Ketamine, Electroconvulsive Therapy Produce Similar Results for Treatment-Resistant Major Depression

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The results show 55.4% of patients in the ketamine group had a response, compared to 41.2% of patients in the ECT group.

The results of a comparison between ketamine and electroconvulsive therapy (ECT) show that ECT is noninferior to ketamine in treating patients with treatment-resistant major depression.1

A team, led by Amit Anand, MD, Department of Psychiatry, Mass General Brigham, and Harvard Medical School, compared the 2 treatments in this patient population.

The Treatments

ECT and subanesthetic intravenous ketamine are both promising options for patients with treatment-resistant major depression. However, investigators have yet to compare the effectiveness of the 2 treatments.

In the open-label, randomized, noninferiority trial, the investigators examined patients referred to ECT clinics for treatment-resistant major depression. Each participant was diagnosed with treatment-resistant major depression without psychosis and were assigned to receive either ketamine or ECT.

In the initial 3 week treatment phase, each patient was treated with either ECT 3 times per week or ketamine 0.5 mg per kilogram of body weight over 40 minutes twice per week.

The investigators sought primary outcomes of a response to treatment, assessed as a decrease of ≥50% from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report; scores range from 0 to 27, with higher scores indicating greater depression.

There was a noninferiority margin of -10 percentage points.

The investigators also sought secondary outcomes of the scores on memory tests and patient-reported quality of life.

Following the initial treatment phase, each patient who had a response were followed up with over a 6 month period.

The Comparison

The study included 403 patients who underwent randomization at 5 clinical sites, with 200 patients treated with ketamine and 203 patients in the ECT group. Ultimately 38 patients had withdrawn prior to initiation of the assigned treatment.

The final analysis included 195 patients in the ketamine group and 170 patients in the ECT group.

The results show 55.4% of patients in the ketamine group had a response, compared to 41.2% of patients in the ECT group (difference, 14.2 percentage points; 95% confidence interval [CI], 3.9-24.2; P <0.001 for the noninferiority of ketamine to ECT).

ECT was also associated with a decrease in memory call after 3 weeks of treatment mean [±SE] decrease in the T-score for delayed recall on the Hopkins Verbal Learning Test–Revised, −0.9±1.1 in the ketamine group vs. −9.7±1.2 in the ECT group; scores range from −300 to 200, with higher scores indicating better function), with gradual recovery found during follow-up.

There were similar improvements found in the 2 trial groups based on patient-reported quality-of-life.

In the safety analysis, the investigators found ECT was associated with musculoskeletal adverse effects and ketamine was associated with dissociation.

"Ketamine was noninferior to ECT as therapy for treatment-resistant major depression without psychosis," the authors wrote.


Anand, A., Mathew, S. J., Sanacora, G., Murrough, J. W., Goes, F. S., Altinay, M., Aloysi, A. S., Asghar-Ali, A. A., Barnett, B. S., Chang, L. C., Collins, K. A., Costi, S., Iqbal, S., Jha, M. K., Krishnan, K., Malone, D. A., Nikayin, S., Nissen, S. E., Ostroff, R. B., … Hu, B. (2023). Ketamine versus ECT for nonpsychotic treatment-resistant major depression. New England Journal of Medicine, 388(25), 2315–2325.