Advances in ketamine therapy for multiple psychiatric disorders
Zhang Kai, Cheng Zhaoyang, Wang Yuting
Sichuan jingshen weisheng September 5, 2025 DOI: 10.11886/scjsws20250531003 via DOAJ
Summary
AI-generated from the abstractKetamine, a non-competitive NMDA receptor antagonist, produces rapid antidepressant effects in treatment-resistant depression and suicidal ideation through NMDA receptor blockade, AMPA receptor activation, and upregulation of BDNF/mTOR signaling. Its enantiomers esketamine and R-ketamine differ in efficacy and mechanisms. Intranasal esketamine has been approved in Europe, the United States, and China for treatment-resistant depression, showing rapid alleviation of depressive symptoms and acute suicidal ideation. R-ketamine may offer longer-lasting effects and an improved safety profile. Safety concerns include dissociation, cognitive impairment, and abuse liability.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Intranasal esketamine |
| Topics | Esketamine Ketamine |
| Keywords | Rapid antidepressant Nmda receptor Psychiatric disorders |
| Key finding | Ketamine and its enantiomers show rapid antidepressant effects in treatment-resistant depression and suicidal ideation, with intranasal esketamine approved for clinical use and R-ketamine potentially offering longer-lasting effects and improved safety. |
Abstract
Ketamine， a non-competitive N-methyl-D-aspartate （NMDA） receptor antagonist， has gained increasing attention for its rapid antidepressant effects in treatment-resistant depression （TRD） and suicidal ideation. Its mechanisms include NMDA receptor blockade， AMPA receptor activation， and upregulation of BDNF/mTOR signaling. Its enantiomers， esketamine and R-ketamine， as well as its metabolites， exhibit differences in efficacy and mechanisms. Intranasal esketamine has been approved in the Europe， United States， and China for TRD， demonstrating rapid efficacy in alleviating depressive symptoms and acute suicidal ideation. In contrast， R-ketamine demonstrates potential for longer-lasting effects and a improved safety profile. This review summarizes recent advances in the pharmacology， pharmacokinetics， and clinical applications of ketamine and its enantiomers in depressive disorders， bipolar disorder， substance use disorders， post-traumatic stress disorder and obsessive-compulsive disorder. Despite ketamine's multifaceted therapeutic potential， safety concerns such as dissociation， cognitive impairment， and abuse liability warrant continued attention.［Funded by Key Project of Natural Science Research for Universities of Anhui Provincial Education Department （number， 2023AH050647）； Anhui Provincial Department of Education Outstanding Young Talent Support Program Project 2022 （number， gxyqZD2022022）］