***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 determine the efficacy of divalproex ( extended release ) in the treatment of acute nonrefractory bipolar depression . METHOD In a stratified , double-blind , r and omized , placebo-controlled trial , 18 acutely depressed bipolar out patients ( DSM-IV criteria ) received either divalproex monotherapy ( target dose level , 70 - 90 ng/dL ) ( N = 9 ) or placebo ( N = 9 ) for 6 weeks . Patients were recruited between January 2004 and May 2005 . Clinical assessment on the Montgomery-Asberg Depression Rating Scale ( MADRS ) determined primary efficacy . RESULTS The divalproex treatment group showed significantly greater reduction in MADRS scores compared to placebo ( group x time interaction , p = .0078 ) . Absolute effect size of estimated MADRS total score reduction over time was 13.6 points with divalproex versus 1.4 points with placebo ( p = .003 , linear growth curve model ) . St and ardized effect size was large ( Cohen d = 0.81 ) . MADRS item analyses demonstrated improvement in core mood symptoms more than in anxiety or insomnia symptoms . There was also a modest but significant association between MADRS and Mania Rating Scale scores in the divalproex group ( r = 0.29 , df = 51 , p = .03 ) , but not in the placebo group ( r = -0.15 , df = 35 , p = .36 ) . CONCLUSIONS Divalproex appeared to be an effective treatment for acute nonrefractory bipolar depression , which is consistent with previous small r and omized studies . Some evidence of benefit in the depressive mixed state was observed . Confirmation or refutation with larger r and omized clinical trials is warranted . CLINICAL TRIAL REGISTRATION Clinical Trials.gov identifier NCT00226343 BACKGROUND To our knowledge , this is the first prospect i ve natural history study of weekly symptomatic status of patients with bipolar I disorder ( BP-I ) during long-term follow-up . METHODS Analyses are based on ongoing prospect i ve follow-up of 146 patients with Research Diagnostic Criteria BP-I , who entered the National Institute of Mental Health ( Bethesda , Md ) Collaborative Depression Study from 1978 through 1981 .  Weekly affective symptom status ratings were analyzed by polarity and severity , ranging from asymptomatic , to subthreshold levels , to full-blown major depression and mania . Percentages of follow-up weeks at each level as well as number of shifts in symptom status and polarity during the entire follow-up period were examined . Finally , 2 new measures of chronicity were evaluated in relation to previously identified predictors of chronicity for BP-I. RESULTS Patients with BP-I were symptomatically ill 47.3 % of weeks throughout a mean of 12.8 years of follow-up . Depressive symptoms ( 31.9 % of total follow-up weeks ) predominated over manic/hypomanic symptoms ( 8.9 % of weeks ) or cycling/mixed symptoms ( 5.9 % of weeks ) . Subsyndromal , minor depressive , and hypomanic symptoms combined were nearly 3 times more frequent than syndromal-level major depressive and manic symptoms ( 29.9 % vs 11.2 % of weeks , respectively ) . Patients with BP-I changed symptom status an average of 6 times per year and polarity more than 3 times per year . Longer intake episodes and those with depression-only or cycling polarity predicted greater chronicity during long-term follow-up , as did comorbid drug-use disorder . CONCLUSIONS The longitudinal weekly symptomatic course of BP-I is chronic . Overall , the symptomatic structure is primarily depressive rather than manic , and subsyndromal and minor affective symptoms predominate . Symptom severity levels fluctuate , often within the same patient over time . Bipolar I disorder is expressed as a dimensional illness featuring the full range ( spectrum ) of affective symptom severity and polarity OBJECTIVE Determine the efficacy and tolerability of olanzapine/fluoxetine combination ( OFC ) for treatment of acute bipolar I depression compared with lamotrigine . METHOD The 7-week , acute phase of a r and omized , double-blind study compared OFC ( 6/25 , 6/50 , 12/25 , or 12/50 mg/day ; N = 205 ) with lamotrigine ( [ LMG ] titrated to 200 mg/day ; N = 205 ) in patients with DSM-IV-diagnosed bipolar I disorder , depressed . The