Guidelines for the Treatment of Functional Dyspepsia

Sam Ryong Jee; Hye-Kyung Jung; Byung Hoon Min; Kee Don Choi; Poong-Lyul Rhee; Young Woo Kang; Sang In Lee

doi:10.4166/kjg.2011.57.2.67

Journal List > Korean J Gastroenterol > v.57(2) > 1006838

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Jee, Jung, Min, Choi, Rhee, Kang, Lee, and The Korean Society of Neurogastroenterology and Motility: Guidelines for the Treatment of Functional Dyspepsia

Special Review

Korean J Gastroenterol 2011;57(2):67-81.

Published online: 4 October 2011

DOI: https://doi.org/10.4166/kjg.2011.57.2.67

Guidelines for the Treatment of Functional Dyspepsia

Sam Ryong Jee, Hye-Kyung Jung¹, Byung Hoon Min², Kee Don Choi³, Poong-Lyul Rhee², Young Woo Kang⁴, Sang In Lee⁵; The Korean Society of Neurogastroenterology and Motility

Department of Internal Medicine, Inje University College of Medicine, Busan, Korea

¹Ewha Womans University School of Medicine, Seoul, Korea

²Sungkyunkwan University School of Medicine, Seoul, Korea

³University of Ulsan College of Medicine, Seoul, Korea

⁴Seoul, Konyang University College of Medicine, Daejeon, Korea

⁵Yonsei University College of Medicine, Seoul, Korea

Correspondence to: Poong-Lyul Rhee, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Irwon-dong, Gangnam-gu, Seoul 135-710, Korea. Tel: +82-2-3410-3409, Fax: +82-2-3410-6983, E-mail: plrhee@skku.edu

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Functional dyspepsia (FD) is defined as the presence of symptoms thought to originate in the gastroduodenal area, in the absence of any organic, systemic, or metabolic disease that is likely to explain the symptoms. Based on the available evidence and consensus opinion, thirteen consensus statements for the treatment of FD were developed using the modified Delphi approach. Proton pump inhibitor, prokinetics, and histamine 2 receptor antagonists are effective for the treatment of FD. Mucosal protecting agents, fundus relaxant, and drugs for visceral hypersensitivity can improve symptoms in FD. Antacids and antidepressants may help improving symptoms in FD. Comparing endoscopy with ‘test and treat' of Helicobacter pylori, endoscopy may be more effective initial strategy for managing patients with FD in Korea given high incidence of gastric cancer and low cost of endoscopy. Helicobacter pylori eradication can be one of the therapeutic options for patients with FD. Psychotherapy is effective for those who have severe symptoms and refractoriness. Further studies are strongly needed to develop better treatment strategies for Korean patients with FD.

Keywords: Functional, Dyspepsia, Treatment, Guideline

References

1. Management of dyspepsia: report of a working party. Lancet. 1988; 1:576–579.

2. Talley NJ, Stanghellini V, Heading RC, Koch KL, Malagelada JR, Tytgat GN. Functional gastroduodenal disorders. Gut. 1999; 45(Suppl 2):II37–II42.

3. Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders. Gastroenterology. 2006; 130:1466–1479.

4. Jung HK, Keum BR, Jo YJ, Jee SR, Rhee PL, Kang YW. Diagnosis of functional dyspepsia: a systematic review. Korean J Gastroenterol. 2010; 55:296–307.

5. Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology. 2006; 130:1377–1390.

6. Talley NJ, Lam SK, Goh KL, Fock KM. Management guidelines for uninvestigated and functional dyspepsia in the Asia-Pacific region: First Asian Pacific Working Party on Functional Dyspepsia. J Gastroenterol Hepatol. 1998; 13:335–353.

7. Talley NJ, Vakil NB, Moayyedi P. American gastroenterological association technical review on the evaluation of dyspepsia. Gastroenterology. 2005; 129:1756–1780.

8. National Institute for Clinical Excellence. Dyspepsia: Managing dyspepsia in adults in primary care. www.nice.org.uk/pdf/CG-017fullguideline.pdf. 2004.

9. Veldhuyzen van Zanten SJ, Bradette M, Chiba N, et al. Evidence-based recommendations for short- and long-term management of uninvestigated dyspepsia in primary care: an update of the Canadian Dyspepsia Working Group (CanDys) clinical management tool. Can J Gastroenterol. 2005; 19:285–303.

10. Scottish Intercollegiate Guidelines Network. Dyspepsia: A national clinical guideline. www.sign.ac.uk/pdf/sign68.pdf. 2003.

11. Lee KJ. Evidence based guideline for diagnosis and treatment: therapeutic guideline for functional dyspepsia. Korean J Neurogastroenterol Motil. 2005; 11:25–29.

