CYP2C19 variation and citalopram response

David A. Mrazek, Joanna M Biernacka, Dennis J. O'Kane, John L. Black, Julie M Cunningham, Maureen S. Drews, Karen A. Snyder, Susanna R. Stevens, Augustus John Rush, Richard M Weinshilboum

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Objective: Variations in cytochrome P450 (CYP) genes have been shown to be associated with both accelerated and delayed pharmacokinetic clearance of many psychotropic medications. Citalopram is metabolized by three CYP enzymes. CYP2C19 and CYP3A4 play a primary role in citalopram metabolism, whereas CYP2D6 plays a secondary role. METHODS: The Sequenced Treatment Alternatives to Relieve Depression sample was used to examine the relationship between variations in the CYP2C19 and CYP2D6 genes and remission of depressive symptoms and tolerance to treatment with citalopram. The primary analyses were of the White non-Hispanic patients adherent to the study protocol (n=1074). RESULTS: Generally, patients who had CYP2C19 genotypes associated with decreased metabolism were less likely to tolerate citalopram than those with increased metabolism, although this difference was not statistically significant (P=0.06). However, patients with the inactive 2C19*2 allele had significantly lower odds of tolerance (P=0.02). Patients with the poor metabolism CYP2C19 genotype-based category who were classified as citalopram tolerant were more likely to experience remission (P=0.03). No relationship between CYP2D6 genotype-based categories and either remission or tolerance was identified, although exploratory analyses identified a potential interaction between CYP2C19 and CYP2D6 effects. CONCLUSION: Despite several limitations including the lack of serum drug levels, this study showed that variations in CYP2C19 were associated with tolerance and remission in a large sample of White non-Hispanic patients treated with citalopram.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalPharmacogenetics and Genomics
Volume21
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Citalopram
Cytochrome P-450 CYP2D6
Cytochrome P-450 Enzyme System
Genotype
Depression
Cytochrome P-450 CYP3A
Genes
Cytochrome P-450 CYP2C19
Pharmacokinetics
Alleles
Therapeutics
Serum
Pharmaceutical Preparations

Keywords

  • citalopram
  • cytochrome P450 2C19
  • cytochrome P450 2D6
  • pharmacogenomics
  • remission
  • tolerance

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

Cite this

CYP2C19 variation and citalopram response. / Mrazek, David A.; Biernacka, Joanna M; O'Kane, Dennis J.; Black, John L.; Cunningham, Julie M; Drews, Maureen S.; Snyder, Karen A.; Stevens, Susanna R.; Rush, Augustus John; Weinshilboum, Richard M.

In: Pharmacogenetics and Genomics, Vol. 21, No. 1, 01.2011, p. 1-9.

Research output: Contribution to journalArticle

Mrazek, DA, Biernacka, JM, O'Kane, DJ, Black, JL, Cunningham, JM, Drews, MS, Snyder, KA, Stevens, SR, Rush, AJ & Weinshilboum, RM 2011, 'CYP2C19 variation and citalopram response', Pharmacogenetics and Genomics, vol. 21, no. 1, pp. 1-9. https://doi.org/10.1097/FPC.0b013e328340bc5a
Mrazek, David A. ; Biernacka, Joanna M ; O'Kane, Dennis J. ; Black, John L. ; Cunningham, Julie M ; Drews, Maureen S. ; Snyder, Karen A. ; Stevens, Susanna R. ; Rush, Augustus John ; Weinshilboum, Richard M. / CYP2C19 variation and citalopram response. In: Pharmacogenetics and Genomics. 2011 ; Vol. 21, No. 1. pp. 1-9.
@article{f6a6afca316e4a6bbd345956dff1e4fc,
title = "CYP2C19 variation and citalopram response",
abstract = "Objective: Variations in cytochrome P450 (CYP) genes have been shown to be associated with both accelerated and delayed pharmacokinetic clearance of many psychotropic medications. Citalopram is metabolized by three CYP enzymes. CYP2C19 and CYP3A4 play a primary role in citalopram metabolism, whereas CYP2D6 plays a secondary role. METHODS: The Sequenced Treatment Alternatives to Relieve Depression sample was used to examine the relationship between variations in the CYP2C19 and CYP2D6 genes and remission of depressive symptoms and tolerance to treatment with citalopram. The primary analyses were of the White non-Hispanic patients adherent to the study protocol (n=1074). RESULTS: Generally, patients who had CYP2C19 genotypes associated with decreased metabolism were less likely to tolerate citalopram than those with increased metabolism, although this difference was not statistically significant (P=0.06). However, patients with the inactive 2C19*2 allele had significantly lower odds of tolerance (P=0.02). Patients with the poor metabolism CYP2C19 genotype-based category who were classified as citalopram tolerant were more likely to experience remission (P=0.03). No relationship between CYP2D6 genotype-based categories and either remission or tolerance was identified, although exploratory analyses identified a potential interaction between CYP2C19 and CYP2D6 effects. CONCLUSION: Despite several limitations including the lack of serum drug levels, this study showed that variations in CYP2C19 were associated with tolerance and remission in a large sample of White non-Hispanic patients treated with citalopram.",
keywords = "citalopram, cytochrome P450 2C19, cytochrome P450 2D6, pharmacogenomics, remission, tolerance",
author = "Mrazek, {David A.} and Biernacka, {Joanna M} and O'Kane, {Dennis J.} and Black, {John L.} and Cunningham, {Julie M} and Drews, {Maureen S.} and Snyder, {Karen A.} and Stevens, {Susanna R.} and Rush, {Augustus John} and Weinshilboum, {Richard M}",
year = "2011",
month = "1",
doi = "10.1097/FPC.0b013e328340bc5a",
language = "English (US)",
volume = "21",
pages = "1--9",
journal = "Pharmacogenetics and Genomics",
issn = "1744-6872",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - CYP2C19 variation and citalopram response

