Skip to main content

Advertisement

SpringerLink
Log in

New therapies for functional bowel diseases

  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

During recent years, a greater understanding of the pathophysiology of functional bowel disease, and a surge of interest in this challenge among pharmacologists, basic scientists, and clinical investigators, have led to novel insights and promising therapies. The evidence to support current therapies in nonculcer dyspepsia and irritable bowel syndrome (IBS) is reviewed, and some of the novel therapeutic approaches on the threshold of clinical application are described.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Barbara L, Camilleri M, Corinaldesi R, et al.: Definition and investigation of dyspepsia: consensus of an international hoc working party. Dig Dis Sci 1989, 34:1272–1276.

    Article  PubMed  CAS  Google Scholar 

  2. Veldhuyzen van Zanten SJO, Cleary C, Talley NJ, et al.: Drug treatment of functional dyspepsia: a systematic analysis of trial methodology with recommendations for design of future trials. Am J Gastroenterol 1996, 91:660–671.

    PubMed  CAS  Google Scholar 

  3. American Gastroenterological Association medical position statement: evaluation of dyspepsia. Gastroenterology 1998, 114:579–581.

    Google Scholar 

  4. Fisher RS, Parkman HP: Management of nonulcer dyspepsia. N Engl J Med 1998, 19:1376–1381.

    Article  Google Scholar 

  5. Talley NJ, Meineche-Schmidt V, Pare P, et al.: Efficacy of omeprazole in functional dyspepsia: double-blind, randomized, placebo-controlled trials (the Bond and Opera studies). Aliment Pharmacol Ther 1998, 12:1055–1065.

    Article  PubMed  CAS  Google Scholar 

  6. Samsom M, Verhagen MAMT, van Berge Henegouwen GP, Smout AJPM: Abnormal clearance of exogenous acid and increased acid sensitivity of the proximal duodenum in dyspeptic patients. Gastroenterology 1999, 116:515–520.

    Article  PubMed  CAS  Google Scholar 

  7. Halter F, Miazza B, Brignoli R: Cisapride or cimetidine in the treatment of functional dyspepsia: results of a double-blind, randomized, Swiss multicentre study. Scand J Gastroenterol 1994, 29:618–623.

    PubMed  CAS  Google Scholar 

  8. Jian R, Ducrot F, Ruskone A, et al.: Symptomatic, radionuclide and therapeutic assessment of chronic idiopathic dyspepsia: a double-blind placebo-controlled evaluation of cisapride. Dig Dis Sci 1989, 34:657–664.

    Article  PubMed  CAS  Google Scholar 

  9. Corinaldesi R, Stanghellini V, Raiti C, et al.: Effect of chronic administration of cisapride on gastric emptying of a solid meal and on dyspeptic symptoms in patients with idiopathic gastroparesis. Gut 1987, 28:300–305.

    PubMed  CAS  Google Scholar 

  10. Ghoos YF, Maes BD, Geypens BJ, et al.: Measurement of gastric emptying rate of solids by means of a carbonlabeled octanoic acid breath test. Gastroenterology 1993, 104:1640–1647.

    PubMed  CAS  Google Scholar 

  11. Choi MG, Camilleri M, Burton DD, et al.: [13C]octanoic acid breath test for gastric emptying of solids: accuracy, reproducibility, and comparison with scintigraphy. Gastroenterology 1997, 112:1155–1162.

    Article  PubMed  CAS  Google Scholar 

  12. Talley NJ, Vakil N, Ballard ED, Fennert MB: Absence of benefit of eradicating Helicobacter pylori in patients with nonulcer dyspepsia. N Engl J Med 1999, 341:1106–1111. See annotation below.

    Article  PubMed  CAS  Google Scholar 

  13. Blum AL, Talley NJ, O'Morain C, et al.: Lack of effect of treating Helicobacter pylori infection in patients with nonulcer dyspepsia. N Engl J Med 1998, 339:1875–1881. These papers demonstrate the lack of efficacy of H. pylori eradication in nonulcer dyspepsia.

    Article  PubMed  CAS  Google Scholar 

  14. McColl KEL, Murray LS, El-Omar E, et al.: Symptomatic benefit from eradicating Helicobacter pylori infection in patients with nonulcer dyspepsia. N Engl J Med 1998, 339:1869–1874.

