***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: BACKGROUND To evaluate the effectiveness of quetiapine extended release once daily in  bipolar depression .  METHODS Double-blind , placebo-controlled study in acutely depressed adults with bipolar I or II disorder , with or without rapid cycling . Patients were r and omized to 8 weeks of quetiapine extended release ( XR ) 300 mg daily monotherapy or placebo . The primary outcome measure was change from baseline to Week 8 in MADRS total score . RESULTS Quetiapine XR 300 mg once daily ( N=133 ) showed significantly greater improvement in depressive symptoms compared with placebo ( N=137 ) from Week 1 ( p<0.001 ) through to Week 8 ( p<0.001 ) . Mean change in MADRS total score at Week 8 was -17.4 in the quetiapine XR group and -11.9 in the placebo group ( p<0.001 ) . Response ( > or=50 reduction in MADRS total score ) and remission ( MADRS total score < or=12 ) rates at Week 8 were significantly higher with quetiapine XR ( p<0.001 ) compared with placebo ( p<0.05 ) . Quetiapine XR improved core symptoms of depression . The most common adverse events associated with quetiapine XR were dry mouth , somnolence , and sedation . Greater weight gain was observed in patients on  quetiapine  XR relative to placebo . LIMITATIONS Fewer patients with bipolar II disorder included , only one fixed dose tested and the lack of an active comparator . CONCLUSIONS Quetiapine XR ( 300 mg ) once daily monotherapy was significantly more effective than placebo for treating episodes of depression in bipolar I disorder , throughout the 8-week study , with significance observed as early as Day 7 . Adverse events were consistent with the known effects of quetiapine OBJECTIVE The authors examined long-term effectiveness and study retention during open-label quetiapine treatment for rapid cycling bipolar disorder . METHODS An open-label , nonr and omized trial was conducted in 41 patients with rapid-cycling bipolar disorder ( type I=33 , type II=7 , NOS=1 ) who received flexibly dosed quetiapine monotherapy ( n=19 ) or add-on therapy ( n=22 ) for up to one year . Linear growth curves were calculated to assess longitudinal changes in depression and mania . RESULTS Linear growth curves demonstrated highly significant reductions in manic ( p<.0001 ) and depressive ( p<.0001 ) symptoms . Effect sizes were large against manic symptoms ( add-on therapy : Cohen 's d=0.66 ; monotherapy : Cohen 's d=0.75 ) but small-to-moderate against depression ( monotherapy : d=0.29 ; add-on therapy : d=0.40 ) . Most patients ( 68 % ) prematurely terminated the protocol ( mean duration : 18.0+/-16.9 weeks , mean dose : 195.6+/-196.1 mg/day ) , most often because of the need for additional psychotropic treatments . LIMITATIONS The study protocol involved an open label design with no placebo or active comparator group . The sample size provided adequate statistical power to detect large but not medium or small within-group effects . Premature dropout during the first six months precluded inferences about longer-term treatment outcome . CONCLUSIONS These observational findings provisionally suggest some benefit with quetiapine for both manic and depressive symptoms in rapid cycling bipolar disorder , at dosages somewhat lower than previously described either for mania or bipolar depression . The relatively high dropout rate underscores the complexity of rapid cycling bipolar disorder and likely necessity for pharmacotherapy adjustments over time OBJECTIVE The aim of this study was to evaluate the efficacy and tolerability of quetiapine and paroxetine monotherapy for major depression in bipolar disorder . METHOD 740 patients ( 478 bipolar I , 262 bipolar II ) with major depressive episodes ( DSM-IV ) were r and omly assigned to quetiapine 300 mg/d ( n = 245 ) , quetiapine 600 mg/d ( n = 247 ) , paroxetine 20 mg/d ( n = 122 ) , or placebo ( n = 126 ) for 8 weeks . The primary end point was the change from baseline in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score . The study was conducted from May 2005 to May 2007 . RESULTS Mean MADRS score change from baseline at 8 weeks was -16.19 for quetiapine 300 mg , -16.31 for quetiapine 600 mg , -13.76 for paroxetine , and -12.60 for placebo ( P < .001 for both quetiapine doses , P = .313 for paroxetine , vs placebo ) . Quetiapine-treated ( both doses ) , but not paroxetine-treated , patients showed significantly greater improvements ( P < or = .05 ) in most secondary outcomes measures at week 8 versus the placebo group . Paroxetine significantly improved Hamilton Anxiety Rating Scale scores versus placebo ( P < .05 ) but not MADRS or Hamilton Depression Rating Scale ( HDRS ) scores . Both quetiapine doses were associated with greater improvements than paroxetine for MADRS and HDRS scores . The most common adverse events were dry mouth , somnolence , sedation , and dizziness with quetiapine ( both doses ) and dry mouth , sedation , headache , insomnia , and nausea with paroxetine . The incidence of treatment-emergent mania/hypomania was lower with quetiapine compared with paroxetine and placebo . CONCLUSIONS Quetiapine ( 300 or 600 mg/d ) , but not paroxetine , was more effective than placebo for treating acute depressive episodes in bipolar I and II disorder . Quetiapine treatment was generally well tolerated . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00119652 Background The current article is a systematic review concerning the efficacy and safety of aripiprazole in the treatment of bipolar disorder . Methods A systematic Medline and repositories search concerning the usefulness of aripiprazole in bipolar disorder was performed , with the combination of the words ' aripiprazole ' and ' bipolar ' . Results The search returned 184 articles and was last up date d on 15 April 2009 . An additional search included repositories of clinical trials and previous systematic review s specifically in order to trace unpublished trials . There were seven placebo-controlled r and omised controlled trials ( RCTs ) , six with comparator studies and one with add-on studies . They assessed the usefulness of aripiprazole in acute mania , acute bipolar depression and during the maintenance phase in comparison to placebo , lithium or haloperidol . Conclusion Aripiprazole appears effective for the treatment and prophylaxis against mania . The data on bipolar depression are so far negative , however there is a need for further study at lower dosages . The most frequent adverse effects are extrapyramidal signs and symptoms , especially akathisia , without any significant weight gain , hyperprolactinaemia or laboratory test changes CONTEXT Evidence of psychosocial disability in bipolar disorder is based primarily on bipolar I disorder ( BP-I ) and does not relate disability to affective symptom severity and polarity or to bipolar II disorder ( BP-II ) . OBJECTIVE To provide detailed data on psychosocial disability in relation to symptom status during the long-term course of BP-I and BP-II . DESIGN A naturalistic study with 20 years of prospect i ve , systematic follow-up . SETTING Inpatient and outpatient treatment facilities at 5 US academic centers . Patients One hundred fifty-eight patients with BP-I and 133 patients with BP-II who were followed up for a mean ( SD ) of 15 ( 4.8 ) years in the National Institute of Mental Health Collaborative Depression Study . MAIN OUTCOME MEASURES The relationship , by r and om regression , between Range of Impaired Functioning Tool psychosocial impairment scores and affective symptom status in 1-month periods during the long-term course of illness from 6-month and yearly Longitudinal Interval Follow-up Evaluation interviews . RESULTS Psychosocial impairment increases significantly with each increment in depressive symptom severity for BP-I and BP-II and with most increments in manic symptom severity for BP-I. Subsyndromal hypomanic symptoms are not disabling in BP-II , and they may even enhance functioning . Depressive symptoms are at least as disabling as manic or hypomanic symptoms at corresponding severity levels and , in some cases , significantly more so . At each level of depressive symptom severity , BP-I and BP-II are equally impairing . When asymptomatic , patients with bipolar disorder have good psychosocial functioning , although it is not as good as that of well controls . CONCLUSIONS Psychosocial disability fluctuates in parallel with changes in affective symptom severity in BP-I and BP-II . Important findings for clinical management are the following : ( 1 ) depressive episodes and symptoms , which dominate the course of BP-I and BP-II , are equal to or more disabling