12. Jones R, Lydeard S. Prevalence of symptoms of dyspepsia in the community. BMJ. 1989; 298:30–32.

13. Lieberman D, Fennerty MB, Morris CD, Holub J, Eisen G, Sonnenberg A. Endoscopic evaluation of patients with dyspepsia: results from the national endoscopic data repository. Gastroenterology. 2004; 127:1067–1075.

14. Ryu KH, Kim YH, Son HJ, et al. Various causes of dyspepsia: to determine organic and functional cause of dyspepsia. Korean J Gastrointest Motil. 1998; 4:112–117.

15. van Kerkhoven LA, Laheij RJ, Meineche-Schmidt V, Veldhuy-zenvan Zanten SJ, de Wit NJ, Jansen JB. Functional dyspepsia: not all roads seem to lead to rome. J Clin Gastroenterol. 2009; 43:118–122.

16. Guyatt GH, Cook DJ, Jaeschke R, Pauker SG, Schünemann HJ. Grades of recommendation for antithrombotic agents: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008; 133(6 Suppl):123S–131S.

17. Barbera R, Feinle C, Read NW. Abnormal sensitivity to duodenal lipid in patients with functional dyspepsia. Eur J Gastroenterol Hepatol. 1995; 7:1051–1057.

18. Barbera R, Feinle C, Read NW. Nutrient-specific modulation of gastric mechanosensitivity in patients with functional dyspepsia. Dig Dis Sci. 1995; 40:1636–1641.

19. Tack J, Bisschops R, Sarnelli G. Pathophysiology and treatment of functional dyspepsia. Gastroenterology. 2004; 127:1239–1255.

20. Boekema PJ, Samsom M, Roelofs JM, Smout AJ. Effect of coffee on motor and sensory function of proximal stomach. Dig Dis Sci. 2001; 46:945–951.

21. Lee SI. Functional cyspepsia. J Korean Med Assoc. 2005; 48:48–60.

22. Talley NJ, Meineche-Schmidt V, Paré P, et al. Efficacy of omeprazole in functional dyspepsia: double-blind, randomized, placebo-controlled trials (the Bond and Opera studies). Aliment Pharmacol Ther. 1998; 12:1055–1065.

23. Jones RH, Baxter G. Lansoprazole 30 mg daily versus ranitidine 150 mg b.d. in the treatment of acid-related dyspepsia in general practice. Aliment Pharmacol Ther. 1997; 11:541–546.

24. Moayyedi P, Soo S, Deeks J, Delaney B, Innes M, Forman D. Pharmacological interventions for non-ulcer dyspepsia. Cochrane Database Syst Rev. 2006; (4):CD001960.

25. Blum AL, Arnold R, Stolte M, Fischer M, Koelz HR. Short course acid suppressive treatment for patients with functional dyspepsia: results depend on Helicobacter pylori status. The Frosch Study Group. Gut. 2000; 47:473–480.

26. Talley NJ, Lauritsen K. The potential role of acid suppression in functional dyspepsia: the BOND, OPERA, PILOT, and ENCORE studies. Gut. 2002; 50(Suppl 4):iv36–iv41.

27. Bolling-Sternevald E, Lauritsen K, Aalykke C, et al. Effect of profound acid suppression in functional dyspepsia: a double-blind, randomized, placebo-controlled trial. Scand J Gastroenterol. 2002; 37:1395–1402.

28. Wong WM, Wong BC, Hung WK, et al. Double blind, randomised, placebo controlled study of four weeks of lansoprazole for the treatment of functional dyspepsia in Chinese patients. Gut. 2002; 51:502–506.

29. Farup PG, Hovde O, Torp R, Wetterhus S. Patients with functional dyspepsia responding to omeprazole have a characteristic gastro-oesophageal reflux pattern. Scand J Gastroenterol. 1999; 34:575–579.

30. Gerson LB. Triadafilopoulos G. A prospective study of oesophageal 24-h ambulatory pH monitoring in patients with functional dyspepsia. Dig Liver Dis. 2005; 37:87–91.

31. Peura DA, Kovacs TO, Metz DC, Siepman N, Pilmer BL, Talley NJ. Lansoprazole in the treatment of functional dyspepsia: two double-blind, randomized, placebo-controlled trials. Am J Med. 2004; 116:740–748.

32. van Zanten SV, Armstrong D, Chiba N, et al. Esomeprazole 40mg once a day in patients with functional dyspepsia: The randomized placebo-controlled “ENTER” trial. Am J Gastroenterol. 2006; 101:2096–2106.