    Article  PubMed  CAS  Google Scholar 

  15. Clouse RE: Antidepressants for functional gastrointestinal syndromes. Dig Dis Sci 1994, 39:2352–2363.

    Article  PubMed  CAS  Google Scholar 

  16. Gorelick AB, Koshy SS, Hooper FG, et al.: Differential effects of amitriptyline on perception of somatic and visceral stimulation in healthy humans. Am J Physiol 1998, 275:G460-G466.

    PubMed  CAS  Google Scholar 

  17. Mertz H, Fass R, Kodner A, et al.: Effect of amitriptyline on symptoms, sleep, and visceral perception in patients with functional dyspepsia. Am J Gastroenterol 1998, 93:160–165.

    Article  PubMed  CAS  Google Scholar 

  18. Thumshirn M, Camilleri M, Choi MG, Zinsmeister AR: Modulation of gastric sensory and motor functions by nitrergic and alpha2-adrenergic agents in humans. Gastroenterology 1999, 116:573–585.

    Article  PubMed  CAS  Google Scholar 

  19. Read NW, Abitbol JL, Bardhan KD, et al.: Efficacy and safety of the peripheral kappa agonist fedotozine versus placebo in the treatment of functional dyspepsia. Gut 1997, 41:664–668.

    Article  PubMed  CAS  Google Scholar 

  20. Zerbib F, Bruley des Varannes S, Oriola RC, et al.: Alosetron does not affect the visceral perception of gastric distension in healthy subjects. Aliment Pharmacol Ther 1994, 8:403–407.

    Article  PubMed  CAS  Google Scholar 

  21. Tack J, Piessevaux H, Coulie B, et al.: Role of impaired gastric accommodation to a meal in functional dyspepsia. Gastroenterology 1998, 115:1346–1352. Comprehensive study documenting which symptoms require accommodation.

    Article  PubMed  CAS  Google Scholar 

  22. Thumshirn M, Camilleri M, Saslow SB, et al.: Gastric accommodation in non-ulcer dyspepsia and the roles of Helicobacter pylori infection and vagal function. Gut 1999, 44:55–64. Report on mesenteric sensation in nonulcer dyspepsia.

    Article  PubMed  CAS  Google Scholar 

  23. Tack J, Coulie B, Wilmer A, et al.: Influence of sumatriptan on gastric fundus tone and on the perception of gastric distention in man. Gut 2000, 46:468–473.

    Article  PubMed  CAS  Google Scholar 

  24. Tack J, Piessevaux H, Coulie B, et al.: A placebo-controlled trial of buspirone, a fundus-relaxing drug, in functional dyspepsia: effect on symptoms and gastric sensory and motor function [abstract]. Gastroenterology 1999, 116:A325.

    Google Scholar 

  25. Manning AP, Thompson WG, Heaton KW, Morris AF: Towards a positive diagnosis of the irritable bowel. Br Med J 1978, 2:653–654. Original paper emphasizing positive symptom-based diagnosis of irritable bowel syndrome.

    Article  PubMed  CAS  Google Scholar 

  26. Talley NJ, Phillips SF, Melton LJ, et al.: Diagnostic value of the Manning criteria in irritable bowel syndrome. Gut 1990, 31:77–81.

    PubMed  CAS  Google Scholar 

  27. Thompson WG, Dotevall G, Drossman DA, et al.: Irritable bowel syndrome: guidelines for the diagnosis. Gastroenterol Int 1989, 2:92–95.

    Google Scholar 

  28. Thompson WG, Longstreth GF, Drossman DA, et al.: Functional bowel disorders and functional abdominal pain. Gut 1999, 45(suppl II):II43-II47.

    Article  PubMed  Google Scholar 

  29. Drossman DA, Whitehead WE, Camilleri M: Irritable bowel syndrome: a technical review for practice guideline development. Gastroenterology 1997, 112:2120–2137. Authoritative review of irritable bowel syndrome.

