Evaluation and Treatment of Patients with Persistent Reflux Symptoms Despite Proton Pump Inhibitor Treatment

Despite the exceptional efficacy of proton pump inhibitors (PPIs) in healing reflux esophagitis complicating gastroesophageal reflux disease (GERD), up to 40% of patients who take PPIs for GERD complain of persistent GERD symptoms. There is no clear consensus on the type, dosing, and duration of PPI therapy required to establish a diagnosis of PPI-refractory GERD symptoms, but most authorities do not consider patients "PPI-refractory" unless they have been on double-dose PPIs. This article discusses the mechanisms that might underlie heartburn that does not respond PPIs and an approach to the management of patients with PPI-refractory GERD symptoms.