tegaserod and Heartburn

While functional heartburn (FH) and functional dyspepsia (FD) are recognized clinical entities, symptoms often overlap across both disorders. Despite their frequency, little is known of the underlying pathophysiology of overlapping symptoms. This study evaluated the effect of the 5-HT(4) agonist, tegaserod, on visceral sensitivity and symptom improvement in patients with overlapping symptoms of FH and FD.. Patients with overlapping symptoms of FH and FD (ROME II) and mechanical hypersensitivity (Barostat examination) were randomized to tegaserod 6 mg bid or placebo for 2 weeks with treatment crossover after a 2-week washout period. Esophageal and gastric Barostat sensory tests were performed and patients rated their overall symptoms at study end. When carry-over was detected, data were presented for period 1 only. Safety was also assessed.. Sixty patients were screened of whom 30 were randomized and 25 completed. Mechanical hypersensitivity was reported by 83% of 47 patients completing esophageal and gastric baseline Barostat examinations. Tegaserod did not significantly alter balloon volume to pain (primary variable); however, pressure to gastric pain increased (p = 0.044 vs. placebo). The severity of heartburn, regurgitation, early fullness, and bloating was significantly lower following tegaserod vs. placebo treatment (p = 0.026, p = 0.021, p = 0.016, and p = 0.030). Overall symptom improvement was reported by 52% tegaserod vs. 32% placebo patients (p = 0.275), and treatment was well tolerated.. Results suggest that tegaserod may increase the gastric pain threshold and decrease the severity of individual symptoms in patients with overlapping FH and FD. However, these findings must be considered within the context of the study limitations, including the small number of subjects, potential for and presence of a carry-over effect, along with the impact of Barostat balloon use on the assessment of gastric function.

Topics: Cross-Over Studies; Double-Blind Method; Dyspepsia; Female; Gastrointestinal Agents; Heartburn; Humans; Indoles; Male; Pain Measurement; Placebos; Serotonin Receptor Agonists

To evaluate the potential role of tegaserod in the management of functional dyspepsia (FD) and gastroesophageal reflux disease (GERD) in patients with chronic constipation and to determine the possible efficacy of tegaserod on solid-phase gastric emptying and gastric hypersensitivity.. This was an exploratory open-label trial of tegaserod therapy for dyspepsia and reflux symptoms in patients with chronic constipation. The study cohort consisted of 90 patients randomized to three treatment groups for a study period of 4 weeks (tegaserod 6 mg, twice daily; esomeprazole 40 mg, once daily; tegaserod 6 mg, twice daily plus esomeprazole 40 mg, once daily). Twenty healthy volunteers provided control values. Clinical symptoms were evaluated by one of the investigators using a Gastrointestinal Symptom Rating Scale (GSRS). Solid-phase gastric emptying and colonic transit were measured by the radiopaque barium marker method, and the water load test (WLT) was used to evaluate gastric sensation and the function of proximal stomach. The proportions of patients with complete relief of epigastric pain /discomfort, epigastric fullness, early satiety and heartburn in the tegaserod group and the tegaserod plus esomeprazole group were compared with the esomeprazole group, respectively.. The mean global gastrointestinal (GI) scores of all three treatment groups reported using the GSRS showed the same trend, with decreasing scores over the 4-week study period indicating a reported decreasing severity of symptoms that was significantly different from baseline values. Patients in the tegaserod plus esomeprazole group reported the lowest global GI scores after 4 weeks, as expected. Solid-phase gastric emptying (GER) and colonic transit (CTT) increased significantly in the tegaserod 6 mg twice daily group compared with baseline. These parameters did not change in the esomeprazole group at week 4 compared with baseline. In terms of gastric sensation, in the tegaserod group, the proportions of patients with hypersensitivity of the first perception threshold did not change at week 2 or week 4 compared with baseline; however, in this group and in the tegaserod plus esomeprazole group, the proportions of patients with hypersensitivity of discomfort threshold decreased significantly at week 4 compared with baseline. In the esomeprazole group, there were no changes in the proportions of patients with hypersensitivity of the first perception threshold and discomfort threshold at week 2 or 4 compared with baseline. No severe adverse events were recorded, and the medications were in general well-tolerated.. Tegaserod is effective and safe at improving dyspepsia and reflux symptoms in patients with chronic constipation, and tegaserod plus esomeprazole is superior to esomeprazole alone in the resolution of epigastric pain/discomfort and heartburn.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Anti-Ulcer Agents; Chronic Disease; Cohort Studies; Constipation; Drug Therapy, Combination; Dyspepsia; Esomeprazole; Female; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Transit; Heartburn; Humans; Indoles; Male; Middle Aged; Serotonin 5-HT4 Receptor Agonists; Treatment Outcome

Tegaserod, a 5-HT4-receptor partial agonist, effectively treats irritable bowel syndrome with constipation. The role of tegaserod in functional disorders of the upper gastrointestinal (GI) tract is unclear. The aims of this study were to determine if tegaserod improves esophageal pain with mechanical and chemical stimuli, GI symptom profile, and global preference in patients with functional heartburn.. Patients with functional heartburn, as defined by Rome II criteria, underwent esophageal barostat and acid-infusion sensory tests. Mechanical hypersensitivity was required for entry. The baseline GI symptom profile was rated before treatment. Patients were blinded to treatment and randomly assigned to tegaserod 6 mg twice daily or placebo for 14 days, and crossed-over to the alternate treatment after 7 to 10 days of washout. Patients underwent sensory tests and rated GI symptoms after each treatment. Global treatment preference was completed at the end of the study.. Forty-two patients (15 men, 27 women; age, 20-68 y) completed the study. The predominant baseline symptoms in addition to heartburn included upper-abdominal pain, upper-abdominal discomfort, regurgitation, chest pain, early satiety, and postmeal bloating. Tegaserod significantly increased balloon pressure to pain (P = .04) and the mean (P = .002) and maximum wall tension at pain (P = .0004). Tegaserod did not alter pain with acid infusion. Tegaserod significantly decreased the frequency of occurrence of heartburn/acid reflux (P = .004), regurgitation (P = .048), and distress from regurgitation (P = .039). The global preference for tegaserod was 63.4% vs 12.2% for placebo.. Tegaserod improved the esophageal pain threshold to mechanical distention, and distressing upper-GI symptoms in patients with functional heartburn.

Topics: Adult; Aged; Compliance; Cross-Over Studies; Double-Blind Method; Esophagus; Female; Gastroesophageal Reflux; Gastrointestinal Agents; Heartburn; Humans; Indoles; Male; Middle Aged; Pain Threshold; Patient Satisfaction; Severity of Illness Index; Treatment Outcome