CYTOCHROME P4502D6 GENOTYPE DOES NOT DETERMINE RESPONSE TO CLOZAPINE

1 The atypical antipsychotic drug clozapine, used in the treatment of resistant schizophrenia, is metabolized partly by the hepatic cytochro me P450 enzyme CYP2D6. Two phenotypes with respect to the activity of the enzyme are recognized (extensive metabolisers (EM) and poor metabo lisers (PM)), resulting from allelic variation in the gene, CYP2D6. 2 Genotype was determined in 123 schizophrenic patients currently being treated with clozapine, in order to determine if EM or PM status influ ences response to this drug. Patients were divided into responders and non-responders using the Global Assessment Scale, and genotyped for t he A and B poor metaboliser mutations by digesting PCR products with H paII or BstNI. 3 Fifty-nine patients were heterozygous for allele B an d for allele A. Eight patients were determined as poor metabolisers si nce they were homozygous either for A and B. Poor metabolisers were eq ually distributed between responders and non responders and no correla tion between CYP2D6 alleles and response to clozapine was found. 4 The results are consistent with recent findings showing that CYP1A2, rath er than CYP2D6, is the major enzyme responsible for the metabolism of clozapine.