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Pharmacogenetic investigation of response to duloxetine treatment in generalized anxiety disorder

The Pharmacogenomics Journal volume 13, pages 280–285 (2013)Cite this article

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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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Acknowledgements

We thank Dr Alexandra Heinloth, Ms Laura Tyler and Ms Barbara McLean for writing and editorial assistance. The parent studies were registered at: http://www.clinicaltrials.gov/ct2/home: NCT00122850, NCT00122863, NCT00122837, and NCT00191061. This work was supported by Eli Lilly and Company and/or any of its subsidiaries.

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Authors and Affiliations

  1. Department of Psychiatry, Psychiatric Pharmacogenomics Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    R H Perlis

  2. Eli Lilly and Company, Indianapolis, IN, USA

    B Fijal

  3. PharmaNet/i3, Ann Arbor, MI, USA

    S Dharia

  4. Lilly USA, LLC, Indianapolis, IN, USA

    J P Houston

  5. Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA

    J P Houston

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  1. R H Perlis
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Correspondence to J P Houston.

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Competing interests

Dr Fijal is a full-time employee of Eli Lilly and Company and Dr Houston is a full-time employee of Lilly USA, LLC. Both are minor stockholders of Eli Lilly and Company. Dr Perlis has received honoraria or consulting fees from Eli Lilly and Company, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer and Proteus, and is a stockholder in Concordant Rater Systems, LLC. Ms Dharia is a full-time employee of PharmaNet/i3, a division of inVentiv.

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Perlis, R., Fijal, B., Dharia, S. et al. Pharmacogenetic investigation of response to duloxetine treatment in generalized anxiety disorder. Pharmacogenomics J 13, 280–285 (2013). https://doi.org/10.1038/tpj.2011.62

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  • DOI: https://doi.org/10.1038/tpj.2011.62

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