ORLANDO – The tricyclic antidepressant nortriptyline is often prescribed for treatment of nausea, vomiting, and abdominal pain from gastroparesis, but results from a randomized clinical trial suggest that it doesn’t really work, investigators said at the annual Digestive Disease Week.
In a double-masked trial, 15 weeks of treatment with nortriptyline was no better than placebo for management of overall symptoms of idiopathic gastroparesis, reported Dr. Henry P. Parkman from Temple University in Philadelphia.
Although patients started on a 10-mg dose of nortriptyline had early improvement in nausea, this benefit disappeared as the dosage increased. In addition, 19 of the 65 patients assigned to the tricyclic antidepressant (TCA) opted to discontinue treatment early, primarily because of side effects, Dr. Parkman reported.
"Further studies will be needed to determine the role for TCAs and other neuromodulators in patients with idiopathic and also other etiologies of gastroparesis, and also to look at specific symptoms’ improvement associated with TCAs in gastroparesis," he said.
The investigators observed that the practice of treating idiopathic gastroparesis with TCAs is not well supported by clinical evidence, and took it on themselves to see whether they could gather sufficient evidence for or against the efficacy of these agents for this indication.
They chose nortriptyline because of its relatively low anticholinergic side effects, and used a dose-escalating scheme similar to that used in clinical practice.
They enrolled 130 patients into a placebo-controlled, parallel-group trial. Patients randomized to nortriptyline received it at a starting dose of 10 mg daily, which was escalated every 3 weeks to 25, 50, and finally 75 mg.
At the end of the 15 weeks, there were no significant differences between the groups in the primary endpoint, overall symptomatic improvement as measured by change in the 45-point, 9-symptom Gastroparesis Cardinal Symptom Index (GCSI). In all, 15 patients who received the TCA had at least a 50% decline from baseline GCSI score over two consecutive 3-week visits, compared with 14 patients on placebo.
Patients on nortriptyline did have a significant decline in both nausea (P = .04) and abdominal pain (P = .004) at the first visit, but this difference disappeared on subsequent visits.
At the end of the study, patients on the TCA also reported a greater improvement in appetite (P = .03), and showed a nonsignificant trend toward ability to finish a meal (P = .08). Patients on nortriptyline also had a slight gain in body mass index of 0.5 kg/m2, compared with a slight loss of –0.2 kg/m2 among patients on placebo (P = .03).
More than three times as many patients on nortriptyline stopped treatment early (19 vs. 6, P = .007), primarily because of side effects.
The investigators concluded that the role of TCAs and other neuromodulators for the treatment of idiopathic gastroparesis and other forms of gastrointestinal paralysis needs further exploration.
The study was funded by the National Institutes of Health. Dr. Parkman reported serving on advisory committees and review panels for Tranzyme, and consulting for Evoke, SmartPill, and other companies.