irritable bowel syndrome - cecitycme statement: the american college of physicians is accredited by...

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their habits of critical inquiry and balanced judgement, and to contribute to better patient care. Disclosures: Mark Pimentel, MD, FRCPC, current

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Irritable Bowel Syndrome View online at http://pier.acponline.org/physicians/diseases/d144/d144.html

Module Updated: 2014-02-27

CME Expiration: 2017-02-27

Author

Mark Pimentel, MD, FRCPC

Table of Contents

1. Diagnosis ..........................................................................................................................2

2. Consultation ......................................................................................................................9

3. Therapy ............................................................................................................................11

4. Patient Counseling ..............................................................................................................19

5. Follow-up ..........................................................................................................................21

References ............................................................................................................................22

Glossary................................................................................................................................25

Tables ...................................................................................................................................27

http://pier.acponline.org/physicians/diseases/d144/d144.html

Irritable Bowel Syndrome


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1. Diagnosis Top

Make a positive diagnosis with history and physical exam, reserving appropriate diagnostic tests only to exclude other conditions.

1.1 Look for symptoms of bowel dysfunction associated with abdominal pain

or discomfort.

Recommendations

• IBS is generally defined by abdominal pain or discomfort in association with altered bowel habits

occurring over a period of at least 3 months.

• Use the validated Rome I or II and Manning symptom criteria to make an accurate and reliable

diagnosis. The Rome criteria were most recently updated (Rome III) in 2005.

• See table Symptom Criteria for Irritable Bowel Syndrome.

Evidence

• A 2009 systematic review by the American College of Gastroenterology task force on IBS concluded

that IBS is defined by abdominal pain or discomfort in association with altered bowel habits

occurring over a period of at least 3 months. Individual symptoms have limited accuracy for

diagnosing IBS (1).

• The sensitivity of Rome criteria (after exclusion of red flags) is 65% with a specificity of 100% by

one analysis, compared with the consultant's final diagnosis and negative endoscopic evaluation

(2).

• The positive predictive value is 98% with a 2-year follow-up. Manning criteria (>3/6 positive)

sensitivity and specificity vary by study; however, without exclusion of red flags, the average

sensitivity is approximately 60% and the specificity is approximately 80% (2).

• Diagnostic accuracy of Manning criteria is better in women, younger patients, and when more

criteria are positive (3).

• Rome III criteria were published in 2006 (4; 5).

Rationale

• IBS has been considered a diagnosis of exclusion, but this approach leads to unnecessary

additional tests.

• Clinical and epidemiologic studies have led to the development of symptom-based diagnostic

criteria, but these cannot accurately discriminate IBS from other disorders.

Comments

• Rome II criteria have been developed by expert consensus, requiring pain-related criteria to be

positive. This reduction in symptom criteria is based on factor analysis showing pain-related

symptoms to relate to a single factor and the other symptoms not to relate to the pain factor (6).

Rome criteria do not discriminate IBS from other GI disorders. In 2010, IBS was defined as

irregular bowel function (7). This better discriminates IBS from other diseases.

1.2 Note that alarm symptoms or red flags indicate higher probability of

another disease.

Recommendations

• Recognize that when red flags are present, patients should have more intensive evaluation to

exclude organic disease. Red flags include

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Significant weight loss

Nocturnal awakenings due to GI symptoms

Blood mixed in the stool

Family history of colon cancer or IBD

Recent antibiotic use

Recent onset of symptoms, progressive symptoms

Symptom onset after age 50

Fevers

• Anemia or any abnormal laboratory findings are not consistent with IBS and should be evaluated.

Evidence

• Red flags have been identified as negatively associated with IBS by studies (8) or by expert

consensus (9).

• Red flags were associated with a positive GI evaluation and a diagnosis other than IBS in a series

of 317 patients with GI symptoms (2).

Rationale

• Red flags are not symptoms of IBS; when present, they are suggestive of another diagnosis.

Comments

• Nocturnal symptoms have been reported by many patients; however, the distinction must be made

whether they sleep poorly and note GI symptoms when they wake, or feel that the GI symptoms

cause them to wake. In the absence of red flags, Rome criteria have been noted as a reliable

indicator. However, because IBS is so common, the pretest probability of a diagnosis of IBS is

artificially inflated.

1.3 To strengthen diagnostic certainty, look for other symptoms that suggest IBS.

Recommendations

• Inquire about

Prominent gastrocolic reflex

Alternating constipation and diarrhea

Excess bloating and gas

Chronicity of the symptoms >2 years, especially if waxing and waning

History of acute gastroenteritis or travel before the onset of the IBS symptoms

Evidence

• A 2006 meta-analysis of eight studies showed an association between acute gastroenteritis and the

development of postinfectious IBS. Ten percent of persons with acute gastroenteritis may go on to

develop IBS (10).

• Alternating constipation and diarrhea, excess gas and flatulence, and chronicity of the symptoms

>2 years, especially if waxing and waning, have been identified as predictive factors for the

development of IBS (8).

Rationale

• These symptoms have been proven more likely in IBS than in controls or have been identified by

expert consensus, but are not part of the validated Rome or Manning criteria.

• Acute gastroenteritis is a precipitant of IBS in an otherwise healthy individual.

Comments



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• In many studies, despite pain being a diagnostic criterion for IBS, bloating is the most bothersome

symptom for the patient. Bloating is not reflected in the Rome III criteria.

1.4 Note that the physical examination is usually normal in IBS except for

mild abdominal tenderness.

Recommendations

• Look for a tender sigmoid colon loop, but this is not a specific or sensitive finding.

• Include testing the stool for occult blood as part of the physical exam.

• Any significant findings on physical exam should be evaluated appropriately.

Evidence

• A tender loop of colon is palpated in approximately 60% of patients. The sigmoid or descending

colon is the most common area (11; 12).

• The 2002 American Gastroenterological Association position statement recommended that

abnormal physical findings should be further evaluated as appropriate (13).

Rationale

• Tenderness and spasm of the sigmoid are consistent with IBS; other findings are not, as IBS is a

disorder of regulation of colon function, not structure.

Comments

• The negative physical exam is part of the definition of IBS, although it has not been specifically

validated. The finding of occult blood in the stool should lead to additional imaging tests, such as

colonoscopy or flexible sigmoidoscopy with barium enema. However, the yield of this evaluation

will be low in young patients with typical symptoms and no red flags. One case of hemorrhoids and

two fissures were found in 15 young patients positive for occult blood with typical IBS symptoms

(Rome I criteria) (14).

1.5 Recognize that there are no specific diagnostic tests for IBS.

Recommendations

• Focus initial evaluation on excluding relevant GI disorders.

• Consider flexible sigmoidoscopy to exclude colitis or obstructing lesions of the colon.

• Note that sigmoidoscopy may be helpful when it produces more pain than expected and reproduces

the patient's symptoms.

• Base further evaluation on symptom subtypes, severity, and clinical judgment.

• Colonoscopy should be performed in patients with alarm features and all patients older than age

50.

