Ketamine for depression

Jelen, LA and Stone, James (2021) Ketamine for depression. International Review of Psychiatry, 33 (3). pp. 207-228. ISSN 0954-0261

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Over the last two decades, the dissociative anaesthetic agent ketamine, an uncompetitive N-Methyl-D-Aspartate (NMDA) receptor antagonist, has emerged as a novel therapy for treatment-resistant depression (TRD), demonstrating rapid and robust antidepressant effects within hours of administration. Ketamine is a racemic mixture composed of equal amounts of (S)-ketamine and (R)-ketamine. Although ketamine currently remains an off-label treatment for TRD, an (S)-ketamine nasal spray has been approved for use in TRD (in conjunction with an oral antidepressant) in the United States and Europe. Despite the promise of ketamine, key challenges including how to maintain response, concerns regarding short and long-term side-effects and the potential for abuse remain. This review provides an overview of the history of ketamine, its use in psychiatry and its basic pharmacology. The clinical evidence for the use of ketamine in depression and potential adverse effects associated with treatment are summarized. A synopsis of some of the putative neurobiological mechanisms underlying ketamine’s rapid-acting antidepressant effects is provided before finally outlining future research directions, including the need to identify biomarkers for predicting response and treatment targets that may be used in the development of next-generation rapid-acting antidepressants that may lack ketamine’s side-effects or abuse potential.

Item Type: Article
Additional Information: This is an Accepted Manuscript of an article published by Taylor & Francis in International Review of Psychiatry on 11th February 2021, available at:
Keywords: (S)-ketamine, Ketamine, antidepressant, depression, mechanism of action, Antidepressive Agents, Depression, Depressive Disorder, Treatment-Resistant, Humans, Ketamine, Receptors, N-Methyl-D-Aspartate
Schools and Departments: Brighton and Sussex Medical School > Neuroscience
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 20 Jun 2022 19:35
Last Modified: 21 Jun 2022 07:01

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