Pathophysiology of irritable bowel syndrome

Authors Andrew B Chun, MD Arnold Wald, MD Section Editor Nicholas J Talley, MD, PhD Deputy Editor Peter A L Bonis, MD

Last literature review version 17.1: January 2009 | This topic last updated: April 22, 2008 (More)

INTRODUCTION — Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause. It is the most commonly diagnosed gastrointestinal condition and comprises 25 to 50 percent of all referrals to gastroenterologists [1] . IBS also accounts for a significant number of visits to primary care physicians and is the second highest cause of absenteeism after the common cold [2] .

This topic review will summarize the current state of knowledge concerning the pathogenesis of IBS. The clinical manifestations, diagnosis, and therapy of this disorder are presented separately. (See "Clinical manifestations and diagnosis of irritable bowel syndrome" and see "Treatment of irritable bowel syndrome").

PATHOPHYSIOLOGY — The pathophysiology of IBS remains uncertain. Hereditary and environmental factors are likely to have a role [3] . Many studies have reported abnormal gastrointestinal motility, visceral hypersensitivity, psychologic dysfunction, and emotional stress in patients with IBS. Despite intensive

investigations, the results have often been conflicting and no physiologic or psychologic abnormality has been found to be specific for this disorder.

Gastrointestinal motility — The symptoms of IBS have traditionally focused attention on colonic motility. A number of different findings have been obtained: One study described 3 cpm (contractions per minute) in the unstimulated colon in patients with IBS compared to 6 cpm in controls [4] . Other reports, however, found basal motility to be increased in IBS, but these changes were also found in psychoneurotic patients without bowel symptoms [5] . The "gastro-colonic" response to test meals or sham feeding in patients with IBS results in prolonged rectosigmoid motor activity compared to normals [6] . Stress, anger, intravenous cholecystokinin, and colonic perfusion of deoxycholic acid also increase colonic motility in IBS, but these findings occur in control subjects as well.

These and other studies of motility in IBS have been plagued by inconsistent results and the wide range of normal findings. No predominant pattern of motor activity has emerged as a marker for IBS.

As in the colon, the results of small bowel motility in IBS have been inconsistent. Decreased fasting amplitude and cycle length of migrating motor complexes (MMC) and increased frequency of clustered contractions have been found [7] . These changes have also been demonstrated in patients without symptoms of IBS.

Some investigators have described a shortening of the fed motor pattern after meals [8] . However, other studies have not been able to reproduce this finding.

Visceral afferent hypersensitivity — Perception in the gastrointestinal (GI) tract results from stimulation of various chemoreceptors and mechanoreceptors in the gut wall. These receptors transmit signals via afferent neural pathways to the dorsal horn of the spinal cord and ultimately to the brain. Several studies have focused on selective hypersensitization of visceral afferent nerves in the gut as a possible biologic marker for IBS. The following observations have been noted: Increased colonic sensitivity was strongly influenced by a psychological tendency to report pain and urgency rather than increased neurosensory sensitivity in a study involving balloon distension of the descending colon [9] . Rectal distension in patients with IBS increases cerebral cortical activity more than in controls [10] . Patients who complain of bloating and excess gas actually had volumes of gas in

the GI tract similar to asymptomatic controls but exhibit impaired handling of intestinal gas loads [11,12] . More recent studies demonstrate that the intestinal dysfunction in gas propulsion is magnified by relatively low intraluminal lipid loads, suggesting that patients with IBS exhibit hypersensitivity to a lipid induced modulating mechanism [13] . About one-half of patients with IBS (mainly those with constipation) have a measurable increase in abdominal girth associated with bloating, although this may not be related to the volume of intestinal gas [14] .

In addition, many patients with IBS have lower tolerance for rectal distension with a balloon than controls [15,16] . This possible increase in sensitivity appears to be specific for visceral afferents since patients with IBS have normal or even increased thresholds to somatic pain [17] . Repetitive stimulation of the sigmoid colon can induce visceral hyperalgesia in the rectum in patients with IBS, but not in controls [18] . This response occurs even in patients who do not initially exhibit afferent hypersensitivity. These observations have led to the hypothesis that sigmoid contractions that are naturally associated with stress and response to meals may induce transient visceral hyperalgesia in IBS. Visceral hyperalgesia in IBS is not specific to the colon but can be demonstrated at different sites in the gut [19] .

Visceral hyperalgesia is only found in a subset of patients with IBS. As an example, community based patients who report IBS symptoms, but do not seek medical attention, do not have visceral hyperalgesia [20] . This observation suggests that psychologic distress or chronic healthcare seeking behavior may contribute to the sensitization of visceral afferents in some patients.

Visceral hyperalgesia may not be a specific biological marker for IBS. It also occurs in the absence of bowel symptoms in patients with other chronic pain syndromes, including esophageal chest pain, angina pectoris with normal coronary arteries, and fibromyalgia [21] . (See appropriate topic reviews.)

It is still unclear whether visceral hyperalgesia is mediated by the local gastrointestinal nervous system, by central modulation from the brain, or some combination of the two. In one report, for example, control subjects had increased activity in the anterior cingulate cortex of the brain in response to rectal distension, whereas patients with IBS had increased activity in the left prefrontal cortex [22] . However, a subsequent study using functional MRI in a larger group of patients found normal patterns of regional cerebral activation in response to rectal distension but activity was much higher in IBS than controls [23] . These

suggesting a possible common link. most of whom were derived from tertiary referral centers. tachykinins. psychologic factors have been hypothesized to account for all or part of the increased pain sensitivity exhibited by patients with IBS [26] . Candidate mediators include serotonin. A study in which fullthickness jejunal biopsies were obtained in 10 patients with severe IBS found an increase in lymphocyte infiltration in the myenteric plexus in nine patients and neuron degeneration in six patients [30] . In a longitudinal study of perceptual responses to rectal stimulation. Thus. Furthermore. . Other studies have demonstrated a correlation between abdominal pain in IBS and the presence of activated mast cells in proximity to colonic nerves [31. A study in humans suggested that the development and maintenance of visceral hypersensitivity may in part depend upon the N-methyl-Daspartate (NMDA) receptor [25] . The extent to which these observations might contribute to the pathogenesis of IBS in the general population remains unclear as only a small number of patients have been studied. Similar observations have been made in patients with presumed postinfectious IBS (see "Postinfectious" below). and neurotrophins [24] . bradykinin.32] . The NMDA receptor is located on dorsal horn neurons of the spinal cord. substance P.observations support the theory that central nervous system processing of visceral afferent impulses may be important in IBS. The term "postdysenteric bowel disturbance" has been proposed to describe this disorder [33] . Selective attention to gastrointestinal sensation and disease attribution are thought to be the major contributing factors. calcitonin gene-related peptide. which receive primary afferent input from the gastrointestinal organs. the conclusion that there is a purely biologic basis for visceral hyperalgesia in IBS may be premature. patients with IBS normalized during repeated testing over 12 months although there were no changes in either symptoms or psychological profiles [27] . Microscopic inflammation — Detailed immunohistologic investigation has revealed mucosal immune system activation in a subset of patients with irritable bowel syndrome (mostly those with the diarrhea predominant type) [28. Postinfectious — The development of irritable bowel syndrome following infectious enteritis has been suspected clinically based upon a history of an acute diarrheal illness preceding the onset of irritable bowel symptoms in some patients.29] .

