The authors of this study carried out a double-blind, randomised controlled trial comparing step-up versus step-down therapy to improve understanding of the best treatment for initial management of dyspepsia in primary care. The study was based in the Netherlands and patients aged 18 years or older consulting with their Family doctor (GP) for new onset dyspepsia were eligible for enrolment. Overall, 312 GPs agreed to participate in the study and 664 patients were randomly allocated to receive stepwise treatment with antacid (aluminium oxide 200 mg/magnesium hydroxide 400 mg), H2-receptor antagonist (ranitidine 150 mg bd), and proton pump inhibitor (pantoprazole 40 mg od) (step-up; n=341), or these drugs in the reverse order (step-down; n=323). Each step lasted 4 weeks and treatment only continued with the next step if symptoms persisted or relapsed within 4 weeks. Primary outcome measures used in the study were symptom relief and cost-effectiveness of initial management at 6 months. Analysis was carried out on an intention to treat (ITT) basis; the ITT population consisted of all patients with data for the primary outcome at 6 months. When evaluating results, 332 patients in the step-up, and 313 in the step-down group reached an endpoint with sufficient data for evaluation; the main reason for dropout was loss to follow-up. The results found (from source):

- Treatment success after 6 months was achieved in 238 (72%) patients in the step-up group and 219 (70%) patients in the step-down group (odds ratio 0•92, 95% CI 0•7—1•3).
- The average medical costs were lower for patients in the step-up group than for those in the step-down group (€228 vs €245; p=0•0008), which was mainly because of costs of medication.
- Combined (direct medical and indirect) mean costs were lower for patients in the step-up group than for patients in the step-down group (€426 vs €460; p=0•02).
- One or more adverse drug events were reported by 94 (28%) patients in the step-up and 93 (29%) patients in the step-down group.
- All were minor events, including (other) dyspeptic symptoms, diarrhoea, constipation, and bad/dry taste.

The authors note limitations to their study, including the point that in clinical practice, a GP would probably not pursue a step-down approach when a patient is not responding to initial proton pump inhibitors. They conclude that although treatment success with either step-up or step-down treatment is similar, the step-up strategy is more cost effective at 6 months for initial treatment of patients with new onset dyspeptic symptoms in primary care. They also note, “Nonetheless, patients on initial empirical treatment with proton pump inhibitor (step-down) show an earlier response, especially in the small subgroup with predominant reflux symptoms. Furthermore, the difference in cost-effectiveness declines when calculations are based on prices of generic acid-suppressive medication. These data provide important information for management protocols of patients with new onset dyspepsia in general practice.”

A related editorial discusses the results of this study and the author writes, “For costs, it is debatable whether the economic analysis showed that the step-up approach was more cost effective. The 8% (€426 vs €460) difference in cost was entirely due to differences in drug prices, and is probably not clinically meaningful. But more importantly the differences disappeared when costing was done with generic prices for all drugs.” He adds that although the findings of the study are interesting, they are not likely to change current management and makes suggestions on how patients presenting in primary care could be managed.