CYP2C19 genotype predicts steady state escitalopram concentration in GENDEP

Huezo-Diaz, P. et al. (2012) CYP2C19 genotype predicts steady state escitalopram concentration in GENDEP. Journal of Psychopharmacology, 26(3), pp. 398-407. (doi: 10.1177/0269881111414451) (PMID:21926427) (PMCID:21926427)

Full text not currently available from Enlighten.


In vitro work shows CYP2C19 and CYP2D6 contribute to the metabolism of escitalopram to its primary metabolite, N-desmethylescitalopram. We report the effect of CYP2C19 and CYP2D6 genotypes on steady state morning concentrations of escitalopram and N-desmethylescitalopram and the ratio of this metabolite to the parent drug in 196 adult patients with depression in GENDEP, a clinical pharmacogenomic trial. Subjects who had one CYP2D6 allele associated with intermediate metabolizer phenotype and one associated with poor metabolizer (i.e. IM/PM genotypic category) had a higher mean logarithm escitalopram concentration than CYP2D6 extensive metabolizers (EMs) (p = 0.004). Older age was also associated with higher concentrations of escitalopram. Covarying for CYP2D6 and age, we found those homozygous for the CYP2C19*17 allele associated with ultrarapid metabolizer (UM) phenotype had a significantly lower mean escitalopram concentration (2-fold, p = 0.0001) and a higher mean metabolic ratio (p = 0.0003) than EMs, while those homozygous for alleles conferring the PM phenotype had a higher mean escitalopram concentration than EMs (1.55-fold, p = 0.008). There was a significant overall association between CYP2C19 genotypic category and escitalopram concentration (p = 0.0003; p = 0.0012 Bonferroni corrected). In conclusion, we have demonstrated an association between CYP2C19 genotype, including the CYP2C19*17 allele, and steady state escitalopram concentration.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Campbell, Dr Desmond
Authors: Huezo-Diaz, P., Perroud, N., Spencer, E. P., Smith, R., Sim, S., Virding, S., Uher, R., Gunasinghe, C., Gray, J., Campbell, D., Hauser, J., Maier, W., Marusic, A., Rietschel, M., Perez, J., Giovannini, C., Mors, O., Mendlewicz, J., McGuffin, P., Farmer, A. E., Ingelman-Sundberg, M., Craig, I. W., and Aitchison, K. J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Journal of Psychopharmacology
ISSN (Online):1461-7285
Published Online:17 September 2011

University Staff: Request a correction | Enlighten Editors: Update this record