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

Background: Ketamine, electroconvulsive therapy (ECT), and their combination are effective for treating severe depression, but few large-scale studies have compared these. Methods: 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 posttreatment. This study was registered on PROSPERO (CRD42023476740). Results: 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 MontgomeryAsberg Depression Rating Scale (MADRS); highest rank probability again for ECT, followed by ketamine + ECT, ketamine, placebo. Conclusions: 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.