Evidence

• A 2009 systematic review by the American College of Gastroenterology task force on IBS found

that although testing in IBS is frequently performed, few if any test results are abnormal, which

contributes to the overall cost of IBS. They concluded that in the absence of red flags, routine

testing with CBC, chemistry panel, thyroid function tests, stool for ova and parasites, and

abdominal imaging is unwarranted. They did recommend that colonoscopic imaging should be

performed in patients with alarm findings to rule out organic disease and in all patients older than

age 50 for the purpose of colorectal cancer screening (1).

• Rectal and colonic balloon studies have shown hypersensitivity of the intestines in 55% to 93% of

subjects (15; 16; 17).

http://www.gastrojournal.org/article/S0016-5085(02)00480-8/fulltext




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• In one study, the positive predictive value of fecal calprotectin for organic disease was 76%, and

the negative predictive value for organic disease was 89%. That is, if fecal calprotectin is normal, 9

of 10 patients did not have organic disease (and are likely to have IBS). An ESR >10 had a positive

predictive value of 62% and a negative predictive value of 69% (18).

Rationale

• Sigmoidoscopy can identify colitis when the distal colon and rectum is involved.

• Sigmoidoscopy may be more uncomfortable for patients and reproduce their symptoms because

the disorder is characterized by abnormal sensitivity of the intestines.

• Blood work may identify organic (non-IBS) disease.

• A CBC and ESR are reasonable to evaluate for anemia, elevated sedimentation rate, or

leukocytosis, findings not compatible with IBS.

1.6 Use symptom-based diagnostic evaluation to exclude structural and inflammatory lesions of the GI tract that can mimic IBS. Realize that

differential diagnosis varies in patients with constipation, diarrhea, and pain-predominant symptoms.

Recommendations

• Recognize that for patients who fulfill Rome or Manning criteria,

A history and physical exam (with stool occult blood testing) is the primary method of evaluation and is often sufficient

A CBC (and possibly an ESR) should be considered to screen for inflammatory or neoplastic causes of abdominal pain

The subsequent diagnostic approach should be based on specific symptoms, limiting evaluation to fulfillment of the Rome or Manning criteria if no alarm symptoms are present

Evaluation should be expanded when there is greater likelihood of organic disease, e.g., increasing age (especially older than 50), family history of colon cancer or IBD, and recent onset of progressive symptoms

Evidence

• The Rome criteria plus the absence of red flags had a positive predictive value of 98%; there was

one case of ulcerative proctitis and one of hyperthyroidism (2).

Rationale

• When warning symptoms are absent and Rome criteria have been satisfied, the risk for overlooking

a different medical condition if the history and physical exam suggest IBS and the occult blood test,

CBC, and ESR results are normal may be as low as 1% to 3%.

Comments

• The difficulty with reliability testing of the Rome criteria is that compared with colon cancer, IBD, or

celiac disease, IBS is much more common. Therefore, it is likely that a diagnosis of IBS would be

correct most of the time.

1.7 Consider partial colonic obstruction or non-IBS causes of colonic

dysmotility in patients with constipation.

Recommendations

• Offer fiber/osmotic laxative treatment to patients younger than 50 with mild, chronic constipation-

predominant symptoms and no red flags before additional diagnostic tests.

• Obtain colonic imaging in patients older than 50 or in younger patients with alarm features

including new onset, severe or refractory symptoms, or with a family history of colon cancer by



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colonoscopy or flexible sigmoidoscopy with barium enema to exclude a neoplastic or other

obstruction.

• Use clinical judgment to modify for less or more evaluation as the clinical situation warrants.

• See table Differential Diagnosis of Irritable Bowel Syndrome.

Evidence

• A 2009 systematic review by the American College of Gastroenterology task force on IBS

recommends that colonoscopic imaging should be performed in patients with alarm findings to rule

out organic disease and in all patients older than 50 for the purpose of colorectal cancer screening

(1).

• The 2002 American Gastroenterological Association position statement recommended colonoscopy

for patients older than 50 years. In younger patients, they recommended that performing a

colonoscopy or sigmoidoscopy should be determined by clinical features (13).

Rationale

• Colonic dysmotility without IBS means either no pain or another explanation for symptoms, such as

neurologic disorder, pelvic floor disorder, or colonic inertia (transit through the colon of >72 hours,

with predominantly right colon delay).

• Colon imaging will rule out obstruction.

• Nonobstructive causes of colonic symptoms may be due to dysmotility secondary to medications,

neurologic disease, hypothyroidism, pelvic floor dysfunction, or colonic inertia (markedly delayed

colon transit, greater than 5 days).

Comments

• Additional diagnostic testing may be indicated depending on clinical judgment.

1.8 Perform a more extensive diagnostic evaluation in patients with diarrhea-predominant symptoms to address a broader differential diagnosis, including

IBD, celiac disease, chronic infection, effects of medication and diet, and other conditions.

Recommendations

• Study young patients with mild chronic symptoms with flexible sigmoidoscopy, and examine stools

for ova and parasites × 3 (in addition to CBC).

• Obtain colonic imaging in patients with refractory, severe, or new-onset symptoms and patients

older than 50 by colonoscopy or flexible sigmoidoscopy with barium enema (in addition to testing

for ova and parasites and CBC).

• Consider further testing if colonic imaging and ova and parasite evaluation is normal, and specific

items in the history and physical exam suggest other diagnoses.

• Consider serologic screening for celiac sprue.

• Consider lactose breath testing when lactose maldigestion remains a concern despite dietary

modification.


Evidence

• The 2009 systematic review by the American College of Gastroenterology task force on IBS stated

that in patients with typical IBS symptoms and no alarm feature, routine blood tests and abdominal

imaging are not recommended. However, it is important that clinicians be aware of the differential

diagnosis for chronic diarrhea. In patients with chronic, diarrhea-predominant IBS, further testing






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should be considered, such as serologic screening for celiac sprue and lactose breath testing for

lactose maldigestion (1).

Rationale

• Colonic imaging will identify inflammatory conditions and melanosis coli (which can indicate

surreptitious laxative use), and in older patients, screen for colorectal neoplasms.

• Other noncolonic causes of diarrhea and pain, although difficult to completely exclude without

additional testing, are unlikely if the patient satisfies Rome criteria and lacks alarm symptoms.

Comments

• Additional testing may be indicated depending on clinical features.

• Twenty-four-hour stool collection for quantification of volume may be helpful in large-volume or

watery diarrhea to confirm severity and indicate secretory diarrhea if the volume is over 1 liter.

Volumes over 350 to 400 mL suggest other causes. Normal stool volume is ≤200 mL per day.

• A spot or 24-hour fecal fat test can show malabsorption.

• Evaluation of stool for C. difficile may be helpful if the patient has taken antibiotics recently.

• Routine bacterial cultures are not indicated for chronic diarrhea lasting more than a month. There

is a syndrome of IBS after dysentery, in which patients develop typical symptoms after resolution

of an acute episode of dysentery. This condition may take 6 months to resolve, and in susceptible

persons with risk factors such as age, type of organism, gender, and severity of gastroenteritis, as

well as psychological factors, can lead to chronic IBS. Awareness of this condition can limit the

evaluation for a persistent infectious agent in this situation.

