Genetic predictors of antidepressant side effects: A grouped candidate gene approach in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study

Karen Hodgson, Rudolf Uher, Andrew A. Crawford, Glyn Lewis, Michael C. O'Donovan, Robert Keers, Mojca Z. Dernovšek, Ole Mors, Joanna Hauser, Daniel Souery, Wolfgang Maier, Neven Henigsberg, Marcella Rietschel, Anna Placentino, Katherine Aitchison, Anne Farmer, Oliver Davis, Peter McGuffin

Résultat de recherche: Articleexamen par les pairs

12 Citations (Scopus)

Résumé

Background: The unwanted side effects associated with antidepressants are key determinants of treatment adherence in depression; propensity to experience these adverse drug reactions (ADRs) may be influenced by genetic variation. However, previous work attempting to ascertain the genetic variants involved has had limited success, in part due to the range of ADRs reported with antidepressants. Method: ADRs reported with antidepressant treatment were categorised using their likely pharmacological basis; adrenergic, cholinergic, serotonergic and histaminergic. To identify genetic predictors of susceptibility to each group of ADRs, a candidate gene analysis was performed with data from 431 depressed patients (from a total sample size of 811 patients) enrolled in the Genome-Based Therapeutic Drugs for Depression (GENDEP) project, who were randomly allocated to receive treatment with escitalopram or nortriptyline. Data from 474 patients treated with citalopram or reboxetine in the GenPod project (total sample of 601 patients) were used for replication of significant findings. Results: We found no significant predictors of presumed adrenergic, cholinergic and histaminergic ADRs. Putative serotonergic ADRs were significantly associated with variation in the gene encoding the serotonin 2C receptor (HTR2C, rs6644093, odds ratio (OR)=1.72, 95% confidence interval (CI)=1.31- 2.25, p=7.43×10-5) in GENDEP. However, this finding was not replicated in GenPod. Conclusions: The association between serotonergic side effects and variation in the HTR2C gene in the GENDEP sample supports the hypothesis that serotonin receptor-mediated mechanisms underlie these adverse reactions, however this finding was not replicated in GenPod.

Langue d'origineEnglish
Pages (de-à)142-150
Nombre de pages9
JournalJournal of Psychopharmacology
Volume28
Numéro de publication2
DOI
Statut de publicationPublished - févr. 2014
Publié à l'externeOui

Note bibliographique

Funding Information:
The GENDEP project was funded by the European Commission Framework 6 Grant, EC Contract Ref.: LSHB-CT-2003–503428. Lundbeck provided both nortriptyline and escitalopram free of charge for the GENDEP study. GlaxoSmithKline, the Medical Research Council, the Biomedical Research Centre for Mental Health at the Institute of Psychiatry and South London and Maudsley NHS Foundation Trust (funded by the United Kingdom National Institute for Health Research of the Department of Health) contributed to the funding of the sample collection at the Institute of Psychiatry, London, through add-on projects or latterly staff funding. The GenPod study was funded by the Medical Research Council (G0200243) and supported by the Mental Health Research Network. The sponsors had no role in the design and conduct of the study, in data collection, analysis, interpretation or writing the paper.

ASJC Scopus Subject Areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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