Ketamine and electroconvulsive therapy for severe depression: A network meta-analysis of efficacy and safety

Ketamine, electroconvulsive therapy (ECT), and their combination are effective for treating severe depression, but few large-scale studies have compared these. We searched databases for randomized controlled trials (RCTs) using ketamine, ECT, ketamine+ECT, or placebo for severe depression. Standardized measures were efficacy outcomes. Risk of bias was assessed. Stata and ADDIS were used for network meta-analysis (NMA) comparing efficacy and adverse reactions post-treatment. This study was registered on PROSPERO (CRD42023476740). 17 RCTs with 1370 patients were included. NMA showed ECT and ketamine improved Hamilton Depression Rating Scale (HDRS) versus placebo; other comparisons not significant. Rank probabilities showed highest probability for ECT, followed by ketamine+ECT, ketamine, placebo. No differences in Montgomery-Asberg Depression Rating Scale (MADRS); highest rank probability again for ECT, followed by ketamine+ECT, ketamine, placebo. Analysis suggests ECT superior to ketamine and their combination for improving depressive severity, but individualized treatment selection warranted. Higher adverse reactions with ketamine+ECT need further study for optimized combined use.