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Drugs

, Volume 74, Issue 16, pp 1849–1870 | Cite as

Current and Emerging Pharmacotherapeutic Options for Irritable Bowel Syndrome

  • Jose L. BarbozaEmail author
  • Nicholas J. Talley
  • Baharak Moshiree
Review Article

Abstract

Treatment of irritable bowel syndrome (IBS) is challenging for both primary care physicians and gastroenterologists because of the heterogeneity of the patient population and the multifactorial pathophysiologies responsible for the symptoms in IBS. This review focuses on the current and emerging pharmacological treatments for IBS. Many of the current medications used to treat this disorder have distinct properties such as efficacy for different symptoms, safety profiles, contraindications, costs, dosing regimens, treatment duration and long-term data. All of these factors, in addition to patient preference and cognitive, food and environmental triggers, must be considered prior to any medication selection. This review will focus on randomized controlled trials with a general uniformity in study design, a rigorous patient selection and appropriate treatment durations. We will also discuss other exciting emerging treatments for IBS such as the µ-opioid receptor (agonists and antagonists), selective κ-opioid receptor agonists, anti-inflammatory drugs, serotonergic agents, bile acid modulators and intestinal bile acid transporters, which may prove promising in treating our patients.

Keywords

Melatonin Irritable Bowel Syndrome Rifaximin Tegaserod Irritable Bowel Syndrome Symptom 
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.

Notes

Acknowledgments

Our sincere thanks to Glen Whelan, Pharm.D., for help with the figures in our manuscript.

Funding and Conflicts Statement

Jose Barboza has no conflicts of interest to report. Baharak Moshiree has received grants and consulting fees/honorarium from Prometheus Laboratory and has no other conflicts of interest to report. Nicholas Talley has received grant/research support from Abbott Pharmaceuticals, Ironwood, Janssen, Prometheus, Rome III Study, Salix liS Study, Takeda, and owns patents for biomarkers of irritable bowel syndrome.

