Skip to main content

Advertisement

SpringerLink
Log in

Serotonergic agents in the treatment of functional gastrointestinal disorders

  • Published:
Current Treatment Options in Gastroenterology Aims and scope Submit manuscript

Opinion statement

  • Functional gastrointestinal disorders are exceptionally common, cause a great deal of suffering, and are extremely challenging to treat. Current therapies, usually targeted at possible abnormalities of gut contractility, are often disappointing and there is a real need for a new approach to treatment.

  • Over the last decade, there has been an increase in our understanding of potential pathophysiologic processes involved in these conditions resulting in novel therapeutic agents based on this information. Serotonin receptor modulators are one such example of this approach, but their development has met with a number of difficulties mainly centered around issues of safety and trial design.

  • It is becoming increasingly apparent that a drug universally effective in all forms of functional gastrointestinal disorders is unlikely to emerge unless some centrally acting compound can achieve this goal. Thus, the current approach of targeting specific subgroups is probably the best strategy.

  • Many patients with functional gastrointestinal disorders do not even bother to consult the medical profession because of the lack of benefit from any currently available treatments. Thus, if a new effective drug is developed, even for a subgroup, demand is likely to be substantial, leading to an even greater burden on already stretched drug budgets.

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

    Article  PubMed  CAS  Google Scholar 

  2. Talley NJ, Silverstein MD, Agreus L, et al.: AGA technical review: evaluation of dyspepsia. American Gastroenterology Association. Gastroenterology 1998, 114:582–595.

    Article  PubMed  CAS  Google Scholar 

  3. Lea R, Whorwell PJ: Quality of life in the irritable bowel syndrome. Pharmacoeconomics 2001, 19:643–653.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  5. Akehurst R, Kaltenthaler E: Treatment of irritable bowel syndrome: a review of randomised controlled trials. Gut 2001, 48:272–282.

    Article  PubMed  CAS  Google Scholar 

  6. Steadman CJ, Talley NJ, Phillips SF, et al.: Selective 5-HT3 receptor antagonism with ondansetron as treatment for diarrhoea predominant irritable bowel syndrome: a pilot study. Mayo Clinic Proc 1992, 67:732–738.

    CAS  Google Scholar 

  7. Prior A, Read NW: Reduction of rectal sensitivity and post prandial motility by granisetron, a 5-HT3 antagonist, in patients with diarrhoea predominant irritable bowel syndrome. Aliment Pharmacol Ther 1993, 7:175–180.

    Article  PubMed  CAS  Google Scholar 

  8. Kamm MA: Review article: the complexity of drug development for irritable bowel syndrome. Aliment Pharmacol Ther 2002, 16:343–351. An interesting article discussing the recent history and difficulties in development of drug treatments for irritable bowel syndrome.

    Article  PubMed  CAS  Google Scholar 

  9. Talley NJ: Serotonergic neuroenteric modulators. Lancet 2001, 358:2061–2068. A very useful review of serotonergic drugs and their effects on the gut.

    Article  PubMed  CAS  Google Scholar 

  10. Jailwala J, Imperiale TF, Kroenke K: Pharmacological treatment of the irritable bowel syndrome: a systematic review of randomised controlled trials. Ann Inter Med 2000, 133:136–147. This is one of several meta-analyses and systematic reviews of treatments for irritable bowel syndrome. It is also worthwhile reading Poynard’s meta-analysis of smooth muscle relaxants. Alimentary Pharmacol Ther 2001, 15:355-361; and Jackson’s meta-analysis of antidepressants. Am J Med 2000, 108:65-72.

    CAS  Google Scholar 

  11. De Ponti F, Tonini M: Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs 2000, 61:317–332.

    Article  Google Scholar 

  12. Sanger GJ: 5-hydroxytryptamine and functional bowel disorders. Neurogastroenterol Motil 1996, 8:319–331. A very useful review of the roles played by 5-hydroxytryptamine and its receptors, focusing on their relevance to functional gastrointestinal disorders.

    PubMed  CAS  Google Scholar 

  13. Miura M, Lawson DC, Clary EM, et al.: Central modulation of rectal distension induced blood pressure changes by alosetron, a 5-HT3 receptor antagonist. Dig Dis Sci 1999, 44:20–24.

