Impact of CYP2D6 Genotype on Steady-State Serum Concentrations of Risperidone and 9-Hydroxyrisperidone in Patients Using Long-Acting Injectable Risperidone

An increased risk of adverse effects and discontinuation of risperidone therapy is observed in patients with impaired cytochrome P450 2D6 (CYP2D6) function on oral risperidone therapy. The present study is the first to investigate the impact of CYP2D6 genotype on serum concentrations of risperidone and 9-hydroxyrisperidone in patients using injectable long-acting risperidone. Two hundred three patients were divided into groups according to administered risperidone formulation (long-acting injection; n = 90) and CYP2D6 genotype. Dose-adjusted serum concentrations were compared using the CYP2D6*1/*1 subgroup as reference. The total serum concentration of risperidone plus 9-hydroxyrisperidone was 80% (P < 0.03) and 32% (P < 0.03) higher, whereas the risperidone-9-hydroxyrisperidone ratios were 6.3-fold (P < 0.01) and 12.5-fold (P < 0.01) higher in the CYP2D6def/def (def means defective allele, ie, CYP2D6*3, *4, *5, or *6) subgroup for long-acting and oral risperidone, respectively. In conclusion, CYP2D6 genotype significantly affects the pharmacokinetics of both oral and long-acting risperidone formulations.