1.9 Recognize that patients with pain-predominant symptoms may have

partial or intermittent small intestinal obstruction, Crohn's disease, aerophagia, or pancreaticobiliary disease.

Recommendations

• Recognize that

A flat and upright abdominal radiograph during an episode of pain may show unrecognized bowel obstruction, aerophagia, or retained stool

Serum amylase and liver enzyme levels may diagnose pancreatic and biliary disease if symptoms are

compatible

A small bowel radiograph can exclude Crohn's disease if symptoms are refractory

CT scanning for neoplasms and miscellaneous conditions will have low yield if there are no alarm symptoms


Evidence

• The 2002 American Gastroenterological Association position statement on IBS recommended that

for patients with pain as the predominant symptom of IBS, a plain abdominal x-ray performed

during an episode of pain is recommended to exclude bowel obstruction and other abdominal

pathology (13).

Rationale

• These tests are useful to exclude obstruction of the bowel, pancreatic disease, Crohn's disease, or

tumors that could mimic pain-predominant IBS.

Comments




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• Other rare conditions that may cause pain-predominant abdominal symptoms with some bowel

dysfunction include intestinal angina (generally associated with weight loss and occult blood) and

endometriosis (in general cyclic with menses).



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2. Consultation Top

Consider referral to a gastroenterologist when needed for help in making or confirming the diagnosis of IBS. Consider consultation with gastroenterologists and mental health professionals.

2.1 Consider referral to a gastroenterologist in cases of diagnostic

uncertainty or for specialized diagnostic procedures, especially when patients do not respond to initial management or need reassurance.

Recommendations

• Consider specialty evaluation by a gastroenterologist when

Patients do not fit Rome or Manning criteria

Patients meet Rome or Manning criteria but have alarm symptoms

Patients do not respond to initial management and may require further evaluation

Evidence

• This recommendation is based on the 2002 American Gastroenterological Association position

statement on IBS (13).

Rationale

• Approximately 30% of a gastroenterology practice includes patients with IBS, providing experience

with diagnosis and exclusion of relevant disorders.

Comments

• Gastroenterologists and surgeons can perform endoscopic evaluation, which is part of a symptom-

based evaluation.

2.2 Consider GI consultation when management strategies are not effective.

Recommendations

• Consider consultation with a gastroenterologist to

Revisit the diagnosis to confirm that it is correct and to determine the need for additional testing

Determine the need for advanced treatments

Diagnose a superimposed disorder (e.g., reflux) that requires additional therapy

Evidence

• None.

Rationale

• A gastroenterology practice can include up to 50% of patients with functional bowel disorders.

• Gastroenterologists may have greater knowledge of treatment options due to increased familiarity

with the disorder and increased educational opportunities.

2.3 Consider consulting mental health professionals, primarily psychologists,

in managing abdominal pain as well as psychosocial stressors or disorders.

Recommendations

• Consider referral to a mental health professional for patients with major depression, anxiety

disorder, bipolar disorder, or other serious psychological disease.





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• Explore factors thought to be a major contributor to the symptoms, including

Drug or alcohol addiction

History of unresolved loss or abuse

Marital discord (family counseling may be indicated)

• Before psychological referral, be sure to

Identify obstacles to the referral (fear of transference of care, stigmatization by psychological referral,

reimbursement issues)

Explain that psychosocial stressors are cofactors exacerbating alterations in brain-gut function, not the sole cause

Explain that the referral will not replace the interaction between the medical doctor and the patient

Explain that psychological treatment is intended to reduce the pain and gut dysfunction

• See table Irritable Bowel Severity.

Evidence

• Severe life stress has been found immediately before the onset of functional bowel disorders (19).

• Failure to resolve chronic life stress is highly associated with persistent symptoms (20).

• Six sessions of cognitive-behavioral treatment over 3 months has been proven effective for

symptoms to 1 year compared with education alone (21).

Rationale

• Psychosocial stressors are key factors that determine if, when, and where patients present for

evaluation and management.

• Psychological therapy reduces pain and improves stool form.

• Good prognostic signs for improvement with psychotherapy are presence of anxiety or depression,

association of stress and symptom exacerbation, and absence of extra-abdominal or constant pain.



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3. Therapy Top

Use non-drug therapies, such as reassurance, education, stress management, dietary modification, and strengthening the physician-patient relationship, before using medication. Consider drug therapy to reduce pain and diarrhea or constipation.

3.1 Reassure patients that their symptoms are not due to a life-threatening

disorder, and educate them in order to develop effective self-management strategies.

Recommendations

• Reassure patients by making a firm diagnosis using established criteria and excluding organic

diseases by focused evaluation.

• Educate patients that symptoms are real and not imagined, with pathophysiologic causes, and that

patients can control some of the triggers of their symptoms.

Evidence

• Retrospective analysis of outpatient charts at a referral center indicates a correlation between

patient education, including discussion of psychosocial stressors, with reduced future visits (22).

Rationale

• Reduction in anxiety can benefit the symptoms as well as reducing use of health care resources.

• Education can reduce future health care use by developing patient self-management skills.

• Avoid the negative diagnosis pitfall: “We have run many tests and cannot find anything, therefore

you must have IBS.”

• The patient may suspect that the physician is unable to find the true diagnosis, may not accept IBS

as the cause of symptoms, and may want additional tests.

Comments

• Although patients are relieved to learn that IBS is not life threatening, the risk is that it

marginalizes their complaints. Conservative measures often have little benefit.

3.2 Identify brain-gut triggers of symptoms, including life stresses and comorbid psychological disturbances.

Recommendations

• Identify life stresses and psychological disturbances by obtaining an initial complete psychosocial

history.

• Factors identified as chronic life stress are

Marital/romantic life

Employment

Family

Illness in self or family member

Financial

• Factors that respond to psychotherapy are

Emotional distress (sadness, anhedonia, vegetative symptoms of depression, anxiety, sleep disorder)

• Factors more common in tertiary care patients with IBS are

http://annals.org/article.aspx?articleid=708357



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Early life or current trauma, including losses or abuse

Generalized anxiety disorder and worry

• Ask patients to complete a daily diary of symptoms including entries for stressors, moods, events,

thoughts, and diet. Use this evaluation to

Help patients focus on the role of psychosocial stressors rather than the pain and bowel function alone

Help patients develop self-management capabilities, particularly to identify associated mood disturbance or

maladaptive thoughts

Determine the need for referral to a mental health professional

Evidence

• In a prospective study, 117 consecutive patients with IBS were assessed for life stress and

symptom intensity at study entry, 6 and 16 months. The results found that chronic life stress

predicted subsequent symptom intensity. No patient exposed to even one chronic highly

threatening stressor improved clinically (by 50%) over the 16 months, and all patients who

improved did so in the absence of such a stressor (20).

• A study used self-administered questionnaires by 789 students and hospital employees. The results

showed that in the group with bowel dysfunction, stressors were temporally associated with bowel

dysfunction (23).