study was conducted from November 2003 to August 2004 . RESULTS Completion rates were similar between treatments ( OFC , 66.8 % vs. LMG , 65.4 % ; p = .835 ) . OFC-treated patients had significantly greater improvement than lamotrigine-treated patients in change from baseline across the 7-week treatment period on the Clinical Global Impressions-Severity of Illness scale ( primary outcome ) ( p = .002 , effect size = 0.26 ) , Montgomery-Asberg Depression Rating Scale ( MADRS ) ( p = .002 , effect size = 0.24 ) , and Young Mania Rating Scale total scores ( p = .001 , effect size = 0.24 ) . Response rates did not significantly differ between groups when defined as > or = 50 % reduction in MADRS score ( OFC , 68.8 % vs. LMG , 59.7 % ; p = .073 ) . Time to response was significantly shorter for OFC-treated patients ( median days [ 95 % CI ] = OFC , 17 [ 14 to 22 ] vs. LMG , 23 [ 21 to 34 ] ; p = .010 ) . There was a significant difference in incidence of " suicidal and self-injurious behavior " adverse events ( OFC , 0.5 % vs. LMG , 3.4 % ; p = .037 ) . Somnolence , increased appetite , dry mouth , sedation , weight gain , and tremor occurred more frequently ( p < .05 ) in OFC-treated patients than lamotrigine-treated patients . Weight , total cholesterol , and triglyceride levels were significantly elevated in OFC-treated patients compared with lamotrigine-treated patients ( all p < or = .001 ) . CONCLUSIONS Patients with acute bipolar I depression had statistically significantly greater improvement in depressive and manic symptoms , more treatment-emergent adverse events , greater weight gain , and some elevated metabolic factors with OFC than lamotrigine . Treatment differences were of modest size BACKGROUND Episodes of depression are the most frequent cause of disability among patients with bipolar disorder . The effectiveness and safety of st and ard antidepressant agents for depressive episodes associated with bipolar disorder ( bipolar depression ) have not been well studied . Our study was design ed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania . METHODS In this double-blind , placebo-controlled study , we r and omly assigned subjects with bipolar depression to receive up to 26 weeks of treatment with a mood stabilizer plus adjunctive antidepressant therapy or a mood stabilizer plus a matching placebo , under conditions generalizable to routine clinical care . A st and ardized clinical monitoring form adapted from the mood-disorder modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders , fourth edition , was used at all follow-up visits . The primary outcome was the percentage of subjects in each treatment group meeting the criterion for a durable recovery ( 8 consecutive weeks of euthymia ) . Secondary effectiveness outcomes and rates of treatment-emergent affective switch ( a switch to mania or hypomania early in the course of treatment ) were also examined . RESULTS Forty-two of the 179 subjects ( 23.5 % ) receiving a mood stabilizer plus adjunctive antidepressant therapy had a durable recovery , as did 51 of the 187 subjects ( 27.3 % ) receiving a mood stabilizer plus a matching placebo ( P=0.40 ) . Modest nonsignificant trends favoring the group receiving a mood stabilizer plus placebo were observed across the secondary outcomes . Rates of treatment-emergent affective switch were similar in the two groups . CONCLUSIONS The use of adjunctive , st and ard antidepressant medication , as compared with the use of mood stabilizers , was not associated with increased efficacy or with increased risk of treatment-emergent affective switch . Longer-term outcome studies are needed to fully assess the benefits and risks of antidepressant therapy for bipolar disorder . ( Clinical Trials.gov number , NCT00012558 [ Clinical Trials.gov ] . ) Chinese herbal medicines possess the therapeutic potential for mood disorders . This double-blind , r and omized , placebo-controlled study was design ed to evaluate the efficacy and side effects of the herbal medicine called Free and Easy W and erer Plus ( FEWP ) as an adjunct to carbamazepine ( CBZ ) in patients with bipolar disorders . One hundred and twenty-four bipolar depressed and 111 manic patients were r and omized to treatment with CBZ alone , CBZ plus FEWP , or equivalent placebo  for 12 weeks . CBZ was initiated at 300mg/day and FEWP was given at a fixed dose of 36g/day . Efficacy measures included the Hamilton Rating Scale for Depression , Montgomery-Asberg Depression Rating Scale , Young Mania Rating Scale , Bech-Rafaelsen Mania Scale , and Clinical Global Impression-Severity ( CGI-S ) .  