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Official reprint from UpToDate www.uptodate.com ©2013 UpToDate

AuthorArnold Wald, MD

Section EditorNicholas J Talley, MD, PhD

Deputy EditorShilpa Grover, MD, MPH

Treatment of irritable bowel syndrome

Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Nov 2013. | This topic last updated: May 7, 2013.

INTRODUCTION — Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by chronic abdominalpain and altered bowel habits in the absence of any organic disorder. The approach to therapy of IBS will be reviewedhere. The clinical manifestations and diagnosis of this disorder are discussed separately. (See "Clinical manifestationsand diagnosis of irritable bowel syndrome".)

GENERAL PRINCIPLES — Irritable bowel syndrome (IBS) is a chronic condition with no known cure. As a result, thefocus of treatment should be on relief of symptoms and addressing the patient's concerns. An important question toanswer is why the patient is seeking help at this time. Recent exacerbating factors (medications, dietary changes),concerns about serious illness, stressors, hidden agendas (disability claims, requests for opiates), or psychiatriccomorbidities are critical to establish when developing the optimum therapy [1].

Therapeutic relationship — The most important component of treatment lies in the establishment of a therapeuticphysician-patient relationship. The doctor should be non-judgmental, establish realistic expectations with consistentlimits, and involve the patient in treatment decisions [1]. Patients with established, positive physician interactions havefewer IBS-related follow-up visits [2].

The importance of the therapeutic relationship in IBS was emphasized in a study that investigated the components of theplacebo effect and patient-provider interaction in 262 patients with IBS [3]. Group 1 was assigned to a waitlist only,whereas Group 2 received sham acupuncture with little interaction with a health care provider (HCP). Group 3 receivedsham acupuncture but had much more interaction with a HCP. At both three and six weeks, the level of improvement inGroup 3 was significantly better than Group 2, which in turn was significantly better than Group 1. The conclusion wasthat placebo effects are significant in IBS and that the patient-HCP interaction is the key part of that effect.

Patient education — Education of the proposed mechanisms of IBS helps to validate the patient's illness experienceand sets the basis for therapeutic interventions. (See "Pathophysiology of irritable bowel syndrome".) Patients should beinformed of the chronic and benign nature of IBS, and also informed that the diagnosis (if well-established) is not likely tobe changed, and that he or she should have a normal life span. In a 29-year follow-up study of 112 patients from theMayo Clinic, for example, only 10 of 112 patients developed an organic gastrointestinal disease; patient survival wassimilar to expected survival [2]. (See "Patient information: Irritable bowel syndrome (Beyond the Basics)".)

Dietary modification — A careful dietary history may reveal patterns of symptoms related to specific foods. A number ofdietary interventions have been proposed but their efficacy has not been well established.

Lactose — Given the similarity that may occur in symptoms of IBS and lactose intolerance, an empiric trial of alactose free diet should be considered in patients suspected of having irritable bowel syndrome [4,5]. Some patientsdiagnosed with irritable bowel syndrome may have undiagnosed lactose intolerance and can have lasting clinical

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improvement when placed on a lactose restricted diet [5]. (See "Lactose intolerance".)

Exclusion of gas-producing foods — Exclusion of foods that increase flatulence (beans, onions, celery, carrots,raisins, bananas, apricots, prunes, brussel sprouts, wheat germ, pretzels, and bagels) should be considered in patientswho complain of gas [6]. Underlying visceral hyperalgesia in IBS may explain the exaggerated discomfort experiencedwith consumption of gas-producing foods. (See "Intestinal gas and bloating" and "Patient information: Gas and bloating(Beyond the Basics)" and "Pathophysiology of irritable bowel syndrome".)

Food allergies — The role of food allergy in IBS is unclear. While it is possible that food allergy has a role in thedevelopment of symptoms, there are no reliable means to identify such individuals. Testing for serum immunoglobulinsdirected at specific dietary antigens (and elimination of responsible foods) has been proposed but the relationshipbetween results of such testing and improvement of symptoms requires additional study before such an approach canbe recommended [7]. Other methods used in evaluating food allergies (eg, skin prick testing, RAST testing and atopypatch testing) have not been well studied in IBS. (See "Diagnostic evaluation of food allergy".)

Gluten sensitivity — Gluten sensitivity (without overt celiac disease) has been proposed as a cause of functionalbowel disorders but there are few convincing studies that have evaluated such a relationship in terms of pathogenesis ortreatment of IBS [8-10]. It is also unclear if gluten sensitivity is itself a separate clinical entity [8,11-15].

