Prophylactic Ketamine: Current Knowledge and Future Directions

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.