Overlap of functional dyspepsia and GERD - Diagnostic and treatment implications

Nature Reviews Gastroenterology and Hepatology

Volumn 10, Issue 3, 2013, Pages 175-186

  Quigley, Eamonn M M ^a   Lacy, Brian E ^b  

^a UNIVERSITY COLLEGE CORK   (Ireland)

^b DARTMOUTH HITCHCOCK MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACOTIAMIDE; ALEMCINAL; AMITRIPTYLINE; ANTACID AGENT; CIMETIDINE; CISAPRIDE; CITALOPRAM; ERYTHROMYCIN; FAMOTIDINE; GUANINE NUCLEOTIDE BINDING PROTEIN; HERBACEOUS AGENT; HISTAMINE H2 RECEPTOR ANTAGONIST; IMIPRAMINE; INTESTINE CONTRACTION STIMULATING AGENT; ITOPRIDE; METOCLOPRAMIDE; NIZATIDINE; PLACEBO; PROKINETIC AGENT; PROTON PUMP INHIBITOR; RABEPRAZOLE; RANITIDINE; SEROTONIN NORADRENALIN REUPTAKE INHIBITOR; SEROTONIN UPTAKE INHIBITOR; STW 5 II; SUCRALFATE; TEGASEROD; TRICYCLIC ANTIDEPRESSANT AGENT; UNCLASSIFIED DRUG; UNINDEXED DRUG; VENLAFAXINE;

ACUPUNCTURE; ALTERNATIVE MEDICINE; ANXIETY DISORDER; CLINICAL EFFECTIVENESS; COMORBIDITY; DEPRESSION; DIGESTIVE SYSTEM DISEASE; DOSE RESPONSE; DRUG EFFECT; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DYSPEPSIA; ENDOSCOPY; ESOPHAGITIS; ESOPHAGUS PAIN; G PROTEIN BETA3 SUBUNIT GENE; GASTRIC DYSMOTILITY; GASTRIC PH MONITORING; GASTROESOPHAGEAL REFLUX; GENE LOCUS; GENETIC ANALYSIS; GENETIC POLYMORPHISM; HELICOBACTER PYLORI; HUMAN; INFECTION COMPLICATION; INFLAMMATION; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; QUESTIONNAIRE; REVIEW; STOMACH EMPTYING; STOMACH PH; SYMPTOM; UNSPECIFIED SIDE EFFECT; VISCERAL HYPERSENSITIVITY;

ANTACIDS; ANTIDEPRESSIVE AGENTS, TRICYCLIC; COMORBIDITY; DISEASE MANAGEMENT; DYSPEPSIA; GASTROESOPHAGEAL REFLUX; HISTAMINE ANTAGONISTS; HUMANS; PREVALENCE;

EID: 84875223634     PISSN: 17595045     EISSN: 17595053     Source Type: Journal    
DOI: 10.1038/nrgastro.2012.253     Document Type: Review

References (150)

1. Cornish, J. et al. A meta-Analysis on the influence of inflammatory bowel disease on pregnancy. Gut 56, 830-837 (2007
2. Zelinkova, Z. et al. Effects of discontinuing anti-Tumor necrosis factor therapy during pregnancy on the course of inflammatory bowel disease and neonatal exposure. Clin. Gastroenterol. Hepatol. http://dx.doi.org/10.1016/ j.cgh.2012.10.024
3. Dominitz, J. A., Young, J. C. & Boyko, E. J. Outcomes of infants born to mothers with inflammatory bowel disease: A population-based cohort study. Am. J. Gastroenterol. 97, 641-648 (2002
4. Reddy, D., Murphy, S. J., Kane, S. V., Present, D. H. & Kornbluth, A. A. Relapses of inflammatory bowel disease during pregnancy: In-hospital management and birth outcomes. Am. J. Gastroenterol. 103, 1203-1209 (2008
5. Singh, S., Sedgh, G. & Hussain, R. Unintended pregnancy: Worldwide levels, trends, and outcomes. Stud. Fam. Plann. 41, 241-250 (2010
6. Habal, F. M. & Huang, V. W. Review article: A decision-making algorithm for the management of pregnancy in the inflammatory bowel disease patient. Aliment. Pharmacol. Ther. 35, 501-515 (2012
7. Zelinkova, Z. et al. High intra-uterine exposure to infliximab following maternal anti-TNF treatment during pregnancy. Aliment. Pharmacol. Ther. 33, 1053-1058 (2011
8. Mahadevan, U. et al. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organisation: Pregnancy and pediatrics. Am. J. Gastroenterol. 106, 214-223 (2011
9. Mahadevan, U. et al. PIANO: A 1000 patient prospective registry of pregnancy outcomes in women with IBD exposed to immunomodulators and biologic therapy [abstract]. Gastroenterology 142 (Suppl. 5), S149 (2012
