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Serotonin receptor 2A (HTR2A) gene polymorphism predicts treatment response to venlafaxine XR in generalized anxiety disorder

The Pharmacogenomics Journal volume 13, pages 21–26 (2013)Cite this article

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Abstract

Generalized anxiety disorder (GAD) is a chronic psychiatric disorder with significant morbidity and mortality. Antidepressant drugs are the preferred choice for treatment; however, treatment response is often variable. Several studies in major depression have implicated a role of the serotonin receptor gene (HTR2A) in treatment response to antidepressants. We tested the hypothesis that the genetic polymorphism rs7997012 in the HTR2A gene predicts treatment outcome in GAD patients treated with venlafaxine XR. Treatment response was assessed in 156 patients that participated in a 6-month open-label clinical trial of venlafaxine XR for GAD. Primary analysis included Hamilton Anxiety Scale (HAM-A) reduction at 6 months. Secondary outcome measure was the Clinical Global Impression of Improvement (CGI-I) score at 6 months. Genotype and allele frequencies were compared between groups using χ2 contingency analysis. The frequency of the G-allele differed significantly between responders (70%) and nonresponders (56%) at 6 months (P=0.05) using the HAM-A scale as outcome measure. Similarly, using the CGI-I as outcome, the G-allele was significantly associated with improvement (P=0.01). Assuming a dominant effect of the G-allele, improvement differed significantly between groups (P=0.001, odds ratio=4.72). Similar trends were observed for remission although not statistically significant. We show for the first time a pharmacogenetic effect of the HTR2A rs7997012 variant in anxiety disorders, suggesting that pharmacogenetic effects cross diagnostic categories. Our data document that individuals with the HTR2A rs7997012 single nucleotide polymorphism G-allele have better treatment outcome over time. Future studies with larger sample sizes are necessary to further characterize this effect in treatment response to antidepressants in GAD.

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Acknowledgements

This research was supported by US Public Health Research Grant MH065963 (KR) and K08MH080372 (FWL). The data for this study were collected between 2005 and 2009. We want to thank Wyeth Laboratories for providing all study medication. We also thank Rachel Hodge for technical assistance in genotyping and Dana Patsch for assisting in management and quality assurance for this project. This study was registered under clinical trails.gov.Identifier NCT00183274. KR has received honoraria and served as a consultant or on advisory boards to Cephalon, Eli Lilly, Hoffman-La Roche, Jazz Pharmaceuticals, Johnson & Johnson, Novartis Pharmaceuticals, Pfizer, Epix (PreDix) Pharmaceuticals and PGx Health LLC. KR received research grants (issued to the University of Pennsylvania) from AstraZeneca, Epix Pharmaceuticals, Genaissance Pharmaceuticals (PGxHealth LLC), NIMH, Pamlab, Pfizer and Wyeth Laboratories. All other authors report no financial relationships with commercial interests.

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Authors and Affiliations

  1. Department of Psychiatry, Mood & Anxiety Disorders Section, University of Pennsylvania School of Medicine, Philadelphia, PA

    F W Lohoff, T D Aquino, B Etemad & K Rickels

  2. USA,

    F W Lohoff, T D Aquino, B Etemad & K Rickels

  3. Department of Psychiatry, Psychiatric Pharmacogenetics Laboratory, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, Philadelphia, PA

    F W Lohoff, S Narasimhan & P K Multani

  4. USA,

    F W Lohoff, S Narasimhan & P K Multani

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  1. F W Lohoff
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  5. B Etemad
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  6. K Rickels
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Correspondence to F W Lohoff.

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Lohoff, F., Aquino, T., Narasimhan, S. et al. Serotonin receptor 2A (HTR2A) gene polymorphism predicts treatment response to venlafaxine XR in generalized anxiety disorder. Pharmacogenomics J 13, 21–26 (2013). https://doi.org/10.1038/tpj.2011.47

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