Gastroenterology

Gastroenterology

Volume 149, Issue 2, August 2015, Pages 340-349.e2
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: A Multicenter, Randomized Controlled Study

https://doi.org/10.1053/j.gastro.2015.04.020Get rights and content

Background & Aims

Antidepressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or postprandial fullness. However, there is little evidence of the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of antidepressant therapy on symptoms, gastric emptying (GE), and meal-induced satiety in patients with FD.

Methods

We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use antidepressants. Patients (n = 292; 44 ± 15 years old, 75% were female, 70% with dysmotility-like FD, and 30% with ulcer-like FD) were randomly assigned to groups given placebo, 50 mg amitriptyline, or 10 mg escitalopram for 10 weeks. The primary end point was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (of 12). Secondary end points included GE time, maximum tolerated volume in Nutrient Drink Test, and FD-related quality of life.

Results

An adequate relief response was reported by 39 subjects given placebo (40%), 51 given amitriptyline (53%), and 37 given escitalopram (38%) (P = .05, after treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were >3-fold more likely to report adequate relief than those given placebo (odds ratio = 3.1; 95% confidence interval: 1.1−9.0). Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10-week period in any group. Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE (odds ratio = 0.4; 95% confidence interval: 0.2−0.8). Both antidepressants improved overall quality of life.

Conclusions

Amitriptyline, but not escitalopram, appears to benefit some patients with FD, particularly those with ulcer-like (painful) FD. Patients with delayed GE do not respond to these drugs. ClinicalTrials.gov ID: NCT00248651.

Section snippets

Study Overview

This National Institutes of Health (DK065713)−funded, multicenter, randomized double-blind parallel group trial (Clinicaltrials.gov ID: NCT00248651) comparing 12 weeks of amitriptyline, escitalopram, and matching placebo pills is summarized in Figure 1. Institutional Review Board approval was obtained at each site. Written informed consent was obtained from each subject. Mayo Clinic Rochester monitored each site, centralized data storage, and analyzed the data. Data and Safety Monitoring Board

Subjects

Overall, 399 FD patients were screened at 8 sites (Figure 2). A total of 341 individuals met eligibility criteria and 292 subjects (97 placebo, 97 amitriptyline, and 98 escitalopram) were randomized. Sample demographic and physiologic characteristics are summarized in Table 2. Mean age was 44 years, 219 (75%) were female, and 250 (86%) were Caucasian. A total of 289 (99%) had documented endoscopy data within 5 years of recruitment; 231 (80%) had an endoscopy within a year of recruitment. Median

Discussion

Because the pathophysiology of FD remains poorly understood and a variety of treatment classes are available, health care providers do face uncertainty in selecting therapies for patients with FD. Options used in practice with limited or no data include antispasmodics, analgesics, over-the-counter remedies, as well as antidepressants to treat visceral hypersensitivity.8 This multicenter randomized, double-blind, placebo-controlled trial comparing placebo, amitriptyline, and escitalopram in FD

Acknowledgments

The investigators would like to thank the National Institute of Diabetes and Digestive and Kidney Diseases staff (Dr Patricia Roebuck, Rebecca Torrance, Rebekkah Van Raaphorst, Dr Frank Hamilton, and Dr Jose Serrano); the Data and Safety Monitoring Board members (Drs Henry Parkman, Brooks Cash, William Chey, Rona Levy, James Tonascia); the study coordinators (Verna J. Skinner, Mayo Clinic Jacksonville; Jason Bratten, Northwestern University; Jessica Chevalier, Dartmouth-Hitchcock Medical

References (40)

  • J. Tack et al.

    Functional dyspepsia—symptoms, definitions and validity of the Rome III criteria

    Nat Rev Gastroenterol Hepatol

    (2013)
  • S. Kindt et al.

    Impaired gastric accommodation and its role in dyspepsia

    Gut

    (2006)
  • B.E. Lacy et al.

    Functional dyspepsia: the economic impact to patients

    Aliment Pharmacol Ther

    (2013)
  • B.E. Lacy et al.

    Review article: current treatment options and management of functional dyspepsia

    Aliment Pharmacol Ther

    (2012)
  • A.C. Ford et al.

    Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis

    Gut

    (2009)
  • M. Otaka et al.

    New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline

    Aliment Pharmacol Ther

    (2005)
  • V.P. Tan et al.

    Treatment of functional dyspepsia with sertraline: a double-blind randomized placebo-controlled pilot study

    World J Gastroenterol

    (2012)
  • M.E. Lynch

    Antidepressants as analgesics: a review of randomized controlled trials

    J Psychiatry Neurosci

    (2001)
  • R.E. Clouse

    Antidepressants for functional gastrointestinal syndromes

    Dig Dis Sci

    (1994)
  • R.E. Clouse et al.

    Antidepressant therapy in 138 patients with irritable bowel syndrome: a five-year clinical experience

    Aliment Pharmacol Ther

    (1994)
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    Conflicts of interest These authors disclose the following: Nicholas J. Talley: Research support: National Health and Medical Research Council, Australia; National Institutes of Health; Abbott, Forest, Ironwood, Janssen, Pfizer, Prometheus, Rome Foundation. G. Richard Locke, III: Research support: Ironwood. Yuri A. Saito: Research support: Pfizer, Ironwood. Scientific Advisory Board: Salix. Colin W. Howdin: Consultant for Takeda, Otsuka, Forest, Ironwood and Salix. Speaking honoraria from Otsuka, Takeda, Forest, Ironwood and GlaxoSmithKline International. Brian E. Lacy: Scientific Advisory Board for Takeda, Ironwood, and Prometheus. Bincy P. Abraham: Research support: UCB. Consultant: Prometheus. Scientific Advisory Board for Janssen, Abbvie, UCB, Shire. Speaker: Janssen, Abbvie, UCB, Prometheus, Santaurus. Paul Moayyedi: Speakers honoraria: Shire, Forest and AstraZeneca. Chair partly funded by an unrestricted donation to McMaster University from AstraZeneca. Linda M. Herrick: Research support: Ironwood. The remaining authors disclose no conflicts.

    Funding This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (DK065713). Forest Pharmaceuticals provided the escitalopram and identical placebo for the study.

    Author names in bold designate shared co-first authorship.

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