Time matters for metas: a systematic review and meta-analysis of ect vs ketamine for depression incorporating time.
Stevan Nikolin, Clara Massaneda-Tuneu, Louise Brettell, Colleen Loo
Translational Psychiatry January 23, 2026 DOI: 10.1038/s41398-026-03806-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Peer reviewed |
|---|---|
| Sample size | 731 |
| Population | Participants diagnosed with major depressive disorder |
| Interventions | Electroconvulsive therapy Ketamine |
| Topics | Depression Esketamine Ketamine |
| Citations | 1 |
| Key findings | ECT produced a faster rate of improvement in depressive symptoms than ketamine, with a predicted moderate efficacy advantage after four weeks. |
Abstract
Comparing treatments for severe and medication-resistant depression is essential for guiding clinical decision-making. 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. We systematically searched PubMED (MEDLINE), Embase, and Cochrane Library databases for studies published up to 31 November 2024. 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. 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. Efficacy was assessed by change in depression symptoms from baseline on a standardised measurement tool. 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. 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.
Comparable studies
Other systematic reviews and meta-analyses on ketamine for depression, most cited first.