Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode: A Systematic Review and Meta-analysis

This meta-analysis (s=6) explored data from clinical trials investigating the clinical efficacy of ketamine (n=178) and electroconvulsive therapy (ECT) (n=162) in participants with a major depressive episode. The overall standardized mean difference (SMD) for ECT when compared with ketamine was -0.69, which suggests ECT is more efficacious than ketamine for depression severity. No significant difference was observed in measures of cognition/memory or serious adverse events.


“Importance: Whether ketamine is as effective as electroconvulsive therapy (ECT) among patients with major depressive episodes remains unknown.

Objective: To systematically review and meta-analyze data about the clinical efficacy and safety of ketamine and ECT in patients with major depressive episode.

Data Sources: PubMed, MEDLINE, Cochrane Library, and Embase were systematically searched using Medical Subject Headings (MeSH) terms and text keywords from database inception through April 19, 2022, with no language limits. Two authors also manually and independently searched all relevant studies in US and European clinical trial registries and Google Scholar. Included were studies that involved (1) a diagnosis of depression using standardized diagnostic criteria, (2) intervention/comparator groups consisting of ECT and ketamine, and (3) depressive symptoms as an efficacy outcome using standardized measures.

Data Extraction and Synthesis: Data extraction was completed independently by 2 extractors and cross-checked for errors. Hedges g standardized mean differences (SMDs) were used for improvement in depressive symptoms. SMDs with corresponding 95% CIs were estimated using fixed- or random-effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed.

Main Outcomes and Measures: Efficacy outcomes included depression severity, cognition, and memory performance. Safety outcomes included serious adverse events (eg, suicide attempts and deaths) and other adverse events.

Results: Six clinical trials comprising 340 patients (n = 162 for ECT and n = 178 for ketamine) were included in the review. Six of 6 studies enrolled patients who were eligible to receive ECT, 6 studies were conducted in inpatient settings, and 5 studies were randomized clinical trials. The overall pooled SMD for depression symptoms for ECT, when compared with ketamine, was −0.69 (95% CI, −0.89 to −0.48; Cochran Q, P = .15; I2 = 39%), suggesting an efficacy advantage for ECT compared with ketamine for depression severity. Significant differences were not observed between groups for studies that assessed cognition/memory or serious adverse events. Both ketamine and ECT had unique adverse effect profiles (ie, ketamine: lower risks for headache and muscle pain; ECT: lower risks for blurred vision, vertigo, diplopia/nystagmus, and transient dissociative/depersonalization symptoms). Limitations included low to moderate methodological quality and underpowered study designs.

Conclusions and Relevance: Findings from this systematic review and meta-analysis suggest that ECT may be superior to ketamine for improving depression severity in the acute phase, but treatment options should be individualized and patient-centred.

Authors: Taeho G. Rhee, Sung R. Shim, Brent P. Forester, Andrew A. Nierenberg, Roger S. McIntyre, George I. Papakostas, John H. Krystal, Gerard Sanacora & Samuel T. Wilkinson

Summary of Efficacy and Safety of Ketamine vs Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is the gold standard treatment for TRD, but it is underused due to healthcare professional and patient barriers. Additionally, ECT has long been associated with adverse cognitive effects.

Since 2000, low doses of ketamine delivered intravenously have shown rapid and robust antidepressant effects in patients with TRD. However, ketamine is not currently approved by regulatory agencies for the treatment of depression.

Study details

Compounds studied

Topics studied

Study characteristics
Meta-Analysis Literature Review

340 Humans