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 have evidence of bleeding or other alarm symptoms, or who are over age 50 should have an endoscopy performed first.
Treatment 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 (PPI). Most patients will improve with this treatment.
- If an ulcer is seen but H. pylori are not present, patients are usually treated with PPIs 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 PPIs. These patients do not need antibiotics to treat H. pylori. Other possible causes of their symptoms should also be considered.
Most patients who do not have risk factors for complications are treated without first having an endoscopy. The type of treatment is decided based on a patient's symptoms, and on the results of 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 PPI. If this dose is not effective, doubling the dose will occasionally 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 antibiotics to treat H. pylori. Those who have an ulcer are more likely to respond to antibiotic treatment. Because an endoscopy is not done before treatment in the test and treat strategy, patients who do not have an ulcer are also treated with antibiotics. Even if they test positive for H. pylori, patients who do not have an actual ulcer are less likely to have a full response to antibiotics.
- When the test and treat approach is used, patients who do not respond to treatment, or whose symptoms return relatively quickly will often need an 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, in part because H. pylori in the intestinal tract protects against GERD and possibly other conditions. There is also concern about the overuse of antibiotics, which can contribute to the emergence of antibiotic-resistant bacteria.
Antibiotic and Combination Drug Regimens for the Treatment of H. pylori
The established treatment for H. pylori infection is a combination of antibiotics plus a PPI. Current standard therapy includes three medicines, two antibiotics plus a PPI, called triple therapy. Quadruple therapy refers to four medicines, in various combinations. For any of these regimens, the medicines may be taken in stages, one after another. This is called sequential therapy. Medicines may also be taken at the same time. This is called concomitant therapy. Due to the growing resistance to certain antibiotics and areas where standard therapy cure rates are somewhat low, various combinations and timing of medications are now under study.
Reported cure rates for H. pylori range from 70 to 90% after triple therapy regimen (antibiotics plus PPI) treatment. Eradication rates are higher for when bismuth subsalicylate (Pepto-Bismol) is added to the regimen. The standard treatment regimen uses two antibiotics and a PPI:
- PPIs. These drugs include omeprazole (Prilosec), lansoprazole (Prevacid), esomeprazole (Nexium), pantoprazole (Protonix) 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 others) and amoxicillin (Amoxil and others). The antibiotic metronidazole (Flagyl, generic) may be used instead of amoxicillin in patients who are allergic to penicillin. Tetracycline is sometimes recommended in place of a standard antibiotic.
- Bismuth may be recommended along with antibiotics (see below).
Patients typically take combination treatment for at least 14 days. A 7-day regimen is another option, but some research suggests that 14 days of therapy with antibiotics and PPIs is more effective at eradicating H. pylori. When quadruple therapy (without bismuth) is taken at the same time (concomitant therapy), cure rates appear similar to when the medicines are taken sequentially.
Combination products such as Helidac Therapy, Prevpac and Pylera are available.
Follow-Up. Follow-up testing to check that the bacteria have been eliminated 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 10 to 20% of patients, typically when they do not follow their prescribed treatment. Compliance with standard antibiotic regimens may be poor for the following reasons:
- Three drug regimens are complicated, expensive, and require many pills. Simpler regimens are being developed.
- About 30% of patients experience side effects from the antibiotic regimen. Gastrointestinal problems are very common, and severe diarrhea can occur. Probiotic bacteria and yeasts can help reduce these adverse effects.
Treatment may also fail if patients harbor strains of H. pylori that are resistant to antibiotics. When this happens, different drugs are tried.
Re-infection after Successful Treatment. Studies in developed countries indicate that once the bacteria are eliminated, recurrence rates are below 1% per year. Re-infection 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, re-infection rates are 6 to 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 may work as well as NSAIDs and cause less gastrointestinal distress. However, following numerous reports of cardiovascular events with COX-2 inhibitors, only Celecoxib (Celebrex) is still available, and it must be used with great care. (Regular NSAIDs also increase the risk of cardiovascular events.)
Naproxen. Naproxen (Aleve, Naprosyn) reduces hormones that lead to pain and inflammation in the body. Naproxen plus misoprostol or a PPI may be recommended in patients who are on low-dose aspirin therapy, or who are at risk of ulcer and have high cardiovascular disease risk
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. However, patients who take high doses of acetaminophen for long periods of time are at risk for liver damage, particularly if they drink alcohol. Acetaminophen also may pose a small risk for serious kidney complications in people who already have kidney disease, although it remains the drug of choice for patients with impaired kidney function. The current recommended maximum daily dose of acetaminophen is 4 grams (4,000 mg). Patients should be aware that over 600 drug products contain acetaminophen. The FDA has called for manufacturers to limit the amount of acetaminophen to 325 mg per dose, tablet, or capsule in all combination products.
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. A combination of tramadol and acetaminophen (Ultracet) provides more rapid pain relief than tramadol alone, and more long-term relief than acetaminophen alone. Side effects of tramadol include dependence and abuse, nausea, and itching, but tramadol does not cause the same severe gastrointestinal problems as NSAIDs.
- If patients need to continue taking NSAIDs, they should use the lowest possible dose. NSAIDs may also be combined with misoprostol or PPI for those at moderate risk of ulcer.
The American College of Gastroenterology has made recommendations about the prevention of ulcers in patients using NSAIDs. Doctors should consider whether their patients are at high, moderate, or low risk for gastrointestinal and cardiovascular problems. Depending on a patient's risk factors, the doctor may recommend any NSAID, naproxen only, a COX-2 inhibitor, one of these, or none of the three.
Some patients take either a PPI or misoprostol along with their NSAID. Before starting a patient on long-term NSAID therapy, the physician should consider testing for H. pylori.
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