title: Effect of nortriptyline on brain responses to painful esophageal acid infusion in patients with non-erosive reflux disease.
abstract: BACKGROUND
  Non-erosive reflux disease (NERD) patients generally present with heartburn as the main symptom. Antidepressants might help to relieve heartburn by acting on the esophagus-brain axis. We aimed to assess the effect of nortriptyline on behavioral and brain responses to painful esophageal acid infusion in NERD patients evaluated with functional magnetic resonance imaging (fMRI).
  
  
  METHODS
  In a randomized double-blind crossover design, 20 NERD patients off proton pump inhibitors (36.1 ± 9.3 years, 75% women) were assigned to 21 days of nortriptyline and placebo, in counterbalanced order, with a 21 days washout period in between both treatment periods. Changes in acid-induced brain response on fMRI and heartburn perception were assessed and at the end of each treatment.
  
  
  RESULTS
  Nortriptyline significantly reduced the acid-induced brain response in prefrontal cortex (median [IQR]: -1.9 [-4.5 to -0.1] vs -0.3 [-2.5 to 2.3]; p = 0.050), caudate (-3.0 [-5.1 to -0.01] vs 0.48 [-1.9 to 3.1]; p = 0.029), insula (-2.4 [-4.8 to -0.6] vs -0.2 [-1.5 to 1.5]; p = 0.029), cingulate (-4.2 [-8.8 to -0.1] vs -0.6 [-1.8 to 3.0]; p = 0.017), and hippocampus (-2.7 [-6.0 to 0.5] vs -0.04 [-2.3 to 1.9]; p = 0.006) in comparison with placebo. However, there was no significant difference between nortriptyline and placebo in clinical outcomes and side effects.
  
  
  CONCLUSIONS
  Nortriptyline decreased the brain response to esophageal acid infusion more markedly than placebo, but without clinical significance.
authors.affiliation: Faculdade de Medicina, Universidade de Passo Fundo (UPF), Passo Fundo, Brazil; Programa de Pós-Graduação: Ciências em Gastroenterologia e Hepatologia, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: C M
authors.initials: CM
authors.lastname: Forcelini
authors.forename: J C
authors.initials: JC
authors.lastname: Tomiozzo
authors.forename: R
authors.initials: R
authors.lastname: Farré
authors.forename: L
authors.initials: L
authors.lastname: Van Oudenhove
authors.forename: S M
authors.initials: SM
authors.lastname: Callegari-Jacques
authors.forename: M
authors.initials: M
authors.lastname: Ribeiro
authors.forename: B H
authors.initials: BH
authors.lastname: Madalosso
authors.forename: F
authors.initials: F
authors.lastname: Fornari
mesh_terms: D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004947:Esophagus / Q000187:drug effects; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006356:Heartburn / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology / Q000523:psychology; D006801:Humans; D006851:Hydrochloric Acid / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D009661:Nortriptyline / Q000627:therapeutic use*; D058748:Pain Perception / Q000187:drug effects* / Q000502:physiology
chemical_list: D000929:Antidepressive Agents, Tricyclic; D009661:Nortriptyline; D006851:Hydrochloric Acid
keywords: NERD; esophageal acid infusion; functional MRI; heartburn; nortriptyline