A comprehensive review of the clinical progress of esketamine: From anesthesia to antidepressant therapy.
Medicine May 1, 2026 Hai-Lin Hu, Qi-Zhou Huang, Ping-Xia Xie
Esketamine, the S-enantiomer of ketamine, is a rapid-acting antidepressant that works primarily by blocking N-methyl-D-aspartate receptors, quickly modulating glutamate signaling and neuroplasticity. In anesthesia, it provides effective sedation with little respiratory depression. In psychiatry, intravenous and intranasal esketamine produce rapid antidepressant effects in treatment-resistant depression, with response rates of 50% to 70% within 24 hours. However, long-term safety data are limited, and concerns about dissociative symptoms, cognitive impairment, and abuse potential persist. The FDA approved intranasal esketamine for treatment-resistant depression in 2019, while other countries have adopted varying restrictions. Its use requires careful patient selection, monitoring, and risk management.