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.
Amalesh Honnekeri (2026) studied this question.