33. Goves J, Oldring JK, Kerr D, et al. First line treatment with omeprazole provides an effective and superior alternative strategy in the management of dyspepsia compared to antacid/algi-nate liquid: a multicentre study in general practice. Aliment Pharmacol Ther. 1998; 12:147–157.

34. Meineche-Schmidt V, Krag E. Antisecretory therapy in 1017 patients with ulcerlike or refluxlike dyspepsia in general practice. Eur J Gastroenterol Hepatol. 1997; 3:125–130.

35. Gotthard R, Bodemar G, Brodin U, Jönsson KA. Treatment with cimetidine, antacid, or placebo in patients with dyspepsia of unknown origin. Scand J Gastroenterol. 1988; 23:7–18.

36. Nyrén O, Adami HO, Bates S, et al. Absence of therapeutic benefit from antacids or cimetidine in non-ulcer dyspepsia. N Engl J Med. 1986; 314:339–343.

37. al-Quorain A, Larbi EB, al-Shedoki F. A double-blind, randomized, placebo-controlled trial of cisapride in Saudi Arabs with functional dyspepsia. Scand J Gastroenterol. 1995; 30:531–534.

38. Bekhti A, Rutgeerts L. Domperidone in the treatment of functional dyspepsia in patients with delayed gastric emptying. Postgrad Med J. 1979; 55(Suppl 1):30–32.

39. Champion MC, MacCannell KL, Thomson AB, et al. A double-blind randomized study of cisapride in the treatment of nonulcer dyspepsia. The Canadian Cisapride Nud Study Group. Can J Gastroenterol. 1997; 11:127–134.

40. Chung JM. Cisapride in chronic dyspepsia: results of a double-blind, placebo-controlled trial. Scand J Gastroenterol Suppl. 1993; 195:11–14.

41. de Groot GH, de Both PS. Cisapride in functional dyspepsia in general practice. A placebo-controlled, randomized, double-blind study. Aliment Pharmacol Ther. 1997; 11:193–199.

42. De Nutte N, Van Ganse W, Witterhulghe M, Defrance P. Relief of epigastric pain in nonulcer dyspepsia: controlled trial of the promotility drug cisapride. Clin Ther. 1989; 11:62–68.

43. Francois I, De Nutte N. Nonulcer dyspepsia: effect of the gastrointestinal prokinetic drug cisapride. Curr Ther Res. 1987; 41:891–898.

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

45. Hannon R. Efficacy of cisapride in patients with nonulcer dyspepsia. A placebo-controlled study. Curr Ther Res. 1987; 42:814–822.

46. Hansen JM, Bytzer P, Schaffalitzky de Muckadell OB. Placebo-controlled trial of cisapride and nizatidine in unselected patients with functional dyspepsia. Am J Gastroenterol. 1998; 93:368–374.

47. Holtmann G, Gschossmann J, Mayr P, Talley NJ. A randomized placebo-controlled trial of simethicone and cisapride for the treatment of patients with functional dyspepsia. Aliment Pharmacol Ther. 2002; 16:1641–1648.

48. Holtmann G, Talley NJ, Liebregts T, Adam B, Parow C. A placebo-controlled trial of itopride in functional dyspepsia. N Engl J Med. 2006; 354:832–840.

49. Kellow JE, Cowan H, Shuter B, et al. Efficacy of cisapride therapy in functional dyspepsia. Aliment Pharmacol Ther. 1995; 9:153–160.

50. Matsueda K, Hongo M, Sasaki D, et al. Therapeutic efficacy of novel agent (Z-338) in functional dyspespsia (FD). Gastroenterology. 2005; 128(Suppl 1):A467.

51. Rösch W. Cisapride in non-ulcer dyspepsia. Results of a placebo-controlled trial. Scand J Gastroenterol. 1987; 22:161–164.

52. Talley NJ, Verlinden M, Snape W, et al. Failure of a motilin receptor agonist (ABT-229) to relieve the symptoms of functional dyspepsia in patients with and without delayed gastric emptying: a randomized double-blind placebo-controlled trial. Aliment Pharmacol Ther. 2000; 14:1653–1661.

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

54. Wood SF, Penney SC, Cochran KM. Cisapride in functional dyspepsia: a double-blind, placebo-controlled randomized trial in general practice patients. Scand J Gastroenterol Suppl. 1993; 195:5–10.

55. Yeoh KG, Kang JY, Tay HH, et al. Effect of cisapride on functional dyspepsia in patients with and without histological gastritis: a double-blind placebo-controlled trial. J Gastroenterol Hepatol. 1997; 12:13–18.

56. Veldhuyzen van Zanten SJ, Jones MJ, Verlinden M, Talley NJ. Efficacy of cisapride and domperidone in functional (nonulcer) dyspepsia: a metaanalysis. Am J Gastroenterol. 2001; 96:689–696.