A trial of 34 patients examined the effect of a gluten-free diet in patients without celiac disease [16]. Patients were eitherHLA-DQ2 and HLA-DQ8 negative or had normal duodenal biopsies. Patients in the gluten arm received two glutencontaining bread slices and one muffin per day, whereas the control patients received placebos. Patients in the glutengroup were more likely to report inadequate symptom control compared with the placebo group (68 versus 40 percent).

Carbohydrate malabsorption — One theory related to IBS (and inflammatory bowel disease [IBD]) suggests thatsymptoms may be at least in part related to impaired absorption of carbohydrates. The theory holds that fermentableoligo-, di-, and monosaccharides and polyols (FODMAPs) in patients with IBS or IBD enter the distal small bowel andcolon where they are fermented, leading to symptoms and increased intestinal permeability (and possibly inflammation)[17].

Some examples of FODMAPs include:

Fructans (found in wheat, onions, and artichokes)Galactans (found in legumes, cabbage, and Brussels' sprouts)LactoseFructoseSorbitolXylitolMannitol

Avoidance of carbohydrates has been a long-popularized non-pharmacologic approach to reducing symptoms in IBS(and possibly modifying disease in IBD) [18] but there have been few contemporary studies. Fructose intolerance hasbeen suggested as a possible form of carbohydrate malabsorption contributing to IBS [19].

Studies examining FODMAP restriction in patients with IBS have suggested a clinical benefit:

A randomized trial with 25 patients found that patients who were given fructose and/or fructans were more likelyto report inadequate symptom control compared with patients who were given glucose (70 to 79 percent versus14 percent) [20]. In addition, symptoms were induced in a dose-dependent manner and mimicked the patients’previous IBS symptoms.

A single-blind crossover trial gave 15 healthy volunteers and 15 patients with IBS diets that were either low (9

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g/day) or high (50 g/day) in FODMAPs [21]. Patients with IBS had a significant increase in gastrointestinalsymptoms and lethargy while on the high FODMAPs diet, whereas healthy volunteers only reported increasedflatus production while on the high FODMAPs diet.

Another small crossover trial of patients with IBS-D found a clinical benefit with a very low carbohydrate diet (20 gof carbohydrates per day) [22].

While diets low in FODMAPS have not been definitively shown to be of benefit, it is reasonable for patients to undergo atrial of a low FODMAPS diet, provided that their nutritional status is being monitored.

Fiber — An increase in the intake of fiber is often recommended, either through diet or the use of commercial bulkingsupplements. However, not all authorities agree. A systematic review found no beneficial effect for bulking agents overplacebo for improvement of abdominal pain, global assessment or symptom scores. Subgroup analyses showed nosignificant benefit with either insoluble or soluble fibers [23]. A decrease in fiber intake to 12 g per day (particularlyinsoluble fiber such as bran) was suggested in a British guideline, because of the potential of fiber to exacerbatesymptoms [24].

Proposed mechanisms for fiber's beneficial effects include: enhancement of water holding properties of the stool;formation of gels to provide lubrication; bulking of the stool; and binding of agents such as bile [25]. Despite theirwidespread use, a systematic review that included 13 randomized controlled trials found no convincing evidence that thecommonly-used bulking agents were more effective than placebo at relieving global IBS symptoms [26]. Although theefficacy of fiber supplements has not been proven, some improvement has been demonstrated in patients with IBSwhose primary complaints are abdominal pain and constipation [27].

Synthetic fiber supplements such as polycarbophil and methylcellulose are more soluble than natural fibers (psyllium).However, whether the synthetic supplements cause less bloating or are more effective than natural fiber supplementshas not been determined. Some patients may experience increased bloating and gaseousness due to colonicmetabolism of non-digestible fiber.

Because of its safety and frequent placebo effect, a trial of fiber is reasonable in all patients with IBS, especially thosewith constipation-predominant symptoms. Dosages of fiber supplements such as wheat bran or psyllium should betitrated to symptoms. Administration of one-half to one tablespoon once a day is a good starting dose.

