Cleveland Clinic

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Table of Contents

Published May 12, 2003

Bo Shen, MD

Bo Shen, MD

Department of
Gastroenterology

Edy E. Soffer, MD

Edy E. Soffer, MD

Department of
Gastroenterology

Print Chapter

Copyright 2003
The Cleveland Clinic Foundation

  

Irritable bowel syndrome (IBS) is common in the general population and has significant medical and socioeconomic impact. Its pathophysiology is still not clear, and the diagnosis and management are often challenging. It is desirable to make a positive diagnosis rather than to rely on diagnosis of exclusion. A step-by-step approach for management and a realistic goal of therapy is advocated. An effective treatment strategy should address the dominant symptoms, their severity, and psychosocial factors.

 

Chapter Outline

     Definition

     Prevalence

     Pathophysiology

     Signs and
     Symptoms

     Diagnosis

     Therapy

     Outcomes

     References

National Guidelines

Rome II Diagnostic Criteria for the Functional Gastrointestinal Disorders

 

 

 
DEFINITION

IBS is defined on the basis of the recently modified Rome criteria (Rome II criteria) as the presence for at least 12 weeks (not necessarily consecutive) in the preceding 12 months of abdominal discomfort or pain that cannot be explained by a structural or biochemical abnormality and that has at least two of following three features: (1) pain is relieved with defecation, and its onset is associated (2) with a change in the frequency of bowel movements (diarrhea or constipation) or (3) with a change in the form of the stool (loose, watery, or pellet-like).1,2 Although the Rome II criteria were not designed to be a management guideline, it is currently a "gold standard" for the diagnosis of IBS.

PREVALENCE

IBS is the most commonly diagnosed gastrointestinal (GI) condition and is one of the most common functional GI disorders seen in clinical practice.3 Estimates of prevalence vary, largely due to the differences between epidemiologic studies (eg, the use of different diagnostic criteria, population selection, and data sources). Approximately 10% to 20% of the general adult population in the United States report symptoms compatible with IBS. However, only 15% of those affected actually seek medical attention.4,5 IBS accounts for 12% of primary care and 28% of gastroenterological practice (41% of all functional GI disorders).6 Patients often experience the onset of symptoms as young adults, but the prevalence is similar in the elderly. Women are diagnosed with IBS more than twice as often as men.

The financial burden of IBS is high. In the United States, IBS results in an estimated $8 billion in direct medical costs and $25 billion in indirect costs annually.7 IBS has a major impact on the quality of life of those afflicted. Aspects of social and professional life are affected, with increased absenteeism from work, missed job opportunities, and limited social interaction.8

PATHOPHYSIOLOGY

So far, no physiologic mechanism unique to IBS has been identified. Rather, it is currently viewed as a biopsychosocial disorder resulting from an interaction between increased visceral hypersensitivity, altered gut motility, and psychological factors.9 Additionally, persistent neuroimmune interactions after infectious gastroenteritis may lead to sensory dysfunction.

Visceral Hypersensitivity
Many studies have shown that in patients with IBS, both awareness and pain caused by balloon distention in the large and small bowel are experienced at significantly lower balloon volumes than those reported by healthy subjects.10-12 However, It is not known at what level of pain signal transmission (starting at the receptor in the gut wall, through the spinal cord to the brain) this increased sensitivity is expressed, but it is selective to visceral stimuli, as patients with IBS have normal or even decreased sensitivity to somatic stimuli.11,13,14

Abnormal Gut Motility
The changes in gut motility observed in IBS are qualitative, with no distinct pattern that can distinguish patients from healthy subjects. Two major changes are observed: (1) enhanced gut transit in some patients with diarrhea-predominant IBS and decreased gut transit in some patients with constipation-predominant IBS; and (2) increased motility compared with healthy subjects in response to various stimuli, such as psychological stress, meals, and balloon inflation in the gut.9

Psychosocial Factors
IBS has long been dismissed as a psychosomatic condition, since it has no clear etiology or pathophysiology. Psychological stress and emotional events, eg, physical or sexual abuse, can result in GI symptoms in healthy subjects, but they affect patients with IBS to a greater degree. The common psychological symptoms associated with IBS are depression, somatization, anxiety, hostility, phobia, and paranoia. Up to 50% of patients with IBS meet criteria for a psychiatric diagnosis as compared with an average of 20% with organic GI disorders and 15% of control subjects.6 Although there are no psychological or psychiatric disorders specific to IBS, identification of such disorders may help in planning psychological or psychopharmacologic treatment.