References

  1. 1.
    Brandt LJ, Chey WD, Foxx-Orenstein AE, Schiller LR, Schoenfeld PS, Spiegel BM, et al. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol. 2009;104(Suppl 1):S1–35.PubMedGoogle Scholar
  2. 2.
    Dean BB, Aguilar D, Barghout V, Kahler KH, Frech F, Groves D, Ofman JJ. Impairment in work productivity and health-related quality of life in patients with IBS. Am J Manag Care. 2005;11(1 Suppl):S17–26.PubMedGoogle Scholar
  3. 3.
    Longstreth GF, Wilson A, Knight K, Wong J, Chiou CF, Barghout V, Frech F, Ofman JJ. Irritable bowel syndrome, health care use, and costs: a US managed care perspective. Am J Gastroenterol. 2003;98(3):600–7.PubMedGoogle Scholar
  4. 4.
    Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012;10(7):712–721.e4. (Epub 2012 Mar 15).PubMedGoogle Scholar
  5. 5.
    Sandler RS, Everhart JE, Donowitz M, Adams E, Cronin K, Goodman C, Gemmen E, Shah S, Avdic A, Rubin R. The burden of selected digestive diseases in the United States. Gastroenterology. 2002;122(5):1500–11.PubMedGoogle Scholar
  6. 6.
    Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130(5):1480–91.PubMedGoogle Scholar
  7. 7.
    Mearin F, Lacy BE. Diagnostic criteria in IBS: useful or not? Neurogastroenterol Motil. 2010;24:791–801.Google Scholar
  8. 8.
    Manning AP, Thompson WG, Heaton KW, Morris AF. Towards positive diagnosis of the irritable bowel. Br Med J. 1978;2(6138):653–4.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Saito YA, Locke GR, Talley NJ, Zinsmeister AR, Fett SL, Melton LJ 3rd. A comparison of the Rome and Manning criteria for case identification in epidemiological investigations of irritable bowel syndrome. Am J Gastroenterol. 2000;95(10):2816–24.PubMedGoogle Scholar
  10. 10.
    Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Müller-Lissner SA. Functional bowel disorders and functional abdominal pain. Gut. 1999;45(Suppl 2):II43–7.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130(5):1480–91.PubMedGoogle Scholar
  12. 12.
    Dang J, Ardila-Hani A, Amichai MM, Chua K, Pimentel M. Systematic review of diagnostic criteria for IBS demonstrates poor validity and utilization of Rome III. Neurogastroenterol Motil. 2012;24(9):853–e397.Google Scholar
  13. 13.
    Ford AC, Moayyedi P. Meta-analysis: factors affecting placebo response rate in the irritable bowel syndrome. Aliment Pharmacol Ther. 2010;32:144–58.PubMedGoogle Scholar
  14. 14.
    Asare F, Störsrud S, Simrén M. Meditation over medication for irritable bowel syndrome? On exercise and alternative treatments for irritable bowel syndrome. Curr Gastroenterol Rep. 2012;14(4):283–9.PubMedGoogle Scholar
  15. 15.
    Patel SM, Stason WB, Legedza A, Ock SM, Kaptchuk TJ, Conboy L, Canenguez K, Park JK, Kelly E, Jacobson E, Kerr CE, Lembo AJ. The placebo effect in irritable bowel syndrome trials: a meta-analysis. Neurogastroenterol Motil. 2005;17(3):332–40.PubMedGoogle Scholar
  16. 16.
    Gordon S, Ameen V, Bagby B, Shahan B, Jhingran P, Carter E. Validation of irritable bowel syndrome Global Improvement Scale: an integrated symptom end point for assessing treatment efficacy. Dig Dis Sci. 2003;48(7):1317–23.PubMedGoogle Scholar
  17. 17.
    Tack J, Fried M, Houghton LA, Spicak J, Fisher G. Systematic review: the efficacy of treatments for irritable bowel syndrome—a European perspective. Aliment Pharmacol Ther. 2006;24(2):183–205 (Review).PubMedGoogle Scholar
  18. 18.
    Ford AC, Talley NJ, Spiegel BM, Foxx-Orenstein AE, Schiller L, Quigley EM, Moayyedi P. Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ. 2008;13(337):a2313.Google Scholar
  19. 19.
    Bijkerk CJ, de Wit NJ, Muris JW, Whorwell PJ, Knottnerus JA, Hoes AW. Soluble or insoluble fibre in irritable bowel syndrome in primary care? Randomised placebo controlled trial. BMJ. 2009;27(339):b3154.Google Scholar
  20. 20.
    Ruepert L, Quartero AO, de Wit NJ, van der Heijden GJ, Rubin G, Muris JW. Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev (Online). 2011(8):CD003460.Google Scholar
  21. 21.
