Dr. Rockafellow is a clinical assistant professor of pharmacy and Dr. Berardi is a professor of pharmacy at the University of Michigan College of Pharmacy, Ann Arbor, Michigan.
Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder characterized by recurring symptoms of abdominal pain, discomfort, and bloating accompanied by changes in stool frequency or form lasting at least 3 months.1,2
IBS is a symptom complex and is not associated with any structural abnormality or biochemical marker. Patients are classified into subtypes as having diarrhea-predominant IBS (IBS-D), constipation-predominant IBS (IBS-C), or mixed IBS (IBS-M), in which diarrhea alternates with constipation. IBS is prevalent in 7% of North Americans, is 1.5 times more common in women than in men, and occurs more often in individuals younger than 50 years of age.1
IBS patients have an impaired quality of life, lower work productivity, visit physicians more often, and consume more medications than those without IBS.1
Patient Assessment and Triage
Most patients initially self-treat with OTC medications because they are unaware that they may have IBS. The pharmacist should assess whether selftreatment is appropriate or whether the individual may have IBS or a more serious disorder and should seek further medical evaluation. Exclusions to selftreatment include the following:
• Frequent abdominal pain, discomfort, bloating
• Frequent diarrhea, constipation, or alternating constipation with diarrhea
• Rectal bleeding, anemia, unintended weight loss, fever
• Nocturnal symptoms
• Family history of colorectal cancer, inflammatory bowel disease, or celiac sprue
Most IBS patients believe that certain foods cause or exacerbate their symptoms and thus exclude these foods from their diet.1,3
Insufficient evidence exists, however, to support exclusion diets or food allergy testing once lactose intolerance and celiac sprue are excluded.1,3
Alternatively, patients may find it helpful to keep a food diary to determine if gas-producing foods (eg, beans, cabbage, onions, broccoli), carbonated beverages, sorbital, lactose, or wheat aggravate their symptoms and then avoid or limit them to determine if symptoms improve.
Many IBS patients who seek medical care suffer from anxiety or depression and benefit from psychological therapies, including cognitive-behavioral therapy, hypnotherapy, and dynamic psychotherapy.1-3
Although insufficient evidence exists to support relaxation therapy, some patients will obtain relief of some symptoms through relaxation techniques or regular exercise.
Pharmacologic treatment is aimed at relieving the predominant GI symptom, but the goal should be to improve the overall or global symptoms, including altered stool frequency and consistency, abdominal pain and discomfort, bloating, and quality of life.
Abdominal Pain and Discomfort
Antispasmodics (eg, hyoscyamine, dicyclomine) may provide short-term relief of abdominal pain and discomfort in IBS, but support for long-term efficacy is not available.1,3
Most evidence exists for hyoscyamine with limited data for dicyclomine, but very few trials are recent and many are not of high quality.1-3
These agents act on cholinergic receptors to reduce abdominal pain and discomfort associated with smooth muscle spasm. Antispasmodics are associated with adverse effects (eg, dry mouth, blurred vision, dizziness, urinary retention), which may limit their use and should be avoided in IBS-C or IBS-M, as they may worsen constipation.
The tricyclic antidepressants (TCAs) have been well studied in moderate-tosevere IBS and show improvement in overall global well-being and a reduction in abdominal pain, especially when abdominal pain is the prominent symptom. 1-3
Amitriptyline and desipramine are most commonly prescribed for IBS patients. In contrast to the higher antidepressant dosages used to treat coexisting depression and anxiety, lower daily doses are used to relieve abdominal pain. Most benefit is seen in patients with persistent IBS-D who are able to tolerate the undesirable side effects.
Selective Serotonin Reuptake Inhibitors
The selective serotonin reuptake inhibitors (SSRIs) are often preferred for abdominal pain and discomfort because they are better tolerated than the TCAs. Five randomized controlled trials (RCTs) have evaluated the SSRIs in IBS patients.1-4
Benefit appears limited to improvement in general wellbeing, except in 2 trials in which relief of abdominal pain was observed.3
No reports have been published comparing SSRIs with low-dose TCAs. A trial of an SSRI is reasonable in an IBS patient with abdominal pain, however. Avoid paroxetine in IBS-C and IBS-M because of the risk of constipation.
Loperamide is the antidiarrheal of choice for treating IBS-D, as it improves stool consistency and reduces stool frequency.1-4
It is the only antidiarrheal that has been adequately evaluated for IBS-D in RCTs.3
Loperamide does not improve abdominal pain, discomfort, bloating, or global IBS symptoms. IBS-D patients should take loperamide before meals if postprandial diarrhea is anticipated. Antidiarrheals should be used cautiously in patients with IBS-M.
