Pharmacogenetic investigation of response to duloxetine treatment in generalized anxiety disorder

Pharmacogenomics J. 2013 Jun;13(3):280-5. doi: 10.1038/tpj.2011.62. Epub 2012 Jan 17.


We examined genetic associations with duloxetine response in generalized anxiety disorder (GAD). Three pooled studies in patients with GAD receiving duloxetine 60-120 mg per day (N=164) or placebo (N=95) were used. Associations between 825 single-nucleotide polymorphisms (SNPs) in 61 candidate genes with change in Hamilton Anxiety Scale scores were examined with set-based testing (adjusted for the number of SNPs within each gene); sets with two-sided adjusted P≤0.05 were examined using repeated measure analysis. Follow-up analysis explored associations of these SNPs with change in Hamilton Rating Scale for Depression-Anxiety Subscale in a 6-week study in duloxetine-treated patients with major depressive disorder (MDD) (N=241). Variants in corticotropin-releasing hormone receptor 1 (CRHR1), dopamine receptor D3 (DRD3), nuclear receptor subfamily group C, member 1 (NR3C1) and phosphodiesterase 1A (PDE1A) were associated with duloxetine response in GAD. Only rs4792888 in CRHR1 showed modest evidence of association with duloxetine response in MDD (P=0.029 in GAD, P=0.054 in MDD). In conclusion, CRHR1 variation merits investigation in pathophysiology of anxiety and its treatment response.

Trial registration: NCT00122837 NCT00122850 NCT00122863 NCT00191061.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anxiety Disorders / genetics*
  • Anxiety Disorders / pathology
  • Biomarkers, Pharmacological
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / genetics*
  • Duloxetine Hydrochloride
  • Female
  • Genetic Association Studies*
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide
  • Psychiatric Status Rating Scales
  • Receptors, Corticotropin-Releasing Hormone / genetics*
  • Thiophenes / administration & dosage*


  • Biomarkers, Pharmacological
  • Receptors, Corticotropin-Releasing Hormone
  • Thiophenes
  • CRF receptor type 1
  • Duloxetine Hydrochloride

Associated data