Intuitive pharmacogenetic dosing of risperidone according to CYP2D6 phenotype extrapolated from genotype in a cohort of first episode psychosis patients

Risperidone (R) is the most prescribed antipsychotic drug for patients with a first episode of psychosis (FEP). In a naturalistic cohort of chronic psychiatric inpatients, we demonstrated that clinicians adjust R dosage by CYP2D6 activity, despite being blinded to the genotype, which we described as an “intuitive pharmacogenetic” process. The aim of the present study is to replicate our previous findings of intuitive pharmacogenetic in a cohort of FEP patients using CYP2D6 phenotype extrapolated from genotypes. 70 FEP patients, under baseline treatment with R monotherapy were genotyped using the iPLEX® ADME PGx multiplex panel and TaqMan® Genotyping and Copy Number Assays. Plasma concentrations of R and its metabolite, 9-hydroxyrisperidone (9-OH), were determined. The predictive properties of those variables associated with R dosage were tested using a multiple linear regression model as well as regression trees. Significant differences in the mean daily dosage of R among CYP2D6 phenotypes were observed (Kruskal-Wallis test p=0.02): PM (4.00±2.3 mg/mL), IM (4.56±2.44), EM (6.22±4.0 mg/day) and UM (10.20±4.91 mg/day). However, non-significant differences were observed in the R/9-OH ratio or in the Concentration/Dose ratio. Regression tree provided better estimations of R dosage than the multiple linear regression model (MAE=0.958 and R2=0.871). We confirm the “intuitive pharmacogenetic” dosing of R according to the CYP2D6 phenotype in a FEP cohort. The results presented provides a rationale for the clinical use of CYP2D6 genotyping in personalized medicine.