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 .
OBJECTIVE Efficacy and safety of long-term use of antidepressants ( AD ) in bipolar disorder ( BD ) patients remains highly controversial .
Here we performed a meta- analysis of r and omized controlled trials ( RCTs ) exploring the efficacy and safety of long-term AD use in BD patients .
Effectiveness and Safety of the Combination of Fluoxetine and Olanzapine in Outpatients With Bipolar Depression: An Open-Label, Randomized, Flexible-Dose Study in Puerto Rico
We studied the effectiveness of olanzapine/fluoxetine combination ( OFC ) treatment of  bipolar depressive episode ( 7 weeks , study period 1 [ SP1 ] ) . Study period 1 responders ( mean modal daily OFC dosage , 10.8/27.8 mg ) were r and omized to OFC continuation treatment or olanzapine ( OLZ ) monotherapy starting at 10 mg ( 12 weeks , SP2 ) . Seventy-three percent of the 114 patients who entered into SP2 completed the trial .  The Montgomery-Åsberg Depression Rating Scale total score changes from baseline in SP1 ( primary outcome ) were significant ( −20 ± 10 , P < 0.001 ) and , during SP2 , worsened for patients in the OLZ group ( OFC vs OLZ , −0.4 ± 7.55 vs + 8.2 ± 14.1 , respectively ; P < 0.001 ) . During SP1 , 69 % responded and 59 % remitted . During SP2 , significantly more patients in the OFC group maintained response ( 31.3 % vs 12.5 % ) and remission ( 71.4 % vs 39.6 % ) than patients in the OLZ group . Treatment-emergent adverse events with OFC ( SP1 and SP2 ) included increased appetite , increased weight , somnolence , anxiety , insomnia , and depressed mood . Since visit 1 , the mean weight increases ( in pounds ) were 4.8 ± 6.8 for SP1 ( P < 0.001 ) and 6.3 ± 10.3 ( OFC ) or 10.7 ± 11.3 ( OLZ ) for SP2 ; 50 % ( OLZ ) and 33 % ( OFC ) of the patients had a 7 % or higher weight increase . For cholesterol , triglycerides , and low-density lipoprotein levels and some hepatic enzymes , there were statistically and clinical ly significant changes in both study periods but no differences between the SP2 groups . Study limitations included the open-label design and exclusion of the SP1 nonresponders from SP2 . These study results suggest that improvements result ing from 7 weeks of acute OFC treatment of a bipolar depressive episode are maintained in responders for an additional 12 weeks with OFC , but switching to OLZ alone may result in symptom worsening
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 .
OBJECTIVE Efficacy and safety of long-term use of antidepressants ( AD ) in bipolar disorder ( BD ) patients remains highly controversial .
Here we performed a meta- analysis of r and omized controlled trials ( RCTs ) exploring the efficacy and safety of long-term AD use in BD patients .