Advertisement

Current gut-directed therapies for irritable bowel syndrome

  • Howard Y. Chang
  • Eoin C. Kelly
  • Anthony J. Lembo
Article

Opinion statement

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that can present with a wide array of symptoms that make treatment difficult. Current therapies are directed at relieving symptoms of abdominal pain or discomfort, bloating, constipation, and diarrhea. Pharmacologic agents used to treat IBS-associated pain include myorelaxants, peppermint oil, and peripherally acting opiates. Dicyclomine and hyoscyamine, the two myorelaxants available in the United States, have not been proven effective in reducing abdominal pain in patients with IBS. The efficacy of peppermint oil is debated, but methodological problems with existing studies preclude definitive judgment. Loperamide is ineffective for relief of abdominal pain. For IBS patients with excessive abdominal bloating, a small number of studies suggest that bacterial eradication with gut-directed antibiotics and bacterial reconstitution with nonpathogenic probiotics may reduce flatulence. For constipation-predominant (C-IBS) symptoms, current treatment options include fiber supplementation, polyethylene glycol, and tegaserod. Soluble fibers (ispaghula, calcium polycarbophil, psyllium) are more effective than insoluble fibers (wheat bran, corn fiber) in alleviating global symptoms and relieving constipation, although fiber in general has marginal benefit in treatment of overall IBS symptoms. Polyethylene glycol increases bowel frequency in chronic constipation, but its overall efficacy against IBS is unclear. Tegaserod, a 5-HT4 agonist, demonstrates superiority over placebo in improving bowel frequency and stool consistency and alleviating abdominal pain and bloating in women with C-IBS. Overall global symptoms are modestly improved with tegaserod when compared with placebo. Additional agents under investigation for C-IBS include the ClC2 chloride channel opener lubiprostone, μ-opioid receptor antagonist alvimopan, and 5-HT4 agonist renzapride. For diarrhea-predominant (D-IBS) symptoms, available therapies include loperamide, alosetron, and clonidine. Alosetron, a 5-HT3 antagonist, is superior to placebo for reducing bowel frequency, improving stool consistency, and relieving abdominal pain in women with D-IBS. However, alosetron is available under a restricted license because of concerns for ischemic colitis and severe constipation necessitating colectomy. Clonidine may be helpful in alleviating global symptoms for D-IBS patients.

