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Dan Roden
Faculty Member
Last active: 3/24/2020

CYP2D6 genotype and adverse events to risperidone in children and adolescents.

Oshikoya KA, Neely KM, Carroll RJ, Aka IT, Maxwell-Horn AC, Roden DM, Van Driest SL
Pediatr Res. 2019 85 (5): 602-606

PMID: 30661084 · PMCID: PMC6435416 · DOI:10.1038/s41390-019-0305-z

BACKGROUND - There are few and conflicting data on the role of cytochrome P450 2D6 (CYP2D6) polymorphisms in relation to risperidone adverse events (AEs) in children. This study assessed the association between CYP2D6 metabolizer status and risk for risperidone AEs in children.

METHODS - Children ≤18 years with at least 4 weeks of risperidone exposure were identified using BioVU, a de-identified DNA biobank linked to electronic health record data. The primary outcome of this study was AEs. After DNA sequencing, individuals were classified as CYP2D6 poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers.

RESULTS - For analysis, the 257 individuals were grouped as poor/intermediate metabolizers (n = 33, 13%) and normal/ultrarapid metabolizers (n = 224, 87%). AEs were more common in poor/intermediate vs. normal/ultrarapid metabolizers (15/33, 46% vs. 61/224, 27%, P = 0.04). In multivariate analysis adjusting for age, sex, race, and initial dose, poor/intermediate metabolizers had increased AE risk (adjusted odds ratio 2.4, 95% confidence interval 1.1-5.1, P = 0.03).

CONCLUSION - Children with CYP2D6 poor or intermediate metabolizer phenotypes are at greater risk for risperidone AEs. Pre-prescription genotyping could identify this high-risk subset for an alternate therapy, risperidone dose reduction, and/or increased monitoring for AEs.

MeSH Terms (16)

Adolescent Alleles Child Cytochrome P-450 CYP2D6 Electronic Health Records Female Genotype Humans Male Pharmacogenetics Phenotype Polymorphism, Genetic Retrospective Studies Risk Risperidone Treatment Outcome

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