A new study suggests we need to monitor liver enzymes on ketamine and esketamine
STUDY: Lovell GFM et al, General Hospital Psychiatry 2026;100:196–205
STUDY TYPE: Systematic review
FUNDING: Independent
Background
Ketamine is linked to liver damage in recreational use and high doses, but what about therapeutic doses?
The Study
This systematic review screened 635 studies and included 13 — five randomized controlled trials, three observational studies, and five case reports — covering 1,017 patients treated with ketamine or esketamine (Spravato) primarily for major depressive disorder or bipolar disorder.
Across the five randomized controlled trials (879 participants), 75 hepatic adverse events were reported, mostly mild, transient aminotransferase elevations. No cases met Hy’s Law criteria, which is the FDA’s benchmark for predicting serious drug-induced liver injury.
Observational studies identified three cases of liver impairment. Case reports described more severe presentations, including bile duct dilation and elevated enzymes up to five times the upper limit of normal, but all resolved with dose reduction or discontinuation. A large long-term esketamine trial (n = 680) found that 8% experienced hepatic adverse events, but none were attributed to the drug.
Pharmacovigilance Data
- In the FDA Adverse Event Reporting System (FAERS) database, there is disproportionately more hepatoxicity linked to ketamine and esketamine than lithium.
- Agencies in France and Canada also found links.
Limitations: This is a possibility, but not definitive proof, but the small sample sizes we have may miss rare events.
Practice Implications
- Liver injury is a rare risk with many medications, and while this data is incomplete it is possible with ketamine and esketamine.
- Consider monitoring with long-term use, and in patients with other liver risks like diabetes or alcohol use history. If enzymes climb significantly, reduce the dose or stop and recheck.
— Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
What’s Your Take? Share in Comments
- Have you seen liver problems on ketamine or esketamine?
