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

Sam Mostafa; Thomas M Polasek; Chad A Bousman; Daniel J Müeller; Leslie J Sheffield; Joel Rembach; Carl Mj Kirkpatrick

doi:10.2217/pgs-2022-0104

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

Pharmacogenomics. 2022 Oct;23(15):857-867. doi: 10.2217/pgs-2022-0104. Epub 2022 Sep 28.

Authors

Sam Mostafa^{1

2}, Thomas M Polasek^{1

3

4}, Chad A Bousman^{5

6

7

8

9}, Daniel J Müeller^{10

11}, Leslie J Sheffield², Joel Rembach², Carl Mj Kirkpatrick¹

Affiliations

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.

PMID: 36169629
DOI: 10.2217/pgs-2022-0104

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.

Keywords: pharmacogenomics; phenoconversion dose optimisation; psychiatry.

Publication types

Review

MeSH terms

Cytochrome P-450 CYP2D6 / genetics
Cytochrome P-450 Enzyme System / genetics
Decision Support Systems, Clinical*
Pharmacogenetics
Psychiatry*

Substances

Cytochrome P-450 CYP2D6
Cytochrome P-450 Enzyme System