Expired CME Article

Irritable Bowel Syndrome: A Practical Review

Authors: Mihaela Podovei, MD, Braden Kuo, MD

Abstract

The epidemiology and current understanding of the pathophysiology of irritable bowel syndrome is reviewed, beginning with a historical perspective. The roles of genetics, environment, allergy, infection and inflammation, bacterial overgrowth, hormones and motility abnormalities are discussed. Using the current evidence-based literature, the practical approach of diagnosis and treatment is outlined, including traditional modalities and newer therapeutic agents such as serotonin modulators.


Key Points


* Irritable bowel syndrome (IBS) is a functional bowel disorder in which abdominal pain or discomfort is associated with defecation or changes in bowel habits, with symptoms present for at least 12 weeks out of the previous 12 months.


* IBS is a common disorder, more commonly present in women, that accounts for 28% of the visits to gastroenterologist.


* Diagnosis is based on the clinical symptoms, keeping the investigations to a minimum.


* Symptomatic treatment depends on the predominant symptom: antidiarrheal drugs in diarrhea-predominant IBS, fiber and laxatives in constipation-predominant IBS, antispasmodics for abdominal pain.


* If the initial treatment fails to improve symptoms or if changes suggestive of organic disease appear, more investigations/referral may be necessary.


* Newer drugs to be used are antidepressants, 5-HT3 antagonists (alosetron) for diarrhea-predominant IBS, 5-HT4 agonists (tegaserod) for constipation-predominant IBS.

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References

1. Longstreth GF, Thompson WG, Chevy WD, et al. Functional bowel disorders. Gastroenterology2006;130:1480–1491.
 
2. Manning AP, Thompson WG, Heaton KW, et al. Towards positive diagnosis of the irritable bowel. Br Med J 1978;2:653–654.
 
3. Kruis W, Thieme C, Weinzierl M, et al. A diagnostic score for the irritable bowel syndrome: its value in the exclusion of organic disease. Gastroenterology 1984;87:1–7.
 
4. Talley NJ, Zinsmeister AR, Van Dyke C, et al. Epidemiology of colonic symptoms and the irritable bowel syndrome. Gastroenterology 1991;101:927–934.
 
5. Drossman DA, Li Z, Andruzzi E, et al. U.S. householder survey of functional gastrointestinal disorders: prevalence, sociodemography, and health impact. Dig Dis Sci 1993;38:1569–1580.
 
6. Saito YA, Locke GR, Talley NJ, et al. A comparison of the Rome and Manning criteria for case identification in epidemiological investigations of irritable bowel syndrome. Am J Gastroenterol2000;95:2816–2824.
 
7. Schuster MM. Defining and diagnosing irritable bowel syndrome. Am J Manag Care 2001;7 (Suppl 8):S246–S251.
 
8. National Ambulatory Medical Care Survey. National Center for Health Statistics. Available at:http://www.cdc.gov/nchs/about/major/ahcd/namcsdes.htm. Accessed April 2006.
 
9. Mitchell CM, Drossman DA. Survey of the AGA membership relating to patients with functional gastrointestinal disorders. Gastroenterology 1987;92:1282–1284.
 
10. Talley NJ, Gabriel SE, Harmsen WS, et al. Medical costs in community subjects with irritable bowel syndrome. Gastroenterology 1995;109:1736–1741.
 
11. Sandler RS, Everhart JE, Donowitz M, et al. The burden of selected digestive diseases in the United States. Gastroenterology 2002;122:1500–1511.
 
12. Harvey RF, Mauad EC, Brown AM. Prognosis in the irritable bowel syndrome: a 5-year prospective study. Lancet 1987;1:963–965.
 
13. Cumming W. Electro-galvanism in a peculiar affection of the mucous membrane of the bowels.London Medical Gazette 1849:969–973.
 
