The mainstay of pharmacological therapy for GERD is gastric acid suppression with proton pump inhibitors (PPIs), which are superior to histamine-2 receptor antagonists for healing erosive esophagitis and achieving symptomatic relief. However, up to one-third of patients may not respond to PPI therapy, creating the need for alternative treatments. Potential approaches include transient lower esophageal sphincter relaxation inhibitors, augmentation esophageal defense mechanisms by improving esophageal clearance or enhancing epithelial repair, and modulation of sensory pathways responsible for GERD symptoms. This review discusses the effectiveness of acid suppression and the data on alternative pharmacological approaches for the treatment of GERD.
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