Beyond Anesthesia: Ketamine's Expanding Role in Chronic Pain and Psychiatric Disorders.

Objective: This review explores ketamine's expanding role in managing both chronic pain and mental health conditions, focusing on its pharmacologic mechanisms, clinical applications, and therapeutic potential. We assess its analgesic properties, FDA-approved application in the form of Spravato (esketamine) for depression, and off-label use for analgesia and psychiatric disorders.

Methods: A systematic search of PubMed, Cochrane Library, and Scopus databases identified studies on ketamine's efficacy and safety in chronic pain and psychiatric disorders. The analysis included randomized controlled trials (RCTs), observational studies, and systematic reviews.

Results: Ketamine has demonstrated significant efficacy in managing chronic pain in neuropathic pain, fibromyalgia, and complex regional pain syndrome (CRPS), especially in treatment-resistant cases. Mental health comorbidities are common in chronic pain populations, with up to 50% experiencing depression or anxiety. Ketamine's N-methyl-D-aspartate (NMDA) receptor antagonism not only underlies its analgesic effects but also contributes to rapid antidepressant responses in treatment-resistant depression (TRD) and acute suicidal ideation, as evidenced by its FDA-approved formulation, Spravato (esketamine). Beyond depression, emerging evidence supports ketamine's potential use in anxiety disorders, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and certain substance use disorders. However, its psychomimetic effects, safety concerns, and unclear long-term impact warrant careful clinical oversight.

Conclusion: Ketamine presents a versatile therapeutic strategy for managing chronic pain and a wide range of mental health disorders, signifying its potential to bridge the gap in treatment-resistant cases. Ongoing research is needed to optimize dosing strategies, assess long-term safety, and integrate ketamine into multidisciplinary care models. This approach emphasizes personalized patient care and comprehensive monitoring to navigate the complexities of coexisting chronic pain and mental health challenges.