Evidence for Pharmacogenomic Effects on Risperidone Outcomes in Pediatrics

Area of Science:

• Pharmacogenomics
• Pediatric Psychiatry
• Clinical Pharmacology

Background:

• Risperidone is a widely used antipsychotic in pediatric populations.
• Adverse events (AEs) associated with risperidone can impact treatment adherence and outcomes.
• Genetic variability, particularly in drug-metabolizing enzymes and receptors, may influence individual responses to risperidone.

Purpose of the Study:

• To investigate the association between specific genetic variants and the occurrence of adverse events (AEs) in children and adolescents treated with risperidone.
• To identify genetic factors that could predict the risk of risperidone-related AEs in pediatric patients.

Main Methods:

• A cohort of 257 children and adolescents (≤18 years) with at least 4 weeks of risperidone exposure was analyzed.
• Genotypes for CYP2D6, CYP3A4, CYP3A5, DRD2, DRD3, HTR2A, HTR2C, ABCG2, and ABCB1 were assessed.
• AE frequency was correlated with metabolizer status and specific genetic variants using Fisher exact tests and logistic regression.

Main Results:

• Adverse events were significantly more frequent in CYP2D6 poor/intermediate metabolizers (PMs/IMs) compared to normal/rapid/ultrarapid metabolizers (NMs/RMs/UMs).
• HTR2A-rs6311 heterozygotes and homozygotes showed fewer AEs than wild types in multivariable analysis.
• In the final model, CYP2D6 metabolizer status (AOR 2.6) and HTR2A-rs6311 (AOR 0.6) were associated with AEs.

Conclusions:

• Children and adolescents who are CYP2D6 PMs/IMs may have an elevated risk of risperidone-related adverse events.
• CYP2D6 genetic variants demonstrate consistent association with AEs and hold potential for clinical application in risperidone therapy.
• Further research is needed for HTR2A-rs6311 due to limited data, despite observed associations.