    Klaschik E, Nauck F, Ostgathe C. Constipation—modern laxative therapy. Support Care Cancer. 2003;11(11):679–85.PubMedGoogle Scholar
  22. 22.
    Khalif IL, Quigley EM, Makarchuk PA, Golovenko OV, Podmarenkova LF, Dzhanayev YA. Interactions between symptoms and motor and visceral sensory responses of irritable bowel syndrome patients to spasmolytics (antispasmodics). J Gastrointest Liver Dis. 2009;18(1):17–22.Google Scholar
  23. 23.
    Clavé P, Acalovschi M, Triantafillidis JK, et al. Randomised clinical trial: otilonium bromide improves frequency of abdominal pain, severity of distention and time to relapse in patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2011;34(4):432–42.PubMedGoogle Scholar
  24. 24.
    Chang FY, Lu CL, Luo JC, Chen TS, Chen MJ, Chang HJ. The evaluation of otilonium bromide treatment in Asian patients with irritable bowel syndrome. J Neurogastroenterol Motil. 2011;17(4):402–10.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Khanna R, Macdonald JK, Levesque BG. Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis. J Clin Gastroenterol. 2013.Google Scholar
  26. 26.
    Henningsen P, Zimmermann T, Sattel H. Medically unexplained physical symptoms, anxiety and depression: a meta-analytic review. Psychosom Med. 2003;65:528–33.PubMedGoogle Scholar
  27. 27.
    Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology. 2002;122:1140–56.PubMedGoogle Scholar
  28. 28.
    Solmaz M, Kavuk I, Sayar K. Psychological factors in the irritable bowel syndrome. Eur J Med Res. 2003;8:549–56.PubMedGoogle Scholar
  29. 29.
    Chial HJ, Camilleri M, Burton D, et al. Selective effects of serotonergic psychoactive agents on gastrointestinal functions in health. Am J Physiol Gastrointest Liver Physiol. 2003;284:G130–7.PubMedGoogle Scholar
  30. 30.
    Drossman DA, Toner BB, Whitehead WE, Diamant NE, Dalton CB, Duncan S, Emmott S, Proffitt V, Akman D, Frusciante K, Le T, Meyer K, Bradshaw B, Mikula K, Morris CB, Blackman CJ, Hu Y, Jia H, Li JZ, Koch GG, Bangdiwala SI. Cognitive–behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders. Gastroenterology. 2003;125(1):19–31.PubMedGoogle Scholar
  31. 31.
    Brennan, et al. Duloxetine in the treatment of irritable bowel syndrome: an open-label pilot study. Hum Psychopharmacol Clin Exp. 2009;24:423–8.Google Scholar
  32. 32.
    Drossman DA. Beyond tricyclics: new ideas for treating patients with painful and refractory functional gastrointestinal symptoms. Am J Gastroenterol. 2009;104:2897–902.PubMedGoogle Scholar
  33. 33.
    Ford AC, Talley NJ, Schoenfeld PS, Quigley EM, Moayyedi P. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis. Gut. 2009;58(3):367–78.PubMedGoogle Scholar
  34. 34.
    Masand PS, Pae CU, Krulewicz S, Peindl K, Mannelli P, Varia IM, Patkar AA. A double-blind, randomized, placebo-controlled trial of paroxetine controlled-release in irritable bowel syndrome. Psychosomatics. 2009;50(1):78–86.PubMedGoogle Scholar
  35. 35.
    Kuiken SD, Tytgat GN, Boeckxstaens GE. The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo-controlled study. Clin Gastroenterol Hepatol. 2003;1(3):219–28.PubMedGoogle Scholar
  36. 36.
    Vahedi H, Merat S, Rashidioon A, Ghoddoosi A, Malekzadeh R. The effect of fluoxetine in patients with pain and constipation-predominant irritable bowel syndrome: a double-blind randomized-controlled study. Aliment Pharmacol Ther. 2005;22(5):381–5.PubMedGoogle Scholar
  37. 37.
    Tack J, Broekaert D, Fischler B, Van Oudenhove L, Gevers AM, Janssens. A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut. 2006;55(8):1095–103.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Vahedi H, Merat S, Momtahen S, Kazzazi AS, Ghaffari N, Olfati G, Malekzadeh R. Clinical trial: the effect of amitriptyline in patients with diarrhoea-predominant irritable bowel syndrome. Aliment PharmacolTher. 2008;27(8):678–84.Google Scholar
  39. 39.
    Talley NJ, Kellow JE, Boyce P, et al. Antidepressant therapy (imipramine and citalopram) for irritable bowel syndrome: a double-blind, randomized, placebo-controlled trial. Dig Dis Sci. 2008;53(1):108–15.PubMedGoogle Scholar
