CYP2D6 Phenotype Influences Aripiprazole Tolerability in Pediatric Patients with Mood Disorders.

Abstract

Objective: To determine the effect of CYP2D6 metabolizer status on aripiprazole tolerability in pediatric patients with mood disorders. Methods: We retrospectively reviewed electronic medical record data for 277 patients ≤18 years of age (at the time of CYP2D6 testing) with a mood disorder, receiving oral aripiprazole, and CYP2D6 genotyped as part of routine care. The maximum aripiprazole dose and concomitant medications were extracted from the medical record. The reason for aripiprazole discontinuation was determined to be from side effects (e.g., weight gain, akathisia, GI upset), nonresponse, or other reasons (e.g., financial). Associations with CYP2D6 were analyzed using multivariate linear regression models and chi-square tests. Results: Of the 277 patients (mean age: 14.3 ± 2.4), 57% were normal metabolizers (NMs), 37% were intermediate metabolizers (IMs), 5% were poor metabolizers (PMs), and 1.4% were ultrarapid metabolizers (UMs). A total of 72.2% of the cohort were concomitantly taking a CYP2D6 inhibitor, resulting in phenoconversion. Accounting for phenoconversion resulted in 27% phenoconverted NMs (pNMs), 24% phenoconverted IMs (pIMs), 48% phenoconverted PMs (pPMs), and <1% phenoconverted ultrarapid metabolizers. CYP2D6 pPMs discontinued treatment due to side effects more often than any other CYP2D6 group (67% for pPM, 51% pIM, 57% pNM, chi-square p = 0.024). Body mass index percentile change was associated with the CYP2D6 phenotype (p = 0.038), the time on aripiprazole (p = 0.001), and the number of concomitant CYP2D6 substrates (p = 0.044) in multivariable models. Conclusions: Phenoconverted CYP2D6 metabolizer status is associated with aripiprazole discontinuation. In addition, dose adjustments based on CYP2D6 metabolizer status and concomitant medications could improve aripiprazole treatment outcomes.