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: As many as 45 % of patients with major depressive episode also meet DSM-IV criteria for bipolar II ( BP II ) disorder . Although some clinicians advocate using a mood stabilizer in treating BP II depression , antidepressant monotherapy has been less well studied in this disorder . As part of a prospect i ve , placebo-controlled , relapse-prevention study in 839 patients , the efficacy and safety of short- and long-term fluoxetine treatment in patients with BP II major depression compared with patients with unipolar ( UP ) major depression was retrospectively examined . Eighty-nine BP II patients ( mean age , 41+/-11 years ) were compared with 89 age- and gender-matched UP patients and with 661 unmatched UP patients ( mean age , 39+/-11 years ) . All received short-term fluoxetine therapy at 20 mg daily for up to 12 weeks . Complete remission was defined as a final Hamilton Rating Scale for Depression score < or = 7 by week 9 that was then maintained for 3 additional weeks . Remitted patients were then r and omly assigned to receive double-blind treatment with one of the following : ( 1 ) fluoxetine 20 mg daily for 52 weeks ; ( 2 ) fluoxetine for 38 weeks , then placebo for 14 weeks ; ( 3 ) fluoxetine for 14 weeks , then placebo for 38 weeks ; or ( 4 ) placebo for 52 weeks . Antidepressant efficacy was similar in BP and UP patients during short-term therapy . Discontinuation for lack of efficacy was lower in BP II ( 5 % ) than in UP ( 12 % ) patients ( p = not significant [ NS ] ) , whereas dropouts for adverse events were similar in BP II ( 11 % ) and UP ( 9 % ) patients . During long-term relapse-prevention therapy , relapse rates were similar in BP II and UP patients ( p = NS ) . During short-term fluoxetine therapy , three BP II ( 3.8 % ) versus no matched UP ( p = NS ) and 0.3 % unmatched UP ( p = 0.01 ) patients had a " manic switch . " During long-term fluoxetine therapy , one ( 2 % ) BP II and three ( 1 % ) unmatched UP patients ( one taking placebo ) had a manic switch ( p = NS ) . In conclusion , fluoxetine may be a safe and effective antidepressant monotherapy for the short-term treatment of BP II depression with a relatively low manic switch rate . Fluoxetine may also be effective in relapse-prevention therapy in patients with BP II disorder CONTEXT The phenomenology of bipolar I disorder affects treatment and prognosis . OBJECTIVE To describe the duration of bipolar I mood episodes and factors associated with recovery from these episodes . DESIGN Subjects with Research Diagnostic Criteria bipolar I disorder were prospect ively followed up for as long as 25 years . The probability of recovery over time from multiple successive mood episodes was examined with survival analytic techniques , including a mixed-effects grouped-time survival model . SETTING Five US academic medical centers . PARTICIPANTS Two hundred nineteen subjects with bipolar I disorder . MAIN OUTCOME MEASURES Level of psychopathology was assessed with the Longitudinal Interval Follow-up Evaluation every 6 months for the first 5 years of follow-up and annually thereafter . RESULTS The median duration of bipolar I mood episodes was 13 weeks . More than 75 % of the subjects recovered from their mood episodes within 1 year of onset . The probability of recovery was significantly less for an episode with severe onset ( psychosis or severe psychosocial impairment in week 1 of the episode ) ( hazard ratio [ HR ] = 0.746 ; 95 % confidence interval [ CI ] , 0.578 - 0.963 ; P = .02 ) and for subjects with greater cumulative morbidity ( total number of years spent ill with any mood episode ) ( HR = 0.917 ; 95 % CI , 0.886 - 0.948 ; P < .001 ) . Compared with the probability of recovery from a major depressive episode , there was a significantly greater probability of recovery from an episode of mania ( HR = 1.713 ; 95 % CI , 1.373 - 2.137 ; P < .001 ) , hypomania ( HR = 4.502 ; 95 % CI , 3.466 - 5.849 ; P < .001 ) , or minor depression ( HR = 2.027 ; 95 % CI , 1.622 - 2.534 ; P < .001 ) and , conversely , a significantly reduced probability of recovery from a cycling episode ( switching from one pole to the other without an intervening period of recovery ) ( HR = 0.438 ; 95 % CI , 0.351 - 0.548 ; P < .001 ) . CONCLUSIONS The median duration of bipolar I mood episodes was 13 weeks , and the probability of recovery was significantly decreased for cycling episodes , mood episodes with severe onset , and subjects with greater cumulative morbidity In a small study of up to 3 years ' duration comparison of the value of amitriptyline alone versus amitriptyline + lithium in unipolar cases ( 27 patients ) and of that of lithium alone versus amitriptyline + lithium in bipolar cases ( 13 patients ) showed no advantage for the combination treatments in terms of efficacy in reducing depressive relapses . There was no effect of treatment , developing depression or developing hypothyroidism upon the psychological tests which were conducted during this prolonged study . Observer and self ratings detected an increase in depression before relapse was clearly present , but of the various psychological assessment s conducted only arousal showed changes in association with developing and definite relapse . The prescription of lithium but not amitriptyline + lithium or amitriptyline alone was associated with significant increases in blood pressure 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 