Dyspepsia responsive to acid suppression therapy: reflux disease or duodenal hypersensitivity?

Abstract

dMtwehw : Dr. A.J.P.M. SmouC Department of Gwstroen&rology, University Medical Canter, P.O. Box 85500, GA, UtrechC, Thw Netherlends. Fax: +37 -3U-2505533. Acid suppression therapy (antacids, HZ-receptor antagonists and proton pump inhibitors) is frequently used in the management of functional dyspepsia. Aim of the present investigation was to evaluate: 1) whether there is sufficient evidence for the efficacy of gastric secretion inhibitors in functional dyspepsia, and 2) at which site(s) of the gastric intestinal tract do acid inhibitors accomplish their beneficial effects. The observation that gastric acid secretion is normal in patients with functional dyspepsia does not provide much rationale for the use of acid suppression therapy in this syndrome. In addition, randomised placebocontrolled trials on Hz-receptor antagonists in functional dyspepsia have produced conflicting results. Recently, more convincing evidence for the efficacy of inhibition of acid secretion has been obtained in studies using proton pump inhibitors. It is important to realise that the definition of functional dyspepsia has undergone a significant change with the introduction of the so-called Rome II criteria. Whereas before the introduction of these criteria functional dyspepsia was categorized into ulcer-like, dysmotility-like and reflux-like, the latter category was deleted in the Rome II criteria. It was felt that in the presence of significant reflux symptoms (heartburn and acid regurgitation), the patient’s condition should be labelled as gastrooesophageal reflux disease, rather than as functional dyspepsia. However, most of the studies investigating the effect of gastric acid inhibition on dyspeptic symptoms used inclusion criteria dating from the pre-Rome II era. As a consequence, all of these studies included a subset of patients with significant reflux symptoms and there is no incontrovertible evidence that Hz-receptor antagonists or proton pump inhibitors have a beneficial effect in patients with functional dyspepsia without any reflux symptom. For instance, in the “Bond” and “Opera” studies in which the effect of omeprazole on dyspeptic symptoms was investigated, 143 of the 1248 patients included were classified as having reflux-like dyspepsia. In the total group of patients, complete symptom relief was obtained in 28.2, 36.0, and 38.2% of the patients using placebo, omeprazole 10 mg and omeprazole 20 mg daily, respectively. After stratification of the patients into dysmotility-like, ulcer-like and reflux-like dyspepsia, it was found that the most pronounced effect occurred in patients with reflux-like dyspepsia. In this subgroup, complete symptom relief was obtained in 23,45 and 53% of the patients with placebo, omeprazole 10 mg and omeprazole 20 mg, respectively. In the ulcer-like subgroup the effect was far less pronounced and, in the dysmotility-like group, no beneficial effect of omeprazole vs placebo was found. Observations like these indicate that the beneficial effect of gastric acid inhibiting drugs in functional dyspepsia is largely based on their effect in a subgroup with gastro-oe-