AU - Mrazek, David A.

AU - Biernacka, Joanna M

AU - O'Kane, Dennis J.

AU - Black, John L.

AU - Cunningham, Julie M

AU - Drews, Maureen S.

AU - Snyder, Karen A.

AU - Stevens, Susanna R.

AU - Rush, Augustus John

AU - Weinshilboum, Richard M

PY - 2011/1

Y1 - 2011/1

N2 - Objective: Variations in cytochrome P450 (CYP) genes have been shown to be associated with both accelerated and delayed pharmacokinetic clearance of many psychotropic medications. Citalopram is metabolized by three CYP enzymes. CYP2C19 and CYP3A4 play a primary role in citalopram metabolism, whereas CYP2D6 plays a secondary role. METHODS: The Sequenced Treatment Alternatives to Relieve Depression sample was used to examine the relationship between variations in the CYP2C19 and CYP2D6 genes and remission of depressive symptoms and tolerance to treatment with citalopram. The primary analyses were of the White non-Hispanic patients adherent to the study protocol (n=1074). RESULTS: Generally, patients who had CYP2C19 genotypes associated with decreased metabolism were less likely to tolerate citalopram than those with increased metabolism, although this difference was not statistically significant (P=0.06). However, patients with the inactive 2C19*2 allele had significantly lower odds of tolerance (P=0.02). Patients with the poor metabolism CYP2C19 genotype-based category who were classified as citalopram tolerant were more likely to experience remission (P=0.03). No relationship between CYP2D6 genotype-based categories and either remission or tolerance was identified, although exploratory analyses identified a potential interaction between CYP2C19 and CYP2D6 effects. CONCLUSION: Despite several limitations including the lack of serum drug levels, this study showed that variations in CYP2C19 were associated with tolerance and remission in a large sample of White non-Hispanic patients treated with citalopram.

AB - Objective: Variations in cytochrome P450 (CYP) genes have been shown to be associated with both accelerated and delayed pharmacokinetic clearance of many psychotropic medications. Citalopram is metabolized by three CYP enzymes. CYP2C19 and CYP3A4 play a primary role in citalopram metabolism, whereas CYP2D6 plays a secondary role. METHODS: The Sequenced Treatment Alternatives to Relieve Depression sample was used to examine the relationship between variations in the CYP2C19 and CYP2D6 genes and remission of depressive symptoms and tolerance to treatment with citalopram. The primary analyses were of the White non-Hispanic patients adherent to the study protocol (n=1074). RESULTS: Generally, patients who had CYP2C19 genotypes associated with decreased metabolism were less likely to tolerate citalopram than those with increased metabolism, although this difference was not statistically significant (P=0.06). However, patients with the inactive 2C19*2 allele had significantly lower odds of tolerance (P=0.02). Patients with the poor metabolism CYP2C19 genotype-based category who were classified as citalopram tolerant were more likely to experience remission (P=0.03). No relationship between CYP2D6 genotype-based categories and either remission or tolerance was identified, although exploratory analyses identified a potential interaction between CYP2C19 and CYP2D6 effects. CONCLUSION: Despite several limitations including the lack of serum drug levels, this study showed that variations in CYP2C19 were associated with tolerance and remission in a large sample of White non-Hispanic patients treated with citalopram.

KW - citalopram

KW - cytochrome P450 2C19

KW - cytochrome P450 2D6

KW - pharmacogenomics

KW - remission

KW - tolerance

UR - http://www.scopus.com/inward/record.url?scp=78650676790&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650676790&partnerID=8YFLogxK

U2 - 10.1097/FPC.0b013e328340bc5a

DO - 10.1097/FPC.0b013e328340bc5a

M3 - Article

C2 - 21192344

AN - SCOPUS:78650676790

VL - 21

SP - 1

EP - 9

JO - Pharmacogenetics and Genomics

JF - Pharmacogenetics and Genomics

SN - 1744-6872

IS - 1

ER -