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

Abstract

Background & Aims Anti-depressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or post-prandial fullness. However, there is little evidence for the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of anti-depressant therapy effects on symptoms, gastric emptying (GE), and mealinduced 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 anti-depressants. Subjects (n=292; 44±15 y old, 75% 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 endpoint was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (out of 12). Secondary endpoints included GE time, maximum tolerated volume in a 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, following treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were more than 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 anti-depressants 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.

ACG and CAG Clinical Guideline: Management of Dyspepsia

“…A systematic review ( 72 ) identifi ed 13 RCTs evaluating psychotropic drugs in FD. Th ere were three trials (126)(127)(128) involving 339 FD patients comparing TCAs with placebo. Th ere was a statistically signifi cant eff ect in reducing dyspepsia symptoms (RR=0.74; 95% CI=0.61-0.91) with an NNT of six (95% CI=6-18).…”

“…Th ere was a statistically signifi cant eff ect in reducing dyspepsia symptoms (RR=0.74; 95% CI=0.61-0.91) with an NNT of six (95% CI=6-18). Th ere were two trials ( 128,129 ) involving 388 FD patients comparing SSRIs with placebo. Th ere was no statistically signifi cant eff ect of SSRI therapy on dyspepsia symptoms (RR=1.01; 95% CI=0.89-1.15) ( 72 ).…”

“…Delayed gastric emptying, using either scintigraphic tests or breath tests, has been identifi ed in up to 30% of patients with FD, although the extent of this delay is usually mild ( 12,180,182 ). A recent, large-multicenter trial, using a validated 4-h solid phase gastric-emptying scan protocol with all studies read at one center, found that 21% of patients meeting Rome II criteria for FD had delayed gastric emptying ( 128 ). Symptoms of FD may also arise due to a prior infection (viral, bacterial, protozoal), visceral hypersensitivity, medications, duodenal eosinophilia, and abnormal or excess feedback from the upper small intestine ( 180,181,184 ).…”

Functional dyspepsia

“…Centrally acting neuro modulators are overall superior to placebo in improving functional dyspepsia, and this effect could occur in the absence of major depressive or anxiety comorbidity 200 . However, the benefit was limited to antipsychotics (D(2) dopamine receptor antagonists) and tricyclic antidepressants (which are particularly effective in EPS 201 ). Selective serotonin reuptake inhibitors and serotonin-noradrenalin reuptake inhibitors seem to have no beneficial effects, based on available studies 178,201 .…”

“…However, the benefit was limited to antipsychotics (D(2) dopamine receptor antagonists) and tricyclic antidepressants (which are particularly effective in EPS 201 ). Selective serotonin reuptake inhibitors and serotonin-noradrenalin reuptake inhibitors seem to have no beneficial effects, based on available studies 178,201 . 175 , with the exception of Helicobacter pylori eradication, the preferred treatment options depend on the subtype of functional dyspepsia (epigastric pain syndrome or postprandial distress syndrome; in patients with overlapping features, treatment should address the most prevalent symptoms) 3, 175 .…”