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[CYP2D6 and CYP2C19 genotyping: effectivity in psychiatric practice]

A B Koopmans, D J Vinkers, H W Hoek

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    Summary
    This summary is machine-generated.

    Genetically determined differences in CYP2D6 and CYP2C19 metabolism affect over 75% of the population. Dose adjustments based on CYP2D6 genotype did not improve outcomes for patients on antipsychotic medication.

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    Area of Science:

    • Pharmacogenomics
    • Clinical Psychiatry
    • Drug Metabolism

    Background:

    • International guidelines suggest adjusting medication doses for individuals with altered CYP2D6 and CYP2C19 metabolism to enhance efficacy and reduce side effects.
    • The clinical benefit of genotype-guided dose adjustments remains uncertain.

    Purpose of the Study:

    • To update knowledge on CYP2D6 and CYP2C19 genotyping in psychiatry, considering ethnic diversity.
    • To evaluate the prevalence of non-normal metabolizer phenotypes and the effectiveness of genotype-guided dose adjustments.

    Main Methods:

    • A meta-analysis assessed the prevalence of poor, intermediate, and ultrarapid metabolizer phenotypes for CYP2D6 and CYP2C19.
    • Genotyping was performed on 166 Antilleans and 269 psychiatric patients in Curaçao.
    • Dose adjustments were evaluated in 45 non-normal CYP2D6 metabolizers on antipsychotic medication.

    Main Results:

    • Worldwide, an estimated 36% and 62% of individuals exhibit non-normal predicted phenotypes for CYP2D6 and CYP2C19, respectively.
    • Significant interethnic variability in phenotype prevalence was observed.
    • No significant differences in phenotypes were found between psychiatric patients, general populations, and European cohorts.
    • Dose adjustments based on CYP2D6 phenotype did not yield beneficial effects in non-normal metabolizers.

    Conclusions:

    • Over 75% of the global population possesses a non-normal CYP2D6 and/or CYP2C19 phenotype.
    • Current international guidelines for CYP2D6 phenotype-guided dose adjustment showed no benefit in patients receiving long-term antipsychotic treatment.
    • Further research into CYP genotyping in psychiatric care is essential.