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Five randomized controlled trials (RCTs) have compared racemic ketamine, mostly administered intravenously in the dose of 0.5 mg/kg across 40-45 minutes, with right unilateral or bilateral electroconvulsive therapy (ECT). These RCTs were conducted in samples of severely ill patients with mostly unipolar depression (with or without psychotic features) who were referred for ECT. Of these, 2 RCTs were of reasonably adequate quality to inform clinical practice; one, in fact, was large (n = 186) and had a 1-year post-treatment follow-up. In these RCTs, ECT emerged as a clearly superior treatment with regard to response rate, remission rate, time to response, time to remission, and magnitude of improvement at treatment endpoint; however, relapse rate and time to relapse did not differ between ECT and ketamine groups. ECT appeared superior in older patients and in those with psychotic depression, as well. These findings notwithstanding, response and remission rates with ketamine appeared sufficiently impressive for ketamine to be viewed as a viable alternative to ECT in severely depressed patients who are referred for ECT. Notably, in such patients ketamine does not appear to have dramatic antidepressant action; rather, the benefits evolve across a course of 6 or more alternate day, thrice weekly sessions, validating the concept of a course of ketamine treatment that is administered much as ECT is. Finally, whereas the high relapse rates after successful remission encourage the use of ECT and ketamine as continuation therapy, continuation ketamine must be carefully supervised in patients who are prone to substance abuse.

Insights for the Use of Ketamine From Randomized Controlled Trials That Compared Ketamine With Electroconvulsive Therapy in Severe Depression