The predominant symptom was diarrhea. In severe infection. Pathogens included Escherichia coli O157:H7 and Campylobacter jejuni. abdominal cramps. Another systematic review found that risk factors included young age. Another possible explanation is the development of idiopathic bile acid malabsorption. disruption of mucosal nerves may lead to irritability [44] . which may respond to cholestyramine [45. The severity of illness may reflect the degree to which the organism invades the mucosa [43] .46] . 95% CI 4. Persistence of symptoms in these patients appears to be at least partly related to psychological factors [42] . Although this study was potentially limited by several possible sources of bias (particularly recall bias). anxiety and depression [41] . it at least suggests that a subset of patients may become more focused on bowel complaints following acute infection. During follow-up.7-11. One of the largest prospective studies included a total of 2069 individuals who had been exposed to contaminated drinking water after heavy rainfall [36] .Few controlled studies have investigated this topic in detail. A systematic review of eight studies estimated a prevalence of postinfectious IBS in 10 percent of patients with a history of bacterial gastroenteritis compared with about 1 percent of controls (odds ratio 7. Independent risk factors included younger age and female sex. prolonged fever. and prolonged diarrhea. In this report. and (during the outbreak) bloody stools. weight loss. and that bowel complaints in these patients can be a source of significant disability.3. but persistent irritable bowel symptoms have been noted in approximately 10 to 30 percent of patients after acute bacterial infection [33-39] .1) [40] . An increase in . There were 904 cases of self-reported gastroenteritis and several documented positive stool cultures including 27 cases of hemolytic uremic syndrome. significantly more individuals with self-reported gastroenteritis fulfilled the Rome I criteria for IBS compared with controls (28 versus 10 percent). The cause of persistent or new bowel symptoms following acute infection is uncertain although several theories have been proposed: One possible explanation is suggested by the association of persistent symptoms with more severe acute illness. The outbreak spawned development of a prospective cohort study (known as the Walkerton Health Study) to evaluate long-term outcomes in affected individuals. patients who had vomiting as part of their initial illness were less likely to develop persistent bowel symptoms. Similar risk factors were noted in another study [33] .

phobias. Alteration in fecal microflora — The complex ecology of the fecal microflora has led to speculation as to whether perturbations in its composition could be associated with diseases including IBS.enteroendocrine cells. Emerging data suggest that the fecal micribiota in individuals with IBS differs from healthy controls [53] . Additional studies are needed to validate these observations and to understand whether they are pathophysiologically significant. Reduced disaccharidase activity with resulting malabsorption of dietary sugars has been observed following enteric infections [50] . These observations need to be considered in the context of several biases that may be inherent in the studies described above. Psychosocial dysfunction — Many patients with IBS who present to a tertiary referral center exhibit increased anxiety. or may have developed inflammatory bowel disease following infection. Thus. not all studies have detected an increase in IBS following acute infectious diarrhea [52] . One study suggested that increased numbers of enterochromaffin cells and depression were independent predictors of developing post-infectious IBS [49] . T lymphocytes. In one report. One potentially important observation is that patients with preexisting IBS may be more likely to present to their physician with bacterial gastroenteritis compared with those without IBS [51] . These patients rarely meet criteria for a major psychiatric diagnosis. patients with IBS symptoms who do not seek medical attention are indistinguishable psychologically from healthy controls [54] . epidemiologic studies examining the rate of IBS following bacterial gastroenteritis may have overestimated the rate at which new symptoms develop. Furthermore. Some patients may have had previously occult inflammatory bowel disease. However. these changes persisted for more than one year [47] . Neither a reduction in enteroendocrine cells nor improvement in symptoms was observed in a controlled trial of prednisolone of patients with post-infectious IBS [48] . depression. Patients with IBS are more likely than controls to have a history of physical or sexual abuse [55] and/or a learned pattern of illness behavior originating in . The implication of these observations is that psychiatric distress may influence the experience of IBS but does not cause the symptoms. Patients treated with antibiotics may develop diarrhea related to alteration in colonic flora. and gut permeability has been demonstrated following acute Campylobacter enteritis. and somatization.

Having a parent with IBS was a greater independent predictor for IBS than having an affected twin. Similar findings have been observed in animal models. One study evaluating the association between IBS and abuse found that patients with IBS were more likely to express neuroticism than those without this disorder [56] . but none have been proven to have a role. These include: Carbohydrate malabsorption (such as lactose or fructose intolerance) Bile acid malabsorption Neurohumoral or neuroimmune stress responses Elevated levels of short chain fatty acids in the stool Bacterial overgrowth An increased concentration of intestinal serine proteases INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients. One study found that concordance rates for IBS were twice as high in monozygotic compared to dizygotic twins [3] . Emerging data suggest that overactivity in the brain CRF and CRFreceptor signaling system contributes to anxiety disorders and depression [57] . this response can be blunted by the administration of a CRF receptor antagonist with no effect on the hypothalamopituitary-adrenal axis [58] . Intravenous administration of CRF increases abdominal pain and colonic motility in IBS patients to a higher degree than normal controls. (See "Patient information: Irritable bowel syndrome"). www. One unifying hypothesis concerning the role of stress and psychoneuroticism in IBS is based upon corticotropin releasing factor (CRF). The relationship between learned behavior and genetics in IBS is still being elucidated.uptodate.childhood. which includes this and other topics. . Furthermore. Neuroticism was associated with abuse during childhood and adulthood. a peptide released from the paraventricular nucleus and now considered to be a major mediator of the stress response [57] . or to refer patients to our public web site. The investigators hypothesized a causal pathway whereby abuse leads to the expression of neuroticism that in turn leads to IBS. We encourage you to print or e-mail this topic Other possible mechanisms — Several other factors that may mimic or exaggerate existing symptoms of IBS have been investigated.

