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CYP2C19 variation and citalopram response

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

Pharmacogenetics and Genomics: January 2011 - Volume 21 - Issue 1 - p 1–9
doi: 10.1097/FPC.0b013e328340bc5a
ORIGINAL ARTICLES
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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.

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Departments of aPsychiatry and Psychology

bLaboratory Medicine and Pathology

cMolecular Pharmacology and Experimental Therapeutics

dDivision of Biomedical Statistics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA

eClinical Sciences, Duke-NUS Graduate Medical School Singapore, Republic of Singapore

Correspondence to David A. Mrazek, MD, Department of Psychiatry and Psychology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA Tel: +1 507 284 8891; fax: +1 507 255 9416; e-mail: mrazek.david@mayo.edu

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.pharmacogeneticsandgenomics.com).

Received March 18, 2010

Accepted September 21, 2010

© 2011 Lippincott Williams & Wilkins, Inc.