Adjunctive antidepressants for the acute treatment of bipolar depression: A systematic review and meta-analysis

•The present study focused on the effect and safety of antidepressants when used with therapeutic dose of mood stabilizers or antipsychotic medications.•Included studies in databases in English, Chinese, and French, which yielded more studies.•There is no evidence of adjunctive antidepressants clinically improving response rate or depressive symptoms for acute bipolar depression.•When used together with mood stabilizers or antipsychotics, antidepressants are well tolerated, without increasing the risk for mood switch in patients with acute bipolar depression in the short term. Long-term effects should still be considered according to evidence from other studies.•Antidepressants used with antipsychotics had a small but significantly better response rate compared to antipsychotics alone, which was not seen with antidepressants used with mood stabilizers. However, studies included in the favorable subgroup are mostly comprised of studies comparing patients taking olanzapine monotherapy versus the olanzapine-fluoxetine combination (OFC). In clinical practice, the risks and benefits of choosing between OFC and a currently approved antipsychotic as monotherapy for bipolar depression should be carefully considered.