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Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2D6, CYP2C19 and non-SSRI/non-TCA antidepressants

European Journal of Human Genetics (2024)Cite this article

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Abstract

The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate pharmacogenetics implementation in clinical practice by developing evidence-based guidelines to optimize pharmacotherapy based on pharmacogenetic test results. The current guideline describes the gene-drug interaction between CYP2D6 and venlafaxine, mirtazapine and duloxetine. In addition, the interaction between CYP2C19 and mirtazapine and moclobemide is presented. The DPWG identified a gene-drug interaction that requires therapy adjustment for CYP2D6 and venlafaxine. However, as the side effects do not appear to be related to plasma concentrations, it is not possible to offer a substantiated advice for dose reduction. Therefore, the DPWG recommends avoiding venlafaxine for CYP2D6 poor and intermediate metabolisers. Instead, an alternative antidepressant, which is not, or to a lesser extent, metabolized by CYP2D6 is recommended. When it is not possible to avoid venlafaxine and side effects occur, it is recommended to reduce the dose and monitor the effect and side effects or plasma concentrations. No action is required for ultra-rapid metabolisers as kinetic effects are minimal and no clinical effect has been demonstrated. In addition, a gene-drug interaction was identified for CYP2D6 and mirtazapine and CYP2C19 and moclobemide, but no therapy adjustment is required as no effect regarding effectiveness or side effects has been demonstrated for these gene-drug interactions. Finally, no gene-drug interaction and need for therapy adjustment between CYP2C19 and mirtazapine and CYP2D6 and duloxetine were identified. The DPWG classifies CYP2D6 genotyping as being “potentially beneficial” for venlafaxine, indicating that genotyping prior to treatment can be considered on an individual patient basis.

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Data availability

All data and material are either included in the Supplementary information or publicly available (i.e., the published articles, PubMed). The guidelines and background information are available on the website of the Royal Dutch Pharmacists Association (KNMP) [21]. The guidelines and background information will also be available on PharmGKB.org.

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Acknowledgements

We want to thank Leonora Grandia for performing the first systematic review for venlafaxine in 2005, Anna de Goede for performing the first systematic review for duloxetine in 2006, Inge Holsappel for performing the third systematic review for duloxetine in 2016 and Yasmina Laouti for performing the third systematic review for CYP2D6 and mirtazapine in 2020.

Funding

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 668353. The DPWG received funding from the Royal Dutch Pharmacists Association.

Author information

Authors and Affiliations

  1. Department of Clinical Chemistry, St Jansdal Hospital, Harderwijk, The Netherlands

    Lianne Beunk

  2. Royal Dutch Pharmacists Association (KNMP), The Hague, The Netherlands

    Marga Nijenhuis & Bianca Soree

  3. Pharmacy Boterdiep, Groningen, The Netherlands

    Nienke J. de Boer-Veger

  4. Pharmacy De Katwijkse Apotheek, Katwijk, The Netherlands

    Anne-Marie Buunk

  5. Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands

    Henk-Jan Guchelaar & Jesse J. Swen

  6. Department of Family Medicine, Mayo Clinic, Rochester, MN, USA

    Elisa J. F. Houwink

  7. Department of Clinical Pharmacy, Wilhelmina Hospital, Assen, The Netherlands

    Arne Risselada

  8. Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

    Gerard A. P. J. M. Rongen

  9. Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands

    Gerard A. P. J. M. Rongen

  10. Department of Clinical Chemistry, Erasmus MC University Medical Center, Rotterdam, The Netherlands

    Ron H. N. van Schaik

  11. Department of Pharmaceutical Analysis, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands

    Daan Touw

  12. Department of Clinical Pharmacy & Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Daan Touw

  13. Department of Clinical Pharmacy, Division Laboratories, Pharmacy and Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands

    Vera H. M. Deneer

  14. Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

    Vera H. M. Deneer

  15. Department of Psychiatry, Parnassia Group, Amsterdam, Netherlands

    Roos van Westrhenen

  16. Institute of Psychiatry, Psychology&Neuroscience (IoPPN), King’s College London, London, UK

    Roos van Westrhenen

  17. St. John’s National Academy of health Sciences, Bangalore, India

    Roos van Westrhenen

Authors
  1. Lianne Beunk
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Contributions

LB drafted the manuscript. RW supervised drafting of the manuscript and contributed to conceiving the work and interpretation of the results. MN performed most of the literature searches and article summaries, and suggested clinical decision support texts. BS had the clinical decision support texts translated in English and published them. NBV, AB, HJG, EJHF, AR, GAR, RHNS, JJS and DT contributed to conceiving the work and interpretation of the results. VHMD contributed to conceiving the work and interpretation of the results and led the meetings in which the DPWG decided about the article summaries and clinical decision supports texts. In addition, all authors revised the manuscript and approved the final version.

Corresponding author

Correspondence to Marga Nijenhuis.

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Beunk, L., Nijenhuis, M., Soree, B. et al. Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2D6, CYP2C19 and non-SSRI/non-TCA antidepressants. Eur J Hum Genet (2024). https://doi.org/10.1038/s41431-024-01648-1

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