Abstract
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.
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Acknowledgements
Data extraction and formatting was performed by Christian Shaffer, Vanderbilt University Medical Center. This work used a dataset from Vanderbilt University Medical Center’s BioVU, which is supported by institutional funding and by the CTSA grant UL1 TR000445 from NIH/NCATS. This work was also supported by NIH/NCATS KL2 TR000446 (S.L.V.D.), Burroughs Wellcome Fund IRSA 1015006 (S.L.V.D.), and the NIH/NIGMS Clinical Pharmacology Training Program 5T32 GM007569 (K.A.O. and K.M.N.).
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K.A.O. conceptualized and designed the study, designed the data collection instruments, collected the data, interpreted the data, and revised the manuscript. K.M.N. analyzed and interpreted the data, drafted the initial manuscript, and revised the manuscript. R.J.C. collected the data and revised the manuscript. I.T.A. analyzed the data and revised the manuscript. A.C.M.-H. revised the manuscript. D.M.R. designed the study and revised the manuscript. S.L.V.D. conceptualized and designed the study, reviewed the data collection instruments, coordinated and supervised data collection, and revised the manuscript. All authors gave final approval of this version of the article.
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S.L.V.D. has been an invited speaker to Merck. The other authors declare no competing interests.
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Oshikoya, K.A., Neely, K.M., Carroll, R.J. et al. CYP2D6 genotype and adverse events to risperidone in children and adolescents. Pediatr Res 85, 602–606 (2019). https://doi.org/10.1038/s41390-019-0305-z
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DOI: https://doi.org/10.1038/s41390-019-0305-z
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