Korean J Gastroenterol.  2015 Aug;66(2):70-74. 10.4166/kjg.2015.66.2.70.

Underlying Mechanisms and Management of Refractory Gastroesophageal Reflux Disease

  • 1Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea. kjleemd@hotmail.com


The prevalence of gastroesophageal reflux disease (GERD) in South Korea has increased over the past 10 years. Patients with erosive reflux disease (ERD) shows better response to proton pump inhibitors (PPIs) than those with non-erosive reflux disease (NERD). NERD is a heterogeneous condition, showing pathological gastroesophageal reflux or esophageal hypersensitivity to reflux contents. NERD patients with pathological gastroesophageal reflux or hypersensitivity to acid may respond to PPIs. However, many patients with esophageal hypersensitivity to nonacid or functional heartburn do not respond to PPIs. Therefore, careful history and investigations are required when managing patients with refractory GERD who show poor response to conventional dose PPIs. Combined pH-impedance studies and a PPI diagnostic trial are recommended to reveal underlying mechanisms of refractory symptoms. For those with ongoing reflux-related symptoms, split dose administration, change to long-acting PPIs or PPIs less influenced by CYP2C19 genotypes, increasing dose of PPIs, and the addition of alginate preparations, prokinetics, selective serotonin reuptake inhibitors, or tricyclic antidepressants can be considered. Pain modulators, selective serotonin reuptake inhibitors, or tricyclic antidepressants are more likely to be effective for those with reflux-unrelated symptoms. Surgery or endoscopic per oral fundoplication may be effective in selected patients.


Gastroesophageal reflux; Hypersensitivity; Heartburn; Proton pump inhibitors

MeSH Terms

Anti-Ulcer Agents/therapeutic use
Cytochrome P-450 CYP2C19/genetics
Esophageal pH Monitoring
Gastroesophageal Reflux/drug therapy/metabolism/*pathology
Proton Pump Inhibitors/therapeutic use
Anti-Ulcer Agents
Cytochrome P-450 CYP2C19
Proton Pump Inhibitors
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