Schuster. RC. M.Use of UpToDate is subject to the Subscription and License Agreement. M. N Engl J Med 1975. Pryde. Lipid-induced intestinal gas retention in irritable bowel syndrome. Enteric and central contributions to intestinal dysmotility in irritable bowel syndrome. Azpiroz. GM. Lawal. Rectosigmoid motility response to sham feeding in irritable bowel syndrome: Evidence of a cephalic phase. M. Sarna. Whitehead. Gastroenterology 2002. KC. and predictive values of pain sensory thresholds. Zighelboim. WJ Jr. Campbell. specificity. Gill. RL. et al. 48:14. 130:26. SI. Gastroenterology 1981. Increased colonic pain sensitivity in irritable bowel syndrome is the result of an increased tendency to report pain rather than increased neurosensory sensitivity. V. Lasser. SF. MM. Munakata. Snape. F. Enck. Levitt. Skoubo-Kristensen. SM. Renault. R. Kellow. WE. Phillips. OS. Gastroenterology 2002. IJ. A. 98:1208. Jones. J. 121:799. Visceral perception in irritable bowel syndrome: Rectal and gastric responses to distension and serotonin type 3 . Gastroenterology 1991. F. B. Rectal distention testing in patients with irritable bowel syndrome: Sensitivity. KR. Gastroenterol Clin North Am 1991. Salvioli. 131:1003. JE. J. et al. Serra. Malagelada. Prolonged ambulant recordings of small bowel motility demonstrate abnormalities in the irritable bowel syndrome. Palsson. The role of intestinal gas in functional abdominal pain. and patients with irritable bowel syndrome. Dig Dis Sci 1992. Colonic myoelectric activity in the irritable bowel syndrome. Kern. 93:727. Gut 2001. JR. Scand J Gastroenterol 1989. Kellow. et al. 70:326. JR. H. 56:1202. Trimble. Wingate. Bond. Boivin. Impaired transit and tolerance of intestinal gas in the irritable bowel syndrome. Serra. 293:524. 24:53. Irritable bowel syndrome in twins: Heredity and social learning both contribute to etiology. Plourde. Tolerance for rectosigmoid distension in irritable bowel syndrome. 80:893. Levy. L. Gastroenterology 2001. B. 40:1607. Carlson. Repetitive sigmoid stimulation induces rectal hyperalgesia in patients with irritable bowel syndrome. JM. WE. Latimer. A. 123:700. GM. Gastroenterology 1990. Patients with irritable bowel syndrome have greater pain tolerance than normal subjects. Lea. et al. J. Azpiroz. et al. Colonic motor and myoelectrical activity: A comparative study of normal subjects. Farouk. REFERENCES Everhart. Dorn. Cohen. 20:269. et al. Farzaneh. J. NJ. R. D. MD. et al. Jepsen. M. DL. Gut 2007. 37:168. P. Eckersley. A. JE. Sidhu. Irritable bowel syndrome in office based practice in the United States. Elsborg. Novel evidence for hypersensitivity of visceral sensory neural circuitry in irritable bowel syndrome patients. H. RB. Houghton. Gastroenterology 1987. S. Heightened visceral sensation in functional gastrointestinal disease is not sitespecific. LA. Naliboff. Malagelada. 98:1187. Evidence for a generalized disorder of gut sensitivity. Whitehead. E. Holtkotter. SD. Cook. Jones. Collins. et al. Agrawal. PF. et al. Gastroenterology 2006. 122:1771. Gastroenterology 1990. A. Talley. psychoneurotic patients. Thiwan. Bouin. Dig Dis Sci 1995. Gastroenterology 1976. JE. van Eeden. 100:998. Diagnostic evaluation of the irritable bowel syndrome. Gastroenterology 2006. et al. P. Gastroenterology 1997. Relationship of abdominal bloating to distention in irritable bowel syndrome and effect of bowel habit. 112:55. B. JH. S.

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It is the most commonly diagnosed gastrointestinal condition. MD Last literature review version 17. A population based study in Europe found an overall prevalence of 11. Inc. However. however. young patients and the elderly.5 percent (a value similar to that noted in reports in the United States). MD Section Editor J Thomas LaMont. MD Deputy Editor Peter A L Bonis. | Subscription and License Agreement Licensed to: Bala Shanmugam Clinical manifestations and diagnosis of irritable bowel syndrome Authors Andrew B Chun.© 2009 UpToDate. IBS affects men and women. younger patients and women are more likely to be diagnosed with IBS. All rights reserved. MD Arnold Wald. 2009 (More) INTRODUCTION — Irritable bowel syndrome (IBS) is a gastrointestinal syndrome characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause. A systematic review estimated that there is an overall 2:1 female predominance in North America [3] . . The prevalence of IBS in North America estimated from population-based studies is approximately 10 to 15 percent [1-6] .1: January 2009 | This topic last updated: February 4. the prevalence varied widely among countries [7] .

while defecation often provides some relief.16] . Several factors. These include: Pain associated with anorexia. Chronic abdominal pain — Abdominal pain in IBS is usually described as a crampy sensation with variable intensity and periodic exacerbations. This constellation is extremely rare in IBS unless there is concurrent major psychologic illness. The severity of the pain may range from mildly annoying to debilitating. (See "Pathophysiology of irritable bowel syndrome" and see "Treatment of irritable bowel syndrome"). and consistency of the .gastro.Only about 15 percent of those affected actually seek medical attention [1. However. The pathophysiology and therapy of this disorder are presented separately. However. frequency. and is the second highest cause of work absenteeism after the common cold [12] . it is important to elicit a careful history of the volume. the location and character of the pain can vary widely [15. some clinical features are clearly not compatible with the syndrome and should prompt an investigation for organic diseases. with some studies suggesting annual direct and indirect costs of up to $30 billion [13] .org/wmspage. The AGA guideline for irritable bowel syndrome [14] . awakens the patient from sleep. IBS also accounts for a significant number of visits to primary care physicians. Such pain is not characteristic of IBS. Altered bowel habits — By definition. Nevertheless.8-10] . Despite the variability of abdominal pain in IBS.cfm?parm1=4453. since the range of normal bowel habits is quite broad. can be accessed through the AGA web site at http://www. The pain is generally located in the lower abdomen. IBS has been associated with increased health care costs. however. or weight loss.2. such as emotional stress and eating. Pain that is progressive. as well as other AGA guidelines. the absolute number of patients is still so large that IBS in its various forms comprises 25 to 50 percent of all referrals to gastroenterologists [11] . or prevents sleep. patients with IBS complain of altered bowel habits. the symptom complex of chronic abdominal pain and altered bowel habits remains the nonspecific yet primary characteristic of IBS [15] . This topic review will discuss the clinical manifestations and diagnosis of IBS. CLINICAL MANIFESTATIONS — Patients with IBS can present with a wide array of symptoms which include both gastrointestinal and extraintestinal complaints. may exacerbate the pain. malnutrition. often on the left side.

and increased urinary frequency and urgency [18] . Constipation — Constipation may last from days to months. dysphagia. These include impaired sexual function. Approximately one-half of all patients with IBS complain of mucus discharge with stools. Large volume diarrhea. and inappropriate use of enemas and laxatives. dyspareunia. (See "Pathophysiology of irritable bowel syndrome"). intermittent dyspepsia. Patients may also experience a sense of incomplete evacuation even when the rectum is empty. In one study. 99 percent of normal subjects reported between three bowel movements per day to three bowel movements per week [17] . nocturnal diarrhea. including gastroesophageal reflux. Extraintestinal symptoms — Patients with IBS often complain of a broad range of non-gastrointestinal symptoms. and non-cardiac chest pain. Diarrhea — Diarrhea is usually characterized as frequent loose stools of small to moderate volume. most often in the morning or after meals. constipation. nausea. bloody stools. They are also more likely to have hypertension. The normal frequency of bowel movements is variable. (See "Pathophysiology of irritable bowel syndrome"). are common in patients with IBS [15] . alternating diarrhea and constipation. A subgroup of patients describe an acute viral or bacterial gastroenteritis which then leads to a subsequent disorder characteristic of diarrhea-predominant IBS. . and rheumatologic syndromes. Patients with IBS also frequently complain of abdominal bloating and increased gas production in the form of flatulence or belching. or normal bowel habits alternating with either diarrhea and/or constipation. called post-infectious IBS. Most bowel movements are preceded by lower abdominal cramps and urgency even to the point of fecal incontinence and may be followed by a feeling of incomplete evacuation. with interludes of diarrhea or normal bowel function. for example. Patients with IBS complain of diarrhea. prolonged time on the toilet.20] . reactive airway disease. This can lead to straining with defecation. dysmenorrhea. Stools are often hard and may be described as pellet shaped. including fibromyalgia [19. and greasy stools are not associated with IBS and suggest an organic disease. Stools generally occur during waking hours. Other gastrointestinal symptoms — Upper gastrointestinal symptoms. early satiety.patient's stools.

