Treatment with medication

Histamine receptor antagonists (H2 blockers)

In the past, for GERD symptoms and mild esophagitis (inflammation of the esophagus due to acid and bile backwashing into the esophagus), the mainstay of therapy has been a class of drugs known as histamine receptor antagonists (H2 blockers). These drugs work by blocking the histamine receptors on the acid producing cells in the stomach, blocking one of the mechanisms by which acid is secreted. These drugs decrease acid production, but since other mechanisms can stimulate gastric cells to secrete acid, the production of acid continues. Still, for many patients who have GERD, these drugs result in much improvement in their symptoms, especially when combined with lifestyle changes that limit reflux of stomach contents into the esophagus.

The H2 blockers have been in use since the 1970's and have no known serious side-effects. Many can now be purchased over-the-counter. Some examples of these drugs are cimetidine (Tagamet®), famotidine (Pepcid®), nizatidine (Axid®), and ranitadine (Zantac®). If a patient's symptoms are relieved with these medications, they are much less expensive than the more potent acid inhibitors, a class of drugs known as proton pump inhibitors. However about 50% of patients with erosive esophagitis will not get relief of their symptoms or healing of their esophagus on the usual doses of these drugs. Higher doses of these drugs may be used with some success, but the expense of the drugs goes up with the dose. Some of the H2 blockers interact with other medications that a patient might be taking. Anyone taking prescription medication should always ask their doctor about any possible drug interactions, including interactions with any over-the-counter drugs that are taken.

Proton pump inhibitors (PPIs)

For many patients who have GERD, especially those with severe GERD and complications - including Barrett's esophagus, use of a class of drugs known as proton pump inhibitors (PPIs) is indicated. These drugs have been in use for more than a decade and have an excellent safety profile. Examples of these drugs are esomeprazole (Nexium®), lansoprazole (Prevacid®), omeprazole (Prilosec® and Zegerid), pantoprazole (Protonix®) and rabeprazole (Aciphex®). Prilosec can now be purchased over-the-counter without a prescription (Prilosec OTC). The PPIs disable the acid pump of the acid producing stomach cell, such that it cannot pump the acid out of the cell. Therefore, the majority of acid secretion is stopped. These medications also lessen bile reflux into the esophagus. Although proton pump inhibitors stop acid secretion, they do not cause problems with digestion of food. This may be due to the fact that bile and pancreatic enzymes are largely responsible for the digestion of food. As acid inhibits bacterial growth in the upper GI tract, there are greater numbers of bacteria in the upper GI tract of patients on these drugs but this does not appear to cause problems.

PPIs are more effective in healing erosive esophagitis as compared to the H2 blockers. They are much more effective in controlling reflux symptoms in patients who have severe GERD, including patients who have Barrett's esophagus. They also have the advantage of once a day dosing as compared to two to four times per day dosing of the H2 blockers. They are, however, more expensive when compared to standard doses of H2 blockers.

In some patients who have severe GERD, including Barrett's esophagus, the standard dose of a PPI does not adequately control symptoms or heal injury to the lining of the esophagus. In many of these instances, breakthrough heartburn occurs at night. Some formal pH studies of acid reflux in patients who are on these medications have shown that up to 78% of symptomatic patients still have significant reflux of acid at night. Either taking these drugs in the morning on an empty stomach, higher doses of the drugs, or twice a day dosing may be necessary to better control acid secretion and heartburn symptoms.

In the past, the main concern with long-term use of PPIs was the possible development of a rare stomach tumor called a carcinoid that occurred in rats given high doses of these drugs. During early use of these drugs, physicians placed patients on a temporary (a short six to eight week) course to heal esophagitis, stopped the drug, and prescribed H2 blockers as maintenance therapy. However, in most cases of severe GERD, including Barrett's esophagus, patients' symptoms and esophagitis recurred after PPIs were discontinued. Fortunately, after more than a decade and a half of clinical use, these drugs have an excellent safety profile and in the mid-1990's, the cancer warning was removed by the US Food and Drug Administration (FDA). Recently, observational studies have raised concerns about the possibility of an increased risk of community acquired pneumonia and Clostridium difficile infections (causes colon inflammation and diarrhea) in patients on long-term PPI therapy. Additional studies are needed.  However, because serious side-effects are rare and the complications or adverse side-effects of GERD can be serious, PPIs are considered safe for long-term use in patients who have GERD. 

