Progress, potential and pitfalls of ketamine as a treatment for depression
Expert Opinion on Pharmacotherapy – January 22, 2026
Source: OpenAlex
Summary
Intravenous ketamine and intranasal esketamine have shown strong antidepressant effects, supported by numerous clinical trials involving thousands of participants. Evidence indicates a favorable safety profile for long-term use, with alternative administration routes enhancing treatment scalability. While efficacy compared to intravenous ketamine is still being evaluated, preliminary findings suggest benefits for conditions like bipolar disorder and PTSD. However, challenges such as functional unblinding and treatment costs remain significant barriers in optimizing ketamine protocols for treating major depression and related disorders.
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.