A later report substantiated the usefulness of these symptoms in 361 outpatients: 81 had IBS. These symptoms included relief of pain with bowel movements. and in men. In the above study. or a feeling of incomplete bowel movement. the latter observation has also been noted in other reports [22. The sensitivity and specificity to discriminate IBS from all patients without IBS were 42 and 85 percent. discordant data have also been reported. respectively. In an effort to standardize clinical research protocols. and a sense of incomplete emptying.23] . et al formulated a symptom complex suggestive of IBS (show table 1) [21] . This concept originated in 1978 when Manning. which was revised in 1999 and then again in 2005 [15] . efforts have been made to standardize the diagnosis of IBS using symptom based criteria. The following results were noted: The likelihood of IBS was proportional to the number of Manning's criteria (show table 2). In one study. an international working team published a consensus definition in 1992 called the Rome criteria.DIAGNOSTIC CRITERIA — In the absence of a biologic disease marker. three of the core Manning criteria (loose stools. the predictive ability of the Manning criteria was reduced in the elderly. passage of mucus. abnormal stool form (lumpy/hard or loose/watery). defecation straining. IBS was defined as a functional group of discomfort or bowel disorders in which abdominal pain is associated with defecation or a change in bowel habit and with features of disordered defecation (show table 3). passing mucus and bloating. The sensitivity and specificity to discriminate IBS from organic gastrointestinal disease were 58 and 74 percent. more frequent bowel movements with onset of pain. . Supportive symptoms that are not part of the Rome III criteria include: abnormal stool frequency (≤ 3 bowel movements per week or >3 bowel movements per day). looser and more frequent stools with onset of pain. 101 had organic gastrointestinal disease. and pain relieved by defecation) equally applied to both genders. urgency. Four subtypes of IBS were also recognized: IBS with constipation (hard or lumpy stools ≥ 25 percent and loose (mushy) or watery stools <25 percent of bowel movements) IBS with diarrhea (loose (mushy) or water stools ≥ 25 percent and hard or lumpy stools <5 percent of bowel movements) Mixed IBS (hard or lumpy stools ≥ 25 percent and loose (mushy) or watery stools ≥ 25 percent of bowel movements Unsubtyped IBS (insufficient abnormality of stool consistency to meet the above subtypes). respectively. the other three criteria were not useful for making the diagnosis of IBS in any patient subgroups [24] . However. and 145 were controls [22] .

30] . can be accessed through the AGA web site at http://www. However. a consensus statement issued by the American Gastroenterological Association recommends that the diagnosis of IBS should be based upon the identification of positive symptoms consistent with the condition (as summarized by the Rome criteria) and excluding in a cost-effective manner other conditions with similar clinical presentations. Other criteria have also been proposed (such as the Kruis criteria) but are uncommonly used [26-28] . emphasis should be placed upon identifying a symptom complex compatible with IBS and then using prudent. The first step in diagnosis is a careful assessment of the patient's symptoms. and/or diarrhea [25] . A careful history may identify dietary factors and medications . abdominal pain. Considering the available data and the above limitations. The AGA guideline for irritable bowel syndrome [14] . A nonjudgmental series of open-ended questions helps to establish a caring physicianpatient relationship. results in individual studies have been variable. Furthermore. the predictive values of the criteria depend upon the prevalence of IBS and organic disease in the individual practice setting.The Rome criteria have been criticized for overemphasis on abdominal pain and failure to emphasize postprandial urgency. as well as other AGA guidelines. diagnostic testing except in those patients with "alarm" or atypical symptoms or laboratory abnormalities such as anemia or electrolyte disturbances. to avoid unnecessary and costly testing. DIAGNOSTIC APPROACH — Many physicians place great importance on the exclusion of organic causes of symptoms compatible with IBS. As discussed Although the overall sensitivity and specificity are high. A 2009 position statement issued by the American College of Gastroenterology (ACG) suggests specific forms of testing be guided by the clinical setting (show table 4) [3] . the diagnosis of IBS can be made on the basis of classic symptoms in most patients.gastro. A number of studies have assessed the accuracy of the Rome and Manning criteria in a variety of practice settings [27] .cfm? parm1=4453. albeit not exhaustive. providing a rationale for ongoing studies that are attempting to further refine these criteria [29. As a result. The Rome and Manning criteria provide guidelines to identify patients with suspected IBS. some investigators continue to use the Manning criteria or a combination of both.

Others. Initial diagnostic studies — Multiple diagnostic tests have been recommended for patients with IBS symptoms. (See "Approach to the adult with acute diarrhea in developed countries").37] . (See "Lactose intolerance" and see "Etiology and evaluation of chronic constipation in adults"). including IBS patients [3] . although they may help to reassure an anxious patient. We occasionally perform this procedure in younger patients with persistent diarrhea to exclude inflammatory bowel disease [34] . since stool weight in excess of 300 g per day or increased fecal fat is unlikely in IBS [15] . However. serum testing for celiac disease using IgA antibody to tissue transglutaminase (tTG) is recommended [33] . have recommended colonoscopy for patients over the age of 50 [35] . (See "Clinical features and diagnosis of malabsorption"). Stated differently. there is limited evidence supporting the routine performance of specific diagnostic testing in patients without alarm features and in those without diarrhea. Routine flexible sigmoidoscopy and biopsy have a low diagnostic yield and are not cost-effective in IBS. including the American Gastroenterological Association Patient Care Committee. Nevertheless. sorbitol [32] . as noted above. Mucosal biopsies should be performed in those with persistent and continuous diarrhea to exclude microscopic colitis. . As noted above. and magnesium containing antacids that may cause diarrhea. In patients with diarrhea as the predominant symptom who have risk factors for a parasitic infection (such as recent foreign travel to a developing country). a limited number of diagnostic studies can rule out organic illness in the majority of patients: Routine laboratory studies such as a complete blood count are normal in IBS. Examples include lactose [31] . This limited diagnostic approach rules out organic disease in over 95 percent of patients [36.that mimic or exacerbate symptoms of IBS. some amount of testing is usually performed. In patients who have symptoms suggestive of IBS based upon the Rome III criteria (show table 3) and no alarm symptoms or signs on the history and physical examination. The ACG position statement emphasizes that routine use of colon cancer screening tools is recommended for all patients ≥ 50 years old. (See "Diagnosis of celiac disease"). A 24-hour stool collection may sometimes be useful if osmotic or secretory diarrhea or malabsorption is suspected. less than 5 percent of patients with organic disease will be incorrectly diagnosed with IBS using this diagnostic strategy. A normal C-reactive protein is useful in excluding an underlying inflammatory condition causing symptoms. and medications such as anticholinergic drugs and calcium channel blockers that can cause constipation. we suggest that three separate and fresh stools be examined for ova and parasites. (See "Lymphocytic and collagenous colitis (microscopic colitis)").

