Low-dose imipramine for refractory functional dyspepsia: a randomised, double-blind, placebo-controlled trial
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AbstractBackground
Guidelines recommend the use of neuromodulators in patients with functional dyspepsia not responding to proton pump inhibitors (PPIs) and prokinetics; however, there is a lack of data from randomised controlled trials supporting their use. We aimed to assess the safety and efficacy of imipramine, a tricyclic antidepressant (TCA), in treatment-refractory functional dyspepsia.

Methods
In this single-centre, double-blind, randomised controlled trial, we enrolled consecutive patients with Rome II functional dyspepsia aged 18–80 years. Eligible patients were Helicobacter pylori-negative, had a normal upper gastrointestinal endoscopy and abdominal ultrasound, and remained symptomatic after open-label treatment with 8 weeks of esomeprazole and 4 weeks of domperidone. Patients completed questionnaires assessing dyspepsia symptoms, mood, and insomnia, and were then randomly assigned (1:1) via a computer-generated list of random numbers to receive imipramine (at a dose of 25 mg once nightly for the first 2 weeks, and then 50 mg thereafter) or placebo for 12 weeks. The primary endpoint was overall satisfactory relief of global dyspepsia symptoms at 12 weeks, via patient-reported assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00164775, and is completed.

Findings
Between Sept 11, 2005, and Aug 20, 2010, 107 patients with treatment-refractory functional dyspepsia were randomly assigned to receive imipramine (n=55) or placebo (n=52). Relief of global dyspepsia symptoms at 12 weeks occurred in 35 (63·6%, 95% CI 50·4–75·1) of 55 patients on imipramine compared with 19 (36·5%, 95% CI 24·8–50·1) of 52 on placebo (p=0·0051). Ten (18%) patients on imipramine discontinued the study due to adverse events (three dry mouth, two constipation, two drowsiness, and one each insomnia, palpitations, and blurred vision), compared with four (8%) on placebo (one dry mouth and constipation, and one each palpitations, worsening of gastro-oesophageal reflux, and limb paraesthesia). There were no serious adverse events.

Interpretation
Low-dose imipramine should be considered as a possible therapy for patients with functional dyspepsia refractory to both PPIs and prokinetics, although patients should be cautioned about the adverse event profile.

Funding
None.
All Author(s) ListCheong PK, Ford AC, Cheung CKY, Ching JYL, Chan Y, Sung JJY, Chan FKL, Wu JCY
Journal nameLancet Gastroenterology and Hepatology
Year2018
Month12
Volume Number3
Issue Number12
PublisherElsevier Inc
Pages837 - 844
ISSN2468-1253
LanguagesEnglish-United Kingdom

Last updated on 2021-14-01 at 00:44