Atypical Antipsychotics and Metabolic Dysfunction-Associated Steatotic Liver Disease in Children and Adolescents: A Systematic Review

Objective Atypical antipsychotics (AAP) are commonly prescribed to children and adolescents and are associated with important adverse effects, including weight gain and metabolic syndrome. Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is the most common pediatric liver disease and is associated with serious complications, including liver cirrhosis. Given that MASLD and AAP are associated with liver cirrhosis and metabolic syndrome, a systematic review and meta-analysis was conducted to examine the association between AAP and MASLD in children and adolescents. Methods The systematic review examined studies exploring MASLD in subjects younger than 18 years taking AAP. All studies published in the English language between 1950 and 2020 were screened following PRISMA (Preferred Reporting items for Systematic Reviews and Meta-Analysis) guidelines. Results A total of 407 articles were initially retrieved, although only 3 studies met inclusion criteria. These included retrospective cohort and case-control studies with varying sample sizes and methodologies. Shedlock et al found increased obesity related risks in children with autism spectrum disorder; Kumra et al observed risperidone induced hepatotoxicity; and Mouzaki et al linked psychotropic use with more severe MASLD. Meta-analysis showed a small and statistically insignificant positive association between AAP and MASLD, with significant heterogeneity among studies, indicating a need for careful interpretation of results. Risk of bias ratings varied from fair to good. Conclusion These findings will serve as a foundation for future studies, assist in devising interventions, and may help to reform clinical guidelines for using AAP in children and adolescents to ensure patient safety.