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

Abstract

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.

Figure 1. Study Design

There was a screening period of 0–4 weeks before randomization on day 1. Two on-site visits were required prior to randomization, with a third visit if a gastric accommodation study was performed (Mayo Clinic sites only). Study visits were monthly during the treatment phase. Weekly assessments were performed by phone during the treatment period, and then monthly during the follow up period.

Figure 2. Screening, Randomization, and Follow-up

After screening the ineligible and unwilling, 292 were randomized to one of three treatment arms, with 224 (77%) completing the Treatment phase. 292 were included in the Intention-To-Treat (ITT) analysis; 205 were included in the Per-Protocol analysis.

Figure 3. Primary End point: Adequate Relief

A. Adequate relief of overall FD symptoms were reported by 39 (40%) in the placebo arm, 51 (53%) in the amitriptyline arm, and 38 (38%) in the escitalopram arm. B. Patient with ulcer-like FD had higher reports of adequate relief of FD symptoms in those receiving amitriptyline. C. Patients with dysmotility-like FD did not respond differently between the three treatment arms. D. Among subjects with normal gastric emptying at baseline, adequate relief was reported by 34 (44%) in the placebo arm, 45 (58%) in the amitriptyline arm, 31 (40%) in the escitalopram arm. E. Among subjects with delayed gastric emptying at baseline, adequate relief was reported by 5 (25%) in the placebo arm, 6 (30%) in the amitriptyline arm, and 6 (29%) in the escitalopram arm. Delayed gastric emptying was defined as <84% emptying at 4 hours.

Figure 3. Primary End point: Adequate Relief

A. Adequate relief of overall FD symptoms were reported by 39 (40%) in the placebo arm, 51 (53%) in the amitriptyline arm, and 38 (38%) in the escitalopram arm. B. Patient with ulcer-like FD had higher reports of adequate relief of FD symptoms in those receiving amitriptyline. C. Patients with dysmotility-like FD did not respond differently between the three treatment arms. D. Among subjects with normal gastric emptying at baseline, adequate relief was reported by 34 (44%) in the placebo arm, 45 (58%) in the amitriptyline arm, 31 (40%) in the escitalopram arm. E. Among subjects with delayed gastric emptying at baseline, adequate relief was reported by 5 (25%) in the placebo arm, 6 (30%) in the amitriptyline arm, and 6 (29%) in the escitalopram arm. Delayed gastric emptying was defined as <84% emptying at 4 hours.

Figure 3. Primary End point: Adequate Relief

A. Adequate relief of overall FD symptoms were reported by 39 (40%) in the placebo arm, 51 (53%) in the amitriptyline arm, and 38 (38%) in the escitalopram arm. B. Patient with ulcer-like FD had higher reports of adequate relief of FD symptoms in those receiving amitriptyline. C. Patients with dysmotility-like FD did not respond differently between the three treatment arms. D. Among subjects with normal gastric emptying at baseline, adequate relief was reported by 34 (44%) in the placebo arm, 45 (58%) in the amitriptyline arm, 31 (40%) in the escitalopram arm. E. Among subjects with delayed gastric emptying at baseline, adequate relief was reported by 5 (25%) in the placebo arm, 6 (30%) in the amitriptyline arm, and 6 (29%) in the escitalopram arm. Delayed gastric emptying was defined as <84% emptying at 4 hours.

Figure 4. Odds ratios for Adequate Relief

By pairwise comparisons, the amitriptyline group had a greater odds of adequate relief than the escitalopram group. Those with delayed gastric emptying had a lower odds of adequate relief compared to those with normal gastric emptying. Age: 10 year increments. Sex: Female vs. Male. HADS anxiety: 2 points. Weight group: Obese vs. Non-Obese. FD subtype: Ulcer-Like vs. Dysmotility-Like. Gastric Emptying: Delayed vs. Non-Delayed. Meal-Induced Satiety: Abnormal vs. Normal.