10. Ben-Horin, S. et al. Detection of infliximab in breast milk of nursing mothers with inflammatory bowel disease. J. Crohns Colitis 5, 555-558 (2011
11. Gilja, O. H., Hausken, T., Wilhelmsen, I. & Berstad, A. Impaired accommodation of proximal stomach to a meal in functional dyspepsia. Dig. Dis. Sci. 41, 689-696 (1996
12. Tack, J., Piessevaux, H., Coulie, B., Caenepeel, P. & Janssens, J. Role of impaired gastric accommodation to a meal in functional dyspepsia. Gastroenterology 115, 1346-1352 (1998
13. Kim, D. Y. et al. Noninvasive measurement of gastric accommodation in patients with idiopathic nonulcer dyspepsia. Am. J. Gastroenterol. 96, 3099-3105 (2001
14. Stanghellini, V. et al. Risk indicators of delayed gastric emptying of solids in patients with functional dyspepsia. Gastroenterology 110, 1036-1042 (1996
15. Tack, J., Bisschops, R. & Sarnelli, G. Pathophysiology and treatment of functional dyspepsia. Gastroenterology 127, 1239-1255 (2004
16. Quigley, E. M. Review article: Gastric emptying in functional gastrointestinal disorders. Aliment. Pharmacol. Ther. 20 (Suppl. 7), 56-60 (2004
17. Penagini, R. et al. Motor function of the proximal stomach and visceral perception in gastro-oesophageal reflux disease. Gut 42, 251-257 (1998
18. Vu, M. K. et al. Motor and sensory function of the proximal stomach in reflux disease and after laparoscopic Nissen fundoplication. Am. J. Gastroenterol. 94, 1481-1489 (1999
19. Gonlachanvit, S., Maurer, A. H., Fisher, R. S. & Parkman, H. P. Regional gastric emptying abnormalities in functional dyspepsia and gastro-oesophageal reflux disease. Neurogastroenterol. Motil. 18, 894-904 (2006
20. van Lelyveld, N., Scheffer, R., Mundt, M. & Samsom, M. Partial gastric volumes and upper abdominal sensations in functional dyspeptic and GERD patients: A 3D ultrasonographic study. Am. J. Gastroenterol. 101, 1845-1852 (2006
21. Miyamoto, M., Manabe, N. & Haruma, K. Efficacy of the addition of prokinetics for proton pump inhibitor (PPI) resistant non-erosive reflux disease (NERD) patients: Significance of frequency scale for the symptom of GERD (SSG) on decision of treatment strategy. Intern. Med. 49, 1469-1476 (2010
22. Futagami, S. et al. The prokinetic effect of mosapride citrate combined with omeprazole therapy improves clinical symptoms and gastric emptying in PPI-resistant NERD patients with delayed gastric emptying. J. Gastroenterol. 45, 413-421 (2010
23. Shindo, T. et al. Comparison of gastric emptying and plasma ghrelin levels in patients with functional dyspepsia and non-erosive reflux disease. Digestion 79, 65-72 (2009
24. Kindt, S. et al. Relationship between symptom pattern, assessed by the PAGI-SYM questionnaire, and gastric sensorimotor dysfunction in functional dyspepsia. Neurogastroenterol. Motil. 21, 1183-e105 (2009
25. Keohane, J. & Quigley, E. M. Functional dyspepsia: The role of visceral hypersensitivity in its pathogenesis. World J. Gastroenterol. 12, 2672-2676 (2006
26. George, A. A., Tsuchiyose, M. & Dooley, C. P. Sensitivity of the gastric mucosa to acid and duodenal contents in patients with nonulcer dyspepsia. Gastroenterology 101, 3-6 (1991
27. Samsom, M., Verhagen, M. A., vanBerge Henegouwen, G. P. & Smout, A. J. Abnormal clearance of exogenous acid and increased acid sensitivity of the proximal duodenum in dyspeptic patients. Gastroenterology 116, 515-520 (1999
28. Lee, K. J., 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. 286, G278-G284 (2004
29. Cicala, M. et al. Intra-oesophageal distribution and perception of acid reflux in patients with non-erosive gastro-oesophageal reflux disease. Aliment. Pharmacol. Ther. 18, 605-613 (2003