than corresponding levels of manic or hypomanic symptoms ; ( 2 ) subsyndromal depressive symptoms , but not subsyndromal manic or hypomanic symptoms , are associated with significant impairment ; and ( 3 ) subsyndromal hypomanic symptoms appear to enhance functioning in BP-II To determine the efficacy and tolerability of olanzapine/fluoxetine combination ( OFC ) compared with lamotrigine ( Lam ) for long-term treatment of bipolar I depression , this 25-wk , r and omized , double-blind study compared OFC ( 6/25 , 6/50 , 12/25 , or 12/50 mg/d , n=205 ) with Lam titrated to 200 mg/d ( n=205 ) in patients with bipolar I disorder , depressed . A protocol -specified analysis of 7-wk outcomes was previously reported . Outcome measures included Clinical Global Impressions-Severity of Illness ( CGI-S ) ( primary ) , Montgomery-Asberg Depression Rating Scale ( MADRS ) , and Young Mania Rating Scale ( YMRS ) scores .  OFC-treated patients had significantly greater improvement than Lam-treated patients over 25 wk on CGI-S ( p=0.008 ) , MADRS ( p=0.005 ) , and YMRS ( p<0.001 ) scores , and from baseline across visits from week 5 ( titration complete ) to the end of the study on CGI-S ( p=0.043 ) , MADRS ( p=0.017 ) , and YMRS ( p=0.001 ) scores . Of patients in remission after the 7-wk acute phase , there was no significant difference between treatment groups in the incidence of relapse ( MADRS > 15 , p=0.528 ) . Rate of treatment-emergent mania was not significantly different by treatment ( p=0.401 ) . OFC-treated patients had more frequent ( p<0.05 ) somnolence , increased appetite , dry mouth , sedation , weight gain , and tremor ;  Lam-treated patients had more frequent insomnia . There was a significant difference in incidence of treatment-emergent cholesterol > or = 240 ( p<0.001 ) and in weight gain of > or = 7 % ( p<0.001 ) in favour of the Lam group . Patients with bipolar I depression had significantly greater symptom improvement over 25 wk on OFC compared with Lam . There was no treatment difference in incidence of relapse .  OFC-treated patients had more treatment-emergent adverse events and greater incidence of weight gain and hypercholesterolaemia Objectives : Bipolar disorder ( BD ) is a disabling and often chronic condition . Patients with BD suffer from depression at least one-third of the time , but they do not always respond well to conventional mood stabilizers . Attempts to treat them with antidepressants can provoke a switch to mania or increased cycling . Our open-label trial aim ed to assess the long-term response of patients with bipolar depression to the addition of quetiapine to their usual treatment . Our study also sought to assess the safety and tolerability of quetiapine in patients with BD . Method : To meet inclusion criteria for the study , patients had a DSM-IV diagnosis of type I or II BD , were aged 18 years and older , currently suffered from depression with a score of > 18 on the Hamilton Depression Rating Scale ( HDRS ) , and had no change in antidepressant use for at least 3 weeks prior to the study . We added quetiapine to patients ' medication and attempted to increase the dosage to at least 400 mg daily . Outcome was measured at baseline and once monthly for 12 months on the HDRS , the Young Mania Rating Scale , the Clinical Global Impression Scale ( CGI ) , and the Abnormal Involuntary Movement Scale . Results : There were 19 patients enrolled in the study ( 6 men and 13 women ) , 2 of whom dropped out because they could not tolerate the drug . Seventeen completed at least 2 assessment s , and 7 patients completed the full 12-month trial . Data for the 17 patients ( that is , last observation 
    Output:
    
Short-term studies suggested that patients treated with quetiapine monotherapy were significantly more likely than patients treated with placebo and further active comparators to achieve higher response and remission rates as well as more clinical improvements at the endpoint .
Maintenance studies suggested that the combination of quetiapine and mood stabilizers was significantly better than placebo plus mood stabilizers for the prevention of both depressive and manic relapses .
Quetiapine was generally well tolerated .
In conclusion , quetiapine could have some advantages over traditional treatments for the treatment of bipolar depression