Pharmacogenetics and phenoconversion: the influence on side effects experienced by psychiatric patients

Frontiers in Genetics

Genetics

Wiepke Cahn¹  Ingeborg Wilting²  Manon G. den Uil²  Hannelotte W. Hut²  Kay R. Wagelaar³  Vera H. M. Deneer⁴  Heshu Abdullah-Koolmees⁵ 

[1] Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, Netherlands;Division Laboratories, Pharmacy and Biomedical Genetics, Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, Netherlands;Division Laboratories, Pharmacy and Biomedical Genetics, Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, Netherlands;Department of Clinical Pharmacy, Medisch Spectrum Twente, Enschede, Netherlands;Division Laboratories, Pharmacy and Biomedical Genetics, Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, Netherlands;Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands;Pharmacy and Clinical Pharmacology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands;Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands;

关键词: pharmacogenetics;    phenoconversion;    side effects;    psychiatric drugs;    CYP2C19;    CYP2D6;   

DOI  :  10.3389/fgene.2023.1249164

 received in 2023-06-28, accepted in 2023-08-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction: Preventing side effects is important to ensure optimal psychopharmacotherapy and therapeutic adherence among psychiatric patients. Obtaining the pharmacogenetic profile of CYP2C19 and CYP2D6 can play an important role in this. When the genotype-predicted phenotype shifts because of the use of co-medication, this is called phenoconversion. The aim was to study the influence of the pharmacogenetic (PGx) profile and phenoconversion on side effects experienced by psychiatric patients.Methods: A retrospective cohort study was performed using data from 117 patients from a psychiatric outpatient clinic. Patients were genotyped with a psychiatric PGx panel and side effects were evaluated using the Udvalg for Kliniske Undersølgelser side effects rating scale (UKU).Results: Of all patients, 10.3% and 9.4% underwent phenoconversion (any shift in predicted phenotype) for CYP2C19 and CYP2D6 respectively. No significant associations were found between the phenotype and UKU-score. 75% of the patients with an Intermediate metabolizer (IM) or Poor metabolizer (PM) phenoconverted phenotype of CYP2C19 experienced nausea and vomiting compared to 9.1% of the Normal metabolizer (NM) and Ultrarapid metabolizer (UM) patients (p = 0.033). 64% of the patients with an IM or PM phenoconverted phenotype of CYP2D6 experienced the side effect depression compared to 30.4% NMs and UMs (p = 0.020). CYP2D6 IM and PM patients had a higher concentration-dose ratio than NM patients (p < 0.05).Discussion: This study underlines the importance to consider phenoconversion when looking at a patient’s genotype. This is important for a better prediction of the phenotype and preventing possible side effects under a specific psychopharmacotherapy.

【 授权许可】

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Copyright © 2023 den Uil, Hut, Wagelaar, Abdullah-Koolmees, Cahn, Wilting and Deneer.