Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
Peters
Eric J
EJ
Department of Psychiatry and Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America.
Slager
Susan L
SL
Kraft
Jeffrey B
JB
Jenkins
Greg D
GD
Reinalda
Megan S
MS
McGrath
Patrick J
PJ
Hamilton
Steven P
SP
D016022:Case-Control Studies; D015283:Citalopram / Q000493:pharmacokinetics*; D002986:Clinical Trials as Topic; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003863:Depression / Q000188:drug therapy*; D004351:Drug Resistance / Q000235:genetics*; D004361:Drug Tolerance / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012074:Remission Induction; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics*
D015283:Citalopram; D003577:Cytochrome P-450 Enzyme System; D017367:Selective Serotonin Reuptake Inhibitors