Neurotransmitter Imbalance
Ninety-five percent of serotonin is in the GI tract, within enterochromaffin cells, neurons, mast cells, and smooth muscle cells. When released by enterochromaffin cells, serotonin stimulates extrinsic vagal afferent nerve fibers and intrinsic enteric afferent nerve fibers, resulting in such physiologic responses as intestinal secretion and the peristaltic reflex and in such symptoms as nausea, vomiting, abdominal pain, and bloating.15 Preliminary evidence suggests that patients with IBS have increased serotonin levels in plasma and in the rectosigmoid colon.16,17 Other neurotransmitters that may play a role in IBS include calcitonin gene-related peptide, nitric oxide, and vasoactive intestinal peptide

Latent or Potential Celiac Disease
The concept of latent/potential celiac disease has recently been introduced into the pathogenesis of IBS. Abdominal symptoms in the absence of mucosal abnormalities are features of both IBS and latent or potential celiac disease.18 In a study of genetic, serologic, and histologic markers of celiac disease in 102 patients with diarrhea-predominant IBS, 35% of the patients had positive findings for HLA-DQ2, 23% had increased intraepithelial lymphocyte counts, and 30% had increased celiac disease-associated antibodies in the duodenal aspirates, including antibodies against gliadin, tissue tranglutaminase, β-lactoglobulin, and ovalbumin.18 Stool frequency and intestinal IgA level decreased significantly under a gluten-free diet in a subgroup of IBS patients with positive HLA-DQ2 and positive intestinal celiac disease-associated antibodies when compared with IBS patients without these markers.18

Infection and Inflammation
Clinical, epidemiologic, and physiologic studies have shown that acute, transient GI infection is associated with a syndrome that, in many instances, meets diagnostic criteria for the diagnosis of IBS. In a subgroup of patients with IBS, their condition appeared to be preceded by an enteric infection, such as Campylobacter jejuni, with increased inflammatory cell response.19,20 IBS and small-intestinal bacterial overgrowth may share similar symptoms. In a study of 202 patients with IBS, 157 (78%) had small-intestinal bacterial overgrowth. Eradication of bacterial overgrowth improved patients' abdominal symptoms.21 Intraepithelial lymphocytes, lamina propria CD3 cells and CD25 cells, neutrophils, and mast cells are increased in patients with IBS.20 Exact mechanisms by which the inflammatory changes cause the symptomatology are not clear. The inflammatory response may be associated with activating enterochromaffin cells to produce 5-hydroxytryptamine (5-HT) and CD3 cells to produce cytokines, which in turn leads to enhanced motility, increased intestinal permeability, and lowered visceral sensation thresholds.19,20,22 In one prospective study of postinfectious IBS, it was found that patients whose symptoms remained 3 months after an enteric infection had not only increased mucosal cellularity but also had had increased psychosocial distress at the time of the infection. Lowered visceral sensation thresholds and increased motility were present after the infection regardless of whether or not the symptoms remained.23 Therefore, the microscopic inflammation and its physiologic effects on motility and sensation contribute to, but are not always sufficient for, the clinical explanation of IBS pain.24

SIGNS AND SYMPTOMS

Patients with IBS can present with a wide variety of GI and extraintestinal symptoms. However, the symptom complex of chronic abdominal pain and altered bowel habits that cannot be explained by identifiable structural or biochemical abnormalities is the main clinical pattern of IBS.

Chronic abdominal pain in IBS is usually described as a crampy sensation with varying intensity and periodic exacerbation. The pain is generally located in the lower abdomen, although the location and character of the pain can also vary. Emotional stress and eating may exacerbate the pain, whereas defecation often provides some relief. Progressive pain that awakens the patient from sleep or prevents sleep should prompt a search for causes other than IBS.

Since the range of normal bowel habits is broad, a careful history should include the volume, frequency, and consistency of the patient's stool. The frequency of bowel movements in normal individuals is variable, and it can range from three times a day to three times per week. Patients with IBS complain of diarrhea, constipation, alternating diarrhea and constipation, or normal bowel habits alternating with either diarrhea or constipation.

Diarrhea
Diarrhea is generally characterized as a condition of frequent loose stools of small and moderate volume. Bowel movement generally occurs during waking hours, most often in the morning or after meals. Most bowel movements are preceded by urgency and may be followed by a feeling of incomplete evacuation. Nocturnal diarrhea, bloody stools, dehydration, or weight loss are not features of IBS.