30. Hopwood, D., Milne, G. & Logan, K. R. Electron. microscopic changes in human oesophageal epithelium in oesophagitis. J. Pathol. 129, 161-167 (1979
31. Tobey, N. A., Carson, J. L., Alkiek, R. A. & Orlando, R. C. Dilated intercellular spaces: A morphological feature of acid reflux-damaged human esophageal epithelium. Gastroenterology 111, 1200-1205 (1996
32. Vela, M. F., Craft, B. M., Sharma, N., Freeman, J. & Hazen-Martin, D. Refractory heartburn: Comparison of intercellular space diameter in documented GERD vs. functional heartburn. Am. J. Gastroenterol. 106, 844-850 (2011
33. Yang, M. et al. Quantitative assessment and characterization of visceral hyperalgesia evoked by esophageal balloon distention and acid perfusion in patients with functional heartburn, nonerosive reflux disease, and erosive esophagitis. Clin. J. Pain 26, 326-331 (2010
34. Savarino, E. et al. The role of nonacid reflux in NERD: Lessons learned from impedance-pH monitoring in 150 patients off therapy. Am. J. Gastroenterol. 103, 2685-2693 (2008
35. Peura, D. A., Haber, M. M., Hunt, B. & Atkinson, S. Helicobacter pylori-negative gastritis in erosive esophagitis, nonerosive reflux disease or functional dyspepsia patients. J. Clin. Gastroenterol. 44, 180-185 (2010
36. Marshall, J. K. et al. Incidence and epidemiology of irritable bowel syndrome after a large waterborne outbreak of bacterial dysentery. Gastroenterology 131, 445-450 (2006
37. Zanini, B. et al. Incidence of post-infectious irritable bowel syndrome and functional intestinal disorders following a water-borne viral gastroenteritis outbreak. Am. J. Gastroenterol. 107, 891-899 (2012
38. Hanevik, K., Dizdar, V., Langeland, N. & Hausken, T. Development of functional gastrointestinal disorders after Giardia lamblia infection. BMC Gastroenterol. 9, 27 (2009
39. Mearin, F. et al. Dyspepsia and irritable bowel syndrome after a Salmonella gastroenteritis outbreak: One-year follow-up cohort study. Gastroenterology 129, 98-104 (2005
40. Dizdar, V., Gilja, O. H. & Hausken, T. Increased visceral sensitivity in Giardia-induced postinfectious irritable bowel syndrome and functional dyspepsia. Effect of the 5HT3-Antagonist ondansetron. Neurogastroenterol. Motil. 19, 977-982 (2007
41. Futagami, S. et al. Migration of eosinophils and CCR2-/CD68-double positive cells into the duodenal mucosa of patients with postinfectious functional dyspepsia. Am. J. Gastroenterol. 105, 1835-1842 (2010
42. Ford, A. C. et al. Prevalence of uninvestigated dyspepsia 8 years after a large waterborne outbreak of bacterial dysentery: A cohort study. Gastroenterology 138, 1727-1736 (2010
43. Parry, S. D. et al. Does bacterial gastroenteritis predispose people to functional gastrointestinal disorders? A prospective, community-based, case-control study. Am. J. Gastroenterol. 98, 1970-1975 (2003
44. Tack, J. et al. Clinical and pathophysiological characteristics of acute-onset functional dyspepsia. Gastroenterology 122, 1738-1747 (2002
45. Quigley, E. M. M. & Craig, O. F. Irritable bowel syndrome; update on pathophysiology and management. Turk. J. Gastroenterol. 23, 313-322 (2012
46. Craig, O. F., Hyland, N. P. & Quigley, E. M. Functional dyspepsia: Eosinophils, macrophages, and the postinfectious state. Gastroenterology 140, 1092-1095 (2011
47. Talley, N. J. et al. Non-ulcer dyspepsia and duodenal eosinophilia: An adult endoscopic population-based case-control study. Clin. Gastroenterol. Hepatol. 5, 1175-1183 (2007
