Progress, potential and pitfalls of ketamine as a treatment for depression

A large body of evidence from clinical trials and real-world studies supports the antidepressant effects of intravenous ketamine and intranasal esketamine. Larger studies have provided reassuring safety data, including for long-term treatment. Alternative routes of administration show promise for scalability, but their efficacy relative to intravenous ketamine remains unclear. Preliminary data suggest ketamine may also be effective for bipolar disorders, personality disorders, posttraumatic stress, and obsessive-compulsive disorder. Further research is needed to optimize protocols, such as combining ketamine with other interventions. Challenges include functional unblinding, expectancy-related bias, and treatment costs.

Study at a glance

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.