Approximately one third or more of the adults in the industrialized world have recurrent dyspeptic symptoms, although most do not have peptic ulcer disease or gastro-esophageal reflux. The term “nonulcer dyspepsia” is often used to describe this condition. The pathogenesis of nonulcer dyspepsia is unknown, but patients often are treated with antacids or histamine H2 blockers with mixed results. More recent data have implicated Helicobacter pylori as a contributing factor in patients with dyspeptic symptoms, similar to its established role in the pathogenesis of peptic ulcer disease. Blum and colleagues evaluated the effectiveness of a variety of antimicrobial agents that are commonly used to eradicate H. pylori in improving the symptoms associated with nonulcer dyspepsia.
Patients were eligible for this randomized double-blind study if they had had dyspeptic symptoms for at least six months but had no history of peptic ulcer disease or gastro-esophageal reflux. Other inclusion criteria consisted of normal baseline endoscopic findings and positive results on biopsy, rapid urease testing or urea breath testing for H. pylori. During a one-week run-in period in which no treatment was given, patients were asked to rate and record their symptoms at bedtime, using a scale in which a score of zero indicated no symptoms and a score of 6 indicated very severe symptoms. Only patients who reported moderate to very severe symptoms were enrolled in the study. Exclusion criteria included a history of serious disease, use of H2-antagonists, prostaglandins or prokinetic agents within seven days of the study, or use of proton-pump inhibitors, antibiotics or bismuth compounds one month before the study began.
Patients were randomized to receive a one-week course of either 20 mg of omeprazole twice daily, 1,000 mg of amoxicillin and 500 mg of clarithromycin twice daily, or 20 mg of omeprazole twice daily, as well as placebo antibiotics. Patients were examined one week after treatment, then again one month later, followed by quarterly visits for one year. Upper endoscopy and biopsy, along with urea breath testing for H. pylori, were repeated at months 3 and 12. Abnormal histologic findings on gastric biopsy, a positive urea breath test, or both constituted responses positive for H. pylori. In addition to these studies, patient quality of life was assessed four times: at randomization, one week after treatment, and once every six months until the study was complete. Ratings were quantified with two survey instruments in which the severity of symptoms was assessed.
A total of 348 patients were enrolled, and 245 completed the study. Mean patient age was 47 years, approximately two thirds of the patients were women and 88 percent were white. Treatment success was the same in both groups, as was the percentage of patients with minimal or no symptoms at each follow-up visit. Mean symptom ratings were also similar at follow-up visits—1.73 and 1.74, respectively. Overall, patients' quality of life improved but not significantly, and two thirds of the patients reported an improvement in symptoms after treatment. H. pylori was eradicated in 79 percent of the patients who received multiple antibiotics, compared with only 3 percent of the patients in the omeprazole group. Symptom relief was reported in 31 percent of cured patients who received multiple medications, compared with 26 percent of patients who remained H. pylori-positive. No serious adverse events were reported in either group; however, 63 percent of the patients who received antibiotics reported having diarrhea.
The authors conclude that although the eradication of H. pylori with multiple antibiotics has been shown to prevent or cure peptic ulcer disease, it does not relieve symptoms in patients with nonulcer dyspepsia any better than treatment with omeprazole alone.