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Update on Pharmacotherapy for Irritable Bowel Syndrome

  • Large Intestine (B Cash and S Khan, Section Editors)
  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Irritable bowel syndrome (IBS) is a functional GI disorder that affects a large percentage of the population and presents a significant socio-economic burden on the society. In this article, we reviewed the evidence supporting various pharmacological treatment options for IBS.

Recent Findings

Rifaximin, eluxadoline, and alosetron have demonstrated that they reduce symptom severity improving quality of life in patients with IBS–diarrhea. Ramosetron is a promising agent in development. Peppermint oil has also demonstrated a positive impact on some symptoms of IBS. For IBS with constipation, traditional laxatives have failed to demonstrate significant benefit. However, lubiprostone, linaclotide, and plecanatide have demonstrated improvement of IBS with constipation in large, placebo-controlled trials. Tenapanor, a sodium/hydrogen exchanger 3 inhibitor, appears to be a promising treatment option in the pipeline.

Summary

There are multiple pharmacologic agents with a variety of mechanisms that have demonstrated efficacy in IBS with diarrhea and constipation. There are no established pharmacologic agents for IBS with a mixed bowel pattern. There is a promising pipeline for additional novel therapies for IBS.

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References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Quigley EM, Fried M, Gwee KA, Khalif I, Hungin AP, Lindberg G, et al. World Gastroenterology Organization global guidelines irritable bowel syndrome: a global perspective update September 2015. J Clin Gastroenterol. 2016;50(9):704–13.

    Article  Google Scholar 

  2. Canavan C, West J, Card T. Review article: the economic impact of the irritable bowel syndrome. Aliment Pharmacol Ther. 2014;40(9):1023–34.

    Article  CAS  Google Scholar 

  3. Occhipinti K, Smith JW. Irritable bowel syndrome: a review and update. Clin Colon Rectal Surg. 2012;25(1):46–52.

    Article  Google Scholar 

  4. Drossman DA, Hasler WL. Rome IV-functional GI disorders: disorders of gut-brain interaction. Gastroenterology. 2016;150(6):1257–61.

    Article  Google Scholar 

  5. Lacy BE, Patel NK. Rome criteria and a diagnostic approach to irritable bowel syndrome. J Clin Med. 2017;6(11).

    Article  Google Scholar 

  6. Lucak S. Irritable bowel syndrome and ischemic colitis: evidence supporting the increased use of alosetron. Ther Adv Gastroenterol. 2012;5(4):215–8.

    Article  Google Scholar 

  7. Cremonini F, Nicandro JP, Atkinson V, Shringarpure R, Chuang E, Lembo A. Randomised clinical trial: alosetron improves quality of life and reduces restriction of daily activities in women with severe diarrhoea-predominant IBS. Aliment Pharmacol Ther. 2012;36(5):437–48.

    Article  CAS  Google Scholar 

  8. Camilleri M, Northcutt AR, Kong S, Dukes GE, McSorley D, Mangel AW. Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial. Lancet. 2000;355(9209):1035–40.

    Article  CAS  Google Scholar 

  9. Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364(1):22–32.

    Article  CAS  Google Scholar 

  10. Pimentel M, Chang C, Chua KS, Mirocha J, DiBaise J, Rao S, et al. Antibiotic treatment of constipation-predominant irritable bowel syndrome. Dig Dis Sci. 2014;59(6):1278–85.

    Article  CAS  Google Scholar 

  11. Lembo A, Pimentel M, Rao SS, Schoenfeld P, Cash B, Weinstock LB, et al. Repeat treatment with rifaximin is safe and effective in patients with diarrhea-predominant irritable bowel syndrome. Gastroenterology. 2016;151(6):1113–21.

    Article  CAS  Google Scholar 

  12. Wade PR, Palmer JM, McKenney S, Kenigs V, Chevalier K, Moore BA, et al. Modulation of gastrointestinal function by MuDelta, a mixed μ opioid receptor agonist/ μ opioid receptor antagonist. Br J Pharmacol. 2012;167(5):1111–25.

