Guidelines For The Use Of Ketamine For Treatment-Resistant Depression
April 12, 2021   

An international expert opinion on the use of ketamine for treatment-resistant depression (TRD) was recently published. Although the various formulations of ketamine have not been compared directly in randomized controlled trials, intranasal esketamine and intravenous ketamine have the strongest evidence of short-term efficacy and safety in patients with TRD, particularly in the context of adult major depressive disorder. Intranasal esketamine also has evidence of efficacy and safety for TRD maintenance treatment up to one year. Despite this evidence, legitimate concerns about long-term efficacy, safety, tolerability, patient selection, and risk for substance abuse remain for both intravenous ketamine and intranasal esketamine. The most common side effects of ketamine, irrespective of formulation, are dissociation, psychotomimetic, neurologic/cognitive, hemodynamic, genitourinary, and liability for abuse. Guidelines for ketamine implementation at point-of-care include the following considerations: patient selection, ketamine dosing and frequency, and setting, personnel, and monitoring (see Table 1 for summary). Ketamine efficacy has not been directly compared to other TRD treatments; however, the guidelines recommend considering 1) ketamine or esketamine or 2) electroconvulsive therapy or repetitive transcranial magnetic stimulation. Factors such as efficacy, tolerability, patient preference, and cost should also be considered when selecting from TRD treatment options.


McIntyre RS et al. Am J Psychiatry 2021; Epub ahead of print. Abstract

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