Proton pump inhibitor-refractory gastroesophageal reflux disease: challenges and solutions

Joseph Mermelstein,1 Alanna Chait Mermelstein,2 Maxwell M Chait3 1Gasteroenterology and Nutrition Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 3Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA Abstract: A significant percentage of patients with gastroesophageal reflux disease (GERD) will not respond to proton pump inhibitor (PPI) therapy. The causes of PPI-refractory GERD are numerous and diverse, and include adherence, persistent acid, functional disorders, nonacid reflux, and PPI bioavailability. The evaluation should start with a symptom assessment and may progress to imaging, endoscopy, and monitoring of esophageal pH, impedance, and bilirubin. There are a variety of pharmacologic and procedural interventions that should be selected based on the underlying mechanism of PPI failure. Pharmacologic treatments can include antacids, prokinetics, alginates, bile acid binders, reflux inhibitors, and antidepressants. Procedural options include laparoscopic fundoplication and LINX as well as endoscopic procedures, such as transoral incisionless fundoplication and Stretta. Several alternative and complementary treatments of possible benefit also exist. Keywords: PPI failure, resistant GERD, acid-related diseases, gastroesophageal reflux disease, acid reflux, proton pump inhibitor