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New drugs—and some respect—for IBSRevised guidelines and targeted therapies are leading to a new view of the condition From the September ACP Observer, copyright © 2003 by the American College of Physicians. By Margie Patlak
Long disparaged as a "wastebasket disease," irritable bowel syndrome (IBS) appears to be gaining newfound respect among researchers, drug makers and gastroenterologists. The question now: Will other physicians begin to recognize IBS as a treatable condition, or will they continue to view it as a largely psychosomatic illness? Researchers have made major strides in detecting the physiologic underpinnings of IBS as well as the nature of patients' "gut-brain" interactions. At the same time, drug makers now offer treatments that specifically target a broad range of IBS symptoms. And gastroenterologists have identified the signs of IBS that can lead to a definitive diagnosis, crafting guidelines to help physicians distinguish IBS from other conditions. But as many gastroenterologists are quick to point out, much of the progress being made on IBS has been lost on general practitioners. Rapid advances have created a "very big gap between primary care and gastroenterology," said Douglas A. Drossman, FACP, co-director of the University of North Carolina Center for Functional Gastrointestinal and Motility Disorders at Chapel Hill. "Primary care doctors are not up to speed." To help close that gap, here is an overview of the latest developments in IBS research and treatment. Help with the diagnosis Until recently, physicians lacked a clear definition of what exactly constituted an IBS diagnosis. The condition required a diagnosis of exclusion, frustrating physicians and patients alike—and generally hampering treatment. Even worse, arriving at an IBS diagnosis made many physicians fear they had missed a more dangerous condition such as colon cancer. Without any real guidance, it was difficult to feel sure that an IBS diagnosis didn't mean you were overlooking something more serious. With the advent of new guidelines, known as the "Rome criteria," however, diagnosing irritable bowel syndrome has become more straightforward. The latest version of the criteria—Rome II—was developed by international experts and published in 2000. The criteria point to IBS as a genuine, treatable disorder. The guidelines "give physicians something to hang a diagnosis on," said gastroenterologist Brian Lacy, MD, PhD, director of the Marvin M. Schuster Center for Digestive and Motility Disorders at Johns Hopkins Bayview Medical Center in Baltimore. According to the Rome II criteria, patients suffering from IBS have experienced several specific symptoms for at least 12 weeks during the previous year. The guidelines emphasize that IBS is a multifaceted condition that involves not only a faulty defecation pattern, but pain. (For more on the Rome criteria, see "The Rome II diagnostic criteria for irritable bowel syndrome," below.) "If they don't have pain, they don't have IBS," Dr. Lacy said, "even if they have diarrhea 15 times a day or go to the bathroom only once a month." While the guidelines still require physicians to rule out other conditions such as functional diarrhea or pelvic floor disorders, both of which are similar to IBS, experts say the criteria reduce much of the diagnostic uncertainty by limiting the range of other possible conditions. You don't need to run most patients through an extensive battery of tests to reach a diagnosis. Last year, both the American Gastroenterological Association and the American College of Gastroenterology (ACG) issued position statements that agree with that diagnostic approach. The organizations identified key "alarm signals" that should alert you to other potential diagnoses when working with possible IBS patients. Those signals include blood in the stool, unexplained weight loss, anemia, chronic severe diarrhea, recurring fever and a family history of colon cancer. In the absence of such red flags, however, the statements claimed that the Rome II criteria are nearly 100% specific in diagnosing IBS—and that the risk of missing another disease is negligible. While you may feel compelled to list several problems like pain, bloating and constipation when treating IBS patients, Dr. Lacy said that approach is unnecessary. "These patients have one unifying diagnosis—IBS—that should make it easier to treat them," he explained. "You need to think about treating this whole constellation of symptoms." Performing fewer tests to make an IBS diagnosis benefits not only health plans, but patients themselves. Excessive testing can distress patients, noted gastroenterologist George F. Longstreth, MD, chief of gastroenterology at Kaiser Permanente Medical Care Program in San Diego. "Too many tests sometimes create more anxiety," he said, a factor that can be a real liability when research suggests that IBS patients may have more pronounced intestinal reactions to stress than other patients. (For more on the "gut-brain" connection, see "IBS: An anatomy of what goes wrong in the body," below.) And while internists instinctively worry about missing another disease, they need to guard against making the opposite mistake: confusing IBS symptoms for those of other medical conditions. Studies have shown, for example, that IBS patients are more likely to have their gallbladders removed or to have a hysterectomy. "IBS patients shouldn't automatically have their gallbladders taken out," Dr. Longstreth said. "Their pain may be due to IBS." New breed of drugs Along with new diagnostic guidelines, physicians can now offer new treatments. What's remarkable about the latest drugs to treat IBS—alosetron and tegaserod—is that they treat several IBS symptoms, not just a single complaint.
