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.
Assuntos
Antidepressivos Tricíclicos/uso terapêutico , Encéfalo/efeitos dos fármacos , Refluxo Gastroesofágico/tratamento farmacológico , Azia/tratamento farmacológico , Nortriptilina/uso terapêutico , Percepção da Dor/efeitos dos fármacos , Adulto , Encéfalo/fisiologia , Mapeamento Encefálico , Estudos Cross-Over , Método Duplo-Cego , Esôfago/efeitos dos fármacos , Feminino , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/fisiopatologia , Azia/etiologia , Azia/fisiopatologia , Azia/psicologia , Humanos , Ácido Clorídrico/farmacologia , Imageamento por Ressonância Magnética , Masculino , Percepção da Dor/fisiologiaRESUMO
BACKGROUND: The association between nutcracker oesophagus, gastro-oesophageal reflux and their symptoms is controversial. AIM: To evaluate the association of nutcracker oesophagus with chest pain and dysphagia controlling for gastro-oesophageal reflux. METHODS: From a database of 935 consecutive patients investigated with oesophageal manometry and pH-metry, we selected all patients with nutcracker oesophagus including diffuse and segmental patterns. Patients with normal oesophageal peristalsis served as controls. Symptoms assessment, manometry testing and 24h oesophageal pH monitoring off acid-suppressive medications were performed following a standardized protocol. The associations between nutcracker oesophagus and symptoms were assessed by logistic regression analysis. RESULTS: Nutcracker oesophagus was found in 60 patients (6.4%), of which 30 had diffuse nutcracker oesophagus and 30 had segmental nutcracker oesophagus. The control group was composed by 656 patients with normal oesophageal peristalsis. Diffuse nutcracker oesophagus was associated with chest pain (odds ratio 4.3; 95% CI 1.9-9.9; P<0.0001) and dysphagia (odds ratio 5.3; 95% CI 2.3-12.2; P<0.0001), whereas segmental nutcracker oesophagus was associated with chest pain (odds ratio 2.8; 95% CI 1.1-6.9; P=0.026), controlling for total oesophageal acid exposure, age, sex and lower oesophageal sphincter (LOS) pressure. CONCLUSION: This study suggests that both diffuse and segmental nutcracker oesophagus should be regarded as meaningful abnormalities and not mere manometric curiosities.