A historical review of antidepressant effects of ketamine and its enantiomers.
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| Abstract |
The robust antidepressant effects of (R,S)-ketamine are among the most important discoveries in mood research over the last half century. Off-label use of (R,S)-ketamine, which is an equal mixture of (R)-ketamine and (S)-ketamine, has become especially popular in the United States (US) for treatment-resistant depression. On March 5, 2019, the US Food and Drug Administration approved an (S)-ketamine nasal spray for use in treatment-resistant depression, though its use has been limited to certified medical offices or clinics. On December 19, 2019, (S)-ketamine nasal spray was approved for the same indication in Europe. However, despite its potential for benefit, there are several concerns about the efficacy of (S)-ketamine nasal spray. Accumulating evidence from preclinical studies show that (R)-ketamine has greater potency and longer lasting antidepressant effects than (S)-ketamine in animal models of depression, and that (R)-ketamine has fewer detrimental side effects than either (R,S)-ketamine or (S)-ketamine. As such, clinical studies of (R)-ketamine in humans are now underway by Perception Neuroscience Ltd. In this article, we review the brief history of (R,S)-ketamine and its two enantiomers as novel antidepressants. We also discuss the mechanisms of ketamine's antidepressant actions.
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| Authors | Yan Wei, Lijia Chang, Kenji Hashimoto |
| Journal | Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 190 Pg. 172870 (03 2020) ISSN: 1873-5177 [Electronic] United States |
| PMID | 32035078 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review) |
| Copyright | Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved. |
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