LAUSR

BACKGROUND CYP2C19 is a hepatic enzyme involved in the metabolism of antidepressants associated with increased gastrointestinal bleed (GIB) risk. The aim of our study is to explore a possible association between loss of function CYP2C19 genotypes and GIB in South-Asian ancestry participants prescribed antidepressants. METHODS Genes & Health participants with a record in Barts Health NHS Trust (N 22,753) were studied using a cross-sectional approach. CYP2C19 diplotypes were assessed and metabolizer type inferred from consortia guidance. Fisher's exact test was used to compare prevalence of GIB in different metabolizer categories. Multivariable regression was used to test for association between antidepressant prescriptions and GIB and between CYP2C19 metabolizer state and GIB in the sub cohort prescribed antidepressants. RESULTS Antidepressants were frequently prescribed (47%, N= 10,612). 864 participants (4%) had a GIB; 534 (62%) had been prescribed a CYP2C19 metabolized antidepressant. There was an independent association between antidepressant prescriptions and GIB events (OR 1.8, CI 1.5-2.0, p <0.0001). There was no relationship between CYP2C19 inferred poor (p 0.56) or intermediate (p 0.53) metabolizer status and GIB in those prescribed an antidepressant in unadjusted analysis. A multivariable logistic regression model did not show an independent association between poor (p 0.54) or intermediate (p 0.62) CYP2C19 metabolizers and GIB in the sub cohort prescribed antidepressants. CONCLUSIONS CYP2C19 dependent antidepressants are associated with increased GIB prevalence. GIB appeared independent from CYP2C19 metabolizer genotype in individuals who had been prescribed antidepressants. Precision dosing based on CYP2C19 genetic information alone is unlikely to reduce GIB prevalence.