CE/CME

Irritable Bowel Syndrome: Evidence-based Treatment

Clinician Reviews. 2014 January;24(1):44-51

References

1. Brandt LJ, Chey WD, Foxx-Orenstein AE, et al; American College of Gastroenterology Task Force on Irritable Bowel Syndrome. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol. 2009;104(suppl 1):S1-S35.

2. Wald A. Irritable bowel syndrome—diarrhoea. Best Pract Res Clin Gastroenterol. 2012;26:573-580.

3. Drossman DA, Camilleri M, Mayer EA, Whitehead WE. AGA technical review on irritable bowel syndrome. Gastroenterology. 2002;123:2108-2131.

4. World Gastroenterology Organization. Irritable bowel syndrome: a global perspective (2009). www.worldgastroenterology.org/assets/downloads/en/pdf/guidelines/20_irritable_bowel_syndrome.pdf. Accessed December 16, 2013.

5. Olden KW. Diagnosis of irritable bowel syndrome. Gastroenterology. 2002;122:1701-1714.

6. Engsbro AL, Begtrup LM, Kjeldsen J, et al. Patients suspected of irritable bowel syndrome—cross-sectional study exploring the sensitivity of Rome III criteria in primary care. Am J Gastroenterol. 2013;108:972-980.

7. Lehrer JK. Irritable bowel syndrome differential diagnoses. Medscape. http://emedicine.medscape.com/article/180389-overview. Accessed December 16, 2013.

8. Kaptchuk TJ, Kelley JM, Conboy LA, et al. Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome. BMJ. 2008;336:999-1003.

9. Böhmer CJ, Tuynman HA. The effect of a lactose-restricted diet in patients with a positive lactose tolerance test, earlier diagnosed as irritable bowel syndrome: a 5-year follow-up study. Eur J Gastroenterol Hepatol. 2001; 13:941-944.

10. Vazquez-Roque MI, Camilleri M, Smyrk T, et al. A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function. Gastroenterology. 2013;144:903-911.

11. Biesiekierski JR, Newnham ED, Irving PM, et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol. 2011;106:508-514.

12. Ruepert L, Quartero AO, de Wit NJ, et al. Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev. 2011;10(8):CD003460.

13. Shepherd SJ, Parker FC, Muir G, Gibson PR. Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence.Clin Gastroenterol Hepatol. 2008;6:765-771.

14. Ong DK, Mitchell SB, Barrett JS, et al. Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome. J Gastroenterol Hepatol. 2010;25:1366-1373.

15. Austin GL, Dalton CB, Hu Y, et al. A very low-carbohydrate diet improves symptoms and quality of life in diarrhea-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol. 2009;7:706-708.

16. Johannesson E, Simrén M, Strid H, et al. Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial. Am J Gastroenterol. 2011;106:915-922.

17. Lackner JM, Jaccard J, Krasner SS, et al. Self-administered cognitive behavior therapy for moderate to severe irritable bowel syndrome: clinical efficacy, tolerability, feasibility. Clin Gastroenterol Hepatol. 2008;6:899-906.

18. Ford AC, Talley NJ, Schoenfeld PS, et al. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis. Gut. 2009;58:367-378.

19. Jailwala J, Imperiale TF, Kroenke K. Pharmacologic treatment of the irritable bowel syndrome: a systematic review of randomized, controlled trials. Ann Intern Med. 2000;133:136-147.

20. Parkes GC, Sanderson JD, Whelan K. Treating irritable bowel syndrome with probiotics: the evidence. Proc Nutr Soc. 2010;69:187-194.

21. Awad RA, Camacho S. A randomized, double-blind, placebo-controlled trial of polyethylene glycol effects on fasting and postprandial rectal sensitivity and symptoms in hypersensitive constipation-predominant irritable bowel syndrome. Colorectal Dis. 2010;12:1131-1138.

22. Andresen V, Montori VM, Keller J, et al. Effects of 5-hydroxytryptamine (serotonin) type 3 antagonists on symptom relief and constipation in nonconstipated irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Clin Gastroenterol Hepatol. 2008;6: 545-555.

23. FDA. Lotronex (alosetron hydrochloride) tablets. www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm172946.htm. Accessed December 16, 2013.

