Progress, potential and pitfalls of ketamine as a treatment for depression
Diana Orsini, Sara Di Luch, Gabrielle F. M. Lovell, Joshua D. Rosenblat
Expert Opinion on Pharmacotherapy January 22, 2026 DOI: 10.1080/14656566.2026.2637587 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Depression |
| Interventions | Intravenous ketamine Intranasal esketamine |
| Topics | Depression Ketamine Esketamine |
| Keywords | Antidepressant Clinical trial Depression economics Nasal administration Anesthesia Intensive care medicine |
| Key findings | Evidence supports the antidepressant effects of intravenous ketamine and intranasal esketamine, with adequate safety data for long-term treatment, though challenges remain regarding bias and cost. |
Abstract
Evidence supporting the use of intravenous ketamine and intranasal esketamine for depression has dramatically increased with a large number of clinical trials and real-world effectiveness studies supporting antidepressant effects. Larger studies have provided reassuring data supporting an adequate safety profile, including safety data with long-term treatment. Alternative routes of administration have shown promise for improving scalability; however, efficacy as compared to intravenous ketamine remains unclear. Promising preliminary data support ketamine's efficacy in other conditions, such as bipolar disorders, personality disorders, posttraumatic stress, and obsessive-compulsive disorder. Further research is needed to optimize protocols, such as combining ketamine with other interventions. Functional unblinding, expectancy-related bias, and treatment costs remain challenges for the field.