Ketamine pharmacotherapy for major depressive disorder: A narrative review
Progress in Neuro-Psychopharmacology and Biological Psychiatry February 27, 2026 Chris H. Miller, Angela Hickman, Caitlin Baten et al. 2 citations
Ketamine, originally developed as an anesthetic, has emerged as a novel treatment for major depressive disorder (MDD) and treatment-resistant depression (TRD). Its antidepressant properties were discovered serendipitously, leading to FDA approval for TRD and MDD with suicidal ideation. The drug acts primarily as an NMDA receptor antagonist, triggering a paradoxical AMPA-mediated glutamate surge that promotes synaptogenesis and neuroplasticity. Intravenous ketamine and intranasal esketamine differ in dosing, bioavailability, and onset. Common adverse effects include dissociation, sedation, and hypertension. Efficacy studies show mixed-to-positive results, with non-inferiority to established treatments like electroconvulsive therapy. Future research aims to develop predictive markers for personalized medicine.