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 1017 patients receiving ketamine primarily for major depressive disorder (MDD) and bipolar disorder (BD). Across RCTs ( n = 879), 75 hepatic adverse events were reported, predominantly mild and transient aminotransferase elevations, with rare cases of liver impairment, but no cases meeting Hy's Law criteria. Observational studies identified three instances of liver impairment, RCTs identified one case as indicated by elevated bilirubin, and case reports described more severe presentations, including bile duct dilation and gall bladder distention, which improved with dose reduction or discontinuation. Evidence identified here suggests that ketamine at dosing regimens typically used for mood disorders may cause liver enzyme elevations, but impaired liver function and serious hepatotoxicity appears rare. However, considering the instances of impaired liver function identified herein and real-world data associating severe drug-induced liver injury (DILI) with higher exposures, routine liver monitoring remains justified throughout ketamine treatment. • Ketamine has shown promise as a rapid acting treatment for mood and related disorders. • Across RCTs, hepatic adverse events were uncommon, predominantly mild and transient. • Observational studies identified occasional rare cases of impaired liver function. • Impaired liver function and serious hepatotoxicity appears rare with ketamine for MDD