  40. 40.
    Weinland, et al. Cognitive factors affect treatment response to medical and psychological treatments in functional bowel disorders. Am J Gastroenterol. 2010;105:1397–406.PubMedGoogle Scholar
  41. 41.
    Ford AC, Spiegel BM, Talley NJ, Moayyedi P. Small intestinal bacterial overgrowth in irritable bowel syndrome: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2009;7(12):1279–86.PubMedGoogle Scholar
  42. 42.
    Kassinen A, Krogius-Kurikka L, Makivuokko H, et al. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology. 2007;133:24e33.Google Scholar
  43. 43.
    Rajilić-Stojanović M, Biagi E, Heilig HG, Kajander K, Kekkonen RA, Tims S, de Vos WM. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology. 2011;141:1792–801.PubMedGoogle Scholar
  44. 44.
    Barbara G, Stanghellini V, Cremon C, De Giorgio R, Gargano L, Cogliandro R, Pallotti F, Corinaldesi R. Probiotics and irritable bowel syndrome: rationale and clinical evidence for their use. J Clin Gastroenterol. 2008;42(Suppl 3 Pt 2):S214–7.PubMedGoogle Scholar
  45. 45.
    Moayyedi P, Ford AC, Talley NJ, Cremonini F, Foxx-Orenstein AE, Brandt LJ, Quigley EM. The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut. 2010;59(3):325–32.PubMedGoogle Scholar
  46. 46.
    Brenner DM, Moeller MJ, Chey WD, Schoenfeld PS. The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review the utility of probiotics in the treatment of IBS. Am J Gastroenterol. 2009;104:1033–49.PubMedGoogle Scholar
  47. 47.
    Yoon JS, Sohn W, Lee OY, Lee SP, Lee KN, Jun DW, Lee HL, Yoon BC, Choi HS, Chung WS, Seo JG. Effect of multispecies probiotics on irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Gastroenterol Hepatol. 2014;29(1):52–9.PubMedGoogle Scholar
  48. 48.
    Ducrotté P, Sawant P, Jayanthi V. Clinical trial: lactobacillus plantarum 299v (DSM 9843) improves symptoms of irritable bowel syndrome. World J Gastroenterol. 2012;18(30):4012–8.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Roberts LM, McCahon D, Holder R, Wilson S, Hobbs FD. A randomised controlled trial of a probiotic ‘functional food’ in the management of irritable bowel syndrome. BMC Gastroenterol. 2013;7(13):45.Google Scholar
  50. 50.
    Krueger D, Gruber L, Buhner S, Zeller F, Langer R, Seidl S, et al. The multi-herbal drug STW 5 (Iberogast) has prosecretory action in the human intestine. Neurogastroenterol Motil. 2009;21(11):1203–e110.Google Scholar
  51. 51.
    Melzer J, Rösch W, Reichling J, Brignoli R, Saller R. Meta-analysis: phytotherapy of functional dyspepsia with the herbal drug preparation STW 5 (Iberogast). Aliment Pharmacol Ther. 2004;20(11–12):1279–87.PubMedGoogle Scholar
  52. 52.
    Madisch A, Holtmann G, Plein K, Hotz J. Treatment of irritable bowel syndrome with herbal preparations: results of a double-blind, randomized, placebo-controlled, multi-centre trial. Aliment Pharmacol Ther. 2004;19(3):271–9.PubMedGoogle Scholar
  53. 53.
    Radwan P, Skrzydlo-Radomanska B, Radwan-Kwiatek K, Burak-Czapiuk B, Strzemecka J. Is melatonin involved in the irritable bowel syndrome? J Physiol Pharmacol. 2009;60(Suppl 3):67–70.PubMedGoogle Scholar
  54. 54.
    Roberts-Thomson IC, Knight RE, Kennaway DJ, Pannall PR. Circadian rhythms in patients with abdominal pain syndromes. Aust N Z J Med. 1988;18(4):569–74.PubMedGoogle Scholar
  55. 55.
    Song GH, Leng PH, Gwee KA, Moochhala SM, Ho KY. Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised, double blind, placebo controlled study. Gut. 2005;54(10):1402–7 (Epub 2005 May 24).PubMedPubMedCentralGoogle Scholar
  56. 56.
    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(1):191–6.PubMedGoogle Scholar
  57. 57.
    Chapman RW, Stanghellini V, Geraint M, Halphen M. Randomized clinical trial: macrogol/PEG 3350 plus electrolytes for treatment of patients with constipation associated with irritable bowel syndrome. Am J Gastroenterol. 2013;108(9):1508–15.PubMedGoogle Scholar
  58. 58.
    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(11):1131–8.PubMedGoogle Scholar