48. Walker, M. M. et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment. Pharmacol. Ther. 29, 765-773 (2009
49. Walker, M. M. et al. Implications of eosinophilia in the normal duodenal biopsy -An association with allergy and functional dyspepsia. Aliment. Pharmacol. Ther. 31, 1229-1236 (2010
50. Ronkainen, J. et al. Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults: The population-based Kalixanda study. Gut 56, 615-620 (2007
51. Almansa, C., Devault, K. R. & Achem, S. R. A comprehensive review of eosinophilic esophagitis in adults. J. Clin. Gastroenterol. 45, 658-664 (2011
52. Schäppi, M. G. et al. Mast cell-nerve interactions in children with functional dyspepsia. J. Pediatr. Gastroenterol. Nutr. 47, 472-480 (2008
53. Gargala, G. et al. Duodenal intraepithelial T lymphocytes in patients with functional dyspepsia. World J. Gastroenterol. 13, 2333-2338 (2007
54. Kindt, S., Tertychnyy, A., de Hertogh, G., Geboes, K. & Tack, J. Intestinal immune activation in presumed post-infectious functional dyspepsia. Neurogastroenterol. Motil. 21, 832-e56 (2009
55. Liebregts, T. et al. Small bowel homing T cells are associated with symptoms and delayed gastric emptying in functional dyspepsia. Am. J. Gastroenterol. 106, 1089-1098 (2011
56. Ronkainen, J. et al. Lymphocytic oesophagitis, a condition in search of a disease? Gut 61, 1776 (2012
57. Creed, F. Somatisation in functional dyspepsia: Integrating gastric physiology with psychological state. Gut 57, 1642-1643 (2008
58. Van Oudenhove, L. et al. Determinants of symptoms in functional dyspepsia: Gastric sensorimotor function, psychosocial factors or somatisatioñGut 57, 1666-1673 (2008
59. Oh, J. H. et al. Relationship between psychological factors and quality of life in subtypes of gastroesophageal reflux disease. Gut Liver 3, 259-265 (2009
60. Lee, K. J., Kwon, H. C., Cheong, J. Y. & Cho, S. W. Demographic, clinical, and psychological characteristics of the heartburn groups classified using the Rome III criteria and factors associated with the responsiveness to proton pump inhibitors in the gastroesophageal reflux disease group. Digestion 79, 131-136 (2009
61. Moayyedi, P., Talley, N. J., Fennerty, M. B. & Vakil, N. Can the clinical history distinguish between organic and functional dyspepsiä JAMA 295, 1566-1576 (2006
62. Numans, M. E. & de Wit, N. J. Reflux symptoms in general practice: Diagnostic evaluation of the Carlsson-Dent gastroesophageal reflux disease questionnaire. Aliment. Pharmacol. Ther. 17, 1049-1055 (2003
63. Klauser, A. G., Schindlbeck, N. E. & Muller-Lissner, S. A. Symptoms in gastro-oesophageal reflux disease. Lancet 335, 205-208 (1990
64. Moayyedi, P. & Axon, A. T. R. The usefulness of the likelihood ratio in the diagnosis of dyspepsia and gastro-oesophageal reflux disease. Am. J. Gastroenterol. 4, 3122-3125 (1999
65. Garcia-Rodriguez, L. A. et al. Natural history of chest pain in GERD [abstract]. Gut 54 (Suppl. VII), A75 (2005
66. El-Serag, H. B. & Sonnenberg, A. Comorbid occurrence of laryngeal or pulmonary disease with esophagitis in US military veterans. Gastroenterology 113, 755-760 (1997
67. Gislason, T. et al. Respiratory symptoms and nocturnal gastro-oesophageal reflux: A population based study of young adults in three European countries. Chest 121, 158-163 (2002
68. Cremonini, F., Wise, J., Moayyedi, P. & Talley, N. Diagnostic and therapeutic use of PPIs in non-cardiac chest pain: A meta-Analysis. Am. J. Gastroenterol. 100, 1226-1232 (2005
