In patients with proton-pump inhibitor (PPI) resistant reflux symptoms, ambulatory 24 h pH impedance monitoring can be used to assess whether a relationship exists between symptoms and reflux episodes. Using this technique it has been suggested that patients with typical reflux symptoms and a normal upper endoscopy should be subclassified as follows: normal endoscopy and abnormal distal acid esophageal exposure (patients with acid reflux); normal endoscopy, with normal distal acid esophageal exposure and a positive symptom association for either acid or nonacid reflux (patients with hypersensitive esophagus); and normal endoscopy, normal distal acid esophageal exposure and a negative symptom association for acid and nonacid reflux (patients with functional heartburn). Although for patients with a normal endoscopy and abnormal distal acid esophageal exposure more aggressive acid suppression can be recommended, managing patients with hypersensitive esophagus and functional heartburn remains a real challenge.Therefore, investigators have evaluated the role of tricyclic antidepressants or selective-serotonin reuptake inhibitors (SSRIs) in influencing esophageal perception. Imipramine has been shown to decrease pain perception in healthy male volunteers and improve symptoms of patients with chest pain and normal coronary angiograms. Trazodone improved symptoms in patients with esophageal contraction abnormalities, while administration of SSRIs lowered chemical and mechanical sensitivity and benefited patients with diffuse esophageal spasm. Furthermore, in a recent study conducted by our group, citalopram administered once daily for 6 months was effective in a select group of patients with hypersensitive esophagus, suggesting that there is a role for SSRIs in the treatment of this disorder.