  59. 59.
    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.PubMedGoogle Scholar
  60. 60.
    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.PubMedGoogle Scholar
  61. 61.
    Johanson JF, Drossman DA, Panas R, Wahle A, Ueno R. Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2008;27(8):685–96.PubMedGoogle Scholar
  62. 62.
    Busby RW, Bryant AP, Bartolini WP, et al. Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit. Eur J Pharmacol. 2010;649:328–35.PubMedGoogle Scholar
  63. 63.
    Castro J, Harrington AM, Hughes PA, et al. Linaclotide inhibits colonic nociceptors and relieves abdominal pain via guanylate cyclase-C and extracellular cyclic guanosine 3′,5′-monophosphate. Gastroenterology. 2013;145:1334–46.PubMedGoogle Scholar
  64. 64.
    Rao S, Lembo AJ, Shiff SJ, Lavins BJ, Currie MG, Jia XD, Shi K, MacDougall JE, Shao JZ, Eng P, Fox SM, Schneier HA, Kurtz CB, Johnston JM. 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(11):1714–24 (quiz p.1725).PubMedPubMedCentralGoogle Scholar
  65. 65.
    Chey WD, Lembo AJ, Lavins BJ, Shiff SJ, Kurtz CB, Currie MG, MacDougall JE, Jia XD, Shao JZ, Fitch DA, Baird MJ, Schneier HA, Johnston JM. 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(11):1702–12.PubMedGoogle Scholar
  66. 66.
    Johanson JF, Wald A, Tougas G, Chey WD, Novick JS, Lembo AJ, et al. Effect of tegaserod in chronic constipation: a randomized, double-blind, controlled trial. Clin Gastroenterol Hepatol. 2004;2(9):796–805.PubMedGoogle Scholar
  67. 67.
    Evans BW, Clark WK, Moore DJ, Whorwell PJ. Tegaserod for the treatment of irritable bowel syndrome and chronic constipation. Cochrane Database Syst Rev (Online). 2007(4):CD003960.Google Scholar
  68. 68.
    Loughlin J, Quinn S, Rivero E, Wong J, Huang J, Kralstein J, et al. Tegaserod and the risk of cardiovascular ischemic events: an observational cohort study. J Cardiovasc Pharmacol Ther. 2010;15(2):151–7.PubMedGoogle Scholar
  69. 69.
    US Food and Drug Administration. Zelnorm (tegaserod maleate) information. May 5, 2012. http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm103223.htm. Accessed 01 2014.Google Scholar
  70. 70.
    Camilleri M, Kerstens R, Rykx A, Vandeplassche L. A placebo-controlled trial of prucalopride for severe chronic constipation. N Engl J Med. 2008;358(22):2344–54.PubMedGoogle Scholar
  71. 71.
    Quigley EM, Vandeplassche L, Kerstens R, et al. Clinical trial: the efficacy, impact on quality of life, and safety and tolerability of prucalopride in severe chronic constipation-a 12 week, randomized, double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2009;29:315–28.PubMedGoogle Scholar
  72. 72.
    Tack J, van Outryve M, Beyens G, et al. Prucalopride (Resolor) in the treatment of severe chronic constipation in patients dissatisfied with laxatives. Gut. 2009;58:357–65.PubMedGoogle Scholar
  73. 73.
    Camilleri M, McKinzie S, Burton D, Thomforde GM, Zinsmeister AR, Bouras EP. Prucalopride accelerates small bowel and colonic transit in patients with chronic functional constipation (FC) or constipation-predominant irritable bowel syndrome (C-IBS). Gastroenterology. 2000;118(4):A845.Google Scholar
  74. 74.
    George AM, Meyers NL, Hickling RI. Clinical trial: renzapride therapy for constipation-predominant irritable bowel syndrome—multicentre, randomized, placebo-controlled, double-blind study in primary healthcare setting. Aliment PharmacolTher. 2008;27(9):830–7.Google Scholar
  75. 75.
    Lembo AJ, Cremonini F, Meyers N, Hickling R. Clinical trial: renzapride treatment of women with irritable bowel syndrome and constipation—a double-blind, randomized, placebo-controlled, study. Aliment PharmacolTher. 2010;31(9):979–90.Google Scholar
  76. 76.
    Tack J, Broekaert D, Fischler B, Van Oudenhove L, Gevers AM, Janssens J. A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut. 2006;55(8):1095–103.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Hovdenak N. Loperamide treatment of the irritable bowel syndrome. Scand J Gastroenterol. 1987;130(Suppl):81–4.Google Scholar
