If lifestyle modifications do not resolve symptoms, medical therapy is usually the appropriate next step for the treatment of GERD. For many patients, a daily regimen of medical therapy controls heartburn and reflux symptoms. Sufferers with more severe symptoms may only experience partial symptom control with medical therapy.
Acid suppression is the main function of medical therapy for GERD. There are three types of medications commonly used to treat GERD: antacids, h2-receptors (H2RAs) and proton pump inhibitors (PPIs). Some drugs are available as over the counter (OTC) medications and others are available by prescription only. PPIs are the most commonly used drug to treat GERD symptoms and heal esophagitis.
Medication can control symptoms such as heartburn by reducing the acidity of reflux. Because medication does not change the amount or quantity of reflux, it often does not resolve other symptoms such as difficulty swallowing, frequent regurgitation or chronic respiratory problems. Further, if the medication regimen is stopped, reflux-related symptoms typically recur, creating a dependence on these drugs. Over time, the medications can also lose effectiveness, requiring higher doses or more powerful drugs.
Types of Medical Therapy
Antacids directly neutralize gastric acid and provide rapid but temporary relief. Accordingly, antacids are usually consumed in frequent doses as necessary. Most antacids, such as Alka-Seltzer, Maalox, Mylanta and Rolaids, are available over the counter.
H2 receptor antagonists (H2RAs) reduce the amount of acid produced in the stomach by inhibiting the release of histamine, the principal stimulus for acid secretion in the stomach. Clinical trials evaluating histamine for the treatment of GERD demonstrated only modest benefit over placebo. A review of multiple studies demonstrated a 50-75% rate of symptom control and tissue healing when using H2RAs. Further, several studies have revealed pharmacologic tolerance to H2RAs as early as two weeks after therapy initiation.
Proton Pump Inhibitors (PPIs) are the most effective medical therapy to treat GERD. PPIs block the mechanism that produces stomach acid. This lowers the acidity of the digestive juices, the acidity of associated reflux, and thus reduces reflux symptoms. Examples of different prescription PPIs include omeprazole (Prilosec, Zegerid), lansoprazole (Prevacid), pantoprazole (Protonix), rabeprazole (Aciphex), and esomeprazole (Nexium). Prilosec and Prevacid, among others, are also available in over-the-counter strength.
An analysis of 43 randomized trials demonstrated average tissue healing rates of 84% of patients with esophagitis. While effective at reducing the acidity of digestive juices in the upper GI tract, PPIs do not address anatomic deficiencies which often are the root cause of abnormal reflux.
Long-Term PPI Use
PPIs are generally approved by the FDA for 8 weeks of use for the healing of esophagitis. While safe and effective for most patients, studies evaluating long-term PPI use demonstrate a series of undesirable side effects including:
- Increased risk of hip-fracture and osteoporosis with long-term PPI use (>1 year). One study concluded that use of PPIs for >7 years is associated with the significantly increased risk of an osteoporosis-related fracture. Read the FDA Drug Safety Communication: Possible increased risk of fractures of the hip, wrist, and spine with the use of PPIs.
- Vitamin B12 deficiency: In older adults, vitamin B12 plays an important role in DNA synthesis and neurologic function.
- Drug interactions with Plavix (clopidogrel): A study found that concurrent use of clopidogrel and PPIs was associated with an increased risk (27%) of reinfarction.[5,6]
- Increased risk of pneumonia: A review and meta-analysis showed that the overall risk of community- and hospital-acquired pneumonia was higher among people using PPIs and H2RAs.
- Increased risk of fundic gland polyps: Long-term PPI use (>1 year) is associated with up to a 4x increase in the risk of fundic gland polyps. Though these polyps have always been regarded as benign lesions, there have been case reports of fundic gland polyps harboring severe dysplasia or gastric adenocarcinoma.
- Reduced gallbladder motility: Short-term PPI therapy reduces gallbladder motility in healthy subjects. Chronic PPI therapy may pose a risk for long-term gallbladder dysfunction and biliary complications.
- Development of hypomagnesemia: Long-term PPI use can induce depletion of total body magnesium stores and present with severe complications of hypomagnesemia. Read the FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of PPIs.
- Increased risk of bacterial gastroenteritis: Regardless of treatment duration, patients currently on PPIs had a 2.9x increased risk of acute bacterial gastroenteritis. Doubling the PPI dose increased the risk to 5x versus patients not on PPIs.
- Increased risk of small intestinal bacterial overgrowth (SIBO): PPIs suppress the gastric acid barrier which can alter the gastrointestinal bacterial population. The prevalence of SIBO, a clinical condition characterized by different degrees of malabsorption, increased after 1 year of treatment with PPIs.
- May mask the symptoms of Barrett’s Esophagus: One study found that PPI dosages beyond those required to heal GERD symptoms and endoscopic signs of reflux esophagitis may be detrimental.
If you are concerned about the possible adverse effects of long-term PPI usage, consult your physician about your options.
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 Targownik LE, et al. Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ 2008; 179(4): 319-26.
 Dharmarajan TS, et al. Do Acid-Lowering Agents Affect Vitamin B12 Status in Older Adults. JAMDA 2008; 9: 162-167.
 Ho PM, et al. Risk of Adverse Outcomes Associated with Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Acute Coronary Syndrome. JAMA 2009; 301(9): 937-944.
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 Eom CS, et al. Use of acid-suppressive drugs and risk of pneumonia: systematic review and meta-analysis. CMAJ 2010.
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 Cahan MA, et al. Proton pump inhibitors reduce gallbladder function. Surg Endosc 2006; 20: 1364-1367.
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 Lombardo L, et al. Increased Incidence of Small Intestinal Bacterial Overgrowth During Proton Pump Inhibitor Therapy. Clin Gastroenterology and Hepatology 2010; 8:504-508.
 Feagins LA, et al. Acid Has Antiproliferative Effects in Nonneoplastic Barrett’s Epithelial Cells. Am J Gastroenterol 2007; 102:10-20.