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.

Summary Background Pregabalin is a calcium channel α2δ ligand that modifies visceral hypersensitivity in IBS patients. Clinical data for pregabalin in IBS are lacking. Aim To test the efficacy of pregabalin on gastrointestinal symptoms in IBS patients. Methods A double‐blind, placebo‐controlled trial was performed. Adults meeting IBS Rome III criteria with ≥3 pain attacks per month were randomised to pregabalin 225 mg vs placebo twice daily for 12 weeks. Questionnaires were completed weekly. The primary endpoint was average pain Bowel Symptom Scale (BSS) scores weeks 9‐12. An intention‐to‐treat analysis of covariance evaluated treatment effects on quantitative endpoints, adjusting for age and gender. Adequate relief and change in pain score were assessed using a chi‐squared test. Results Eighty‐five patients were recruited and randomised. Sample characteristics include: mean age 39.4 (SD = 14.6); 73 (86%) female; 37 (44%) IBS‐D, 29 (35%) IBS‐M, 18 (21%) IBS‐C. The pregabalin arm had lower average pain‐BSS scores weeks 9‐12 (25 vs 42, P = 0.008). Compared with placebo, the overall IBS BSS severity score was lower in the pregabalin arm (26 vs 42, P = 0.009). Differences were observed for the diarrhoea‐BSS and bloating‐BSS scores (P = 0.049 and 0.016, respectively). No differences between groups were seen for constipation‐BSS scores. Adequate relief was not different between the two arms (46% vs 36%, P = 0.35). 63% pregabalin vs 45% placebo had a change in pain score ≥30 at week 12 from baseline (P = 0.10). Post‐treatment IBS‐QoL scores did not differ between groups. Conclusion This trial suggests that pregabalin may be beneficial for IBS abdominal pain, bloating and diarrhoea.

Amitriptyline (50 mg) improves FD symptoms but does not delay gastric emptying, even in patients with baseline delayed gastric emptying. GA improved with low-dose ADTx; the precise mechanism of action is unknown warranting further study.