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Gene-drug pairings for antidepressants and antipsychotics: level of evidence and clinical application

Molecular Psychiatry volume 27, pages 593–605 (2022)Cite this article

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Abstract

Substantial inter-individual discrepancies exist in both therapeutic effectiveness and adverse effects of antidepressant and antipsychotic medications, which can, in part, be explained by genetic variation. Here, we searched the Pharmacogenomics Knowledge Base for gene-antidepressant and gene-antipsychotic pairs with the highest level of evidence. We then extracted and compared the associated prescribing recommendations for these pairs developed by the Clinical Pharmacogenomics Implementation Consortium, the Dutch Pharmacogenetics Working Group or approved product labels in the US, Canada, Europe, and Asia. Finally, we highlight key economical, educational, regulatory, and ethical issues that, if not appropriately considered, can hinder the implementation of these recommendations in clinical practice. Our review indicates that evidence-based guidelines are available to assist with the implementation of pharmacogenetic-guided antidepressant and antipsychotic prescribing, although the maximum impact of these guidelines on patient care will not be realized until key barriers are minimized or eliminated.

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Fig. 1: Flow diagram outlining the study process for identifying and selecting the gene-drug pairings.
Fig. 2: Factors contributing to pharmacogenomic test development and implementation.

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Acknowledgements

CAB is supported by the Alberta Children’s Hospital Research Foundation and the University of Calgary Cumming School of Medicine. DJM is supported by the Canadian Institutes of Health Research (CIHR Operating Grant PJT - 169114), the Centre for Addiction and Mental Health Foundation (Joanne Murphy Professorship), and the Canadian Biomarker Integration Network for Depression (CAN-BIND). LEM received partial funding from the Jasmine Quigley Memorial Award, as part of the University of Toronto Institute of Medical Science Summer Undergraduate Research Program. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of these organizations.

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Author notes

  1. These authors contributed equally: Lara E. Murphy and Trehani M. Fonseka.

Authors and Affiliations

  1. Pharmacogenetics Research Clinic, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Lara E. Murphy, Trehani M. Fonseka & Daniel J. Müller

  2. Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Lara E. Murphy & Daniel J. Müller

  3. Departments of Medical Genetics, Psychiatry, Physiology & Pharmacology, and Community Health Sciences, University of Calgary, Calgary, AB, Canada

    Chad A. Bousman

  4. Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada

    Chad A. Bousman

  5. Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada

    Chad A. Bousman

  6. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada

    Daniel J. Müller

  7. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Daniel J. Müller

  8. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany

    Daniel J. Müller

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  1. Lara E. Murphy
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Contributions

All authors had full access to the data presented in this review and take responsibility for the integrity of the data and the accuracy of the data interpretation. Study concept and design: TMF, DJM, LEM. Acquisition of data: TMF, LEM. Interpretation of data: TMF, LEM, CAB, DJM. Drafting of the paper: TMF, LEM. Critical revision of the paper for important intellectual content: TMF, LEM, CAB, DJM. Study supervision: DJM. All authors have given approval for the final version of the article to be published.

Corresponding author

Correspondence to Daniel J. Müller.

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Competing interests

DJM and CAB are members of the Clinical Pharmacogenomics Implementation Consortium. TMF and LEM have no conflicts to declare. DJM was a co-investigator on two pharmacogenetic studies where genetic test kits were provided as in-kind contributions by Myriad Neuroscience. DJM did not receive any payments or any equity, stocks, or options from any pharmacogenetic companies. DJM is also a co-inventor on two patents assessing risk for antipsychotic-induced weight gain (pending). CAB is founder and equity holder in Sequence2Script Inc.

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Murphy, L.E., Fonseka, T.M., Bousman, C.A. et al. Gene-drug pairings for antidepressants and antipsychotics: level of evidence and clinical application. Mol Psychiatry 27, 593–605 (2022). https://doi.org/10.1038/s41380-021-01340-6

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