Treatment:

Deciding which treatment is best for patients with symptoms of dyspepsia or peptic ulcer disease depends on a number of factors. An endoscopy to identify any ulcers and test for H. pylori probably gives the best guidance for treatment. However, dyspepsia is such a common reason for a doctor's visit that many people are treated initially based on their symptoms and blood or breath H. pylori test results. This approach (called test and treat) is considered an appropriate option for most patients. Patients who do not have any evidence of bleeding or other alarm symptoms, and who are over age 55 should have an endoscopy performed first.

Approach to Patients Who Are Not Taking NSAIDs

If an endoscopy is performed soon after the patient first visits a doctor for symptoms, treatment is based on the results of the endoscopy:

• If an ulcer is seen and the patient is infected with H. pylori, treatment for the infection is started, followed by 4 to 8 weeks of treatment with a proton pump inhibitor. Most patients will improve with this treatment.
• If an ulcer is seen but H. pylori is not present, patients are usually treated with proton pump inhibitors for 8 weeks.
• If no ulcer is seen and the patient is not infected with H. pylori, the first treatment attempt will usually be with proton pump inhibitors. These patients do not need antibiotics to treat H. pylori. Other possible causes of their symptoms should also be considered.

As mentioned above, most patients who do not have risk factors for additional complications are treated without first having an endoscopy. The decision of which treatment to use is based on the types of symptoms patients have, and on the results of their H. pylori blood or breath tests.

Patients who are not infected with H. pylori are given a diagnosis of functional (non-ulcer) dyspepsia. These patients are most commonly given 4 to 8 weeks of a proton pump inhibitor. If this dose is not effective, occasionally doubling the dose will relieve symptoms. If there is still no symptom relief, patients may have an endoscopy. However, it is unlikely that an ulcer is present. In this group of patients, symptoms may not fully improve.

• Patients who test positive for H. pylori infection will receive an antibiotic regimen that eradicates H. pylori. Those who have an ulcer are more likely to respond to such treatment. Unfortunately, because an endoscopy is not performed before treatment in the test and treat strategy, patients who do not have an ulcer are also treated with antibiotics. Even if they are positive for H. pylori, these patients are less likely to have a full response.
• When the test and treat approach is used, those who do not respond to treatment, or whose symptoms return relatively quickly, will often need an upper endoscopy.

There is considerable debate about whether to test for H. pylori and treat infected patients who have dyspepsia but no clear evidence of ulcers.

• Increased risk for gastroesophageal reflux disease (GERD). A number of studies suggest that H. pylori in the intestinal tract protects against GERD, which in severe cases can be a risk factor for cancer of the esophagus. Eliminating H. pylori may also have other adverse effects.
• Overuse of antibiotics. There is concern that using antibiotics when there is no clear evidence of ulcers will lead to unnecessary antibiotic prescriptions and increase the risk for side effects. Overuse may also contribute to a growing public health problem -- the emergence of antibiotic-resistant bacteria.
• Because the number of people infected with H. pylori is declining in the United States, and therefore the number of people being helped by this approach is declining, the test and treat approach is becoming expensive.

Antibiotic and Combination Drug Regimens for the Treatment of H. pylori

Reported cure rates for H. pylori range from 70 - 90% after antibiotic treatment. The standard treatment regimen uses two antibiotics and a PPI:

• PPIs. These drugs include omeprazole (Prilosec), lansoprazole (Prevacid), esomeprazole (Nexium), and rabeprazole (Aciphex). PPIs are important for all types of peptic ulcers, and are a critical partner in antibiotic regimens. They reduce acidity in the intestinal tract, and increase the ability of antibiotics to destroy H. pylori.
• Antibiotics. The standard antibiotics are clarithromycin (Biaxin) and amoxicillin. Some doctors substitute the antibiotic metronidazole (Flagyl) for either clarithromycin or amoxicillin.

Patients typically take this combination treatment for at least 14 days. Many studies, however, suggest that a 7-day treatment may work just as well.

Follow-Up. Follow-up testing for the bacteria should be done no sooner than 4 weeks after therapy is completed. Test results before that time may not be accurate.

