Key Points

• Lifestyle modifications remain an integral component in the management of GERD.
• Histamine-2 receptor antagonists are well tolerated and most useful in patients with nocturnal reflux, when used as an adjunct to daytime proton pump inhibitor therapy.
• Promotility drugs have a limited role in the treatment of GERD and their use is often limited by their side effect profile.
• Proton pump inhibitors are the mainstay of both acute and chronic treatment regimes for GERD.
• Proton pump inhibitors are well tolerated, and further research is needed to evaluate their side effect profile, especially regarding renal disease and dementia.

The medical therapy for gastroesophageal reflux disease (GERD) is based on knowledge of the pathophysiology of the disease and a defined set of goals based on symptom presentation and severity of mucosal damage. The ideal medical therapy would augment lower esophageal sphincter (LES) pressure and/or reduce the number of transient LES relaxations, improve esophageal clearance of refluxed gastric contents, accelerate gastric emptying, augment mucosal resistance, and neutralize gastric acidity. Unfortunately, no single drug or drug class addresses all these potential pathogenic mechanisms. In fact, most therapies are directed only at acid control (antacids, H₂-receptor antagonists [H₂RAs], and proton pump inhibitors [PPIs]) yet result in excellent symptom relief and healing of the esophagitis. The expenditure in the United States alone for these antacid medications exceeds $10 billion per year.

The rationale for GERD therapy depends on a careful definition of specific aims. In patients without esophagitis, the therapeutic goals are simply to relieve the acid-related symptoms and to prevent frequent symptomatic relapses. In patients with esophagitis, the goals are to relieve symptoms and to heal the esophagitis while attempting to prevent further relapses and the development of complications (stricture, hemorrhage, or Barrett’s esophagus). These goals are set against a complex background: GERD is a chronic disease that waxes and wanes in intensity, and relapses are common.