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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.

SUBMITTER: Mrazek DA

PROVIDER: S-EPMC3090085 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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CYP2C19 variation and citalopram response.

Mrazek David A DA Biernacka Joanna M JM O'Kane Dennis J DJ Black John L JL Cunningham Julie M JM Drews Maureen S MS Snyder Karen A KA Stevens Susanna R SR Rush Augustus John AJ Weinshilboum Richard M RM

Pharmacogenetics and genomics 20110101 1

<h4>Objective</h4>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.<h4>Methods</h4>The Sequenced Treatment Alternatives to Relieve Depression sample was used to examine the relationship between variations in the CYP2C19 and CYP2D ...[more]

PMID: 21192344

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Project description:Few data exist to help clinicians predict likelihood of treatment response in individual patients with major depressive disorder (MDD). Our aim was to identify subgroups of MDD patients with differential treatment outcomes based on presenting clinical characteristics. We also sought to quantify the likelihood of treatment success based on the degree of improvement and side effects after 2 and 4 weeks of selective serotonin reuptake inhibitor (SSRI) pharmacotherapy.We analyzed data from the first treatment phase of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, in which subjects with a DSM-IV diagnosis of MDD were treated for 8-14 weeks with open-label citalopram. A receiver operating characteristic (ROC) analysis was conducted to determine homogenous subgroups with different rates of response and remission in depressive symptoms. Included predictor variables were initial clinical characteristics, initial improvement, and side effects after 2 and 4 weeks of SSRI treatment. The primary outcome measures were treatment response (defined as a greater than 50% reduction in 17-item Hamilton Depression Rating Scale [HDRS-17] score from baseline) and remission (defined as an HDRS-17 score ? 17).Baseline clinical characteristics were able to identify subgroups from a low likelihood of response of 18% (income < $10,000, comorbid generalized anxiety disorder, < 16 years of education; P < .01) to a high likelihood of response of 68% (income ? $40,000, no comorbid posttraumatic stress disorder; P < .01). Among baseline clinical characteristics, employment status (N = 2,477; ?²? = 78.1; P < .001) and income level (N = 2,512; ?²? = 77.7; P < .001) were the most informative in predicting treatment outcome. For the models at weeks 2 and 4, treatment success was best predicted by early symptom improvement.Socioeconomic data such as low income, education, and unemployment were most discriminative in predicting a poor response to citalopram, even with disparities in access to care accounted for. This finding implies that socioeconomic factors may be more useful predictors of medication response than traditional psychiatric diagnoses or past treatment history.ClinicalTrials.gov identifier: NCT00021528.

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CYP2C19 variation and citalopram response.

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CYP2C19 variation and citalopram response.

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