14. Ryle JA. Chronic spasmodic affections of the colon. Lancet 1928;2:1115–1119.
 
15. Hollander E. Mucous colitis due to food allergy with a report of five cases. Am J Med Sci1927;174:495–500.
 
16. Bockus HL, Bank J, Wilkinson SA. Neurogenic mucous colitis. Am J Med Sci 1928;176:813–823.
 
17. Kellow JE, Phillips SF. Altered small bowel motility in irritable bowel syndrome is correlated with symptoms. Gastroenterology 1987;92:1885–1893.
 
18. Kellow JE, Phillips SF, Miller LJ, et al. Dysmotility of the small intestine in irritable bowel syndrome.Gut 1988;29:1236–1243.
 
19. Chey WY, Jin HO, Lee MH, et al. Colonic motility abnormality in patients with irritable bowel syndrome exhibiting abdominal pain and diarrhea. Am J Gastroenterol 2001;96:1499–1506.
 
20. Mathias JR, Clench MH. Relationship of reproductive hormones and neuromuscular disease of the gastrointestinal tract. Dig Dis 1998;16:3–13.
 
21. Mathias JR, Clench MH, Abell TL, et al. Effect of leuprolide acetate in treatment of abdominal pain and nausea in premenopausal women with functional bowel disease: a double-blind, placebo-controlled, randomized study. Dig Dis Sci 1998;43:1347–1355.
 
22. Mathias JR, Ferguson KL, Clench MH. Debilitating ‘functional’ bowel disease controlled by leuprolide acetate, gonadotropin-releasing hormone (GnRH) analog. Dig Dis Sci 1989;34:761–766.
 
23. Ruigomez A, Garcia Rodriguez LA, Johansson S, et al. Is hormone replacement therapy associated with an increased risk of irritable bowel syndrome? Maturitas 2003;44:133–140.
 
24. Heitkemper MM, Cain KC, Jarrett ME, et al. Symptoms across the menstrual cycle in women with irritable bowel syndrome. Am J Gastroenterol 2003;98:420–430.
 
25. Morris-Yates A, Talley NJ, Boyce PM, et al. Evidence of a genetic contribution to functional bowel disorder. Am J Gastroenterol 1998;93:1311–1317.
 
26. Levy RL, Jones KR, Whitehead WE, et al. Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology. Gastroenterology 2001;121:799–804.
 
27. Levy RL, Whitehead WE, Von Korff MR, et al. Intergenerational transmission of gastrointestinal illness behavior. Am J Gastroenterol 2000;95:451–456.
 
28. Drossman DA, Leserman J, Nachman G, et al. Sexual and physical abuse in women with functional or organic gastrointestinal disorders. Ann Intern Med 1990;113:828–833.
 
29. Drossman DA, Talley NJ, Leserman J, et al. Sexual and physical abuse and gastrointestinal illness: review and recommendations. Ann Intern Med 1995;123:782–794.
 
30. Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome. Am J Gastroenterol 2000;95:3503–3506.
 
31. 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.
 
32. Pimentel M, Mayer AG, Park S, et al. Methane production during lactulose breath test is associated with gastrointestinal disease presentation. Dig Dis Sci 2003;48:86–92.
 
33. Pimentel M, Lin HC, Enayati P, et al. Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile activity. Am J Physiol Gastrointest Liver Physiol2006;290:G1089–G1095.
 
34. Pimentel M, Kong Y, Park S. IBS subjects with methane on lactulose breath test have lower postprandial serotonin levels than subjects with hydrogen. Dig Dis Sci 2004;49:84–87.
 
35. Ragnarsson G, Bodemar G. Pain is temporally related to eating but not to defaecation in the irritable bowel syndrome (IBS): patients’ description of diarrhea, constipation and symptom variation during a prospective 6-week study. Eur J Gastroenterol Hepatol 1998;10:415–421.
 
36. Rogers J, Raimundo AH, Misiewicz JJ. Cephalic phase of colonic pressure response to food. Gut1993;34:537–543.
 
37. Bentley SJ, Pearson DJ, Rix KJ. Food hypersensitivity in irritable bowel syndrome. Lancet1983;2:295–297.
 
38. Farah DA, Calder I, Benson L, et al. Specific food intolerance: its place as a cause of gastrointestinal symptoms. Gut 1985;26:164–168.
 
