The pharmacogenetics of CYP2D6 and CYP2C19 in a case series of antidepressant responses

Frontiers in Pharmacology

Pharmacology

Paul K. L. Chin¹  Martin A. Kennedy²  Ping Siu Kee²  Simran D. S. Maggo³ 

[1] Department of Medicine, University of Otago, Christchurch, New Zealand;Department of Clinical Pharmacology, Christchurch Hospital, Christchurch, New Zealand;Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand;Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand;Department of Pathology, Center for Personalized Medicine, Children’s Hospital Los Angeles, Los Angeles, CA, United States;

关键词: antidepressant;    Adverse drug reaction;    drug response;    CYP2D6;    CYP2C19;    Psychiatry;    clinical utility;    pharmacogenetics;   

DOI  :  10.3389/fphar.2023.1080117

 received in 2022-10-25, accepted in 2023-02-08,  发布年份 2023

来源: Frontiers

【 摘 要 】

Pharmacogenetics has potential for optimizing use of psychotropics. CYP2D6 and CYP2C19 are two clinically relevant pharmacogenes in the prescribing of antidepressants. Using cases recruited from the Understanding Drug Reactions Using Genomic Sequencing (UDRUGS) study, we aimed to evaluate the clinical utility of genotyping CYP2D6 and CYP2C19 in antidepressant response. Genomic and clinical data for patients who were prescribed antidepressants for mental health disorders, and experienced adverse reactions (ADRs) or ineffectiveness, were extracted for analysis. Genotype-inferred phenotyping of CYP2D6 and CYP2C19 was carried out as per Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. A total of 52 patients, predominantly New Zealand Europeans (85%) with a median age (range) of 36 years (15–73), were eligible for analysis. Thirty-one (60%) reported ADRs, 11 (21%) ineffectiveness, and 10 (19%) reported both. There were 19 CYP2C19 NMs, 15 IMs, 16 RMs, one PM and one UM. For CYP2D6, there were 22 NMs, 22 IMs, four PMs, three UMs, and one indeterminate. CPIC assigned a level to each gene-drug pair based on curated genotype-to-phenotype evidence. We analyzed a subgroup of 45 cases, inclusive of response type (ADRs/ineffectiveness). Seventy-nine (N = 37 for CYP2D6, N = 42 for CYP2C19) gene-drug/antidepressant-response pairs with CPIC evidence levels of A, A/B, or B were identified. Pairs were assigned as ‘actionable’ if the CYP phenotypes potentially contributed to the observed response. We observed actionability in 41% (15/37) of CYP2D6-antidepressant-response pairs and 36% (15/42) of CYP2C19-antidepressant-response pairs. In this cohort, CYP2D6 and CYP2C19 genotypes were actionable for a total of 38% pairs, consisting of 48% in relation to ADRs and 21% in relation to drug ineffectiveness.

【 授权许可】

Unknown   
Copyright © 2023 Kee, Maggo, Kennedy and Chin.