Pharmacogenomics of risperidone in autism spectrum disorder: a minireview

Risperidone is one of the most widely prescribed antipsychotics for the management of irritability and associated behavioral symptoms in autism spectrum disorder (ASD), yet clinical response and adverse-effect risk vary widely among individuals. Pharmacogenomic (PGx) research has sought to explain this variability, with accumulating evidence pointing to contributions from metabolic, transporter, and neurotransmitter pathways. In this narrative minireview, we synthesize current findings on PGx factors influencing risperidone outcomes in children and adolescents with ASD. <i>CYP2D6</i> emerges as the most robust predictor of pharmacokinetics and toxicity, while pharmacodynamic associations involving dopaminergic, serotonergic, and metabolic pathways in genes such as <i>ABCB1</i>, <i>DRD3</i>, <i>HTR2A</i>, <i>HTR2C</i>, and <i>LEP</i> remain inconsistent and largely derived from small cohorts. We also discuss methodological challenges in assessing treatment response, current clinical guidelines, barriers to implementation, and emerging approaches including polygenic models, pharmacoepigenomics, and machine learning. Together, the available evidence points to both the promise and the limitations of PGx in guiding safer and more individualized risperidone therapy in ASD.