Review: Causes of, and therapeutic approaches for, proton pump inhibitor-resistant gastroesophageal reflux disease in Asia

Proton pump inhibitors (PPIs) are the most widely used drugs for treatment of gastroesophageal reflux disease. However, approximately 20% of patients with reflux esophagitis and 40% of those with nonerosive reflux diseases complain of troublesome symptoms, even during treatment with PPIs. In patients with reflux esophagitis, dose escalation and co-administration with a histamine H 2 -receptor antagonist are potential approaches, since the major cause of PPI resistance is incomplete suppression of gastric acid secretion. On the other hand, for patients with nonerosive reflux disease, switching from PPIs to pain modulators is often necessary for improvement of symptoms, since 25% of patients with nonerosive reflux disease have symptoms not caused by gastroesophageal acid reflux. Therapeutic approaches for PPI-resistant patients with reflux esophagitis and nonerosive reflux diseases are considered according to pathogenesis