Irritable bowel syndrome (IBS) is the most common functional gastrointestinal (GI) disorder with worldwide prevalence rates ranging from 8-23%. Other functional GI disorders include functional dyspepsia, functional diarrhea and chronic constipation. IBS commonly affects all age, gender, and sociodemographic groups. It is seen more commonly in women (60-75%) and has been estimated to affect 14-24% of women and 5-19% of men. IBS is characterized by abdominal pain and/or discomfort and alterations in bowel habits, e.g. diarrhea and/or constipation. It has been estimated that about one-third of IBS patients have mainly constipation, i.e. constipation-predominant IBS.

Two published reviews of treatment trials in IBS have concluded that there is limited effectiveness of medications. Drug therapy is best used in IBS patients with symptoms refractory to physician counseling and dietary manipulations. First line treatment is usually aimed at treating the most bothersome symptom because of the lack of effective treatment for the overall improvement of multiple symptoms.

Treatment of constipation-predominant IBS includes increasing fiber intake and fluids, discontinuing any medications that cause constipation, and taking laxatives, stool softeners or enemas as needed. Many of the medications to treat constipation may not relieve or even worsen bloating, gas and abdominal pain or discomfort. Up to this time, there has been no available medication that has been shown to improve abdominal discomfort and bowel function better than placebo (inactive pill). Recently, there have been new medications in development which have been shown to be beneficial for the treatment of IBS.

One of these medications is Tegaserod which is a selective partial agonist that acts on the serotonin type-4 (5HT4) receptors in the intestines. These receptors are located on the nerves of the intestine, and when activated can increase motor function, thereby increasing the movement of food, gas and stool through the bowels. The exact mechanism of its effect on decreasing abdominal pain is not known. Over 5000 individuals (healthy individuals and IBS patients) have been treated with Tegaserod in research studies. Tegaserod has been shown to accelerate stomach emptying and transit through the small and large intestine in healthy individuals and those with constipation-predominant IBS. In three large clinical trials for the treatment of constipation-predominant IBS, Tegaserod has been shown to relieve overall symptoms of IBS including abdominal pain/discomfort and bowel movements compared to placebo treatment (see Figure). Tegaserod was found to be beneficial in female patients with IBS but not in male patients. However, the number of males recruited into these studies were much smaller than the females, and therefore the effectiveness of this medication for males with IBS may not have been sufficiently determined and may require further studies.

There is available safety data concerning Tegaserod. Almost 1900 patients with IBS have been treated with Tegaserod for >85 days and more than 300 patients for >330 days. Approximately 12% of IBS patients treated with Tegaserod developed transient diarrhea compared to 5% of patients who received placebo. There were 4 cases of cholecystectomy (removal of the gall bladder) in the Tegaserod group and one in the placebo group. The incidence of cholecystectomy in the Tegaserod group is consistent with that in the general IBS population, and there was no statistical difference in number of cholecystectomy between those patients on drug, and those on placebo. Thus, even though no causal association has been found between Tegaserod and gallstone disease, the FDA is requesting that cholecystectomies be further studied prior to approving the medication.

In summary, Tegaserod is a new medication which has been shown to be effective in the treatment of abdominal pain/discomfort and constipation in female patients with IBS. As a consequence of its heightened safety concerns, Tegaserod was not approved by the FDA for the treatment of IBS at this point (please see Director’s page). There are planned or ongoing Tegaserod studies for treatment of other disorders such as gastroesophageal reflux disease, functional dyspepsia and chronic constipation. Hopefully future studies will determine Tegaserod to be an effective and safe medication to treat a whole range of functional GI disorders. At the present time, Tegaserod remains under evaluation by the FDA.

References:
Mueller-Lissner S, Fumagalli I, Bardham KD, et al. Tegaserod, a 5HT4 receptor partial agonist relieves key symptoms of irritable bowel syndrome. Gastroenterology 2000;118:A175 (abstract).

Camilleri M. Review article:Tegaserod. Aliment Pharmacol Ther 2001;15:277-289.
Farthing MJG. Irritable bowel syndrome: new pharmaceutical approaches to treatment. Balliere’s Clinical Gastroenterology 1999;13:461-471.