Pharmacogenomics in psychiatry – the challenge of cytochrome P450 enzyme phenoconversion and solutions to assist precision dosing

Author:

Mostafa Sam12ORCID,Polasek Thomas M134ORCID,Bousman Chad A56789ORCID,Müeller Daniel J1011ORCID,Sheffield Leslie J2ORCID,Rembach Joel2ORCID,Kirkpatrick Carl MJ1ORCID

Affiliation:

1. Centre for Medicine Use & Safety, Monash University, Parkville, Victoria, 3052, Australia

2. MyDNA Life, Australia Limited, South Yarra, Victoria, Australia

3. Certara, Princeton, NJ 08540, USA

4. Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia

5. Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne & Melbourne Health, Melbourne, Victoria, 3010, Australia

6. The Cooperative Research Centre (CRC) for Mental Health, Carlton, Victoria, 3053, Australia

7. Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, T2N 1N4, Canada

8. Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, T2N 1N4, Canada

9. Departments of Medical Genetics, Psychiatry, & Physiology & Pharmacology, University of Calgary, Calgary, Alberta, T2N 1N4, Canada

10. Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

11. Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8, Canada

Abstract

Pharmacogenomic (PGx) testing of cytochrome P450 (CYP) enzymes may improve the efficacy and/or safety of some medications. This is facilitated by increased availability and affordability of genotyping, the development of clinical practice PGx guidelines and regulatory support. However, the common occurrence of CYP phenoconversion, a mismatch between genotype-predicted CYP phenotype and the actual CYP phenotype, currently limits the application of PGx testing for precision dosing in psychiatry. This review proposes a stepwise approach to assist precision dosing in psychiatry via the introduction of PGx stewardship programs and innovative PGx education strategies. A future perspective on delivering precision dosing for psychiatrists is discussed that involves innovative clinical decision support systems powered by model-informed precision dosing.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

Reference48 articles.

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2. Clinical Pharmacogenetics Implementation Consortium. https://cpicpgx.org/guidelines/

3. US FDA. Table of pharmacogenetic associations. www.fda.gov/medical-devices/precision-medicine/table-pharmacogenetic-associations

4. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline forCYP2D6andCYP2C19Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors

5. Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update

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