Pharmacokinetic Genes Do Not Influence Response or Tolerance to Citalopram in the STAR*D Sample
Open Access
- 2 April 2008
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 3 (4), e1872
- https://doi.org/10.1371/journal.pone.0001872
Abstract
We sought to determine whether clinical response or tolerance to the Selective Serotonin Reuptake Inhibitor (SSRI) citalopram is associated with genetic polymorphisms in potentially relevant pharmacokinetic enzymes. We used a two-stage case-control study design in which we split the sample of 1,953 subjects from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial into a discovery (n = 831) and validation set (n = 1,046). Fifteen polymorphisms from five (CYP2D6, ABCB1, CYP2C19, CYP3A4, and CYP3A5) pharmacokinetic genes were genotyped. We examined the associations between these polymorphisms and citalopram response and tolerance. Significant associations were validated in the second stage for those polymorphism found to be statistically significant in the first stage. No genetic polymorphism in the pharmacokinetic genes examined was significantly associated with our response or tolerance phenotypes in both stages. For managing pharmacological treatment with citalopram, routine screening of the common pharmacokinetic DNA variants that we examined appears to be of limited clinical utility.Keywords
This publication has 40 references indexed in Scilit:
- The clinical role of genetic polymorphisms in drug-metabolizing enzymesThe Pharmacogenomics Journal, 2007
- Variation in the Gene Encoding the Serotonin 2A Receptor Is Associated with Outcome of Antidepressant TreatmentAmerican Journal of Human Genetics, 2006
- Phenotype–genotype variability in the human CYP3A locus as assessed by the probe drug quinine and analyses of variant CYP3A4 allelesBiochemical and Biophysical Research Communications, 2005
- Genetic Structure, Self-Identified Race/Ethnicity, and Confounding in Case-Control Association StudiesAmerican Journal of Human Genetics, 2005
- Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug responseMolecular Psychiatry, 2004
- Pharmacogenetics of Antidepressant Medication IntoleranceAmerican Journal of Psychiatry, 2003
- PHARMACOKINETICS OF CITALOPRAM IN RELATION TO GENETIC POLYMORPHISM OF CYP2C19Drug Metabolism and Disposition, 2003
- Metabolism of citalopram enantiomers in CYP2C19/CYP2D6 phenotyped panels of healthy SwedesBritish Journal of Clinical Pharmacology, 2003
- Score Tests for Association between Traits and Haplotypes when Linkage Phase Is AmbiguousAmerican Journal of Human Genetics, 2002
- Is Therapeutic Drug Monitoring a Case for Optimizing Clinical Outcome and Avoiding Interactions of the Selective Serotonin Reuptake Inhibitors?Therapeutic Drug Monitoring, 2000