Low-dose imipramine, a tricyclic antidepressant (TCA), may be a possible treatment option for patients with functional dyspepsia refractory to treatment with proton pump inhibitors (PPIs) or prokinetic agents; however, patients should be made aware of adverse events associated with imipramine use, according to a study published in Lancet Gastroenterology & Hepatology.

A team of investigators from Hong Kong and the United Kingdom conducted a single-center, double-blind, randomized controlled trial (ClinicalTrials.gov Identifier: NCT00164775) to determine the safety and efficacy of imipramine for patients with treatment-refractory functional dyspepsia.

The overall satisfactory relief of global dyspepsia symptoms at week 12 was the primary outcome measured. Secondary outcomes included the effects on total and individual dyspepsia symptom scores, ≥1 day per week of insomnia, and dyspepsia-related quality of life. The investigators also recorded patient withdrawal from the study due to adverse events.

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Patients aged 18 to 80 years with functional dyspepsia according to Rome II criteria who tested negative for Helicobacter pylori infection or for whom H pylori was eradicated with treatment, who had normal upper gastrointestinal endoscopy and abdominal ultrasound examinations, and who were at least moderately symptomatic following open-label treatment with esomeprazole 20 mg once daily (≥8 weeks) and domperidone 10 mg 3 times daily (≥4 weeks) were eligible to participate in the study.

Following completion of a questionnaire measuring symptoms, mood, and insomnia, 107 patients were randomly assigned to receive either imipramine 50 mg once nightly (n=55) or placebo (n=52) for 12 weeks. To reduce side effects, individuals in the imipramine group were given imipramine 25 mg for the first 2 weeks of the study, after which they received 50 mg; to adhere to double-blind consistency, all patients in both groups took 1 tablet for the first 2 weeks and 2 tablets thereafter. A total of 81 patients (76%) — 40 in the imipramine groups and 41 in the placebo group — completed the 12-week treatment and 16-week post-treatment follow-up visit.

Relief of global dyspepsia symptoms was achieved by 63.3% of patients in the imipramine group compared with 36.5% of patients in the placebo group: 18% of patients in the imipramine discontinued the study due to adverse events compared with 8% of participants in the placebo group. No serious adverse events were reported.

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“Although almost [1 in 5] patients experienced intolerable adverse events, the beneficial events outweighed these,” the authors concluded. “TCAs should therefore be considered in all patients with functional dyspepsia who have failed first-line medical therapies, particularly in those with coexistent mood disorder.”



Cheong PK, Ford AC, Cheung CKY, et al. Low-dose imipramine for refractory functional dyspepsia: a randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2018;3(12):837-844.