Constipation
Constipation may last from days to months, with interludes of diarrhea or normal bowel function. Stools are often hard and may be described as pellet-shaped. Patients may also experience a sense of incomplete evacuation even when the rectum is empty. This can lead to straining with defecation, prolonged time on the toilet, and inappropriate use of enemas or laxatives.

Other Gastrointestinal Symptoms
Upper GI symptoms are not uncommon in patients with IBS. These include symptoms of heartburn, dysphagia, nonulcer dyspepsia, nausea, and noncardiac chest pain.25 Patients with IBS often complain of abdominal bloating and increased gas production in the form of flatulence or belching. However, these symptoms occur despite normal volumes of gas in the GI tract and no significant colonic distention.

Extraintestinal Symptoms
Patients with IBS have a high frequency of non-GI symptoms, including rheumatologic symptoms, headache, genitourinary symptoms such as urinary frequency and urgency, dyspareunia, sexual dysfunction, and sleep-related disturbances.26-28

DIAGNOSIS

A diagnosis is based on identifying positive symptoms consistent with IBS and excluding other conditions with similar clinical presentations in a cost effective manner. In the absence of biologic markers, attempts have been made to standardize the diagnosis of IBS using symptom-based criteria. The most commonly used criteria are those proposed by Manning et al in 197829 and the international workshop criteria, which were updated in 1999 as the Rome II criteria.1 In the criteria of Manning et al, the symptoms associated with IBS include relief of pain with bowel movements, looser and more frequent stools with onset of pain, passage of mucus, and a sense of incomplete evacuation. The Rome II criteria included abdominal discomfort or pain for at least 12 weeks in the preceding 12 months (which need not be consecutive) and with two of the following three features: (1) relieved with defecation; (2) onset associated with a change in frequency of stools; and (3) onset associated with a change in form (appearance) of stool. Supportive features include abnormal stool frequency, consistency, abnormal passage of stool, and bloating or abdominal distention. A key feature of the Rome II definition is the presence of abdominal discomfort or pain.

Diagnostic evaluation of patients with IBS can be challenging. It is generally agreed that the initial diagnosis of IBS can be fulfilled when (1) symptom-based diagnostic criteria are met, such as Rome II; (2) negative results are obtained on physical examination; and (3) a cost-effective, conservative set of screening studies has been performed.24 It is important to exclude organic causes of symptoms compatible with IBS. However, to avoid unnecessary and costly testing, the diagnosis of IBS should not be made simply by excluding organic disorders. Emphasis should be placed on identifying a symptom complex compatible with IBS and then using prudent, although not exhaustive, testing to make a positive diagnosis. The Rome and Manning criteria provide guidelines to identify patients with suspected IBS. In 2002, American Gastroetnerological Association (AGA) published a extensive review 30 and position statement 31 regarding pathophysiology, role of psychosocial factors, diagnosis and treatment of IBS. It has been acknowledged that evidence exists for a diagnostic and treatment approach based on predominant symptom, its severity, and any associated psychosocial features, although more studies are needed to understand the mechanism underlying these symptoms and to develop effective treatments (Table 1).

Predominant symptom subtype is helpful for clinicians to determine the type of evaluation. For example, the constipation-predominant symptom, a therapeutic trial of fiber may be sufficient. If symptoms persist, confirmation of slow colonic transit test with a whole gut transit test or evaluation for obstructed defecation (pelvic floor dysfunction) may be indicated. For diarrhea-predominant symptoms, clinical judgment will determine the choice of studies. Particularly for loss/watery stools, a lactose/dextrose hydrogen breath test, celiac serology, small bowel or colon biopsies may be indicated. If negative, a therapeutic trial of lopermide can be ordered. For patients with predominant symptoms of abdominal pain, a plain abdominal X-ray during acute episode to exclude bowel obstruction and other abdominal pathology is recommended. If negative, a therapeutic trial of antispasmodic agent can be tried.31

THERAPY

IBS is a chronic disorder with no specific etiology, and there is no cure. The patient's confidence in the physician's diagnosis, explanation, and reassurance are vital therapeutic tools.

