Prevalence of Pharmacogenomic Actionability in >11,000 Patients Receiving Psychiatric Care

Abstract: Introduction: Most patients with major depressive disorder (MDD) fail first-line antidepressant treatment. Pharmacogenomic (PGx) testing may improve drug selection and/or dosing. The Clinical Pharmacogenetics Implementation Consortium (CPIC) and Food and Drug Administration (FDA) provide resources for drug prescribing based on PGx results. Methods: We retrospectively analyzed PGx tests that were performed as part of routine psychiatric care. We identified actionable CYP2D6 and CYP2C19 phenotypes. “Potentially actionable” results are phenotypes associated with CPIC or FDA PGx guidelines for psychotropics. “Clinically actionable” results are recommendations for medications prescribed prior to testing or considered at the time of testing. Further analysis estimated the impact of CYP2D6 copy number variant (CNV) allele assignment on phenotype. Results: In 11,834 patients, 64% were female and the median age was 29. The most common diagnosis and reason for ordering PGx testing was MDD and a history of neuropsychiatric medication failure. Sixty-five percent of patients had a potentially actionable CYP2D6 or CYP2C19 phenotype. Of 865 patients who attempted and 1,141 patients who considered PGx-guided medications, 22%, and 18% had at least one clinically actionable phenotype. Of 883 patients with CYP2D6 CNVs (7.5% overall), 369 patients (42%) had genotypes where CNV allele assignment changed the phenotype. Conclusion: Prevalence of CYP2D6 and CYP2C19 actionability is high in a large real-world cohort of patients receiving psychiatric care and referred for clinical PGx testing. Comprehensive genotyping, including allele-specific CNVs for CYP2D6, is critical for accurate phenotype assignment and can identify clinically significant drug-gene interactions in psychiatric care.Short Description: Pharmacogenomic (PGx) testing may improve treatment strategies in patients with major depressive disorder. Here, we retrospectively analyzed PGx tests performed during psychiatric care, identified CYP2D6 and CYP2C19 phenotypes, and classified PGx results actionability according to Clinical Pharmacogenetics Implementation Consortium and Food and Drug Administration guidelines. In 11,834 patients who received clinical PGx testing, we identified clinically significant drug-gene interactions and revealed that allele-specific CNV assignment for CYP2D6 was critical for accurate phenotypingName of Sponsoring Organization(s): Tempus and Atrium Health