[CYP2D6 and CYP2C19 genotyping: effectivity in psychiatric practice]

Abstract

Background: International guidelines recommend in patients with an in- or decreased CYP2D6 and CYP2C19 metabolism to adjust the dose of medication metabolized by these enzymes. This is in purpose to increase effectiveness and to lower the risk of side-effects of this medication. However, it is still unclear if dose adjustment based on genotype results in better clinical outcomes.

Aim: To provide an update regarding CYP2D6 and CYP2C19 genotyping in psychiatry in relation to ethnic diversity.To provide an update regarding CYP2D6 and CYP2C19 genotyping in psychiatry in relation to ethnic diversity.

Method: We conducted a comprehensive meta-analysis to the prevalence of non-normal metabolizers as the equivalent of the sum-prevalence of poor, intermediate and ultrarapid metabolizer CYP2D6 and CYP2C19 predicted phenotypes. For the prevalence and effectiveness study, a total of 166 Antilleans living in the Netherlands and 269 psychiatric patients (on the island Curaçao) were genotyped for CYP2D6 and CYP2C19. Of the psychiatric patients, 45 non-normal CYP2D6 metabolizers using medication metabolized by CYP2D6, were included for dose adjustment and were matched with 41 normal metabolizers. All 45 patients were using antipsychotic medication for a minimum of two years. Four months after dose adjustment they were reassessed.

Results: The mean total probability estimates of having a non-normal predicted phenotype worldwide were 36% and 62% for CYP2D6 and CYP2C19, respectively. There was a large interethnic variability (min-max 2.7-61.2% (CYP2D6) and minmax 31.7-80.1% (CYP2C19)). No significant difference was found in the phenotypes of psychiatric patients, Dutch Caribbean subjects from the general population, and European populations. There were no beneficial effects of dose adjustments to phenotype in the non-normal CYP2D6 metabolizers.

Conclusion: More than 75% of the world population has a non-normal CYP2D6 and/or CYP2C19 phenotype. Dose adjustment to the CYP2D6 phenotype according to international guidelines in patients on long-term antipsychotic treatment showed no beneficial effect. Further research to CYP genotyping in psychiatry is warranted.