57. Talley NJ, Tack J, Ptak T, Gupta R, Giguère M. Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials. Gut. 2008; 57:740–746.

58. Cho YK, Choi MG, Kim SH, et al. The effect of mosapride on quality of life in functional dyspepsia. Korean J Gastroenterol. 2004; 43:160–167.

59. Janssens J, Peeters TL, Vantrappen G, et al. Improvement of gastric emptying in diabetic gastroparesis by erythromycin. Preliminary studies. N Engl J Med. 1990; 322:1028–1031.

60. Arts J, Caenepeel P, Verbeke K, Tack J. Influence of erythromycin on gastric emptying and meal related symptoms in functional dyspepsia with delayed gastric emptying. Gut. 2005; 54:455–460.

61. Parkman HP, Hasler WL, Fisher RS. American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology. 2004; 127:1592–1622.

62. Tatsuta M, Iishi H, Nakaizumi A, Okuda S. Effect of treatment with cisapride alone or in combination with domperidone on gastric emptying and gastrointestinal symptoms in dyspeptic patients. Aliment Pharmacol Ther. 1992; 6:221–228.

63. Delattre M, Malesky M, Prinzie A. Symptomatic treatment of non-ulcer dyspepsia with cimetidine. Curr Ther Res. 1985; 37:980–991.

64. Hadi S. Clinical investigation of ranitidine in patients with gastritis. Clin Ther. 1989; 11:590–594.

65. Kato M, Watanabe M, Konishi S, et al. Randomized, double-blind, placebo-controlled crossover trial of famotidine in patients with functional dyspepsia. Aliment Pharmacol Ther. 2005; 21(Suppl 2):S27–S31.

66. Kelbaek H, Linde J, Eriksen J, Mungaard S, Moesgaard F, Bonnevie O. Controlled clinical trial of treatment with cimetidine for non-ulcer dyspepsia. Acta Med Scand. 1985; 217:281–287.

67. Müller P, Hotz J, Franz E, Simon B. Ranitidine in the treatment of non-ulcer dyspepsia. A placebo-controlled study in the Federal Republic of Germany. Arzneimittelforschung. 1994; 44:1130–1132.

68. Nesland AA, Berstad A. Effect of cimetidine in patients with non-ulcer dyspepsia and erosive prepyloric changes. Scand J Gastroenterol. 1985; 20:629–635.

69. Olubuyide IO, Ayoola EA, Okubanjo AO, Atoba MA. Non-ulcer dyspepsia in Nigerians clinical and therapeutic results. Scand J Gastroenterol Suppl. 1986; 124:83–87.

70. Saunders JH, Oliver RJ, Higson DL. Dyspepsia: incidence of a non-ulcer disease in a controlled trial of ranitidine in general practice. Br Med J (Clin Res Ed). 1986; 292:665–668.

71. Singal AK, Kumar A, Broor SL. Cimetidine in the treatment of non-ulcer dyspepsia: results of a randomized double-blind, placebo-controlled study. Curr Med Res Opin. 1989; 11:390–397.

72. Lee KJ, Demarchi B, Demedts I, Sifrim D, Raeymaekers P, Tack J. A pilot study on duodenal acid exposure and its relationship to symptoms in functional dyspepsia with prominent nausea. Am J Gastroenterol. 2004; 99:1765–1773.

73. Lee KJ, Vos R, Janssens J, Tack J. Influence of duodenal acidification on the sensorimotor function of the proximal stomach in humans. Am J Physiol Gastrointest Liver Physiol. 2004; 286:G278–284.

74. Castillo EJ, Camilleri M, Locke GR, et al. A community-based, controlled study of the epidemiology and pathophysiology of dyspepsia. Clin Gastroenterol Hepatol. 2004; 2:985–996.

75. Kim JW, Kim SY, Kim CS, et al. Role of stress in functional dyspepsia. Korean J Gastrointest Motil. 2002; 8:146–152.

76. Lee S, Park M, Choi S, Nah Y, Abbey SE, Rodin G. Stress, coping, and depression in non-ulcer dyspepsia patients. J Psychosom Res. 2000; 49:93–99.

77. Locke GR 3rd, Weaver AL, Melton LJ 3rd, Talley NJ. Psychosocial factors are linked to functional gastrointestinal disorders: a population based nested case-control study. Am J Gastroenterol. 2004; 99:350–357.

78. Haug TT, Svebak S, Wilhelmsen I, Berstad A, Ursin H. Psychological factors and somatic symptoms in functional dyspepsia. A comparison with duodenal ulcer and healthy controls. J Psychosom Res. 1994; 38:281–291.