• A prospective study enrolled 72 IBS patients who had sought medical treatment, 82 persons with

IBS symptoms who had not sought medical treatment, and 84 normal subjects. The results showed

that IBS patients have a higher proportion of abnormal personality patterns, greater illness

behaviors, and lower positive stressful life event scores than IBS nonpatients (P<0.001) and

normal controls (P<0.001); however, IBS nonpatients were not significantly different from normal

controls. The findings suggest that in some cases psychological factors help determine if the

patient presents for medical care (24).

• A prospective questionnaire study enrolled 94 consecutive patients hospitalized for gastroenteritis.

Twenty-two of these patients developed IBS. The results showed that psychological distress was

associated with more persistent inflammation and symptoms in IBS after dysentery (25).

• Psychological therapy is effective for symptoms including pain (21).

• Psychotherapy has costs on the front end, but long-term medical costs may be reduced by

psychotherapy 26).

• Early life or current trauma, including losses or abuse, is more common in some patients with IBS

(27).

• Generalized anxiety and worry are greater in some persons with IBS (28).

Rationale

• Psychological distress can exacerbate IBS and is a therapeutic target for management in patients

with coexisting true psychological disease, especially in the tertiary care setting.

• It is important to identify why the patient is now seeking care because symptoms of IBS are

generally chronic; in patients with preexisting psychological risk factors, psychosocial stressors

trigger the exacerbation and must be addressed.

Comments

• Although stress plays a role in the motor function of the gut, it has not been proven to be a

definitive cause of IBS.

3.3 Consider dietary modification in individual cases, although it has not been

proven effective.

Recommendations



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• Ensure that patients are not lactose intolerant or consuming too much sucralose, caffeine, fructose,

sorbitol, or laxative-containing herbal products.

• Ensure that patients with gas and bloating are not drinking excess carbonated beverages, drinking

with a straw, or chewing gum, all of which can lead to aerophagia.

• Advise against excess intake of fats.

• Advise against eating certain carbohydrates, such as beans, cabbage, broccoli, and cauliflower,

which may be difficult to digest and lead to fermentation and gas production. This is now referred

to as the FODMAP diet (low in fermentable oligo-, di-, and monosaccharides and polyols).

• Tell patients that reducing dietary fiber can reduce bloating, but high dietary fiber may improve

constipation even if it is less likely to decrease pain. Ispaghula husk may be helpful in reducing IBS

symptoms.

• Discourage major exclusion diets and food allergy testing as there is insufficient evidence for these

approaches in the treatment of IBS.

Evidence

• A 2009 systematic review by the American College of Gastroenterology task force on IBS found

that while patients often believe that certain foods exacerbate their IBS symptoms, there was

insufficient evidence that food allergy testing or exclusion diets were efficacious in treating IBS

symptoms (1).

• A 2009 systematic review by the American College of Gastroenterology task force on IBS assessed

dietary fiber, bulking agents, and laxatives for treatment of IBS. Psyllium hydrophilic mucilloid

(ispaghula husk) was found to be moderately effective in reducing global IBS symptoms. Other

agents were either shown not to be more effective than placebo or had insufficient evidence to

draw conclusions (1).

• A prospective, single-blind, crossover design trial enrolled 15 subjects with IBS (Rome III criteria)

and 15 healthy control subjects. Subjects consumed either low or high FODMAP diets for 2 days.

Results showed that breath hydrogen was significantly higher in IBS patients on the high FODMAP

diet. GI symptoms and lethargy were significantly induced by the high FODMAP diet in patients

with IBS, while only increased flatus production was reported by healthy volunteers (29).

• In a cohort study of healthy people and patients with IBS, lipid infusion in the gut led to greater

gas retention than infusion of saline, and the effect was greater in IBS patients (30).

Rationale

• Common sense recommendations directed at the predominant symptom are helpful.

Comments

• Some have suggested fiber is the ultimate GI placebo: it is safe, alters bowel habits, and takes

advantage of the 30% to 80% placebo response seen in most IBS studies (31, 32).

• Studies provide mixed results regarding efficacy of a gluten-free diet in patients with IBS without

celiac gluten sensitivity (33; 34).

3.4 Understand the therapeutic importance of the physician-patient relationship.

Recommendations

• Recognize the importance of reassurance, education, advice, encouragement of a healthy lifestyle,

and interest in the patient.

• Use follow-up visits to reinforce the relationship and any recommendations given.

Evidence





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• Advice regarding healthy diet and exercise, improved management of stress, and appropriate use

of medications is associated with alleviation of symptoms in 80% of patients in an uncontrolled

study (35). Exercise and stress management were particularly associated with alleviation of

symptoms.

Rationale

• The value of the physician–patient relationship is underscored by the high placebo response in IBS.

• When treatment for the disorder is nonpharmacologic, interactions between patient and physician

become paramount; it is through this relationship that education, reassurance, stress

management, encouragement of healthy lifestyles, and avoidance of symptom triggers is made

possible.

Comments

• Education and stress management can be taught by allied health care professionals, including

nurses. A relationship with a health professional other than a physician is also therapeutic.

3.5 Consider antispasmodics to reduce pain.

Recommendations

• Consider prescribing antispasmodics, but note that their efficacy in IBS is limited.

• See table Drug Treatment for Irritable Bowel Syndrome.

Evidence

• A 2009 American College of Gastroenterology systematic review and position statement on IBS

treatment found that certain antispasmodics (hyoscine, cimetropium, and pinaverium) may provide

short-term relief of abdominal pain/discomfort in IBS (grade 2C). However, evidence was not

available regarding long-term efficacy, and evidence for safety and tolerability was limited (1).

Rationale

• Antispasmodics reduce the contractions in the colon and small bowel that may produce diarrhea

and cramps.

Comments

• Antispasmodics are taken before meals if postprandial urgency, diarrhea, and cramping are a

problem.

• The risk for abuse of sedative-antispasmodics is low due to the low doses of sedatives in most

formulations and the combination anticholinergic drugs that cause unpleasant side effects with

dose elevation.

• Peppermint oil appears superior to placebo for treatment of IBS, but the evidence is limited (1).

3.6 Consider tricyclic antidepressants to reduce pain and diarrhea.

Recommendations

• Consider TCAs as second-line agents in patients with mild to moderate IBS with pain-predominant

symptoms; these agents can be used in combination with antispasmodics.

• Note that the required dosage is less than that required for treatment of depression.


Evidence


treatment identified 9 randomized, controlled trials involving 575 IBS patients and compared TCAs

with placebo. The pooled data from these studies showed that TCAs were more effective than

placebo in improving global IBS symptoms (1).





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• A 2012 systematic review studied the frequency in which harm from side effects limited the

effectiveness of antidepressants such as tricyclics. The analysis included 6 studies involving TCAs.

The results showed that for TCAs, an adverse event resulting in discontinuation of the study

medication occurred for every 2.3 patients who benefited from the drug (36).

Rationale

• TCAs generally are useful for chronic pain and may have both CNS effects to alleviate pain and

peripheral effects to reduce sensory nerve activity from the colon.