    Article  PubMed  CAS  Google Scholar 

  30. Camilleri M, Choi MG: Review article: irritable bowel syndrome. Aliment Pharmacol Ther 1997, 11:3–15.

    Article  PubMed  CAS  Google Scholar 

  31. Gwee KA, Leong YL, Graham C, et al.: The role of psychological and biological factors in postinfective gut dysfunction. Gut 1999, 44:400–406.

    Article  PubMed  CAS  Google Scholar 

  32. Klein KB: Controlled treatment trials in the irritable bowel syndrome. Gastroenterology 1988, 95:232–241.

    PubMed  CAS  Google Scholar 

  33. Poynard T, Naveau S, Mory B, Chaput JC: Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 1994, 8:499–510.

    Article  PubMed  CAS  Google Scholar 

  34. Pittler MH, Ernst E: Peppermint oil for irritable bowel syndrome: a critical review and meta-analysis. Am J Gastroenterol 1998, 93:1131–1135.

    Article  PubMed  CAS  Google Scholar 

  35. Jones RH, Holtmann G, Rodrigo L, et al.: Alosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patients. Aliment Pharmacol Ther 1999, 13:1419–1427.

    Article  PubMed  CAS  Google Scholar 

  36. 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.

    PubMed  CAS  Google Scholar 

  37. Vassallo MJ, Camilleri M, Phillips SF, et al.: Colonic tone and motility in patients with irritable bowel syndrome. Mayo Clin Proc 1992, 67:725–731.

    PubMed  CAS  Google Scholar 

  38. Cann PA, Read NW, Holdsworth CD, Barends D: Role of loperamide and placebo in management of irritable bowel syndrome. Dig Dis Sci 1984, 29:239–247.

    Article  PubMed  CAS  Google Scholar 

  39. Read M, Read NW, Barber DC, Duthie HL: Effects of loperamide on anal sphincter function in patients complaining of chronic diarrhea with fecal incontinence and urgency. Dig Dis Sci 1982, 27:807–814.

    Article  PubMed  CAS  Google Scholar 

  40. Rattan S, Culver PJ: Influence of loperamide on the internal anal sphincter in the opossum. Gastroenterology 1987, 93:121–128.

    PubMed  CAS  Google Scholar 

  41. Musial F, Enck P, Kalveram KT, Erckenbrecht JF: The effect of loperamide on anorectal function in normal healthy men. J Clin Gastroenterol 1992, 15:321–324.

    Article  PubMed  CAS  Google Scholar 

  42. Hallgren T, Fasth S, Delbro DS, et al.: Loperamide improves anal sphincter function and continence after restorative proctocolectomy. Dig Dis Sci 1994, 39:2612–2618.

    Article  PubMed  CAS  Google Scholar 

  43. Sun WM, Read NW, Verlinden M: Effects of loperamide oxide on gastrointestinal transit time and anorectal function in patients with chronic diarrhoea and faecal incontinence. Scand J Gastroenterol 1997, 32:34–38.

    Article  PubMed  CAS  Google Scholar 

  44. Sciarretta G, Fagioli G, Fumo A, et al.: 75Se HCAT test in the detection of bile acid malabsorption in functional diarrhoea and its correlation with small bowel transit. Gut 1987, 28:970–975.

    PubMed  CAS  Google Scholar 

  45. Thaysen EH, Pedersen L: Idiopathic bile salt catharsis. Gut 1976, 17:965–970.

    PubMed  CAS  Google Scholar 

  46. Luman W, Williams AJ, Merrick MV, Eastwood MA: Idiopathic bile acid malabsorption: long-term outcome. Eur J Gastroenterol Hepatol 1995, 7:641–645.

    PubMed  CAS  Google Scholar 

  47. Heefner JD, Wilder RM, Wilson JD: Irritable colon and depression. Psychosomatics 1978, 19:540–547.

    PubMed  CAS  Google Scholar 

  48. Hislop IG: Psychological significance of the irritable colon syndrome. Gut 1971, 12:452–457.

    PubMed  CAS  Google Scholar 

  49. Lancaster-Smith MJ, Prout BJ, Pinto T, et al.: Influence of drug treatment on the irritable bowel syndrome and its interaction with psychoneurotic morbidity. Acta Psychiatr Scand 1982, 66:33–41.

