Irritable bowel syndrome (IBS), a chronic condition characterized by recurrent episodes of abdominal pain and alteration of bowel habit, is common and accounts for substantial morbidity and health care costs. The etiology remains unclear, but research has implicated a disorder of the type 3 serotonin (5-HT₃) receptors in the bowel wall. Camilleri and colleagues studied the effect of the 5-HT₃ receptor antagonist, alosetron, on symptoms of IBS.

They recruited female patients from 119 sites for the study. All patients had symptoms meeting the Rome IBS criteria for at least six months before the study and had normal colon anatomy on colonoscopy or equivalent testing. Exclusions included pregnancy, lactation, risk of pregnancy, unstable medical or psychiatric condition, abnormal hepatic or renal function, history of malignancy, and use of specified medications. During an initial two-week screening phase, the 647 women in the study completed daily symptom diaries, noting pain, discomfort and bowel habit. Patients were randomly assigned to treatment for 12 weeks with alosetron (1.0 mg twice daily) or an identical placebo. During the treatment phase and a four-week post-treatment phase, patients reported symptoms on a daily and weekly basis using an automated telephone system. In addition, symptoms and compliance were checked at monthly physician visits.

The patients randomized to alosetron therapy were similar to those given placebo in all important demographic and symptomatic variables. Relief of pain and discomfort was reported by 133 (41 percent) of the patients treated with alosetron and 94 (29 percent) of the patients receiving placebo. The proportion of patients achieving adequate weekly relief of discomfort rose to more than 50 percent within two weeks of beginning alosetron therapy and dropped precipitously to less than 30 percent within one week of discontinuing therapy. The benefit was most marked in patients with diarrhea-dominant forms of IBS. Patients receiving alosetron also reported significant reduction in urgency and stool frequency compared with placebo-treated patients. Stool consistency became firmer in patients receiving alosetron. More than 70 percent of patients treated with alosetron and 65 percent of those receiving placebo reported adverse effects. Constipation was reported by 30 percent of alosetron patients compared with 3 percent of those receiving placebo, and 33 patients in the alosetron group withdrew from the study because of this symptom. Patients in both treatment groups reported a wide variety of other conditions, but no significant differences were found between the groups.

The authors conclude that alosetron significantly improved pain, discomfort, urgency and stool frequency, and increased stool consistency in women with IBS. The greatest drawback to the medication was the occurrence of constipation in about 30 percent of patients. The benefits of alosetron therapy appear to be limited to periods of active treatment. Symptoms recurred promptly on discontinuation of therapy.

editor's note: Alosetron is FDA-labeled for use in women with IBS whose predominant bowel symptom is diarrhea. The FDA based approval on several studies involving more than 1,200 patients. In addition to the constipation noted in the above studies, a concern was raised about the development of acute colitis in four patients. Physicians are urged to ensure that the drug is prescribed only for women with confirmed diarrhea-predominant IBS and to monitor patients for constipation and acute colitis. Despite these concerns, this medication offers the hope of relief to many of the 15 percent of adults who have IBS.—a.d.w.