69. Hammer, J., Eslick, G. D., Howell, S. C., Altiparmak, E. & Talley, N. J. Diagnostic yield of alarm features in irritable bowel syndrome and functional dyspepsia. Gut 53, 666-672 (2004
70. Talley, N. J., Vakil, N. B. & Moayyedi, P. American Gastroenterological Association technical review on the evaluation of dyspepsia. Gastroenterology 129, 1756-1780 (2005
71. Lacy, B. E. & Cash, B. D. A 32-year-old woman with chronic abdominal pain. JAMA 299, 555-565 (2008
72. Greatorex, R. A. & Thorpe, J. A. Clinical assessment of gastro-oesophageal reflux by questionnaire. Br. J. Clin. Pract. 37, 133-135 (1983
73. Locke, G. R., Talley, N. J., Weaver, A. L. & Zinsmeister, A. R. A new questionnaire for gastroesophageal reflux disease. Mayo Clin. Proc. 69, 539-547 (1994
74. Carlsson, R. et al. The usefulness of a structured questionnaire in the assessment of symptomatic gastroesophageal reflux disease. Scand. J. Gastroenterol. 33, 1023-1029 (1998
75. Shaw, M. J. et al. Initial validation of a diagnostic questionnaire for gastroesophageal reflux disease. Am. J. Gastroenterol. 96, 52-57 (2001
76. Moreno Elola-Olaso, C., Rey, E., Rodriguez-Artalejo, F., Locke, G. R. 3rd & Diaz-Rubio, M. Adaptation and validation of a gastroesophageal reflux questionnaire for use on a Spanish population. Rev. Esp. Enferm. Dig. 94, 745-758 (2002
77. Wong, W. M. et al. A validated symptoms questionnaire (Chinese GERDQ) for the diagnosis of gastro-esophageal reflux disease in the Chinese population. Aliment. Pharmacol. Ther. 17, 1407-1413 (2003
78. Wang, J. H. et al. Composite score of reflux symptoms in diagnosis of gastroesophageal reflux disease. World J. Gastroenterol. 10, 3332-3335 (2004
79. [No authors listed] Value of reflux diagnostic questionnaire in the diagnosis of gastroesophageal reflux disease. Chin. J. Dig. Dis. 5, 51-55 (2004
80. Zimmerman, J. Validation of a brief inventory for diagnosis and monitoring of symptomatic gastroesophageal reflux. Scand. J. Gastroenterol. 39, 212-216 (2004
81. Shimoyama, Y. et al. Diagnosis of gastroesophageal reflux disease using a new questionnaire. J. Gastroenterol. Hepatol. 20, 643-647 (2005
82. Horowitz, N., Moshkowitz, M., Halpern, Z. & Leshno, M. Applying data mining techniques in the development of a diagnostic questionnaire for GERD. Dig. Dis. Sci. 52, 1871-1878 (2007
83. Ho, K. Y. et al. Validation of a graded response questionnaire for the diagnosis of gastroesophageal reflux disease in an Asian primary care population. J. Clin. Gastroenterol. 42, 680-686 (2008
84. Kinekawa, F. et al. Is the questionnaire for the assessment of gastroesophageal reflux useful for diabetic patients? Scand. J. Gastroenterol. 40, 1017-1020 (2005
85. Hung, C. S. et al. Clinical application of Carlsson's questionnaire to predict erosive GERD among healthy Chinese. J. Gastroenterol. Hepatol. 20, 1900-1095 (2005
86. Lind, T. et al. Heartburn without esophagitis: Efficacy of omeprazole therapy and features determining therapeutic response. Scand. J. Gastroenterol. 32, 974-979 (1997
87. Mantynen, T. et al. The impact of upper GI endoscopy referral volume on the diagnosis of gastroesophageal reflux disease and its complications: A 1-year cross-sectional study in a referral area with 260,000 inhabitants. Am. J. Gastroenterol. 97, 2524-2529 (2002
88. Richter, J. E. Severe reflux esophagitis. Gastrointest. Endosc. Clin. N. Am. 4, 677-697 (1994
89. Lundell, L. R. et al. Endoscopic assessment of oesophagitis: Clinical and functional correlates and further validation of the Los Angeles classification. Gut 45, 172-180 (1999
