Impact of the ultrarapid CYP2C19*17 allele on serum concentration of escitalopram in psychiatric patients

Recently, a novel allelic variant of cytochrome P450 2C19 encoding ultrarapid enzyme activity was described (denoted CYP2C19*17). The objective of this study was to evaluate the impact of CYP2C19*17 on serum concentration of escitalopram in psychiatric patients. One hundred and sixty-six patients treated with escitalopram were divided into the following subgroups according to CYP2C19 genotype: CYP2C19*17/*17 (n = 7), CYP2C19*1/*17 (n 43), CYP2C19*1/*1 (n 60), CYP2C19*17/def (n 16), CYP2C19*1/def (n = 34), and CYP2C19def/def (n 6) (def defective allele, i. e., CYP2C19*2 or *3). Dose-adjusted serum concentrations of escitalopram were compared using the CYP2C19*1/*1 subgroup as reference. Geometric mean of the escitalopram serum concentration was 42% lower in patients homozygous for CYP2C19*17 (P < 0.01) and 5.7-fold higher in subjects homozygous for defective CYP2C19 alleles (P < 0.001). Of the heterozygous subgroups, only CYP2C19*1/def was significantly different from CYP2C19*1/*1 (P < 0.001). In conclusion, a homozygous CYP2C19*17 genotype is associated with lower serum concentration of escitalopram, which might imply increased risk of therapeutic failure.