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

Ketamine has shown promise as a novel treatment for psychiatric disorders. This narrative expert review provides an update on recent advances in ketamine research. Herein, we narratively summarize (1) new efficacy data from clinical trials, (2) real-world effectiveness data, (3) growing safety data, (4) alternative routes of administration, (5) optimization of treatment protocols, (6) considerations for enantiomer variants, and (7) new potential indications. Lastly, limitations and challenges to the progression of the field will be discussed. 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.