Antipsychotic Monotherapy for Major Depressive Disorder: A Systematic Review and Meta-analysis

Abstract

\n No clinical guidelines currently recommend antipsychotic monotherapy (APM) for major depressive disorder (MDD). Although several randomized controlled trials (RCTs) have compared the effectiveness, efficacy, and safety of APM versus placebo in patients with MDD, no meta-analysis has examined this topic. We conducted a systematic literature search using MEDLINE and Embase to identify relevant RCTs and performed a meta-analysis to compare the following outcomes between APM and placebo: study discontinuation due to all causes, lack of efficacy, and adverse events, changes in total scores on depression severity scales (e.g., Hamilton Depression Rating Scale and Montgomery Åsberg Depression Rating Scale) and in the Clinical Global Impression - Severity scale (CGI-S) score, and individual adverse event rates. A total of 13 identified studies with 14 comparisons involving 3,197 participants that met the eligibility criteria were included in the meta-analysis. No significant difference was found in study discontinuation due to all causes between the APM and placebo groups. However, there were significant differences in study discontinuation due to lack of efficacy in favor of the APM group and study discontinuation due to adverse events in favor of the placebo group. Compared with the placebo group, the APM group was significantly superior in relation to score reduction on the depression severity scales and CGI-S and inferior in relation to 8 of 23 individual adverse events. APM could be a useful treatment option for the acute phase of MDD, although clinicians should be aware of an increased risk of some adverse events.