Nondrug treatments While drug therapies are more successfully targeting IBS, novel treatments like cognitive behavioral therapy are receiving more attention. A small study by British researchers found that the symptoms of three-quarters of IBS patients who had not benefited from dietary or drug therapy significantly improved after just six sessions of cognitive behavioral therapy. Another British study found cognitive behavioral therapy to be significantly more effective than psychotherapy in relieving IBS symptoms. Even more impressive, most of the patients successfully treated in the study found their IBS symptoms hadn't returned more than a year later. While Dr. Lacy said these results are promising, he pointed out that very few people know how to do cognitive behavioral therapy properly. In addition, most insurers won't pay for it. Research into other nondrug therapies has also been encouraging. A study led by Dr. Drossman and published in the July 2003 issue of Gastroenterology found that 70% of IBS patients improved when they received cognitive behavioral therapy directed toward bowel symptoms from a psychotherapist. By comparison, only 37% of subjects in the control group who received only IBS education reported improvement. Although an accompanying editorial in the issue lauded the study's findings, it pointed to some of the same challenges that may stop cognitive behavioral therapy from being widely accepted. Patients tend to prefer pills over psychotherapy, and insurance companies may not pay for treatments. In addition, few psychotherapists have trained in strategies to manage IBS or pain. While many patients may not yet be ready for cutting-edge treatments, IBS experts stress the importance of taking time to educate patients about IBS. One goal should be reassuring them that they don't have a more deadly condition such as ulcerative colitis or colon cancer. "A lot of the improvement IBS patients experience probably comes as a result of them being reassured and having their symptoms explained to them," said Dr. Longstreth. "The doctor is functioning as the placebo." With that in mind, Dr. Lacy said, don't expect any quick cures when working with IBS patients. "Doctors really want to cure things,s but this is not something you can cure," he explained. "You need to take a nice deep breath, realize it's going to be a chronic problem, and don't get discouraged or let your patients get discouraged." Margie Patlak is a freelance science writer in Elkins Park, Pa. The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP. The Rome II diagnostic criteria for irritable bowel syndrome The Rome II criteria define irritable bowel syndrome (IBS) as abdominal discomfort or pain for at least 12 weeks (not necessarily consecutive) in the preceding 12 months, with two of the three following features:
The Rome II criteria state that the following symptoms cumulatively support an IBS diagnosis:
Source: December 2002 Gastroenterology. IBS: An anatomy of what goes wrong in the body Although the precise trigger of irritable bowel syndrome (IBS) remains unknown, researchers in the last decade have made substantial progress in understanding what goes awry in patients who suffer from the condition. Studies have shown that many IBS sufferers are hypersensitive to stimuli in the gut. Their brains process those stimuli differently, and many also have heightened gut-immune responses. As a result, researchers are beginning to look at IBS as an explainable disease rather than as a mysterious disorder. "As more of these abnormalities are being found in IBS, the distinction between a functional disorder and an organic disorder is being blurred," noted George F. Longstreth, MD, chief of gastroenterology at Kaiser Permanente Medical Care Program in San Diego. Researchers at the University of California, Los Angeles, for example, found that when they used an inflatable balloon to distend the rectum and lower colon of IBS patients, PET scans of the brain showed greater activity in the brain's emotion and attention processing centers than in those of normal control subjects given the same stimulus. Those findings were confirmed by researchers at Vanderbilt University who used MRI studies instead of PET scans. "Patients with IBS are hypervigilant," explained Brian Lacy, MD, director of the Marvin M. Schuster Center for Digestive and Motility Disorders at Johns Hopkins Bayview Medical Center in Baltimore. "They listen to their guts too carefully and hear every little contraction, gurgle and peristaltic wave." Other studies have shown that IBS patients have lower visceral pain thresholds and greater gut reactions to psychological stress than control subjects. Those data have led some to hypothesize that a visceral hypersensitivity causes many IBS symptoms. Whether that hypersensitivity originates in the brain or in the nervous system of the gut is unclear. Regardless of its origin, treatments that target the region of the brain shown to be hyperactive in IBS patients can effectively relieve symptoms. That's why therapies like cognitive behavioral therapy, alosetron, low-dose tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs) and cognitive therapy all work. Although abnormalities in brain processing are thought to play a role in IBS, researchers have also found how some symptoms stem from the actions of nerves in the gut. The role of the "gut-brain" connection has recently gained more prominence as researchers continue to uncover its extensive influence on bowel motility, secretion, immune responses and signaling to the central nervous system. Much of that influence gets carried out via the neurotransmitter serotonin. Remarkably, about 95% of the body's serotonin is found in the gut. Two serotonin receptor subtypes, 5-HT3 and 5-HT4, are thought to be responsible for the majority of the neurotransmitter's intestinal effects. It's no surprise, then, that alosetron and tegaserod, the first two drugs shown to affect the broad spectrum of IBS symptoms, target 5-HT3 and 4. SSRIs may also act on the bowel's nervous system, although they are thought to have a greater effect on the brain. There's also preliminary evidence that many IBS patients have a heightened immune response in the gut that includes a boosted number of mast cells, natural killer cells, lymphocytes and serotonin-laden enterochromaffin cells. Interestingly, between 10% and 30% of patients who recover from food poisoning develop IBS, especially if they were under undue psychological stress at the time they developed acute gastroenteritis. "There's one theory that the infection and stress alter the permeability of the gut mucosa so that bacteria or viruses invade the gut where they don't belong," Dr. Lacy said. "This leads to chronic inflammation that could result in disordered motility and sensation by injuring nerves in the gut." The excessive numbers of enterochromaffin cells in some IBS patients could cause many IBS symptoms just by releasing their granules of serotonin. The popular media have given a lot of play to a recent study by Mark Pimentel, MD, a gastroenterologist at Cedars-Sinai Medical Center in Los Angeles. He found that IBS patients were more likely to have an overgrowth of small intestinal bacteria as indicated by a breath test. After seven days of treatment with neomycin, their lactulose breath testing normalized. Experts, however, question the validity of the study, citing several methodological shortcomings like short-term follow-up. "If these patients improved after one week," Dr. Longstreth said, "that's hardly good enough, since IBS naturally waxes and wanes." All the basic research on IBS suggests that in the future, patients with the disorder may be subdivided based on the underlying mechanisms of their symptoms. "We're starting to understand IBS not as a single entity but as a collection of pathophysiological subgroups," said gastroenterologist Douglas A. Drossman, FACP, co-director of the University of North Carolina Center for Functional Gastrointestinal and Motility Disorders at Chapel Hill. "Each subgroup might require different treatment." |
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