American college of gastroenterology monograph on management of irritable bowel syndrome

American Journal of Gastroenterology

Volumn 113, Issue S2, 2018, Pages 1-18

  Ford, Alexander C ^a   Moayyedi, Paul ^b   Chey, William D ^c   Harris, Lucinda A ^d   Lacy, Brian E ^e   Saito, Yuri A ^f   Quigley, Eamonn M M ^g  

^a UNIVERSITY OF LEEDS   (United Kingdom)

^b MCMASTER UNIVERSITY   (Canada)

^c UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^d MAYO CLINIC   (United States)

^e MAYO CLINIC   (United States)

^f MAYO CLINIC   (United States)

^g HOUSTON METHODIST HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALOSETRON; ANTIBIOTIC AGENT; ANTIDEPRESSANT AGENT; ELUXADOLINE; LINACLOTIDE; LOPERAMIDE; LUBIPROSTONE; MACROGOL; MESALAZINE; PEPPERMINT OIL; PLECANATIDE; PREBIOTIC AGENT; PROBIOTIC AGENT; SEROTONIN AGONIST; SPASMOLYTIC AGENT; SYNBIOTIC AGENT; ANTIINFECTIVE AGENT; CHOLINERGIC RECEPTOR BLOCKING AGENT; VEGETABLE OIL;

ARTICLE; COGNITIVE BEHAVIORAL THERAPY; DIET THERAPY; DIETARY FIBER; DIETARY INTAKE; DRUG EFFICACY; EVIDENCE BASED MEDICINE; GASTROENTEROLOGY; HUMAN; HYPNOSIS; IRRITABLE COLON; KINESIOTHERAPY; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; PSYCHODYNAMIC PSYCHOTHERAPY; RELAXATION TRAINING; SYSTEMATIC REVIEW; THERAPY EFFECT; TREATMENT INDICATION; ADMINISTRATION AND DOSAGE; BEHAVIOR THERAPY; CONSTIPATION; DIARRHEA; DIET; DIETARY SUPPLEMENT; EXERCISE; PRACTICE GUIDELINE; RANDOMIZED CONTROLLED TRIAL (TOPIC);

ANTI-BACTERIAL AGENTS; ANTIDEPRESSIVE AGENTS; BEHAVIOR THERAPY; CONSTIPATION; DIARRHEA; DIET; DIETARY FIBER; DIETARY SUPPLEMENTS; EXERCISE; HUMANS; IRRITABLE BOWEL SYNDROME; PARASYMPATHOLYTICS; PLANT OILS; PREBIOTICS; PROBIOTICS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SYNBIOTICS;

EID: 85049076072     PISSN: 00029270     EISSN: 15720241     Source Type: Journal    
DOI: 10.1038/s41395-018-0084-x     Document Type: Article

References (283)

1. Hungin AP, Chang L, Locke GR, et al. Irritable bowel syndrome in the United States: prevalence, symptom patterns and impact. Aliment Pharmacol Ther. 2005;21:1365–75.
2. Lovell RM, Ford AC. Global prevalence of, and risk factors for, irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012; 10:712–21.
3. Lovell RM, Ford AC. Effect of gender on prevalence of irritable bowel syndrome in the community: systematic review and meta-analysis. Am J Gastroenterol. 2012;107:991–1000.
4. Ford AC, Moayyedi P, Lacy BE, et al. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109:S2–26.
5. Mearin F, Lacy BE, Chang L, et al. Bowel disorders. Gastroenterology. 2016;150:1393–407.
6. Ford AC, Lacy BE, Talley NJ. Irritable bowel syndrome. N Engl J Med. 2017;376:2566–78.
7. Cash B, Sullivan S, Barghout V. Total costs of IBS: employer and managed care perspective. Am J Manag Care. 2005;11:S7–16.
8. Longstreth GF, Wilson A, Knight K, et al. Irritable bowel syndrome, health care use, and costs: a U.S. managed care perspective. Am J Gastroenterol. 2003;98:600–7.
9. Ladabaum U, Boyd E, Zhao WK, et al. Diagnosis, comorbidities, and management of irritable bowel syndrome in patients in a large health maintenance organization. Clin Gastroenterol Hepatol. 2012;10:37–45.
10. Lacy BE, Patel H, Guerin A, et al. Variation in care for patients with irritable bowel syndrome in the United States. PLoS One. 2016;11:e0154258.
11. Dean BB, Aguilar D, Barghout V, et al. Impairment in work productivity and health-related quality of life in patients with IBS. Am J Manag Care. 2005;11:S17–26.
12. Creed F, Ratcliffe J, Fernandez L, et al. Health-related quality of life and health care costs in severe, refractory irritable bowel syndrome. Ann Intern Med. 2001;134:860–8.
13. 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.
14. Jaliwala J, Imperiale TF, Kroenke K. Pharmacologic treatment of the irritable bowel syndrome: a systematic review of randomized, controlled trials. Ann Intern Med. 2000;133:136–47.
15. Lesbros-Pantoflickova D, Michetti P, Fried M, et al. Meta-analysis: the treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 2004;20:1253–69.
16. Pittler MH, Ernst E. Peppermint oil for irritable bowel syndrome: a critical review and meta-analysis. Am J Gastroenterol. 1998;93:1131–5.
17. Poynard T, Regimbeau C, Benhamou Y. Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 2001;15:355–61.
18. Quartero AO, Meineche-Schmidt V, Muris J, et al. Bulking agents, antispasmodic and antidepressant medication for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev. 2005;18:CD003460.
19. Tack J, Fried M, Houghton LA, et al. Systematic review: the efficacy of treatments for irritable bowel syndrome-a European perspective. Aliment Pharmacol Ther. 2006;24:183–205.
20. Evans BW, Clark WK, Moore DJ, et al. Tegaserod for the treatment of irritable bowel syndrome and chronic constipation. Cochrane Database Syst Rev. 2007;(4):CD003960.
21. Jones BW, Moore DJ, Robinson SM, et al. A systematic review of tegaserod for the treatment of irritable bowel syndrome. J Clin Pharmacol. 2002;27:343–52.
22. Anonymous. Systematic review on the management of irritable bowel syndrome in the European Union. Eur J Gastroenterol Hepatol. 2007;19:S11–S37.
23. Ford AC, Guyatt GH, Talley NJ, et al. Errors in the conduct of systematic reviews of pharmacological interventions for irritable bowel syndrome. Am J Gastroenterol. 2010;105:280–8.
24. Ford AC, Quigley EM, Lacy BE, et al. Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol. 2014;109:1547–61.
25. Ford AC, Quigley EM, Lacy BE, et al. Effect of antidepressants and psychological therapies, including hypnotherapy, in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2014;109:1350–65.
