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MAY/JUNE 2004

AROUND HARVARD

This article originally appeared in the April 2004 Harvard Women's Health Watch and is provided courtesy of Harvard Health Publications.

Understanding and treating an irritable bowel

Irritable bowel syndrome significantly disrupts life for the women who have it. The good news is that we’re finding better ways to control it.

Irritable bowel syndrome (IBS) affects an estimated 24 million people in the United States. Experts aren’t sure why, but 70% of sufferers are women.

IBS causes recurrent episodes of constipation or diarrhea (or alternating bouts of each) along with cramps, bloating, and gas. For many, “irritable” vastly understates the impact of IBS. Symptoms often interfere with work and other activities. Some women hesitate to leave their homes because they’re embarrassed or don’t want to be very far from a bathroom.

Diagnosing an irritable bowel
There is no test for IBS. A clinician familiar with this condition can usually make a diagnosis just by talking with you and performing a physical exam. She or he will look for specific symptoms (see “Criteria for diagnosing IBS”) and may order routine blood and stool tests and check for lactose intolerance. She or he will also try to rule out other causes such as a thyroid disorder, endometriosis, and other bowel diseases. In some cases, clinicians may recommend a sigmoidoscopy or colonoscopy to examine the colon.

Criteria for diagnosing IBS
IBS is a functional bowel disorder — that is, there is no known disease or structural abnormality behind its symptoms. An IBS diagnosis requires the presence of abdominal pain or discomfort for 12 or more weeks (not necessarily consecutive) in the past 12 months, accompanied by at least two of the following:

relief of abdominal discomfort with defecation
a change in the frequency of bowel movements
a change in stool appearance or form.

These symptoms also suggest IBS:
abnormal stool frequency (more than three times per day or less than
three times per week)
abnormal stool form or consistency
abnormal stool passage (straining, urgency, feeling of incomplete
evacuation)
passage of mucus
bloating or a feeling of abdominal distention.

What causes the symptoms?
Some experts suspect disturbances in the nerves or muscles in the gut cause IBS. Others believe that abnormal processing of gut sensations in the brain may be responsible. For example, well-known research indicates that people with IBS have an unusually heightened awareness of bowel sensations. Some patients may have irregularities in the muscle activity of the colon. And research suggests that a bout with an intestinal virus may set off IBS, particularly when a stressful event follows the illness.

An emerging theory focuses on the neurotransmitter serotonin. Neurotransmitters are chemicals that transmit messages between nerve cells. Most of us have heard about the relationship between depression and serotonin in the brain, but the gut also produces serotonin, which in turn acts on nerves in the digestive tract. Some research suggests that IBS patients who suffer mainly from diarrhea may have increased serotonin levels in the gut, while those with constipation-predominant IBS have decreased amounts.

Emotional factors also play a role. For example, stress often worsens symptoms, and studies suggest that cognitive behavioral therapy, relaxation therapy, and hypnotherapy can help relieve pain and symptoms. Stress management, diet, and exercise have also proven useful.

Treating constipation, diarrhea, and gas
Because there is no cure for IBS, the goal of treatment is to control symptoms.

Constipation. Bulking agents (fiber, bran, and psyllium laxatives) help by moving waste through the intestines; however, they may not be useful for pain or diarrhea, and can cause gas and bloating. When using bulking agents, start slowly and gradually increase your intake. Be sure to drink plenty of fluids.

While there are no good data, most doctors think laxatives can be safe and effective when used judiciously. Stimulant laxatives (bisacodyl and glycerol) may cause abdominal cramping. Laxative herbal teas are also available; start with a weak brew and work up to the strength that works for you.

Diarrhea. Loperamide reduces intestinal muscle contractions and fluid secretion in the gut. Studies show that it helps relieve diarrhea, but not pain. It may not be a good choice for women whose symptoms fluctuate between constipation and diarrhea. A lower-dose form of loperamide is sold over the counter as Imodium. Lomotil (diphenoxylate and atropine) is a prescription drug also used to treat IBS-related diarrhea.

Gas and bloating. Simethicone-based products (Gas-X, Maalox), charcoal, and alpha-galactosidase (Beano) aren’t very effective, and no prescription drugs have proven useful. The best approach is to avoid the foods that trigger gas and bloating. Common offenders include beans, pretzels, bananas, dairy products, carbonated beverages, and raw fruits and vegetables (particularly cabbage, cauliflower, and broccoli). Fructose (a common sweetener) and sorbitol (an artificial sweetener) can also cause bloating and diarrhea.

