Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation
R. Mcintyre, J. Rosenblat, C. Nemeroff, G. Sanacora, J. Murrough, M. Berk, E. Brietzke, S. Dodd, P. Gorwood, R. Ho, D. Iosifescu, Carlos A. López Jaramillo, S. Kasper, Kevin Kratiuk, J. G. Lee, Yena Lee, L. Lui, R. Mansur, G. Papakostas, M. Subramaniapillai, M. Thase, E. Vieta, A. Young, C. Zarate, S. Stahl
American Journal of Psychiatry March 17, 2021 Peer reviewed DOI: 10.1176/appi.ajp.2020.20081251 via Semantic Scholar 694 citations
Summary
Ketamine and esketamine are the first non-monoamine-based antidepressants with rapid-onset efficacy for adults with treatment-resistant depression, offering hope to those who do not recover fully with standard antidepressants. However, concerns remain about their safety, tolerability, and appropriate placement in treatment algorithms. An international group of mood disorder experts synthesizes evidence on efficacy, safety, and tolerability, and provides guidance for clinical implementation, including practice parameters at point of care. Areas of consensus and future research directions are discussed.
Study at a glance
| Design | review |
|---|---|
| Population | adults with treatment-resistant depression |
| Key finding | Ketamine and esketamine are effective rapid-onset treatments for treatment-resistant depression, but safety, tolerability, and implementation guidance remain key considerations. |
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 non-monoaminergic 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.