[Clinical pharmacogenetics in the treatment of schizophrenia].
Numerous investigations on metabolic enzymes, cytochrome P450 (CYP), have been conducted since 1990. In the psychiatric field, the focus has been on CYP2D6, which is a major enzyme involved in metabolism of antidepressants and antipsychotics. Poor metabolizers (deficit metabolizers) for CYP2D6 represent 7% among Caucasians, while they accouut for less than 1% of Asians. The frequency of a mutated allele for CYP2D6*10, which leads to the decrease in CYP2D6 activity, is 40% in Asians. It has been reported that steady-state plasma concentration of haloperidol in subjects with mutated alleles for CYP2D6 is significantly higher than that in subjects without mutated alleles. At the same time, steady-state plasma concentration of risperidone is very different between CYP2D6 genotypes. In addition, several studies suggest that better efficacy or higher scores of side effects are observed in the subjects with mutated alleles for CYP2D6. Recently receptor polymorphism has become a concern and 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 Taq1A have a better response to dopamine antagonists. Association between Ser allele and typical antipsychotics and between Gly allele and atypical antipsychotics has been investigated. There are still no data indicating significant association between dopamine D1 and clinical response to antipsychotics. Clinical pharmacogenetical studies from both a pharmacokinetical and a pharmacogynamical point of view are required in order to introduce and practice individualized medicine in psychiatric field easily.
Saito
Manabu
M
Department of Neuropsychiatry, Hirosaki University, School of Medicine, Japan. smanabu@mama.plala.or.jp
Yasui-Furukori
Norio
N
Kaneko
Sunao
S
D000483:Alleles; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D019389:Cytochrome P-450 CYP2D6