79. Lee KT, Rhee PL, Kim JJ, et al. A study on the psychologic factors in functional dyspepsia. Korean J Med. 1996; 51:595–601.

80. Magni G, di Mario F, Bernasconi G, Mastropaolo G. DSM-III diagnoses associated with dyspepsia of unknown cause. Am J Psychiatry. 1987; 144:1222–1223.

81. Hojo M, Miwa H, Yokoyama T, et al. Treatment of functional dyspepsia with antianxiety or antidepressive agents: systematic review. J Gastroenterol. 2005; 40:1036–1042.

82. Jackson JL, O'Malley PG, Tomkins G, Balden E, Santoro J, Kroenke K. Treatment of functional gastrointestinal disorders with antidepressant medications: a metaanalysis. Am J Med. 2000; 108:65–72.

83. Rubin G, Meineche-Schmidt V, Roberts A, de Wit N. The use of consensus to develop guidelines for the management of Helicobacter pylori infection in primary care. European Society for Primary Care Gastroenterology. Fam Pract. 2000; 17(Suppl 2):S21–S26.

84. Ford AC, Qume M, Moayyedi P, et al. Helicobacter pylori “test and treat” or endoscopy for managing dyspepsia: an individual patient data metaanalysis. Gastroenterology. 2005; 128:1838–1844.

85. Heaney A, Collins JS, Watson RG, McFarland RJ, Bamford KB, Tham TC. A prospective randomised trial of a “test and treat” policy versus endoscopy based management in young Helicobacter pylori positive patients with ulcerlike dyspepsia, referred to a hospital clinic. Gut. 1999; 45:186–190.

86. McColl KE, el-Nujumi A, Murray L, et al. The Helicobacter pylori breath test: a surrogate marker for peptic ulcer disease in dyspeptic patients. Gut. 1997; 40:302–306.

87. Li XB, Liu WZ, Ge ZZ, Chen XY, Shi Y, Xiao SD. Helicobacter pylori "test-and-treat" strategy is not suitable for the management of patients with uninvestigated dyspepsia in Shanghai. Scand J Gastroenterol. 2005; 40:1028–1031.

88. Kim KC, Park HJ, Lee HW, et al. Relation of serum gastrin and pepsinogen levels to serologic recognition of CagA and VacA in Helicobacter pylori infection. Korean J Gastroenterol. 1997; 29:25–34.

89. Park IS, Lee YC, Park HJ, et al. Helicobacter pylori Infection in Korea. Yonsei Med J. 2001; 42:457–470.

90. Hwang IR, Kim JH, Lee KJ, Cho SW. Can Helicobacter pylori serology predict non-ulcer dyspepsia in young dyspeptic patients? Korean J Gastrointest Endosc. 2000; 21:696–703.

91. Blum AL, Talley NJ, O'Moráin C, et al. Lack of effect of treating Helicobacter pylori infection in patients with nonulcer dyspepsia. Omeprazole plus Clarithromycin and Amoxicillin effect one year after treatment (OCAY) study group. N Engl J Med. 1998; 339:1875–1881.

92. Froehlich F, Gonvers JJ, Wietlisbach V, et al. Helicobacter pylori eradication treatment does not benefit patients with nonulcer dyspepsia. Am J Gastroenterol. 2001; 96:2329–2336.

93. Gisbert JP, González L, Calvet X, Roqué M, Gabriel R, Pajares JM. Helicobacter pylori eradication: proton pump inhibitor vs. ranitidine bismuth citrate plus two antibiotics for 1 week-a metaanalysis of efficacy. Aliment Pharmacol Ther. 2000; 14:1141–1150.

94. Lin CK, Hsu PI, Lai KH, et al. One-week quadruple therapy is an effective salvage regimen for Helicobacter pylori infection in patients after failure of standard triple therapy. J Clin Gastroenterol. 2002; 34:547–551.

95. Koskenpato J, Farkkilä M, Sipponen P. Helicobacter pylori eradication and standardized 3-month omeprazole therapy in functional dyspepsia. Am J Gastroenterol. 2001; 96:2866–2872.

96. Malfertheiner P, Bayerdörffer E, Diete U, et al. The GU-MACH study: the effect of 1-week omeprazole triple therapy on Helicobacter pylori infection in patients with gastric ulcer. Aliment Pharmacol Ther. 1999; 13:703–712.

97. McColl KE, Murray LS, Gillen D, et al. Randomised trial of endoscopy with testing for Helicobacter pylori compared with non-invasive H pylori testing alone in the management of dyspepsia. BMJ. 2002; 324:999–1002.

