MedicineNet.com
About Us | Privacy Policy | Site Map
March 21, 2010
MedicineNet home Picture Slideshows Diseases and conditions Symptoms and signs Procedures and tests Medications Picture Image Collection MedTerms medical dictionary Pet Health
Font Size
A
A
A

Irritable Bowel Syndrome (cont.)

How is IBS treated?

The treatment of IBS is a difficult and unsatisfying topic because so few drugs have been studied or have been shown to be effective in treating IBS. Moreover, the drugs that have been shown to be useful have not been substantially effective. This difficult situation exists for many reasons, as follows:

  • Life-threatening illnesses (for example, cancer, heart disease , and high blood pressure), are the diseases that capture the public's interest and, more importantly, research funding. IBS is not a life-threatening illness and has received little research funding. Because of the lack of research, an understanding of the physiologic processes (mechanisms) that are responsible for IBS has been slow to develop. Effective drugs cannot be developed until there is an understanding of these mechanisms.
  • Research in IBS is difficult. IBS is defined by subjective symptoms, (such as pain), rather than objective signs (for instance, the presence of an ulcer). Subjective symptoms are more unreliable than objective signs in identifying homogenous groups of patients. As a result, groups of patients with IBS who are undergoing treatment are likely to contain some patients who do not have IBS, and this may negatively affect the results of the treatment. Moreover, the results of treatment must be evaluated on the basis of subjective responses (such as improvement of pain). In addition to being more unreliable, subjective responses are more difficult to measure than objective responses (such as the healing of an ulcer).
  • Different subtypes of IBS (for example, diarrhea-predominant, constipation-predominant, etc.) are likely to be caused by different physiologic processes (mechanisms). It also is possible, however, that the same subtype may be caused by several different mechanisms in different people. What's more, any drug is likely to affect only one mechanism. Therefore, it is unlikely that any one medication can be effective in all-even most-patients with IBS, even patients with similar symptoms. This inconsistent effectiveness makes the testing of drugs difficult. Indeed, it can easily result in drug trials that demonstrate no efficacy (usefulness) when, in fact, the drug is helping a subgroup of patients.
  • Subjective symptoms are particularly prone to responding to placebos (inactive drugs, or sugar pills). In fact, in most studies, 20% to 40% of patients with IBS will improve if they receive inactive drugs. Now, all clinical trials of drugs for IBS require a placebo-treated group for comparison with the drug-treated group. So, the placebo response means that these clinical trials must utilize large numbers of patients to detect meaningful (significant) differences in improvement between the placebo and drug groups. Therefore, such trials are expensive to conduct.

The lack of understanding of the physiologic processes (mechanisms) that cause IBS has meant that treatment cannot be directed at these mechanisms. Instead, treatment usually is directed at the symptoms, which are primarily constipation, diarrhea, and abdominal pain. These symptoms are not mutually exclusive since patients may have abdominal pain with either constipation or diarrhea. Moreover, periods of constipation may alternate with periods of diarrhea. This variation in symptoms over time can make the treatment of symptoms complex. The psychotropic drugs (antidepressants) and psychological treatments (for example, cognitive behavioral therapy) treat hypothetical causes of IBS (such as abnormal function of sensory nerves and the psyche) rather than the symptoms.

Constipation

Constipation is due to the slow transport (transit) of intestinal contents through the intestines, primarily the colon. This slow transit may be due to either abnormal function of the muscles of the entire colon or just the muscles of the anus and rectum.

The treatment of constipation in IBS usually begins with a trial of the supplements and medications that are used to treat constipation of any cause. In 2002, the FDA approved tegaserod (Zelnorm), the first drug specifically for the treatment of abdominal pain and constipation in women with IBS. However, in March of 2007, the FDA asked Novartis to suspend sales of tegaserod (Zelnorm) in the United States because a retrospective analysis of data by Novartis from more than 18,000 patients showed a slight difference in the incidence of cardiovascular events (heart attacks, strokes and angina) among patients on Zelnorm compared to placebo. The data showed that cardiovascular events occurred in 13 out of 11,614 patients treated with Zelnorm (.11%), compared to one cardiovascular event in 7,031 (.01%) placebo-treated patients. However, it is unclear whether Zelnorm actually causes heart attacks and strokes. Doctors and scientists will be scrutinizing the data to determine the long-term safety of Zelnorm.

