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 bipolar depression: The clinical debate
There are scientific , clinical and cultural aspects to the debate about antidepressants in bipolar depression . In prior communications I ’ve focused on scientific aspects . Over time , as I realized how the scientific evidence seemed unconvincing , I concluded that clinical and cultural aspects were important . Here , besides briefly recapitulating the scientific evidence , I will also comment on clinical and cultural factors . To begin with some rules of clinical research worth making explicit : r and omized data are more valid than observational data , because factors that influence the results besides what we are study ing ( confounding factors ) are only removed by r and omization . Sample size is less relevant ; a large observational study does not contradict a smaller r and omized study . Let ’s keep in mind this basic fact of science ( one can call it evidence -based medicine , EBM , if one wants ) . Given that background , risks and benefits of antidepressants need to be assessed in four categories : acute efficacy , maintenance efficacy , acute manic switch and long-term mood destabilization . These different groupings often overlap and are mixed , leading to confusion
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 .