Treatment of bipolar depression: results from a comprehensive network meta-analysis and updated systematic review.

Depressive episodes present a treatment challenge in bipolar disorder (BD), and an urgent need exists for novel treatment options. This review sought to revisit the results from a recent network meta-analysis (NMA) that examined treatment options for bipolar depression and to update those findings with a complementary systematic review (PROSPERO-ID: CRD42020171726). The NMA was based on the qualitative synthesis of 145 studies and the quantitative analysis of 101 studies investigating acute depression in adults with bipolar depression from inception to April 2023. A complementary systematic review was conducted using MEDLINE, OVID, EMBASE, PsychINFO, CINAHL, LILACS, Cochrane, Web of Science Core Collaboration, and Google Scholar databases from April 2023 to November 2024 to identify the most recent randomized controlled trials on the treatment of bipolar depression. Studies identified via systematic review were subjected to narrative synthesis and quality assessment was completed using revised Cochrane risk of bias tool. The original NMA showed that olanzapine plus fluoxetine, quetiapine, olanzapine, lurasidone, lumateperone, cariprazine, and lamotrigine were more efficacious than placebo in reducing depressive symptoms in BD with good confidence. Several other drugs might also be efficacious, but confidence in the evidence was very low to low. The complementary systematic review identified 24 clinical trials, seven of which had published results suitable for meta-analysis; the remaining 17 studies were either ongoing or completed with no available results. Collectively, the NMA and systematic review findings can inform evidence-based care and the development of international treatment guidelines for bipolar depression.