Genetic differences in cytochrome P450 enzymes and antidepressant treatment response

Karen Hodgson*, Katherine Tansey, Mojca Zvezdana Dernovšek, Joanna Hauser, Neven Henigsberg, Wolfgang Maier, Ole Mors, Anna Placentino, Marcella Rietschel, Daniel Souery, Rebecca Smith, Ian W. Craig, Anne E. Farmer, Katherine J. Aitchison, Sarah Belsy, Oliver S P Davis, Rudolf Uher, Peter McGuffin

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

50 Citations (Scopus)

Abstract

Aims: Antidepressant response varies between patients, possibly due to differences in the rate cytochrome P450 enzymes metabolise antidepressants into inactive compounds. Drug metabolism rates are influenced by common variants in the genes encoding these enzymes. However, it remains unclear whether treatment outcomes can be predicted by either CYP450 genotype or antidepressant serum concentration. Methods: In GENDEP (a pharmacogenetic study of depressed individuals treated with either escitalopram or nortriptyline), serum concentrations of antidepressants and their primary metabolite were measured after eight weeks treatment and variants in CYP2D6 and CYP2C19 were genotyped. Results: Amongst patients taking escitalopram (n=223), the genotype CYP2C19 was significantly associated with escitalopram serum concentrations and desmethylescitalopram:escitalopram ratio. For those taking nortriptyline (n=161), the CYP2D6 genotype was significantly associated with nortriptyline and 10-hydroxynortriptyline serum concentrations and 10-hydroxynortriptyline: nortriptyline ratio. CYP450 genotypes conferring greater enzyme activity were linked to lower drug serum concentrations and higher metabolite:drug ratios. Nonetheless, no significant association was found between either CYP450 genotype or antidepressant serum concentration and treatment response. Conclusions: While there is a significant relationship between the CYP450 genotype and serum concentrations of escitalopram and nortriptyline, the genotypes are not predictive of differences in treatment response for either drug. Furthermore, differences in antidepressant serum concentrations are not associated with variability in treatment response.

Original languageEnglish
Pages (from-to)133-141
Number of pages9
JournalJournal of Psychopharmacology
Volume28
Issue number2
DOIs
Publication statusPublished - 1 Feb 2014

Keywords

  • Antidepressant
  • cytochrome P450 enzymes
  • depression
  • drug metabolism
  • pharmacogenetics

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