Physical activity — Increased physical activity may help with the symptoms of IBS. This was examined in a randomizedtrial that assigned 102 patients to increased physical activity to maintenance of current activity levels [28]. Increasedphysical activity was comprised of 20 to 60 minutes of moderate to vigorous activity three to five days per week. Theamount of physical activity prescribed was determined in part by the patient’s baseline level of activity. Seventy-fivepatients completed the study (38 in the physical activity arm and 37 in the control arm). After 12 weeks, there was atrend toward more patients in the physical activity arm showing clinical improvement in the severity of IBS symptomscompared with the control group (43 versus 26 percent, p = 0.07). In addition, patients in the physical activity arm wereless likely to have clinically significant worsening of their IBS symptoms (8 versus 23 percent, p <0.01).

It is reasonable to recommend increased physical activity for patients with IBS given that these data suggest a potentialbenefit with regard to symptoms as well the general health benefits associated with increased physical activity. (See"Overview of the benefits and risks of exercise", section on 'Benefits of exercise'.)

Psychosocial therapies — Behavioral treatments may be considered for motivated patients who associate symptomswith stressors, although their benefits remain controversial [1,29]. Hypnosis, biofeedback, and psychotherapy help toreduce anxiety levels, encourage health promoting behavior, increase patient responsibility and involvement in thetreatment, and improve pain tolerance [30].

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A 2009 meta-analysis that included 20 placebo-controlled trials of antidepressants in 1278 adults with IBS concludedthat psychological therapy was significantly more effective than control therapy or usual management for at least a 50percent reduction in symptoms (relative risk of IBS symptoms persisting 0.67, 95% CI 0.57 to 0.79) [31]. A similarconclusion was reached by the 2009 position statement on IBS by the American College of Gastroenterology Task Forceon Irritable Bowel Syndrome [26]. A lesser benefit was noted in another systematic review [32].

The mechanism of benefit from psychosocial therapies is unclear. In one randomized controlled trial, mindfulnesstraining, a cognitive behavioral technique, reduced IBS symptom severity, improved health-related quality of life, andreduced distress [33]. However, in another randomized trial, symptom improvement was independent of the effects ofcognitive behavioral therapy in alleviating comorbid psychological distress [34].

MEDICATIONS — Pharmacologic agents are only an adjunct to treatment in irritable bowel syndrome (IBS).Furthermore, the drug chosen varies depending on the patient's major symptoms; diarrhea-predominant IBS is treateddifferently from constipation-predominant disease.

We suggest that the chronic use of drugs be generally minimized or avoided because of the lifelong nature of thisdisorder and the lack of convincing therapeutic benefit. The difficulty in demonstrating efficacy may in part be due to theheterogeneous population diagnosed with IBS, the lack of disease markers, and the high placebo response rates [35].

Antispasmodic agents — Antispasmodic agents are the most frequently used pharmacologic agents in the treatment ofIBS. Certain antispasmodic drugs (hyoscine, cimetropium, and pinaverium) may provide short-term relief but long-termefficacy has not been demonstrated [26]. Peppermint oil may also act as a smooth muscle relaxant (see 'Alternativetherapies' below).

The antispasmodic agents include those that directly affect intestinal smooth muscle relaxation (eg, mebeverine andpinaverine), and those that act via their anticholinergic or antimuscarinic properties (eg, dicyclomine and hyoscyamine)[26]. The selective inhibition of gastrointestinal smooth muscle reduces stimulated colonic motor activity and may bebeneficial in patients with postprandial abdominal pain, gas, bloating, and fecal urgency [36].

A meta-analysis of 23 controlled trials of smooth muscle relaxants found that they were more effective than placebo (riskdifference for global improvement of 22 percent, and overall pain improvement of 53 versus 41 percent) [37]. Only weakevidence for a benefit on abdominal pain and global assessment of symptoms was suggested in a second meta-analysis[38]. A systematic review confirmed the support for short-term use of some antispasmodic drugs [26]. In anothersystematic review, subgroup analyses of different types of antispasmodics found statistically significant benefits forcimetropium/dicyclomine, peppermint oil, pinaverium and trimebutine [23].

Administration of these medications in the treatment of IBS should be on an as needed basis and/or in anticipation ofstressors with known exacerbating effects. Typical doses include:

Dicyclomine 20 mg orally four times daily as neededHyoscyamine 0.125 to 0.25 mg orally or sublingually three to four times daily as neededSustained release hyoscyamine 0.375 to 0.75 mg orally every 12 hours

Antidepressants — Antidepressants have analgesic properties independent of their mood improving effects and maytherefore be beneficial in patients with neuropathic pain [39-42]. The postulated mechanisms of pain modulation withtricyclic antidepressants (TCAs) and possibly serotonin reuptake inhibitors (SSRIs) in IBS are facilitation of endogenousendorphin release, blockade of norepinephrine reuptake leading to enhancement of descending inhibitory painpathways, and blockade of the pain neuromodulator, serotonin [42,43]. TCAs, via their anticholinergic properties, alsoslow intestinal transit time [42], which may provide benefit in diarrhea-predominant IBS [44].

