A comprehensive review of the clinical progress of esketamine: From anesthesia to antidepressant therapy.
Hai-lin Hu, Qi-zhou Huang, Ping-xia Xie
Medicine May 1, 2026 Peer reviewed DOI: 10.1097/md.0000000000048570 via PubMed
Summary
Esketamine, a rapid-acting antidepressant, shows response rates of 50% to 70% for treatment-resistant depression within 24 hours. It works by antagonizing NMDA receptors, affecting glutamatergic signaling and neuroplasticity. While it offers effective sedation in anesthesia with minimal respiratory depression, long-term safety data are limited, raising concerns about dissociative symptoms and cognitive impairment. Regulatory approvals differ globally, highlighting the need for careful patient selection and monitoring.
Study at a glance
| Design | narrative review |
|---|---|
| Population | peer-reviewed literature on esketamine's clinical applications and safety |
| Key finding | Esketamine has demonstrated rapid antidepressant effects in treatment-resistant depression with response rates of 50% to 70% within 24 hours. |
Abstract
Esketamine, the S-enantiomer of ketamine, has emerged as a rapid-acting antidepressant with unique mechanisms. This narrative review synthesizes current evidence on its clinical applications, safety, and regulatory status based on peer-reviewed literature published between January 2000 and March 2024, searched in PubMed, Web of Science, and the Cochrane Library. Esketamine exerts its effects primarily through noncompetitive antagonism of N-methyl-D-aspartate receptors, leading to rapid modulation of glutamatergic signaling and neuroplasticity. In anesthesia, it provides effective sedation with minimal respiratory depression. In psychiatry, intravenous and intranasal esketamine have demonstrated rapid antidepressant effects in treatment-resistant depression, with response rates of 50% to 70% within 24 hours. However, long-term safety data remain limited, and concerns persist regarding dissociative symptoms, cognitive impairment, and abuse potential. Regulatory approvals vary: the Food and Drug Administration approved intranasal esketamine for treatment-resistant depression in 2019, while European and Asian countries have adopted differing restrictions. Esketamine represents a paradigm shift in depression treatment, but its use requires careful patient selection, monitoring, and risk management. Future research should focus on head-to-head comparisons with other rapid-acting interventions, long-term outcomes, and integration into stepped-care models.