Abstract
IMPORTANCE: Comparing treatments for severe and medication-resistant depression is essential for guiding clinical decision-making. OBJECTIVE: In this meta-analysis, we investigate the efficacy of electroconvulsive therapy (ECT) compared to ketamine for the treatment of major depressive disorder (MDD) and address the discrepant results of prior meta-analyses. DATA SOURCES: We systematically searched PubMED (MEDLINE), Embase, and Cochrane Library databases for studies published up to 31 November 2024. STUDY SELECTION: Eligible studies met the following criteria: (1) participants diagnosed with major depression, (2) ECT and ketamine (administered via parenteral routes) treatment arms with comparable treatment durations and assessment periods, and (3) efficacy measured by standardized depression scales at a minimum of two time points. DATA EXTRACTION AND SYNTHESIS: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two independent reviewers assessed study eligibility, evaluated risk of bias (Cochrane Risk of Bias 2 tool), and extracted data from all available time points. A mixed-effects meta-regression analysis incorporated time as a fixed effect - minimising issues arising from temporal discrepancies between studies - and study as a random effect. MAIN OUTCOMES AND MEASURES: Efficacy was assessed by change in depression symptoms from baseline on a standardised measurement tool. RESULTS: Seven studies (731 participants) out of 1220 identified articles were eligible for analysis. Depression scores were significantly lower at baseline in the ketamine group compared to ECT (SMD = -0·28; p = 0·018; 95% CI -0·51-·05). Meta-regression analysis, adjusted for baseline scores, revealed a significant effect of time for standardised mean differences (β = 0·018; p < 0·0001; 95% CI 0·009-0·026), indicating that ECT led to a faster rate of improvement of approximately 0·02 SMD per day, amounting to a predicted SMD = 0·59 (95% CI -0·26-1·43) over four weeks. CONCLUSIONS AND RELEVANCE: ECT resulted in a more rapid reduction of depressive symptoms, with a projected moderate efficacy advantage over ketamine by the end of a four-week course, within the established range for a clinically meaningful benefit.