RESUMO
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. KEY 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 & INFERENCES: Nortriptyline decreased the brain response to esophageal acid infusion more markedly than placebo, but without clinical significance.