General Principles
The treatment strategy is based on the nature and severity of the symptoms, the characters and degree of functional impairment, and the presence of psychosocial difficulties affecting the course of the illness. Patients with mild symptoms usually respond to education, reassurance, and simple treatments not requiring prescription medication. Some patients with moderate symptoms have more disability and require pharmacological therapy directed at altered gut physiology or psychological treatments. A very small group of patients with severe and refractory symptoms see more often at referral centers may be benefit from antidepressant therapy, psychological treatments.31

The treatment goal should be set on relief of symptoms and addressing the patient's concerns.9 An important question is why the patient is seeking help at this time. Possible reasons may include:

  • Recent exacerbating factors (concurrent medical disorders, new medications, dietary changes)
  • Concern about serious illness (recent family death)
  • Environmental stressors (major loss, abuse history)
  • Psychiatric comorbidity (depression, anxiety)
  • Impairment of daily function (recent inability to work)
  • Hidden agenda (disability claims, narcotic requests, laxative abuse, secondary gain)

In a subgroup of patients with clear concurrent psychosocial disturbance, specific treatments for the triggering factors are reasonable. An effective treatment strategy should address the dominant symptoms, their severity, and psychosocial factors.

Therapeutic Relationship and Patient Education
The most important component of treatment is to establish a therapeutic physician-patient relationship coupled with patient education, as proposed by Drossman,9 with the following steps:

  1. Obtain the history through a nonjudgmental and patient-centered interview.
  2. Conduct a careful examination and cost-efficient investigations.
  3. Determine the patient's understanding of the illness and his or her concern ("What do you think is causing your symptoms?")
  4. Provide information regarding proposed mechanisms of IBS, which helps to validate the patient's disease experience and sets the basis for therapeutic interventions.
  5. Explain to patients that their symptoms of IBS are in fact real and not life threatening, but the disease course is likely to be chronic and the diagnosis, if well established, is not likely to be changed, and that he or she should have a normal life span.
  6. Establish realistic expectations with consistent limits ("I appreciate how bad the pain is, but narcotic medication is not indicated"), and involve the patient in treatment decisions ("Let me suggest some treatments for you to consider"). IBS is a condition that can be managed but not cured.

Dietary Modification
A dietary history may reveal patterns of symptoms related to dairy or gas-producing foods. Exclusion of foods that increase flatulence (beans, onions, celery, carrots, raisins, apricots, prunes, brussel sprouts, wheat germ, pretzels, and bagels) should be considered in patients with symptoms of bloating or gas. Underlying visceral hyperalgesia in IBS may explain the exaggerated discomfort experienced with consumption of gas-producing foods.

An increase in the intake of fiber is generally recommended, either through diet or the use of commercial bulking supplements. Although the efficacy of fiber supplements has not been proven, some improvement has been demonstrated in patients with IBS whose primary complaints are abdominal pain and constipation.33,34

Many types of fiber supplements are available, some synthetic, such as polycarbophil or methylcellulose; others are of natural sources such as bran or psyllium compounds. All types of fiber may cause increased bloating and gaseousness due to colonic metabolism of nondigestible fiber.

Because of its safety, a trial of fiber supplementation is advised in patients with IBS, especially those with constipation-predominant symptoms. The amount should be titrated to symptoms, but 10 grams of fiber per day is a good starting dose.

Psychosocial Therapy
Psychological therapy are initiated when symptoms are severe enough to impair health-related quality of life. Mental health referral may also be made for treatment of associated psychiatric disorders, such as major depression or history of physical and sexual abuse that interferes with adjustment to illness. 31

Behavioral treatment may be considered for motivated patients who associate symptoms with stressors. Cognitive-behavioral treatment, interpersonal (psychodynamic) therapy, hypnosis, biofeedback, stress management and relaxation training, and family or group therapy can be tried. They help reduce anxiety levels, encourage health-promoting behaviors, increase patient responsibility and involvement in the treatment, and improve pain tolerance. Factors that favor a good response to psychotherapy include:35

  • Patient is motivated
  • Patient has predominant diarrhea or pain
  • IBS is associated with overt psychiatric symptoms
  • Intermittent pain is exacerbated by stress

Patients with constant abdominal pain do poorly with psychotherapy or hypnotherapy.

Medications
Pharmacologic agents are only adjuvant to treatment of IBS. The drug chosen depends on the patient's major symptoms; diarrhea-predominant IBS is treated differently from constipation-predominant disease. Common strategies are using dietary fiber for constipation; loperamide or diphenoxylate for diarrhea; and anticholinergic, antispasmodic agents, tricyclic antidepressants, or selective serotonin reuptake inhibitors (SSRIs) for pain (Table 2).

