A historical review of antidepressant effects of ketamine and its enantiomers.
Yan Wei, Lijia Chang, Kenji Hashimoto
Pharmacology, Biochemistry, and Behavior February 5, 2020 DOI: 10.1016/j.pbb.2020.172870 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Esketamine Ketamine |
| Citations | 157 |
| Key findings | (R)-ketamine may have greater potency and longer lasting antidepressant effects with fewer side effects than (S)-ketamine or (R,S)-ketamine, based on preclinical evidence. |
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.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cited by 68
- Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Journal of Affective Disorders September 23, 2020
- Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor Molecular Psychiatry May 7, 2021
- Molecular mechanisms of the rapid-acting and long-lasting antidepressant actions of (R)-ketamine. Biochemical Pharmacology July 1, 2020
- Microglial ERK-NRBP1-CREB-BDNF signaling in sustained antidepressant actions of (R)-ketamine Molecular Psychiatry November 24, 2021
- Arketamine, a new rapid-acting antidepressant: A historical review and future directions Neuropharmacology August 14, 2022
and 63 more in the library
Cites 66
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate British Journal of Pharmacology June 1, 1983
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
and 61 more in the library