  78. 78.
    Lavö B, Stenstam M, Nielsen AL. Loperamide in treatment of irritable bowel syndrome—a double-blind placebo controlled study. Scand J Gastroenterol. 1987;130(Suppl):77–80.Google Scholar
  79. 79.
    Efskind PS, Bernklev T, Vatn MH. A double-blind placebo-controlled trial with loperamide in irritable bowel syndrome. Scand J Gastroenterol. 1996;31(5):463–8.PubMedGoogle Scholar
  80. 80.
    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(3):239–47.PubMedGoogle Scholar
  81. 81.
    Krogius-Kurikka L, Lyra A, Malinen E, Aarnikunnas J, Tuimala J, Paulin L, Mäkivuokko H, Kajander K, Palva A. Microbial community analysis reveals high level phylogenetic alterations in the overall gastrointestinal microbiota of diarrhoea-predominant irritable bowel syndrome sufferers. BMC Gastroenterol. 2009;17(9):95.Google Scholar
  82. 82.
    Koo HL, Dupont HL, Huang DB. The role of rifaximin in the treatment and chemoprophylaxis of travelers’ diarrhea. Ther Clin Risk Manag. 2009;5:841–8.PubMedPubMedCentralGoogle Scholar
  83. 83.
    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.PubMedGoogle Scholar
  84. 84.
    Menees SB, Maneerattannaporn M, Kim HM, Chey WD. The efficacy and safety of rifaximin for the irritable bowel syndrome: a systematic review and meta-analysis. Am J Gastroenterol. 2012;107(1):28–35.PubMedGoogle Scholar
  85. 85.
    Pimentel M. Review of rifaximin as treatment for SIBO and IBS. Expert Opin Investig Drugs. 2009;18(3):349–58.PubMedGoogle Scholar
  86. 86.
    Pimentel M, Chatterjee S, Chow EJ, Park S, Kong Y. Neomycin improves constipation-predominant irritable bowel syndrome in a fashion that is dependent on the presence of methane gas: sub analysis of a double-blind randomized controlled study. Dig Dis Sci. 2006;51(8):1297–301.PubMedGoogle Scholar
  87. 87.
    Pimentel M, Morales W, Chua K, Barlow G, Weitsman S, Kim G, Amichai MM, Pokkunuri V, Rook E, Mathur R, Marsh Z. Effects of rifaximin treatment and retreatment in non constipated IBS subjects. Dig Dis Sci. 2011;56(7):2067–72.PubMedGoogle Scholar
  88. 88.
    Schoenfeld P, Pimental M, Chang L, et al. Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation. A pooled analysis of randomized, double-blind, placebo-controlled trials. Aliment Pharmacol Ther. 2014;39(10):1161–8.PubMedPubMedCentralGoogle Scholar
  89. 89.
    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(6):775–82.PubMedGoogle Scholar
  90. 90.
    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.PubMedGoogle Scholar
  91. 91.
    Camilleri M, Chey WY, Mayer EA, Northcutt AR, Heath A, Dukes GE, McSorley D, Mangel AM. A randomized controlled clinical trial of the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome. Arch Intern Med. 2001;161(14):1733–40.PubMedGoogle Scholar
  92. 92.
    Chang L, Ameen VZ, Dukes GE, McSorley DJ, Carter EG, Mayer EA. A dose-ranging, phase II study of the efficacy and safety of alosetron in men with diarrhea-predominant IBS. Am J Gastroenterol. 2005;100(1):115–23.PubMedGoogle Scholar
  93. 93.
    Chang L, Tong K, Ameen V. Ischemic colitis and complications of constipation associated with the use of alosetron under a risk management plan: clinical characteristics, outcomes, and incidences. Am J Gastroenterol. 2010;105(4):866–75.PubMedGoogle Scholar
  94. 94.
    Matsueda K, Harasawa S, Hongo M, Hiwatashi N, Sasaki D. A randomized, double-blind, placebo-controlled clinical trial of the effectiveness of the novel serotonin type 3 receptor antagonist ramosetron in both male and female Japanese patients with diarrhea-predominant irritable bowel syndrome. Scand J Gastroenterol. 2008;43(10):1202–11.PubMedGoogle Scholar
  95. 95.
    Fukudo S, Ida M, Akiho H, Nakashima Y, Matsueda K. Effect of ramosetron on stool consistency in male patients with irritable bowel syndrome with diarrhea. Clin Gastroenterol Hepatol. 2013 (pii: S1542-3565(13)01830-2).Google Scholar
  96. 96.
    Garsed K, Chernova J, Hastings M, Lam C, Marciani L, Singh G, Henry A, Hall I, Whorwell P, Spiller R. A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea. Gut. 2013.Google Scholar