26. Moayyedi P, Quigley EM, Lacy BE, et al. The effect of fiber supplementation on irritable bowel syndrome: a systematic review and meta-analysis. Am J Gastroenterol. 2014;109:1367–74.
27. Moayyedi P, Quigley EM, Lacy BE, et al. The effect of dietary intervention on irritable bowel syndrome: a systematic review. Clin Transl Gastroenterol. 2015;6:e107.
28. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.
29. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.
30. Egger M, Davey-Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.
31. Sterne JA, Sutton AJ, Ioannidis JP, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ. 2011;343:d4002.
32. Harnett T. Consensus-Oriented Decision-Making: the CODM Model for Facilitating Groups to Widespread Agreement: New Society Publishers. 2011.
33. Lee PG, Jackson EA, Richardson CR. Exercise prescriptions in older adults. Am Fam Physician. 2017;95:425–32.
34. Herring MP, Puetz TW, O’Connor PJ, et al. Effect of exercise training on depressive symptoms among patients with a chronic illness: A systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2012;172:101–11.
35. Ohlsson B, Manjer J. Physical inactivity during leisure time and irregular meals are associated with functional gastrointestinal complaints in middle-aged and elder subjects. Scand J Gastroenterol. 2016;51:1299–307.
36. Villoria A, Serra J, Azpiroz F, et al. Physical activity and intestinal gas clearance in patients with bloating. Am J Gastroenterol. 2006;101:2552–7.
37. Song BK, Cho KO, Jo Y, et al. Colon transit time according to physical activity level in adults. J Neurogastroenterol Motil. 2012;18:64–9.
38. Daley AJ, Grimmett C, Roberts L, et al. The effects of exercise upon symptoms and quality of life in patients diagnosed with irritable bowel syndrome: a randomised controlled trial. Int J Sports Med. 2008;29:778–82.
39. Johannesson E, Simren M, Strid H, et al. Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial. Am J Gastroenterol. 2011;106:915–22.
40. Johannesson E, Ringstrom G, Abrahamsson H, et al. Intervention to increase physical activity in irritable bowel syndrome shows long-term positive effects. World J Gastroenterol. 2015;21:600–8.
41. Hayes PA, Fraher MH, Quigley EM. Irritable bowel syndrome: the role of food in pathogenesis and management. Gastroenterol Hepatol (N Y). 2014;10:164–74.
42. McKenzie YA, Bowyer RK, Leach H, et al. British Dietetic Association systematic review and evidence-based practice guidelines for the dietary management of irritable bowel syndrome in adults (2016 update). J Hum Nutr Diet. 2016;29:549–75.
43. Eswaran SL, Chey WD, Han-Markey T, et al. A randomized controlled trial comparing the low FODMAP diet vs. modified NICE guidelines in US adults with IBS-D. Am J Gastroenterol. 2016;111:1824–32.
44. Bohn L, Storsrud S, Liljebo T, et al. Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: a randomized controlled trial. Gastroenterology. 2015;149:1399–.e2.
45. McIntosh K, Reed DE, Schneider T, et al. FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial. Gut. 2017;66:1241–51.
46. Staudacher HM, Lomer MC, Anderson JL, et al. Fermentable carbohydrate restriction reduces luminal bifidobacteria and gastrointestinal symptoms in patients with irritable bowel syndrome. J Nutr. 2012;142:1510–8.
47. Staudacher HM, Lomer MCE, Farquharson FM, et al. Diet low in FOD-MAPs reduces symptoms in patients with irritable bowel syndrome and probiotic restores Bifidobacterium species: A randomized controlled trial. Gastroenterology. 2017;153:936–47.
48. Halmos EP, Power VA, Shepherd SJ, et al. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology. 2014;146:67–75.
49. Hustoft TN, Hausken T, Ystad SO et al. Effects of varying dietary content of fermentable short-chain carbohydrates on symptoms, fecal microenvironment, and cytokine profiles in patients with irritable bowel syndrome. Neurogastroenterol Motil. 2017;29:https://doi.org/10.1111/nmo.
50. Krogsgaard LR, Lyngesen M, Bytzer P. Systematic review: quality of trials on the symptomatic effects of the low FODMAP diet for irritable bowel syndrome. Aliment Pharmacol Ther. 2017;45:1506–13.
51. Chumpitazi BP, Cope JL, Hollister EB, et al. Randomised clinical trial: gut microbiome biomarkers are associated with clinical response to a low FODMAP diet in children with the irritable bowel syndrome. Aliment Pharmacol Ther. 2015;42:418–27.
52. Halmos EP, Christophersen CT, Bird AR, et al. Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut. 2015;64:93–100.
53. Bennet SMP, Bohn L, Storsrud S, et al. Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs. Gut. 2017;https://doi.org/10.1136/gutjnl-2016-313128.
54. Biesiekierski JR, Newnham ED, Irving PM, et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol. 2011;106: 508–14.
55. Shahbazkhani B, Sadeghi A, Malekzadeh R, et al. Non-celiac gluten sensitivity has narrowed the spectrum of irritable bowel syndrome: a double-blind randomized placebo-controlled trial. Nutrients. 2015;7:4542–54.
56. Atkinson W, Sheldon TA, Shaath N, et al. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut. 2004;53:1459–64.
57. Ali A, Weiss TR, McKee D, et al. Efficacy of individualised diets in patients with irritable bowel syndrome: a randomised controlled trial. BMJ Open Gastroenterol. 2017;4:e000164.
58. 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;307:270–2.
59. Manning AP, Heaton KW, Harvey RF, et al. Wheat fibre and irritable bowel syndrome: a controlled trial. Lancet. 1977;310:417–8.
60. Ritchie JA, Truelove SC. Treatment of irritable bowel syndrome with lorazepam, hyoscine butylbromide, and ispaghula husk. BMJ. 1979;278:376–8.
61. 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.
62. Arthurs Y, Fielding JF. Double blind trial of ispaghula/poloxamer in the irritable bowel syndrome. Ir Med J. 1983;76:253.
63. Nigam P, Kapoor KK, Rastog CK, et al. Different therapeutic regimens in irritable bowel syndrome. J Assoc Physicians India. 1984;32:1041–4.
64. Kruis W, Weinzierl M, Schussler P, et al. Comparison of the therapeutic effects of wheat bran, mebeverine and placebo in patients with the irritable bowel syndrome. Digestion. 1986;34:196–201.
65. Lucey MR, Clark ML, Lowndes JO, et al. Is bran efficacious in irritable bowel syndrome? A double blind placebo controlled crossover study. Gut. 1987;28:221–5.
66. Prior A, Whorwell P. Double blind study of ispaghula in irritable bowel syndrome. Gut. 1987;28:1510–3.
67. 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;5:507–13.
