title: Imipramine for Treatment of Esophageal Hypersensitivity and Functional Heartburn: A Randomized Placebo-Controlled Trial.
abstract: OBJECTIVE
  Tricyclic antidepressants could be effective in the treatment of symptoms related to hypersensitive esophagus through their pain-modulating effect. We therefore assessed the benefit of imipramine in patients with esophageal hypersensitivity and functional heartburn.
  
  
  METHODS
  Patients with normal endoscopy findings and typical reflux symptoms despite standard-dose proton-pump inhibitor therapy underwent 24-h pH-impedance monitoring. Patients with established esophageal hypersensitivity or functional heartburn were randomly assigned to receive 8 weeks of either once-daily imipramine 25 mg (n=43) or placebo (n=40). The primary end point was satisfactory relief of reflux symptoms, defined as a >50% reduction in the gastroesophageal reflux disease score. The secondary end point was improvement in quality-of-life (QoL) as assessed by the 36-Item Short Form Health Survey score.
  
  
  RESULTS
  Patients receiving imipramine did not achieve a higher rate of satisfactory relief of reflux symptoms than did patients receiving placebo (intention-to-treat (ITT) analysis: 37.2 vs. 37.5%, respectively; odds ratio (OR), 0.99; 95% confidence interval (CI), 0.41-2.41; per-protocol (PP) analysis: 45.5 vs. 41.2%, respectively; OR, 1.19; 95% CI, 0.45-3.13). Subgroup analysis to assess the efficacy of imipramine for either esophageal hypersensitivity or functional heartburn yielded similar results. Treatment with imipramine provided significant improvement of QoL by PP analysis (72±17 and 61±19, respectively; P=0.048), but ITT analysis did not reveal any differences between imipramine and placebo (68±19 and 61±19, respectively; P=0.26). Adverse events were similar in both groups; however, constipation was more common with imipramine than placebo (51.2 vs. 22.5%, respectively; P=0.01).
  
  
  CONCLUSIONS
  Although low-dose imipramine shows potential QoL benefits, it does not relieve symptoms more effectively than does placebo in patients with either esophageal hypersensitivity or functional heartburn.
authors.affiliation: Department of Medicine, Division of Gastroenterology, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Julajak
authors.initials: J
authors.lastname: Limsrivilai
authors.affiliation: Department of Medicine, Division of Gastroenterology, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Phunchai
authors.initials: P
authors.lastname: Charatcharoenwitthaya
authors.affiliation: Department of Medicine, Division of Gastroenterology, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Nonthalee
authors.initials: N
authors.lastname: Pausawasdi
authors.affiliation: Department of Medicine, Division of Gastroenterology, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Somchai
authors.initials: S
authors.lastname: Leelakusolvong
mesh_terms: D000328:Adult; D000368:Aged; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D004311:Double-Blind Method; D050782:Esophageal pH Monitoring; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications / Q000188:drug therapy*; D006356:Heartburn / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D006941:Hyperesthesia / Q000188:drug therapy*; D007099:Imipramine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D000929:Antidepressive Agents, Tricyclic; D007099:Imipramine