The mechanism whereby tegaserod reduces constipation is interesting. It is the contractions of the intestinal muscles that controls transit of digesting food through the intestine. More contractions speed transit, fewer contractions slow transit. In constipated patients, contractions are fewer. One important factor in the control of the contractions is serotonin. Serotonin is a chemical manufactured by nerves in the intestine. It is released by the nerves and then travels to other nerves where it binds to receptors on the nerves. It is, in scientific terms, a "neurotransmitter" that allows nerves to communicate with each other. When it binds to receptors on nerves that control the contractions of intestinal muscles, serotonin can either promote or prevent contractions depending on the type of receptor it binds to. Binding to some types of receptors causes contractions, and binding to other types of receptors prevents contractions. The serotonin 5-HT4 receptor is a receptor that prevents contractions when serotonin binds to it. Tegaserod blocks the 5-HT4 receptor, prevents serotonin from binding to it, and thereby increases contractions of the intestinal muscles. The increased contractions speed the transit of digesting food. In addition, tegaserod reduces the sensitivity of the intestinal pain-sensing nerves and can thereby reduce the perception of pain.

In a randomized, double blind, placebo-controlled, study involving more than 1000 patients (80% women) with constipation-predominant IBS, tegaserod was found to be more effective than placebo in increasing the frequency of stools, relieving abdominal pain and discomfort, and decreasing the sensations of bloating among women. (There was an insufficient number of men in the study to draw conclusions about the effectiveness of treatment in men.) The beneficial effects of treatment started during the first week of treatment and were sustained throughout the 12-week period of study.

Diarrhea was the only side effect in the tegaserod study. Diarrhea usually occurred early during treatment and resolved quickly even if the treatment was continued. There was no effect of tegaserod on blood counts, liver and kidney tests, electrocardiograms, blood pressure, pulse, and body weight. (A medication similar to tegaserod, called cisapride or Propulsid, which also promoted intestinal muscle contractions, was withdrawn from the market due to rare but potentially fatal effects on the electrical rhythm of the heart. So far, there have been no reports of rhythm disturbances related to tegaserod.) Patients with major liver or kidney disease should not take tegaserod. The safety of tegaserod to the fetus or nursing infants has not been studied and is unknown. Therefore, pregnant or nursing women should avoid tegaserod.

Diarrhea

The most widely studied drug for the treatment of diarrhea in IBS is loperamide (Imodium). Loperamide appears to work by inhibiting (slowing down) the contractions of the muscles of the small intestine and colon. Loperamide is approximately 30% more effective than a placebo in improving symptoms among patients who have diarrhea as the predominant manifestation of their IBS. It is not clear if loperamide reduces abdominal pain. Loperamide can be potent and itself can cause constipation. Therefore, the dose must be carefully adjusted and individualized for each patient. Alosetron (Lotronex) is used to treat diarrhea and abdominal discomfort that occurs in women with severe IBS that does not respond to other simpler treatments.

Alosetron, like tegaserod, affects the serotonin receptors. (See the discussion above of tegaserod.) Alosetron blocks the 5-HT3 receptor, a receptor that causes contractions when serotonin binds to it. Alosetron, by blocking 5-HT3 receptors, prevents serotonin from binding and thereby prevents contractions.

Alosetron was approved by the FDA in February, 2000, but was withdrawn from the market in November, 2000, because of serious, life-threatening, gastrointestinal side effects. In June 2002, it was approved again by the FDA for marketing but in a restricted manner as part of a drug company-sponsored program for managing the risks associated with treatment. Use of alosetron is allowed only among women with severe, diarrhea-predominant, IBS who have failed to respond to conventional treatment for IBS.

The most common side effect with alosetron is constipation. One-quarter to one-third of patients may develop this side effect, but in only 10% (10 out of every 100 patients) will the drug need to be stopped temporarily or permanently.

A rare side effect that has occurred with alosetron is severe intestinal inflammation caused by poor circulation of blood ( ischemic colitis). This complication is life-threatening, may require surgery, and has even caused death in a small number of patients. Therefore, immediate medical attention should be sought if the signs of ischemic colitis (rectal bleeding or a sudden worsening of abdominal pain) occur.

Abdominal pain

The most widely studied drugs for the treatment of abdominal pain are a group of drugs called smooth-muscle relaxants.

The gastrointestinal tract muscle is composed of a type of muscle called smooth muscle. (By contrast, skeletal muscles, such as the biceps, are composed of a type of muscle called striated muscle.) Smooth muscle relaxant drugs reduce the strength of contraction of the smooth muscles but do not affect the contraction of other types of muscles. They are used in IBS with the assumption (not proved) that strong or prolonged contractions of smooth muscles in the intestine-spasms-are the cause of pain in IBS. There are even smooth muscle relaxants that are placed under the tongue, like nitroglycerin for angina, so that they may be absorbed rapidly. Smooth muscle relaxants are approximately 20% more effective than a placebo in reducing abdominal pain. It is not clear if smooth muscle relaxants have a beneficial effect on constipation or diarrhea.

