# FDA: Irritable Bowel Syndrome: A Poorly Understood Disorder



## Jeffrey Roberts (Apr 15, 1987)

http://www.fda.gov/fdac/features/2001/401_ibs.html U.S. Food and Drug AdministrationFDA Consumer magazineJuly-August 2001Table of Contents Irritable Bowel Syndrome: A Poorly Understood DisorderBy Carol LewisIt's the most common gastrointestinal disorder seen by doctors. Abdominal pain, cramps, gas, bloating, diarrhea and constipation are among the symptoms. For years, many thought it was a psychological condition, rather than a physical one. But the discomfort and inconvenience that result from the gut-wrenching pain of irritable bowel syndrome (IBS) are very real. "It feels like you're giving birth over and over again," says Hope Marcus of Miami, Fla.Indeed, people with IBS can't stay out of the bathroom or their stomachs feel like they're tied in knots. Their bowel movements are either frequent and runny or sporadic and unusually hard. Mike Hoffman of West Palm Beach, Fla., says his intestines feel like they're constantly twisting and untwisting, "as though they're being wrung out like a dishrag." Jeffrey Roberts of Hallandale, Fla., says the sudden recurring knife-like pain "doubles you over," while others claim it brings you to your knees. Some liken the pain to a charley horse, but in the gut--pain that is horrendous and then intensifies."And don't picture a diarrhea attack happening in the privacy of your own clean bathroom," says Cynthia Huschle of Tolland, Conn. "Picture it in the bathroom at work, the store, the movie theater, the park, the baseball stadium, or the port-o-potty at the fair."Cynthia M. Huschle, 36, was a teacher forced to give up classroom teaching. The severity of her condition prevents her from instructing a group of children all day. She bought a van that would not only afford her privacy in her "time of need," but also more space. Huschle doesn't mind admitting she keeps an emergency bag in her vehicle that contains essentials such as antidiarrheal tablets and clean underwear, in anticipation of sudden attacks. "The van and the emergency bag give me the ability to get out into the world." IBS is a disorder of the intestine that shows no sign of disease that can be seen or measured. But doctors know that the intestine isn't functioning normally. Second only to the common cold in causing days missed from work, IBS may affect up to 20 percent of Americans--some 54 million people. IBS in women is not inherently different than in men, according to doctors at the American College of Gastroenterology (ACG), but the number of women with IBS is three times greater than the number of men. Researchers say that men are less likely to report the problem, and consequently, few studies on men with IBS have been done. Onset of IBS usually is in late adolescence or early adult life. It rarely appears for the first time after age 50. "It's important that we allay those fears that IBS leads to more serious diseases," says William R. Stern, M.D., a Rockville, Md., gastroenterologist, "so that people can deal with the illness itself." Stern says that those he diagnoses with IBS seem more concerned about potential long-term implications of the illness than focusing on treating the symptoms they actually have. Although IBS is associated with severe pain and discomfort, he says, the illness does not lead to cancer or life-threatening conditions or surgery.Limits of LotronexUntil last year, treatment for IBS relied in most cases on a diet high in fiber, use of antispasmodics and other medications, and recommended lifestyle changes. But many of those options generally treat only a single symptom of IBS. In February 2000, the Food and Drug Administration approved Lotronex (alosetron hydrochloride), the first of a new generation of agents developed specifically to treat the multiple symptoms of IBS in women whose main complaint was diarrhea. Two large clinical trials indicated that the drug was effective in relieving pain and discomfort, reducing the urgency to defecate, and decreasing stool frequency. But as exciting as Lotronex was, its market life was short-lived. Just 10 months after hundreds of thousands of IBS sufferers began taking the drug, it was pulled off pharmacy shelves after several people died and many more suffered serious side effects associated with its use.The FDA closely monitored Lotronex prior to, and after, its approval. Specifically, the agency was concerned about earlier reports of mild-to-moderate intestinal damage resulting from reduced blood flow to the intestine (ischemic colitis) and obstructed or ruptured bowels from complications of severe constipation. An FDA advisory committee--a panel of scientific and medical advisers outside the agency--recommended that both doctors and patients must be informed of the potentially serious adverse effects associated with Lotronex. The FDA updated the health-care professional labeling for the drug, and required the manufacturer, Glaxo Wellcome, now GlaxoSmithKline, to advise users of the risks in writing.However, the FDA began receiving reports of deaths