CBZ monotherapy produced significantly greater improvement on manic measures at week 2 through endpoint and CGI-S of depression at endpoint compared to placebo . CBZ monotherapy also yielded significantly higher clinical response rates than placebo on bipolar depression ( 63.8 % vs. 34.8 % , p=0.044 ) and mania ( 87.8 % vs. 57.1 % , p=0.012 ) . Compared to CBZ monotherapy , adjunctive FEWP with CBZ result ed in significantly better outcomes on the three measures of depression at week 4 and week 8 and significantly greater clinical response rate in depressed subjects ( 84.8 % vs. 63.8 % , p=0.032 ) , but failed to produce significantly greater improvement on manic measures and the response rate in manic subjects . There was a lesser incidence of dizziness and fatigue in the combination therapy compared to CBZ monotherapy . These results suggest that adjunctive FEWP has additive beneficial effects in bipolar patients , particularly for those in depressive phase BACKGROUND This is the first prospect i ve longitudinal study , to our knowledge , of the natural history of the weekly symptomatic status of bipolar II disorder ( BP-II ) . METHODS Weekly affective symptom status ratings for 86 patients with BP-II were based on interviews conducted at 6- or 12-month intervals during a mean of 13.4 years of prospect i ve follow-up . Percentage of weeks at each symptom severity level and the number of shifts in symptom status and polarity were examined . Predictors of chronicity for BP-II were evaluated using new chronicity measures . Chronicity was also analyzed in relation to the percentage of follow-up weeks with different types of somatic treatment . RESULTS Patients with BP-II were symptomatic 53.9 % of all follow-up weeks : depressive symptoms ( 50.3 % of weeks ) dominated the course over hypomanic ( 1.3 % of weeks ) and cycling/mixed ( 2.3 % of weeks ) symptoms . Subsyndromal , minor depressive , and hypomanic symptoms combined were 3 times more common than major depressive symptoms . Longer intake episodes , a family history of affective disorders , and poor previous social functioning predicted greater chronicity . Prescribed somatic treatment did not correlate significantly with symptom chronicity .  Patients with BP-II of brief ( 2 - 6 days ) vs longer ( > or = 7 days ) hypomanias were not significantly different on any measure . CONCLUSIONS The longitudinal symptomatic course of BP-II is chronic and is dominated by depressive rather than hypomanic or cycling/mixed symptoms . Symptom severity fluctuates frequently within the same patient over time , involving primarily symptoms of minor and subsyndromal severity . Longitudinally , BP-II is expressed as a dimensional illness involving the full severity range of depressive and hypomanic symptoms . Hypomania of long or short duration in BP-II seems to be part of the same disease process BACKGROUND Bipolar depression is a major clinical problem that remains under- research ed . The current study was intended to evaluate the effects of the novel antipsychotic risperidone , the selective serotonin reup-take inhibitor ( SSRI ) paroxetine , and the combination in patients with bipolar disorder . METHOD Thirty patients with DSM-IV bipolar ( I or II ) disorder , depressed phase , who were receiving a stable dose of a mood stabilizer were r and omly assigned to 12 weeks of double-blind treatment with risperidone ( plus placebo ) , paroxetine ( plus placebo ) , or the combination of risperidone and paroxetine . Data were gathered from August 
    Output:
    
Combination therapy was not statistically superior to monotherapy .
Weight gain , switching and suicide rates did not differ between groups .
No differences were found between individual medications or drug classes for any outcome .
Mood stabilisers are moderately efficacious for acute bipolar depression .