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 via OpenAlex
Summary
Ketamine and its enantiomers have a long history in anesthesia and are now gaining attention for rapid-acting antidepressant effects in severe depression. Esketamine, the (S)-enantiomer, received approval in the U.S. and Europe in 2019 as a nasal spray for depression, but concerns about long-term efficacy, addiction, and suicide risk persist. In rodent models, arketamine, the (R)-enantiomer, shows superior and longer-lasting antidepressant effects with fewer side effects than esketamine, though human research on arketamine is limited. The article reviews the historical use of ketamine and its enantiomers in anesthesia and psychiatry and explores future directions.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Anxiety Depression Ketamine |
| Keywords | Depression economics Anesthetic Anesthesia |
| Citations | 32 |
| Key finding | 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.