Jukic MM, et al. - Researchers sought to assess how CYP2D6 genetic variability influences risperidone and aripiprazole exposure and treatment in a large patient population. From a therapeutic drug monitoring database at the Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway, data of CYP2D6-genotyped patients treated with risperidone (n=1,288) or aripiprazole (n=1,334) was included. The pharmacokinetic analyses included 725 (56%) risperidone-treated and 890 (67%) aripiprazole-treated patients. Significant changes in risperidone and aripiprazole metabolism attributable to CYP2D6 genotype were noted. In poor and intermediate metabolizers, the genotype resulted in a roughly 1.6 times and 1.4 times increase in risperidone and aripiprazole active moiety exposure vs normal metabolizers, respectively. The findings suggest risperidone and aripiprazole exposure and the therapeutic failure of risperidone are due to a substantial clinical effect of CYP2D6 genotype. This suggests for individualizing risperidone and aripiprazole dosing and treatment optimization, there is value in pre-emptive CYP2D6 genotyping.