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 Current guidelines for the treatment of bipolar type II ( BP II ) major depressive episode ( MDE ) recommend using either mood stabilizer monotherapy or the combination of a mood stabilizer with a selective serotonin reuptake inhibitor ( SSRI ) . These guidelines are the result of concern over SSRI-induced manic switch episodes . We previously showed that fluoxetine monotherapy may be effective as an initial treatment for BP II and BP NOS MDE with a low manic switch rate . We now present the results of a double-blind , placebo-substitution continuation study of fluoxetine monotherapy in BP II and BP NOS patients who have recovered from their MDE . This was a two-phase study . In study phase I , patients received open-label fluoxetine monotherapy 20 mg daily for up to 8 weeks . Responders with a final 17-item Hamilton Rating Scale for Depression ( HAM-D ) score≤9 were enrolled into study phase II which consisted of double-blind , placebo-substitution continuation therapy with fluoxetine 20 mg daily for up to 6 months . Outcome measures included the 17-item HAM-D and Young Mania Rating ( YMR ) scales . Changes in YMR scores were assessed using generalized estimating equation analysis . Relapse was assessed using Kaplan – Meier survival analysis and Fisher 's exact test . In study phase II , 43 % of fluoxetine-treated patients and 100 % of placebo-treated patients relapsed during continuation therapy ( P=0.08 ) . The mean increase in YMR score in study phase II was slightly higher in the fluoxetine-treated patients ( 3.0±1.8 ) versus placebo-treated patients ( 0.2±0.4 ) ( P=0.01 ) . However , this difference was not clinical ly meaningful . No hypomanic switch episodes were observed during study phase II . Despite the limited sample size result ing in insufficient power to detect statistical significance in relapse rates or change in YMR scores between treatment conditions , these preliminary data appear to support previous observations demonstrating that initial and continuation fluoxetine monotherapy may be safe and effective for some patients with BP II or BP NOS MDE with a low manic switch rate . Larger-scale studies are needed to confirm these findings 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 
    Output:
    
agent
Antidepressants were superior to placebo in reducing new depressive episodes in bipolar disorders without increasing risk of new manic/hypomanic episodes either used as monotherapy or in combination with MS .
Subgroup analyses revealed that greater benefit and lower risk may be achieved in BD II than in BD I. However , compared with MS monotherapy , AD monotherapy significantly increased the risk of affective switch with no improvement in prophylaxis of new depressive episodes .
CONCLUSIONS Reduced new depressive episodes may be achieved by long-term AD treatment with no significantly increased risk of new manic/hypomanic episodes in BD , particularly in BD II .
The elevated risk of affective switch  of AD monotherapy compared with MS monotherapy may be contributed to the protective effect of MS in diminishing manic/hypomanic episodes .
***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: As many as 45 % of patients with major depressive episode also meet DSM-IV criteria for bipolar II ( BP II ) disorder . Although some clinicians advocate using a mood stabilizer in treating BP II depression , antidepressant monotherapy has been less well studied in this disorder . As part of a prospect i ve , placebo-controlled , relapse-prevention study in 839 patients , the efficacy and safety of short- and long-term fluoxetine treatment in patients with BP II major depression compared with patients with unipolar ( UP ) major depression was retrospectively examined . Eighty-nine BP II patients ( mean age , 41+/-11 years ) were compared with 89 age- and gender-matched UP patients and with 661 unmatched UP patients ( mean age , 39+/-11 years ) . All received short-term fluoxetine therapy at 20 mg daily for up to 12 weeks . Complete remission was defined as a final Hamilton Rating Scale for Depression score < or = 7 by week 9 that was then maintained for 3 additional weeks . Remitted patients were then r and omly assigned to receive double-blind treatment with one of the following : ( 1 ) fluoxetine 20 mg daily for 52 weeks ; ( 2 ) fluoxetine for 38 weeks , then placebo for 14 weeks ; ( 3 ) fluoxetine for 14 weeks , then placebo for 38 weeks ; or ( 4 ) placebo for 52 weeks . Antidepressant efficacy was similar in BP and UP patients during short-term therapy . Discontinuation for lack of efficacy was lower in BP II ( 5 % ) than in UP ( 12 % ) patients ( p = not significant [ NS ] ) , whereas dropouts for adverse events were similar in BP II ( 11 % ) and UP ( 9 % ) patients . During long-term relapse-prevention therapy , relapse rates were similar in BP II and UP patients ( p = NS ) . During short-term fluoxetine therapy , three BP II ( 3.8 % ) versus no matched UP ( p = NS ) and 0.3 % unmatched UP ( p = 0.01 ) patients had a " manic switch . " During long-term fluoxetine therapy , one ( 2 % ) BP II and three ( 1 % ) unmatched UP patients ( one taking placebo ) had a manic switch ( p = NS ) . In conclusion , fluoxetine may be a safe and effective antidepressant monotherapy for the short-term treatment of BP II depression with a relatively low manic switch rate . Fluoxetine may also be effective in relapse-prevention therapy in