Antidepressants improve functional dyspepsia symptoms, but how remains unclear
Amitriptyline, a tricyclic antidepressant, improved functional dyspepsia symptoms better than the selective serotonin reuptake inhibitor escitalopram, and neither slowed gastric emptying, according to the results of an international multicenter randomized controlled trial.
Additionally, both amitriptyline (AMI) and escitalopram (ESC) improved gastric accommodation and post-prandial symptoms. While these results support the routine use of antidepressants to treat functional dyspepsia (FD), the precise mechanisms by which they work remain unclear, and further research is therefore warranted, investigators concluded.
“We know a low dose tricyclic can improve the symptoms of functional dyspepsia, particularly epigastric pain, but the mechanisms are unclear,” Nicholas J. Talley, MD, PhD, of the Faculty of Health and Medicine at the University of Newcastle in Australia, told Healio Gastroenterology and Liver Disease.
He and colleagues noted that the diverse pathophysiology of FD makes treatment difficult, as choosing an appropriate therapy based on symptoms may not be reliable. Therefore, they performed this trial to determine if FD and its subtypes with abnormalities in gastric function would respond differently to antidepressant treatment compared with those with normal physiology
“Failure of gastric accommodation is present in a subgroup with functional dyspepsia and in some studies, has been linked to inability to finish a normal sized meal (early satiety),” Talley said by email.
Additionally, “delayed gastric emptying is one of the most common pathophysiologic abnormalities identified in FD patients,” affecting about 30% of them, he and colleagues wrote.
The researchers randomly assigned 292 patients with FD (mean age, 44) to receive either 50 mg of AMI and a placebo for ESC, 10 mg of ESC and a placebo for AMI, or two placebos for 12 weeks.
For the patients treated with AMI, 53% showed improvements in FD symptoms compared with 38% of those treated with ESC and 40% treated with placebo (P = .054).
The researchers tested patients for gastric emptying at baseline and at the end of the 12-week treatment period using scintigraphy-based solid-phase gastric emptying scans. Each scan was done in the morning after an overnight fast using a standardized meal.
The results showed that neither antidepressant altered gastric emptying, even in the 21% of patients who showed delayed gastric emptying at baseline.
“The study ... showed gastric emptying was not slowed by a low-dose tricyclic as might be expected through its anticholinergic effects, although we know those with slow gastric emptying are less likely to improve on therapy,” Talley told Healio Gastroenterology and Liver Disease.
The investigators also tested gastric accommodation in a subset of patients using single-photon emission computed tomography imaging, and found it significantly increased with antidepressant therapy (P = .02).
“While both tricyclics and SSRIs in our study relaxed the fundus, this did not appear to explain the primary symptom benefit of tricyclic therapy,” Talley said.
The investigators also assessed for abnormal satiation using a nutrient drink test, which showed both AMI (P = .04) and ESC (P = .04) improved aggregate symptom scores (ie, abdominal pain, fullness, bloating, and nausea) vs. placebo. Notably, postprandial bloating, “one of the most bothersome symptoms of FD,” improved with both AMI (P = .03) and ESC (P = .02), investigators wrote.
Talley and colleagues concluded that the results of the study provide further evidence that clinicians can use tricyclic antidepressants (TCA) to improve FD symptoms without worrying about causing, or worsening, a patient’s slow gastric emptying. However, they do not yet know the mechanism by which TCAs improve these symptoms and believe it warrants another study.
“Other evidence has implicated duodenal inflammation and dysfunction in functional dyspepsia,” Talley said. “Whether a tricyclic reduces upper intestinal hypersensitivity needs to be determined.” – by Alex Young
Disclosures: The authors report no relevant financial disclosures.