Prophylactic Ketamine: Current Knowledge and Future Directions.

Stress-induced disorders such as depression, anxiety, PTSD, and postpartum depression are increasingly common, yet current treatments are limited. This review examines ketamine as a potential preventive treatment, summarizing preclinical and clinical findings on (R,S)-ketamine and its metabolites (2R,6R)- and (2S,6S)-hydroxynorketamine. It explores underlying mechanisms involving brain regions, circuits, and glutamatergic, dopaminergic, serotonergic, and inflammatory processes. The review also notes limitations including age- and sex-specific efficacy, adverse effects, and legal and ethical concerns. Future research directions and clinical integration are discussed. The literature underscores the need for further study to weigh ketamine's benefits and risks as a prophylactic.

Study at a glance

Abstract

The prevalence of stress-induced disorders, including depression, anxiety, posttraumatic stress disorder, and postpartum depression, has been increasing, while current treatment approaches are limited. As a result, researchers are exploring alternative treatments that include ketamine as a prophylactic against these disorders. This review provides an overview of the current knowledge on the use of ketamine as a prophylactic for stress-induced disorders, including preclinical and clinical findings on (R,S)-ketamine, as well as (2R,6R)- and (2S,6S)-hydroxynorketamine. We also explore the potential underlying mechanisms involved in preventing these disorders, including the brain regions/circuits, as well as glutamatergic, dopaminergic, serotonergic, and inflammatory processes known to be involved, as evidenced by studies with ketamine and its metabolites. Additionally, we highlight the limitations and risks associated with ketamine use, such as age- and sex-specific efficacy, potential long-term and adverse effects, and legal and ethical considerations. Finally, we discuss future research directions, including the implications for clinical practice, integrating ketamine into current treatment approaches, and potential advancements in ketamine-based therapies. Overall, the literature emphasizes the importance of continuing research to better understand the potential benefits and risks of ketamine as a prophylactic for stress-induced disorders.