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 .
Efficacy and safety of long-term fluoxetine versus lithium monotherapy of bipolar II disorder: a randomized, double-blind, placebo-substitution study.
OBJECTIVE The authors examined the safety and efficacy of long-term fluoxetine monotherapy , lithium monotherapy , and placebo therapy in preventing relapse and recurrence of bipolar type II major depressive episode . The authors hypothesized that fluoxetine monotherapy would be superior to lithium monotherapy with a similar hypomanic mood conversion rate . METHOD Patients at least 18 years old who recovered from their major depressive episode during initial open-label fluoxetine monotherapy were r and omly assigned to receive 50 weeks of double-blind monotherapy with fluoxetine at 10 - 40 mg/day , lithium at 300 - 1200 mg/day , or placebo . The primary outcome measure was time to relapse or recurrence . Secondary outcome measures included the proportion of patients remaining well and the frequency of hypomanic symptoms . RESULTS There were no significant differences in clinical or demographic characteristics among the fluoxetine ( N=28 ) , lithium ( N=26 ) , and placebo ( N=27 ) groups . The mean time to relapse was 249.9 days for the fluoxetine group , 156.4 days for the lithium group , and 186.9 days for the placebo group . The hazard of relapse was significantly lower with fluoxetine compared with lithium , and the estimated hazard of relapse with lithium was 2.5 times greater than with fluoxetine . There were no statistically significant or clinical ly meaningful differences in hypomanic symptoms among treatment groups over time . One patient taking fluoxetine and one patient taking placebo discontinued treatment because of hypomania . CONCLUSIONS These findings suggest that long-term fluoxetine monotherapy may provide superior relapse-prevention benefit relative to lithium monotherapy after recovery from bipolar II major depressive episode without an increase in hypomanic mood conversion episodes
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 .