Commonly used smooth muscle relaxants are hyoscyamine (for example, Levsin) and methscopolamine (for example, Pamine). Other drugs combine smooth muscle relaxants with a sedative (for example, Donnatal), but there is no evidence that the addition of sedatives adds to the efficacy (effectiveness) of the treatment.

Psychotropic drugs

Patients with IBS are frequently found to be suffering from depression, but it is unclear if the depression is the cause of IBS, the result of the IBS, or unrelated to the IBS. Several trials have shown that antidepressants are effective in IBS in relieving abdominal pain and, perhaps, diarrhea. The antidepressants work in IBS, however, at relatively low doses that have little or no effect on depression. It is believed therefore, that they are working not by combating depression, but in different ways (through different mechanisms). For example, these drugs have been shown to adjust (modulate) the activity of nerves and to have analgesic (pain-relieving) effects as well. Commonly used psychotropic drugs include the tricyclic antidepressants, amitriptyline (Elavil, Endep), desipramine (Norpramine), and trimipramine (Surmontil). Although studies are encouraging, it is not yet clear whether the newer class of antidepressants, the serotonin-reuptake inhibitors, such as fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil) are effective.

Psychological treatments

Psychological treatments include cognitive-behavioral therapy, hypnosis, psychodynamic or interpersonal psychotherapy, and relaxation/stress management. They have been used in patients with IBS who are psychologically distressed to the point that their quality of life is being impaired. A few studies have shown that psychological treatments can reduce anxiety and other psychological symptoms in addition to reducing IBS symptoms, particularly pain and diarrhea.

Diet

It is unclear if diet has much effect on the symptoms of IBS. Nevertheless, patients often associate their symptoms with specific foods (such as salads, fats, etc.). Although specific foods might worsen IBS, it is clear that they are not the cause of IBS. The common placebo response in IBS also may explain the improvement of symptoms in some people with the elimination of specific foods.

Dietary fiber often is recommended for patients with IBS. Fiber probably is of benefit to IBS patients with constipation, but it does not reduce abdominal pain. Lactose (milk sugar) intolerance often is blamed for diarrhea-predominant IBS, but it does not cause IBS. Because they are both common, lactose intolerance and IBS may coexist. In this situation, restricting lactose will improve, but not eliminate the symptoms. Lactose intolerance is easily determined by testing the effect of lactose (hydrogen breath testing) or trying a strict lactose elimination diet. Intolerance to sugars other than lactose, specifically, fructose, sucrose, and sorbitol, may cause symptoms that are similar to IBS or make IBS worse. It is unlikely, however, that these sugars cause IBS.



Next: Is there a relationship between IBS and small intestinal bacterial overgrowth? »

Share | | | | | More

Irritable Bowel Syndrome - How Was Diagnosis Established

The MedicineNet physician editors ask:

How was the diagnosis of your irritable bowel syndrome established?

Comment submissions for this question have ended. Patient Discussions FAQs
See 20 Viewer Comments

View Comments

Suggested Reading by Our Doctors
MedicineNet Doctors
  • amitriptyline. Elavil, Endep - Learn about amitriptyline ((Elavil, Endep) an antidepressant drug used to treat depression. Drug interactions and side effects are also included in the information.
  • CT Scan (Computerized Axial Tomography) - CT Scan (Computerized Axial Tomography, CAT scan) is a procedure that assists in diagnosing tumors, fractures, bony structures, and infections in the organs and tissues of the body.
  • Abdominal Pain - Learn about abdominal pain (pain in the stomach / abdomen) including causes, symptoms, how abdominal pain is diagnosed, and how abdominal pain is treated.

Latest Medical News

GI Disorders

Get the latest treatment options.


Are you Depressed? Take the Quiz

Your Guide to Symptoms & Signs: Pinpoint Your Pain













Health categories:

Slideshows | Diseases & Conditions | Symptoms & Signs | Procedures & Tests | Medications | Image Collection | Medical Dictionary | Pet Health

Popular health centers:

Allergies | Arthritis | Blood Pressure | Cancer | Chronic Pain | Cold & Flu | Diabetes | Digestion | Eyesight | Health & Living | Healthy Kids

Hearing & Ear | Heart | Infectious Disease | Men's Health | Mental Health | News & Views | Pregnancy | Sexual Health | Skin | Women's Health | More...

MedicineNet.com:

About Us | Newsletters | RSS Feeds | Privacy Policy | Site Map | WebMD® | Medscape® | eMedicine® | eMedicineHealth® | RxList®

This website is certified by Health On the Net Foundation. Click to verify. This site complies to the HONcode standard for trustworthy health information:
verify here.

©1996-2010 MedicineNet, Inc. All rights reserved. Notices and Legal Disclaimer.
MedicineNet does not provide medical advice, diagnosis or treatment. See additional information.