98. Miwa H, Nagahara A, Sato K, et al. Efficacy of 1 week omeprazole or lansoprazole-amoxycillin-clarithromycin therapy for Helicobacter pylori infection in the Japanese population. J Gastroenterol Hepatol. 1999; 14:317–321.

99. Talley NJ, Janssens J, Lauritsen K, Rácz I, Bolling-Sternevald E. Eradication of Helicobacter pylori in functional dyspepsia: randomised double blind placebo controlled trial with 12 months' follow up. The Optimal Regimen Cures Helicobacter Induced Dyspepsia (ORCHID) Study Group. BMJ. 1999; 318:833–837.

100. Kim SH, Hong DY, Kang PS, et al. Community-based Helicobacter pylori screening and its effects on eradication in patients with dyspepsia. Korean J Prev Med. 2000; 33:285–298.

101. Lee EJ, Gham CW, Park TW, et al. The effect of Helicobacter pylori eradication on the improvement of the symptoms in patients with functional dyspepsia and peptic ulcer disease. Korean J Med. 2006; 71:141–148.

102. Chiba N, Van Zanten SJ, Sinclair P, Ferguson RA, Escobedo S, Grace E. Treating Helicobacter pylori infection in primary care patients with uninvestigated dyspepsia: the Canadian adult dyspepsia empiric treatmentHelicobacter pylori positive (CADET-Hp) randomised controlled trial. BMJ. 2002; 324:1012–1016.

103. Stevens R, Baxter G. Benefit of Helicobacter pylori eradication in the treatment of ulcerlike dyspepsia in primary care. Gastroenterology. 2001; 120(Suppl 1):A50.

104. Kwon SB, Lee KL, Kim JS, et al. Antibiotics-associated diarrhea and other gastrointestinal abnormal responses regarding Helicobacter pylori eradication. Korean J Gastroenterol. 2010; 56:229–235.

105. Miwa H, Osada T, Nagahara A, et al. Effect of a gastroprotective agent, rebamipide, on symptom improvement in patients with functional dyspepsia: a double-blind placebo-controlled study in Japan. J Gastroenterol Hepatol. 2006; 21:1826–1831.

106. Talley NJ, Riff DS, Schwartz H, Marcuard SP. Double-blind placebo-controlled multicentre studies of rebamipide, a gastroprotective drug, in the treatment of functional dyspepsia with or without Helicobacter pylori infection. Aliment Pharmacol Ther. 2001; 15:1603–1611.

107. Yang Kim H, Hahm KB, Choi MG, et al. Prospective multicenter trial for the efficacy of ecabet sodium on the relief of dyspepsia in Korean patients with chronic gastritis. J Clin Biochem Nutr. 2007; 41:160–168.

108. Lee JH, Kim JJ, Hahm KB, et al. Efficacy and safety of ecabet sodium on functional dyspepsia: a prospective, double-blinded, randomized, multicenter controlled trial. World J Gastroenterol. 2006; 12:2756–2761.

109. Seol SY, Kim MH, Rew JS, Choi MG. A phase III clinical trial of stillen(TM) for erosive gastritis. Korean J Gastrointest Endosc. 2004; 28:230–236.

110. Sakamoto C, Ogoshi K, Saigenji K, et al. Comparison of the effectiveness of geranylgeranylacetone with cimetidine in gastritis patients with dyspeptic symptoms and gastric lesions: a randomized, double-blind trial in Japan. Digestion. 2007; 75:215–224.

111. Tack J, Piessevaux H, Coulie B, Caenepeel P, Janssens J. Role of impaired gastric accommodation to a meal in functional dyspepsia. Gastroenterology. 1998; 115:1346–1352.

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

113. Van Oudenhove L, Kindt S, Vos R, Coulie B, Tack J. Influence of buspirone on gastric sensorimotor function in man. Aliment Pharmacol Ther. 2008; 28:1326–1333.

114. Tack J, Broeckaert D, Coulie B, Janssens J. The influence of cisapride on gastric tone and the perception of gastric distension. Aliment Pharmacol Ther. 1998; 12:761–766.

115. Tack J, Vos R, Janssens J, Salter J, Jauffret S, Vandeplassche G. Influence of tegaserod on proximal gastric tone and on the perception of gastric distension. Aliment Pharmacol Ther. 2003; 18:1031–1037.

116. Camilleri M, Coulie B, Tack JF. Visceral hypersensitivity: facts, speculations, and challenges. Gut. 2001; 48:125–131.

117. Tack J, Caenepeel P, Fischler B, Piessevaux H, Janssens J. Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia. Gastroenterology. 2001; 121:526–535.

118. Moss HE, Sanger GJ. The effects of granisetron, ICS 205–930 and ondansetron on the visceral pain reflex induced by duodenal distension. Br J Pharmacol. 1990; 100:497–501.

