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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. METHODOLOGY: We used a two-stage case-control study design in which we s...

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Autores principales: Peters, Eric J., Slager, Susan L., Kraft, Jeffrey B., Jenkins, Greg D., Reinalda, Megan S., McGrath, Patrick J., Hamilton, Steven P.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268970/
https://www.ncbi.nlm.nih.gov/pubmed/18382661
http://dx.doi.org/10.1371/journal.pone.0001872
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author Peters, Eric J.
Slager, Susan L.
Kraft, Jeffrey B.
Jenkins, Greg D.
Reinalda, Megan S.
McGrath, Patrick J.
Hamilton, Steven P.
author_facet Peters, Eric J.
Slager, Susan L.
Kraft, Jeffrey B.
Jenkins, Greg D.
Reinalda, Megan S.
McGrath, Patrick J.
Hamilton, Steven P.
author_sort Peters, Eric J.
collection PubMed
description 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. METHODOLOGY: 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.
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spelling pubmed-22689702008-04-02 Pharmacokinetic Genes Do Not Influence Response or Tolerance to Citalopram in the STAR*D Sample Peters, Eric J. Slager, Susan L. Kraft, Jeffrey B. Jenkins, Greg D. Reinalda, Megan S. McGrath, Patrick J. Hamilton, Steven P. PLoS One Research Article 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. METHODOLOGY: 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. Public Library of Science 2008-04-02 /pmc/articles/PMC2268970/ /pubmed/18382661 http://dx.doi.org/10.1371/journal.pone.0001872 Text en Peters et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Peters, Eric J.
Slager, Susan L.
Kraft, Jeffrey B.
Jenkins, Greg D.
Reinalda, Megan S.
McGrath, Patrick J.
Hamilton, Steven P.
Pharmacokinetic Genes Do Not Influence Response or Tolerance to Citalopram in the STAR*D Sample
title Pharmacokinetic Genes Do Not Influence Response or Tolerance to Citalopram in the STAR*D Sample
title_full Pharmacokinetic Genes Do Not Influence Response or Tolerance to Citalopram in the STAR*D Sample
title_fullStr Pharmacokinetic Genes Do Not Influence Response or Tolerance to Citalopram in the STAR*D Sample
title_full_unstemmed Pharmacokinetic Genes Do Not Influence Response or Tolerance to Citalopram in the STAR*D Sample
title_short Pharmacokinetic Genes Do Not Influence Response or Tolerance to Citalopram in the STAR*D Sample
title_sort pharmacokinetic genes do not influence response or tolerance to citalopram in the star*d sample
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268970/
https://www.ncbi.nlm.nih.gov/pubmed/18382661
http://dx.doi.org/10.1371/journal.pone.0001872
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