39. Jones VA, McLaughlan P, Shorthouse M, et al. Food intolerance: a major factor in the pathogenesis of irritable bowel syndrome. Lancet 1982;2:1115–1117.
 
40. McKee AM, Prior A, Whorwell PJ. Exclusion diets in irritable bowel syndrome: are they worthwhile?J Clin Gastroenterol 1987;9:526–528.
 
41. Nanda R, James R, Smith H, et al. Food intolerance and the irritable bowel syndrome. Gut1989;30:1099–1104.
 
42. Petitpierre M, Gumowski P, Girard JP. Irritable bowel syndrome and hypersensitivity to food. Ann Allergy 1985;54:538–540.
 
43. Zwetchkenbaum J, Burakoff R. The irritable bowel syndrome and food hypersensitivity. Ann Allergy1988;61:47–49.
 
44. Serra J, Salvioli B, Azpiroz F, et al. Lipid-induced intestinal gas retention in irritable bowel syndrome. Gastroenterology 2002;123:700–706.
 
45. Bijkerk CJ, de Wit NJ, Stalman WA, et al. Irritable bowel syndrome in primary care: the patients’ and doctors’ views on symptoms, etiology and management. Can J Gastroenterol 2003;17:363–368; quiz 405–366.
 
46. Francis CY, Whorwell PJ. Bran and irritable bowel syndrome: time for reappraisal. Lancet1994;344:39–40.
 
47. Atkinson W, Sheldon TA, Shaath N, et al. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut 2004;53:1459–1464.
 
48. Chaudhary NA, Truelove SC. The irritable colon syndrome: a study of the clinical features, predisposing causes, and prognosis in 130 cases. Q J Med 1962;123:307–322.
 
49. Stewart GT. Post-dysenteric colitis. Br Med J 1950;1:405–409.
 
50. McKendrick MW, Read NW. Irritable bowel syndrome: post salmonella infection. J Infect1994;29:1–3.
 
51. Rodriguez LA, Ruigomez A. Increased risk of irritable bowel syndrome after bacterial gastroenteritis: cohort study. BMJ 1999;318:565–566.
 
52. Thornley JP, Jenkins D, Neal K, et al. Relationship of Campylobacter toxigenicity in vitro to the development of postinfectious irritable bowel syndrome. J Infect Dis 2001;184:606–609.
 
53. van der Veek PP, van den Berg M, de Kroon YE, et al. Role of tumor necrosis factor-alpha and interleukin-10 gene polymorphisms in irritable bowel syndrome. Am J Gastroenterol 2005;100:2510–2516.
 
54. Tornblom H, Lindberg G, Nyberg B, et al. Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome. Gastroenterology 2002;123:1972–1979.
 
55. Gwee KA. Postinfectious irritable bowel syndrome. Curr Treat Options Gastroenterol 2001;4:287–291.
 
56. Gwee KA, Graham JC, McKendrick MW, et al. Psychometric scores and persistence of irritable bowel after infectious diarrhoea. Lancet 1996;347:150–153.
 
57. Gwee KA, Leong YL, Graham C, et al. The role of psychological and biological factors in postinfective gut dysfunction. Gut 1999;44:400–406.
 
58. Spiller RC, Jenkins D, Thornley JP, et al. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut 2000;47:804–811.
 
59. Camilleri M, Atanasova E, Carlson PJ, et al. Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology 2002;123:425–432.
 
60. Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome.Gastroenterology 2004;126:1657–1664.
 
61. Pata C, Erdal E, Yazc K, et al. Association of the -1438 G/A and 102 T/C polymorphism of the 5-Ht2A receptor gene with irritable bowel syndrome 5-Ht2A gene polymorphism in irritable bowel syndrome. J Clin Gastroenterol 2004;38:561–566.
 
