Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: An international expert opinion on the available evidence and implementation

Roger S. McIntyre, Joshua D. Rosenblat, Charles B. Nemeroff, Gerard Sanacora, James W. Murrough, Michael Berk, Elisa Brietzke, Seetal Dodd, Philip Gorwood, Roger Ho, Dan V. Iosifescu, Carlos Lopez Jaramillo, Siegfried Kasper, Kevin Kratiuk, Jung Goo Lee, Yena Lee, Leanna M.W. Lui, Rodrigo B. Mansur, George I. Papakostas, Mehala SubramaniapillaiMichael Thase, Eduard Vieta, Allan H. Young, Carlos A. Zarate, Stephen Stahl

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatments. Ketamine and esketamine represent pharmacologically novel treatment avenues for adults with treatment-resistant depression. In addition to providing hope to affected persons, these agents represent the first nonmonoaminergic agents with proven rapid-onset efficacy in major depressive disorder. Nevertheless, concerns remain about the safety and tolerability of ketamine and esketamine in mood disorders. Moreover, there is uncertainty about the appropriate position of these agents in treatment algorithms, their comparative effectiveness, and the appropriate setting, infrastructure, and personnel required for their competent and safe implementation. In this article, an international group of mood disorder experts provides a synthesis of the literature with respect to the efficacy, safety, and tolerability of ketamine and esketamine in adults with treatment-resistant depression. The authors also provide guidance for the implementation of these agents in clinical practice, with particular attention to practice parameters at point of care. Areas of consensus and future research vistas are discussed.

Original languageEnglish (US)
Pages (from-to)383-399
Number of pages17
JournalAmerican Journal of Psychiatry
Volume178
Issue number5
DOIs
StatePublished - May 2021
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health

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