and more serious complications of ischemic colitis that required blood transfusions or surgery. The agency then met with the manufacturer to develop risk-management options that would ensure the drug's safe use. One option was to allow Lotronex to remain on the market under restricted conditions. "This risk-benefit evaluation was difficult," says Janet Woodcock, M.D., director of the FDA's Center for Drug Evaluation and Research, "because we were aware that many users of Lotronex did not experience these adverse effects." But in November 2000, the manufacturer voluntarily withdrew Lotronex from the market. The removal of Lotronex, however, has resulted in an odd turnabout. Despite the risks, some patients with IBS and their doctors want it back. "The fact is," Marcus says, "there's a drug out there that's helping people. There's no excuse for allowing pain and suffering to continue when there's a remedy." Marcus blames both the manufacturer for withdrawing Lotronex and the FDA for not making it easier for the manufacturer to continue marketing it. She was one of thousands of Lotronex users who contacted Woodcock personally to protest the drug's withdrawal. "Most of the letters have focused on the severity of some cases of irritable bowel syndrome," Woodcock says, "and the need for continued access to an effective treatment."Mark Birns, M.D., a gastroenterologist in Rockville, Md., thinks Lotronex "came out at too high a dose." He believes the drug simply needs to be relabeled, or its dosage altered. In a practice with two other physicians, Birns says neither he nor his partners have seen a single case of ischemic colitis in the hundreds of patients they treat.Still, consumer advocate groups, like Public Citizen in Washington, D.C., argue that a drug with the potential to threaten life does not belong in the marketplace, especially since IBS is not life threatening. The group insists there is no way to predict who is at risk for complications.For now, the FDA is working with the manufacturer to address the safety issues surrounding Lotronex. Woodcock adds that the agency plans not only to develop better tools to protect those who may be harmed by new medications, but also to ensure that medicines are available for those who need them. Understanding IBSIBS is one of three major "functional intestinal disorders"--a general term for conditions that show no physical evidence of disease in the intestines upon examination, and the cause of which does not show up in a blood test or an X-ray.According to the National Institutes of Health, people with IBS seem to have colons that are more sensitive and reactive than usual, so they respond to stimuli that would not bother most people. Eating, stress, gas, depression, and other ordinary events can cause the colon to overreact. Certain medications and foods, such as milk products in lactose-intolerant people, dietary fats, corn, and wheat, are known to trigger spasms in some people. Sometimes these spasms delay the passage of stool, leading to constipation.IBS often is mistaken for colitis and is commonly referred to as spastic colon--terms which are "inadequate, inaccurate or both," says Marvin M. Shuster, M.D., a gastroenterologist at Johns Hopkins Bayview Medical Center in Baltimore. Colitis, for example, means that the colon is inflamed, and IBS does not cause inflammation."Irritable bowel syndrome is the most suitable and accurate term used by doctors," Shuster says, because it emphasizes that the condition is a "motor disorder manifesting irritability" that "involves many areas of the gut."Jeffrey Roberts, 40, has IBS flare-ups once or twice a month. Despite the pain and diarrhea he's had for 25 years, he's always been able to get around without much restriction. Still, he keeps a "bag-of-tricks-to-go" in anticipation of an emergency. Shortly after he formed an IBS self-help group, he was amazed to learn that people's lives could be affected so dramatically by IBS. "I just kept thinking, could my IBS ever get that bad?" Marcelo A. Barreiro, M.D., a medical officer in FDA's division of gastrointestinal and coagulation drug products, explains that most people assume that the brain alone controls all activity in the body. In fact, he says, the gut has its own independent nervous system that regulates the processes of digesting food and eliminating solid waste. "There's a network of nerve cells within the wall of the gut--the gut nervous system--that does not depend on the brain for its minute-to-minute function," Barreiro says, but rather, "responds to its inputs under various conditions."Under stress, for example, the brain sends conflicting messages to the gut that may exaggerate the irritability of the gut nervous system. Barreiro says that with IBS, the connections between the brain that is the central nervous system, and the gastrointestinal, or gut, system, also known as the enteric nervous system, "appear to be out of sync." (See "IBS and the Gastrointestinal (Enteric) Nervous System.")Douglas A. Drossman, M.D., of the University of North Carolina in Chapel Hill, emphasizes