Keywords

Irritable Bowel Syndrome Main Side Effect Main Drug Interaction Loperamide Ischemic Colitis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Saito YA, Schoenfeld P, Locke GR, III: The epidemiology of irritable bowel syndrome in North America: a systematic review. Am J Gastroenterol 2002, 97:1910–1915.PubMedGoogle Scholar
  2. 2.
    Thompson WG, Longstreth GF, Drossman DA, et al.: Functional bowel disorders and functional abdominal pain. Gut 1999, 45(Suppl 2):II43-II47.PubMedCrossRefGoogle Scholar
  3. 3.
    Agreus L, Svardsudd K, Nyren O, Tibblin G: Irritable bowel syndrome and dyspepsia in the general population: overlap and lack of stability over time. Gastroenterology 1995, 109:671–680.PubMedCrossRefGoogle Scholar
  4. 4.
    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.PubMedGoogle Scholar
  5. 5.
    Poynard T, Regimbeau C, Benhamou Y: Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 2001, 15:355–361.PubMedCrossRefGoogle Scholar
  6. 6.
    Lavo B, Stenstam M, Nielsen AL: Loperamide in treatment of irritable bowel syndrome-a double-blind placebo controlled study. Scand J Gastroenterol Suppl 1987, 130:77–80.PubMedGoogle Scholar
  7. 7.
    Efskind PS, Bernklev T, Vatn MH: A double-blind placebocontrolled trial with loperamide in irritable bowel syndrome. Scand J Gastroenterol 1996, 31:463–468.PubMedGoogle Scholar
  8. 8.
    Hovdenak N: Loperamide treatment of the irritable bowel syndrome. Scand J Gastroenterol Suppl 1987, 130:81–84.PubMedGoogle Scholar
  9. 9.
    Lesbros-Pantoflickova D, Michetti P, Fried M, et al.: Metaanalysis: the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 2004, 20:1253–1269. A comprehensive, systematic review of treatment options available for IBS.PubMedCrossRefGoogle Scholar
  10. 10.
    Dapoigny M, Abitbol JL, Fraitag B: Efficacy of peripheral kappa agonist fedotozine versus placebo in treatment of irritable bowel syndrome. A multicenter doseresponse study. Dig Dis Sci 1995, 40:2244–2249.PubMedCrossRefGoogle Scholar
  11. 11.
    Delgado-Aros S, Chial HJ, Camilleri M, et al.: Effects of a kappa-opioid agonist, asimadoline, on satiation and GI motor and sensory functions in humans. Am J Physiol Gastrointest Liver Physiol 2003, 284:G558-G566.PubMedGoogle Scholar
  12. 12.
    Delgado-Aros S, Chial HJ, Cremonini F, et al.: Effects of asimadoline, a kappa-opioid agonist, on satiation and postprandial symptoms in health. Aliment Pharmacol Ther 2003, 18:507–514.PubMedCrossRefGoogle Scholar
  13. 13.
    Liu JH, Chen GH, Yeh HZ, et al.: Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial. J Gastroenterol 1997, 32:765–768.PubMedCrossRefGoogle Scholar
  14. 14.
    Pittler MH, Ernst E: Peppermint oil for irritable bowel syndrome: a critical review and metaanalysis. Am J Gastroenterol 1998, 93:1131–1135.PubMedCrossRefGoogle Scholar
  15. 15.
    Houghton LA, Whorwell PJ: Towards a better understanding of abdominal bloating and distension in functional gastrointestinal disorders. Neurogastroenterol Motil 2005, 17:500–511.PubMedCrossRefGoogle Scholar
  16. 16.
    Salvioli B, Serra J, Azpiroz F, et al.: Origin of gas retention and symptoms in patients with bloating. Gastroenterology 2005, 128:574–579.PubMedCrossRefGoogle Scholar
  17. 17.
    Pimentel M, Chow EJ, Lin HC: Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. a double-blind, randomized, placebo-controlled study. Am J Gastroenterol 2003, 98:412–419. This randomized, placebo-controlled study showed that IBS is associated with small intestine bacterial overgrowth based on abnormal LBTs. IBS global symptoms were improved in 11% of placebo-treated patients and 35% of neomycin-treated patients. Subset analysis showed that 75% of neomycintreated patients who had LBTs that normalized reported global symptom improvement.PubMedGoogle Scholar
  18. 18.
    Nucera G, Gabrielli M, Lupascu A, et al.: Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth. Aliment Pharmacol Ther 2005, 21:1391–1395.PubMedCrossRefGoogle Scholar
  19. 19.
