Ketamine vs electroconvulsive therapy for hard-to-treat depression: pooled results

The question

For people whose depression has not responded to standard treatments, does intravenous ketamine work as well as electroconvulsive therapy (ECT), a long-established brain stimulation treatment given under anaesthetic?

What they did

Researchers searched four large research databases up to 2 October 2024 for clinical trials and randomised controlled trials that directly compared ketamine with ECT in treatment-resistant major depressive disorder. Six studies met their criteria, covering 353 people who received ketamine and 323 who received ECT. They pooled the results to compare response, symptom scores, remission, relapse and side effects.

What they found

No statistically significant difference was found between the two treatments on any outcome measured. Response to treatment was similar (risk ratio 1.03, 95% confidence interval 0.78 to 1.37), as were depression scores on the MADRS rating scale (weighted mean difference 0.98, 95% CI -5.04 to 7.00), remission (RR 0.65, 95% CI 0.16 to 2.64) and relapse (RR 0.93, 95% CI 0.50 to 1.72). The number of people reporting adverse events was also similar (RR 0.72, 95% CI 0.47 to 1.10). The authors concluded ketamine was not inferior to ECT, while calling for further studies.

The fine print

Only six studies and fewer than 700 people in total were included, and the statistical inconsistency between studies was very high for response, MADRS scores and remission (I-squared values of 77% to 95%), meaning the studies disagreed considerably. “No significant difference” is not the same as proof that the treatments are equivalent; the confidence intervals were wide enough to include meaningful differences in either direction. The abstract does not report ketamine doses, number of sessions, ECT technique or how long people were followed. This summary is based on the abstract alone.

What it means

Across the available head-to-head trials, ketamine performed about as well as ECT for treatment-resistant depression, with a similar number of people reporting side effects, but the evidence base is small and the studies varied widely in their results.

Evidence grade: Moderate. A meta-analysis of six clinical trials, but it mixes trial types and shows very high inconsistency between studies for most outcomes.

This summary is based on the study’s published abstract.