Hepatic adverse events associated with ketamine and esketamine: A population-based disproportionality analysis.
Angela T H Kwan, Moiz Lakhani, Kayla M Teopiz, Sabrina Wong, Gia Han Le, Roger Ho, Taeho Greg Rhee, Bing Cao, Joshua D. Rosenblat, Rodrigo B. Mansur, Roger S McIntyre
Journal of Affective Disorders April 1, 2025 DOI: 10.1016/j.jad.2025.01.054 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational pharmacovigilance study Peer reviewed |
|---|---|
| Population | Reports in the US FDA Adverse Event Reporting System (FAERS) for individuals prescribed ketamine or esketamine |
| Interventions | Ketamine Esketamine |
| Topics | Esketamine Ketamine |
| Keywords | Drug-induced liver injury Hepatobiliary disorders Hepatotoxicity Hy's rule Liver function tests Suicidality Treatment resistant depression Drug safety Depression treatments Liver toxicity Ketamine therapy Adverse effects |
| Citations | 11 |
| Key findings | Ketamine showed disproportionately lower reporting of several hepatobiliary disorders but higher reporting of hepatic function abnormalities and cytolysis compared to acetaminophen, while esketamine showed disproportionately higher reporting of hepatic failure. |
Abstract
To determine whether there is disproportionate reporting of hepatobiliary disorders in the United States (US) FDA Adverse Event Reporting System (FAERS) for individuals prescribed ketamine or esketamine. We identified Medical Dictionary for Regulatory Activities (MedDRA) terms in the FAERS related to hepatobiliary disorders. Formulations of ketamine and esketamine were evaluated for the proportionality of reporting for each hepatobiliary disorder parameter using the reporting odds ratio (ROR). We also estimated the lower limits of 95 % confidence intervals of information components (IC025) to determine whether the association was significant. Acetaminophen was used as the positive reference agent and lithium as the neutral reference agent. We observed disproportionately lower reporting of hepatitis, liver disorder, liver injury, drug-induced liver injury, hepatic failure, and acute hepatic failure for ketamine compared to acetaminophen. Additionally, we observed disproportionately higher reporting of hepatic function abnormalities and hepatic cytolysis for ketamine compared to acetaminophen. For esketamine, we did not find disproportionate reporting of any hepatobiliary toxicity relative to acetaminophen. However, for ketamine, there was disproportionate lower reporting of hepatic function abnormalities, liver disorder and hepatic cirrhosis. In contrast, for esketamine, there was disproportionately higher reporting of hepatic failure. Although causality has not been established, the data support recommendations for periodic monitoring of liver function tests, as well as clinical surveillance for stigmata of hepatobiliary disease in individuals receiving chronic exposure to ketamine and esketamine.
Comparable studies
Other observational and cohort studies on esketamine, most cited first.
Citations in the library
Cited by 8
- Real world effectiveness of maintenance ketamine infusions for treatment-resistant depression in major depressive disorder and bipolar disorder. Psychiatry Research August 15, 2025
- Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis. Pharmaceuticals May 9, 2025
- Exploratory non-randomized clinical trial of subcutaneous esketamine in treatment-resistant depression: Effects of ketamine-assisted psychotherapy Journal of Affective Disorders August 10, 2026
- Treating addiction with an addictive drug: the ketamine paradox revisited Frontiers in Psychiatry July 9, 2026
- Progress, potential and pitfalls of ketamine as a treatment for depression Expert Opinion on Pharmacotherapy January 22, 2026
and 3 more in the library
Cites 8
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Taming the Ketamine Tiger Anesthesiology August 6, 2010
- Ketamine: 50 Years of Modulating the Mind Frontiers in Human Neuroscience November 29, 2016
- Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression New England Journal of Medicine October 4, 2023
- Recent Advances in the Treatment of Treatment-Resistant Depression: A Narrative Review of Literature Published from 2018 to 2023 Current Psychiatry Reports April 1, 2024
and 3 more in the library