Antipsychotic Safety in Liver Disease: A Narrative Review and Practical Guide for the Clinician

Abstract

Background: Clinicians treating psychiatric disorders in medically ill patients need a comprehensive resource for comparing the risk and types of liver injury associated with antipsychotic therapy.

Objective: We conducted a narrative review aimed at developing a comprehensive resource comparing antipsychotics with regard to risk of inducing or worsening liver injuries, types of liver injury, associated pharmacokinetic changes, dosing, monitoring, and patient counseling recommendations.

Methods: We conducted database searches of LiverTox.nih.gov, DailyMed.nlm.nih.gov, and PubMed through June of 2022. Sources describing premarketing data, observational studies, case reports and case series of antipsychotic-induced liver injuries, types of hepatic dysfunction, interventions, recovery, and treatment for 15 antipsychotics were included. Duplicate reports were excluded. Antipsychotics were graded as low, low to moderate, moderate, moderate to high, or high risk for causing or worsening a liver disease.

Results: Of the 1861 publications, 21 papers met criteria and were included. Evidence shows antipsychotic-induced liver dysfunction is uncommon to rare. Chlorpromazine, clozapine, and olanzapine pose the greatest risk of hepatoxicity; quetiapine and risperidone pose a moderate risk with haloperidol considered to pose low to moderate risk. Paliperidone, aripiprazole, lurasidone, and loxapine are lower-risk agents with no reports of liver failure. Transaminitis that is mild and self-limiting is the most common antipsychotic-induced liver injury followed by hepatocellular disease, steatosis, and mixed liver injury. A careful risk-benefit analysis should guide the decision to discontinue the antipsychotic in cases of severe liver disease. Dose adjustments and careful monitoring are recommended for a mild to moderate disease when the benefits of treating psychosis outweigh the risks. Patients without an existing liver disease initiating a treatment with a higher-risk antipsychotic should be counseled to report symptoms of liver injuries along with regular lab monitoring.

Conclusions: Antipsychotic selection, dosing, monitoring, and counseling should be individualized based on whether a patient has an existing liver disease and if they are receiving an agent that poses a higher risk of liver injury. The consultation-liaison psychiatry provider can guide the primary team in management through thoughtful integration of the known pathophysiologic changes in hepatic disease and risk-benefit analysis of antipsychotic safety profiles.

Keywords: antipsychotic; drug-induced liver injury; hepatotoxicity; liver disease; steatosis.