    Article  CAS  Google Scholar 

  13. Lacy BE. Emerging treatments in neurogastroenterology: eluxadoline - a new therapeutic option for diarrhea-predominant IBS. Neurogastroenterol Motil. 2016;28(1):26–35.

    Article  CAS  Google Scholar 

  14. Dove LS, Lembo A, Randall CW, Fogel R, Andrae D, Davenport JM, et al. Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. Gastroenterology. 2013;145(2):329–38 e1.

    Article  CAS  Google Scholar 

  15. Cash BD, Lacy BE, Schoenfeld PS, Dove LS, Covington PS. Safety of eluxadoline in patients with irritable bowel syndrome with diarrhea. Am J Gastroenterol. 2017;112(2):365–74.

    Article  CAS  Google Scholar 

  16. •• Lembo AJ, Lacy BE, Zuckerman MJ, Schey R, Dove LS, Andrae DA, et al. Eluxadoline for irritable bowel syndrome with diarrhea. N Engl J Med. 2016;374(3):242–53 Results of pivotal trials of eluxadoline for IBS-D. These studies represent some of the best designed and methodologically rigorous trials of an IBS pharmacotherapy.

    Article  CAS  Google Scholar 

  17. Ida M, Nishida A, Akiho H, Nakashima Y, Matsueda K, Fukudo S. Randomized, placebo-controlled, phase IV pilot study of ramosetron to evaluate the co-primary end points in male patients with irritable bowel syndrome with diarrhea. Biopsychosoc Med. 2017;11:8.

    Article  Google Scholar 

  18. Fukudo S, Kinoshita Y, Okumura T, Ida M, Akiho H, Nakashima Y, et al. Ramosetron reduces symptoms of irritable bowel syndrome with diarrhea and improves quality of life in women. Gastroenterology. 2016;150(2):358–66 e8.

    Article  CAS  Google Scholar 

  19. Qi Q, Zhang Y, Chen F, Zuo X, Li Y. Ramosetron for the treatment of irritable bowel syndrome with diarrhea: a systematic review and meta-analysis of randomized controlled trials. BMC Gastroenterol. 2018;18(1):5.

    Article  Google Scholar 

  20. Valentin N, Camilleri M, Carlson P, Harrington SC, Eckert D, O'Neill J, et al. Potential mechanisms of effects of serum-derived bovine immunoglobulin/protein isolate therapy in patients with diarrhea-predominant irritable bowel syndrome. Physiol Rep. 2017;5(5):e13170.

    Article  Google Scholar 

  21. Wilson D, Evans M, Weaver E, Shaw AL, Klein GL. Evaluation of serum-derived bovine immunoglobulin protein isolate in subjects with diarrhea-predominant irritable bowel syndrome. Clin Med Insights Gastroenterol. 2013;6:49–60.

    Article  Google Scholar 

  22. Hills JM, Aaronson PI. The mechanism of action of peppermint oil on gastrointestinal smooth muscle. An analysis using patch clamp electrophysiology and isolated tissue pharmacology in rabbit and guinea pig. Gastroenterology. 1991;101(1):55–65.

    Article  CAS  Google Scholar 

  23. •• Cash BD, Epstein MS, Shah SM. A novel delivery system of peppermint oil is an effective therapy for irritable bowel syndrome symptoms. Dig Dis Sci. 2016;61(2):560–71 One of the few US studies of PO for IBS. This study demonstrated efficacy and tolerability of a novel formulation of PO designed to minimize adverse effects such as heartburn.

    Article  CAS  Google Scholar 

  24. Khanna R, MacDonald JK, Levesque BG. Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis. J Clin Gastroenterol. 2014;48(6):505–12.

    PubMed  Google Scholar 

  25. Weerts ZZRM, Keszthelyi D, Vork L, Aendekerk NCP, Frijlink HW, Brouwers JRBJ, et al. A novel ileocolonic release peppermint oil capsule for treatment of irritable bowel syndrome: a phase I study in healthy volunteers. Adv Ther. 2018;35:1965–78.