A 2009 meta-analysis that included 13 placebo-controlled trials of antidepressants in 789 adults with IBS concluded thatantidepressants were significantly more effective than placebo for the relief of pain and global symptoms (relative risk of

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IBS symptoms persisting 0.66, 95% CI 0.57-0.78) at a duration of therapy ranging from one to three months [31]. Thenumber need to treat to benefit one patient was four. The treatment effects were similar for SSRIs and tricyclicantidepressants. A similar conclusion was reached in a 2009 position statement from the American College ofGastroenterology Task Force on Irritable Bowel Syndrome [26] and in a subsequent systematic review [23].

By contrast, antidepressant efficacy is unproven in children [45]. This was illustrated in a multicenter trial of 83 childrenwith functional gastrointestinal disorders who were randomly assigned to an antidepressant or placebo for four weeks[46]. The primary end point was the child's assessment of pain relief and sense of improvement. At four weeks, therewas no significant difference between amitriptyline and placebo in the frequency of attaining the primary end point (63versus 58 percent, p = 0.85). The authors noted that a longer period of treatment and a higher dose of antidepressantmay have produced different results and that there may be a large placebo effect in children due to multiple factors. Inanother trial of 33 adolescents assigned to an antidepressant or placebo, an antidepressant was effective in reducingdiarrhea and pain after a longer period of treatment (6, 8, and 13 weeks) [47].

Improvement in neuropathic pain with TCAs occurs at lower doses than required for treatment of depression. As a result,if an antidepressant is chosen for the treatment of IBS, low doses should be administered initially and titrated to paincontrol or tolerance. Because of the delayed onset of action, three to four weeks of therapy should be attempted beforeconsidering treatment insufficient and increasing the dose.

Examples of antidepressant medications used in patients with IBS include amitriptyline, imipramine, nortriptyline, anddesipramine. The initial dose should be adjusted based upon tolerance and response. TCAs should be used cautiouslyin patients with constipation. Amitriptyline, nortriptyline, and imipramine can be started at a dose of 10 to 25 mg atbedtime and increased every three to four weeks based upon clinical response and tolerance. Desipramine is used in asimilar fashion beginning at 12.5 to 25 mg at bedtime. If the patient is intolerant of one TCA, another may be tried.Paroxetine (10 to 20 mg daily), fluoxetine (20 to 40 mg daily), sertraline (50 to 100 mg daily), or other antidepressantmedications can be considered if depression is a cofactor [48].

There is less published experience with other antidepressants such as SSRIs or serotonin norepinephrine reuptakeinhibitors (SNRIs), although they are used clinically. Results of the few published trials (mainly with SSRIs) have beeninconsistent [48-53]. As noted above, one meta-analysis concluded that overall treatment effects were similar to tricyclicantidepressants [31]. Subgroup analyses in a systematic review demonstrated a statistically significant improvement inglobal assessment scores with SSRIs and an improvement in abdominal pain and symptom scores with TCAs [23].

Antidiarrheal agents — In diarrhea-prone patients with IBS, the stools characteristically are loose and frequent but ofnormal total daily volume. A systematic review identified three controlled trials evaluating loperamide in the treatment ofIBS [26,54-56]. All were of short duration, enrolled a small number of patients, and did not use standardized criteria foridentifying patients. Overall, the trials suggested that loperamide was more effective than placebo for treatment ofdiarrhea, but not for treatment of global IBS symptoms or abdominal pain. Administration on an as needed basis ispreferred to a regular scheduled dosing in patients with diarrhea. Patients who consistently develop diarrhea after mealsmay benefit from taking a dose before meals. Loperamide should not be used in patients with constipation and should beused only cautiously in those with symptoms alternating between diarrhea and constipation.

Benzodiazepines — Anxiolytic agents are of limited usefulness in IBS because of the risk of drug interactions,habituation, and rebound withdrawal. Furthermore, benzodiazepines may lower pain thresholds by stimulating gammaaminobutyric acid (GABA) receptors, thereby decreasing brain serotonin. They may, however, be useful for short-term(less than two weeks') reduction of acute situational anxiety that may be contributing to symptoms [1].