68. Fowlie S, Eastwood MA, Prescott R. Irritable bowel syndrome: assessment of psychological disturbance and its influence on the response to fibre supplementation. J Psychosom Res. 1992;36:175–80.
69. Rees G, Davies J, Thompson R, et al. Randomised-controlled trial of a fibre supplement on the symptoms of irritable bowel syndrome. J R Soc Health. 2005;125:30–34.
70. Bijkerk CJ, de Wit NJ, Muris JW, et al. Soluble or insoluble fibre in irritable bowel syndrome in primary care? Randomised placebo controlled trial. BMJ. 2009;339:b3154.
71. Cockerell KM, Watkins AS, Reeves LB, et al. Effects of linseeds on the symptoms of irritable bowel syndrome: a pilot randomised controlled trial. J Hum Nutr Diet. 2012;25:435–43.
72. Kamiya T, Shikano M, Tanaka M, et al. Therapeutic effects of biobran, modified arabinoxylan rice bran, in improving symptoms of diarrhea predominant or mixed type irritable bowel syndrome: a pilot, randomized controlled study. Evid Based Complement Altern Med. 2014; 2014:828137.
73. Thabane M, Kottachchi D, Marshall JK. Systematic review and meta-analysis: incidence and prognosis of post-infectious irritable bowel syndrome. Aliment Pharmacol Ther. 2007;26:535–44.
74. Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome. Am J Gastroenterol. 2000;95:3503–6.
75. Jalanka-Tuovinen J, Salojarvi J, Salonen A, et al. Faecal microbiota composition and host-microbe cross-talk following gastroenteritis and in postinfectious irritable bowel syndrome. Gut. 2014;63:1737–45.
76. Codling C, O’Mahony L, Shanahan F, et al. A molecular analysis of fecal and mucosal bacterial communities in irritable bowel syndrome. Dig Dis Sci. 2010;55:392–7.
77. Jeffery IB, O’Toole PW, Ohman L, et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut. 2012;61:997–1006.
78. Tap J, Derrien M, Tornblom H, et al. Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology. 2017;152:111–.e8.
79. Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11:506–14.
80. Alexea O, Bacarea V, Pique N. The combination of oligo-and polysaccharides and reticulated protein for the control of symptoms in patients with irritable bowel syndrome: Results of a randomised, placebo-controlled, double-blind, parallel group, multicentre clinical trial. United European. Gastroenterol J. 2016;4:455–65.
81. Tsuchiya J, Barreto R, Okura R, et al. Single-blind follow up study on the effectiveness of a symbiotic preparation in irritable bowel syndrome. Chin J Dig Dis. 2004;5:169–74.
82. Min YW, Park SU, Jang YS, et al. Effect of composite yogurt enriched with acacia fiber and Bifidobacterium lactis. World J Gastroenterol. 2012;18:4563–9.
83. Kabir MA, Ishaque SM, Ali MS, et al. Role of Saccharomyces boulardii in diarrhea predominant irritable bowel syndrome. Mymensingh Med J. 2011;20:397–401.
84. Ko SJ, Han G, Kim SK, et al. Effect of Korean herbal medicine combined with a probiotic mixture on diarrhea-dominant irritable bowel syndrome: a double-blind, randomized, placebo-controlled trial. Evid Based Complement Altern Med. 2013;2013:824605.
85. Stevenson C, Blaauw R, Fredericks E, et al. Randomized clinical trial: effect of Lactobacillus plantarum 299 v on symptoms of irritable bowel syndrome. Nutrition. 2014;30:1151–7.
86. Sisson G, Ayis S, Sherwood RA, et al. Randomised clinical trial: a liquid multi-strain probiotic vs. placebo in the irritable bowel syndrome-a 12 week double-blind study. Aliment Pharmacol Ther. 2014;40:51–62.
87. Jafari E, Vahedi H, Merat S, et al. Therapeutic effects, tolerability and safety of a multi-strain probiotic in Iranian adults with irritable bowel syndrome and bloating. Arch Iran Med. 2014;17:466–70.
88. Ludidi S, Jonkers DM, Koning CJ, et al. Randomized clinical trial on the effect of a multispecies probiotic on visceroperception in hypersensitive IBS patients. Neurogastroenterol Motil. 2014;26:705–14.
89. Yoon JS, Sohn W, Lee OY, et al. Effect of multispecies probiotics on irritable bowel syndrome: A randomized, double-blind, placebo-controlled trial. J Gastroenterol Hepatol. 2014;29:52–9.
90. Abbas Z, Yakoob J, Jafri W, et al. Cytokine and clinical response to Saccharomyces boulardii therapy in diarrhea-dominant irritable bowel syndrome: A randomized trial. Eur J Gastroenterol Hepatol. 2014;26:630–9.
91. Lorenzo-Zuniga V, Llop E, Suarez C, et al. I.31, a new combination of probiotics, improves irritable bowel syndrome-related quality of life. World J Gastroenterol. 2014;20:8709–16.
92. Pineton de Chambrun G, Neut C, Chau A, et al. A randomized clinical trial of Saccharomyces cerevisiae versus placebo in the irritable bowel syndrome. Dig Liver Dis. 2015;47:119–24.
93. Wong RK, Yang C, Song GH, et al. Melatonin regulation as a possible mechanism for probiotic (VSL#3) in irritable bowel syndrome: A randomized double-blinded placebo study. Dig Dis Sci. 2015;60:186–94.
94. Yoon H, Park YS, Lee DH, et al. Effect of administering a multi-species probiotic mixture on the changes in fecal microbiota and symptoms of irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Clin Biochem Nutr. 2015;57:129–34.
95. Thijssen AY, Clemens CH, Vankerckhoven V, et al. Efficacy of Lactobacillus casei Shirota for patients with irritable bowel syndrome. Eur J Gastroenterol Hepatol. 2016;28:8–14.
96. Spiller R, Pelerin F, Cayzeele Decherf A, et al. Randomized double blind placebo-controlled trial of Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: Improvement in abdominal pain and bloating in those with predominant constipation. U Eur Gastroenterol J. 2016;4: 353–62.
97. Hod K, Sperber AD, Ron Y et al. A double-blind, placebo-controlled study to assess the effect of a probiotic mixture on symptoms and inflammatory markers in women with diarrhea-predominant IBS. Neurogastroenterol Motil. 2017;29:https://doi.org/10.1111/nmo.
98. Pinto-Sanchez MI, Hall GB, Ghajar K, et al. Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: A pilot study in patients with irritable bowel syndrome. Gastroenterology. 2017;153:448–59.
99. Lyra A, Hillila M, Huttunen T, et al. Irritable bowel syndrome symptom severity improves equally with probiotic and placebo. World J Gastroenterol. 2016;22:10631–42.
