Systematic Review and Network Meta-analysis: Second-Generation Antipsychotics in Youth With Bipolar Depression

Abstract Objective To assess the relative efficacy and safety of second-generation antipsychotics for treating major depressive episodes in youth with bipolar disorder. Method A systematic literature review using PRISMA guidelines and network meta-analysis (NMA) of randomized controlled trials (RCTs) of second-generation antipsychotics for bipolar depression in youth (age 10-18 years) was conducted. Efficacy measures included Children's Depression Rating Scale, Revised (CDRS-R) and Clinical Global Impressions–Bipolar Disorder–Severity Depression (CGI-BP-S-depression) and Overall (CGI-BP-S-overall) scores. Available safety outcomes included discontinuations (all-cause, lack of efficacy, adverse events), metabolic parameters (weight change, cholesterol, triglycerides, glucose), changes in prolactin, and somnolence. Results from the NMA were reported as mean changes from baseline or odds ratios (OR) with 95% credible intervals (CrIs). Results Four RCTs comparing placebo to lurasidone, quetiapine (one each for immediate and extended-release), and the olanzapine-fluoxetine combination (OFC) met all the inclusion criteria. Lurasidone and OFC demonstrated similar and statistically significant improvements in CDRS-R, but quetiapine did not (lurasidone: -5.70 [-8.66, -2.76]; OFC: -5.01 [-8.63, -1.38]; quetiapine: -1.85 [-5.99, 2.27]). Lurasidone had smaller changes in weight, cholesterol and triglycerides from baseline compared to OFC and quetiapine. There were no differences in changes in glucose levels among antipsychotics. In addition, lurasidone was associated with smaller change in prolactin levels compared to OFC but not quetiapine. Conclusion Evidence from four studies in this NMA indicated lurasidone and OFC, but not quetiapine, were efficacious for the treatment of bipolar depression in youth. Lurasidone was associated with less weight gain and smaller impact on cholesterol and triglycerides compared with quetiapine and OFC.