5-hydroxytryptamine (serotonin) 3 receptor antagonists — 5-hydroxytryptamine-3 receptor antagonists (such asalosetron, cilansetron, ondansetron and granisetron) modulate visceral afferent activity from the gastrointestinal tract andmay improve abdominal pain [57,58]. A meta-analysis that included 14 randomized controlled trials in IBS (involving

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alosetron or cilansetron,) found a benefit in global improvement in IBS and relief of abdominal pain and discomfort [59].

Alosetron was developed for use in IBS based upon its favorable effects on colonic motility and secretion and on afferentneural systems [60]. In clinical trials the drug was most effective in female patients in whom diarrhea was predominant.However, the drug was associated with ischemic colitis and serious complications related to severe constipation,prompting the Food and Drug Administration (FDA) to remove it from the market in the United States. Evaluation of post-marketing data and demand from a subset of patients who had responded to treatment has prompted the FDA to bringthe drug back to the market under tight control. (See "Alosetron hydrochloride (Lotronex) for irritable bowel syndrome".)

5-hydroxytryptamine (serotonin) 4 receptor agonists — Agonists of the 5-hydroxytryptamine-4 (5-HT4) receptorstimulate the release of neurotransmitters and increase colonic motility, providing a rationale for their use in constipationpredominant IBS [61]. The first of this class of drugs (tegaserod {Zelnorm}, a partial 5-HT4 receptor agonist) wasapproved for IBS and constipation but removed from the market in March 2007 because of cardiovascular side-effects.

Lubiprostone — Lubiprostone is a locally acting chloride channel activator that enhances chloride-rich intestinal fluidsecretion. Lubiprostone has been approved by the United States Food and Drug Administration for treatment of irritablebowel syndrome with constipation in women 18 years and older. However, its role continues to be determined. Therehave been no comparisons with other options for treatment of IBS with constipation and its long-term safety remains tobe established. Furthermore, the placebo response in the studies above was far lower than most studies of IBS and it isnot intuitive why a secretory agent would improve symptoms other than constipation in a disorder such as IBS. Untilfurther data are available (and because it is expensive compared with other options), it is best reserved for patients withIBS and severe constipation in whom other approaches have been unsuccessful.

Approval was based upon two multicenter placebo-controlled trials involving 1154 adults (92 percent women) withirritable bowel syndrome and constipation who were randomly assigned to lubiprostone (8 micrograms twice daily) orplacebo for 12 weeks [62]. Patients randomized to lubiprostone were significantly more likely to achieve an overallresponse (18 versus 10 percent). Serious adverse events were similar to placebo. The most common adverse event wasnausea (8 versus 4 percent). A follow-up open-label study involving 522 patients showed that benefits continued orimproved at 52 weeks. The approved dose (8 micrograms twice daily) is lower than the approved dose for treatment ofchronic idiopathic constipation.

Guanylate cyclase agonists — Linaclotide is a guanylate cyclase agonist that stimulates intestinal fluid secretion andtransit. Linaclotide has been approved by the US Food and Drug Administration for treatment of IBS with constipation ata dose of 290 micrograms daily [63]. However, the long-term risks of linaclotide are unknown and therefore its role onthe treatment of IBS with constipation remains to be determined.

Approval was based upon two randomized controlled phase III trials [64,65]. In one randomized controlled trial, 800patients with IBS with constipation were randomly assigned to linaclotide (266 micrograms daily) or placebo for 12weeks followed by a four-week withdrawal period [64]. During the withdrawal period, patients previously randomized toplacebo received linaclotide, and patients who originally received linaclotide were randomized to either linaclotide orplacebo. After 12 weeks, the percentage of patients meeting the composite endpoint (≥30 percent reduction inabdominal pain, ≥3 complete and spontaneous bowel movements (CSBM), increase in ≥1 CSBM from baseline; in thesame week) was significantly greater with linaclotide compared with placebo (34 versus 21 percent). Patients whoreceived linaclotide also demonstrated a significant improvement in secondary endpoints of abdominal pain/discomfort,bloating, straining, stool consistency, number of CSBMs and spontaneous bowel movements per week, compared withplacebo. After the initial 12 weeks, patients originally given linaclotide and who remained on linaclotide showedsustained improvement in abdominal pain, but patients who were switched to placebo experienced recurrence ofabdominal pain. Patients initially randomized to placebo had significant improvement in abdominal pain within one weekafter being switched to linaclotide. Diarrhea was the most common side effect causing discontinuation of treatment in 5.7percent of patients treated with linaclotide compared with 0.3 percent in patients receiving with placebo. A second

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randomized controlled trial assessed the efficacy of long-term use of linaclotide [65]. In this trial, 804 patients with IBSwith constipation were randomly assigned to receive linaclotide (266 micrograms daily) or placebo for 26 weeks. Patientsrandomized to linaclotide demonstrated a significant improvement in the same composite primary endpoint comparedwith placebo (38 versus 14 percent).