In most cases, drug treatment relieves ulcer symptoms. However, symptom relief does not always indicate treatment success, just as persistent dyspepsia does not necessarily mean that treatment has failed. Heartburn and other GERD symptoms can get worse and require acid-suppressing medication.

Failure. Treatment fails in about 15% of patients, typically when they do not follow their prescribed treatment. Compliance with standard antibiotic regimens may be poor for the following reasons:

• The triple-drug regimens are complicated and require many pills. Helicide and other two-drug combination pills may help offset this problem.
• About 30% of patients experience side effects from the H. pylori regimen. Gastrointestinal problems are very common, and severe diarrhea can occur.

Treatment may also fail if the patients harbor strains of H. pylori that are resistant to the antibiotics. When this happens, different drugs are tried.

Reinfection after Successful Treatment. Studies in developed countries indicate that once the bacteria are eliminated, recurrence rates are below 1% per year. Reinfection with the bacteria is possible, however, in areas where the incidence of H. pylori is very high and sanitary conditions are poor. In such regions, reinfection rates are 6 - 15%.

Treatment of NSAID-induced ulcers

If patients are diagnosed with NSAID-caused ulcers or bleeding, they should:

• Get tested for H. pylori and, if they are infected, take antibiotics.
• Possibly use a PPI. Studies suggest that these medications lower the risk for NSAID-caused ulcers, although they do not completely prevent them.

Healing Existing Ulcers. A number of drugs are used to treat NSAID-caused ulcers. PPIs -- omeprazole (Prilosec), lansoprazole (Prevacid), or esomeprazole (Nexium) -- are used most often. Other drugs that may be useful include H2 blockers, such as famotidine (Pepcid AC), cimetidine (Tagamet), and ranitidine (Zantac). Sucralfate is another drug used to heal ulcers and reduce the stomach upset caused by NSAIDs.

People with chronic pain may try a number of other medications to minimize the risk of ulcers associated with NSAIDs.

• COX-2 Inhibitors (Coxibs). Coxibs block an inflammation-promoting enzyme called COX-2. This drug class was initially thought to work as well as NSAIDs and cause less gastrointestinal distress. Although the use of COX-2 inhibitors may decrease uncomplicated ulcers, they do not seem to reduce the incidence of more serious gastrointestinal events. Also, following numerous reports of cardiovascular events with COX-2 inhibitors, only Celecoxib (Celebrex) is still available. (Regular NSAIDs also increase the risk of cardiovascular events.)
• Arthrotec. Arthrotec is a combination of misoprostol and the NSAID diclofenac. It may reduce the risk for gastrointestinal bleeding. This drug can cause miscarriage at any stage of pregnancy and therefore should not be used during pregnancy.
• Acetaminophen.Acetaminophen (Tylenol, Anacin-3) is the most common alternative to NSAIDs. It is inexpensive and generally safe. Acetaminophen poses far less of a gastrointestinal risk than NSAIDs. Until recently, the recommended maximum daily dose was 4 grams (4,000 mg). An FDA advisory panel in June 2009 recommended lowering the maximum daily dose. Patients who take high doses of acetaminophen for long periods of time are also at risk for liver damage, particularly if they drink alcohol. Acetaminophen also may pose a small risk for serious kidney complications in people with preexisting kidney disease, although it remains the drug of choice for patients with impaired kidney function.
• Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties, but is not as addictive. However, dependence and abuse have been reported. Tramadol can cause nausea, but it does not cause severe gastrointestinal problems as NSAIDs can. Some patients experience severe itching. A combination of tramadol and acetaminophen (Ultracet) provides more rapid pain relief than tramadol alone, and more durable relief than acetaminophen alone. Side effects are the same as for each of these medications.
• If patients need to continue taking NSAIDs, they should use the lowest possible dose.

The American College of Gastroenterology has recently made recommendations about the prevention of ulcers in patients using NSAIDs. A patient's physician must consider whether they are at high, moderate, or low risk for gastrointestinal and cardiovascular problems. Depending on your risk factors, your doctor may recommend any NSAID, naproxen only, a COX-2 inhibitor, one of these, or none of the three. Some patients take either a proton pump inhibitor or misoprostol along with their NSAID. Before starting a patient on long-term NSAID therapy, a physician should consider testing for H. pylori.