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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. mrazek.david@mayo.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Mrazek
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Biernacka
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: O'Kane
authors.forename: John L
authors.initials: JL
authors.lastname: Black
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Maureen S
authors.initials: MS
authors.lastname: Drews
authors.forename: Karen A
authors.initials: KA
authors.lastname: Snyder
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Stevens
authors.forename: Augustus John
authors.initials: AJ
authors.lastname: Rush
authors.forename: Richard M
authors.initials: RM
authors.lastname: Weinshilboum
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000502:physiology; D015283:Citalopram / Q000009:adverse effects / Q000627:therapeutic use*; D065731:Cytochrome P-450 CYP2C19; D003863:Depression / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D004361:Drug Tolerance / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D014644:Genetic Variation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012074:Remission Induction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19