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Published on: November 14, 2017
Pharmacogenetic investigation of response to duloxetine treatment in generalized anxiety disorder
R H Perlis1, B Fijal, S Dharia
1Psychiatric Pharmacogenomics Laboratory, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Abstract:
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.
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