From the Guidelines
Risperidone has a higher risk of elevated Alanine Transaminase (ALT) levels compared to other antipsychotics, and therefore, alternative antipsychotics such as quetiapine or aripiprazole may be preferred in terms of liver safety. While all antipsychotics can potentially cause liver enzyme elevations, medications like risperidone tend to have higher rates of ALT elevation, especially in adolescent males, as reported in a study by Kumra et al., 1997, cited in 1. The exact mechanism behind antipsychotic-induced liver enzyme elevation involves metabolic stress on hepatocytes, with some medications creating more oxidative stress than others. Key points to consider when prescribing antipsychotics include:
- Obtaining baseline liver function tests before starting treatment
- Monitoring periodically, especially during the first few months of therapy
- Being cautious with patients who have pre-existing liver disease, alcohol use disorder, or those taking other hepatotoxic medications. It is essential to weigh the benefits and risks of each antipsychotic and consider the individual patient's profile before making a treatment decision, as noted in 1.
From the Research
Antipsychotic Comparison
When comparing antipsychotics in terms of the risk of elevated liver enzyme ALT, several studies provide insight:
- A 2007 study 2 found that among patients treated with olanzapine, risperidone, and quetiapine, 27.2% showed asymptomatic increases in ALT, AST, GGT, and serum bilirubin levels in the first month, with 22.7% showing abnormalities in liver function tests after 6 months.
- A 2022 case report 3 highlighted the potential for olanzapine to contribute to hepatotoxicity, especially in patients with underlying liver disease, suggesting that stopping the medication can help clarify its role in liver injury.
- A 2018 prospective study 4 of children and adolescents on second-generation antipsychotics found that less than 3% showed an increase in ALT or AST levels, with no clinically significant increases observed.
- A 2012 systematic review 5 noted that all antipsychotics can cause liver function test abnormalities, with a median prevalence of 32%, but most abnormalities are asymptomatic and transient.
- A 2023 narrative review 6 graded antipsychotics by their risk of inducing or worsening liver injuries, with quetiapine and risperidone considered moderate risk, and olanzapine posing a higher risk.
Risk Assessment
Based on the available evidence:
- Olanzapine is associated with a higher risk of liver enzyme elevations and hepatotoxicity, especially in patients with underlying liver disease 3, 6.
- Quetiapine and risperidone are considered to pose a moderate risk of liver injury 6.
- The risk of elevated ALT levels is generally lower for quetiapine and risperidone compared to olanzapine, although all antipsychotics can cause liver function test abnormalities 2, 4, 5.
Monitoring and Management
Given the potential risks:
- Regular monitoring of liver function tests is recommended, especially for patients with risk factors for liver disease or those taking higher-risk antipsychotics like olanzapine 2, 6.
- A careful risk-benefit analysis should guide the decision to discontinue or adjust antipsychotic treatment in cases of severe liver disease 6.