New Remedies for a Frustrating Illness. But Do They Work?

* By MARY DUENWALD * Published: December 7, 2004 The women in the television commercial pull up their shirts to display the words "abdominal pain," "bloating" or "constipation" scrawled in black marker on their abdomens. Some viewers probably respond by reaching for the remote control. But others may be prompted to ask their doctors whether Zelnorm, the Novartis drug in the advertisement, can actually ease the symptoms of irritable bowel syndrome. The answer, experts say, is, "It depends." Zelnorm is one of two drugs - the other is Lotronex from GlaxoSmithKline - approved by the Food and Drug Administration for the treatment of irritable bowel syndrome, or I.B.S., a disorder that is estimated to affect about 45 million Americans. Twice as many women as men suffer from it. Their search for relief is often frustrating, because it has no single cause and no cure, and doctors are sometimes dismissive of patients' complaints. The symptoms vary. About a third of sufferers have constipation, another third have diarrhea and the rest alternate between the two. Bloating after meals and lower abdominal pain are also common, as are severe fatigue, sleep difficulties, low interest in sex, hopelessness and tension, a recent study in The Archives of Internal Medicine says. Zelnorm, the trade name for tegaserod, has been shown to be effective in treating the syndrome in large clinical trials. It works just for people who suffer constipation. A chief side effect is diarrhea. "Because I.B.S. is so heterogeneous, an agent that may treat one symptom can potentially exacerbate another one," said Dr. Robert S. Fisher of the Temple School of Medicine in Philadelphia. Zelnorm is specifically approved for women, but also prescribed for men. Most studies of its safety and effectiveness have been conducted mainly on women. Doctors say that people with irritable bowel syndrome typically require both medications and changes in their routines, the exact regimen depending on a patient's symptoms and their severity. The syndrome was once thought to be simply a visceral response to stress, because doctors could find no biological explanation. As a result, many patients felt that their doctors gave their problem short shrift or, worse, implied it was all in their heads. "People with I.B.S. are sensitized to doctors' thinking they're crazy," Dr. Fisher said. Recent studies indicate that the syndrome may arise from problems in the working of the colon and in the connection between the brain and the colon.

"The brain and bowels are wired with a series of nerves," Dr. Brennan M. R. Spiegel, a gastroenterologist at the University of California, Los Angeles, said. "If you have I.B.S., you're wired up in a slightly different way, and that can cause diarrhea, constipation or pain." Studies have shown that people with the syndrome are more sensitive to colon pain and that their brains process the pain abnormally. Stress and anxiety can lead to symptoms or worsen them, but those factors do not cause the disorder, experts say. Abnormal functioning of serotonin in the colon also appears to promote irritable bowel syndrome. In the brain, serotonin is thought to influence mood. But in the colon, where 95 percent of the body's serotonin is found, it helps produce the normal contractions of peristalsis. Zelnorm stimulates serotonin receptors, enhancing peristalsis and relieving constipation. Alosetron, sold as Lotronex, works in an opposite manner, blocking serotonin receptors and slowing peristalsis. Lotronex is for patients whose primary symptom is diarrhea. But the F.D.A. restricts its use because in some patients it has caused extreme diarrhea or restricted blood supply to the colon, problems that have in some cases been fatal. Patients given alosetron have to sign releases stating that they understand its risks. Bacteria may also play a role. Dr. Henry C. Lin of the University of Southern California and others have found that in many patients bacteria that normally reside just in the large intestine move into the small intestine, where they interfere with digestion and generate excess gas, producing symptoms. Because bloating and pain often occur to cut back on foods that seem to set caffeine, alcohol, fats and milk. For constipation, doctors recommend fiber after meals, patients are advised off the worst symptoms, including mild cases of the syndrome with laxatives like Metamucil or FiberCon.

Loperamide - Imodium or Kaopectate, for example - can relieve diarrhea. Low doses of old-fashioned antidepressants like amitriptyline and desipramine have been shown to relieve abdominal pain. Newer antidepressants like Prozac do not seem to be as effective. More helpful, studies suggest, are techniques like cognitive therapy and hypnosis, which Dr. Spiegel says may help patients "get some control over their own symptoms."