Sub-Analysis of CYP-GUIDES Data: Assessing the Prevalence and Impact of Drug-Gene Interactions in an Ethnically Diverse Cohort of Depressed Individuals

Abstract

Introduction: Minority groups are underrepresented in pharmacogenomics (PGx) research. Recent sub-analysis of CYP-GUIDES showed reduced length of stay (LOS) in depressed patients with CYP2D6 sub-functional status. Our primary objective was to determine whether PGx guided (G) versus standard treatment (S) influenced LOS among different race/ethnic groups. Secondary objectives included prevalence of drug-gene interactions (DGIs) and readmission rates (RAR). Methods: Retrospective sub-analysis of CYP-GUIDES data comprising CYP2D6 phenotypes was reclassified using standardized CYP2D6 genotype to phenotype recommendations from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group (DPWG). The Mann-Whitney test was used to determine differences in LOS between groups G and S and Kruskal Wallis test to compare LOS among different race/ethnic groups. Logistic regression was used to determine covariates associated with RAR. Results: This study included 1,459 patients with 67.3% in G group (n = 982). The majority of patients were White (57.5%), followed by Latinos (25.6%) and Blacks (12.3%). Although there were no differences in LOS between G and S groups, Latinos had significant shorter LOS than Whites (p = 0.002). LOS was significantly reduced by 5.6 days in poor metabolizers in group G compared to S (p = 0.002). The proportion of supra functional and ultra-rapid metabolizers (UMs) were 6 and 20.3% using CYP-GUIDES and CPIC/DPWG definitions, respectively. Prevalence of DGIs was 40% with significantly fewer DGIs in Blacks (p < 0.001). Race/ethnicity was significantly associated with RAR (aOR 1.30; p = 0.003). Conclusion: A greater number of patients were classified as CYP2D6 UMs using CPIC/DPWG definitions as compared to CYP-GUIDES definitions. This finding may have clinical implications for using psychotropics metabolized by CYP2D6.

Keywords: CYP2D6 phenotype; depression; drug-gene interactions; ethnicity; length of stay; race.

FIGURE 1

(A) Prevalence of CYP2D6 Phenotypes stratified by groups G and S. (B) Prevalence of CYP2D6 Phenotypes stratified by ethinicity for the total study population.

FIGURE 2

Summary of number of psychotropic medication administrations among Groups G and S stratified by CYP2D6 functional status. (A): Number of psychotropic medication among Groups G and S in poor metabolizers. (B): Number of psychotropic medication among Groups G and S in intermediate metabolizers. (C): Number of psychotropic medication among Groups G and S in normal metabolizers. (D): Number of psychotropic medication among Groups G and S in ultra-rapid metabolizers.