119. Read NW, Bardhan KD, Whorwell PJ, et al. Fedotozine in functional dyspepsia: results of a 6-week placebo-controlled multicenter therapeutic trial. Gastroenterology. 1995; 108(Suppl):A676.

120. Boulant J, Fioramounti J, Dapoiguy M, Bommelear G, Bueno L. Cholecystokinin and nitric oxide in transient lower esophageal sphincter relaxation to gastric distension in dogs. Gastroenterology. 1994; 107:1059–1066.

121. Bradette M, Delvaux M, Stsumont G, Fioramonti J, Bueno L, Frexinos J. Octreotide increases thresholds of colonic visceral perception in IBS patients without modifying muscle tone. Dig Dis Sci. 1994; 39:1171–1178.

122. Talley NJ, Owen BK, Boyce P, Paterson K. Psychological treatments for irritable bowel syndrome: a critique of controlled treatment trials. Am J Gastroenterol. 1996; 91:277–283.

123. Calvert EL, Houghton LA, Cooper P, Morris J, Whorwell PJ. Longterm improvement in functional dyspepsia using hypnotherapy. Gastroenterology. 2002; 123:1778–1785.

124. Soo S, Forman D, Delaney BC, Moayyedi P. A systematic review of psychological therapies for nonulcer dyspepsia. Am J Gastroenterol. 2004; 99:1817–1822.

125. Bates S, Sjoden PO, Nyren O. Behavioral treatment of non-ulcer dyspepsia. Scand J Behav Ther. 1988; 17:155–165.

126. Haug TT, Wilhelmsen I, Svebak S, Berstad A, Ursin H. Psychotherapy in functional dyspepsia. J Psychosom Res. 1994; 38:735–744.

127. Hamilton J, Guthrie E, Creed F, et al. A randomized controlled trial of psychotherapy in patients with chronic functional dyspepsia. Gastroenterology. 2000; 119:661–669.

128. Calvert EL, Houghton LA, Cooper P, Morris J, Whorwell PJ. Longterm improvement in functional dyspepsia using hypnotherapy. Gastroenterology. 2002; 123:1778–1785.

Fig. 1.

Flow chart for searching strategy.

Table 1.

Grading Recommendations¹⁶

Grade of recommendation / description	Benefit vs. risk and burdens	Methodological quality of supporting evidence	Implications
1A. Strong recommendation, high-quality evidence	Benefits clearly outweigh risk and burden, or vice versa	RCTs without important limitations or overwhelming evidence from observational studies	Strong recommendation, can apply to most patients in most circumstances. Further evidence is unlikely to change our confidence in the estimate of effect
1B. Strong recommendation, moderate-quality evidence	Benefits clearly outweigh risk and burden, or vice versa	RCTs with important limitations (inconsistent results, methodological flaws, indirect, or imprecise) or exceptionally strong evidence from observational studies	Strong recommendation, can apply to most patients in most circumstances. Higher quality evidence may well change our confidence in the estimate of effect
1C. Strong recommendation, low-quality or very low-quality evidence	Benefits clearly outweigh risk and burden, or vice versa	Observational studies or case series	Strong recommendation, can apply to most patients in most circumstances. Higher quality evidence is very likely to change our confidence in the estimate of effect
2A. Weak recommendation, high-quality evidence	Benefits closely balanced with risk and burden	RCTs without important limitations or overwhelming evidence from observational studies	Weak recommendation, best action may differ depending on circumstances or patients' or societal values. Further evidence is unlikely to change our confidence in the estimate of effect
2B. Weak recommendation, moderate-quality evidence	Benefits closely balanced with risk and burden	RCTs with important limitations (inconsistent results, methodological flaws, indirect, or imprecise) or exceptionally strong evidence from observational studies	Weak recommendation, best action may differ depending on circumstances or patients' or societal values. Higher quality evidence may well change our confidence in the estimate of effect
2C. Weak recommendation, low-quality or very low-quality evidence	Uncertainty in the estimates of benefits, risks and burden; benefits, risk and burden may be closely balanced	Observational studies or case series	Very weak recommendations; other alternatives may be equally reasonable. High quality evidence is very likely to change our confidence in the estimate of effect

RCT, randomized controlled trial.

Table 2.

