ECT vs Ketamine for Major Depressive Disorder: New Data

Megan Brooks

April 12, 2023

Electroconvulsive therapy (ECT) appears to have a small advantage over ketamine for improving depressive symptoms in adults with a major depressive episode, results of a new review show.

"Although ECT is superior to ketamine for patients with a major depressive episode (MDE), our findings suggest that the therapeutic advantage may be smaller than what was demonstrated in prior analyses," first author Vikas Menon, MD, Department of Psychiatry, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, India, told Medscape Medical News.

"This supports a recommendation for a trial of ketamine before a trial of ECT for patients with MDE, though this recommendation is limited by the small size and number of existing trials," Menon said.

The study was published online today in JAMA Psychiatry.

Questions Remain

The meta-analysis included five trials of 278 adults with MDE (141 treated with ketamine and 137 with ECT).

In the main analysis, posttreatment depression ratings showed a trend for lower scores with ECT compared with ketamine (standardized mean difference [SMD], −0.39; 95% CI, −0.81 to 0.02). 

In a sensitivity analysis of the two methodologically stronger trials, ECT was superior to ketamine (pooled SMD −0.45; 95% CI, −0.75 to −0.14).

ECT was also superior to ketamine in terms of response rates (risk ratio [RR] 1.27; 95% CI, 1.06 - 1.53) and remission rates (RR, 1.43; 95% CI, 1.12 - 1.82).

There were no significant between-group differences for number of sessions to response and remission and for cognitive outcomes.

Key limitations of the analysis were the small number of studies with limited sample sizes and a high risk of bias in all trials.

"There is a need for more comparative studies with adequate sample size in non-inferiority designs, examining a wider range of benefits and side effects, and followed up for longer durations, to answer clinically relevant questions about the nature and durability of observed benefits with ketamine," said Menon.

"In patients with MDE for whom the administration of ECT is limited by restricted availability of the treatment, concerns about its cognitive adverse effects, negative patient attitudes, and other issues, clinicians may consider a trial of ketamine," he added.

"Important Research"

Several experts offered perspective on the analysis in a statement from the UK-based nonprofit Science Media Centre, which was not involved with the conduct of this study.

Rupert McShane, MD, psychiatrist at the University of Oxford, UK, noted that ECT and ketamine are both "potent" treatments for depression and this meta-analysis shows that they are, "broadly speaking, equally as good as each other with perhaps a slight advantage for ECT."

"Whether or not there is a difference depends on exactly how you define it and how you cut the data. Despite the slight advantage for ECT in this analysis, the authors support using ketamine before ECT, especially in patients who are worried about the cognitive risks of ECT. This seems sensible," McShane said.

Allan Young, MBChB, clinical psychiatrist at King's College London, UK, noted that both ketamine and ECT have been shown to help some patients with treatment-resistant depression.

"Clearly the relative benefits of these two treatments need to be understood better, but this review of the existing literature suggests that ECT may benefit some more than ketamine," said Young.

"There is evidence that ketamine with ECT may add little extra benefit but much more work needs to be done to fully understand how these treatments fit best into the treatment pathway for major depressive episodes. However, based on this evidence, ECT clearly still merits a place in the treatment pathway," Young added.

George Kirov, PhD, clinical professor, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK, said while the study is conducted well, most of the evidence is coming from one large trial conducted in Sweden.

"The other studies add small numbers of patients and the authors even present a sensitivity analysis after removing studies of poor quality, thus leaving only two studies and exposing even further the dependence of the results on one single study." Kirov noted. 

"The small studies should not be blamed for their size, as this is very difficult research to perform. On the other hand, the trends were in the same direction," he added.

With those caveats in mind, Kirov said he still thinks this is "important research. It establishes the superiority of ECT against an active comparator (ketamine) which is very popular now and accepted to be quite effective."

The study had no specific funding. Menon reports no relevant financial relationships. McShane is former chair of the ECT and Related Treatments Committee, Royal College of Psychiatrists and runs a ketamine clinic and an ECT service. Young has received compensation for lectures and advisory boards for AstraZeneca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allergan, Bionomics, Sumitomo Dainippon Pharma, COMPASS, and Sage; and has served as principal investigator on a trial of intranasal esketamine in treatment-resistant depression. Kirov has no interest to declare other than running the ECT service in Cardiff.

JAMA Psychiatry. Published online April 12, 2023. Abstract

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