Work

Sex and age effects on prevalence of CYP2C19 and CYP2D6 Phenoconversion risk over time in patients with psychosis

Year: 2025

Type: article

Abstract: Pharmacogenetics in psychiatry may have benefits for medication treatment success. However, medication regimes leading to drug-drug interactions and potential phenoconversion of actionable pharmacogenetic phenotypes challenge the application of pharmacogenetics. Although polypharmacy is common, its impact in patients with psychosis is understudied, even though these patients might benefit from pharmacogenetics-guided medication adjustment. Here, we investigated the impact of two pharmacogenes relevant in psychiatric practice, CYP2C19 and CYP2D6, and the effect of sex and age. Medication use and predicted occurrence of phenoconversion was examined in a sample of patients with psychosis over a period of approximately six years. Bayesian statistics were applied to examine longitudinal effects. Our results show that women used more medications, including CYP2C19 and CYP2D6 inhibitors and (actionable) substrates. No significant sex or age differences were found for phenoconversion of either enzyme. A sex-effect on CYP2C19 inhibitor use was found but appeared to be driven by weakly inhibiting oral contraceptives, which were reported only in women. The phenoconversion rate for both enzymes appeared to change over time, suggesting that phenoconversion is a dynamic state that may affect patients differently over their lifetime. To further improve treatment in this patient population, long-term and regular updated medication monitoring in (pharmacogenetic) research as well as application in practice are recommended. • Polypharmacy, common in psychiatric practice, may increase phenoconversion risk. • Risk of polypharmacy may be affected by patient sex and age, and differ over time. • CYP2C19 and CYP2D6 phenoconversion rate was unaffected by sex nor age. • Polypharmacy, including use of actionable CYP substrates, was more likely in women. • Phenoconversion showed a dynamic nature over time.

Source: Progress in Neuro-Psychopharmacology and Biological Psychiatry

DOI: 10.1016/j.pnpbp.2025.111363