Randomized Controlled Trials of Proton Pump Inhibitors for Functional Dyspepsia

Author	Study design and ITT population	Treatment	Key findings
Blum et al.²⁵	2-wk, multicenter, double-blind placebo-controlled, 792 patients with normal endoscopy, Rome for dyspepsia.	Ranitidine 150 mg od in the evening or omeprazole 10 mg od or 20 mg od in the morning vs. placebo	Omeprazole 20 mg per day improved dyspeptic symptoms in patients infected with H. pylori to a greater extent than in those who were H. pylori negative.
Talley et al.²⁶	4-wk, double blind, placebo-controlled, 1262 patients	Omeprazole 10 mg od or 20 mg od vs. placebo	Statistical improvement in GSRS between omeprazole 20 mg and placebo but not 10 mg and placebo.
Wong et al.²⁸	4-wk, double blind, placebo-controlled, 453 patients	Lansoprazole 30 mg od vs. lansoprazole 15 mg od vs. placebo	Proton pump inhibitor was not superior to placebo for the management of functional dyspepsia in Chinese patients.
Peura et al.³¹	8-wk, double blind, placebo-controlled, 921 patients	Lansoprazole 30 mg od vs. lansoprazole 15 mg od vs. placebo	Lansoprazole 15 mg or 30 mg was better than placebo in reducing symptoms of upper abdominal discomfort accompanied by at least some symptoms of heartburn.
Veldhuyzen et al.³²	8-wk, placebo-controlled, 502 patients	Esomeprazole 40 mg od vs. placebo	Esomeprazole was significantly more effective than placebo for symptom relief at 4 wk.

ITT, intention to treat; H. pylori, Helicobacter pylori; GSRS, gastrointestinal symptom rating scale.

Table 3.

Randomized Controlled Trials of Prokinetics for Functional Dyspepsia

Author	Study design and ITT population	Treatment	Key findings
al-Quorain et al.³⁷	4-wk, randomized double blind, 89 FD	Cisapride 10 mg t.d.s. vs. placebo	Reduced postprandial bloating, epigastric pain, early satiety, epigastric burning (p＜ 0.05)
Bekhti et al.³⁸	4-wk, randomized double blind, 40 FD	Domperidone 10 mg t.d.s. vs. placebo	Reduced FD symptoms (p＜0.05)
Chung⁴⁰	4-wk, randomized double blind, 29 FD	Cisapride 10 mg t.d.s. vs. placebo	Reduced bloating and epigastric discomfort (p＜0.05); improved global symptoms (p＜0.05)
de Groot et al.⁴¹	4-wk, randomized double blind, 121 FD	Cisapride 10 mg t.d.s. vs. placebo	Not superior to placebo in overall symptoms improvement
Halleback et al.⁴⁴	6-wk, randomized double blind, 606 FD	Mosapride 7.5 mg t.d.s. vs. placebo	Not superior to placebo in overall symptoms improvement
Holtmann et al.⁴⁸	8-wk, randomized double blind	Itopride 200 mg t.d.s. vs. placebo	Reduced pain and fullness (p＜0.05); improved global symptoms (p＜0.05)
Talley et al.⁵²	4-wk, randomized double blind	ABT-229 10 mg b.d.s. vs. placebo	Not superior to placebo in upper abdominal discomfort improvement
Talley et al.⁵⁷	8-wk, randomized double blind	Itopride 100 mg t.d.s. vs. placebo	Not superior to placebo in overall symptoms improvement
Arts et al.⁶⁰	Randomized double blind	Erythromycin 200 mg iv vs. placebo	Not superior to placebo in overall symptoms improvement

FD, functional dyspepsia.

Table 4.

Randomized Controlled Trials of Histamine 2 Receptor Antagonists for Functional Dyspepsia

Author	Study design and ITT population	Treatment	Key findings
Gotthard et al.³⁵	6-wk, randomized double blind; Rome criteria not used	Cimetidine 400 mg b.i.d., antacid 10 ml q.i.d., vs. placebo	Cimetidine was superior in relieving pain and nausea (p＜0.01), bloating (NS)
Hansen et al.⁴⁶	2-wk, randomized, double blind; Rome criteria not used	Nizatidine 300 mg q.d., cisapride 10 mg t.i.d., vs. placebo	Global symptoms: nizatidine was not superior to placebo.
Kato et al.⁶⁵	4-wk, randomized double blind, crossover; Rome II criteria	Famotidine 20 mg b.i.d., vs. placebo	Reduced pain (p＜0.01), indigestion, reflux symptom (p＜0.05)
Muller et al.⁶⁷	4-wk, randomized, double blind; Rome criteria not used	Ranitidine 150 mg b.i.d., vs. placebo	Disappearance of all dyspeptic symptoms: ranitidine was superior to placebo (p＜0.05)
Singal et al.⁷¹	4-wk, randomized, double blind; Rome criteria not used	Cimetidine 400 mg b.i.d., vs. placebo	Cimetidine was superior in relieving abdominal pain (p＜0.05)

TOOLS

Similar articles