Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: A Multicenter, Randomized Controlled Study

Gastroenterology. 2015 Aug;149(2):340-9.e2. doi: 10.1053/j.gastro.2015.04.020. Epub 2015 Apr 25.


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.

Keywords: Abdominal Pain; Antidepressant; Functional Dyspepsia; Functional Gastrointestinal Disorder.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Amitriptyline / administration & dosage
  • Amitriptyline / therapeutic use*
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Citalopram / administration & dosage
  • Citalopram / therapeutic use*
  • Double-Blind Method
  • Drinking / drug effects
  • Dyspepsia / drug therapy*
  • Dyspepsia / physiopathology
  • Dyspepsia / psychology
  • Female
  • Gastric Emptying / drug effects
  • Humans
  • Male
  • Middle Aged
  • Quality of Life*
  • Satiation / drug effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Time Factors
  • Treatment Outcome


  • Antidepressive Agents, Tricyclic
  • Serotonin Uptake Inhibitors
  • Citalopram
  • Amitriptyline

Associated data

  • ClinicalTrials.gov/NCT00248651