Ketamine works just as well as “gold standard” for treatment-resistant major depression, says study

A new study published in NEJM adds to the growing body of research on the effectiveness of ketamine for treatment-resistant depression (TRD). Results from the ELEKT-D randomized trial found that when it came to improving treatment-resistant major depression in outpatients without psychotic features, ketamine worked just as well as electroconvulsive therapy (ECT).

ECT and subanesthetic intravenous ketamine are both currently used for treatment-resistant major depression, but the comparative effectiveness of the two treatments remains uncertain.

The open-label trial randomized 403 patients with nonpsychotic treatment-resistant major depression to either ketamine or ETC.

“At the conclusion of the 3-week, randomized, active-treatment phase, 41% of the patients in the ECT group and 55% of those in the ketamine group reported a 50% or greater reduction in symptoms, findings that are consistent with moderate-to-excellent responses to treatment,” wrote Robert Freedman, MD, from the University of Colorado Denver School of Medicine, in an accompanying editorial.

Ketamine—an type of psychedelic drug called a dissociative—was FDA-approved in 2019 as a prescription nasal spray, esketamine (Spravato—Janssen Pharmaceuticals, Inc.), for TRD. According to the official medication guidelines, it must be administered to patients under the supervision of a trained medical professional.

Study findings from 2019 published in the American Journal of Psychiatry first demonstrated the effectiveness of ketamine for TRD. Ketamine versus placebo resulted in clinically and statistically significant decreases in depression scores. In both groups, patients continued taking antidepressants out of concern of not treating TRD. In another study from 2019 published in JAMA Psychiatry, researchers found that nasal ketamine had longer-term efficacy and helped patients stay in stable remission 16 weeks into treatment.