that "stress does not cause IBS," although it may aggravate the symptoms. Therefore, minimizing stress is for many, but not necessarily all people, an important part of coping with IBS.Another Point of ViewNot all doctors agree that IBS should be labeled a syndrome--a group of symptoms that collectively indicate or characterize a disease. Some physicians traditionally have considered the symptoms to be mostly psychological because they could not find something physically wrong to explain the trouble. Others, like Howard Spiro, M.D., a retired Yale University School of Medicine professor, worry that the catch-all term "IBS" has become a marketing tool that will send thousands of basically healthy people running to their doctors demanding prescriptions. Spiro, who continues his practice as a consulting gastroenterologist, believes that irritable bowel for many people is an emotional response to the troubles and incidents of everyday life, which he says have always led to digestive problems, and probably always will. "Recognizing an irritable bowel is one thing," he adds. "Deeming it the equivalent of a disease is another."On the other hand, Spiro recognizes that some people, like Marcus, complain of abdominal pains that are far more than a simple annoyance. Marcus is often awakened by excruciating cramps about every hour in the middle of the night, and seldom, if ever, can commit to activities outside her home. Spiro believes that research behind new drugs is certainly worth reviewing in the hope that future developments will successfully calm, for whatever the reasons, an overactive intestine.Hope Marcus, 53, has had IBS for 12 years. The severity of her condition forced her to close down a business and work from home. Until she began taking Lotronex, she couldn't leave the house. Unexpected hemorrhoid surgery in October 2000, quelled Marcus' IBS symptoms, deceiving her into thinking she was cured. When the pain and diarrhea returned four months later, "I didn't worry because I had a month's supply of Lotronex." Now that the drug is no longer available, Marcus worries constantly about the day she will use her last pill. Drossman says that in about 65 percent of the population with IBS, the condition isn't severe enough to prompt them to see a doctor. They may have pain in the gut from time to time that bothers them, "but it's possible they may not even recognize it as a clinical condition." In a significant number of women with IBS who have severe constipation or other bowel disorders, doctors also uncovered a history of sexual or physical abuse. Some say that such experiences may make people unusually sensitive and vulnerable to their bodily sensations.In a recent issue of the American Journal of Gastroenterology, a relatively small study piqued the interest of many as another possibility to understanding and treating IBS. Scientists at Cedars-Sinai Medical Center in Los Angeles looked at the possibility that there may be excess bacteria in the small intestine, causing symptoms similar to IBS. Further research is being carried out to determine the mechanism by which bacterial overgrowth occurs.Whatever the cause, doctors agree on one thing: IBS symptoms can be controlled when people work with their doctors to find the best combination of treatments. Treating IBSNearly all people with IBS can be helped, but no single treatment works for everyone. The first step is a personal evaluation of history, stress level and diet. People who can identify particular foods or types of stress that bring on the problem should avoid them. For most, especially those who tend to be constipated, regular physical activity helps keep the gastrointestinal tract functioning normally.In general, doctors say a normal diet is best. People with abdominal distension and increased gas should avoid beans, cabbage, and other foods that are difficult to digest. Sorbitol, an artificial sweetener used in dietetic foods and in some drugs and chewing gums, should not be eaten in large amounts. Fructose (a common sugar found in fruits, berries, and some plants) should be eaten only in small amounts. A low-fat diet helps some people.Hoffman spent years eliminating foods from his diet in a desperate effort to relieve the excruciating abdominal pain that gripped him after meals. "I went from cutting certain things out of my diet to cutting the right things out," Hoffman says. Although he's been in remission for five years, he says the awful truth is, "If I eat a bowl of spaghetti, I'll be in pain by tomorrow night."Mike Hoffman's symptoms of alternating constipation and diarrhea began when he was 8 years old. Through the years, he has tried over-the-counter remedies and some doctor-prescribed medicines, popping as many as 20 pills a day. "By the time I was 40, I was a gastrointestinal cripple." After a bout with IBS, Hoffman says his internal organs would ache for days, as though he'd been beaten with a baseball bat. For the last five years, as long as he eliminates certain foods from his diet, he remains symptom free. But a substantial number of Americans