Mast cell stabilizers — Ketotifen is a mast cell stabilizer that has been studied for the treatment of IBS based upon thetheory that mast cell activation contributes to visceral hypersensitivity. In a randomized trial of 60 patients, the use ofketotifen for eight weeks increased the threshold for discomfort with rectal distension in patients who werehypersensitive to rectal balloon distension at baseline, but not in those with normal sensitivity at baseline [66]. Whilethere was a suggestion of symptom improvement in patients who received ketotifen compared with those who receivedplacebo, the results did not reach statistical significance.

Antibiotics — Some patients with IBS have shown improvement when treated with antibiotics [67-71]. Most of theimprovement has been in symptoms of bloating, abdominal pain, or altered bowel habits.

In a report of two randomized trials (TARGET 1 and TARGET 2) with 1260 patients with IBS without constipation,rifaximin, a nonabsorbable antibiotic, led to symptomatic improvement in global IBS symptoms and bloating [71].Patients were assigned to receive either rifaximin 550 mg three times daily or placebo for a total of 14 days and werethen followed for 10 weeks. During the first four weeks of follow-up, patients who received rifaximin were more likely toreport adequate relief of IBS symptoms than patients who received placebo (41 versus 32 percent). They also weremore likely to report adequate relief of bloating (40 versus 30 percent). Patients who received rifaximin continued toreport better symptom relief during the remainder of the follow-up period. In a meta-analysis of five randomizedcontrolled trials, rifaximin was more efficacious than placebo for global IBS symptom improvement (OR 1.57) and wassignificantly more likely to be associated with decreased bloating than placebo (OR 1.55) [72].

The mechanisms leading to the benefit are unclear but may be due to suppression of gas producing bacteria in thecolon. Such studies do not prove the hypothesis that bacterial overgrowth in the small intestine underlies the symptomsof most patients with IBS. Furthermore, in one report, lactulose breath testing (the method used for suggesting bacterialovergrowth in some of these studies) did not discriminate patients with IBS from healthy controls [73]. Thus, therelationships between bacterial overgrowth, benefits of antibiotics in patients with IBS, and methods to test for bacterialovergrowth in IBS require further study.

Given the modest benefit and relatively short-term follow-up demonstrated in the trials of rifaximin, we do not suggest theroutine use of antibiotics in patients with IBS. However, in patients with moderate to severe IBS without constipation(particularly those with bloating) who have failed to respond to all other therapies, including a low carbohydrate diet andelimination of fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs), it is reasonable to consider two-week trial of rifaximin (see 'Carbohydrate malabsorption' above).

Alternative therapies — Multiple alternative forms of therapy for IBS have been suggested, such as herbs, probiotics,acupuncture, and enzyme supplementation [74-78]. Their role remains uncertain. (See "Probiotics for gastrointestinaldiseases", section on 'Irritable bowel syndrome'.)

Peppermint oil has been studied in randomized trials [79-81]:

One trial included 90 patients with irritable bowel syndrome [79]. Patients were assigned to receive either adelayed release capsule with 187 mg of peppermint oil or placebo three times daily 30 minutes before meals foreight weeks. At baseline, the most common symptoms were abdominal pain, distention, and flatulence. Sixtypatients completed the study (33 in the treatment arm and 27 in the control arm). At the end of the study, morepatients in the treatment arm who completed the study reported being free from abdominal pain or discomfort (43versus 22 percent in the per protocol analysis, 31 versus 13 percent in the intention to treat analysis).

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A second trial included 57 patients and assigned the patients to 225 mg of peppermint oil (28 patients) or placebo(29 patients) twice daily for four weeks [80]. The loss to follow-up in this trial was less than in the first (11 percentin the treatment arm and 10 percent in the control arm). After four weeks of treatment, more patients in thetreatment arm reported at least a 50 percent reduction in symptoms than in the control arm (75 versus 38 percentin the per protocol analysis, 64 versus 34 percent in the intention to treat analysis).

