Confirmed: ECT Tops Ketamine for Major Depression

Megan Brooks

October 19, 2022

Electroconvulsive therapy (ECT) is more effective than intravenous (IV) ketamine for patients experiencing a major depressive episode (MDE) in new findings that are in line with the KetECT study ― the first head-to-head trial of ketamine and ECT.

As reported by Medscape Medical News, the KetECT trial was published earlier this year. It showed that ECT was more effective than IV ketamine for hospitalized patients with severe depression. ECT yielded higher remission rates and a greater reduction of symptoms.

Despite the apparent superiority of ECT over ketamine, the researchers of the current meta-analysis caution that treatment options for MDE "should still be individualized and patient-centered because ketamine's faster antidepressant effects may still be desirable for certain patients with severe MDE who require quick recovery from the severity of depression."

The study was published online October 19 in JAMA Psychiatry.

Confirmatory Data

The review included six clinical trials with 340 patients with MDE. Of those patients, 162 were treated with ECT, and 178 were treated with ketamine. The mean age of the participants ranged from 37 to 52 years.

The primary efficacy outcome of interest was improvement of depressive symptoms.

ECT was superior to ketamine across different depressive symptom measures, report Taeho Greg Rhee, PhD, with the University of Connecticut School of Medicine, in Farmington, and colleagues.

The standardized mean difference (SMD) was -0.59 (95% CI, -0.85 to -0.33) on the Montgomery-Åsberg Depression Rating Scale.

The SMD was -0.83 (95% CI, -1.22 to -0.44] on the Hamilton Depression Rating Scale and -0.86 (95% CI, -1.50 to -0.22) on the Beck Depression Inventory.

The overall pooled SMD for ECT, when compared with ketamine, was -0.69 (95% CI, -0.89 to -0.48), indicating that ECT was more efficacious than ketamine.

The researchers did not find any moderating effects of various factors, including age, male sex, and presence of psychotic features.

For cognition and memory performance, one study reported that the ketamine group outperformed the ECT group in cognition, but the effect size was small to moderate.

A separate study that reported memory performance found no difference between ketamine and ECT, though this study was likely underpowered to detect such differences, with a total sample size of 32.

"Because of underpowered study designs, no firm conclusions regarding cognition and memory performance can be made in this meta-analysis. Future research should address this issue," the investigators write.

Unique Side Effects

Ketamine and ECT had unique adverse effect profiles.

With ketamine, there was a lower risk of headache and muscle pain but a higher risk of transient dissociative or depersonalization symptoms. With ECT, there was a lower risk of blurred vision, vertigo, and diplopia/nystagmus.

Only one study reported suicide attempts and suicide deaths, for which there was no marked difference between ECT and ketamine.

A limitation of the meta-analysis is the low to moderate methodologic quality of the studies that were included, as well as the use of different ketamine and/or ECT treatment protocols, which could have influenced efficacy and safety outcomes.

The researchers note that more research is needed to optimize long-term treatment outcomes for both ketamine and ECT to prevent relapse, "which is of key importance for clinical practice."

The study had no specific funding. Rhee currently serves as a co–editor-in-chief of Mental Health Science and will receive honorarium payments annually from the publisher, John Wiley & Sons. A complete list of the authors' relevant financial relationships is available with the original article.

JAMA Psychiatry. Published online October 19, 2022. Abstract

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