• The benefit of TCAs in patients with IBS seems to be independent of the anticholinergic effects or

an antidepressant effect.

• Side effects can limit use and may affect compliance. The constipating side effect leads to frequent

withdrawal from TCAs.

Comments

• Best results are obtained with a low starting dose and gradual dose escalation as tolerated. This

reduces side effects, which often decrease with time.

3.7 Consider saline-type laxatives for constipation not responsive to fiber

supplementation.

Recommendations

• Use saline cathartics, such as polyethylene glycol, for treatment of constipation-predominant IBS

• Note that use of fiber supplementation is often inadequate for relief of constipation symptoms.


Evidence


treatment found that PEG was shown to improve stool frequency but not abdominal pain; however,

the evidence was limited (1).

• A prospective, randomized study of PEG 3350 plus electrolytes randomly assigned patients with

confirmed constipation associated with IBS to receive PEG 3350+E (n=68) or placebo (n=71) for

28 days. The number of weekly spontaneous bowel movements during week 4 was significantly

more in the PEG-treated group (PEG 3350+E, 4.40±2.581; placebo, 3.11±1.937; P<0.0001).

There was no difference in the mean severity score for abdominal discomfort/pain in patients

treated with PEG compared with placebo. However, for patients treated with PEG 3350+E, the pain

score was significantly reduced compared with the run-in period (37).

Rationale

• Distention of the colon caused by stool is poorly tolerated by patients with colonic hypersensitivity

to distention.

• Bloating, discomfort, and pain may be relieved by regular stool evacuation.

Comments

• Regular use of stimulant cathartics, such as senna, cascara, and phenolphthalein, should be

avoided due to the risk for cramps, tachyphylaxis, and possibly development of a markedly slow

“cathartic colon.”

3.8 Use antidiarrheal agents for diarrhea symptoms.

Recommendations

• Use loperamide as a first-line agent for diarrhea. It can be taken as needed or on a scheduled basis

depending on severity and frequency.




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Evidence


treatment identified 2 double-blind, randomized, controlled trials that compared loperamide with

placebo in patients with diarrhea-predominant IBS. The review found that loperamide was an

effective agent for treatment of diarrhea in patients with IBS as it improved both stool frequency

and stool consistency. However, the antidiarrheal agent was not more effective than placebo for

reducing abdominal pain (1).

Rationale

• Mu opiate receptors (stimulated by loperamide) reduce propagating contractions and increase

segmenting contractions in the bowel that slow transit and allow more time to absorb water.

Comments

• Repeated use of loperamide appears safe. Use of other antidiarrheal agents is also likely to be

effective.

3.9 Consider 5-HT3 receptor antagonist for severe, refractory, diarrhea-

predominant IBS in women.

Recommendations

• Consider the 5-HT3 antagonist alosetron, 1 mg po bid, for treatment of women with severe

diarrhea-predominant IBS.

• Understand that because of the increased risk for ischemic colitis, it should be reserved for women

with severe IBS symptoms causing significant quality-of-life impairment.

• Be aware that prescribing doctors must register with the manufacturer and enroll in the Prescribing

Program for Lotronex, and patients must sign a consent form to begin therapy.


Evidence


treatment identified 8 placebo-controlled trials that evaluated alosetron use in 4,987 patients. The

finding was that the 5-HT3 antagonist alosetron was effective at relieving global IBS symptoms in

male and female patients with diarrhea-predominant IBS (1).

• A 2012 systematic review evaluated 8 clinical trials involving alosetron and found that alosetron

has a high potential for harm (36).

Rationale

• IBS can cause severe quality-of-life impairment.

• Alosetron (a 5-HT3 receptor antagonist) is effective for IBS symptoms, leading to adequate relief

for patients with diarrhea-predominant IBS.

• Blockade of the 5-HT3 receptor increases colonic compliance, reduces intestinal transit, and reduces

pain and diarrhea.

3.10 Consider SSRI antidepressants for patients with severe IBS.

Recommendations

• Consider prescribing paroxetine to improve quality of life in patients with severe IBS with

associated psychological stress.


Evidence


http://www.lotronexppl.com/

http://www.lotronexppl.com/




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treatment found that SSRIs were effective at relieving global IBS symptoms and abdominal pain.

However, there were limited data on the safety and tolerability of these agent in patients with IBS

(1).

• In a double-blind, randomized, controlled trial, healthy adult patients with IBS were treated first

with a high-fiber diet. After this run-in period, they were randomly assigned to treatment with

either paroxetine (n=38) or placebo (n=43). Overall well-being improved more with paroxetine

than with placebo (63.3% vs, 26.3%; P=0.01), but abdominal pain, bloating, and social functioning

did not improve significantly with paroxetine compared with placebo (38).

Rationale

• Quality of life may improve in patients with severe IBS treated with SSRIs.

• This may be primarily a psychological effect; however, benefits could include pain alleviation as

well.

Comments

• There is only limited controlled data for the use of SSRI agents.

3.11 Consider antibiotic therapy for patients with refractory IBS.

Recommendations

• Consider prescribing a nonabsorbable antibiotic for patients with IBS who have failed other

therapies.


Evidence


treatment identified 3 well-designed randomized, controlled trials that evaluated rifaximin in 545

patients with IBS. They noted that the majority of the patients in rifaximin trials had diarrhea-

predominant IBS. They concluded that rifaximin was effective for global improvement of IBS and

for bloating. There were no data available to support the long-term safety and effectiveness for

treatment of IBS (1).

• A 2012 systematic review and meta-analysis identified 5 studies that were included in the analysis.

They found that rifaximin was more effective than placebo for improvement of global IBS

symptoms (OR, 1.57 [CI, 1.23 to 1.96]). Serious adverse events were similar with rifaximin and

placebo (39).

Rationale

• Studies suggest that nonabsorbable antibiotics (specifically rifaximin) offer relief of global IBS,

stool consistency, abdominal pain, and bloating.

Comments

• Neomycin is another nonabsorbable antibiotic that has been studied for treatment of IBS (40; 41).

• Rifaximin is currently not FDA-approved for treatment of IBS.

3.12 Consider secretagogue therapy for patients who have IBS with

constipation.

Recommendations

• Consider prescribing lubiprostone, 8 μg twice daily, for adult women who have IBS with

constipation.

• Consider prescribing linaclotide, 290 μg once daily, for adults with IBS with constipation.





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Evidence


found that lubiprostone, 8 μg twice daily, was effective in relieving global IBS symptoms in women

with constipation-predominant IBS (1).

• A randomized, double-blind, placebo-controlled study of oral linaclotide, 290 μg once daily for 12

weeks, enrolled 800 patients with IBS with constipation. A primary end point was defined as

improvement of 30% or more in average daily worst-abdominal-pain score and an increase by ≥1

complete spontaneous bowel movement from baseline (same week) for at least 50% of the weeks

assessed. This endpoint was met by 136/405 linaclotide-treated patients (33.6%) compared with

83/395 placebo-treated patients (21.0%) (P<0.0001). Diarrhea, the most common adverse event,

resulted in discontinuation of 5.7% of linaclotide-treated patients and 0.3% of placebo-treated

patients (42).