100. Gade J, Thorn P. Paraghurt for patients with irritable bowel syndrome. Scand J Prim Health Care. 1989;7:23–26.
101. Nobaek S, Johansson ML, Molin G, et al. Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome. Am J Gastroenterol. 2000;95:1231–8.
102. Niedzielin K, Kordecki H, Birkenfeld B. A controlled, double blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome. Eur J Gastroenterol Hepatol. 2001;13:1143.
103. Kim HJ, Camilleri M, McKinzie S, et al. A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2003;17:895–904.
104. Kajander K, Hatakka K, Poussa T, et al. A probiotic mixture alleviates symptoms in irritable bowel syndrome patients: a controlled 6-month intervention. Aliment Pharmacol Ther. 2005;22:387–94.
105. Kim HJ, Vazquez Roque MI, Camilleri M, et al. A randomized controlled trial of a probiotic combination VSL#3 and placebo in irritable bowel syndrome with bloating. Neurogastroenterol Motil. 2005;17:687–96.
106. Niv E, Naftali T, Hallak R, et al. The efficacy of Lactobacillus reuteri ATCC 55730 in the treatment of patients with irritable bowel syndrome-A double blind, placebo-controlled, randomized study. Clin Nutr. 2005;24: 925–31.
107. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128:541–51.
108. Kim YG, Moon JT, Lee KM, et al. The effects of probiotics on symptoms of irritable bowel syndrome. Korean J Gastroenterol. 2006;47:413–9.
109. Simren M, Syrous A, Lindh A, et al. Effects of Lactobacillus Plantarum 299V on symptoms and rectal sensitivity in patients with irritable bowel syndrome (IBS)-A randomized double blind controlled trial. Gastroenterology. 2006;130:A600.
110. Whorwell PJ, Altringer L, Morel J, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol. 2006;101:1581–90.
111. Guyonnet D, Chassany O, Ducrotte P, et al. Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double blind, controlled trial. Aliment Pharmacol Ther. 2007;26:475–86.
112. Drouault-Holowacz S, Bieuvelet S, Burckel A, et al. A double blind randomized controlled trial of a probiotic combination in 100 patients with irritable bowel syndrome. Gastroenterol Clin Biol. 2008;32:147–52.
113. Enck P, Zimmerman K, Menke G, et al. A mixture of Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) for treatment of the irritable bowel syndrome-A randomized controlled trial with primary care physicians. Neurogastroenterol Motil. 2008;20:1103–9.
114. Kajander K, Myllyluoma E, Rajilic-Stojanovic M, et al. Clinical trial: multispecies probiotic supplementation alleviates the symptoms of irritable bowel syndrome and stabilizes intestinal microbiota. Aliment Pharmacol Ther. 2008;27:48–57.
115. Sinn DH, Song JH, Kim HJ, et al. Therapeutic effect of Lactobacillus acidophilus-SDC 2012, 2013 in patients with irritable bowel syndrome. Dig Dis Sci. 2008;53:2714–8.
116. Zeng J, Li YQ, Zuo XL, et al. Clinical trial: effect of active lactic acid bacteria on mucosal barrier function in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2008;28:994–1002.
117. Agrawal A, Houghton LA, Morris J, et al. Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2009;29:104–14.
118. Enck P, Zimmerman K, Menke G, et al. Randomized controlled treatment trial of irritable bowel syndrome with a probiotic E.-coli preparation (DSM17252) compared to placebo. Z Gastroenterol. 2009;47:209–14.
119. Hong KS, Kang HW, Im JP, et al. Effect of probiotics on symptoms in Korean adults with irritable bowel syndrome. Gut Liver. 2009;3:101–7.
120. Williams EA, Stimpson J, Wang D, et al. Clinical trial: a multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study. Aliment Pharmacol Ther. 2009;29:97–103.
121. Simren M, Ohman L, Olsson J, et al. Clinical trial: the effects of a fermented milk containing three probiotic bacteria in patients with irritable bowel syndrome-A randomized, double-blind, controlled study. Aliment Pharmacol Ther. 2010;31:218–27.
122. Choi CH, Jo SY, Park HJ, et al. A randomized, double-blind, placebo-controlled multicenter trial of Saccharomyces boulardii in irritable bowel syndrome: Effect on quality of life. J Clin Gastroenterol. 2011;45:679–83.
123. Guglielmetti S, Mora D, Gschwender M, et al. Randomised clinical trial: Bifidobacterium bifidum MIMBb75 significantly alleviates irritable bowel syndrome and improves quality of life-A double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2011;33:1123–32.
124. Michail S, Kenche H. Gut microbiota is not modified by randomized,double-blind, placebo-controlled trial of VSL#3 in diarrhea-predominant irritable bowel syndrome. Probiotics Antimicrob Proteins. 2011;3:1–7.
125. Ringel-Kulka T, Palsson OS, Maier D, et al. Probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 versus placebo for the symptoms of bloating in patients with functional bowel disorders: a double-blind study. J Clin Gastroenterol. 2011;45:518–25.
126. Sondergaard B, Olsson J, Ohlson K, et al. Effects of probiotic fermented milk on symptoms and intestinal flora in patients with irritable bowel syndrome: a randomized, placebo-controlled trial. Scand J Gastroenterol. 2011;46:663–72.
127. Cha BK, Jung SM, Choi CH, et al. The effect of a multispecies probiotic mixture on the symptoms and fecal microbiota in diarrhea-dominant irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. J Clin Gastroenterol. 2012;46:220–7.
128. Cui S, Hu Y. Multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study. Int J Clin Exp Med. 2012;5:238–44.
129. Dapoigny M, Piche T, Ducrotte P, et al. Efficacy and safety profile of LCR35 complete freeze-dried culture in irritable bowel syndrome: a randomized, double-blind study. World J Gastroenterol. 2012;18:2067–75.
130. Ducrotte P, Sawant P, Jayanthi V. Clinical trial: Lactobacillus plantarum 299v (DSM 9843) improves symptoms of irritable bowel syndrome. World J Gastroenterol. 2012;18:4012–8.
131. Farup PG, Jacobsen M, Ligaarden SC, et al. Probiotics, symptoms, and gut microbiota: What are the relations? A randomized controlled trial in subjects with irritable bowel syndrome. Gastroenterol Res Pract. 2012;2012:214102.
132. Kruis W, Chrubasik S, Boehm S, et al. A double-blind placebo-controlled trial to study therapeutic effects of probiotic Escherichia coli Nissle 1917 in subgroups of patients with irritable bowel syndrome. Int J Colorectal Dis. 2012;27:467–74.
133. Begtrup LM, de Muckadell OB, Kjeldsen J, et al. Long-term treatment with probiotics in primary care patients with irritable bowel syndrome-a randomised, double-blind, placebo controlled trial. Scand J Gastroenterol. 2013;48:1127–35.
