Clinical Question: Is a dosage of 40 mg of omeprazole per day more effective than a dosage of 20 mg per day for primary care patients with dyspepsia?

Setting: Outpatient (primary care)

Study Design: Randomized controlled trial (double-blinded)

Allocation: Concealed

Synopsis: A common strategy in primary care for patients with dyspepsia and no alarm symptoms is to prescribe a proton pump inhibitor. This pragmatic study took place in a Danish primary care research network with 103 participating physicians and 829 patients. Adults presenting with dyspepsia (thought to be acid-related) and no alarm symptoms were randomized to treatment with omeprazole in a dosage of 40 mg per day, omeprazole in a dosage of 20 mg per day, or placebo. Alarm symptoms were defined as rectal bleeding or hematemesis, unintended weight loss, vomiting, dysphagia, jaundice, or other signs of serious disease. Groups were similar at baseline, with a mean age of 50 years; 58 percent were women. Allocation was concealed and outcomes were assessed blindly, with analysis by intention to treat.

Patients were treated for two weeks, and then medications were discontinued. During the remaining year of observation, in which 92 percent of patients participated, the author tracked the time until symptom relapse and the use of health care resources. The most common symptoms in both groups were epigastric pain, regurgitation, heartburn, bloating, and pain at night. Symptoms were rated as moderate by 63 percent of patients and severe by 15 percent.

At two weeks, sufficient relief was reported more often by subjects in the 40-mg and 20-mg omeprazole groups than in the placebo group (71.0, 69.6, and 43.0 percent, respectively), as was complete relief (66.4, 63.0, and 34.9 percent, respectively). The number needed to treat was between three and four for both outcomes. Results were similar for Helicobacter pylori-positive and H. pylori-negative patients. Most patients in all three groups had a symptom relapse during the year following their initial treatment.

Bottom Line: Omeprazole in a dosage of 20 mg per day is highly effective for the treatment of acid-related dyspepsia. There is no advantage to higher dosages, and relapse following the initial two-week treatment period is common. (Level of Evidence: 1b)