Paroxetine-Induced Conversion of Cytochrome P450 2D6 Phenotype and Occurence of Adverse Eects

The paper is focused on a comparison of the distribution of side eects of treatment with paroxetine within a group of 30 patients genotyped and phenotyped for their CYP 2D6 metabolic status. Genotyping procedure showed that the patient group did not include any in- dividual with poor metabolizer (PM) genotype; on the other hand, most patients (24) were classied as PMs by virtue of their phenotype, which suggests that a con- version to the poor metabolic phenotype (\phenocopy") occurred, probably as a consequence of a long-term administration of the strong CYP 2D6 inhibitor parox- etine. As to the occurence of common adverse eects, no marked dierence between subjects converted into the PM group and those who had no history of such con- version was found. A signicantly higher incidence of sexual dysfunction ( p< 0:05) was, nevertheless, recorded in patients with the PM phenotype. The results of the study may provide evidence that it is the metabolic phe- notype status, rather than the genetically given enzyme capacity (CYP 2D6 geno- type), that is relevant for the actual toleration of treatment with CYP 2D6 in- hibitors.