The updated recommendations state that recent research supports testing for and treatment of H. pylori rather than empiric acid suppression.

In its revised Guidelines for the Management of Dyspepsia, the American College of Gastroenterology (ACG) defines this frequently encountered entity in broad terms: chronic upper abdominal pain or discomfort (i.e., a subjective negative feeling, which may include fullness or early satiety), with the exclusion of heartburn, which is presumed to be gastroesophageal reflux disease (GERD) until proven otherwise.

“Chronic dyspepsia occurs daily or weekly for months or longer,” notes Nicholas J. Talley, MD, professor of medicine at Mayo Clinic College of Medicine in Rochester, Minn., and lead author of the guidelines. “Most people have it recurrently for years.”

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Indications for endoscopy

As in the ACG’s previous (1998) guidelines, cancer risk is a key factor in decision-making about prompt esophagogastroduodenoscopy (EGD) (see Figure 1). Since this risk rises with age, the Guidelines recommend the procedure for patients older than 55, particularly those with new onset of symptoms. The threshold is subject to debate. Some European guidelines recommend age 65 as the cutoff, and some published earlier by other U.S. organizations have suggested 45 as the threshold for new-onset symptoms. “The vast majority of people with dyspepsia won’t have cancer,” says Dr. Talley. “We chose 55 as the threshold because curable cancer is so rare in younger people.”

For patients at any age, indications for prompt EGD (which may detect ulcer and GERD as well as malignancy) include alarm symptoms like bleeding, anorexia, unexplained weight loss, and progressive difficulty in swallowing, as well as family history of upper GI cancer and personal history of peptic ulcer. “If you don’t take a thorough history, these red flags may be overlooked,” cautions Dr. Talley. “Ask about them.”

Other options — H. pylori

For dyspepsia that does not require prompt EGD, the Guidelines endorse two options: testing for and treatment of Helicobacter pylori infection or a trial of antisecretory therapy. “The Guidelines offer the choice but come down on the side of addressing H. pylori first,” Dr. Talley says. “It’s not how dyspepsia has been managed [traditionally] in primary care, where acid suppression is generally emphasized.”

The 1998 Guidelines made a similar recommendation, “but there wasn’t as much evidence to back it up,” observes Dr. Talley. The intervening years have seen several double-blind randomized controlled trials and meta-analyses that validate the approach.

The choice between test-and-treat and a trial of acid suppression might well take the practice setting into account, the Guidelines suggest. Investigating and treating H. pylori is preferable when the prevalence of infection reaches 10%, while below that, empiric acid-suppression therapy is likely to be more cost-effective. The rates of H. pylori are well above 10% in African-American, Latino, and first-generation immigrant populations, and in general, acid suppression will likely be indicated only in practices largely limited to upper-middle-class patients.

The choice of H. pylori test, the Guidelines say, is “critical.” They endorse the urea breath test and stool antigen test as accurate and noninvasive. Both are preferable to serologic tests and are widely available.

When findings are positive, the treatment of choice is combined proton pump inhibitor (PPI) therapy (at double the standard daily dose), amoxicillin (1 g b.i.d.), and clarithromycin (500 mg b.i.d.) for 7-10 days. Metronidazole (400 mg b.i.d.) may replace amoxicillin for patients sensitive to penicillin. An alternative strategy combines bismuth, metronidazole, and tetracycline with a PPI for 14 days.

The Guidelines endorse H. pylori eradication even for patients with nonulcer dyspepsia. This represents a departure from earlier recommendations and reflects more recent data, Dr. Talley notes. Besides ameliorating symptoms, treating infection will reduce the risk of future ulcers and perhaps gastric cancer as well.

Concerns have arisen that eradicating H. pylori may increase the risk of GERD, but it appears the issue has clinical relevance only with the small subset of patients who are predisposed to GERD and in whom acid secretion is impaired by severe gastritis.

On the other hand, a stronger case may be made for eradication of H. pylori in all patients requiring long-term acid-suppression therapy.

Empiric antisecretory therapy

When acid suppression is chosen as initial treatment, PPIs should be considered the agents of choice. Several meta-analyses suggest a better symptomatic outcome with these than with H2-receptor antagonists or alginate.

If the patient’s symptoms fail to resolve after two to four weeks of acid suppression, the Guidelines term it “reasonable” to step up therapy, although the support comes primarily in the form of expert opinion rather than data. In practical terms, this will probably mean increasing dosage, perhaps to the standard dose twice daily, Dr. Talley says.

Stepping up to other agents isn’t viable because of the dearth of effective alternatives. Extremely limited data support cisapride, which is no longer available in the United States, and there have been no trials of other prokinetic agents for uninvestigated dyspepsia. When successful, acid suppression should be suspended after four to eight weeks, followed by a similar course of treatment if symptoms recur. Although there are no data to validate a long-term PPI regimen for dyspepsia, this is “worth considering in some patients,” the Guidelines say.

A patient who fails to improve with empiric antisecretory therapy should be tested and treated for H. pylori, and vice versa. Those who respond to neither should be considered candidates for EGD.

Further investigation

The management of endoscopy-negative (i.e., functional) dyspepsia that fails to respond to antisecretory and H. pylori therapy presents a clinical challenge. No drugs have been shown to be of value, and data to support the use of simethicone, herbal preparations, and psychological and behavioral interventions are extremely limited. The efficacy of dietary therapy has not been established, although such modifications as increasing the frequency of smaller meals and avoiding high-fat foods appear to be of value to some patients and might merit a trial.

A diagnostic reappraisal may be worthwhile, the Guidelines suggest. “It is at this point that a primary-care clinician might consider consulting with a GI specialist,” Dr. Talley advises. Less common conditions like celiac disease or inflammatory disorders are unlikely to be responsible, but they may be worthy of investigation.

When dyspepsia is judged to be functional, the clinician can play a useful role in reassurance. “It’s important to give the condition a label, to communicate that ‘there’s nothing to worry about,’ without dismissing it as ‘nothing wrong with you,’ ” Dr. Talley says.

The ACG’s Guidelines for the Management of Dyspepsia were published in the American Journal of Gastroenterology (2005;100:2324-2337). They are available online free of charge at: (accessed January 10, 2007).

Mr. Sherman is a medical writer in New York City.