• A randomized, double-blind, placebo-controlled study of oral linaclotide, 290 μg once daily for 26

weeks, enrolled 804 patients with IBS with constipation. A primary endpoint was defined as a

patient who reported improvement of 30% or more from baseline in average daily worst-

abdominal-pain score and an increase of ≥1 complete spontaneous bowel movement from

baseline, both in the same week, for 6/12 weeks or more. The results showed that 33.7% of

linaclotide-treated patients were responders vs. 13.9% of placebo-treated patients (P<0.0001).

The incidence of adverse events was similar between the two treatment groups, except for

diarrhea, which caused discontinuation in 4.5% of linaclotide-treated patients vs. 0.2% of placebo-

treated patients (43).

Rationale

• Lubiprostone increases secretion of small bowel fluid and loosens stool consistency by affecting

chloride channels in the intestine.

• Linaclotide increases secretion of small bowel fluid by acting as a guanylate cyclase C agonist.

Comments

• Lubiprostone is FDA-approved for treatment of IBS with constipation in women aged 18 years or

older.

• Linaclotide is FDA-approved for treatment of IBS with constipation in adults.

• Lubiprostone and linaclotide are contraindicated in patients with known or suspected mechanical GI

obstruction.




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4. Patient Counseling Top

Stress key elements about the pathophysiology, effective self-management strategies, and prognosis.

4.1 Explain what is currently understood about IBS.

Recommendations

• Explain that pain and bowel dysfunction can be understood in terms of intestinal spasms combined

with increased sensitivity and reactivity to food and stool boluses.

• Explain that standard medical testing will not identify these abnormalities to validate their

complaints despite normal evaluation.

• Explain that CNS triggers include psychosocial stressors and psychological states, which modulate

gut function, and that the patient has the potential to control these.

• Explain that acute gastroenteritis may be a trigger for IBS.

Evidence

• In an uncontrolled longitudinal study, 52 consecutive adult outpatients with IBS attended a

structured class that taught health-promoting modifications of lifestyle. Participants completed the

Health-Promoting Lifestyle Profile and selected items from a Bowel Disease Questionnaire before

the class and 1 month and 6 months later. The results showed that response rates at 1 and 6

months were 75% and 83%, respectively (35).

• A 2006 meta-analysis included 8 studies of postinfectious IBS. All of the studies reported an

increased risk for IBS following infectious gastroenteritis. The median prevalence of IBS in the

infectious gastroenteritis groups was 9.8% compared with 1.2% in control groups (sign-rank test,

P=0.01) (10).

Rationale

• Patient understanding of brain-gut dysfunction is useful to explain the variety of symptoms, the

lack of anatomic or histologic abnormality, and the basis for self-management.

• A good explanation of symptoms and the reason evaluation results have been negative helps

reassure the patient.

Comments

• There are many theories about the pathogenesis of IBS, including alterations in the brain-gut axis,

acute gastroenteritis, serotonin dysfunction, and, more recently, altered gut flora. However, it is

likely that these are all part of an integrated pathophysiologic event that leads to hypersensitivity

of the intestines to distention, abnormal intestinal motility, and exaggerated CNS effects on the

gut. Attempting to explain to patients what is known may be helpful in overall management.

4.2 Stress that self-management is feasible and important.

Recommendations

• Explain that IBS generally is a chronic condition and that patients can treat themselves by taking

medication as needed, avoiding psychosocial stressors, and controlling dietary or other triggers.

Evidence

• Self-management is a goal recommended by expert consensus (44).

Rationale

• Dysfunction of gut and nerves influencing the gut is likely a trait rather than a temporary state and

can be modified by a few medications with modest effects.




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• These medications are used as needed and are best controlled by the patient.

• Modulation of the CNS influence on the gut is a primary area for intervention.

• Ultimately the patient can gain control of the disorder by controlling psychosocial triggers or

responses to them.

4.3 Reassure the patient regarding the good long-term prognosis.

Recommendations

• Explain to patients that

Although the disorder is chronic and relapsing, there are no known long-term complications

There is no known risk for cancer

Exacerbation of symptoms is often induced by psychosocial stressors

Evidence

• When patient concerns are addressed in the initial physician visit, follow-up visits are fewer (22).

Rationale

• Explanation of the prognosis can reduce both the patient's anxiety and their need for health care.



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5. Follow-up Top

Follow patients to monitor for alarm symptoms, change in therapy, and management of psychosocial stressors.

5.1 Reassess symptoms over time and after an initial therapeutic trial to ensure that a more serious disorder is not overlooked.

Recommendations

• Ensure symptoms are not progressive (atypical for IBS).

• Ensure alarm symptoms do not develop.

• If alarm symptoms or signs are found, these must be evaluated appropriately.

• If symptoms are refractory and persistent, consider additional diagnostic tests or referral.

• Ensure that the patient has an appropriate understanding of the disease.

Evidence

• The strategy of initial conservative (limited) evaluation, confirmed by clinical follow-up, is advised

by experts (45).

• The initial diagnosis is generally durable if based on proper criteria. The incidence of new GI

diagnoses within 2 years of diagnosis of IBS (based on Rome criteria, no red flags, and negative

sigmoidoscopy) was 0 in 30 in one study (2).

Rationale

• By following a patient's response to initial therapy and their long-term symptoms, a more

conservative initial diagnostic strategy may be pursued.

• The risk for serious organic disorders mimicking IBS is less likely if symptoms are chronic and

fluctuating.

5.2 Monitor changes in symptoms (such as pain, constipation, and diarrhea)

and impairment of lifestyle to determine the need for changes in therapy.

Recommendations

• Make therapeutic changes when symptom exacerbations cause impairment in quality of life

according to treatment guidelines as outlined in the Therapy section.

• Treat temporary symptoms with minor alterations in lifestyle and with reassurance.

• Address symptom flare-ups due to psychosocial stress expeditiously.

Evidence

• Consensus.

Rationale

• Symptoms of IBS fluctuate, requiring ongoing changes in management.

• Reassurance and advice regarding stress is often helpful.