24. FDA. Lotronex (alosetron hydrochloride) information. www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm110450.htm. Accessed December 16, 2013.

25. Drossman DA, Chey WD, Johanson JF, et al. Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome—results of two randomized, placebo-controlled studies. Aliment Pharmacol Ther. 2009;29:329-341.

26. Lunsford TN, Harris LA. Lubiprostone: evaluation of the newest medication for the treatment of adult women with constipation-predominant irritable bowel syndrome. Int J Womens Health. 2010;2:361-374.

27. Pimentel M, Lembo A, Chey WD, et al; TARGET Study Group. Rifaximin therapy for patients with irritable bowel syndrome without constipation.
N Engl J Med. 2011;364:22-32.

28. Tack J. Antibiotic therapy for the irritable bowel syndrome.N Engl J Med. 2011;364:81-82.

29. Rao S, Lembo AJ, Shiff SJ, et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol. 2012;107:1714-1724.

30. Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol. 2012;107:1702-1712.

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Pharmacologic Treatment
Prescription and OTC medications serve an adjunctive role in the management of IBS.¹ Efficacy trials in the IBS population are limited by disease heterogeneity, lack of disease markers, and high placebo response rates.¹⁹

Antispasmodics. Prescription antispasmodics, such as dicyclomine, have been shown to offer short-term relief of IBS-related abdominal pain; however, long-term outcomes are unknown. Possible adverse effects such as dizziness, dry mouth, blurred vision, and sluggishness may limit their use. Peppermint oil is considered an alternative to prescription antispasmodics and has been found to improve global IBS symptoms (RR, 2.25).¹²

Probiotics. A number of trials, systematic reviews, and meta-analyses have addressed the effect of probiotics on IBS symptoms. Meta-analyses found an RR of 0.72 to 0.77 for persistent IBS symptoms in patients using probiotics.²⁰ Because probiotics can be beneficial, with relatively low cost and minimal associated risks, it is reasonable to consider a trial of probiotics, especially the specific strains offering the most promising results, such as Bifidobacterium infantis 35624 and Escherichia coli DSM 17252. Like most IBS treatments, it is unlikely that probiotics will benefit all IBS patients.²⁰

Antidepressants. Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) were found to be effective in reducing the risk for persistent IBS symptoms in adults (RR, 0.66; NNT, 4).^12,18 TCAs can slow gastrointestinal transit time, which may be beneficial to patients with IBS-D but a drawback to those with IBS-C. SSRIs, such as fluoxetine, are especially appropriate for patients with concurrent anxiety or depression. Note that three to four weeks of treatment with antidepressants are required to see benefits.¹

Others. Loperamide has been reported to significantly improve stool frequency and consistency in patients with IBS-D and IBS-M but not global IBS symptoms.^1,2 Polyethylene glycol has been shown to be effective in treating adults with isolated constipation, but it was not superior to placebo in adults with IBS-C.²¹

A systematic review found that the 5-HT3 receptor antagonist alosetron offered clinical benefit to patients with IBS-D and IBS-M.²² However, due to reports of ischemic colitis and severe constipation, the FDA removed the drug from the US market in 2000. Ultimately, postmarketing data and patient demand brought the drug back onto the market in 2002, but it can be prescribed only with careful regulation and only for women with severe, refractory IBS-D.^23,24

A locally acting chloride channel activator, lubiprostone, offers clinical benefit to patients with IBS-C and chronic constipation.²⁵ Because of its unknown long-term effects, high expense, and lack of comparison data to other IBS-C treatments, this drug should only be given to women with severe refractory IBS-C.²⁶

Two large multicenter RCTs found that a two-week course of rifaximin, a nonabsorbable antibiotic, reduced global IBS symptoms, especially bloating, in patients with IBS without constipation. The benefits continued through 10 weeks of follow-up.²⁷ Prescribing rifaximin for the treatment of IBS is an off-label use and should be limited to patients with IBS-D who have not responded to currently available symptom-directed therapies. In addition, the lack of evidence for long-term benefits as well as the potential for development of antibiotic resistance should be borne in mind when using this drug.²⁸

Linaclotide is approved for IBS-C, based on two large RCTs with 12- and 26-week follow-up periods. Treatment group participants reported substantial improvement in IBS-C symptoms. Approximately 5% of participants discontinued treatment due to diarrhea.^29,30

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