Pharmacogenomic Insights in Psychiatric Care: Uncovering Novel Actionability, Allele-Specific CYP2D6 Copy Number Variation, and Phenoconversion in 15,000 Patients

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Authors Joseph Stanton, Jai Patel, Sarah Morris, Raul Torres, Brooke Rhead, Chris Vlangos, Daniel Müller, Lisa Brown, Hailey Lefkofsky, Muneer Ali, Francisco De La Vega, Kathleen Barnes, Anthony Zoghbi, and Marcus Badgeley

Pharmacogenomic testing has emerged as an aid in clinical decision making for psychiatric providers, but more data is needed regarding its utility in clinical practice and potential impact on patient care. In this cross-sectional study, we determined the real-world prevalence of pharmacogenomic actionability in patients receiving psychiatric care. Potential actionability was based on the prevalence of CYP2C19 and CYP2D6 phenotypes, including CYP2D6 allele-specific copy number variations (CNVs). Combined actionability additionally incorporated CYP2D6 phenoconversion and the novel CYP2C -TG haplotype in patients with available medication data. Across 15,000 patients, 65% had potentially actionable CYP2D6 and CYP2C19 phenotypes, and phenotype assignment was impacted by CYP2D6 allele-specific CNVs in 2% of patients. Of 4,114 patients with medication data, 42% had CYP2D6 phenoconversion from drug interactions and 20% carried a novel CYP2C haplotype potentially altering actionability. A total of 87% had some form of actionability from genetic findings and/or phenoconversion, and genetic variation detected via next-generation sequencing led to phenotype reassignment in 22% of individuals overall (2% in CYP2D6 and 20% in CYP2C19). Ultimately, pharmacogenomic testing using next-generation sequencing identified potential actionability in most patients receiving psychiatric care. Early pharmacogenomic testing may provide actionable insights to aid clinicians in drug prescribing to optimize psychiatric care.