We encourage you to print or e-mail this topic review. INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients. normal diagnostic studies at this point in the evaluation suggest it is reasonable to begin a trial of symptomatic therapy. patients with refractory or severe IBS may be gently questioned about physical and sexual abuse once a physician-patient relationship has been established [38] .org/wmspage. Consideration should also be given to psychologic factors that may influence the patient to seek medical attention [39. the symptom complex of chronic abdominal pain and altered bowel habits remains the nonspecific yet primary characteristic of IBS.40] .Thus. patients with predominantly diarrhea should have a work-up similar to other patients with chronic diarrhea (show algorithm 2A-B). because of the positive correlation between abuse and certain gastrointestinal illness patterns. (See "Treatment of irritable bowel syndrome"). can be accessed through the AGA web site at http://www. a more extensive evaluation should be considered in patients who have had a change or progression of symptoms. or to refer patients to our public web site. personal concern about a serious disease precipitated by the recent death of a family member from a gastrointestinal disease may be the primary motivator to seek attention at this particular time. (See "Patient information: Irritable bowel syndrome").uptodate. However. In addition. www. (See "Treatment of irritable bowel syndrome"). The diagnostic evaluation depends upon the predominant symptoms: patients with predominantly constipation should have a work-up similar to other patients with chronic constipation (show algorithm 1) (see "Etiology and evaluation of chronic constipation in adults"). Other diagnostic studies — It may be reasonable to consider additional diagnostic studies in patients who do not respond to general treatment measures. as well as other AGA guidelines.gastro. which includes this and other topics. The presence of persistent symptoms does not mean that the diagnosis was However. SUMMARY AND RECOMMENDATIONS Patients with IBS can present with a wide array of symptoms which include both gastrointestinal and extraintestinal complaints. As an example.cfm?parm1=4453. The American Gastroenterological Association (AGA) technical review for the evaluation and management of chronic diarrhea [41] . Patients can be reevaluated in three to six weeks to assess the response to treatment. Many physicians place great importance on the exclusion of organic causes of symptoms compatible with .

95:2816. et al. AP. 101:927. EJ. a limited number of diagnostic studies can rule out organic illness in many patients and a sizeable number require no testing at all. S. AR. BMJ 1992. D. Tack. JE. Nevertheless. The prevalence. et al. However. KW. AC. Saunders. Hahn. As discussed above. Ford. Gastroenterology 1991. Van Dyke. L. An evidence-based position statement on the management of irritable bowel syndrome. WB. LJ. Heaton. 103:1229. Zhiming. Aliment Pharmacol Ther 2003. Maier. Andruzzi. US householders survey of functional gastrointestinal disorders: Prevalence. Locke. Irritable bowel syndrome in the general population. Dig Dis Sci 1993. C. Am J Gastroenterol 2009. Am J Gastroenterol 2000. there is limited evidence supporting the routine performance of specific diagnostic testing in patients without alarm features and in those without diarrhea. Differences between individuals with self-reported irritable bowel syndrome (IBS) and IBS-like symptoms. diagnostic testing. WG. Whorwell. F. Epidemiology of colonic symptoms and the irritable bowel syndrome. Forman. Bailey. DA. to avoid unnecessary and costly testing. Talley. However. Drossman. et al. 104:S1. O'Donnell. Zinsmeister. Multiple diagnostic tests have been recommended for patients with IBS symptoms. albeit not exhaustive. as noted above. and health impact. . Functional gastrointestinal disorders in Canada: first population-based survey using Rome II criteria with suggestions for improving the questionnaire. Mearin. Renault. sociodemography. 38:1569. Pare. Hungin. Am J Gastroenterol 2008. J. AG. NJ. 47:225. In patients who have symptoms suggestive of IBS based upon the Rome III criteria (show table 3) and no alarm symptoms or signs on the history and physical examination. the diagnosis of IBS can often be made with confidence in a positive fashion based on a typical presentation rather than by only excluding organic disorders. 304:87. PF. emphasis should be placed upon identifying a symptom complex compatible with IBS and then using prudent. 17:643. FEM. P. NJ. Thompson. BA. 42:2585.IBS. et al. PJ. (See "Diagnostic approach" above). et al. Dig Dis Sci 1997. E. 102:1962. Irritable bowel syndrome: a 10-yr natural history of symptoms and factors that influence consultation behavior. YA. et al. Braddon. GR. Irvine. The Rome and Manning criteria provide guidelines to identify patients with suspected IBS. Jones. Saito. Dig Dis Sci 2002. R. Use of UpToDate is subject to the Subscription and License Agreement. A comparison of the Rome and Manning criteria for case identification in epidemiological investigations of irritable bowel syndrome. WC. patterns and impact of irritable bowel syndrome: an international survey of 40 000 subjects. Everhart. Irritable bowel syndrome in office based practice in the United States. REFERENCES Talley. Gastroenterology 1992. Lydeard. some amount of testing is usually obtained. Symptoms of irritable bowel syndrome in a British urban community: Consulters and nonconsulters. American College of Gastroenterology IBS Task Force.

