Evaluating the potential risk of ketamine-induced hepatotoxicity in the treatment of mood and anxiety disorders: A systematic review.
Gabrielle F M Lovell, Shreya Vasudeva, Diana K Orsini, Sara Di Luch, Sabrina Wong, Gia Han Le, Roger S McIntyre, Eddie Y Liu, Joshua D Rosenblat
General hospital psychiatry January 1, 2026 Peer reviewed DOI: 10.1016/j.genhosppsych.2026.04.005 via PubMed
Summary
Ketamine treatment for major depressive disorder and bipolar disorder may lead to mild and transient liver enzyme elevations, with 75 hepatic adverse events reported among 879 patients in randomized controlled trials. Serious liver impairment is rare, with only a few cases noted. However, due to potential risks associated with higher exposures, routine liver monitoring during ketamine treatment is recommended.
Study at a glance
| Design | systematic review |
|---|---|
| Sample size | 1,017 |
| Population | patients receiving ketamine primarily for major depressive disorder and bipolar disorder |
| Key finding | Ketamine may cause liver enzyme elevations, but serious hepatotoxicity appears rare. |
Abstract
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.