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Glossary Top

5HIAA 5-hydroxyindoleacetic acid

bid twice daily

BPH benign prostatic hypertrophy

CBC complete blood count

CD4 cluster of differentiation 4

CI

confidence interval

CKD chronic kidney disease

CMV cytomegalovirus

CNS

central nervous system

CrCl creatinine clearance

CT computed tomography

CYP

cytochrome P450 isoenzyme

ECG electrocardiogram

ELISA enzyme-linked immunosorbent assay

ERCP endoscopic retrograde cholangiopancreatography

ESR

erythrocyte sedimentation rate

FDA Food and Drug Administration

FODMAP

fermentable oligo-, di-, monosaccharides and polyols

GI

gastrointestinal

HIV human immunodeficiency virus

IBD inflammatory bowel disease

IBS irritable bowel syndrome



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IM

intramuscular

MAOI monoamine oxidase inhibitor

NMS neuroleptic malignant syndrome

OR

odds ratio

PEG polyethylene glycol

PEG 3350+E polyethylene glycol 3350 plus electrolytes

P-gp P-glycoprotein

po oral

prn as needed

q12h every 12 hours

qd

once daily

qhs every night

qid

four times daily

SSRI

selective serotonin-reuptake inhibitor

TCA tricyclic antidepressants

tid three times daily

TSH thyroid-stimulating hormone

VIP vasoactive intestinal polypeptide



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Tables Top

Differential Diagnosis of Irritable Bowel Syndrome

Disease Characteristics

Constipation-predominant symptoms

PARTIAL COLON OBSTRUCTION

A. IBD-stricture May cause colonic strictures with obstipation.

Colonoscopy vs. barium enema and flexible sigmoidoscopy

B. Colon cancer May cause colonic strictures with obstipation.


C. Post-diverticulitis or ischemic stricture May cause colonic strictures with obstipation.


NON-OBSTRUCTIVE COLONIC DYSMOTILITY

A. Colonic inertia (colon transit >72 h, predominantly right colon delay) Very infrequent bowel movements.

Sitzmark transit study: capsule with 24 markers taken day 1, 2, 3. Abdominal film day 4, 7. Count all

markers on x-ray for total colon transit (in hours) (46)

B. Pelvic floor dysfunction* Straining, self-digitation, nonrelaxing, nondescending anal canal during defecation effort.

Careful rectal exam to evaluate lack of pelvic descent or anal relaxation with defecation effort.

Balloon expulsion study.

Anorectal manometry.

Defecography

C. Neurologic disease* Parkinson's disease, autonomic dysfunction (Shy-Drager), multiple sclerosis.

History and neurologic exam

D. Medication* Opiates, cholestyramine, calcium channel blockers, anticholinergic medications.

Drug history

E. Hypothyroidism* Variety of symptoms and signs.

Serum TSH

Diarrhea-predominant symptoms

INFLAMMATORY BOWEL DISEASE

A. Crohn's disease Diarrhea may be from inflammatory exudate, motility changes, small bowel overgrowth, or bile salt

malabsorption.

Colonoscopy, small bowel barium radiograph

B. Ulcerative colitis Likely to have rectal bleeding.

Colonoscopy







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C. Microscopic colitis* Generally middle-aged and older women with autoimmune disease (especially thyroiditis).

Colonoscopy/flexible sigmoidoscopy and biopsy

INFECTIONS

A. Parasites Giardia lamblia, stream and well water, frequent dyspepsia and bloating.

Ova and parasites × 3, stool Giardia antigen, metronidazole trial

B. Parasites Ascaris lumbricoides, Entamoeba histolytica, especially if travel to developing regions.

Ova and parasites × 3

C. Parasites Strongyloides stercoralis, especially if travel to Third World, but also seen in Kentucky and Tennessee.

Ova and parasites × 3

D. Bacteria Clostridium difficile if antibiotics taken.

Stool ELISA, flexible sigmoidoscopy for pseudomembranes

E. Bacteria IBS after dysentery may persist for months after infection with bacteria.

Compatible history, possible initial positive stool culture

MALABSORPTION

A. Small bowel overgrowth Due to small bowel dysmotility, partial obstruction, blind loop, or jejunal diverticulosis.

Abdominal radiograph, small bowel barium radiograph, lactulose breath test, antibiotic trial

B. Sprue* (gluten-sensitive enteropathy) May present with diarrhea, usually steatorrhea.

Usually steatorrhea, positive gliadin, endomysial serum antibodies; endoscopy with small bowel biopsy

is gold standard

C. Lactose intolerance* Especially in blacks, Hispanics, and Asians.

Avoidance trial, lactose breath test

D. Medication and diet* Gas-producing foods, such as beans and cabbage may cause bloating and flatulence; caffeine may

cause hypermotility and diarrhea; sorbitol is present in diet candy, gum, and medications; magnesium

is present in vitamins and antacids; medications may cause diarrhea (e.g., colchicine). Many “herbal”

products taken as vitamins or for “health” may contain senna, aloe, and other herbal cathartics.

Diet and drug history

OTHER

A. Postgastrectomy syndrome Postprandial symptoms.

History of problems worse after gastric surgery

B. HIV enteropathy May have chronic GI infections, such as cryptosporidium, CMV, blastocystis hominis, amoeba species.

Clinical suspicion, HIV test, low CD4

C. GI endocrine tumor Carcinoid, gastrinoma, VIPoma.*

Urine 5HIAA, fasting gastrin (followed by secretin stimulation test), serum VIP

Pain-predominant symptoms

A. Aerophagia, bloating Patient may be anxious (nervous air swallowing), can be exacerbated by antireflux surgery.

Abdominal radiograph with pain




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B. Intermittent small bowel obstruction More likely with history of previous abdominal surgeries.

Abdominal radiograph with pain, small bowel barium radiograph

C. Crohn's disease Small intestine or colon involvement.

Small bowel barium radiograph, colonoscopy

D. Acute intermittent porphyria Rare. May have elevated liver enzymes and neurologic symptoms during attack.

Serum and urine porphyrins, especially porphobilinogen, and delta aminolevulinic acid

E. Ischemia Intestinal angina, especially in vasculopaths; food aversion; weight loss; pain 15-40 min after meals.

Mesenteric angiogram

F. Chronic pancreatitis Usually alcoholics, some idiopathic cases. Pain usually epigastric, radiates to back and more persistent

than usual IBS.

Abdominal radiograph for calcifications, CT scan, ERCP, endoscopic ultrasound

G. Lymphoma of GI tract Generally weight loss.

CT scan, small bowel radiograph

H. Endometriosis Menstrual associated symptoms, pelvic symptoms. GI involvement rare.

Laparoscopy

5HIAA = 5-hydroxyindoleacetic acid; CD4 = cluster of differentiation 4; CMV = cytomegalovirus; CT = computed tomography; ELISA = enzyme-linked immunosorbent assay; ERCP = endoscopic retrograde

cholangiopancreatography; GI = gastrointestinal; HIV = human immunodeficiency virus; IBD = inflammatory bowel disease; IBS = irritable bowel syndrome; TSH = thyroid-stimulating hormone; VIP =

vasoactive intestinal polypeptide.

*Unlikely alone to cause abdominal pain.





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Drug Treatment for Irritable Bowel Syndrome

Drug or Drug Class Dosing Side Effects Precautions Clinical Use

Antispasmodics Generally given prn, especially before

meals

Drowsiness, confusion, xerostomia,

constipation, urinary retention, visual

impairment, tachycardia

Avoid with severe ulcerative colitis, GI

obstruction, glaucoma, elderly. Caution

with cardiac disease, pulmonary

disease, hyperthyroidism, BPH,

peripheral neuropathy, hepatic disease,

CKD

To reduce pain

Dicyclomine (Bentyl) PO: 20-40 mg qid. IM: 20 mg q4-6h

for 1-2 days. Maximum total daily dose

80 mg IM

Hyoscyamine (Levsin, Anaspaz) Regular-release or sublingual: 0.125-0.25 mg q4h or prn. Extended-release:

0.375-0.75 mg q12h or 0.375 mg q8h.