    Sharara AI, Aoun E, Abdul-Baki H, et al.: A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence. Am J Gastroenterol 2006, 101:326–333.PubMedCrossRefGoogle Scholar
  20. 20.
    Pimenel M, Park S, Kong Y, et al.: Rifaximin, a nonabsorbable antibiotic, improves the symptoms of irritable bowel syndrome: a double-blinded randomized controlled study. Am J Gastroenterol 2005, 100:S324.Google Scholar
  21. 21.
    Dear KL, Elia M, Hunter JO: Do interventions which reduce colonic bacterial fermentation improve symptoms of irritable bowel syndrome? Dig Dis Sci 2005, 50:758–766.PubMedCrossRefGoogle Scholar
  22. 22.
    Nobaek S, Johansson ML, Molin G, et al.: Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome. Am J Gastroenterol 2000, 95:1231–1238.PubMedCrossRefGoogle Scholar
  23. 23.
    O’Mahony L, McCarthy J, Kelly P, et al.: Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology 2005, 128:541–551.PubMedCrossRefGoogle Scholar
  24. 24.
    Kim HJ, Camilleri M, McKinzie S, et al.: A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2003, 17:895–904.PubMedCrossRefGoogle Scholar
  25. 25.
    Kim HJ, Vazquez Roque MI, Camilleri M, et al.: A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating. Neurogastroenterol Motil 2005, 17:687–696.PubMedCrossRefGoogle Scholar
  26. 26.
    Cann PA, Read NW, Holdsworth CD: What is the benefit of coarse wheat bran in patients with irritable bowel syndrome? Gut 1984, 25:168–173.PubMedGoogle Scholar
  27. 27.
    Chiba T, Kudara N, Sato M, et al.: Colonic transit, bowel movements, stool form, and abdominal pain in irritable bowel syndrome by treatments with calcium polycarbophil. Hepatogastroenterology 2005, 52:1416–1420.PubMedGoogle Scholar
  28. 28.
    Bijkerk CJ, Muris JW, Knottnerus JA, et al.: Systematic review: the role of different types of fibre in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 2004, 19:245–251. A good review of the efficacy of fiber in treating C-IBS and the difference between soluble and insoluble fibers.PubMedCrossRefGoogle Scholar
  29. 29.
    Hebden JM, Blackshaw E, D’Amato M, et al.: Abnormalities of GI transit in bloated irritable bowel syndrome: effect of bran on transit and symptoms. Am J Gastroenterol 2002, 97:2315–2320.PubMedCrossRefGoogle Scholar
  30. 30.
    Khoshoo V, Armstead C, Landry L: Effect of a laxative with and without tegaserod in adolescents with constipation predominant irritable bowel syndrome. Aliment Pharmacol Ther 2006, 23:191–196.PubMedCrossRefGoogle Scholar
  31. 31.
    Lubiprostone: RU 0211, SPI 0211. Drugs R D 2005, 6:245-248.Google Scholar
  32. 32.
    Liu SS, Hodgson PS, Carpenter RL, Fricke JR, Jr: ADL 8-2698, a trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine, prevents gastrointestinal effects of intravenous morphine without affecting analgesia. Clin Pharmacol Ther 2001, 69:66–71.PubMedCrossRefGoogle Scholar
  33. 33.
    Gonenne J, Camilleri M, Ferber I, et al.: Effect of alvimopan and codeine on gastrointestinal transit: a randomized controlled study. Clin Gastroenterol Hepatol 2005, 3:784–791.PubMedCrossRefGoogle Scholar
  34. 34.
    Camilleri M: Alvimopan, a selective peripherally acting mu-opioid antagonist. Neurogastroenterol Motil 2005, 17:157–165.PubMedCrossRefGoogle Scholar
  35. 35.
    Prather CM, Camilleri M, Zinsmeister AR, et al.: Tegaserod accelerates orocecal transit in patients with constipationpredominant irritable bowel syndrome. Gastroenterology 2000, 118:463–468.PubMedCrossRefGoogle Scholar
  36. 36.
    Coffin B, Farmachidi JP, Rueegg P, et al.: Tegaserod, a 5-HT4 receptor partial agonist, decreases sensitivity to rectal distension in healthy subjects. Aliment Pharmacol Ther 2003, 17:577–585.PubMedCrossRefGoogle Scholar
  37. 37.
    Muller-Lissner SA, Fumagalli I, Bardhan KD, et al.: Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. Aliment Pharmacol Ther 2001, 15:1655–1666.PubMedCrossRefGoogle Scholar
  38. 38.
    Novick J, Miner P, Krause R, et al.: A randomized, doubleblind, placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation. Aliment Pharmacol Ther 2002, 16:1877–1888. This large, multicenter, randomized, placebo-controlled trial showed that tegaserod is effective for alleviating global symptoms, bowel frequency, abdominal pain, and bloating in women with C-IBS.PubMedCrossRefGoogle Scholar