patients with BP II disorder CONTEXT The phenomenology of bipolar I disorder affects treatment and prognosis . OBJECTIVE To describe the duration of bipolar I mood episodes and factors associated with recovery from these episodes . DESIGN Subjects with Research Diagnostic Criteria bipolar I disorder were prospect ively followed up for as long as 25 years . The probability of recovery over time from multiple successive mood episodes was examined with survival analytic techniques , including a mixed-effects grouped-time survival model . SETTING Five US academic medical centers . PARTICIPANTS Two hundred nineteen subjects with bipolar I disorder . MAIN OUTCOME MEASURES Level of psychopathology was assessed with the Longitudinal Interval Follow-up Evaluation every 6 months for the first 5 years of follow-up and annually thereafter . RESULTS The median duration of bipolar I mood episodes was 13 weeks . More than 75 % of the subjects recovered from their mood episodes within 1 year of onset . The probability of recovery was significantly less for an episode with severe onset ( psychosis or severe psychosocial impairment in week 1 of the episode ) ( hazard ratio [ HR ] = 0.746 ; 95 % confidence interval [ CI ] , 0.578 - 0.963 ; P = .02 ) and for subjects with greater cumulative morbidity ( total number of years spent ill with any mood episode ) ( HR = 0.917 ; 95 % CI , 0.886 - 0.948 ; P < .001 ) . Compared with the probability of recovery from a major depressive episode , there was a significantly greater probability of recovery from an episode of mania ( HR = 1.713 ; 95 % CI , 1.373 - 2.137 ; P < .001 ) , hypomania ( HR = 4.502 ; 95 % CI , 3.466 - 5.849 ; P < .001 ) , or minor depression ( HR = 2.027 ; 95 % CI , 1.622 - 2.534 ; P < .001 ) and , conversely , a significantly reduced probability of recovery from a cycling episode ( switching from one pole to the other without an intervening period of recovery ) ( HR = 0.438 ; 95 % CI , 0.351 - 0.548 ; P < .001 ) . CONCLUSIONS The median duration of bipolar I mood episodes was 13 weeks , and the probability of recovery was significantly decreased for cycling episodes , mood episodes with severe onset , and subjects with greater cumulative morbidity In a small study of up to 3 years ' duration comparison of the value of amitriptyline alone versus amitriptyline + lithium in unipolar cases ( 27 patients ) and of that of lithium alone versus amitriptyline + lithium in bipolar cases ( 13 patients ) showed no advantage for the combination treatments in terms of efficacy in reducing depressive relapses . There was no effect of treatment , developing depression or developing hypothyroidism upon the psychological tests which were conducted during this prolonged study . Observer and self ratings detected an increase in depression before relapse was clearly present , but of the various psychological assessment s conducted only arousal showed changes in association with developing and definite relapse . The prescription of lithium but not amitriptyline + lithium or amitriptyline alone was associated with significant increases in blood pressure 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 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 Current guidelines for the treatment of bipolar type II ( BP II ) major depressive episode ( MDE ) recommend using either mood stabilizer monotherapy or the combination of a mood stabilizer with a selective serotonin reuptake inhibitor ( SSRI ) . These guidelines are the result of concern over SSRI-induced manic switch episodes . We previously showed that fluoxetine monotherapy may be effective as an initial treatment for BP II and BP NOS MDE with a low manic switch rate . We now present the results of a double-blind , placebo-substitution continuation study of fluoxetine monotherapy in BP II and BP NOS patients who have recovered from their MDE . This was a two-phase study . In study phase I , patients received open-label fluoxetine monotherapy 20 mg daily for up to 8 weeks . Responders with a final 17-item Hamilton Rating Scale for Depression ( HAM-D ) score≤9 were enrolled into study phase II which consisted of double-blind , placebo-substitution continuation therapy with fluoxetine 20 mg daily for up to 6 months . Outcome measures included the 17-item HAM-D and Young Mania Rating ( YMR ) scales . Changes in YMR scores were assessed using generalized estimating equation analysis . Relapse was assessed using Kaplan – Meier survival analysis and Fisher 's exact test . In study phase II , 43 % of fluoxetine-treated patients and 100 % of placebo-treated patients relapsed during continuation therapy ( P=0.08 ) . The mean increase in YMR score in study phase II was slightly higher in the fluoxetine-treated patients ( 3.0±1.8 ) versus placebo-treated patients ( 0.2±0.4 ) ( P=0.01 ) . However , this difference was not clinical ly meaningful . No hypomanic switch episodes were observed during study phase II . Despite the limited sample size result ing in insufficient power to detect statistical significance in relapse rates or change in YMR scores between treatment conditions , these preliminary data appear to support previous observations demonstrating that initial and continuation fluoxetine monotherapy may be safe and effective for some patients with BP II or BP NOS MDE with a low manic switch rate . Larger-scale studies are needed to confirm these findings 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 
    Output:
    