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

C. Andrade

Journal of Clinical Psychiatry March 28, 2022 DOI: 10.4088/jcp.22f14451 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Randomized Peer reviewed
Population Severely ill patients with mostly unipolar depression (with or without psychotic features) referred for ECT
Interventions Racemic ketamine Electroconvulsive therapy (ECT)
Dose 0.5 mg/kg
Duration 40-45 minutes per ketamine infusion; one trial had 1-year post-treatment follow-up; ketamine course of 6 or more alternate day, thrice weekly sessions
Topics Depression Esketamine Ketamine
Key findings Across five randomized trials, ECT was clearly superior to racemic ketamine for response rate, remission rate, time to response, time to remission, and magnitude of improvement at treatment endpoint, and appeared superior in older patients and those with psychotic depression; relapse rate and time to relapse did not differ. Ketamine's response and remission rates were nonetheless described as sufficiently impressive to view it as a viable alternative to ECT, with benefits evolving over a course of six or more sessions.

Abstract

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.

Comparable studies

Other systematic reviews and meta-analyses on ketamine for depression, most cited first.

Study Year Design Participants
Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... 2015 Systematic review and meta-analysis
Side-effects associated with ketamine use in depression: a systematic review. Patients with depression 2018 Systematic review
Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression 2020 Systematic review and meta-analysis n = 1,877
Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Patients with major depressive disorder or bipolar depression 2016 Systematic review and meta-analysis n = 588
The use of ketamine as an antidepressant: a systematic review and meta‐analysis People with major depressive disorder or bipolar disorder receiving ketamine infusion 2015 Meta-analysis n = 437

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