Pharmacogenetics and phenoconversion: the influence on side effects experienced by psychiatric patients
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...
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| Format: | Article |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1249164/full |
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| author | Manon G. den Uil Hannelotte W. Hut Kay R. Wagelaar Kay R. Wagelaar Heshu Abdullah-Koolmees Heshu Abdullah-Koolmees Wiepke Cahn Ingeborg Wilting Vera H. M. Deneer Vera H. M. Deneer |
| author_facet | Manon G. den Uil Hannelotte W. Hut Kay R. Wagelaar Kay R. Wagelaar Heshu Abdullah-Koolmees Heshu Abdullah-Koolmees Wiepke Cahn Ingeborg Wilting Vera H. M. Deneer Vera H. M. Deneer |
| author_sort | Manon G. den Uil |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T13:21:13Z |
| format | Article |
| id | doaj.art-3defa2258bf84c2cace1a461959d62b2 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-12T13:21:13Z |
| publishDate | 2023-08-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-3defa2258bf84c2cace1a461959d62b22023-08-25T18:50:59ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-08-011410.3389/fgene.2023.12491641249164Pharmacogenetics and phenoconversion: the influence on side effects experienced by psychiatric patientsManon G. den Uil0Hannelotte W. Hut1Kay R. Wagelaar2Kay R. Wagelaar3Heshu Abdullah-Koolmees4Heshu Abdullah-Koolmees5Wiepke Cahn6Ingeborg Wilting7Vera H. M. Deneer8Vera H. M. Deneer9Division Laboratories, Pharmacy and Biomedical Genetics, Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, NetherlandsDivision Laboratories, Pharmacy and Biomedical Genetics, Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, NetherlandsDivision Laboratories, Pharmacy and Biomedical Genetics, Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, NetherlandsDepartment of Clinical Pharmacy, Medisch Spectrum Twente, Enschede, NetherlandsPharmacy and Clinical Pharmacology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsDivision of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, NetherlandsDepartment of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, NetherlandsDivision Laboratories, Pharmacy and Biomedical Genetics, Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, NetherlandsDivision Laboratories, Pharmacy and Biomedical Genetics, Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, NetherlandsDivision of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, NetherlandsIntroduction: 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.https://www.frontiersin.org/articles/10.3389/fgene.2023.1249164/fullpharmacogeneticsphenoconversionside effectspsychiatric drugsCYP2C19CYP2D6 |
| spellingShingle | Manon G. den Uil Hannelotte W. Hut Kay R. Wagelaar Kay R. Wagelaar Heshu Abdullah-Koolmees Heshu Abdullah-Koolmees Wiepke Cahn Ingeborg Wilting Vera H. M. Deneer Vera H. M. Deneer Pharmacogenetics and phenoconversion: the influence on side effects experienced by psychiatric patients Frontiers in Genetics pharmacogenetics phenoconversion side effects psychiatric drugs CYP2C19 CYP2D6 |
| title | Pharmacogenetics and phenoconversion: the influence on side effects experienced by psychiatric patients |
| title_full | Pharmacogenetics and phenoconversion: the influence on side effects experienced by psychiatric patients |
| title_fullStr | Pharmacogenetics and phenoconversion: the influence on side effects experienced by psychiatric patients |
| title_full_unstemmed | Pharmacogenetics and phenoconversion: the influence on side effects experienced by psychiatric patients |
| title_short | Pharmacogenetics and phenoconversion: the influence on side effects experienced by psychiatric patients |
| title_sort | pharmacogenetics and phenoconversion the influence on side effects experienced by psychiatric patients |
| topic | pharmacogenetics phenoconversion side effects psychiatric drugs CYP2C19 CYP2D6 |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1249164/full |
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