From the Guidelines
Risperidone is generally not considered significantly hepatotoxic, with only mild, transient elevations in liver enzymes reported in some patients. While there have been reports of liver enzyme abnormalities and fatty infiltrates associated with risperidone therapy, particularly in adolescent males with obesity 1, these cases are rare and often resolve with cessation of the drug.
Key Points to Consider
- The risk of hepatotoxicity with risperidone is considered low, and routine liver function monitoring is not typically required for patients taking this medication unless they have pre-existing liver disease or other risk factors.
- Patients should be advised to report any symptoms of liver problems, such as jaundice, dark urine, or right upper quadrant pain.
- If liver enzyme elevations do occur, they are usually mild and often resolve without discontinuation of the medication.
- In rare cases where significant liver injury is suspected, the drug should be stopped, and alternative antipsychotics with even lower hepatotoxicity profiles may be considered.
Clinical Implications
It is essential to weigh the benefits of risperidone therapy against the potential risks, including hepatotoxicity. Given the low risk of severe liver injury associated with risperidone, it is reasonable to initiate treatment with this medication in patients who do not have pre-existing liver disease or other risk factors. However, baseline liver functions should be checked prior to initiating treatment, with periodic monitoring during ongoing therapy, as recommended by the American Academy of Child and Adolescent Psychiatry 1.
From the FDA Drug Label
While the pharmacokinetics of risperidone in subjects with liver disease were comparable to those in young healthy subjects, the mean free fraction of risperidone in plasma was increased by about 35% because of the diminished concentration of both albumin and α1-acid glycoprotein RISPERIDONE doses should be reduced in patients with liver disease [see DOSAGE AND ADMINISTRATION ( 2.4)].
Risperidone may be hepatotoxic in the sense that it requires dose reduction in patients with liver disease. However, there is no direct evidence of hepatotoxicity in the provided drug labels. The labels only mention that the pharmacokinetics of risperidone are altered in patients with liver disease, and that dose reduction is recommended in such cases 2.
From the Research
Risperidone Hepatotoxicity
- Risperidone has been associated with hepatotoxicity in several case reports, with evidence suggesting a probable association between risperidone use and hepatotoxicity 3, 4, 5, 6.
- The mechanism of risperidone-induced hepatotoxicity is not fully understood, but it is thought to be related to the drug's metabolism and the individual's genetic predisposition, such as CYP2D6 genotype 4.
- Case reports have described patients developing hepatotoxicity after starting risperidone, with symptoms including elevated liver enzymes, asthenia, and weight loss 3, 4, 5, 6.
- In some cases, the hepatotoxicity was severe enough to require discontinuation of the drug, and alternative antipsychotic medications were used instead 3, 4, 5, 6.
- However, in some cases, risperidone was cautiously rechallenged in patients who showed marked psychiatric improvement with the drug, despite initial liver enzyme elevation 7.
Monitoring and Prevention
- It is recommended to obtain baseline liver function tests before starting risperidone and to regularly monitor liver enzyme levels during therapy to screen for potential hepatotoxicity 4, 5, 6.
- Patients who develop hepatotoxicity during risperidone therapy may benefit from treatment with an alternative antipsychotic with a different chemical structure 3.
- The risk of hepatotoxicity may be increased in patients taking other medications, such as fluoxetine, and regular monitoring is recommended in these cases 5.