90. Vigneri, S. et al. A comparison of five maintenance therapies for reflux esophagitis. N. Engl. J. Med. 333, 1106-1110 (1995
91. Kahrilas, P. J. et al. American Gastroenterological Association medical position statement on the management of gastroesophageal reflux disease. Gastroenterology 135, 1383-1391 (2008
92. Sharma, P. et al. A feasibility trial of narrow band imaging endoscopy in patients with gastroesophageal reflux disease. Gastroenterology 133, 454-464 (2007
93. Amano, Y. et al. Does magnifying endoscopy improve the diagnosis of erosive esophagitis? J. Gastroenterol. Hepatol. 23, 1063-1068 (2008
94. Small, P. K. et al. Importance of reflux symptoms in functional dyspepsia. Gut 36, 189-192 (1995
95. Bolling-Sternevald, E. et al. Effect of profound acid suppression in functional dyspepsia: A double-blind, randomized, placebo-controlled trial. Scand. J. Gastroenterol. 37, 1395-1402 (2002
96. Tack, J. et al. Prevalence of acid reflux in functional dyspepsia and its association with symptom profile. Gut 54, 1370-1376 (2005
97. Stacher, G. et al. Gastric emptying: A contributory factor in gastro-oesophageal reflux activity. Gut 47, 661-666 (2000
98. McCallum, R. W., Berkowitz, D. M. & Lerner, E. Gastric emptying in patients with gastroesophageal reflux. Gastroenterology 80, 285-291 (1981
99. Keshavarzian, A., Bushnell, D. L., Sontag, S., Yegelwel, E. J. & Smid, K. Gastric emptying in patients with severe reflux esophagitis. Am. J. Gastroenterol. 86, 738-742 (1991
100. Sarnelli, G. et al. Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia. Am. J. Gastroenterol. 98, 783-788 (2003
101. Maes, B. D., Ghoos, Y. F., Hiele, M. I. & Rutgeerts, P. J. Gastric emptying rate of solids in patients with nonulcer dyspepsia. Dig. Dis. Sci. 42, 1158-1162 (1997
102. Lacy, B. E. Functional dyspepsia and gastroparesis: One disease or twöAm. J. Gastroenterol. 107, 1615-1620 (2012
103. Sontag, S. J. Rolling review: Gastro-oesophageal reflux disease. Aliment. Pharmacol. Ther. 7, 293-298 (1993
104. Bell, N. J. V. & Hunt, R. H. Role of gastric acid suppression in the treatment of gastro-oesophageal reflux disease. Gut 33, 118-125 (1992
105. Moayyedi, P. et al. Pharmacological interventions for non-ulcer dyspepsia. Cochrane Database of Systematic Reviews, Issue 4. Art. No.: CD001960 http://dx.doi.org/10.1002/ 14651858.CD001960.pub3
106. Chiba, N., De Gara, C. J., Wilkinson, J. M. & Hunt, R. H. Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: A meta-Analysis. Gastroenterology 112, 1798-1810 (1997
107. Khan, M., Santana, J., Donnellan, C., Preston, C. & Moayyedi, P. Medical treatments in the short term management of reflux oesophagitis. Cochrane Database of Systematic Reviews, Issue 2. Art. No.: CD003244 http://dx.doi.org/10.1002.CD003244.pub2
108. Kahrilas, P. J. Gastroesophageal reflux disease. N. Engl. J. Med. 359, 1700-1707 (2008
109. Kahrilas, P. J., Howden, C. W. & Hughes, N. Response of regurgitation to proton pump inhibitor therapy in clinical trials of gastroesophageal reflux disease. Am. J. Gastroenterol. 106, 1419-1425 (2011
110. Tominaga, K. et al. Rikkunshito improves symptoms in PPI-refractory GERD patients: A prospective, randomized, multicenter trial in Japan. J. Gastroenterol. 47, 284-292 (2012
111. Wong, W. M. et al. Double blind, randomised, placebo controlled study of four weeks of lansoprazole for the treatment of functional dyspepsia in Chinese patients. Gut 51, 502-506 (2002
112. Peura, D. A. et al. Lansoprazole in the treatment of functional dyspepsia: Two double-blind, randomized, placebo-controlled trials. Am. J. Med. 116, 740-748 (2004