    Article  PubMed  CAS  Google Scholar 

  14. Kozlowski CM, Green A, Grundy D, et al.: The 5HT3 receptor antagonist alosetron inhibits the colorectal distension induced depressor response and spinal c-fos expression in the anaesthetised rat. Gut 2000, 46:474–480.

    Article  PubMed  CAS  Google Scholar 

  15. Delvaux M, Louvel D, Mamet JP, et al.: Effects of alosetron on responses to colonic distension in patients with irritable bowel syndrome. Aliment Pharmacol Ther 1998, 12:849–855.

    Article  PubMed  CAS  Google Scholar 

  16. Bardhan KD, Bodemar G, Geldof H, et al.: A double blind, randomised, 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. This study, and the following three are the important studies of alosetron in IBS.

    Article  PubMed  CAS  Google Scholar 

  17. 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. This is one of the major defining studies for alosetron.

    Article  PubMed  CAS  Google Scholar 

  18. 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 

  19. Camilleri M, Chey WY, Mayer EA, et al.: A randomised controlled trial of the serotonin type 3 receptor antagonist alosetron in women with diarrhoea predominant irritable bowel syndrome. Arch Intern Med 2001, 161:1733–1740. This is one of the major defining studies for alosetron.

    Article  PubMed  CAS  Google Scholar 

  20. Jones RH, Holtmann G, Rodrigo L, et al.: Alosetron relieves pain and improves bowel function compared with mebeverine in female non constipated irritable bowel syndrome patients. Aliment Pharmacol Ther 1999, 13:1419–1427. This is one of the major defining studies for alosetron, using mebererine as a comparison.

    Article  PubMed  CAS  Google Scholar 

  21. Talley NJ, Van Zanten SV, Saez LR, et al.: A dose ranging, placebo controlled, randomised trial of alosetron in patients with functional dyspepsia. Aliment Pharmacol Ther 2001, 15:525–537.

    Article  PubMed  CAS  Google Scholar 

  22. Costall B, Naylor RJ: Anxiolytic potential of 5HT3 receptor antagonists. Pharmacol Toxicol 1992, 70:157–162.

    Article  PubMed  CAS  Google Scholar 

  23. Watson ME, Lacey L, Kong S: Alosetron improves quality of life in women with diarrhoea predominat irritable bowel syndrome. Am J Gastroenterol 2001, 96:455–459.

    Article  PubMed  CAS  Google Scholar 

  24. Richter JE: Efficacy of cisapride on symptoms and healing of gastro-oesophageal reflux disease: a review. Scand J Gastroenterol Suppl 1989, 165:19–27.

    PubMed  CAS  Google Scholar 

  25. Hallerback BI, Bommelaer G, Bredberg E, et al.: Dose finding study of mosapride in functional dyspepsia: a placebo-conrolled, randomised study. Aliment Pharmacol Ther 2002, 16:959–967.

    Article  PubMed  CAS  Google Scholar 

  26. Veldhuyzen van Zanten SJ, Jones MJ, Verlinden M, et al.: Efficacy of cisapride and domperidone in functional (nonulcer) dyspepsia: a meta-analysis. Am J Gastroenterol 2001, 96:689–696.

    PubMed  CAS  Google Scholar 

  27. Ruth M, Hamelin B, Rohss K, et al.: The effect of Mosapride, a novel prokinetic, on acid reflux variables in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther 1998, 12:35–40.

    Article  PubMed  CAS  Google Scholar 

  28. Camilleri M: Review article: tegaserod. Aliment Pharmacol Ther 2001, 15:277–289.

    Article  PubMed  CAS  Google Scholar 

  29. Muller-Lissner SA, Talley NJ, Drossman DA, et al.: Tegaserod, a 5HT4 receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. Aliment Pharmacol Ther 2001, 15:1655–1666. This is one of the major tegaserod treatment trials demonstrating efficacy.

    Article  PubMed  CAS  Google Scholar 

  30. Lefkowitz M, Ligozio G, Glebas K, et al.: Tegaserod provides relief of symptoms in female patients with irritable bowel syndrome (IBS) suffering from abdominal pain and discomfort, bloating and constipation. Gastroenterology 2001, Abstract 104:A22. This is another major tegaserod trial demonstrating symptomatic improvement.