The chronic use of drugs should be minimized or avoided because of the lifelong nature of the disorder and the lack of convincing therapeutic benefit. The difficulty in demonstrating efficacy may in part be due to the heterogeneous population diagnosed with IBS, the lack of disease markers, and high placebo response rates.36

Smooth Muscle Relaxant Agents
Smooth muscle relaxants include those directly affecting intestinal smooth muscle relaxation (eg, mebeverine, pinaverine) and those that act in similar fashion via anticholenergic pathways (eg, dicyclomine, hyoscyamine). The rationale for using smooth muscle relaxants to treat patients with IBS is based on the hypothesis that intestinal dysmotility results in abdominal pain, bloating, and disturbed defecation. Overall, the published trials with smooth muscle relaxants were generally of short duration and included small numbers of patients. These agents may be beneficial in patients with postprandial abdominal pain, gas, bloating, and fecal urgency. In a recent meta-analysis of randomized, controlled trials, 13 of 16 studies of smooth muscle relaxants showed these agents to be efficacious in global or symptomatic improvement.37 The meta-analysis of the effects of smooth muscle relaxants found them to be helpful, with 4.1 patients needing to be treated for each therapeutic success, although the effect on patient symptoms was relatively modest.37 In a separate meta-analysis, four smooth muscle relaxants which directly affect intestinal smooth muscle relaxation (cimetropium, pinaverium, otionium, and trimebutine) have been consistently shown to be efficacious.38 However, these smooth muscle relaxants are currently not approved in the United States. There are few data on dicyclomine (Bemote, Bentyl, Di-Spaz), an agent widely in use in the United States.39 Common side effects of anticholinergic agents are dry mouth, dizziness, blurred vision, drowsiness, and tachycardia. Because of these side effects and the intermittent nature of pain in IBS, we advise using such agents on an as-needed basis or in anticipation of stressors with known exacerbating effects. Hyoscyamine (Anaspaz, Cystospaz, Levsin, Neoquess) can be given for pain at a dose of 0.125 mg to 0.25 mg sublingually or orally, tid to qid, or sustained-release tablets 0.375 mg to 0.75 mg orally q12h. The typical dose of dicyclomine is 20 mg orally tid to qid or tid to qid prn.

Antidepressants
Antidepressants are purported to be beneficial and are often used in patients with chronic refractory symptoms. These drugs are particularly helpful in patients with comorbid depressive and anxiety disorders. In addition, antidepressants have analgesic properties independent of their psychotropic effects, and may therefore be beneficial in patients with neuropathic pain.40 In a meta-analysis of 11 published, randomized trials of antidepressants in functional bowel disorders, antidepressants were shown to be effective in improving symptoms.39 The odds ratio for improvement with antidepressant therapy from the pooled data of seven randomized trials was 4.2 (95% confidence interval, 2.3 to 7.9), with three patients needing to be treated for each therapeutic success and with substantial improvement in severity of pain.41 With regard to IBS, tricyclic antidepressants and possibly SSRIs modulate visceral afferent activity from the GI tract and may improve abdominal pain.42 Tricyclic antidepressants are helpful in patients with diarrhea-predominant IBS,43 possibly because of the constipating effect of this class of drugs. Conversely, if SSRIs are to be used, they should be avoided in patients with diarrhea-predominant IBS because diarrhea is a side effect of some of these agents, such as sertraline. Because antidepressants, regardless of the type used, must be taken on a continuous basis, they should be used in patients who suffer from frequent symptoms.

Improvement in neuropathic pain with tricyclic antidepressants occurs at lower doses than those required for treatment of depression. Thus, low doses should be tried initially and titrated to pain control or tolerance. Because of the delayed onset of action, 3 to 4 weeks of therapy should be attempted before considering treatment insufficient and increasing the dose. The medications often used include amitriptyline (Elavil, Endep) 10 to 25 mg orally qhs, and imipramine (Tofranil) 25 to 50 mg orally qhs. The initial dose should be adjusted based upon tolerance and response.

Although SSRIs are increasingly preferred over tricyclic agents because of their low adverse-effect profile, they have not been evaluated for use in IBS, and data on the use of SSRIs in IBS are limited.37,42 As with tricyclic antidepressants, treatment should start with low doses of paroxetine (Paxil) 20 mg orally qd; fluoxetine (Prozac, Sarafem) 20 mg orally qd; or sertraline (Zoloft) 100 mg orally qd.

Antidiarrheal Agents
Loperamide (Imodium, Kaopectate II, Maalox Anti-Diarrheal, Pepto Diarrhea Control) has been shown to be beneficial in diarrhea-predominant IBS by slowing whole-gut transit and enhancing intestinal water and electrolyte absorption.44 It does not require a prescription and is the antidiarrheal drug of choice. Diphenoxylate (Lofene, Logen, Lomenate, Lomotil, Lonox, Lo-trol, Low-Quel), can be tried next if loperamide is not effective.

