title: Effects of antidepressants in patients with functional esophageal disorders or gastroesophageal reflux disease: a systematic review.
abstract: OBJECTIVE
  Patients with functional esophageal disorders present with symptoms of chest pain, heartburn, dysphagia, or globus in the absence of any structural abnormality. Visceral hypersensitivity is a feature of these functional disorders, and might be modulated by antidepressant therapy. We evaluated evidence for the efficacy of antidepressant therapy for symptoms associated with esophageal visceral hypersensitivity in patients with functional esophageal disorders or gastroesophageal reflux disease (GERD).
  
  
  METHODS
  We performed a systematic search of the Cochrane Comprehensive Trial Register, MEDLINE, and EMBASE (through February 2014). We analyzed relevant randomized, placebo-controlled trials reporting the effect of antidepressant therapy on experimentally induced esophageal sensation or intensity, or frequency of heartburn, chest pain, dysphagia, or globus.
  
  
  RESULTS
  The search strategy identified 378 articles; 15 described randomized controlled trials that were eligible for inclusion. In addition, 1 conference abstract and 2 case reports were included, providing the best available evidence on specific symptoms. Esophageal pain thresholds increased by 7% to 37% after antidepressant therapy. Antidepressant therapy reduced functional chest pain over a range from 18% to 67% and reduced heartburn in patients with GERD over a range of 23% to 61%. One study included patients with globus and none of the studies included patients with functional heartburn or functional dysphagia.
  
  
  CONCLUSIONS
  Based on a systematic review, antidepressants modulate esophageal sensation and reduce functional chest pain. There is limited evidence that antidepressants benefit a subgroup of patients with GERD. More controlled trials are needed to investigate the effects of antidepressants on functional esophageal disorders.
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Pim W
authors.initials: PW
authors.lastname: Weijenborg
authors.affiliation: Department of Gastroenterology and Hepatology, Universitair Ziekenhuis Antwerpen, Antwerpen, Belgium.
authors.forename: Heiko S
authors.initials: HS
authors.lastname: de Schepper
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: André J P M
authors.initials: AJ
authors.lastname: Smout
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: a.j.bredenoord@amc.uva.nl.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Bredenoord
mesh_terms: D000928:Antidepressive Agents / Q000008:administration & dosage*; D004935:Esophageal Diseases / Q000188:drug therapy*; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D005767:Gastrointestinal Diseases / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents
keywords: Esophagus; Functional Gastrointestinal Disorders; Pain Modulation; Visceral Nociception