DDW: Chronic Constipation Treatments: A Review of the Evidence

WASHINGTON, May 23 -- Anorectal biofeedback, probiotics, and the type-2 chloride channel activator lubiprostone all seem to be effective therapeutic options in chronic constipation. PEG 3550 is only for short-term use.

So said panelists who presented the latest evidence-based approaches for treating chronic constipation at an industry-sponsored symposium held here in conjunction with Digestive Disease Week.

They also reviewed the status of tegaserod and other 5-HT agonists.

Looking first at biofeedback, Nicholas J. Talley, M.D., Ph.D., of the Mayo Clinic in Rochester, Minn., noted that a randomized controlled trial published online this year by the journal Diseases of the Colon and Rectum confirmed the efficacy of the technique in chronic constipation.

In the study, biofeedback patients had significantly more unassisted bowel movements after three months than those on placebo, Dr. Talley said. About 65% of patients said they were satisfied with the treatment, compared with less than 40% of the placebo group (P=0.017).

He also referred to a study published last year in Gastroenterology that showed that biofeedback compared favorably to the osmotive laxative PEG 3550. Nearly 80% of the biofeedback-treated patients reported major improvement in symptoms, compared with less than 30% of the patients treated with PEG 3550 (P<0.01), Dr. Talley said.

However, noted Brooks D. Cash, M.D., of the Uniformed Services University of the Health Sciences, in Bethesda, Md., the laxative PEG 3550 is indicated only for short-term (no more than two weeks) treatment of constipation, not for long-term treatment. For that indication, the drug is supported by a series of well-designed studies, and it has a "grade A" recommendation from the American College of Gastroenterology task force, he said.

The drug became available in a non-prescription, over-the-counter form in March of this year, Dr. Cash said, noting that the non-prescription formulation should be used for no more than seven days.

Dr. Cash also reviewed recent events surrounding 5-HT agonists. Tegaserod was withdrawn from the market on March 30, 2007, because of reports of serious cardiovascular adverse events, including myocardial infarction, he said. The 5-HT agonist pergolide was withdrawn at about the same time because of similar concerns, he added.

The 5-HT agonist alosetron was suspended from the market in November 2000 because of reports of ischemic colitis and severe constipation. However, Dr. Cash said, the drug was re-introduced with a risk management program in April of 2002. It's indicated for women with severe irritable bowel syndrome.

In contrast, probiotics are getting increasing attention among gastroenterologists, Dr. Cash said. In a recent parallel, double-blind study of 72 healthy adult volunteers, the daily ingestion of fermented milk containing Bifidobacterium animalis decreased total colonic transit time by 21% and sigmoid transit time by 39%, he noted. The study suggests that regular intake of probiotics may help achieve a more regular intestinal transit, he said.

The type-2 chloride channel activator lubiprostone, approved by the FDA in January 2006 for the treatment of chronic idiopathic constipation in adults, is also proving to be an effective option, said Eugene Chang, M.D., of the University of Chicago, Ill.

In a two-week, randomized, placebo-controlled trial published last year, lubiprostone demonstrated slowed gastric emptying but accelerated small intestinal and colonic transit times in healthy subjects, Dr. Chang said.

Chloride and bicarbonate secretion are important to normal physical functioning of the gastrointestinal tract because they provide an aqueous phase for digestion and absorption of food, hydrate mucus, and purge intestinal pathogens and noxious agents, Dr. Chang said.

Studies published in the American Journal of Gastroenterology in 2005 found that, compared with placebo, lubiprostone increased the number of spontaneous bowel movements after four weeks and was associated with the onset of a first spontaneous bowel movement in 61% of treated patients compared with 31% of placebo-treated patients (P<0.0001), added Dr. Cash.

Lubiprostone has been shown to be well-tolerated with short-term (four weeks) and long-term (six to 12 months) use, he said. The most common adverse events associated with this medication included nausea, diarrhea, and headache, he said, adding that nausea can be decreased if the drug is taken with food.

Arnold Wald, M.D., of the University of Wisconsin at Madison, reviewed the diagnostic tests most commonly used identify constipation. These include colonoscopy, colon transit studies, the balloon expulsion test, and anorectal manometry, he said.

While the clinical evidence supporting the latter three was good, Dr. Wald noted, the evidence that colonoscopy is useful for diagnosing constipation is poor. It simply has a "low yield" in detecting chronic constipation, he said.

Chronic constipation is a multi-symptom disorder that leads to an estimated 2.5 million office visits and between 30,000 and 90,000 hospitalizations per year, the presenters noted.