From the Guidelines
Antipsychotic medications, particularly second-generation antipsychotics, can increase the risk of developing steatosis liver due to their metabolic side effects, and baseline liver function tests with periodic monitoring are recommended. The association between antipsychotics and liver steatosis is attributed to weight gain, insulin resistance, and dyslipidemia, which are common side effects of these medications 1. Patients on antipsychotics should be monitored for signs of liver disease, and preventive measures such as weight management, regular exercise, and a healthy diet are essential.
Some antipsychotics, such as olanzapine, clozapine, and quetiapine, pose a higher risk of liver steatosis due to their significant metabolic impact. In contrast, antipsychotics like aripiprazole, ziprasidone, and lurasidone may have a lower risk of liver steatosis and can be considered as alternative treatment options for patients who develop signs of liver disease. The mechanism behind antipsychotic-induced steatosis involves disruption of lipid metabolism in the liver, increased peripheral lipolysis, and altered insulin signaling pathways, which can lead to fat accumulation in the liver.
Key considerations for managing patients on antipsychotics include:
- Baseline liver function tests before starting treatment
- Periodic monitoring of liver function tests every 3-6 months
- Weight management and regular exercise
- A healthy diet to prevent metabolic abnormalities
- Consideration of alternative antipsychotics with lower metabolic impact if signs of liver steatosis develop. Although the study by Kumra et al. (1997) cited in 1 highlights the importance of monitoring liver function in patients on antipsychotics, particularly risperidone, the general principles of monitoring and prevention can be applied to all patients on antipsychotic medications.
From the Research
Antipsychotics and Steatosos Liver
- Antipsychotic-induced liver dysfunction is uncommon to rare, with chlorpromazine, clozapine, and olanzapine posing the greatest risk of hepatotoxicity 2
- Quetiapine and risperidone pose a moderate risk, while haloperidol is considered to pose low to moderate risk 2
- Transaminitis that is mild and self-limiting is the most common antipsychotic-induced liver injury, followed by hepatocellular disease, steatosis, and mixed liver injury 2
- A careful risk-benefit analysis should guide the decision to discontinue the antipsychotic in cases of severe liver disease, with dose adjustments and careful monitoring recommended for mild to moderate disease 2
- Patients without an existing liver disease initiating treatment with a higher-risk antipsychotic should be counseled to report symptoms of liver injuries along with regular lab monitoring 2
Liver Function Test Abnormalities
- Liver function test abnormalities were found in about 10% of schizophrenic patients treated with antipsychotics, with treatment with depot phenothiazines inducing alteration in these tests more frequently than treatment with other antipsychotics 3
- Transaminases concentrations were slightly elevated in study patients compared to healthy controls, but without statistical significance 3
- Alkaline phosphatase showed higher values in schizophrenic patients, while albumin and bilirubin were lower in study patients 3
- Asymptomatic increases in liver enzymes are common but significant liver enzyme elevations are rare during atypical antipsychotic treatment 4, 5
Management of Antipsychotic-Induced Liver Injury
- Strategies exist for managing and treating adverse effects, especially metabolic and movement adverse effects, allowing better personalization of antipsychotic choice 6
- 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 2
- 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 2