113. van Zanten, S. V. et al. Esomeprazole 40 mg once a day in patients with functional dyspepsia: The randomized, placebo-controlled "ENTER" trial. Am. J. Gastroenterol. 101, 2096-2106 (2008
114. van Rensburg, C. et al. Efficacy and safety of pantoprazole 20 mg once daily treatment in patients with ulcer-like functional dyspepsia. Curr. Med. Res. Opin. 24, 2009-2018 (2008
115. Wang, W. H. et al. Effects of proton-pump inhibitors on functional dyspepsia: A meta-Analysis of randomized placebo-controlled trials. Clin. Gastroenterol. Hepatol. 5, 178-185 (2007
116. Hameeteman, W. Clinical studies of sucralfate in reflux esophagitis: The European experience. J. Clin. Gastroenterol. 13 (Suppl. 2), 816-826 (1991
117. Williams, R. M. et al. Multicenter trial of sucralfate suspension for the treatment of reflux esophagitis. Am. J. Med. 83 (Suppl. 3B), 61-71 (1987
118. Misra, S. P., Dwivedi, M., Misra, V. & Agarwal, S. K. Sucralfate versus ranitidine in non-ulcer dyspepsia: Results of a prospective, randomized, open, controlled trial. Indian J. Gastroenterol. 11, 7-8 (1992
119. McCallum, R. W., Kline, M. M., Curry, N. & Sturdevant, R. A. Comparative effects of metoclopramide and bethanechol on lower esophageal sphincter pressure in reflux patients. Gastroenterology 68, 1114-1118 (1975
120. McCallum, R. W., Fink, S. M., Lerner, E. & Berkowitz, D. M. Effects of metoclopramide and bethanechol on delayed gastric emptying present in gastroesophageal reflux patients. Gastroenterology 84, 1573-1577 (1983
121. Saco, L. S. et al. Double-blind controlled trial of bethanechol and antacid versus placebo and antacid in the treatment of erosive esophagitis. Gastroenterology 82, 1369-1373 (1982
122. Orenstein, S. R., Lofton, S. W. & Orenstein, D. M. Bethanechol for pediatric gastroesophageal reflux: A prospective, blind, controlled study. J. Pediatr. Gastroenterol. Nutr. 5, 549-555 (1986
123. Champion, G., Richter, J. E., Singh, S., Schan, C. & Nellans, H. Effects of oral erythromycin on esophageal pH and pressure profiles in patients with gastroesophageal reflux disease. Dig. Dis. Sci. 39, 129-137 (1994
124. Pasricha, P. J., Pehlivanov, N., Sugumar, A. & Jankovic, J. Drug Insight: From disturbed motility to disordered movement -A review of the clinical benefits and medicolegal risks of metoclopramide. Nat. Clin. Pract. Gastroenterol. Hepatol. 3, 138-148 (2006
125. Quigley, E. M. M. Cisapride. What can we learn from the rise and fall of a prokinetic? J. Dig. Dis. 12, 147-156 (2011
126. Vakil, N. et al. Tegaserod treatment for dysmotility-like functional dyspepsia: Results of two randomized, controlled trials. Am. J. Gastroenterol. 101, 1906-1919 (2008
127. Holtmann, G., Talley, N. J., Liebregts, T., Adam, B. & Parow, C. A placebo-controlled trial of itopride in functional dyspepsia. N. Engl. J. Med. 354, 832-840 (2006
128. Talley, N. J., 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 57, 740-746 (2008
129. Hallerbäck, B. I. et al. Dose finding study of mosapride in functional dyspepsia: A placebo-controlled, randomized study. Aliment. Pharmacol. Ther. 16, 959-967 (2002
130. Tack, J. et al. A dose-ranging, placebo-controlled, pilot trial of acotiamide in patients with functional dyspepsia. Neurogastroenterol. Motil. 21, 272-280 (2009
131. Matsueda, K. et al. Clinical trial: Dose-dependent therapeutic efficacy of acotiamide hydrochloride (Z-338) in patients with functional dyspepsia -100 mg t.i.d. is an optimal dose. Neurogastroenterol. Motil. 22, 618-e173 (2010
