Ketamine has proved itself as a rapid-acting and effective treatment for depression

Scientists discovered positive effects of intravenous ketamine for treatment-resistant depression.


Both subanesthetic intravenous ketamine and electroconvulsive therapy (ECT) are presently used to treat severe depression that has not responded to other therapies. Still, it is unclear which one is more successful.

Ketamine was compared to ECT to see if it was non-inferior for patients with unipolar depression who were resistant to treatment but weren’t psychotic. The results were positive.

For the study, scientists conducted an open-label, randomized, noninferiority trial involving patients referred to ECT clinics for treatment-resistant major depression. While the 40-minute ketamine infusion is a modest dose of a routinely used anesthetic in which patients are awake, ECT requires general anesthesia for a brief time. Patients were randomly divided into two groups and studied for the effects of ECT and ketamine.

A standard course of three weeks of ECT was administered to patients in the ECT arm on Mondays, Wednesdays, and Fridays of each week. Patients randomly assigned to receive ketamine got it twice weekly for three weeks. A popular depression questionnaire assessed the patients a few days after three weeks. They searched for patients who showed at least a 50% reduction in depression severity scores as the primary end measure.

At the end of the three weeks of treatment, ketamine had a response rate of 55%, while ECT had a response rate of 41%. With 170 patients randomly assigned to ECT and 195 randomly assigned to ketamine, the sample size was the largest study ever conducted. Nearly 100 individuals were enrolled for this research at the Baylor location. While ketamine was linked to brief sensations of isolation on treatment days, ECT was linked to memory disruption that lingered for a few months after treatment.

Dr. Sanjay Mathew, a primary investigator of the Baylor site, said, “Statistically, it was a robust finding showing that ketamine was non-inferior to ECT. This study can give clinicians and patients confidence that ketamine is a reasonable and safe alternative to ECT, at least for the short-term management of treatment-resistant, nonpsychotic depression.”

Journal Reference:

  1. Amit Anand, Sanjay J. Mathew et al. Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. The New England Journal of Medicine. DOI: 10.1056/NEJMoa2302399