    PubMed  CAS  Google Scholar 

  50. Onghena P, Houdenhove BV: Antidepressant-induced analgesia in chronic non-malignant pain: a meta-analysis of 39 placebo-controlled studies. Pain 1992, 49:205–219.

    Article  PubMed  CAS  Google Scholar 

  51. Myren J, Groth H, Larssen SE, Larsen S: The effect of trimipramine in patients with the irritable bowel syndrome. Scand J Gastroenterol 1982, 17:871–875.

    PubMed  CAS  Google Scholar 

  52. Myren J, Lovland B, Larssen S-E, Larsen S: A double-blind study of the effect of trimipramine in patients with the irritable bowel syndrome. Scand J Gastroenterol 1984, 19:835–843.

    PubMed  CAS  Google Scholar 

  53. Greenbaum DS, Mayle JE, Vanegeren LE, et al.: The effects of desipramine on IBS compared with atropine and placebo. Dig Dis Sci 1987, 32:257–266.

    Article  PubMed  CAS  Google Scholar 

  54. Gram LF: Fluoxetine. N Engl J Med 1994, 20:1354–1361.

    Article  Google Scholar 

  55. Whorwell PJ, Prior A, Faragher EB: Hypnotherapy in irritable bowel syndrome. Lancet 1984, 2:1232–1234.

    Article  PubMed  CAS  Google Scholar 

  56. Svedlund J: Psychotherapy in irritable bowel syndrome: a controlled outcome study. Acta Psychiatr Scand 1983, 67:1–86.

    Google Scholar 

  57. Guthrie E, Creed F, Dawson D, Tomerson B: A controlled trial of psychological treatment for the irritable bowel syndrome. Gastroenterology 1991, 100:450–457.

    PubMed  CAS  Google Scholar 

  58. Dapoigny M, Abitbol JL, Fraitag B: Efficacy of peripheral kappa agonist, fedotozine, vs. placebo in treatment of irritable bowel syndrome: a multicenter dose-response study. Dig Dis Sci 1995, 40:2244–2249.

    Article  PubMed  CAS  Google Scholar 

  59. Camilleri M, Mayer EA, Drossman DA, et al.: Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5HT3-receptor antagonist. Aliment Pharmacol Ther 1999, 13:1149–1159. See annotation below.

    Article  PubMed  CAS  Google Scholar 

  60. Camilleri M, Northcutt AR, Kong S, et al.: The efficacy and safety of alosetron in female patients with irritable bowel syndrome: a randomised, placebo controlled trial. Lancet 2000 355:1035–1040. Two reports on novel therapy for irritable bowel syndrome.

    Article  PubMed  CAS  Google Scholar 

  61. Prather CM, Camilleri M, Zinsmeister AR, et al.: Tegaserod accelerates orocecal transit in patients with constipationpredominant irritable bowel syndrome. Gastroenterology 2000, 118:463–468.

    Article  PubMed  CAS  Google Scholar 

  62. Lefkowitz M, Shi Y, Schmitt C, et al.: The 5HT4 partial agonist, tegaserod, improves abdominal discomfort/pain and normalizes altered bowel function in irritable bowel syndrome (IBS). Am J Gastroenterol 1999, 94:396.

    Google Scholar 

  63. Coremans G, Kerstens R, De Pauw M, Stevens M: Effects of a new enterokinetic drug, prucalopride, on symptoms of patients with severe chronic constipation: a double-blind, placebo-controlled pilot study [abstract]. Gastroenterology 1999, 116:A978.

    Google Scholar 

  64. Coulie B, Tack J, Vos R, Janssens J: Influence of the 5-HT1A agonist buspirone on rectal tone and on the perception of rectal distension in man. Gastroenterology 1998, 114:G3046.

    Google Scholar 

  65. Viramontes B, Malcolm A, Szarka L, et al.: Dose-related effects of a2-adrenergic agent, clonidine, on human gastrointestinal motor, transit and sensory functions [abstract]. Gastroenterology 2000, 118:A666.

    Article  Google Scholar 

  66. Camilleri M: Pharmacology and clinical experience with alosetron. Exp Opin Invest Drugs 2000, 9:1–13.

    Article  Google Scholar 

  67. von der Ohe MR, Camilleri M, Kvols LK: A 5-HT3 antagonist corrects the postprandial colonic hypertonic response in carcinoid diarrhea. Gastroenterology 1994, 106:1184–1189.

