Electroconvulsive Therapy Bests Ketamine in Treating Major Depressive Episodes

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Electroconvulsive therapy was superior to ketamine in a sensitivity analysis of methodologically stronger trials and also was better in study-defined response and remission for patients with major depressive episodes.

New research continues to support the use of electroconvulsive therapy (ECT) as the better option compared to ketamine in treating patients with major depressive episodes (MDE).1

A team, led by Vikas Menon, MD, Department of Psychiatry, JIPMER, compared depression rating outcomes in patients treated with ketamine compared to electroconvulsive therapy for adults with major depressive episodes and compared response and remission rates, the number of sessions to response and remission, and adverse effects.


While effective, the use of ECT has been limited by negative attitudes toward the treatment, as well as by its cognitive adverse effects and geographical variations in its availability. There remains a need for quantitively synthesis of completed studies to better guide research and clinical practice.

In the study, the investigators searched various databases from inception to May 15, 2022 for parallel-group randomized controlled trials that compared ketamine and electroconvulsive therapy in patients with major depressive episodes.

The investigators sought efficacy outcomes of 1 week or nearest posttreatment depression ratings, 1 week or nearest study-defined response and remission rates, and number of sessions to treatment response and remission. They also sought safety outcomes of reported adverse effects.

The team performed random-effects meta-analyses to see if the outcomes could differ at the population level in different parts of the world. They also looked at various additional relevant data.

The Trials

Overall, there were 5 trials identified involving 141 patients treated with ketamine and 137 patients treated with electroconvulsive therapy.

The results show an overall pooled standardized mean difference for posttreatment depression rating of -0.39 (95% confidence interval [CI], -0.81 to 0.02; I2 = 45%; 5 RCTs).

In a sensitivity analysis, the investigators found posttreatment depression ratings were significantly lower in the ECT group than it was in the ketamine cohort (SMD, −0.45; 95% CI, −0.75 to −0.14; I2 = 6%; 2 RCTs; n = 211).

For the efficacy outcome, ECT was superior to ketamine in a sensitivity analysis of methodologically stronger trials (SMD, -0.45; 95% CI, -0.75 to -0.14; I2 = 6%; 2 RCTs).

Electroconvulsive therapy also bested ketamine for study-defined response (risk ratio [RR], 1.27; 95% CI, 1.06-1.53; I2 = 0%; 3 RCTs) and remission (RR, 1.43; 95% CI, 1.12-1.82; I2 = 0%; 2 RCTs) rates.

The analysis also showed a pooled SMD in the difference in number of sessions required for response of 0.68 (95% CI, −0.80 to 2.16; I2 = 87%; 2 RCTs; n = 139).

There were no significant differences found between the 2 groups for number of sessions to response and remission, as well as for the cognitive outcomes (SMD, 0.13; 95% CI, −0.57 to 0.83; I2 = 1%; 2 RCTs; n = 34).

Some key limitations were the small number of studies included in the analysis, the limited sample size, and the high risk of bias in all of the trials.

“The findings of this study suggest that ECT may be superior to ketamine for improving depressive symptoms in adults with an MDE,” the authors wrote. “However, the advantage is small, and therefore, for many patients, especially those who want to be protected against cognitive risks, a trial of ketamine may be worth considering before a trial of ECT.”


Menon V, Varadharajan N, Faheem A, Andrade C. Ketamine vs Electroconvulsive Therapy for Major Depressive Episode: A Systematic Review and Meta-analysis. JAMA Psychiatry. Published online April 12, 2023. doi:10.1001/jamapsychiatry.2023.0562