134. Roberts LM, McCahon D, Holder R, et al. A randomised controlled trial of a probiotic ‘functional food’ in the management of irritable bowel syndrome. BMC Gastroenterol. 2013;13:45.
135. Ghoshal UC, Srivastava D, Misra A, et al. A proof-of-concept study showing antibiotics to be more effective in irritable bowel syndrome with than without small-intestinal bacterial overgrowth: a randomized, double-blind, placebo-controlled trial. Eur J Gastroenterol Hepatol. 2016;28: 281–9.
136. Lombardo L, Schembri M. A reason why lactose-free diet can be clinically ineffective in lactose intolerance patients. U Eur Gastroenterol J. 2015;3:A54.
137. Lembo A, Pimentel M, Rao SS, et al. Repeat treatment with rifaximin is safe and effective in patients with diarrhea-predominant irritable bowel syndrome. Gastroenterology. 2016;151:1113–21.
138. 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;98:412–9.
139. Sharara AI, Aoun E, Abdul-Baki H, et al. A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence. Am J Gastroenterol. 2006;101:326–33.
140. Pimentel M, Park S, Mirocha J, et al. The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial. Ann Intern Med. 2006;145:557–63.
141. Lembo A, Zakko SF, Ferreira NL, et al. Rifaximin for the treatment of diarrhea-associated irritable bowel syndrome: Short term treatment leading to long term sustained response. Gastroenterology. 2008;134:A545.
142. Pimentel M, Lembo A, Chey WD, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364:22–32.
143. Schoenfeld P, Pimentel M, Chang L, et al. Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: a pooled analysis of randomised, double-blind, placebo-controlled trials. Aliment Pharmacol Ther. 2014;39:1161–8.
144. Acosta A, Camilleri M, Shin A, et al. Effects of rifaximin on transit, permeability, fecal microbiome, and organic acid excretion in irritable bowel syndrome. Clin Transl Gastroenterol. 2016;7:e173.
145. Soldi S, Vasileiadis S, Uggeri F, et al. Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach. Clin Exp Gastroenterol. 2015;8:309–25.
146. Kim MS, Morales W, Hani AA, et al. The effect of rifaximin on gut flora and Staphylococcus resistance. Dig Dis Sci. 2013;58:1676–82.
147. Zeber-Lubecka N, Kulecka M, Ambrozkiewicz F, et al. Limited prolonged effects of rifaximin treatment on irritable bowel syndrome-related differences in the fecal microbiome and metabolome. Gut Microbes. 2016;7:397–413.
148. www.accessdata.fda.gov/drugsatfda_docs/label/2015/021361s012lbledt. pdf. 2015.
149. Rai RR, Dwivedi M, Kumar N. Efficacy and safety of drotaverine hydrochloride in irritable bowel syndrome: a randomized double-blind placebo-controlled study. Saudi J Gastroenterol. 2014;20:378–82.
150. Zheng L, Lai Y, Lu W, et al. Pinaverium reduces symptoms of irritable bowel syndrome in a multi-center, randomized controlled trial. Clin Gastroenterol Hepatol. 2015;13:1285–92.
151. Misra SC, Pandey RM. Efficacy of drotaverine in irritable bowel syndrome: a double blind, randomized, placebo-controlled clinical trial. Am J Gastroenterol. 2000;95:2544.
152. Schafer VE, Ewe K. The treatment of irritable colon. Efficacy and tolerance of buscopan plus, buscopan, paracetamol and placebo in ambulatory patients with irritable colon. Fortschr Med. 1990;108:488–92.
153. Centonze V, Imbibo BP, Campanozzi F, et al. Oral cimetropium bromide, a new antimuscarinic drug, for long-term treatment of irritable bowel syndrome. Am J Gastroenterol. 1988;83:1262–6.
154. Dobrilla G, Imbibo BP, Piazzi L, et al. Long term treatment of irritable bowel syndrome with cimetropium bromide: a double blind placebo controlled clinical trial. Gut. 1990;31:355–8.
155. Passaretti S, Guslandi M, Imbibo BP, et al. Effects of cimetropium bromide on gastrointestinal transit time in patients with irritable bowel syndrome. Aliment Pharmacol Ther. 1989;3:276.
156. Delmont J. Interet de l’adjonction d’un antispasmodique musculotrope au traitement des constipations douloureuses des colopathies fonctionnelles par le son. Med Chir Dig. 1981;10:365–70.
157. Levy C, Charbonnier A, Cachin M. Pinaverium bromide and functional colonic disease (double-blind study). Sem Hop Ther. 1977;53:372–4.
158. Virat J, Hueber D. Colopathy pain and dicetel. Prat Med. 1987;43:32–34.
159. Fielding JF. Double blind trial of trimebutine in the irritable bowel syndrome. Ir Med J. 1980;73:377–9.
160. Ghidini O, Saponati G, Intrieri L. Single drug treatment for irritable colon: Rociverine versus trimebutine maleate. Curr Ther Res Clin Exp. 1986;39:541–8.
161. Moshal MG, Herron M. A clinical trial of trimebutine (Mebutin) in spastic colon. J Int Med Res. 1979;7:231–4.
162. D’Arienzo A. D’Agostino L. L’ottilonio bromuro nel trattamento della s¡ndrome del colon irritabile. Rass Int Clin Ter. 1980;60:649–56.
163. Glende M, Morselli-Labate AM, Battaglia G, et al. Extended analysis of a double blind, placebo-controlled, 15-week study with otilinium bromide in irritable bowel syndrome. Eur J Gastroenterol Hepatol. 2002;14:1331–8.
164. Gilvarry J, Kenny A, Fielding JF. The non-effect of pirenzipine in dietary resistant irritable bowel syndrome. Ir J Med Sci. 1989;158:262.
165. Mitchell SA, Mee AS, Smith GD, et al. Alverine citrate fails to relieve the symptoms of irritable bowel syndrome: Results of a double-blind, randomized, placebo-controlled trial. Aliment Pharmacol Ther. 2002;16: 1187–95.
166. Piai G, Mazzacca G. Prifinium bromide in the treatment of the irritable colon syndrome. Gastroenterology. 1979;77:500–2.
167. Page JG, Dirnberger GM. Treatment of the irritable bowel syndrome with Bentyl (dicyclomine hydrochloride). J Clin Gastroenterol. 1981;3:153–6.
168. Baldi F, Corinaldesi R, Ferrarini F, et al. Clinical and functional evaluation of octilonium bromide in the treatment of irritable bowel syndrome: a double-blind controlled trial. Clin Trials J. 1983;20:77–88.
169. Castiglione F, Daniele B, Mazzacca G. Therapeutic strategy for the irritable bowel syndrome. Ital J Gastroenterol. 1991;23:53–55.
