How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing?

Beatriz Carvalho Henriques,Diego Lapetina,Katherine J Aitchison,Joshua Hague,Michael S Carr,Esther H Yang,Vasyl Yavorskyy

doi:10.3389/fgene.2020.491895

Abstract

Many genetic variants in drug metabolizing enzymes and transporters have been shown to be relevant for treating psychiatric disorders. Associations are strong enough to feature on drug labels and for prescribing guidelines based on such data. A range of commercial tests are available; however, there is variability in included genetic variants, methodology, and interpretation. We herein provide relevant background for understanding clinical associations with specific variants, other factors that are relevant to consider when interpreting such data (such as age, gender, drug–drug interactions), and summarize the data relevant to clinical utility of pharmacogenetic testing in psychiatry and the available prescribing guidelines. We also highlight areas for future research focus in this field.

Highlights

Genome-wide association studies (GWAS) and related multi-omic strategies lend themselves well to phenotypes with polygenic modes of inheritance
A recent study conducted by Lesche et al (2020) on the impact of genotype of various cytochrome P450 (CYP) enzymes and the presence of known inducers and inhibitors demonstrated that, for patients prescribed clozapine, a greater percentage of the variation in plasma concentration of this medication was explained by smoking status than by CYP1A2 genotyping information
A 50% reduction of the standard dosage for the three drugs is recommended for PM status, with and titration to response, or considering using an alternative medication not metabolized by CYP2D6

Summary

Introduction

Genome-wide association studies (GWAS) and related multi-omic strategies lend themselves well to phenotypes with polygenic modes of inheritance. A recent study conducted by Lesche et al (2020) on the impact of genotype of various CYP enzymes (including CYP1A2) and the presence of known inducers and inhibitors demonstrated that, for patients prescribed clozapine, a greater percentage of the variation in plasma concentration of this medication was explained by smoking status than by CYP1A2 genotyping information (in a cohort where 82% of individuals tested positive for the CYP1A2∗1F variant).

Results

Conclusion