For patients who have Barrett's esophagus, it is unknown whether PPIs prevent cancer. Despite the wide-spread use of PPIs during the past 15 years, Barrett's cancers have continued to increase in the US and in Western Europe at about the same rate as before PPI therapy. There are some recent studies that report that dysplasia (pre-cancerous changes in the Barrett's tissue as seen by the pathologist under the microscope) is decreased in patients who use PPIs, but little evidence that these medications prevent cancer. Because many patients who have dysplasia, especially low-grade dysplasia , do not not develop cancer during long-term follow-up, prevention of cancer is the important goal. At the present time, PPIs are prescribed to Barrett's patients for treatment of GERD symptoms.

Pro-kinetic agents

Pro-kinetic agents, another class of drugs, increase the ability of the stomach to empty its contents, including acid and bile, into the intestine. In the past, before wide-spread use of PPIs, these drugs were used together with H2 blockers to relieve GERD symptoms in patients who did not get relief of their symptoms on H2 blockers alone. Since the most widely used pro-kinetic drug, cisapride, has been withdrawn from the US drug market due to cardiac (heart) side-effects, and PPIs have been safe and effective in controlling GERD long-term, prokinetic agents are not used much today for the treatment of GERD.

Endoscopic therapies for GERD

Endoscopic therapies are the newest treatment for GERD and became available for clinical use in 2000. These therapies all attempt to tighten or thicken the area near the gastroesophageal junction (where the esophagus joins the top part of the stomach) to keep acid and bile out of the esophagus and into the stomach. The FDA (The Food and Drug Administration) approved therapies are: EndoCinch® which involves endoscopic suturing (sewing) of the gastroesophageal junction; the Stretta™ procedure which involves delivery of radiofrequency energy to the gastroesophageal junction and ENTERYX® which involves injection of a substance into the gastroesophageal junction. Recently, the manufacturer of the ENTERYX® procedure kit voluntarily recalled the ENTERYX® kit due to problems with some injections going through the wall of the esophagus into the chest cavity. Some serious complications have occurred, even death. The recall is indefinite and at the present time, physicians have been advised to immediately stop using ENTERYX®

Multiple other endoscopic GERD therapies are also under investigation. They are all performed through an upper endoscope and the experience for the patient is similar to having an upper endoscopy. So far these therapies have been reported to be relatively safe with few serious complications, although serious complications have been reported, including, rarely, patient deaths.

Overall, it is reported that 6 months after one of these therapies, 58% to 85% of patients no longer need their acid controlling medication (one study reported that 100% are off their medications after the Stretta procedure). Most patients say that their heartburn is improved. Most studies reported that esophageal acid exposure (as measured by the esophageal pH probe) is not reduced in most patients. Some studies reported that esophagitis was not improved in patients who had esophagitis prior to the procedure.

Although large numbers of patients have undergone endoscopic therapies, there are very few formal publications of how well patients do. Furthermore, most of the published studies have been open-label, meaning that all patients in these studies have undergone the procedure and both physician and patient know that a procedure has been performed. Only one study of 64 patients using the Stretta™ procedure was double-blinded and included a sham procedure arm. This means that half the patients underwent upper endoscopy but did NOT have the Stretta procedure and half underwent upper endoscopy with the Stretta procedure. The patients did not know whether their procedure had been the real or sham (fake) procedure. Then the patients were all followed off their acid-controlling medication by another doctor who did not know which patients had received the real therapy and which the sham or fake therapy. Surprisingly, at 6 months, there was no difference between the treatment and sham group in the number of patients off their medication, 58% and 57%, respectively. The esophageal pH (acid) measurements did not change in either group. Of course this is one small study but it raises the question of how much of the early positive effects of these treatments are influenced by positive thinking on the part of the patient (placebo response) and their physician as compared to a real improvement in GERD.

Another problem with the studies that have been performed in patients so far, is that they have not included patients with severe esophagitis (severe inflammation of the esophagus from acid and bile), patients who still have heartburn on their acid-controlling therapy, Barrett's esophagus, patients who have medium or large hiatal hernias, or obese patients. Therefore, there is virtually no information concerning how well these therapies work in these patients.

At the present time, patients who desire to try one of these therapies should still consider it experimental. Some have recommended that these procedures only be performed at medical centers with very experienced staff and as part of a good study. Most experts agree that although these and other future endoscopic therapies hold promise as alternative treatments for GERD, it is still too early to answer some important questions: Who will benefit from these therapies? When should they be performed in patients? Will there be long-term problems in some patients caused by these procedures? Many experts agree that better clinical trials are needed comparing these new endoscopic therapies to conventional medical and surgical therapies for GERD before these questions can be answered.