Influence of the Cytochrome P450 Polymorphism on Clinical Response to Aripiprazole in Patients with Schizophrenia / 대한정신약물학회지

ABSTRACT

OBJECTIVE: Aripiprazole is an atypical antipsychotic drug metabolized partly by the hepatic cytochrome P450 enzyme, CYP2D6. The aim of this study was to investigate the influence of the CYP2D6 polymorphism on the pharmacokinetics of and clinical response to aripiprazole. METHODS: The study followed a prospective, multicenter, single-medication group design and involved a 26-week study of aripiprazole treatment in Korean patients with schizophrenia. Eighty-nine patients with schizophrenia were recruited and divided into 4 groups according to CYP2D6 genotype homozygous extensive metabolizer (EM), heterozygous EM, intermediate metabolizer (IM), and poor metabolizer (PM). During the 26 weeks of the study, the pharmacokinetics of the blood samples was analyzed at week 3 and week 8 of drug administration. We used the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Barnes Akathisia Scale (BAS) for akathisia, the Simpson Angus Scale (SAS) for Par-kinsonism, the Abnormal Involuntary Movement Scale (AIMS) for tardive dyskinesia, and metabolic profiles as clinical measures. RESULTS: The sample was divided into 4 schizophrenia subgroups (homozygous EM, n=15; heterozygous EM, n=47; IM, n=22; PM, n=5). Pharmacokinetics analyses showed that patients with poorer functional alleles (PM) had smaller clearance and more than twice as long half-lives compared to those with homozygous EMs characterized by two functional alleles. PMs tended to show higher AUCs than EMs. Over the 26-week treatment period, however, no significant differences in the clinical responses (changes in the PANSS scores) were observed. The prevalence of extra-pyramidal symptoms (Parkinsonism, tardive dyskinesia, akathisia) did not differ among these groups despite the pharmacokinetic differences. CONCLUSION: Despite its relatively small sample size, this study suggested that the CYP2D6 polymorphism might not constitute the major factor contributing to the clinical response to and adverse effects of aripiprazole.