et al. 130:1480. Gastroenterol Clin North Am 1991. Upton. Melton. SJ. Hyams. Gut 1990. A. NJ. KW. Irritable bowel syndrome defined by factor analysis: Gender and race comparisons. JB. Beretta. Thompson. Gut 1986. LJ. Lancet 1980. et al. AR. JH. Kruis. Towards a positive diagnosis of the irritable bowel. WD. Gastroenterology 1983. Evidence. Am J Gastroenterol 1999. FL. Gastroenterology 2006. Suarez. Donowitz. Carter. Arch Intern Med 2001. Sanders. 358:1504. Phillips. Weinzierl. Morris. C. 100:68. M. AM. 333:1. et al. 107:20S. 87:1. 97:2812. Br Med J 1978. Thieme. Gastroenterology 1991. JI. Talley. DP. AM. Cuevas. Manning. Camilleri. Connell. WG. Site of pain from the irritable bowel. WD. NJ. Hurlstone. Bat. Andersen. Mayer. Thompson. 123:2108. EW 3rd. WT. Comorbidity of fibromyalgia with medical and psychiatric disorders. MG. Creed. 37:164. 27:37. E. Association of adult coeliac disease with irritable bowel syndrome: a case-control study in patients fulfilling ROME II criteria referred to secondary care. N Engl J Med 1995. Choi. et al. WG. et al. A diagnostic score for the irritable bowel syndrome. W. Diagnostic value of the Manning criteria in irritable bowel syndrome. RC. JL. MW. et al. Dig Dis Sci 1995. 161:2081. G. Chey. JE. Everhart. BD. Predictive value of the Rome criteria for diagnosing the irritable bowel syndrome. WH. The utility of diagnostic tests in irritable bowel syndrome patients: a systematic review. 40:2647. Sorbitol intolerance: An unappreciated cause of functional gastrointestinal complaints. Schuster. ET. Whitehead. Taub. 2:443. Gastroenterology 2002. Drossman. Gastroenterology 1991. Functional bowel disorders. 100:998. White. et al. WE. The burden of selected digestive diseases in the United States. J. Savaiano. et al. Pope. 94:2912. 5470:1095. L. MJ. Airway responsiveness to inhaled methacholine in patients with irritable bowel syndrome. et al. Swarbrick. MD. Depew. Diagnostic criteria for the irritable bowel syndrome. Its value in the exclusion of organic disease. C. GF. Schoenfeld. 31:77. 107:5S. Orsenigo. Whorwell. JR. Smith. Frigerio. A comparison of symptoms after the consumption of milk or lactose-hydrolyzed milk by people with selfreported severe lactose intolerance. WG. R. DS. Camilleri. M.and consensusbased practice guidelines for the diagnosis of irritable bowel syndrome. DA. Irvine. PJ. Diagnostic approach to the patient with irritable bowel syndrome. Hammer. Hudson. AGA technical review on irritable bowel syndrome. Irritable bowel . 84:30. GF. 2:653. Aliment Pharmacol Ther 1997. 20:269. Am J Med 1992. Irritable bowel syndrome.Gastroenterology 1991. Longstreth. G. Chey. Munck. Diagnostic evaluation of the irritable bowel syndrome. et al. Gastroenterology 1984. AF. Stevens. et al. SF. Hegarty. 11:3. Paterson. Irritable bowel syndrome: Still far from a positive diagnosis. AP. Gender differences in Manning criteria in the irritable bowel syndrome. Dig Dis Sci 1992. et al. Goldenberg. 92:363. M. Talley. DS. Vanner. Variation of bowel habit in two population samples. McCallum. Cook. L. Fass. Levitt. M. Gastroenterology 2002. M. JE. Hilton. MM. Am J Med 1999. Longstreth. Cash. JS. Roberts. LK. Svendsen. Vancouver. EA. CT. et al. Heaton. 123:2105. Schmulson. Non-colonic features of irritable bowel syndrome. Lancet 2001. Sandler. 100:591. RS. 122:1500. HG. Gastroenterology 2002. G. DA. Pimentel. P. Am J Gastroenterol 2002. M. American Gastroenterological Association medical position statement: irritable bowel syndrome. DL. et al. Br Med J 1965. FH. Am J Med 1999. Chang. Greenbaum.

Katon. Ann Intern Med 1992. Gastroenterology 1999. Ann Intern Med 1995. Lin. A 5-year follow-up study. Fine. Schiller. All rights reserved. Drossman. 2009 (More) INTRODUCTION — Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits in the absence of any organic disorder. WJ. 20:415.syndrome-prognosis and diagnostic safety. The irritable bowel syndrome: Review and a graduated multi-component treatment approach. DA. DA. J. Talley. Scand J Gastroenterol 1985. Leserman. 92:7S. Panic disorder: Relationship to high medical utilization. NJ. Inc. MD Last literature review version 17. Sexual and physical abuse and gastrointestinal illness. M. | Subscription and License Agreement Licensed to: Bala Shanmugam Treatment of irritable bowel syndrome Author Arnold Wald. PhD Deputy Editor Peter A L Bonis. 116:1009. et al. AGA technical review on the evaluation and management of chronic diarrhea. 116:1464. KD. Thompson. MD Section Editor Nicholas J Talley. Von Korff. © 2009 UpToDate. WG. The .1: January 2009 | This topic last updated: February 6. MD. Drossman. LR. 123:782. E. The approach to therapy of IBS will be reviewed here. Am J Med 1992.

or psychiatric comorbidity are critical to establish when developing the optimum therapy [1] . The doctor should be non-judgmental. Group 3 received sham acupuncture but had much more interaction with their HCP. An important question to answer is why the patient is seeking help at this time. stressors. establish realistic expectations with consistent limits. hidden agenda (disability claims. As a result. (See "Patient information: Irritable bowel syndrome"). and involve the patient in treatment decisions [1] . Recent exacerbating factors (medications. and that he or she should have a normal life span. concerns about serious illness. patient survival was similar to expected survival [2] . only 10 of 112 patients developed an organic gastrointestinal disease. Patients should be informed of the chronic and benign nature of IBS. the level of improvement in Group 3 was significantly better than Group 2. Patients with established. that the diagnosis (if well-established) is not likely to be changed. Group 1 was assigned to a waitlist only. Therapeutic relationship — The most important component of treatment lies in the establishment of a therapeutic physician-patient relationship. which in turn was significantly better than Group 1. dietary changes). The importance of the therapeutic relationship in IBS was emphasized in a study that investigated the components of the placebo effect and patient-provider interaction in 262 patients with IBS [3] . the focus of treatment should be on relief of symptoms and in addressing the patient's concerns. Patient education — Education of the proposed mechanisms of IBS helps to validate the patient's illness experience and sets the basis for therapeutic interventions. GENERAL PRINCIPLES — IBS is a chronic condition with no known cure. (See "Clinical manifestations and diagnosis of irritable bowel syndrome"). At both three and six weeks. . positive physician interactions have fewer IBS-related follow-up visits [2] . for example.clinical manifestations and diagnosis of this disorder are discussed separately. requests for opiates). The conclusion was that placebo effects are significant in IBS and the patient-health care provider interaction is the key part of that effect. In a 29-year follow-up study of 112 patients from the Mayo Clinic. whereas Group 2 received sham acupuncture with little interaction with a health care provider (HCP). (See "Pathophysiology of irritable bowel syndrome").

bananas. prunes. onions. (See "Lactose intolerance"). pretzels. An increase in the intake of fiber is often recommended. and binding of agents such as bile [10] . The proposed beneficial effects of fiber mechanisms of action include: enhancement of water holding properties of the stool. apricots. a systematic review that included 13 randomized controlled trials found no convincing evidence that the commonly-used bulking agents were more effective than placebo at relieving global IBS symptoms [11] . Underlying visceral hyperalgesia in IBS may explain the exaggerated discomfort experienced with consumption of gas-producing foods. Exclusion of foods that increase flatulence (beans. (See "Pathophysiology of irritable bowel syndrome"). because of the potential of fiber to exacerbate symptoms [9] . Similar symptoms may arise from excessive consumption of fructose containing beverages in patients predisposed to fructose intolerance [6] . Some patients diagnosed with irritable bowel syndrome may have undiagnosed lactose intolerance and can have lasting clinical improvement when placed on a lactose restricted diet [5] . Testing for serum immunoglobulins directed at specific dietary antigens (and elimination of responsible foods) has been proposed but the relationship between results of such testing and improvement of symptoms requires additional study before such an approach can be recommended [8] . brussels sprouts. Whether elimination of other specific foods is beneficial is unclear.5] . While it is possible that food allergy or intolerance may have a role in the development of symptoms. and bagels) should be considered in patients who complain of gas [7] .Dietary modification — A careful dietary history may reveal patterns of symptoms related to dairy and gas-producing foods. an empiric trial of a lactose free diet should be considered in patients suspected of having irritable bowel syndrome [4. not all authorities agree. wheat germ. celery. Given the similarity that may occur in symptoms of IBS and lactose intolerance. Although the efficacy . Despite their widespread use. However. raisins. bulking of the stool. there are no reliable means to identify such individuals. carrots. (See "Intestinal gas and bloating" and see "Patient information: Gas and bloating"). a decrease in fiber intake to 12 g per day (particularly insoluble fiber such as bran) was suggested in a British guideline. formation of gels to provide lubrication. either through diet or the use of commercial bulking supplements.