A third trial included 110 patients [81]. Patients were assigned to 187 mg of peppermint oil or placebo three to fourtimes daily before meals for one month. Fifty-two patients in the treatment arm (95 percent) and 49 patients in thecontrol arm (89 percent) completed the trial. At the end of the trial, more patients in the treatment arm were painfree (56 versus 8 percent in per protocol analysis, 53 versus 7 percent in the intention to treat analysis). Patientsin the treatment arm also reported more improvement in pain severity, abdominal distention, stool frequency(decreased), borborygmi, and flatulence.

MAJOR SOCIETY GUIDELINES — Guidelines for the management of irritable bowel syndrome (IBS) have been issuedby several organizations. The 2009 position statement from the American College of Gastroenterology Task Force onIrritable Bowel Syndrome includes recommendations on the role of dietary modification, medications, psychological andalternative therapies in the treatment of IBS (table 1) [26].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyondthe Basics." The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, andthey answer the four or five key questions a patient might have about a given condition. These articles are best forpatients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient educationpieces are longer, more sophisticated, and more detailed. These articles are written at the 10 to 12 grade readinglevel and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics toyour patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" andthe keyword(s) of interest.)

Basics topics (see "Patient information: Irritable bowel syndrome (The Basics)")

Beyond the Basics topics (see "Patient information: Irritable bowel syndrome (Beyond the Basics)" and "Patientinformation: High-fiber diet (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS — Treatment of irritable bowel syndrome (IBS) varies with the severity andtype (diarrhea versus constipation predominant) of symptoms that are present.

Mild symptoms

Patients with mild or infrequent symptoms usually have little or no functional impairment or psychologicdisturbance. Thus, we suggest treatment should focus upon the general measures described above (such asestablishment of the physician-patient relationship, patient education, reassurance, dietary modification, and, ifbloating is not a major factor, fiber supplementation) rather than specific pharmacologic therapy (Grade 2C). (See'General principles' above.)

Moderate symptoms

Patients with moderate symptoms of IBS experience disruptions of normal daily activities due to exacerbations ofsymptoms; these patients also may demonstrate psychologic impairment.

th th

th th

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We monitor patients' symptoms for several weeks to help identify precipitating factors, such as lactoseintolerance, excess caffeine, or specific stressors. Modifications in diet, behavioral changes, and psychotherapymay improve the clinical outcome.

Randomized controlled trials evaluating specific pharmacologic agents have demonstrated their superioritycompared with placebo. However, there have been few controlled trials evaluating specific strategies for howthese drugs should be used in conjunction with other types of treatment (such as fiber therapy), how long theyshould be used, or whether they should be given continuously or episodically. We often use pharmacologicintervention to control symptom flares but also use continuous pharmacologic therapy (such as tricyclicantidepressant drugs) for periods of months or years. Our choice of specific therapies is based mainly uponsymptoms and response to empiric trials (see 'Medications' above).

Given the modest benefit and relatively short-term follow-up demonstrated in the trials of rifaximin, we suggestNOT using antibiotics routinely in patients with IBS (Grade 2B). However, in patients with moderate to severe IBSwithout constipation (particularly those with bloating) who have failed to respond to all other therapies, including alow carbohydrate diet and elimination of fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs), itis reasonable to consider a two-week trial of rifaximin. (See 'Antibiotics' above and 'Carbohydrate malabsorption'above.)

Intractable symptoms

A small subset of patients with IBS present to tertiary care centers with severe, unrelenting symptoms that areoften associated with underlying psychiatric impairment and frequent health care utilization. We suggestbehavioral modification and the use of psychoactive drugs in such patients (Grade 2C). (See 'Medications'above.)

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syndrome. Dig Dis Sci 2010; 55:1385.80. Cappello G, Spezzaferro M, Grossi L, et al. Peppermint oil (Mintoil) in the treatment of irritable bowel syndrome: a

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Topic 2631 Version 22.0

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GRAPHICS

2009 American College of Gastroenterology (ACG) recommendationsfor the treatment of irritable bowel syndrome (IBS)

Diet and irritable bowel syndrome

Patients often believe that certain foods exacerbate their IBS symptoms. There is, however,insufficient evidence that food allergy testing or exclusion diets are efficacious in IBS and their routineuse outside of a clinical trial is not recommended.

