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 .
Antidepressants in Type II Versus Type I Bipolar Depression: A Randomized Discontinuation Trial
Background We sought to test the hypothesis that antidepressants ( ADs ) may show preferential efficacy and safety among patients with type II bipolar disorder ( BD , BD-II ) more than patients with type I BD ( BD-I ) . Methods Patients with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , BD-I ( n = 21 ) and BD-II ( n = 49 ) in acute major depressive episodes were treated with ADs plus mood stabilizers to euthymia sustained for 2 months and then r and omized openly to continue or discontinue ADs for up to 3 years . Outcomes were episode recurrences and changes in st and ardized symptom ratings . Results In follow-up averaging 1.64 years , both subgroups showed improvement in depressive episode frequency with AD continuation , but contrary to the hypothesis , more improvement was seen in BD-I than in BD-II ( for type II , mean [ st and ard deviation ] decrease in depressive episodes per year , 0.21 [ 0.26 ] ; for type I , mean ( SD ) decrease , 0.35 [ 0.15 ] ) . Subjects with BD-II who continued on ADs had slightly more depressive , but fewer manic/hypomanic , episodes than subjects with BD-I. No notable differences were seen in either group in time to a recurrence of mood episodes or total time-in-remission . Conclusions The findings do not confirm the hypothesis that long-term AD treatment in patients with BP-II has better outcomes than in patients with BD-I , except somewhat lower risk of manic/hypomanic 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 .