Medical Treatments of GERD

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.

Key points

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The mainstay of pharmacologic therapy for GERD is gastric acid suppression with PPIs, with no major differences among the available PPIs for healing of erosive esophagitis and achieving symptom control.
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PPIs are superior to H2RAs for healing of erosive esophagitis and achieving symptom control.
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TLESR inhibitors have been shown to reduce reflux episodes and symptoms, but at the present time only the GABA-B agonist baclofen is available for this purpose because development of other compounds was stopped due to low efficacy or side effects.
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Esophageal defense mechanisms can be augmented by improving esophageal clearance with prokinetics but this approach is limited by low efficacy and side effects; alternatively, epithelial repair can be enhanced with novel agents such as rebamipide, but data on this form of therapy are very limited.
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Targeting esophageal sensation as a means to treat GERD symptoms may be possible by esophageal mucosal nociceptor blockade or through modulation of afferent signals and their cortical interpretation using compounds such as TRPV1 nociceptor antagonists or antidepressants, or by cognitive techniques like hypnotherapy; as with other interventions, data are limited.