Effectiveness of dietary fiber, bulking agents, and laxatives in themanagement of irritable bowel syndrome

Psyllium hydrophilic mucilloid (ispaghula husk) is moderately effective and can be given a conditionalrecommendation. A single study reported improvement with calcium polycarbophil. Wheat bran orcorn bran is no more effective than placebo in the relief of global symptoms of IBS and cannot berecommended for routine use. Polyethylene glycol (PEG) laxative was shown to improve stoolfrequency - but not abdominal pain - in one small sequential study in adolescents with IBS-C.

Effectiveness of antispasmodic agents, including peppermint oil, in themanagement of irritable bowel syndrome

Certain antispasmodics (hyoscine, cimetropium, pinaverium, and peppermint oil) may provide short-term relief of abdominal pain / discomfort in IBS. Evidence for long-term efficacy is not available.Evidence for safety and tolerability is limited.

Effectiveness of antidiarrheals in the management of irritable bowelsyndrome

The antidiarrheal agent loperamide is not more effective than placebo at reducing pain, bloating, orglobal symptoms of IBS, but it is an effective agent for the treatment of diarrhea, reducing stoolfrequency, and improving stool consistency. Randomized controlled trials comparing loperamide withother antidiarrheal agents have not been performed. Safety and tolerability data on loperamide arelacking.

Effectiveness of antibiotics in the management of irritable bowel syndrome

A short-term course of a nonabsorbable antibiotic is more effective than placebo for globalimprovement of IBS and for bloating. There are no data available to support the long-term safety andeffectiveness of nonabsorbable antibiotics for the management of IBS symptoms.

Effectiveness of probiotics in the management of irritable bowel syndrome

In single organism studies, lactobacilli do not appear effective for patients with IBS; bifidobacteriaand certain combinations of probiotics demonstrate some efficacy.

Effectiveness of the 5-HT receptor antagonists in the management ofirritable bowel syndrome

The 5-HT receptor antagonist alosetron is more effective than placebo at relieving global IBSsymptoms in male and female IBS patients with diarrhea. Potentially serious side effects including

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constipation and colon ischemia occur more commonly in patients treated with alosetron comparedwith placebo. The benefits and harms balance for alosetron is most favorable in women with severeIBS and diarrhea who have not responded to conventional therapies. The quality of evidence forefficacy of 5-HT antagonists in IBS is high.

Effectiveness of 5-HT (serotonin) receptor agonists in the management ofirritable bowel syndrome

The 5-HT receptor agonist tegaserod is more effective than placebo at relieving global IBSsymptoms in female IBS-C patients and IBS-M patients. The most common side effect of tegaserod isdiarrhea. A small number (0.11 percent) of cardiovascular events (myocardial infarction, unstableangina, or stroke) were reported among patients who had received tegaserod in clinical trials.

Effectiveness of the selective C-2 chloride channel activators in themanagement of irritable bowel syndrome

Lubiprostone in a dose of 8 micrograms twice daily is more effective than placebo in relieving globalIBS symptoms in women with IBS-C.

Effectiveness of antidepressant agents in the management of irritable bowelsyndrome

Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) are more effectivethan placebo at relieving global IBS symptoms, and appear to reduce abdominal pain. There arelimited data on the safety and tolerability of these agents in patients with IBS.

Effectiveness of psychological therapies in the management of irritable bowelsyndrome

Psychological therapies, including cognitive therapy, dynamic psychotherapy, and hypnotherapy, butnot relaxation therapy, are more effective than usual care in relieving global symptoms of IBS.

Effectiveness of herbal therapies and acupuncture in the management ofirritable bowel syndrome

Available randomized controlled trials mostly tested unique Chinese herbal mixtures, and appeared toshow a benefit. It is not possible to combine these studies into a meaningful meta-analysis, however,and overall, any benefit of Chinese herbal therapy in IBS continues to potentially be confounded bythe variable components used and their purity. Also, there are significant concerns about toxicity,especially liver failure, with use of any Chinese herbal mixture. A systematic review of trials ofacupuncture was inconclusive because of heterogeneous outcomes. Further work is needed beforeany recommendations on acupuncture or herbal therapy can be made.

IBS: irritable bowel syndrome; IBS-C: constipation-predominant irritable bowel syndrome; IBS-M: mixedirritable bowel syndrome; 5-HT : 5-hydroxytryptamine (serotonin) 3 receptor agonists; 5-HT : 5-hydroxytryptamine (serotonin) 4 receptor agonists.Data from: American College of Gastroenterology IBS Task Force. An Evidence-Based Position Statementon the Management of Irritable Bowel Syndrome. Am J Gastroenterol 2009; 104:S1.

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