[Clinical pharmacogenetics in the treatment of schizophrenia]

Abstract

Numerous investigations on metabolic enzymes, cytochrome P450 (CYP) have been conducted since 1990. In the psychiatric field, CYP2D6, which is a major enzyme involved in the metabolism of antidepressants and antipsychotics, has been focused on. Poor metabolizers (deficit metabolizers) for CYP2D6 are 7% in Caucasians, while they are less than 1% in Asians. Frequency of a mutated allele for CYP2D6*10, which leads to a decrease in CYP2D6 activity, is 40% in Asians. It has been reported that the steady-state plasma concentration of haloperidol in subjects with mutated alleles for CYP2D6 is significantly higher than that in subjects without mutated alleles. On the other hand, the steady-state plasma concentration of risperidone is very different between CYP2D6 genotypes. Recently receptor polymorphism has been studied and an association between clinical response and polymorphism of dopamine and serotonin has been reported. In the dopamine D2, subjects with -141C Ins allele in -141C Ins/Del polymorphism and subjects with A1 allele in Taq 1A have better response to dopamine antagonists. Clinical pharmacogenetical studies from both a phamacokinetical and a pharmacogynamical point of view are required in order to introduce and practice individualized medicine in the psychiatric field easily.