ORLANDO – Amitriptyline, but not escitalopram, significantly topped a placebo to provide sustained symptom relief in some patients with functional dyspepsia, based on early results of the Functional Dyspepsia Treatment Trial.
Approximately half (53%) of patients with functional dyspepsia who were randomized to the tricyclic antidepressant (TCA) amitriptyline reported at least 5 weeks of symptom relief, compared with 38% of patients randomized to the selective serotonin reuptake inhibitor (SSRI) escitalopram and 40% of patients on placebo, reported Dr. Nicholas J. Talley of the Mayo Clinic in Rochester, Minn.
Dr. Nicholas J. Talley
Patients with normal gastric emptying had significantly better relief with amitriptyline than did patients with delayed gastric emptying (P = .006). This finding supported data from a separate study presented at the annual Digestive Disease Week, which showed that another TCA, nortriptyline, was not effective for symptom relief in patients with gastroparesis.
"Our data with amitriptyline also appears, based on at least the first cut of the data, to be negative in slow gastric emptying, which really overlaps with gastroparesis. I don’t think we should be using this drug class in those sorts of patients unless they are depressed or if there is some other indication," Dr. Talley said in an interview.
In the Functional Dyspepsia Treatment Trial (FDTT), investigators at seven centers in the United States and one in Canada screened 400 patients with functional dyspepsia and enrolled a total of 292 patients with a mean age of 44 years. Of these, 208 had dysmotilitylike dyspepsia, characterized by satiety or fullness, and 88 had ulcerlike dyspepsia, characterized by epigastric pain.
Patients were randomized to a placebo, 10 mg escitalopram, or 25 mg amitriptyline during a 2-week run-in phase, followed by 50 mg amitriptyline for a total of 12 weeks. They were evaluated at baseline with gastric-emptying tests, nutrient drink tests, and blood draws; a subset of patients also underwent evaluation of gastric accommodation by single-photon emission computed tomography.
In an intent-to-treat analysis, amitriptyline met the primary endpoint of patient-rated adequate relief for 5 weeks or more (P = .005, vs. placebo and escitalopram each). A treatment response was defined as a report of adequate relief for at least 50% of the 10-week treatment period.
However, when the primary endpoint was broken down by functional dyspepsia subtype, the treatment effect trended toward significance, but did not reach it. Among patients with dysmotilitylike dyspepsia, 46% of those on amitriptyline, 43% on escitalopram, and 41% on placebo reported sustained relief. In the ulcerlike dyspepsia group, the respective rates of reported relief were 67%, 27%, and 39%.
There were no significant differences in reported response rates between men and women, or between obese and nonobese patients, the researchers noted.
In a partial analysis of the Nepean Dyspepsia Index, patients on amitriptyline scored significantly better in the change from baseline on the quality of life sleep disturbance subscale compared with the other treatment groups (P = .01), but not on other quality of life subscales.
Other secondary endpoints, including ratings scales for bowel disease and dyspepsia symptom severity, mood, sleep, and overall clinical impressions were still under evaluation and would be reported at a later date, Dr, Talley said.
The study was sponsored by the National Institutes of Health. Escitalopram was donated by Forest Laboratories. Dr. Talley disclosed that he was previously a consultant to the company.