Serotonin Receptor Agonists and Antagonists
Serotonin receptor agonists and antagonists: 5-HT serves both as a neurotransmitter and as a paracrine signaling molecule in the bowel.15 5-HT is distributed throughout the gut, predominantly within enterochromaffin cells in the mucosal crypts and, to a lesser extent, within the nerve fibers of the myenteric and submucosal plexuses. The concentration of 5-HT in the bowel is substantially greater than that in the brain.15 It is estimated that 95% of the body's 5-HT is synthesized and stored in the enterochromaffin cells of the gut.15 Thus, 5-HT has become a primary focus of recent research.

The postprandial plasma level of 5-HT in patients with diarrhea-predominant IBS is significantly higher than that in healthy controls.16 5-HT3 antagonists were shown to increase colonic compliance, delay colonic transit, improve stool consistency, and increase thresholds for sensation and discomfort during distention of the rectum.45 The only agent of this class approved was alosetron (Lotronex), for treatment of women with diarrhea-predominant IBS. Alosetron produced statistically significant improvement46,47 in abdominal pain, stool consistency, frequency, and urgency in women with IBS, although symptoms rapidly returned after cessation of therapy.47

The Food and Drug Administration (FDA) first approved alosetron in February 2000. After its introduction, serious and life-threatening cases of ischemic colitis and complications of constipation, including deaths, were reported. The cumulative incidence of ischemic colitis in women receiving alosetron was 0.3% in 6 months. The drug was withdrawn from the market in November 2000.

In June 2002, the FDA approved the reintroduction of alosetron. The drug's indication is now limited to the treatment of women with severe, diarrhea-predominant IBS who have failed to respond to conventional therapy. Alosetron has been proved ineffective in male patients with IBS or in constipation-predominant IBS. In children, the safety and effectiveness of the drug have not been established. Geriatric patients may be at a greater risk for complications, such as constipation. Therefore, we do not recommend using alosetron in male, pediatric, or geriatric patients. It should be kept in mind that less than 5% of IBS is considered severe, and only a fraction of severe cases are diarrhea-predominant.

Enrollment in the Lotronex Risk Management Program is mandated by the FDA for physicians who wish to prescribe the drug. Alosetron should not be used patients with (1) constipation; (2) a history of intestinal obstruction, stricture, toxic megacolon, GI perforation or adhesions, ischemic colitis, impaired intestinal circulation, thrombophlebitis, or hypercoagulable state; and (3) current or a history of inflammatory bowel disease or diverticulitis.

For adult women, alosetron should be started at a dosage of 1 mg orally qd for 4 weeks. If, after 4 weeks, the 1-mg qd dosage is well tolerated but does not adequately control IBS symptoms, the dosage can be increased to 1 mg bid, which is the dose used in controlled clinical trials. Alosetron should be stopped in patients who have not had adequate control of IBS symptoms after 4 weeks of treatment with 1 mg bid.

Tegaserod (Zelnorm) is an aminoguanidine-indole with selective and partial 5-HT4-receptor agonist activity. 5-HT4 agonists possess GI stimulatory effects, partially by facilitating enteric cholinergic transmission.48 Tegaserod accelerates transit time through the left colon in healthy individuals,49 and transit time of the upper GI and small bowel in patients with IBS.50 In a recent randomized, double-blind, placebo-controlled study of patients with constipation-predominant IBS, tegaserod, at a dose of 4 mg/d or 12 mg/d, significantly improved abdominal pain, bowel function, and general well-being.51

Patients with constipation-predominant IBS frequently have delayed small-bowel and/or colonic transit.52 In a randomized, placebo-controlled trial of patients with constipation-predominant IBS, tegaserod 2 mg orally, bid, has been shown to accelerate orocecal transit, mostly as a result of shortened small-bowel transit.50 The most-frequent adverse events were related to the GI tract, including abdominal pain, diarrhea, dyspepsia, flatulence, and vomiting. The medication was recently approved by the FDA for the treatment of female patients with constipation-predominant IBS.
OUTCOMES

IBS is a chronic disease with an extremely variable clinical course in the general population. IBS is a "safe" diagnosis; patients with a diagnosis of IBS seldom turn out to suffer from serious organic disease, and the time-honored clinical strategy of reassuring the patient that the diagnosis is benign without significant risk of missing an organic disease is well justified.13,53,54

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