    Article  Google Scholar 

  31. Schoenfeld P, Chey WD, Drossman D, et al. Effectiveness and safety of tegaserod in the treatment of irritable bowel syndrome: A meta-analysis of randomized controlled trials. DDW 2002, T1486.

  32. Tack J, Delia T, Ligozio G, et al.: A phase II placebo controlled trial with tegaserod in functional dyspepsia patients with normal gastric emptying. DDW 2002, oral presentation 154.

  33. Fidelholtz J, Smith W, Rawls S, et al.: Safety and tolerability of tegaserod in patients with irritable bowel syndrome and diarrhea. Am J Gastroenterology 2002, 97:1176–1181.

    Article  CAS  Google Scholar 

  34. Emmanuel AV, Nicholls T, Roy AJ, et al.: Prucalopride improves colonic transit and stool frequency in patients with slow and normal transit constipation. Gastroenterology 2000, 118:A846.

    Google Scholar 

  35. Johanson JF, Miner PB, Parkman HP, et al.: Prucalopride improves bowel movement frequency and symptoms in patients with chronic constipation: results of two double-blind, placebo-controlled trials. Gastroenterology 2000, 118:A175.

    Article  Google Scholar 

  36. Robertson CS, Ledingham SJ, Cooper SM, Evans DF: A double blind dose ranging study of BRL 24924 and metoclopromide on lower oesophageal sphincter pressure in healthy volunteers. Br J Clin Pharmacol 1989, 28:3232–3237.

    Google Scholar 

  37. Stacher G, Steiner G, Gaupmann G, et al.: Effects of the 5-HT3 receptor antagonist, ICS 205-930, on oesophageal motor activity and on lower oesophageal sphincter pressure: A double-blind cross-over study. Hepatogastroenterology 1990, 37(Suppl 2):118–121.

    PubMed  Google Scholar 

  38. Maxton DG, Morris J, Whorwell PJ: Selective 5-hydroxytryptamine antagonism: a role in irritable bowel syndrome and functional dyspepsia? Aliment Pharmacol Ther 1996, 10:595–599.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  40. Sifrim D, Holloway RH, Tack J, et al.: Effect of sumatriptan, a 5HT1 agonist, on the frequency of transient lower esophageal sphincter relaxations and gastroesophageal reflux in healthy subjects. Am J Gastroenterol 1999, 94:3158–3164.

    Article  PubMed  CAS  Google Scholar 

  41. Tack J, Piessevaux H, Coulie B, et al.: Influence of a fundus relaxing drug on meal-related symptoms in dyspeptic patients with hyper-sensitivity to gastric distension. Gastroenterology 1999, 116:A324.

    Google Scholar 

  42. 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. Gastroenterology 1999, 116:A325.

    Google Scholar 

  43. Broekaert D, Vos R, Gevers AM, et al.: A double-blind randomized placebo-controlled crossover trial of citalopram, a selective 5-hydroxytryptamine reuptake inhibitor, in irritable bowel syndrome. Gastroenterology 2001, 120(suppl 1):3250.

    Google Scholar 

  44. Kuiken SD, Burgers P, Tytgat GNJ: Fluoxetine (Prozac) for the treatment of irritable bowel syndrome: a randomized controlled clinical trial. DDW 2002, W1024.

  45. Jackson JL, O’Malley PG, Tomkins G: Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis. Am J Med 2000, 108:65–72.

    Article  PubMed  CAS  Google Scholar 

  46. Mertz H, Fass R, Kodner A: 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 

Download references

Author information

Authors and Affiliations

  1. Department of Academic Medicine, Education and Research Centre, South Manchester, University Hospitals, Manchester, UK

    Richard Lea MBchB, MRCP & Peter J. Whorwell MD, FRCP

Authors
  1. Richard Lea MBchB, MRCP
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter J. Whorwell MD, FRCP
    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

Lea, R., Whorwell, P.J. Serotonergic agents in the treatment of functional gastrointestinal disorders. Curr Treat Options Gastro 5, 293–300 (2002). https://doi.org/10.1007/s11938-002-0052-8

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11938-002-0052-8

Keywords

Search

Navigation