  39. 39.
    Kellow J, Lee OY, Chang FY, et al.: An Asia-Pacific, double blind, placebo controlled, randomised study to evaluate the efficacy, safety, and tolerability of tegaserod in patients with irritable bowel syndrome. Gut 2003, 52:671–676.PubMedCrossRefGoogle Scholar
  40. 40.
    Nyhlin H, Bang C, Elsborg L, et al.: A double-blind, placebo-controlled, randomized study to evaluate the efficacy, safety and tolerability of tegaserod in patients with irritable bowel syndrome. Scand J Gastroenterol 2004, 39:119–126.PubMedCrossRefGoogle Scholar
  41. 41.
    Brinker AD, Mackey AC, Prizont R: Tegaserod and ischemic colitis. N Engl J Med 2004, 351:1361–1364.PubMedCrossRefGoogle Scholar
  42. 42.
    Higgins PD, Davis KJ, Laine L: Systematic review: the epidemiology of ischaemic colitis. Aliment Pharmacol Ther 2004, 19:729–738.PubMedCrossRefGoogle Scholar
  43. 43.
    Cann PA, Read NW, Holdsworth CD, Barends D: Role of loperamide and placebo in management of irritable bowel syndrome (IBS). Dig Dis Sci 1984, 29:239–247.PubMedCrossRefGoogle Scholar
  44. 44.
    Houghton LA, Foster JM, Whorwell PJ: Alosetron, a 5-HT3 receptor antagonist, delays colonic transit in patients with irritable bowel syndrome and healthy volunteers. Aliment Pharmacol Ther 2000, 14:775–782.PubMedCrossRefGoogle Scholar
  45. 45.
    Camilleri M, Mayer EA, Drossman DA, et al.: Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5-HT3 receptor antagonist. Aliment Pharmacol Ther 1999, 13:1149–1159.PubMedCrossRefGoogle Scholar
  46. 46.
    Camilleri M, Northcutt AR, Kong S, et al.: Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial. Lancet 2000, 355:1035–1040.PubMedCrossRefGoogle Scholar
  47. 47.
    Bardhan KD, Bodemar G, Geldof H, et al.: A doubleblind, randomized, placebo-controlled dose-ranging study to evaluate the efficacy of alosetron in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 2000, 14:23–34.PubMedCrossRefGoogle Scholar
  48. 48.
    Lembo T, Wright RA, Bagby B, et al.: Alosetron controls bowel urgency and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome. Am J Gastroenterol 2001, 96:2662–2670.PubMedCrossRefGoogle Scholar
  49. 49.
    Camilleri M: Management of the irritable bowel syndrome. Gastroenterology 2001, 120:652–668.PubMedCrossRefGoogle Scholar
  50. 50.
    Talley NJ: Pharmacologic therapy for the irritable bowel syndrome. Am J Gastroenterol 2003, 98:750–758.PubMedCrossRefGoogle Scholar
  51. 51.
    Center for Drug Evaluation and Research: Lotronex (alosetron hydrochloride) Information. http://www.fda.gov/ cder/drug/infopage/lotronex/lotronex.htm. Accessed February 24, 2005.Google Scholar
  52. 52.
    Cilansetron: KC 9946. Drugs R D 2005, 6:169–173.Google Scholar
  53. 53.
    Malcolm A, Camilleri M, Kost L, et al.: Towards identifying optimal doses for alpha-2 adrenergic modulation of colonic and rectal motor and sensory function. Aliment Pharmacol Ther 2000, 14:783–793.PubMedCrossRefGoogle Scholar
  54. 54.
    Viramontes BE, Malcolm A, Camilleri M, et al.: Effects of an alpha(2)-adrenergic agonist on gastrointestinal transit, colonic motility, and sensation in humans. Am J Physiol Gastrointest Liver Physiol 2001, 281:G1468-G1476.PubMedGoogle Scholar
  55. 55.
    Camilleri M, Kim DY, McKinzie S, et al.: A randomized, controlled exploratory study of clonidine in diarrheapredominant irritable bowel syndrome. Clin Gastroenterol Hepatol 2003, 1:111–121.PubMedCrossRefGoogle Scholar
  56. 56.
    Page JG, Dirnberger GM: Treatment of the irritable bowel syndrome with Bentyl (dicyclomine hydrochloride). J Clin Gastroenterol 1981, 3:153–156.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2006

Authors and Affiliations

  • Howard Y. Chang
  • Eoin C. Kelly
  • Anthony J. Lembo
    • 1
  1. 1.Beth Israel Deaconess Medical Center/Harvard University Medical SchoolBostonUSA

Personalised recommendations