Quantifying the Impact of Phenoconversion on Medications With Actionable Pharmacogenomic Guideline Recommendations in an Acute Aged Persons Mental Health Setting.

Sam Mostafa,Carl M J Kirkpatrick,Thomas M Polasek,Leslie J Sheffield,David Huppert

doi:10.3389/fpsyt.2021.724170

Abstract

Introduction: Polypharmacy and genetic variants that strongly influence medication response (pharmacogenomics, PGx) are two well-described risk factors for adverse drug reactions. Complexities arise in interpreting PGx results in the presence of co-administered medications that can cause cytochrome P450 enzyme phenoconversion.Aim: To quantify phenoconversion in a cohort of acute aged persons mental health patients and evaluate its impact on the reporting of medications with actionable PGx guideline recommendations (APRs).Methods: Acute aged persons mental health patients (N = 137) with PGx and medication data at admission and discharge were selected to describe phenoconversion frequencies for CYP2D6, CYP2C19 and CYP2C9 enzymes. The expected impact of phenoconversion was then assessed on the reporting of medications with APRs.Results: Post-phenoconversion, the predicted frequency at admission and discharge increased for CYP2D6 intermediate metabolisers (IMs) by 11.7 and 16.1%, respectively. Similarly, for CYP2C19 IMs, the predicted frequency at admission and discharge increased by 13.1 and 11.7%, respectively. Nineteen medications with APRs were prescribed 120 times at admission, of which 50 (42%) had APRs pre-phenoconversion, increasing to 60 prescriptions (50%) post-phenoconversion. At discharge, 18 medications with APRs were prescribed 122 times, of which 48 (39%) had APRs pre-phenoconversion, increasing to 57 prescriptions (47%) post-phenoconversion.Discussion: Aged persons mental health patients are commonly prescribed medications with APRs, but interpretation of these recommendations must consider the effects of phenoconversion. Adopting a collaborative care model between prescribers and clinical pharmacists should be considered to address phenoconversion and ensure the potential benefits of PGx are maximised.

Highlights

Polypharmacy and genetic variants that strongly influence medication response are two well-described risk factors for adverse drug reactions
Since many psychotropic medicines have well-established cytochrome P450 2D6 (CYP2D6) and CYP2C19 variants that influence pharmacokinetics, PGx is increasingly being utilised in psychiatry to guide prescribing, for antidepressants
The predicted phenotype frequencies for CYP2D6, CYP2C19 and CYP2C9 are summarised in Table 1, whilst results for VKORC1 are given in Supplementary Table 1

Summary

Introduction

Polypharmacy and genetic variants that strongly influence medication response (pharmacogenomics, PGx) are two well-described risk factors for adverse drug reactions. Polypharmacy, often defined as five or more regular medicines, resulting in harmful drug-drug interactions (DDIs), and the presence of genetic variants that strongly influence medication response (pharmacogenomics, PGx), are two well-described risk factors for ADRs [1,2,3,4]. If the patient is co-prescribed paroxetine, a strong CYP2D6 inhibitor, the patient’s CYP2D6 genotype-predicted phenotype will likely be converted to a poor metaboliser (PM) [7], resulting in greatly reduced morphine formation and diminished analgesia [6]. It is more logical in this scenario to follow the codeine guideline recommendation for a CYP2D6 PM rather than the genotype-predicted NM

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