  97. 97.
    Shin A, Camilleri M, Kolar G, Erwin P, West CP, Murad MH. Systematic review with meta-analysis: highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) in chronic constipation. Aliment Pharmacol Ther. 2014;39(3):239–53.PubMedGoogle Scholar
  98. 98.
    Rao AS, Wong BS, Camilleri M, Odunsi-Shiyanbade ST, McKinzie S, Ryks M, Burton D, Carlson P, Lamsam J, Singh R, Zinsmeister AR. Chenodeoxycholate in females with irritable bowel syndrome–constipation: a pharmacodynamic and pharmacogenetic analysis. Gastroenterology. 2010;139(5):1549–58 (1558.e1).PubMedPubMedCentralGoogle Scholar
  99. 99.
    Wong BS, Camilleri M, McKinzie S, et al. Effects of A3309, an ileal bile acid transporter inhibitor, on colonic transit and symptoms in females with functional constipation. Am J Gastroenterol. 2011;106:2154–64.PubMedGoogle Scholar
  100. 100.
    Tuteja AK, Fang JC, Al-Suqi M, Stoddard GJ, Hale DC. Double-blind placebo-controlled study of mesalamine in post-infective irritable bowel syndrome—a pilot study. Scand J Gastroenterol. 2012;47(10):1159–64.PubMedGoogle Scholar
  101. 101.
    Ching L, Wei T, Matthew L, Jessica W, Anurag A, Sandip S, Stephen F, Matt R, Arvind R, Peter JW, Alan M, Robin CS. A multi-centre, parallel group, randomised placebo controlled trial of mesalazine for treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D). Gastroenterology. 2014;146(5):S-123–4.Google Scholar
  102. 102.
    Barbara G, Cremon C, Bellacosa L, De Giorgio R, Stanghellini V, Corinaldesi R. Randomized placebo controlled multicenter trial of mesalazine in patients with irritable bowel syndrome (IBS). Gastroenterology. 2014;146(5):S-124.Google Scholar
  103. 103.
    Leventer SM, Raudibaugh K, Frissora CL, Kassem N, Keogh JC, Phillips J, Mangel AW. Clinical trial: dextofisopam in the treatment of patients with diarrhoea-predominant or alternating irritable bowel syndrome. Aliment Pharmacol Ther. 2008;27(2):197–206.PubMedGoogle Scholar
  104. 104.
    Dove LS, Lembo A, Randall CW, Fogel R, Andrae D, Davenport JM, McIntyre G, Almenoff JS, Covington PS. Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. Gastroenterology. 2013;145(2):329–38.e1.PubMedGoogle Scholar
  105. 105.
    Mangel AW, Bornstein JD, Hamm LR, Buda J, Wang J, Irish W, Urso D. Clinical trial: asimadoline in the treatment of patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2008;28(2):239–49.PubMedGoogle Scholar
  106. 106.
    Mangel AW, Chaturvedi P. Evaluation of crofelemer in the treatment of diarrhea-predominant irritable bowel syndrome patients. Digestion. 2008;78(4):180–6.PubMedGoogle Scholar
  107. 107.
    Niddam DM, Tsai SY, Lu CL, Ko CW, Hsieh JC. Reduced hippocampal glutamate–glutamine levels in irritable bowel syndrome: preliminary findings using magnetic resonance spectroscopy. Am J Gastroenterol. 2011;106(8):1503–11.PubMedGoogle Scholar
  108. 108.
    Arnold L, Mease P, Silverman S. Pregabalin: an alpha2-delta (alpha2-delta) ligand for the management of fibromyalgia. Am J Manag Care. 2010;16(5 Suppl):S138–43.PubMedGoogle Scholar
  109. 109.
    Houghton LA, Fell C, Whorwell PJ, Jones I, Sudworth DP, Gale JD. Effect of a second-generation alpha2delta ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome. Gut. 2007;56(9):1218–25.PubMedPubMedCentralGoogle Scholar
  110. 110.
    Hattori T, Watanabe S, Kano M, Kanazawa M, Fukudo S. Differential responding of autonomic function to histamine H1 antagonism in irritable bowel syndrome. Neurogastroenterol Motil. 2010;22(12):1284–91 (e335).PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Jose L. Barboza
    • 1
    Email author
  • Nicholas J. Talley
    • 2
    • 3
  • Baharak Moshiree
    • 4
  1. 1.University of South Florida College of PharmacyTampaUSA
  2. 2.University of NewcastleCallaghanAustralia
  3. 3.Mayo ClinicFLUSA
  4. 4.Division of GastroenterologyUniversity of Miami Miller School of MedicineMiamiUSA

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