However. Hypnosis. A systematic review that included 25 controlled studies concluded that psychological interventions may be slightly superior to usual care but with marginal clinical significance and unclear durability of benefit [15] . Furthermore. MEDICATIONS — Pharmacologic agents are only an adjunct to treatment in IBS.of fiber supplements has not been proven.13] . some improvement has been demonstrated in patients with IBS whose primary complaints are abdominal pain and constipation [12] . Synthetic fiber supplements such as polycarbophil and methylcellulose are more soluble than natural fibers (psyllium). biofeedback. One study found that symptom improvement occurred independently of the effects of cognitive behavioral therapy in alleviating comorbid psychological distress [16] . Because of its safety and frequent placebo effect. dynamic psychotherapy and hypnotherapy are more effective than usual care in relieving global symptoms of IBS [11] . Thus. Some patients may experience increased bloating and gaseousness due to colonic metabolism of non-digestible fiber. and improve pain tolerance [14] . increase patient responsibility and involvement in the treatment. although their benefits remain controversial [1. a trial of fiber is reasonable in all patients with IBS. encourage health promoting behavior. diarrhea-predominant IBS is treated differently from constipation-predominant disease. Administration of one-half to one tablespoon once a day is a good starting dose. whether the synthetic supplements cause less bloating or are more effective than natural fiber supplements has not been determined. Dosages of fiber supplements such as wheat bran or psyllium should be titrated to symptoms. Psychosocial therapies — Behavioral treatments may be considered for motivated patients who associate symptoms with stressors. . and psychotherapy help to reduce anxiety levels. Another review concluded that cognitive behavioral therapy. especially those with constipation-predominant symptoms. the drug chosen varies depending on the patient's major symptoms.

gas.375 to 0.25 mg PO or sublingual three times daily or four times daily as needed) or sustained release hyoscyamine (0.We suggest that the chronic use of drugs should generally be minimized or avoided because of the lifelong nature of this disorder and the lack of convincing therapeutic benefit. Their selective inhibition of gastrointestinal smooth muscle reduces stimulated colonic motor activity and may be beneficial in patients with postprandial abdominal pain. Typical doses include dicyclomine (20 mg PO four times daily PRN) and hyoscyamine (0. dicyclomine and hyoscyamine) [11] . and peppermint oil) may provide short-term relief but long-term efficacy has not been demonstrated [11] . and those that act via their anticholinergic or antimuscarinic properties (eg. The difficulty in demonstrating efficacy may in part be due to the heterogeneous population diagnosed with IBS. A meta-analysis of 23 controlled trials of smooth muscle relaxants found that they were more effective than placebo (risk difference for global improvement of 22 percent. and fecal urgency [18] . Administration of these medications in the treatment of IBS should be on an as needed basis and/or in anticipation of stressors with known exacerbating effects. and overall pain improvement of 53 versus 41 percent) [19] .125 to 0. The postulated mechanisms of pain modulation with tricyclic antidepressants (TCAs) and possibly serotonin reuptake inhibitors (SSRIs) in IBS is facilitation of endogenous endorphin release. Only weak evidence for a benefit on abdominal pain and global assessment of symptoms was suggested in a second meta-analysis [20] . cimetropium. and the high placebo response rates [17] . Antispasmodic agents — Antispasmodic agents are the most frequently used pharmacologic agents in the treatment of IBS. bloating. A systematic review confirmed the support for short-term use of some antispasmodics [11] . the lack of disease markers. blockade of norepinephrine . mebeverine and pinaverine). The antispasmodic agents include those that directly affect intestinal smooth muscle relaxation (eg. Certain antispasmodics (hyoscine.75 mg PO every 12 hours). Antidepressants — Antidepressants have analgesic properties independent of their mood improving effects and may therefore be beneficial in patients with neuropathic pain [21-24] . pinaverium.

if an antidepressant is chosen for the treatment of IBS. Tricyclic agents. also slow intestinal transit time [24] . The initial dose should be adjusted based upon tolerance and response. Examples of medications used for this purpose include amitriptyline. Because of the delayed onset of action. or other antidepressant medications can be considered if depression is a cofactor [29] .reuptake leading to enhancement of descending inhibitory pain pathways. and appeared to reduce abdominal pain [11] . enrolled a small number of patients. A later systematic review confirmed that TCAs and SSRIs were more effective than placebo at relieving global IBS symptoms. Overall.25] . There is less published experience with other antidepressants such as SSRIs or serotonin norepinephrine reuptake inhibitors (SNRIs). imipramine. Results of the few published trials (mainly with SSRIs) have been inconsistent [29-33] . and did not use standardized criteria for identifying patients. although they are used clinically. the trials suggested that loperamide was more effective than placebo for treatment of diarrhea. serotonin [24. nortriptyline. A meta-analysis that included 12 placebo controlled trials of antidepressants in functional gastrointestinal disorders concluded that tricyclic antidepressants were associated with improvement in symptoms [27] . three to four weeks of therapy should be attempted before considering treatment insufficient and increasing the dose. the stools characteristically are loose and frequent but of normal total daily volume. A systematic review identified three controlled trials evaluating loperamide in the treatment of IBS [11. Improvement in neuropathic pain with TCAs occurs at lower doses than required for treatment of depression. Antidiarrheal agents — In diarrhea-prone patients with IBS. but not for treatment of global IBS symptoms or abdominal pain. and blockade of the pain neuromodulator. and desipramine (10 to 25 mg at bedtime). via their anticholinergic properties. a placebo-controlled trial found amitriptyline to be significantly more effective in adolescents with IBS [28] . They may therefore be beneficial in diarrhea-predominant IBS [26] . All were of short duration. low doses should be administered initially and titrated to pain control or tolerance. A subsequent. sertraline (100 mg PO daily).34-36] . As a result. TCAs should be used cautiously in patients with constipation. Administration on an as needed basis is preferred to a regular scheduled dosing in . Paroxetine and fluoxetine (20 mg PO daily).

