Ketamine and its two enantiomers in anesthesiology and psychiatry: A historical review and future directions
Kenji Hashimoto, Mingming Zhao, Tingting Zhu, Xingming Wang, Jianjun Yang
Journal of Anesthesia and Translational Medicine July 11, 2024 DOI: 10.1016/j.jatmed.2024.07.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Anxiety Depression Ketamine Esketamine |
| Keywords | Depression economics Anesthetic Anesthesia Antidepressant Adverse effect Anesthesiology Dissociative Pharmacology Intensive care medicine Cognition |
| Citations | 32 |
| Key findings | Arketamine shows superior and longer-lasting antidepressant effects in rodent models compared to esketamine, with fewer side effects, but human research remains limited. |
Abstract
Ketamine, a dissociative anesthetic, is widely utilized in both human and veterinary anesthesia. Its (S)-enantiomer, esketamine, is similarly employed for anesthesia and analgesia. The anesthetic effects of both ketamine and esketamine arise from their antagonism of the N-methyl-D-aspartate receptor (NMDAR). In field of psychiatry, the rapid-acting antidepressant properties of ketamine for severe depression have generated significant interest, resulting in its increased off-label usage in the United States (U.S.). In 2019, esketamine nasal spray received approval for use in both the U.S. and Europe. However, concerns have emerged regarding potential adverse effects, including long-term efficacy, addiction risks, and the potential for increased suicide risk in clinical settings. In contrast, arketamine, the (R)-enantiomer of ketamine, exhibits superior and longer-lasting antidepressant effects in rodent models of depression, with fewer side effects compared to esketamine. Nevertheless, research on the efficacy and safety of arketamine in patients with depression remains limited. This article provides a concise exploration of the historical use of ketamine and its two enantiomers in anesthesia and psychiatry, while also delving into potential future directions for their application in these fields.
Comparable studies
Other narrative reviews on ketamine for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement | |
| KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS | 2016 | Review | |
| Eradicating Suicide at Its Roots: Preclinical Bases and Clinical Evidence of the Efficacy of Ketamine in the Treatment of Suicidal Behaviors | 2018 | Review | |
| Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder Patients with treatment-resistant depressive symptoms as part of major depressive... | 2018 | Narrative review | |
| Ketamine as a Fast Acting Antidepressant: Current Knowledge and Open Questions | 2013 | Review |
Citations in the library
Cited by 17
- Transforming growth factor-β1 mediates the beneficial effects of arketamine on demyelination and remyelination in the brains of cuprizone-treated mice. European Journal of Pharmacology December 15, 2024
- Extending ketamine's antidepressant effects. Science May 8, 2025
- Microglial BDNF modulates arketamine's antidepressant-like effects through cortico-accumbal pathways. Science Advances July 11, 2025
- Arketamine: a scoping review of its use in humans. European Archives of Psychiatry and Clinical Neuroscience December 16, 2024
- Arketamine alleviates cognitive impairments and demyelination in mice with postoperative cognitive dysfunction via TGF-β1 activation. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2025
and 12 more in the library
Cites 98
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- Recent advances in the phencyclidine model of schizophrenia American Journal of Psychiatry October 1, 1991
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
and 93 more in the library