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.

A Bibliometric and Visual Analysis of Single Nucleotide Polymorphism Studies in Depression

“…A study on patients with recurrent depression found that an SNP in CYP2D6 was associated with the efficacy of the antidepressant duloxetine [ 92 ]. The CYP2D6 genotype has also been shown to have a possible impact on the length of hospitalization and risk of hospitalization in patients with major depressive disorder, thereby increasing the disease and financial burden on patients [ 93 ]. Unfortunately, SSRIs are currently ineffective in 60-70% of patients [ 94 - 97 ].…”

CYP2D6 and CYP2C19 Variant Coverage of Commercial Antidepressant Pharmacogenomic Testing Panels Available in Victoria, Australia

“…This allele is uncommon in individuals of European ancestry (0.1%) but is common among those of African ancestry (8.7-10.8%). The omission of this allele means that an individual with this variant could be assigned a metabolizer status discordant with their "true" status (e.g., assigned a normal metabolizer when, in fact, they are an intermediate metabolizer) [21], highlighting the importance of considering ancestry when ordering PGx testing [22,23].…”

A formal framework for generalized reporting methods in parametric settings

“…In their randomized controlled trial, Tortora et al (2020) compared the hospital length of stay (LOS) of an ethnically diverse group of patients with severe depressive disorders that were either given standard therapy (Group S) or genetically-guided therapy (Group G). For our first illustrative example, we followed the sub-analysis of Crutchley & Keuler (2022) in omitting all observations with LOS ≤ 3 days; and fit a logistic regression model for the question how does ethnicity affect the probability of staying hospitalized longer than the overall median LOS (6.625 days), controlling for the variables age, gender, and group assignment (G or S).…”