Pharmacokinetic Genes Do Not Influence Response or Tolerance to Citalopram in the STARD Sample

• Published in: PloS one Vol. 3; no. 4; p. e1872
• Main Authors: Peters, Eric J., Slager, Susan L., Kraft, Jeffrey B., Jenkins, Greg D., Reinalda, Megan S., McGrath, Patrick J., Hamilton, Steven P.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.04.2008; Public Library of Science (PLoS)
• Subjects: Antidepressants; Care and treatment; Case-Control Studies; Citalopram; Citalopram - pharmacokinetics; Clinical Trials as Topic; CYP2D6 protein; Cytochrome; Cytochrome P-450; Cytochrome P-450 Enzyme System - genetics; Cytochrome P450; Deoxyribonucleic acid; Depression (Mood disorder); Depression - drug therapy; DNA; Drug dosages; Drug Resistance - genetics; Drug therapy; Drug Tolerance - genetics; Enzymes; Ethnicity; Female; Gene polymorphism; Genes; Genetic aspects; Genetic polymorphisms; Genetic Predisposition to Disease; Genetic research; Genetic testing; Genetics; Genetics and Genomics/Pharmacogenomics; Genotype; Genotype & phenotype; Health sciences; Humans; Male; Mental depression; Mental Health/Mood Disorders; Mental Health/Psychopharmacology; Metabolism; Metabolites; Mutation; Pharmacokinetics; Pharmacology; Plasma; Polymorphism; Polymorphism, Genetic; Psychiatry; Psychopharmacology; Remission Induction; Selective Serotonin Reuptake Inhibitors - pharmacokinetics; Serotonin; Serotonin uptake inhibitors; Statistical analysis; Studies; New York; San Francisco California; Minnesota; California; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0001872

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.