Ketamine for Treatment-Resistant Unipolar and Bipolar Major Depression: Critical Review and Implications for Clinical Practice

This review (2016) examines the clinical efficacy of ketamine as fast-acting pharmacotherapy for major depressive disorder and bipolar disorder (BP), in light of the available evidence. In the authors’ view, there is insufficient empirical support for the early adoption of ketamine into routine practice, given the lack of data on the longer-term safety of ketamine as an antidepressant therapy, which will require the development of clinical protocols with standardized screening, clinical phenotyping, and follow-up procedures.

Abstract

“There is an urgent need for more rapidly effective pharmacotherapies for major depressive disorder and bipolar disorder (BP) that are efficacious and tolerable for depressed patients who respond poorly to conventional treatments. Multiple controlled trials have now demonstrated a rapid, nonsustained antidepressive response to a single intravenous infusion of ketamine. Early controlled studies of intranasal or serial infusion therapy appear promising. The effective dose for depression is lower than the typical anesthetic doses, and side‐effects are generally mild and transient. The data investigating the adjunctive use of concurrent ketamine in the course of electroconvulsive therapy (ECT) for depression do not suggest efficacy or tolerability. The therapeutic potential of ketamine has stimulated considerable excitement among clinicians, patients, and industry, and has led to the increasing use of ketamine as an off‐label substitute for ECT and other antidepressive treatments. This clinical review of ketamine will assess the evidence‐based use of ketamine and initial clinical implications of further development of a potentially novel treatment for rapid reduction of symptoms in depressed patients.”

Authors: William V. Bobo, Jennifer L. Vande Voort, Paul E. Croarkin, Jonathan G. Leung, Pharm.D., Susannah J. Tye, Ph.D. & Mark A. Frye