62. Mertz H, Naliboff B, Munakata J, et al. Altered rectal perception is a biological marker of patients with irritable bowel syndrome. Gastroenterology 1995;109:40–52.
 
63. Bouin M, Plourde V, Boivin M, et al. Rectal distention testing in patients with irritable bowel syndrome: sensitivity, specificity, and predictive values of pain sensory thresholds. Gastroenterology2002;122:1771–1777.
 
64. Ritchie J. Pain from distension of the pelvic colon by inflating a balloon in the irritable colon syndrome. Gut 1973;14:125–132.
 
65. Whitehead WE, Holtkotter B, Enck P, et al. Tolerance for rectosigmoid distention in irritable bowel syndrome. Gastroenterology 1990;98: 1187–1192.
 
66. Rey E, Diaz-Rubio M. Prevalence of rectal hypersensitivity in patients with irritable bowel syndrome and its clinical subgroups. Rev Esp Enferm Dig 2002;94:247–258.
 
67. Mertz H, Morgan V, Tanner G, et al. Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention. Gastroenterology 2000;118:842–848.
 
68. Silverman DH, Munakata JA, Ennes H, et al. Regional cerebral activity in normal and pathological perception of visceral pain. Gastroenterology 1997;112:64–72.
 
69. Andresen V, Bach DR, Poellinger A, et al. Brain activation responses to subliminal or supraliminal rectal stimuli and to auditory stimuli in irritable bowel syndrome. Neurogastroenterol Motil 2005;17:827–837.
 
70. Hamm LR, Sorrells SC, Harding JP, et al. Additional investigations fail to alter the diagnosis of irritable bowel syndrome in subjects fulfilling the Rome criteria. Am J Gastroenterol 1999;94:1279–1282.
 
71. Tolliver BA, Herrera JL, DiPalma JA. Evaluation of patients who meet clinical criteria for irritable bowel syndrome. Am J Gastroenterol 1994;89:176–178.
 
72. MacIntosh DG, Thompson WG, Patel DG, et al. Is rectal biopsy necessary in irritable bowel syndrome? Am J Gastroenterol 1992;87:1407–1409.
 
73. Francis CY, Duffy JN, Whorwell PJ, et al. Does routine abdominal ultrasound enhance diagnostic accuracy in irritable bowel syndrome? Am J Gastroenterol 1996;91:1348–1350.
 
74. Sanders DS, Carter MJ, Hurlstone DP, et al. Association of adult coeliac disease with irritable bowel syndrome: a case-control study in patients fulfilling ROME II criteria referred to secondary care. Lancet2001;358:1504–1508.
 
75. Manning AP, Heaton KW, Harvey RF. Wheat fibre and irritable bowel syndrome: a controlled trial.Lancet 1977;2:417–418.
 
76. Arthurs Y, Fielding JF. Double blind trial of ispaghula/poloxamer in the irritable bowel syndrome. Ir Med J 1983;76:253.
 
77. Arffmann S, Andersen JR, Hegnhoj J, et al. The effect of coarse wheat bran in the irritable bowel syndrome: a double-blind cross-over study. Scand J Gastroenterol 1985;20:295–298.
 
78. Longstreth GF, Fox DD, Youkeles L, et al. Psyllium therapy in the irritable bowel syndrome: a double-blind trial. Ann Intern Med 1981;95:53–56.
 
79. Prior A, Whorwell PJ. Double blind study of ispaghula in irritable bowel syndrome. Gut1987;28:1510–1513.
 
80. Lucey MR, Clark ML, Lowndes J, et al. Is bran efficacious in irritable bowel syndrome?A double blind placebo controlled crossover study. Gut 1987;28:221–225.
 
81. Cook IJ, Irvine EJ, Campbell D, et al. Effect of dietary fiber on symptoms and rectosigmoid motility in patients with irritable bowel syndrome: a controlled, crossover study. Gastroenterology 1990;98:66–72.
 