    Article  CAS  Google Scholar 

  26. Raschi E, De Ponti F. Lubiprostone: pharmacokinetic, pharmacodynamic, safety and regulatory aspects in the treatment of constipation-predominant irritable bowel syndrome. Expert Opin Drug Metab Toxicol. 2014;10(2):293–305.

    Article  CAS  Google Scholar 

  27. Drossman DA, Chey WD, Johanson JF, Fass R, Scott C, Panas R, 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(3):329–41.

    Article  CAS  Google Scholar 

  28. Chang L, Chey WD, Drossman D, Losch-Beridon T, Wang M, Lichtlen P, et al. Effects of baseline abdominal pain and bloating on response to lubiprostone in patients with irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2016;44(10):1114–22.

    Article  CAS  Google Scholar 

  29. Chey WD, Drossman DA, Johanson JF, Scott C, Panas RM, Ueno R. Safety and patient outcomes with lubiprostone for up to 52 weeks in patients with irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2012;35(5):587–99.

    Article  CAS  Google Scholar 

  30. Love BL, Johnson A, Smith LS. Linaclotide: a novel agent for chronic constipation and irritable bowel syndrome. Am J Health Syst Pharm. 2014;71(13):1081–91.

    Article  CAS  Google Scholar 

  31. Layer P, Stanghellini V. Review article: Linaclotide for the management of irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2014;39(4):371–84.

    Article  CAS  Google Scholar 

  32. Shailubhai K, Comiskey S, Foss JA, Feng R, Barrow L, Comer GM, et al. Plecanatide, an oral guanylate cyclase C agonist acting locally in the gastrointestinal tract, is safe and well-tolerated in single doses. Dig Dis Sci. 2013;58(9):2580–6.

    Article  CAS  Google Scholar 

  33. Miner PB Jr, DeLuca R, LaPortilla M, et al. Plecanatide, a novel uroguanylin analog: a 12-week, randomized, double-blind, placebo-controlled, dose-ranging trial to evaluate efficacy and safety in patients with irritable bowel syndrome with constipation (IBS-C). Am J Gastroenterol. 2014;109:S541.

    Google Scholar 

  34. •• Brenner DM, Fogel R, Dorn SD, Krause R, Eng P, Kirshoff R, et al. Efficacy, safety, and tolerability of plecanatide in patients with irritable bowel syndrome with constipation: results of two phase 3 randomized clinical trials. Am J Gastroenterol. 2018;113(5):735–45 Results of the pivotal trials of plecanatide, demonstrating efficacy for IBS with constipation with low rates of diarrhea.

    Article  CAS  Google Scholar 

  35. King AJ, Siegel M, He Y, Nie B, Wang J, Koo-McCoy S, et al. Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. Sci Transl Med. 2018;10(456):eaam6474.

    Article  Google Scholar 

  36. Zielińska M, Wasilewski A, Fichna J. Tenapanor hydrochloride for the treatment of constipation-predominant irritable bowel syndrome. Expert Opin Investig Drugs. 2015;24(8):1093–9.

    Article  Google Scholar 

  37. Rosenbaum DP, Yan A, Jacobs JW. Pharmacodynamics, safety, and tolerability of the NHE3 inhibitor tenapanor: two trials in healthy volunteers. Clin Drug Investig. 2018;38(4):341–51.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, University of Texas Health Science Center at Houston/McGovern Medical School, 6431 Fannin Street, Houston, TX, 77030, USA

    Akhil Munjal

  2. Division of Gastroenterology, University of Texas Health Science Center at Houston/McGovern Medical School, 6431 Fannin Street, MSB 4.234, Houston, TX, 77030, USA

    Bhavtosh Dedania & Brooks Cash

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  1. Akhil Munjal
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  2. Bhavtosh Dedania
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Correspondence to Brooks Cash.

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Munjal, A., Dedania, B. & Cash, B. Update on Pharmacotherapy for Irritable Bowel Syndrome. Curr Gastroenterol Rep 21, 25 (2019). https://doi.org/10.1007/s11894-019-0692-7

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  • DOI: https://doi.org/10.1007/s11894-019-0692-7

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