170. Pulpeiro A, Marti ML, De Los Santos AR, et al. Propinox en sindrome de intestino irritable. Prensa Med Argent. 2000;87:299–307.
171. Clave 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;34:432–42.
172. 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;61:560–71.
173. Mosaffa-Jahromi M, Lankarani KB, Pasalar M, et al. Efficacy and safety of enteric coated capsules of anise oil to treat irritable bowel syndrome. J Ethnopharmacol. 2016;194:937–46.
174. Lech Y, Olesen KM, Hey H, et al. Treatment of irritable bowel syndrome with peppermint oil. A double-blind investigation with a placebo. Ugeskr Laege. 1988;150:2388–9.
175. Liu JH, Chen GH, Yeh HZ, et al. Enteric-coated peppermint-oil capsules in the treatment of irritable bowel syndrome: a prospective, randomized trial. J Gastroenterol. 1997;32:765–8.
176. Cappello G, Spezzaferro M, Grossi L, et al. Peppermint oil (Mintoil) in the treatment of irritable bowel syndrome: a prospective double blind placebo-controlled randomized trial. Dig Liver Dis. 2007;39:530–6.
177. Capanni M, Surrenti E, Biagini M, et al. Efficacy of peppermint oil in the treatment of irritable bowel syndrome: a randomized, controlled trial. Gazz Med Ital. 2005;164:119–26.
178. Merat S, Khalili S, Mostajabi P, et al. The effect of enteric-coated, delayed-release peppermint oil on irritable bowel syndrome. Dig Dis Sci. 2010;55:1385–90.
179. McKee DP, Quigley EM. Intestinal motility in irritable bowel syndrome: Is IBS a motility disorder? Part 1. Definition of IBS and colonic motility. Dig Dis Sci. 1993;38:1761–2.
180. Irvine EJ, Tack J, Crowell MD, et al. Design of treatment trials for functional gastrointestinal disorders. Gastroenterology. 2016;150:1469–.e1.
181. 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;48:505–12.
182. Lovell RM, Ford AC. Prevalence of gastro-esophageal reflux-type symptoms in individuals with irritable bowel syndrome in the community: a meta-analysis. Am J Gastroenterol. 2012;107:1793–801.
183. Mayer EA, Tillisch K. The brain-gut axis in abdominal pain syndromes. Annu Rev Med. 2011;62:381–96.
184. Fond G, Loundou A, Hamdani N, et al. Anxiety and depression comorbidities in irritable bowel syndrome (IBS): a systematic review and meta-analysis. Eur Arch Psychiatry Clin Neurosci. 2014;264:651–60.
185. Patel P, Bercik P, Morgan DG, et al. Irritable bowel syndrome is significantly associated with somatisation in 840 patients, which may drive bloating. Aliment Pharmacol Ther. 2015;14:13074.
186. Gorard DA, Libby GW, Farthing MJ. Influence of antidepressants on whole gut orocaecal transit times in health and irritable bowel syndrome. Aliment Pharmacol Ther. 1994;8:159–66.
187. Gorard DA, Libby GW, Farthing MJ. Effect of a tricyclic antidepressant on small intestinal motility in health and diarrhea-predominant irritable bowel syndrome. Dig Dis Sci. 1995;40:86–95.
188. Agger JL, Schroder A, Gormsen LK, et al. Imipramine versus placebo for multiple functional somatic syndromes (STreSS-3): A double-blind, randomised study. Lancet Psychiatry. 2017;4:378–88.
189. Heefner JD, Wilder RM, Wilson ID. Irritable colon and depression. Psychosomatics. 1978;19:540–7.
190. 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;17:871–5.
191. Boerner D, Eberhardt R, Metz K, et al. Wirksamkeit und vertraglichkeit eines antidepressivuns beim colon irritabile. Therapiewoche. 1988;38: 201–8.
192. Bergmann M, Heddergott A, Schlosser T. [Die therapie des colon irritabile mit trimipramin (Herphonal)-Eine kontrollierte studie]. Z Klin Med. 1991;46:1621–8.
193. Vij JC, Jiloha RC, Kumar N, et al. Effect of antidepressant drug (doxepin) on irritable bowel syndrome patients. Indian J Psychiatry. 1991;33:243–6.
194. Drossman DA, Toner BB, Whitehead WE, et al. Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders. Gastroenterology. 2003;125:19–31.
195. Kuiken SD, Tytgat GNJ, Boeckxstaens GEE. 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;1:219–28.
196. Tabas G, Beaves M, Wang J, et al. Paroxetine to treat irritable bowel syndrome not responding to high fiber diet: a double-blind placebo-controlled trial. Am J Gastroenterol. 2004;99:914–20.
197. Vahedi H, Merat S, Momtahen S, et al. Clinical trial: the effect of amitriptyline in patients with diarrhea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2008;27:678–84.
198. Vahedi H, Merat S, Rashidioon A, et al. The effect of fluoxetine in patients with pain and constipation-predominant irritable bowel syndrome: a double-blind randomized-controlled study. Aliment Pharmacol Ther. 2005;22:381–5.
199. Tack J, Broekaert D, Fischler B, et al. A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut. 2006;55:1095–103.
200. 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;53:108–15.
201. Abdul-Baki H, El Hajj II, ElZahabi L, et al. A randomized controlled trial of imipramine in patients with irritable bowel syndrome. World J Gastroenterol. 2009;15:3636–42.
202. Masand PS, Pae CU, Krulewicz S, et al. A double-blind, randomized, placebo-controlled trial of paroxetine controlled-release in irritable bowel syndrome. Psychosomatics. 2009;50:78–86.
203. Ladabaum U, Sharabidze A, Levin TR, et al. Citalopram is not effective therapy for nondepressed patients with irritable bowel syndrome. Clin Gastroenterol Hepatol. 2010;8:42–48.
204. Ghadir MR, Habibinejad H, Heidari A, et al. Doxepin is more effective than nortriptyline and placebo for the treatment of diarrhea-predominant irritable bowel syndrome: a randomized triple-blind placebo-controlled trial. Tehran Univ Med J. 2011;69:352–8.
205. Cording M, Derry S, Phillips T, et al. Milnacipran for pain in fibromyalgia in adults. Cochrane Database Syst Rev. 2015;(10):CD008244.
206. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 2014;(1):CD007115.
207. Skljarevski V, Ossanna M, Liu-Seifert H, et al. A double-blind, randomized trial of duloxetine versus placebo in the management of chronic low back pain. Eur J Neurol. 2009;16:1041–8.
208. Skljarevski V, Zhang S, Desaiah D, et al. Duloxetine versus placebo in patients with chronic low back pain: a 12-week, fixed-dose, randomized, double-blind trial. J Pain. 2010;11:1282–90.
209. Konno S, Oda N, Ochiai T, et al. Randomized, double-blind, placebo-controlled phase III trial of duloxetine monotherapy in Japanese patients With chronic low back pain. Spine. 2016;41:1709–17.
