EVALUATING THE POTENTIAL RISK OF KETAMINE-INDUCED HEPATOTOXICITY IN THE TREATMENT OF MOOD AND ANXIETY DISORDERS: A SYSTEMATIC REVIEW

Ketamine is a dissociative anesthetic with potential for treating mood, anxiety, and related disorders; however, concerns have emerged regarding hepatotoxicity in the context of chronic treatment. Systematic searches of PubMed, Scopus, and Ovid databases were conducted from inception to August 2025. Eligible studies included randomized controlled trials (RCTs), observational studies, and case reports/series reporting liver function outcomes following therapeutic ketamine administration for mood, anxiety, or related psychiatric disorders. Of 635 screened records, 13 met inclusion criteria: five RCTs, three observational studies, and five case reports/series, encompassing 1,017 patients receiving ketamine primarily for MDD/TRD and BD/TRBD. Across RCTs (n = 888), 75 hepatic adverse events were reported, predominantly mild and transient aminotransferase elevations, with no cases meeting Hy’s Law criteria. Observational studies identified occasional aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevations and rare instances of impaired liver function. Case reports described more severe presentations, which improved with dose reduction or discontinuation. Evidence suggests that ketamine at dosing regimens typically used for depression may cause liver enzyme elevations, but impaired liver function and serious hepatotoxicity appears rare. However, considering real-world data of severe druginduced liver injury (DILI), routine liver monitoring remains justified throughout ketamine treatment.