    PubMed  Google Scholar 

  68. von der Ohe MR, Hanson RB, Camilleri M: Serotonergic mediation of postprandial colonic tonic and phasic responses in humans. Gut 1994, 35:536–541.

    PubMed  Google Scholar 

  69. Pfannkuche HJ, Buhl T, Gamse R, et al.: The properties of a new prokinetically active drug, SDZ HTF 919 [abstract]. Neurogastroenterol Mot 1995, 7:280.

    Google Scholar 

  70. Hoyer D, Fehlmann D, Langenegger D, et al.: High affinity of SDZ HTF 919 and related molecules for calf and human caudate 5-HT4 receptors. Naunyn-Schmied [abstract]. Arch Pharmacol 1998, 357:R29.

    Google Scholar 

  71. Wiseman LR, Faulds D: Cisapride: an updated review of its pharmacology and therapeutic efficacy as a prokinetic agent in gastrointestinal motility disorders. Drugs 1994, 47:116–152.

    PubMed  CAS  Google Scholar 

  72. Langaker KJ, Morris D, Pruitt R, et al.: The partial 5-HT4 agonist (HTF 919) improves symptoms in constipationpredominant irritable bowel syndrome [abstract]. Digestion 1998, 59:20.

    Google Scholar 

  73. Briejer MR, Meulemans AL, Bosmans J-P, et al.: In vitro pharmacology of the novel enterokinetic R093877 [abstract]. Gastroenterology 1997, 112:A705.

    Google Scholar 

  74. Briejer MR, Ghoos E, Eelen J, Schuurkes JAJ: Serotonin 5HT4 receptors mediate the R093877-induced changes in contractile patterns in the canine colon [abstract]. Gastroenterology 1997, 112:A705.

    Google Scholar 

  75. Camilleri M, McKinzie S, Burton D, et al.: Prucalopride accelerates small bowel and colonic transit in patients with chronic functional constipation (FC) or constipation-predominant irritable bowel syndrome (C-IBS) [abstract]. Gastroenterology 2000, 118:845.

    Article  Google Scholar 

  76. D'Hooghe B, Guillaume D, Medaer R, et al.: Treatment of constipation in multiple sclerosis patients: pilot study with the novel enterokinetic prucalopride [abstract]. Neurogastroenterol Mot 1999, 11:A256.

    Google Scholar 

  77. Miner PB, Nichols T Jr, Silvers DR, et al.: The efficacy and safety of prucalopride in patients with chronic constipation [abstract]. Gastroenterology 1999, 116:A1043.

    Article  Google Scholar 

  78. Nyren O: Secretory abnormalities in functional dyspepsia. Scand J Gastroenterol Suppl 1991, 182:25–28.

    PubMed  CAS  Google Scholar 

  79. Dobrilla G, Comberlato M, Steele A, Vallaperta P: Drug treatment of functional dyspepsia: a meta-analysis of randomized controlled clinical trials. J Clin Gastroenterol 1989, 11:169–177.

    Article  PubMed  CAS  Google Scholar 

  80. Richter JE: Stress and psychologic and environmental factors in functional dyspepsia. Scand J Gastroenterol Suppl 1991, 182:40–46.

    PubMed  CAS  Google Scholar 

  81. Coulie B, Camilleri M: Functional abdominal disorders. In Drug Therapy for Gastrointestinal Liver Diseases. Edited by Farthing M, Ballinger A. London: Martin Dunitz Publishers; in press.

  82. Coulie B, Camilleri M: Irritable bowel syndrome. Clin Perspect Gastroenterol 1999, 2:329–338.

    Google Scholar 

  83. 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.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. GI Unit, Mayo Clinic, Alfred 2-435, 200 First Street SW, 55905, Rochester, MN, USA

    Bernard Coulie MD, PhD & Michael Camilleri MD

Authors
  1. Bernard Coulie MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Camilleri MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Coulie, B., Camilleri, M. New therapies for functional bowel diseases. Curr Gastroenterol Rep 2, 355–363 (2000). https://doi.org/10.1007/s11894-000-0034-8

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11894-000-0034-8

Keywords

Search

Navigation