Gastric pH and Therapeutic Responses to Exsomeprazole in Patients With Functional Dyspepsia: Potential Clinical Implications

Background: Therapy for functional dyspepsia remains a challenge. This study aimed to evaluate esomeprazole (E) versus placebo (P) regarding (1) the effectiveness in providing relief of abdominal pain or discomfort during 16 weeks of therapy in patients with functional dyspepsia having moderate or severe symptoms; (2) the effects on gastric acid suppression and (3) the relationship between symptom relief and gastric pH. Methods: Enrolled patients were randomized to E (n = 38) or P (n = 35) in a double-blind, placebo-controlled trial. Outcomes were measured at four 4-week intervals. Drug dose titrated at each visit, based on relief of abdominal symptoms. The 24-hour gastric pH was monitored at baseline, 4 and 8 weeks. Results: After 4 weeks, 71% of E patients (40 mg) reported satisfactory symptom relief versus 34% of P patients (P < 0.001). When the dose for nonresponders (NR) was titrated to 40 mg twice daily, the E relief rate increased to 82% versus 56% in P group (P < 0.05). During the next 4 weeks, with dose decreased by half in responders, E response rate declined to 69% versus 48% in P group (P < 0.10). When the dose was increased for NR during the last 4 weeks, E rate increased to 83% versus 57% in P group (P < 0.05). At 4 and 8 weeks for E responders and NR, patients' pH >4 value increased significantly compared to baseline. Conclusions: (1) Though E 40 mg once daily is superior to P, some patients benefit from 40 mg twice daily; (2) E, 40 mg once daily, profoundly inhibits gastric acid secretion; (3) intragastric pH monitoring before and after therapy may help address the relationship between symptomatic relief and gastric acid secretion and (4) some patients respond to monitored titrated placebo therapy.