210. Kaplan A, Franzen MD, Nickell PV, et al. An open-label trial of duloxetine in patients with irritable bowel syndrome and comorbid generalized anxiety disorder. Int J Psychiatry Clin Pract. 2014;18:11–5.
211. Greene B, Blanchard EB. Cognitive therapy for irritable bowel syndrome. J Consult Clin Psychol. 1994;62:576–82.
212. Kennedy T, Jones R, Darnley S, et al. Cognitive behaviour therapy in addition to antispasmodic treatment for irritable bowel syndrome in primary care: randomised controlled trial. BMJ. 2005;331:435–7.
213. Payne A, Blanchard EB. A controlled comparison of cognitive therapy and self-help support groups in the treatment of irritable bowel syndrome. J Consult Clin Psychol. 1995;63:779–86.
214. Tkachuk GA, Graff LA, Martin GL, et al. Randomized controlled trial of cognitive-behavioral group therapy for irritable bowel syndrome in a medical setting. J Clin Psychol Med Settings. 2003;10:57–69.
215. Vollmer A, Blanchard EB. Controlled comparison of individual versus group cognitive therapy for irritable bowel syndrome. Behav Ther. 1998;29:19–33.
216. Blanchard EB, Greene B, Scharff L, et al. Relaxation training as a treatment for irritable bowel syndrome. Biofeedback Self Regul. 1993;18: 125–31.
217. Keefer L, Blanchard EB. The effects of relaxation response meditation on the symptoms of irritable bowel syndrome: results of a controlled treatment study. Behav Res Ther. 2001;39:801–11.
218. Lynch PM, Zamble E. A controlled behavioral treatment study of irritable bowel syndrome. Behav Ther. 1989;20:509–23.
219. van der Veek PPJ, van Rood YR, Masclee AAM. Clinical trial: short-and long-term benefit of relaxation training for irritable bowel syndrome. Aliment Pharmacol Ther. 2007;26:943–52.
220. Shinozaki M, Kanazawa M, Kano M, et al. Effect of autogenic training on general improvement in patients with irritable bowel syndrome: a randomized controlled trial. Appl Psychophysiol Biofeedback. 2010;35:189–98.
221. Moser G, Tragner S, Elwira Gajowniczek E, et al. Long-term success of GUT-directed group hypnosis for patients with refractory irritable bowel syndrome: a randomized controlled trial. Am J Gastroenterol. 2013;108:602–9.
222. Galovski TE, Blanchard EB. The treatment of irritable bowel syndrome with hypnotherapy. Appl Psychophysiol Biofeedback. 1998;23:219–32.
223. Simren M, Ringstrom G, Bjornsson ES, et al. Treatment with hypnotherapy reduces the sensory and motor component of the gastrocolonic response in irritable bowel syndrome. Psychosom Med. 2004;66:233–8.
224. Lindfors P, Unge P, Arvidsson P, et al. Effects of gut-directed hypnotherapy on IBS in different clinical settings-Results from two randomized, controlled trials. Am J Gastroenterol. 2012;107:276–85.
225. Neff DF, Blanchard EB. A multi-component treatment for irritable bowel syndrome. Behav Ther. 1987;18:70–83.
226. Heitkemper M, Jarrett ME, Levy RL, et al. Self-management for women with irritable bowel syndrome. Clin Gastroenterol Hepatol. 2004;2: 585–96.
227. Blanchard EB, Schwarz SP, Suls JM, et al. Two controlled evaluations of multicomponent psychological treatment of irritable bowel syndrome. Behav Res Ther. 1992;30:175–89.
228. Sanders KA, Blanchard EB, Sykes MA. Preliminary study of a self-administered treatment for irritable bowel syndrome: Comparison to a wait list control group. Appl Psychophysiol Biofeedback. 2007;32:111–9.
229. Moss-Morris R, McAlpine L, Didsbury LP, et al. A randomized controlled trial of a cognitive behavioural therapy-based self-management intervention for irritable bowel syndrome in primary care. Psychol Med. 2010;40:85–94.
230. Hunt MG, Moshier S, Milonova M. Brief cognitive-behavioral internet therapy for irritable bowel syndrome. Behav Res Ther. 2009;47:797–802.
231. Ljotsson B, Falk L, Wibron Vesterlund A, et al. Internet-delivered exposure and mindfulness based therapy for irritable bowel syndrome-A randomized controlled trial. Behav Res Ther. 2010;48:531–9.
232. Guthrie E, Creed F, Dawson D, et al. A controlled trial of psychological treatment for the irritable bowel syndrome. Gastroenterology. 1991;100:450–7.
233. Creed F, Fernandes L, Guthrie E, et al. The cost-effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome. Gastroenterology. 2003;124:303–17.
234. Zernicke KA, Campbell TS, Blustein PK, et al. Mindfulness-based stress reduction for the treatment of irritable bowel syndrome symptoms: A randomized wait-list controlled trial. Int J Behav Med. 2013;20:385–96.
235. Gaylord SA, Palsson OS, Garland EL, et al. Mindfulness training reduces the severity of irritable bowel syndrome in women: results of a randomized controlled trial. Am J Gastroenterol. 2011;106:1678–88.
236. Shaw G, Srivastava ED, Sadlier M, et al. Stress management for irritable bowel syndrome: a controlled trial. Digestion. 1991;50:36–42.
237. Craske MG, Wolitzky-Taylor KB, Labus J, et al. A cognitive-behavioral treatment for irritable bowel syndrome using interoceptive exposure to visceral sensations. Behav Res Ther. 2011;49:413–21.
238. Fernandez C, Perez M, Amigo I, et al. Stress and contingency management in the treatment of irritable bowel syndrome. Stress Med. 1998;14:31–42.
239. Lackner JM, Jaccard J, Krasner SS, et al. Self-administered cognitive behavior therapy for moderate to severe irritable bowel syndrome: clinical efficacy, tolerability, feasibility. Clin Gastroenterol Hepatol. 2008;6: 899–906.
240. Jarrett ME, Cain KC, Burr RL, et al. Comprehensive self-management for irritable bowel syndrome: randomized trial of in-person vs. combined in-person and telephone sessions. Am J Gastroenterol. 2009;104:3004–14.
241. Boyce PM, Talley NJ, Balaam B, et al. A randomized controlled trial of cognitive behavior therapy, relaxation training, and routine clinical care for the irritable bowel syndrome. Am J Gastroenterol. 2003;98:2209–18.
242. Boltin D, Sahar N, Gil E, et al. Gut-directed guided affective imagery as an adjunct to dietary modification in irritable bowel syndrome. J Health Psychol. 2015;20:712–20.