Maximum total daily dose, 1.5 mg

Tricyclic antidepressants Due to sedation, bedtime dosing may

be preferred

Drowsiness and other CNS side effects,

anticholinergic side effects (such as

constipation, xerostomia, urinary

retention, visual impairment),

orthostatic hypotension, ECG

abnormalities, tremor, nausea, weight

gain, sexual dysfunction

Suicidality, particularly in young

adults. Avoid abrupt discontinuation,

MAOI therapy. Decrease dose with

hepatic disease, elderly. Caution with

decreased GI motility, cardiac disease,

closed-angle glaucoma, BPH, urinary

retention, seizure disorder, thyroid

disease, diabetes, sunlight

For symptom relief in severe IBS

Amitriptyline 10-100 mg qhs Most anticholinergic effects

Desipramine (Norpramin) 10-100 mg qhs More dangerous than other TCAs in

overdose

Fewer anticholinergic effects; less

weight gain

Nortriptyline (Pamelor) 10-100 mg qhs Fewer anticholinergic effects; less

weight gain and fewer GI and sexual side effects

Fiber supplements Take with 8 ounces of liquid Abdominal pain, diarrhea, flatulence, nausea, vomiting

Take 2 hours before or after other drugs

Helpful for constipation but not for pain. May worsen diarrhea

Methylcellulose (Citrucel) 2 g qd-tid, or 1 g up to 6 times daily

Polycarbophil (Fiber Lax, FiberCon) 1000 mg qd-qid

Psyllium (Metamucil) 2.4 g soluble fiber qd-tid

Laxatives

Saline laxative

Polyethylene glycol 3350 (MiraLax) 17 g in 120-240 mL fluid qd for 1-4

days

Abdominal pain, bloating, cramping,

flatulence, nausea, vomiting

For constipation unresponsive to fiber

Osmotic laxatives

Magnesium hydroxide (Milk of

Magnesia)

Regular suspension: 15-60 mL qd.

Concentrated suspension: 15-30 mL

Diarrhea, abdominal cramping, chalky

taste, diuresis, dehydration, nausea,

Avoid if CrCl <10. Caution with CKD



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qd. Chewable tablets: 6-8 tablets qd.

Preferable to give at bedtime

vomiting

Lactulose (Constulose, Constilac, Enulose, Cholac, Generlac)

Initially, 15-30 mL qd. May increase to 60 mL qd

Bloating, flatulence, diarrhea. Very sweet taste

Avoid taking with magnesium hydroxide

Chloride channel activator

Lubiprostone (Amitiza) 8 μg bid with food and water Nausea, vomiting, diarrhea, headache Avoid with history of mechanical GI obstruction. Initial dose is 8 μg qd for

patients with severe hepatic disease

For IBS with constipation

Guanylate cyclase C agonist

Linaclotide 290 μg Diarrhea (severe in many cases) For IBS with constipation

Antidiarrheal

Loperamide (Imodium) 2-4 mg, up to qid. Maximum total daily

dose, 16 mg

Drowsiness, dizziness, xerostomia Caution with hepatic disease. Substrate

for CYPs 3A4, 2C8 and P-gp

For diarrhea-predominant IBS

Serotonin 5HT3 receptor antagonist

Alosetron (Lotronex) 0.5 mg bid for 4 weeks. May increase

to 1 mg bid for 4 weeks. Discontinue if symptoms are not adequately

controlled

Constipation Restricted prescribing program,

serious GI adverse reactions, discontinue immediately with

constipation or ischemic colitis. Avoid

with severe hepatic disease, history of

severe GI disease. Caution with mild-

moderate hepatic disease. Metabolized

by CYP1A2, and by CYPs 2C9 and 3A4

to a lesser extent

For severe, refractory diarrhea-

predominant IBS in women

Selective serotonin-reuptake

inhibitors

Depression doses and lower doses

have been used

Platelet dysfunction, GI side effects,

xerostomia, insomnia, anxiety,

agitation, asthenia, drowsiness,

headache, sexual dysfunction, hyponatremia, rare serotonin

syndrome or NMS

Suicidality, particularly in young

adults. Avoid abrupt discontinuation,

other serotonergic drugs and MAOI

therapy. Drug interactions due to CYP450 metabolism

For symptom relief in severe IBS

Antibiotic

Rifaximin (Xifaxan) 550 mg tid for 2 weeks Nausea, abdominal pain, pruritus,

hypersensitivity reactions, dizziness,

peripheral edema

Caution with severe hepatic disease For IBS without constipation. Use only

if other options have failed. May

provide short-term symptom relief

= first-line agent; = black box warning; bid = twice daily; BPH = benign prostatic hypertrophy; CKD = chronic kidney disease; CNS = central nervous system; CrCl = creatinine clearance; CYP =

cytochrome P450 isoenzyme; ECG = electrocardiogram; GI = gastrointestinal; IBS = irritable bowel syndrome; IM = intramuscular; MAOI = monoamine oxidase inhibitor; NMS = neuroleptic malignant

syndrome; P-gp = P-glycoprotein; PO = oral; prn = as needed; q12h = every 12 hours; qd = once daily; qhs = every night; qid = four times daily; TCA = tricyclic antidepressant; tid = three times daily.

PIER provides key prescribing information for practitioners but is not intended to be a source of comprehensive drug information.



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Symptom Criteria for Irritable Bowel Syndrome

Rome I Criteria for Irritable Bowel syndrome*

At least 3 months of continuous or recurrent symptoms of:

Abdominal pain or discomfort that is:

Relieved with defecation†; and/or

Associated with a change in frequency of stool†; and/or

Associated with a change in consistency of stool†; and

Two or more of the following on at least 25% of occasions or days:

Altered stool frequency (more than 3 bowel movements each day or less than 3 bowel movements each week);

Altered stool form (lumpy/hard or loose/watery stool);

Altered stool passage (straining, urgency, or feeling of incomplete evacuation);

Passage of mucus; and/or

Bloating or feeling of abdominal distension

Manning Criteria

Pain relief with defecation, often

Looser stools at pain onset, often

More frequent stools at pain onset, often

Visible abdominal distention

Mucus per rectum

Feeling of incomplete evacuation, often

* Sensitivity of Rome criteria if red flags absent is 65% and specificity is greater than 95% (2).

† Two of three symptoms present in 12 weeks of the previous year required for Rome II diagnosis (47; 48).



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Irritable Bowel Severity

Severity Mild Moderate Severe

Estimated prevalence 70% 25% 5%

Practice type Primary Specialty Referral

Correlation with gut physiology +++ ++ +

Symptoms constant 0 + ++

Psychosocial difficulties 0 + ++

Health care use + ++ +++

Illness behavior 0 + +++

Psychiatric diagnoses 0 + +++

Used with permission from (45). Copyright © 1997 by the American Gastroenterological Association. Users may not print out or otherwise reproduce copies of this table without written permission of the

American Gastroenterological Association.

irritable bowel syndrome - cecitycme statement: the american college of physicians is accredited by...

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