepressant effect , and was effective in this TRD sample . At the study end point , OFC , fluoxetine , venlafaxine , and low-dose OFC all appeared to be similarly effective BACKGROUND Evaluate the efficacy and tolerability of extended release quetiapine fumarate ( quetiapine XR ) once-daily monotherapy for patients with major depressive disorder ( MDD ) . METHODS In this 10-week , ( 8-week active treatment phase and 2-week drug-discontinuation/tapering phase ) , multicenter , parallel-group , placebo-controlled , double-blind , r and omized , Phase III study ( D1448C00003 : Opal ) , patients initially received quetiapine XR 150 mg/day or placebo . At Week 2 , inadequate responders ( < 20 % reduction in MADRS total score ) were up-titrated to 300 mg/day quetiapine XR or matching placebo for the final 6 weeks . Primary endpoint : change from r and omization to Week 8 in MADRS total score . Secondary endpoints included : MADRS response ( ≥50 % reduction in total score from r and omization ) and changes from r and omization to Week 8 in HAM-D and CGI-S. RESULTS 310 patients were r and omized . At Week 8 , quetiapine XR significantly reduced mean MADRS total score versus placebo ( -16.49 vs -13.10 , respectively ; p<0.01 ) . Mean MADRS score was significantly reduced by quetiapine XR versus placebo at Week 1 ( p<0.05 ) . MADRS response rates were significantly greater at Week 8 for quetiapine XR versus placebo ( 61.9 % vs 48.0 % , respectively ; p<0.05 ) . Significant changes in HAM-D total score and CGI-S were seen at Week 8 for quetiapine XR versus placebo . Withdrawal rates due to AEs were 9.9 % and 2.6 % for quetiapine XR and placebo , respectively . Common AEs ( > 10 % any group during the r and omized phase ) for quetiapine XR and placebo , respectively were dry mouth ( 32.9 % and 6.5 % ) , sedation ( 21.7 % and 1.9 % ) , somnolence ( 20.4 % and 5.2 % ) , and headache ( 10.5 % and 10.3 % ) . LIMITATIONS The study was not design ed to compare quetiapine XR 150 mg/day and 300 mg/day ; it was intended to reflect dose titration that might occur in clinical practice . CONCLUSIONS Quetiapine XR monotherapy is effective in patients with MDD , with symptom improvement seen as early as Week 1 , and tolerability results consistent with the known profile of quetiapine BACKGROUND Due to their favorable side-effect profile , atypical antipsychotic agents offer important therapeutic advantages in mood disorders .  Ziprasidone , an atypical antipsychotic agent with strong 5-HT(1A ) agonist activity , may be particularly useful when used in conjunction with st and ard antidepressants in treatment-resistant depression . The purpose of this study is to test this hypothesis in depressed out patients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor ( SSRI ) . METHOD Twenty patients with major depressive disorder ( MDD ) who had failed to experience a clinical response to an adequate trial of an SSRI were treated with open-label ziprasidone in addition to their SSRI for 6 weeks between February 2002 and December 2002 . MDD was diagnosed with the Structured Clinical Interview for DSM-IV Axis I disorders . Clinical response was defined as a 50 % or greater decrease in depressive symptoms during the course of the trial ( baseline to endpoint ) , as measured by the HAM-D-17 total score . RESULTS Thirteen of 20 patients ( 65.0 % ) completed the trial . Using a completer 
    Output:
    