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 .
Safety and effectiveness of continuation antidepressant versus mood stabilizer monotherapy for relapse-prevention of bipolar II depression: A randomized, double-blind, parallel-group, prospective study.
OBJECTIVE Compare the safety and effectiveness of continuation antidepressant versus mood stabilizer monotherapy for preventing  depressive relapse in bipolar II disorder . METHODS Subjects ≥18 years old with bipolar II depression ( n=129 ) were r and omized to double-blind venlafaxine or lithium monotherapy for 12 weeks . Responders with a ≥50 % reduction in depression score were continued for an additional 6 months of relapse-prevention monotherapy . Primary outcome was depressive relapse during continuation monotherapy . Secondary outcomes included sustained response rate from initiation of treatment to study end-point , relapse hazard , time to relapse , change in mania ratings , and frequency of treatment-emergent sub-syndromal hypomania and /or depressive episodes . RESULTS Venlafaxine produced greater sustained response rate  versus lithium ( p<0.0001 ) ; however , there was no difference in relapse rate  for venlafaxine ( 7.5 % ) versus lithium ( 26.7 % ) ( p=0.079 ) ; relapse hazard ( p=0.073 ) , or time to relapse ( p=0.090 ) between treatment conditions during continuation monotherapy . There were no group differences in mania rating scores over time and no difference in frequency or duration of syndromal or sub-syndromal hypomanic episodes . There were more sub-syndromal depressive episodes  during lithium monotherapy ( p=0.03 ) . LIMITATIONS Sample size was limited by the lower sustained response rate  for lithium versus venlafaxine ; study was not specifically powered to detect differences in treatment-emergent hypomanic or depressive episodes between groups . CONCLUSION Results suggest that continuation venlafaxine monotherapy may provide similar prophylactic effectiveness relative to lithium , with no difference in treatment-emergent hypomanic episodes and without the need for frequent serum lithium level and metabolic monitoring . Larger , prospect i ve trials are needed to confirm these observations
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 .