New horizons in the medical treatment of gastro-oesophageal reflux disease.

Proton pump inhibitors (PPIs) have revolutionized the treatment of gastro-oesophageal reflux disease (GERD). However, nearly 30% of all GERD patients are still symptomatic despite standard dose PPI treatment. Consequently, better treatment options are needed particularly in nonerosive reflux disease (NERD), which provides the largest number of patients that fail PPI. Transient lower esophageal relaxation (TLESR) is the underlying mechanism for most acid reflux events. Therefore, reducing the rate of TLESRs pharmacologically is an attractive therapeutic approach. Some compounds that were evaluated include: anticholinergics, opioids, cholecystokinin antagonists, nitric oxide antagonists, somatostatin, and GABA-B agonists. Currently, the GABA-B agonist baclofen generated the most promising results. Although data regarding GERD is lacking, visceral pain modulation, either pharmacologically or via mind-body interventions, was found to be efficacious in a variety of functional bowel disorders, including functional chest pain of presumed esophageal origin. Finally, intensive research is currently undergoing to develop newer acid suppressive agents. The acid pump inhibitors are reversible competitive inhibitors of the proton pump. These agents are potent suppressors of gastric acid secretion, and their effect is unrelated to food intake. Moreover, they demonstrate a faster onset of action and a predictable dose response effect as compared to the current PPIs. Although some of the preliminary clinical data is promising, thus far none of these agents is commercially available.