No overall symptom improvement with nortriptyline therapy for idiopathic gastroparesis

ORLANDO, Fla. — Patients with idiopathic gastroparesis treated with nortriptyline did not experience overall symptom improvement in a study presented at Digestive Disease Week.

In a multicenter, double masked, parallel-group trial, researchers randomly assigned patients with idiopathic gastroparesis (IG) to either placebo or tricyclic antidepressant nortriptyline daily for 15 weeks. Treated patients initially were assigned 10-mg doses, with escalations every 3 weeks to 25 mg, 50 mg and 75 mg.

Symptom relief was measured at baseline and every 3 weeks using the 45-point, nine-symptom Gastroparesis Cardinal Symptom Index (GCSI). Primary endpoint was 50% or greater GCSI reductions from baseline at two consecutive measurements during the study. All participants had GCSI scores greater than 21 at baseline.

Primary endpoint was met by a similar number of patients in the two groups (23%, treated vs. 21%, placebo; P=.86). Nortriptyline recipients experienced a decrease in symptoms of nausea (P=.04) and abdominal pain (P=.004) at 3 weeks, but these differences from placebo patients did not persist over subsequent assessments.

Improvement to appetite was observed among treated patients at 15 weeks (P=.03), along with an increase to BMI (0.5 kg/m2 compared with –0.2 kg/m2 among placebo recipients; P=.03). Treated patients also trended toward improved ability to finish meals (P=.08).

During the study, 19 treated patients stopped therapy, 10 due to side effects. By comparison six placebo recipients stopped, three from adverse events. Overall incidence of adverse events was similar between groups. Five serious events occurred among treated patients, while one serious event occurred among placebo recipients.

“In this first adequately powered randomized clinical trial of a neuromodulator in idiopathic gastroparesis, nortriptyline did not improve overall symptoms,” researcher Henry P. Parkman, MD, professor of medicine and director of the GI motility laboratory at Temple University School of Medicine, said. “Specific symptoms such as nausea, abdominal pain and loss of appetite may respond to different doses of nortriptyline. Further studies will be needed to determine the role of [tricyclic antidepressants] and other neuromodulators in cases of idiopathic gastroparesis, and also other ideologies of gastroparesis.”

Disclosure: The researchers reported numerous financial disclosures.

For more information:

Parkman HP. #5: Nortriptyline for Idiopathic Gastroparesis: A Multicenter, Randomized, Double-Masked, Placebo-Controlled Trial (NORIG). Presented at: Digestive Disease Week 2013; May 18-21, Orlando, Fla.