82. Toskes PP, Connery KL, Ritchey TW. Calcium polycarbophil compared with placebo in irritable bowel syndrome. Aliment Pharmacol Ther 1993;7:87–92.
 
83. Snook J, Shepherd HA. Bran supplementation in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 1994;8:511–514.
 
84. Soltoft J, Krag B, Gudmand-Hoyer E, et al. A double-blind trial of the effect of wheat bran on symptoms of irritable bowel syndrome. Lancet 1976;1:270–272.
 
85. Ritchie JA, Truelove SC. Treatment of irritable bowel syndrome with lorazepam, hyoscine butylbromide, and ispaghula husk. Br Med J 1979;1:376–378.
 
86. Jalihal A, Kurian G. Ispaghula therapy in irritable bowel syndrome: improvement in overall well-being is related to reduction in bowel dissatisfaction. J Gastroenterol Hepatol 1990;5:507–513.
 
87. Golechha AC, Chadda VS, Chadda S, et al. Role of ispaghula husk in the management of irritable bowel syndrome (a randomized double-blind crossover study). J Assoc Physicians India 1982;30:353–355.
 
88. Hovdenak N. Loperamide treatment of the irritable bowel syndrome. Scand J Gastroenterol Suppl1987;130:81–84.
 
89. Efskind PS, Bernklev T, Vatn MH. A double-blind placebo-controlled trial with loperamide in irritable bowel syndrome. Scand J Gastroenterol 1996;31:463–468.
 
90. Cann PA, Read NW, Holdsworth CD, et al. Role of loperamide and placebo in management of irritable bowel syndrome (IBS). Dig Dis Sci 1984;29:239–247.
 
91. Wheatley D. Irritable colon syndrome treated with an antispasmodic drug. Practitioner1976;217:276–280.
 
92. Page JG, Dirnberger GM. Treatment of the irritable bowel syndrome with Bentyl (dicyclomine hydrochloride). J Clin Gastroenterol 1981;3:153–156.
 
93. Heefner JD, Wilder RM, Wilson ID. Irritable colon and depression. Psychosomatics 1978;19:540–547.
 
94. Steinhart MJ, Wong PY, Zarr ML. Therapeutic usefulness of amitriptyline in spastic colon syndrome.Int J Psychiatry Med 1981;11:45–57.
 
95. Myren J, Groth H, Larssen SE, et al. The effect of trimipramine in patients with the irritable bowel syndrome: a double-blind study. Scand J Gastroenterol 1982;17:871–875.
 
96. Myren J, Lovland B, Larssen SE, et al. A double-blind study of the effect of trimipramine in patients with the irritable bowel syndrome. Scand J Gastroenterol 1984;19:835–843.
 
97. Greenbaum DS, Mayle JE, Vanegeren LE, et al. Effects of desipramine on irritable bowel syndrome compared with atropine and placebo. Dig Dis Sci 1987;32:257–266.
 
98. Vij JG, Jiloha RG, Kumar N. Effect of antidepressant drug (doxepin) on irritable bowel syndrome patients. Indian J Psychiatry 1991:243–246.
 
99. Rajagopalan M, Kurian G, John J. Symptom relief with amitriptyline in the irritable bowel syndrome.J Gastroenterol Hepatol 1998;13:738–741.
 
100. Drossman DA, Toner BB, Whitehead WE, et al. Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders. Gastroenterology2003;125:19–31.
 
101. Jackson JL, O’Malley PG, Tomkins G, et al. Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis. Am J Med 2000;108:65–72.
 
102. 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.
 
103. 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 Ther1999;13:1149–1159.
 
104. 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.
 
105. 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.
 
106. Camilleri M. Review article: tegaserod. Aliment Pharmacol Ther 2001;15:277–289.
 
107. 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.
 
108. Whorwell PJ, Krumholz S, Muller-Lissner SA. Tegaserod has a favorable safety and tolerability profile in patients with constipation-predominant and alternating forms of irritable bowel syndrome.Gastroenterology 2000;118:A1204.
 
