In a randomized, head-to-head trial, intravenous ketamine appeared to be at least as effective as electroconvulsive therapy and had fewer side effects.
Electroconvulsive therapy (ECT) has long been considered to be the gold standard for the treatment of severe or treatment-resistant depression. Over the last decade, ketamine, administered intravenously at subanesthetic doses, is increasingly being used for the treatment of depression in patients who have not responded to traditional antidepressants. In a study funded by PCORI, the Patient-Centered Outcomes Research Institute, Amit Anand, MD, Director of the Translational Clinical Trials Program at Mass General Brigham, compared ketamine with ECT in a group of patients with treatment-resistant depression.
In this open-label, randomized, noninferiority trial, patients with treatment-resistant major depressive disorder (MDD) without psychosis were randomized in a 1:1 ratio to receive ketamine or ECT. Patients enrolled in this study had an unsatisfactory response to two or more adequate trials of antidepressants. Over the course of three weeks, participants received either ECT three times per week or ketamine (0.5 mg per kilogram over 40 minutes) twice per week.
A total of 403 patients underwent randomization at five clinical sites; 200 patients were assigned to the ketamine group and 203 to the ECT group. Ketamine was administered to 195 patients and ECT to 170 patients; 38 patients withdrew before initiating treatment. A total of 55.4% of the patients in the ketamine group and 41.2% of those in the ECT group had a response to treatment, defined > 50% reduction in scores on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (P<0.001 for the noninferiority of ketamine to ECT). Remission (based on QIDS-SR scores) occurred in 32% of the ketamine group and in 20% of the ECT group.
Compared to ketamine, ECT was associated with a more significant declines in memory recall after 3 weeks of treatment with gradual recovery during follow-up. ECT was associated with musculoskeletal adverse effects, whereas ketamine was associated with dissociation. Improvement in patient-reported quality-of-life was similar in the two trial groups.
Ketamine is a Viable Option for Treatment-Resistant Depression
To date, no large, head-to-head trials have compared the effectiveness of ECT to intravenous ketamine for treatment-resistant depression. While a prior relatively small meta-analysis indicated that ECT was more effective than ketamine, the current study indicates that ketamine was noninferior to ECT for treatment-resistant MDD without psychosis. Although response and remission rates look slightly higher for the ketamine group, the study was not large enough to determine whether one treatment was superior to the other but was adequate to indicate noninferiority.
Although ECT is very effective and fast-acting, several factors limit its use. It requires anesthesia and is often associated with memory problems following the treatment. Given the more favorable side effect profile, ketamine may be considered before going to ECT.
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Anand A, Mathew SJ, Sanacora G, Murrough JW, Goes FS, Altinay M, Aloysi AS, Asghar-Ali AA, Barnett BS, Chang LC, Collins KA, Costi S, Iqbal S, Jha MK, Krishnan K, Malone DA, Nikayin S, Nissen SE, Ostroff RB, Reti IM, Wilkinson ST, Wolski K, Hu B. Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. N Engl J Med. 2023 May 24.