5-HT3 Receptor Antagonists
Alosetron, a 5-HT3 receptor antagonist, slows colonic transit and relieves the global symptoms of IBS-D patients.1-4
RCTs confirm benefit in women, but the drug is not as well-studied in men.5
Because alosetron was linked to dose-dependent severe constipation and rare reports of colonic ischemia, it was withdrawn from the US market and later reintroduced at a lower dosage of 0.5 mg twice daily for women with severe IBS-D who do not respond to conventional treatment. Alosetron should be stopped if the patient does not respond to the 1-mg, twice-daily dose after 4 weeks or if severe constipation or signs and symptoms of ischemic colitis develop. Alosetron is regulated by a restrictive prescribing program, which requires the pharmacist to fill only those prescriptions that are affixed with a prescribing program sticker.6
Fiber supplements are often recommended as initial therapy for IBS-C, but inadequate exclusion criteria and unspecified IBS subtypes confound study results.1,3
Psyllium minimally improves IBS global symptoms without reducing abdominal pain.4,7
Although the adverse effects of fiber supplements were not evaluated in many studies, they often exacerbate abdominal bloating, distention, and flatulence. If these agents are used, gradual titration should be advised.
Laxatives, although extensively studied for chronic constipation, have not been studied in RCTs in adults with IBS-C.1,3
A small study in adolescents with IBS-C reports improved stool frequency with polyethylene glycol (PEG) 3350, but no effect on the intensity of abdominal pain.3
Lactulose should be avoided in IBS-C, because it causes intestinal gas production and flatulence. The OTC dose of PEG 3350 (Miralax) is the same as the prescription dose.
5-HT4 Receptor Antagonists
Tegaserod, a 5-HT4 receptor antagonist, was approved by the FDA for the treatment of IBS-C global symptoms, but it was withdrawn from the US market in 2007 because of cardiovascular events associated with its use.
Chloride Channel Activator
Lubiprostone activates chloride channels in the GI tract, increasing fluid secretions and accelerating GI transit.1,3
Originally FDA-approved for chronic constipation at a dose of 24 mcg twice daily, it is now approved for IBS-C global symptoms at a lower daily dosage. RCTs show an overall improvement in abdominal symptoms and bowel movements.3,4
Adverse effects are less frequent with the lower lubiprostone dose, but include nausea (most common), diarrhea, and abdominal distention. 3
Other Agents Used to Treat IBS Symptoms
RCTs of rifaximin, a nonabsorbable antibiotic, has shown improvement in IBS-D global symptoms, especially when bloating was the predominant symptom.3,4
Treatment ranges from 10 to 14 days. Symptom relief lasts about 12 weeks.
Probiotics are taken to restore the natural balance of the GI microenvironment. 8
They are available as single- and multi-species formulations, but Lactobacilli and Bifidobacteria are most studied in IBS. A systematic review3
and a metaanalysis9
in IBS show a trend toward symptom improvement with Bifidobacteria.3
A few RCTs with Bifidobacterium infantis 35624 (Align) and Bifidobacterium animalis DN173010 (Activia) suggest that they reduce IBS symptoms.10
Because probiotics are safe and may be beneficial, they are reasonable adjuncts to IBS therapy.
Complementary and Alternative Therapies
Many IBS patients consider complementary and alternative therapies because current medications do not provide adequate symptom relief.11,12
The use of peppermint oil as an antispasmodic shows benefit in a small number of RCTs.3,11
Chinese herbs may improve symptoms, but concerns about safety limit their use. Further studies are needed to determine if acupuncture is effective.
Patients with IBS-like symptoms often seek advice about the use of OTC medications. The pharmacist should determine if self-treatment is appropriate and should also advise the patient with IBS about the use of medications to treat their symptoms. ■
1. American College of Gastroenterology IBS Task Force. An Evidence-Based Position Statement on the Management of Irritable Bowel Syndrome. Am J Gastroenterol 2009;104:S1-S7.
2. Mayer EA. Irritable bowel syndrome. N Engl J Med 2008:358;1692-9.
3. American College of Gastroenterology IBS Task Force. An Evidence-Based Systematic Review on the Management of Irritable Bowel Syndrome. Am J Gastroenterol 2009;104:S8-S35.
4. Hammerle CW, Surawicz CM. Updates on treatment of irritable bowel syndrome. World J Gastroenterol 2008;14:2639-49.
5. Chang L, Ameen VZ, Dukes GE, et al. A dose ranging, phase II study of the efficacy and safety of alosetron in men with diarrhea-predominant irritable bowel syndrome. Am J Gastroenterol 2005;100:115-23.
6. Lotronix package insert: accessed April 2009 http://www.fda.gov/cder/foi/label/2008/021107s013lbl.pdf.
7. Bijkerk CJ, Muris JW, Knotterus JA et al. Systemic review: the role of different types of fibre in the treatment or irritable bowel syndrome. Aliment Pharmacol Therapy 2004; 19:245-51.
8. Parkes GG, Brostoff J, Whelan K, et al. Gastrointestinal microbiota in irritable bowel syndrome: their role in its pathogenesis and treatment. Am J Gastroenterol 2008;103:1557-67.
9. McFarland LV, Dublin S. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol 2008;14:2650-61.
10. Berardi R. Irritable bowel syndrome: update on medical management and the use of probiotics. US Pharmacist. 2007;(October):77-86.
11. Liu JP, Yang M, Liu YX et al. Herbal medications for treatment of irritable bowel syndrome. Cochrane Database Syst Rev 2006:1 CD004116.
12. Shen YA, Nahas R. Complementary and alternative medicine for treatment of irritable bowel syndrome. Canadian Family Physician 2009; 55:143-147.