109. Schoenfeld P, Chey WD, Drossman D. Effectiveness and safety of tegaserod in the treatment of irritable bowel syndrome: a meta-analysis of randomized controlled trials. Gastroenterology2002;112:A1486.
 
110. Novick J, Miner P, Krause R, et al. A randomized, double-blind, placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation. Aliment Pharmacol Ther 2002;16:1877–1888.
 
111. 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.
 
112. Nyhlin H, Bang C, Elsborg T. Tegaserod is an effective and safe therapy for IBS in a Nordic population. Gastroenterology 2003;124:M1645.
 
113. Cremonini F, Camilleri M, McKinzie S, et al. Effect of CCK-1 antagonist, dexloxiglumide, in female patients with irritable bowel syndrome: a pharmacodynamic and pharmacogenomic study. Am J Gastroenterol 2005;100:652–663.
 
114. Camilleri M, Kim DY, McKinzie S, et al. A randomized, controlled exploratory study of clonidine in diarrhea-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol 2003;1:111–121.
 
115. Corazziari E. Role of opioid ligands in the irritable bowel syndrome. Can J Gastroenterol1999;13(suppl A):71A–75A.
 
116. Dapoigny M, Abitbol JL, Fraitag B. Efficacy of peripheral kappa agonist fedotozine versus placebo in treatment of irritable bowel syndrome: a multicenter dose-response study. Dig Dis Sci 1995;40:2244–2249.
 
117. Delvaux M, Louvel D, Lagier E, et al. The kappa agonist fedotozine relieves hypersensitivity to colonic distention in patients with irritable bowel syndrome. Gastroenterology 1999;116:38–45.
 
118. Masand PS, Gupta S, Schwartz TL, et al. Open-label treatment with citalopram in patients with irritable bowel syndrome: a pilot study. Prim Care Companion J Clin Psychiatry 2005;7:162–166.
 
119. Lecci A, Maggi CA. Peripheral tachykinin receptors as potential therapeutic targets in visceral diseases. Expert Opin Ther Targets 2003;7:343–362.
 
120. Tough IR, Lewis CA, Fozard J, et al. Dual and selective antagonism of neurokinin NK(1) and NK(2) receptor-mediated responses in human colon mucosa. Naunyn Schmiedebergs Arch Pharmacol2003;367:104–108.
 
121. Furness JB. TAK-637: Takeda. Curr Opin Investig Drugs 2001;2:1437–1440.
 
122. Evangelista S. Eziopitant: Pfizer. Curr Opin Investig Drugs 2001;2:1441–1443.
 
123. Xiao WB, Liu YL. Rectal hypersensitivity reduced by acupoint TENS in patients with diarrhea-predominant irritable bowel syndrome: a pilot study. Dig Dis Sci 2004;49:312–319.
 
124. Chan J, Carr I, Mayberry JF. The role of acupuncture in the treatment of irritable bowel syndrome: a pilot study. Hepatogastroenterology 1997;44:1328–1330.
 
125. Forbes A, Jackson S, Walter C, et al. Acupuncture for irritable bowel syndrome: a blinded placebo-controlled trial. World J Gastroenterol 2005;11:4040–4044.
 
126. Rohrbock RB, Hammer J, Vogelsang H, et al. Acupuncture has a placebo effect on rectal perception but not on distensibility and spatial summation: a study in health and IBS. Am J Gastroenterol 2004;99:1990–1997.
 
127. Whorwell PJ, Prior A, Colgan SM. Hypnotherapy in severe irritable bowel syndrome: further experience. Gut 1987;28:423–425.
 
128. Whorwell PJ, Prior A, Faragher EB. Controlled trial of hypnotherapy in the treatment of severe refractory irritable-bowel syndrome. Lancet 1984;2:1232–1234.
 
129. Bensoussan A, Talley NJ, Hing M, et al. Treatment of irritable bowel syndrome with Chinese herbal medicine: a randomized controlled trial. JAMA 1998;280:1585–1589.