243. Thakur ER, Holmes HJ, Lockhart NA, et al. Emotional awareness and expression training improves irritable bowel syndrome: a randomized controlled trial. Neurogastroenterol Motil. 2017;29:https://doi. org/10.1111/nmo.13143.
244. 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.e1-11.
245. Yang Y, Fang J-Y, Guo X, et al. Efficacy and safety of linaclotide in patients with IBS-C: results from a phase 3, randomized, double-blind, placebo-controlled trial in China and other regions. Gastroenterology. 2016;150:S741.
246. Johnston JM, Kurtz CB, MacDougall JE, et al. Linaclotide improves abdominal pain and bowel habits in a phase IIb study of patients with irritable bowel syndrome and constipation. Gastroenterology. 2010;139:1877–86.
247. Chey WD, Lembo AJ, Lavins BJ, et al. 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;107:1702–12.
248. Rao S, Lembo AJ, Shiff SJ, et al. 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;107:1714–24.
249. Brenner DM, Fogel R, Dorn SD 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;113:735-45.
250. Miner P, De Luca R, La Portilla M, et al. Plecanatide, a novel urogunaylin 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.
251. https://ir.synergypharma.com/press-releases/detail/1829/synergy-phar-maceuticals-announces-positive-results-in-first. 2016.
252. https://ir.synergypharma.com/press-releases/detail/1830/synergy-phar-maceuticals-announces-positive-results-in. 2016.
253. Shah ED, Kim HM, Schoenfeld P. Efficacy and tolerability of guanylate cyclase-C agonists for irritable bowel syndrome with constipation and chronic idiopathic constipation: a systematic review and meta-analysis. Am J Gastroenterol. 2018;113:329–38.
254. Drossman DA, Chey WD, Johanson JF, et al. Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome-results of two randomized, placebo-controlled studies. Aliment Pharmacol Ther. 2009;29:329–41.
255. Johanson JF, Drossman DA, Panas R, et al. Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2008;27:685–96.
256. Cryer B, Drossman DA, Chey WD, et al. Analysis of nausea in clinical studies of lubiprostone for the treatment of constipation disorders. Dig Dis Sci. 2017;62:3568–78.
257. Lembo AJ, Lacy BE, Zuckerman MJ, et al. Eluxadoline for irritable bowel syndrome with diarrhea. N Engl J Med. 2016;374:242–53.
258. Dove LS, Lembo A, Randall CW, et al. Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. Gastroenterology. 2013;145:329–38.e1.
259. Hovdenak N. Loperamide treatment of the irritable bowel syndrome. Scand J Gastroenterol. 1987;130:81–84.
260. Lavo B, Stenstam M, Nielsen AL. Loperamide in treatment of irritable bowel syndrome-A double-blind placebo controlled study. Scand J Gastroenterol. 1987;130:77–80.
261. Gershon MD. Review article: Serotonin receptors and transporters-roles in normal and abnormal gastrointestinal motility. Aliment Pharmacol Ther. 2004;20:3–14. suppl 7
262. Gershon MD, Tack J. The serotonin signaling system: From basic understanding to drug development for functional GI disorders. Gastroenterology. 2007;132:397–414.
263. Miller DP, Alfredson T, Cook SF, et al. Incidence of colonic ischemia, hospitalized complications of constipation, and bowel surgery in relation to use of alosetron hydrochloride. Am J Gastroenterol. 2003;98:1117–22.
264. Ford AC, Brandt LJ, Young C, et al. Efficacy of 5-HT 3 antagonists and 5-HT 4 agonists in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2009;104:1831–43.
265. Camilleri M, Mayer EA, Drossman DA, et al. Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5-HT 3 receptor antagonist. Aliment Pharmacol Ther. 1999;13: 1149–59.
266. 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;355:1035–40.
267. Camilleri M, Chey WY, Mayer EA, et al. 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;161:1733–40.
268. Bardhan KD, Bodemar G, Geldof H, et al. A double-blind, randomized, 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.
269. Lembo T, Wright RA, Lotronex Investigator T, et al. Alosetron controls bowel urgency and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome. Am J Gastroenterol. 2001;96:2662–70.
270. Chey WD, Chey WY, Heath AT, et al. Long-term safety and efficacy of alosetron in women with severe diarrhea-predominant irritable bowel syndrome. Am J Gastroenterol. 2004;99:2195–203.
271. Chang L, Ameen VZ, Dukes GE, et al. A dose-ranging, phase II study of the efficacy and safety of alosetron in men with diarrhea-predominant IBS. Am J Gastroenterol. 2005;100:115–23.
272. Krause R, Ameen V, Gordon SH, et al. A randomized, double-blind, placebo-controlled study to assess efficacy and safety of 0.5 mg and 1 mg alosetron in women with severe diarrhea-predominant IBS. Am J Gastroenterol. 2007;102:1709–19.
273. Ford AC, Suares NC. Effect of laxatives and pharmacological therapies in chronic idipathic constipation: Systematic review and meta-analysis. Gut. 2011;60:209–18.
274. 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;12:1131–8.
275. Chapman RW, Stanghellini V, Geraint M, et al. Randomized clinical trial: Macrogol/PEG 3350 plus electrolytes for treatment of patients with constipation associated with irritable bowel syndrome. Am J Gastroenterol. 2013;108:1508–15.
276. Spiller R, Lam C. An update on post-infectious irritable bowel syndrome: role of genetics, immune activation, serotonin and altered microbiome. J Neurogastroenterol Motil. 2012;18:258–68.
277. Bashashati M, Rezaei N, Shafieyoun A, et al. Cytokine imbalance in irritable bowel syndrome: a systematic review and meta-analysis. Neurogastroenterol Motil. 2014;26:1036–48.
278. Martin-Vinas JJ, Quigley EM. Immune response in irritable bowel syndrome: a systematic review of systemic and mucosal inflammatory mediators. J Dig Dis. 2016;17:572–81.
279. Ford AC, Kane SV, Khan KJ, et al. Efficacy of 5-aminosalicylates in Crohn’s disease: systematic review and meta-analysis. Am J Gastroenterol. 2011;106:617–29.
280. Ford AC, Achkar JP, Khan KJ, et al. Efficacy of 5-aminosalicylates in ulcerative colitis: systematic review and meta-analysis. Am J Gastroenterol. 2011;106:601–16.
281. Barbara G, Cremon C, Annese V, et al. Randomised controlled trial of mesalazine in IBS. Gut. 2016;65:82–90.
282. Lam C, Tan W, Leighton M, et al. A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D). Gut. 2016;65:91–9.
283. Aron J, Lin M, Yu J, et al. Mesalamine granules 1500 mg once daily for 12 weeks provides adequate relief of IBS symptoms in irritable bowel syndrome with diarrhea: results from a phase 2 trial. Am J Gastroenterol. 2012;107:S711–S712.