132. Matsueda, K. et al. A placebo-controlled trial of acotiamide for meal-related symptoms of functional dyspepsia. Gut 61, 821-828 (2012
133. Talley, N. J. 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. 14, 1653-1661 (2000
134. Saarto, T. & Wiffen, P. J. Antidepressants for neuropathic pain. Cochrane Database of Systematic Reviews, Issue 4, Art. No.: CD005454. http://dx/doi.org/ 10.1002.14651858.CD005454.pub2
135. Ford, A. C., Talley, N., Schoenfeld, P. S., Quigley, E. M. & Moayyedi, P. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: Systematic review and meta-Analysis. Gut 58, 367-378 (2009
136. Mertz, H. et al. Effect of amitriptyline on symptoms, sleep, and visceral perception in patients with functional dyspepsia. Am. J. Gastroenterol. 93, 160-165 (1998
137. Otaka, M. et al. New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline. Aliment. Pharmacol. Ther. 21 (Suppl. 2), 42-46 (2005
138. Wu, J. C. et al. A randomized, double-blind, placebo-controlled trial of low dose imipramine for treatment of refractory functional dyspepsia (FD) [Abstact]. Gastroenterology 140 (Suppl. 1) S-50 (2011
139. Viazis, N. et al. Selective-serotonin reuptake inhibitors for the treatment of hypersensitive esophagus. A placebo controlled study using esophageal pH-impedance monitoring. Am. J. Gastroenterol. 107, 1662-1667 (2012
140. van Kerkhoven, L. A. et al. Effect of the antidepressant venlafaxine in functional dyspepsia: A randomized, double-blind, placebo-controlled trial. Clin. Gastroenterol. Hepatol. 6, 746-752 (2008
141. Eisenberg, D. M. et al. Trends in alternative medicine use in the United States, 1990-1997: Results of a follow-up national survey. JAMA 280, 1569-1575 (1998
142. Barnes, P. M., Powell-Griner, E., McFann, K. & Nahin, R. L. Complementary and alternative medicine use among adults: United States, 2002. Adv. Data 343, 1-19 (2004
143. Dickman, R. et al. Clinical trial: Acupuncture vs. doubling the proton pump inhibitor dose in refractory heartburn. Aliment. Pharmacol. Ther. 26, 1333-1344 (2007
144. Madisch, A., Holtmann, G., Mayr, G., Vinson, B. & Hotz, J. Treatment of functional dyspepsia with a herbal preparation. A double-blind, randomized, placebo-controlled, multicenter trial. Digestion 69, 45-52 (2004
145. von Arnim, U., Peitz, U., Vinson, B., Gundermann, K. J. & Malfertheiner, P. STW 5, a phytopharmacon for patients with functional dyspepsia: Results of a multicenter, placebo-controlled double-blind study. Am. J. Gastroenterol. 102, 1268-1275 (2007
146. Braden, B., Caspary, W., Borner, N., Vinson, B. & Schneider, A. R. J. Clinical effects of STW 5 (Iberogast) are not based on acceleration of gastric emptying in patients with functional dyspepsia and gastroparesis. Neurogastroenterol. Motil. 21, 632-639 (2009
147. Holtmann, G. et al. Efficacy of artichoke leaf extract in the treatment of patients with functional dyspepsia: A six-week placebo-controlled, double-blind, multicentre trial. Aliment. Pharmacol. Ther. 18, 1099-1105 (2003
148. May, B., Kohler, S. & Schneider, B. Efficacy and tolerability of a fixed combination of peppermint oil and caraway oil in patients suffering from functional dyspepsia. Aliment. Pharmacol. Ther. 14, 1671-1677 (2000
149. Quigley, E. M. & DiBaise, J. K. Non-erosive reflux disease: The real problem in gastro-oesophageal reflux disease. Dig. Liver Dis. 33, 523-527 (2001
150. Quigley, E. M. Functional dyspepsia (FD) and non-erosive reflux disease (NERD): Overlapping or discrete entities? Best Pract. Res. Clin. Gastroenterol. 18, 695-706 (2004