with IBS have more severe symptoms that often do not respond to dietary or lifestyle changes alone. Drugs that slow the function of the gastrointestinal tract and are considered to be antispasmodics, such as Bentyl (dicyclomine hydrochloride), are frequently prescribed. Antidiarrheal drugs, such as Lomotil (diphenoxylate) and Imodium (loperamide), may help people with diarrhea. Antidepressant drugs, mild tranquilizers, psychotherapy, hypnosis, and behavior modification techniques also may bring relief to some people with IBS. Newer brain imaging techniques could help doctors understand the relationship between altered emotional states with pain enhancement and other gastrointestinal symptoms.But doctors say the real key to achieving relief is for people to understand that IBS is a complex disorder with physical and stress-related dimensions. A strong partnership between the informed patient and a knowledgeable doctor can help improve outcomes."Confidence in the diagnosis and educating and reassuring the patient are vital therapeutic tools," says Edy Soffer, M.D., from Ohio's Cleveland Clinic. People who have not responded to lifestyle changes and careful use of over-the-counter medicines, such as fiber supplements, laxatives and antidiarrheal drugs, should consider being evaluated by a gastroenterologist.The Future The FDA and the drug industry currently are developing guidance for clinical trials involving people with IBS that would address many of the safety and effectiveness issues associated with the use of drugs for IBS. Meanwhile, support groups, research organizations, and patient education and advocacy groups, such as the Wisconsin-based International Foundation for Functional Gastrointestinal Disorders (IFFGD), are escalating efforts to educate doctors and patients about the disease. "IBS patients have lived with a juggling act of symptoms," says Nancy J. Norton, president of IFFGD. "But research is targeting very specific things now, and the most important thing to come out of all this is that people are finally recognizing the burden of illness that's associated with IBS." Nancy Norton, 51, started having cramps and diarrhea as a teenager. In her 30s, the symptoms plagued her two weeks out of every month. She only learned she had IBS 15 years ago. Norton founded the International Foundation for Functional Gastrointestinal Disorders (IFFGD), a nonprofit organization that provides practical information and the results of clinical studies to people with IBS. IFFGD brings together leaders in gastroenterology to conferences that attract worldwide professionals. "We're making progress, but we need to continue the research. We can't stop," she says. Once the factors that cause the symptoms and the mechanisms of their production are fully understood, different treatment options will enable people to deal more effectively with the disorder.--------------------------------------------------------------------------------What Makes Irritable Bowel Syndrome (IBS) Different?Understanding IBS is important because it is often confused with other similar digestive disorders, such as inflammatory bowel diseases. Below are the most common digestive disorders, with some characteristic differences that help distinguish one from another.Functional Intestinal Disorders:IBSaffects large intestine (colon or bowel) causes abdominal pain, bloating, diarrhea, constipation does not cause inflammation does not lead to other complications Dyspepsiaaffects upper abdomen or chest causes feeling of fullness, gas, and burning pain can be caused by stomach ulcers, stomach inflammation or stomach cancer can be early warning of a serious disease Inflammatory Bowel Diseases:Crohnï¿½s diseaseaffects any area of gastrointestinal tract causes inflammation sporadically throughout intestine causes diarrhea, crampy abdominal pain, loss of appetite, loss of weight, or skin sores can lead to other complications, such as intestinal obstruction Ulcerative Colitisaffects all or part of only the large intestine causes inflammation and ulcers of the large intestine causes bloody diarrhea, abdominal cramping, fever does not affect the small intestine --------------------------------------------------------------------------------Where to Get More Information:National Digestive Diseases Information ClearinghouseNIH2 Information WayBethesda, MD 208921-800-891-5389 www.niddk.nih.gov/health/digest/nddic.htm The Cleveland Clinic FoundationDepartment of Gastroenterology9500 Euclid AvenueCleveland, OH 441951-800-223-2273 (x48950) www.clevelandclinic.org International Foundation for Functional Gastrointestinal DisordersP.O. Box 17864Milwaukee, WI 532171-888-964-2001 www.iffgd.org The American Gastroenterological Association7910 Woodmont Avenue, 7th FloorBethesda, MD 20814 www.gastro.org American College of Gastroenterology4900 B South 31st StreetArlington, VA 22206(703) 820-7400 www.acg.gi.org Irritable Bowel Syndrome Self-Help GroupP.O. Box 94074Toronto, OntarioCanada M4N 3R1(416) 932-3311 www.ibsgroup.org --C.L.


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