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Ketamine and Esketamine in Neurology and Psychiatry: An Overview.

Amalesh S Honnekeri

Cureus May 1, 2026 Peer reviewed DOI: 10.7759/cureus.108571 via PubMed

Summary

Ketamine and esketamine offer alternative treatment options for patients with treatment-resistant depression (TRD) who do not respond to standard antidepressants. Ketamine is typically given intravenously, while esketamine is administered intranasally under supervision. The review discusses their mechanisms of action, clinical applications, safety profiles, and the need for further research to improve long-term outcomes and patient selection. These treatments highlight the growing role of interventional psychiatry in managing TRD.

Study at a glance

Design narrative review
Key finding Ketamine and esketamine are emerging as important treatment options in the management of treatment-resistant depression.

Abstract

Treatment-resistant depression (TRD) remains a significant clinical concern, particularly in patients who do not achieve adequate response with conventional antidepressant therapies. Ketamine and esketamine, which act on glutamatergic pathways, have been introduced into clinical practice as alternative therapeutic approaches within interventional psychiatry. This narrative review outlines key aspects of ketamine and esketamine use in psychiatric settings, including proposed mechanisms of action, clinical use cases, methods of administration, safety profiles, and areas of ongoing discussion. Ketamine is generally administered intravenously in monitored clinical settings, while esketamine is available as an intranasal formulation used under supervision. Considerations related to tolerability and monitoring requirements are relevant in clinical use. Ketamine and esketamine represent a developing area in the treatment of TRD and highlight the broader emergence of interventional approaches in psychiatry. Additional research is warranted to further characterize long-term outcomes, refine treatment protocols, and better define patient selection criteria.

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