Treating abdominal pain
Antispasmodics relax the muscle of the stomach and intestines. These drugs help relieve abdominal pain, but their benefits for constipation and diarrhea are uncertain. Antispasmodics available in the United States include dicyclomine (Bentyl) and hyoscyamine (Anaspaz, Cystospaz, others). Side effects include dry mouth, sweating, blurred vision, dizziness, constipation, bloating, urinary problems, headaches, and palpitations. Some women find peppermint oil helpful as an antispasmodic, but it can cause heartburn because it also relaxes the band of muscle that helps keep stomach contents from backing up into the esophagus.

Prokinetic agents increase smooth muscle activity and so may help relieve bloating or constipation. Metoclopramide (Reglan) and newer drugs such as tegaserod (Zelnorm) have prokinetic action.

Low doses of tricyclic antidepressants such as amitriptyline (Elavil) or nortriptyline (Aventyl, Pamelor) taken at bedtime appear to alleviate abdominal pain. Some studies suggest that these drugs are most helpful for diarrhea-predominant IBS. Side effects include fatigue, sleepiness, dry mouth, and constipation, which can be severe. It isn’t clear exactly how tricyclics help, but they may reduce nerve sensitivity. Selective serotonin reuptake inhibitor antidepressants have fewer side effects, but haven’t proved useful in IBS. However, they may be beneficial when depression or a mood disorder accompanies IBS.

The pros and cons of probiotics
Probiotics are live bacteria taken in capsule or powder form (or in yogurt). They may help with intestinal troubles by restoring the balance of bacteria in the intestine, and possibly by affecting the immune system.

A number of small studies, as well as anecdotal reports, suggest that probiotics improve IBS symptoms for some people. However, data on their safety and effectiveness are limited.

You can find probiotic supplements in grocery stores, health food stores, and pharmacies and through Web sites. If you’re interested in trying one, talk with your doctor. She or he may be able to offer some guidance.

Serotonin-modulating drugs
One of the most promising approaches to IBS treatment involves medications that alter the action of serotonin in the colon. These drugs act on the serotonin receptors on intestinal nerves — specifically serotonin-3 (5HT3) and serotonin-4 (5HT4) receptors.

Drugs known as 5HT3 receptor antagonists inhibit the action of serotonin in the gut. Alosetron (Lotronex), the first 5HT3 receptor antagonist developed for IBS, had a rocky start. FDA-approved in 2000, Lotronex relieved symptoms for many women with diarrhea-predominant IBS. (The drug doesn’t work in men.) Constipation was the most common side effect. Several months later, reports of severe complications of constipation that resulted in 44 hospitalizations and 5 deaths prompted the manufacturer to withdraw the drug from the market. These complications included intestinal blockages, extreme inflammation and distention of the large intestine, and compromised blood flow to the colon (ischemic colitis).

It was a tremendous disappointment for the many women who benefited from Lotronex. Lobbying by patients and doctors eventually brought this drug back to market in 2002, but only under a tightly controlled prescribing program (for more information, go to www.lotronex.com). A 5HT3 antagonist (cilansetron) is now under study. Preliminary data suggest that this drug offers benefits to both men and women with IBS.

The 5HT4 agonists have the opposite effect of 5HT3 antagonists. Like Lotronex, the 5HT4 agonist tegaserod (Zelnorm) greatly improves symptoms, but this time for women with constipation-predominant IBS. It, too, is effective only in women. Tegaserod speeds up movement of bowel contents through the colon and reduces sensitivity to intestinal nerve stimulation. As you’d expect, diarrhea is the most common side effect.

Moving forward
Many researchers believe that the key to better IBS treatment lies in tweaking the neurotransmitters and hormones related to gastrointestinal motility and sensation. Several newer and more specific compounds are under investigation, including muscarinic-3 receptor antagonists, neurokinin receptor antagonists, and opiate agonists.

As more targeted medications become available, physicians will be able to tailor treatment to individual women. In the meantime, if you have IBS, you’ll want to collaborate with a clinician who has experience treating IBS and who can help you find the best treatment plan for you.

Selected resources
The New Eating Right for a Bad Gut, by James Scala (Dimensions, 2000).

International Foundation for Functional Gastrointestinal Disorders, 888-964-2001 (toll free), www.iffgd.org

The Sensitive Gut, a Harvard Health Publications special health report. To obtain a copy, go to http://www.health.harvard.edu/hhp/publication/view.do?name=SG