Ketamine noninferior to ECT for nonpsychotic treatment-resistant major depression, with some advantages (ELEKT-D)

Reference

Anand A, Mathew SJ, Sanacora G, et al. Ketamine versus ECT for nonpsychotic treatment-resistant major depression. N Engl J Med 2023;388(25):2315-2325.

Synopsis

This study identified 403 patients with nonpsychotic treatment-resistant major depression, defined as an unsatisfactory response to at least 2 antidepressant medications. The patients were randomized to receive intravenous ketamine 0.5 mg/kg twice weekly (dose modification was allowed) or to electroconvulsive therapy (ECT) 3 times per week. Both treatments were given for 3 weeks, and after those 3 weeks the participants could receive any treatment recommended by their physician, including ECT or ketamine. Five patients in the ketamine group and 33 in the ECT group either did not undergo therapy or did not have outcome data, so the results are based on a modified intention-to-treat analysis of those who received treatment. The primary outcome was treatment response at the end of the initial 3-week treatment period, defined as a decrease of 50% or more on the 27-point Quick Inventory of Depressive Symptomatology—Self-Report (QIDS-SR-16) scale. Such a response was seen significantly more often in the ketamine group (55.4% vs 41.2%; absolute difference 14.2%; 3.9% - 24.2%). Remission was also significantly more likely in the ketamine group (32.3% vs 20.0%). Relapse at 6 months occurred less often in the ketamine group (34.5% vs 56.3%). There was no significant difference in quality of life, though. Memory impairment and myalgias were more common in the ECT group, while dissociative symptoms were more common with ketamine. There were numerically more patients reporting suicidal ideation (4 vs 2) in the ketamine group, with one suicide attempt in that group.