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 .
Olanzapine/fluoxetine combination vs. lamotrigine in the 6-month treatment of bipolar I depression.
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
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 .