a partial 5-HT4 receptor agonist) was approved for IBS and constipation but removed from the market in March 2007 because of cardiovascular side-effects.38] . habituation. Alosetron was developed for use in IBS based upon its favorable effects on colonic motility and secretion and afferent neural systems [40] . Benzodiazepines — Anxiolytic agents are of limited usefulness in IBS because of the risk of drug interactions. It has been subsequently reintroduced under an investigational new drug protocol. 5-hydroxytryptamine (serotonin) 3 receptor antagonists — 5-hydroxytryptamine-3 receptor antagonists (such as alosetron. Loperamide should not be used in patients with constipation and should be used only cautiously in those with symptoms alternating between diarrhea and constipation. Patients who consistently develop diarrhea after meals may benefit from taking a dose before meals. Evaluation of post-marketing data and demand from a subset of patients who had responded to treatment has prompted the FDA to bring the drug back to the market under tight control. cilansetron ondansetron and granisetron) modulate visceral afferent activity from the gastrointestinal tract and may improve abdominal pain [37. However. They may. and rebound withdrawal. prompting the Food and Drug Administration (FDA) to remove it from the market in the United States. providing a rationale for their use in constipation predominant IBS [41] . the drug was associated with ischemic colitis and serious complications related to severe constipation. be useful for short-term (less than two weeks') reduction of acute situational anxiety that may be contributing to symptoms [1] . 5-hydroxytryptamine (serotonin) 4 receptor agonists — Agonists of the 5hydroxytryptamine-4 (5-HT4) receptor stimulate the release of neurotransmitters and increase colonic motility. benzodiazepines may lower pain thresholds by stimulating gamma aminobutyric acid (GABA). thereby decreasing brain serotonin. The first of this class of drugs (tegaserod {Zelnorm}. In clinical trials the drug was most effective in female patients in whom diarrhea was predominant.patients with diarrhea. A meta-analysis that included 14 randomized controlled trials in IBS (involving alosetron or cilansetron) found a benefit in global improvement in IBS and relief of abdominal pain and discomfort [39] . . Furthermore. (See "Alosetron hydrochloride (Lotronex) for irritable bowel syndrome"). however.

Approval was based upon two multicenter placebo-controlled trials involving 1154 adults (92 percent women) with irritable bowel syndrome and constipation who were randomly assigned to lubiprostone (8 micrograms twice daily) or placebo for 12 weeks [42] . the placebo response in the studies above was far lower than most studies of IBS and it is not intuitive why a secretory agent would improve symptoms other than constipation in a disorder such as IBS. It received initial approval from the United States Food and Drug Administration for treatment of chronic idiopathic constipation but later also received approval for treatment of irritable bowel syndrome with constipation in women 18 years and older. A follow-up open-label study involving 522 patients showed that benefits continued or improved at 52 weeks. Most of the improvement has been with bloating but not for abdominal pain or altered bowel habits. Such studies do not prove the hypothesis that bacterial overgrowth in the small intestine underlies the symptoms of most patients with IBS. Until further data are available (and because it is expensive compared with other options). The mechanisms leading to the benefit are unclear but may be due to suppression of gas producing bacteria in the colon. Its role continues to be determined. A phase IIb study involving 420 patients with IBS-C (reported in preliminary form) found improvement in stool frequency and in global and individual IBS symptoms [11] . . The approved dose (8 micrograms twice daily) is lower than the approved dose for treatment of chronic idiopathic constipation. Guanylate cyclase agonists — Linaclotide is a guanylate cyclase agonist that stimulates intestinal fluid secretion and transit. Antibiotics — Scattered reports have suggested that some patients with IBS improved with antibiotic treatment [43-46] . Furthermore. Serious adverse events were similar to placebo. it is best reserved for patients with IBS and severe constipation in whom other approaches have been unsuccessful. The most common adverse event was nausea (8 versus 4 percent). There have been no comparisons with other options for treatment of IBS with constipation and its long-term safety remains to be established. Patients randomized to lubiprostone were significantly more likely to achieve an overall response (18 versus 10 percent).Lubiprostone — Lubiprostone is a locally acting chloride channel activator that enhances chloride-rich intestinal fluid secretion.

in one report.uptodate. Mild symptoms — Patients with mild or infrequent symptoms usually have little or no functional impairment or psychologic disturbance.Furthermore. we suggest treatment should focus upon the general measures described above (such as establishment of the physician-patient relationship. probiotics. fiber supplementation) rather than specific pharmacologic therapy (Grade 2C). (See "General principles" above). lactulose breath testing (the method used for suggesting bacterial overgrowth in some of these studies) did not discriminate patients with IBS from healthy controls [47] . www. and. We encourage you to print or e-mail this topic review. . and enzyme supplementation [48-50] . Their role remains uncertain. SUMMARY AND RECOMMENDATIONS — Treatment of IBS varies with the severity and type (diarrhea versus constipation predominant) of symptoms that are present. (See "Probiotics for gastrointestinal disease" section on irritable bowel syndrome). INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients. which includes this and other topics. such as herbs. or to refer patients to our public web site. these patients also may demonstrate psychologic patient education. Thus. Alternative therapies — Multiple alternative forms of therapy for IBS have been suggested. the relationships between bacterial overgrowth. benefits of antibiotics in patients with IBS. dietary modification. and methods to test for bacterial overgrowth in IBS require further study before this approach can be recommended. (See "Patient information: Irritable bowel syndrome"). acupuncture. Thus. Moderate symptoms — Patients with moderate symptoms of IBS experience disruptions of normal daily activities due to exacerbations of symptoms. MAJOR SOCIETY GUIDELINES — Guidelines for the management of IBS have been issued by several organizations including a 2009 guideline from the American College of Gastroenterology (show table 1) [11] . reassurance. if bloating is not a major factor.

Yamada. Kelley. Summers. et al. LA. 13:941. Irritable bowel syndrome. TJ. BMJ 2008. Hasler. et al. Conboy. excess caffeine. such as lactose intolerance. Modifications in diet. FC Jr. Use of UpToDate is subject to the Subscription and License Agreement. Intractable symptoms — A small subset of patients with IBS present to tertiary care centers with severe. or whether they should be given continuously or episodically. C. REFERENCES Drossman. JB Lippincott. DM. We often use pharmacologic intervention to control symptom flares but also use continuous pharmacologic therapy (such as tricyclic antidepressant drugs) for periods of months or years. Owyang. We suggest behavioral modification and the use of psychoactive drugs in such patients (Grade 2C). or specific stressors. 336:999. The irritable bowel syndrome: Review and a graduated multi-component treatment approach. Johlin. 122:107. Am J Gastroenterol 2003. Our choice of specific therapies is based mainly upon symptoms and response to empiric trials (See "Medications" above). PR. 116:1009. In: Textbook of Gastroenterology. 67:710. DA. Thompson. Owens. DK. Fructose intolerance: an under-recognized problem. earlier diagnosed as irritable bowel syndrome: A 5-year follow-up study. Vesa. Kaptchuk. CJ. Role of irritable bowel syndrome in subjective lactose intolerance. Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome. Marteau. T (Ed) 4th edition. HA. RW. et al. there have been few controlled trials evaluating specific strategies for how these drugs should be used in conjunction with other types of treatment (such as fiber therapy). YK. how long they should be used. WL. However. NJ. TH. The effect of a lactose-restricted diet in patients with a positive lactose tolerance test. 98:1348. Am J Clin Nutr 1998. LM. Eur J Gastroenterol Hepatol 2001. Ann Intern Med 1995. Ann Intern Med 1992. JM. Randomized controlled trials evaluating specific pharmacologic agents have demonstrated their superiority compared with placebo. unrelenting symptoms that are often associated with underlying psychiatric impairment and frequent health care utilization. Talley. The irritable bowel syndrome: Long-term prognosis and the physician-patient relationship. WG. Bohmer. (See "Medications" above). Nelson. and psychotherapy may improve the clinical outcome. . behavioral changes.We monitor patients' symptoms for several weeks to help identify precipitating factors. Tuynman. Choi. Seppo.

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