This review (2022) compared the effects of ketamine to electroconvulsive therapy (ECT) in depressed patients who had been initially referred for ECT. In two 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 the treatment endpoint. However, relapse rate and time to relapse did not differ between ECT and ketamine groups.
“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 the 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.”
Author: Chittaranjan Andrade
Esketamine was approved for treatment-resistant depression and depression with suicidal ideation or behavior. It showed dramatic benefits as early as 4 hours after treatment administration.
Racemic ketamine has not been labeled for the treatment of depression, but a large number of placebo- and active-controlled clinical trials have established the efficacy of racemic ketamine in depression.
Ketamine has been compared to ECT in many RCTs, and some RCTs have even suggested that ketamine can replace ECT in clinical practice.
Studies From Iran
In a small rater-blinded RCT, patients with major depressive disorder were randomized to receive IV ketamine or bilateral ECT in 3 alternate-day sessions. Ketamine improved patients’ symptoms in parallel to ECT.
In a slightly larger rater-blinded study, 5 patients with MDD were randomized to receive IV ketamine or bitemporal ECT twice weekly for 6 sessions. Six patients dropped out of treatment administered at suboptimal frequency.
These 3 RCTs were poorly reported and contained incomplete details and even contradictions. They did not state whether or not patients were continued on psychotropic medications during the trial, and they suggested that there was a significant interaction term in each of their efficacy analyses.
In a small rater-blinded RCT, 7 patients with MDD or BD were randomized to receive IV ketamine or ECT. 5 patients had psychotic symptoms associated with depression, and 9 patients had bipolar depression.
Ketamine was administered in the dose of 0.5 mg/kg across 45 minutes, and ECT electrode placement was either bifrontal (n = 9) or right unilateral (n = 4).
Ekstrand et al8 described a large, 6-center, randomized, non-blind comparison of ketamine and ECT in severely ill unipolar depression patients.
Ketamine was dosed at 0.5 mg/kg IV across 40 minutes, and ECT was administered with RUL electrode placement to all patients. Patients received thrice-weekly sessions to remission or to maximum antidepressant benefit, and were followed up at 1 week, 3, 6, and 12 months post-treatment.
Important findings from the study8 are presented in Table 1. ECT had fewer dropouts and treatment failures than ketamine, and more patients responded to and remitted with ECT than with ketamine.
This study found that patients in the treatment groups did not differ with regard to expectations from treatment or fear of negative outcomes, based on visual analog scale ratings.
Ekstrand et al.8 found that ECT was superior to ketamine in many patients, but that ECT administered using right unilateral electrode placement was inferior to bilateral ECT.
Ekstrand et al speculated that continuation therapy with ECT and ketamine might have attenuated relapse rates in patients who relapsed after remitting.