Skip to main content
Log in

Functional Dyspepsia: Diagnostic and Therapeutic Approaches

Drugs Aims and scope Submit manuscript

Abstract

Functional dyspepsia is a common functional gastrointestinal (GI) disorder of gastroduodenal origin, diagnosed clinically in the presence of prototypical symptoms of epigastric pain and meal-related symptoms, and without structural explanation. The most recent diagnostic criteria provide for two functional dyspepsia subtypes, epigastric pain syndrome (EPS) and post-prandial distress syndrome (PDS) based on the predominant symptom pattern. The evaluation of dyspepsia should keep laboratory, imaging, and invasive testing to a minimum, as extensive or repetitive investigations are of rather low diagnostic yield in the absence of localizing symptoms or alarm features. Factors with etiopathologic relationships to functional dyspepsia include micro-inflammation, GI infections, abnormalities of gastroduodenal motility, visceral hypersensitivity, disturbances along the brain-gut axis, and psychological factors; all of these causative mechanisms have potential to partially explain symptoms in some functional dyspepsia patients, thus providing a rationale for the efficacy of a diversity of therapeutic approaches to functional dyspepsia. Management of dyspepsia symptoms relies upon both pharmacologic treatments and non-pharmacologic approaches, including psychological and complementary interventions. The evidence in support of established functional dyspepsia therapies is reviewed, and forms the basis for an effective functional dyspepsia treatment strategy emphasizing the patient’s current symptom severity, pattern, and impact on the function and quality of life of the individual.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  1. Functional Gastrointestinal Disorders. Disorders of gut–brain interaction. Raleigh: Rome Foundation; 2016.

    Google Scholar 

  2. Stanghellini V, Chan FK, Hasler WL, et al. Gastroduodenal disorders. Gastroenterology. 2016;150:1380–92.

    PubMed  Google Scholar 

  3. Talley NJ, Ford AC. Functional dyspepsia. N Engl J Med. 2015;373:1853–63.

    CAS  PubMed  Google Scholar 

  4. Mahadeva S, Goh KL. Epidemiology of functional dyspepsia: a global perspective. World J Gastroenterol. 2006;12:2661–6.

    PubMed  PubMed Central  Google Scholar 

  5. Ford AC, Marwaha A, Sood R, et al. Global prevalence of, and risk factors for, uninvestigated dyspepsia: a meta-analysis. Gut. 2015;64:1049–57.

    PubMed  Google Scholar 

  6. Ford AC, Forman D, Bailey AG, et al. Who consults with dyspepsia? Results from a longitudinal 10-year follow-up study. Am J Gastroenterol. 2007;102:957–65.

    PubMed  Google Scholar 

  7. McBride D, Hardoon S, Walters K, et al. Explaining variation in referral from primary to secondary care: cohort study. BMJ. 2010;341:c6267.

    PubMed  PubMed Central  Google Scholar 

  8. Shaib Y, El-Serag HB. The prevalence and risk factors of functional dyspepsia in a multiethnic population in the United States. Am J Gastroenterol. 2004;99:2210–6.

    PubMed  Google Scholar 

  9. Koloski NA, Talley NJ, Boyce PM. Epidemiology and health care seeking in the functional GI disorders: a population-based study. Am J Gastroenterol. 2002;97:2290–9.

    PubMed  Google Scholar 

  10. Tougas G, Chen Y, Hwang P, Domestic/International Gastroenterology Surveillance Study, et al. Prevalence and impact of upper gastrointestinal symptoms in the Canadian population: findings from the DIGEST study. Am J Gastroenterol. 1999;94:2845–54.

    CAS  PubMed  Google Scholar 

  11. Hirakawa K, Adachi K, Amano K, et al. Prevalence of non-ulcer dyspepsia in the Japanese population. J Gastroenterol Hepatol. 1999;14:1083–7.

    CAS  PubMed  Google Scholar 

  12. Aro P, Talley NJ, Agreus L, et al. Functional dyspepsia impairs quality of life in the adult population. Aliment Pharmacol Ther. 2011;33:1215–24.

    CAS  PubMed  Google Scholar 

  13. Moayyedi P, Mason J. Cost-utility and cost-benefit analyses: how did we get here and where are we going? Eur J Gastroenterol Hepatol. 2004;16:527–34.

    PubMed  Google Scholar 

  14. Lacy BE, Weiser KT, Kennedy AT, et al. Functional dyspepsia: the economic impact to patients. Aliment Pharmacol Ther. 2013;38:170–7.

    CAS  PubMed  Google Scholar 

  15. Brook RA, Kleinman NL, Choung RS, et al. Functional dyspepsia impacts absenteeism and direct and indirect costs. Clin Gastroenterol Hepatol. 2010;8:498–503.

    PubMed  Google Scholar 

  16. Ford AC, Forman D, Bailey AG, et al. Effect of dyspepsia on survival: a longitudinal 10-year follow-up study. Am J Gastroenterol. 2012;107:912–21.

    PubMed  Google Scholar 

  17. Palsson OS, Whitehead WE, van Tilburg MA, et al. Rome IV Diagnostic Questionnaires and Tables for Investigators and Clinicians. Gastroenterology. 2016.

  18. Suzuki H, Kusunoki H, Kamiya T, et al. Effect of lansoprazole on the epigastric symptoms of functional dyspepsia (ELF study): a multicentre, prospective, randomized, double-blind, placebo-controlled clinical trial. United Eur Gastroenterol J. 2013;1:445–52.

    Google Scholar 

  19. Fang YJ, Liou JM, Chen CC, et al. Distinct aetiopathogenesis in subgroups of functional dyspepsia according to the Rome III criteria. Gut. 2015;64:1517–28.

    PubMed  Google Scholar 

  20. Zagari RM, Law GR, Fuccio L, et al. Epidemiology of functional dyspepsia and subgroups in the Italian general population: an endoscopic study. Gastroenterology. 2010;138:1302–11.

    PubMed  Google Scholar 

  21. Tack J, Talley NJ. Functional dyspepsia–symptoms, definitions and validity of the Rome III criteria. Nat Rev Gastroenterol Hepatol. 2013;10:134–41.

    CAS  PubMed  Google Scholar 

  22. Ford AC, Bercik P, Morgan DG, et al. Validation of the Rome III criteria for the diagnosis of irritable bowel syndrome in secondary care. Gastroenterology. 2013;145(1262–70):e1.

    Google Scholar 

  23. Vakil N, Moayyedi P, Fennerty MB, et al. Limited value of alarm features in the diagnosis of upper gastrointestinal malignancy: systematic review and meta-analysis. Gastroenterology. 2006;131:390–401 (quiz 659–60).

    PubMed  Google Scholar 

  24. Moayyedi P, Talley NJ, Fennerty MB, et al. Can the clinical history distinguish between organic and functional dyspepsia? JAMA. 2006;295:1566–76.

    CAS  PubMed  Google Scholar 

  25. Sayuk GS, Elwing JE, Lustman PJ, et al. High somatic symptom burdens and functional gastrointestinal disorders. Clin Gastroenterol Hepatol. 2007;5:556–62.

    PubMed  Google Scholar 

  26. Whitehead WE, Palsson OS, Levy RR, et al. Comorbidity in irritable bowel syndrome. Am J Gastroenterol. 2007;102:2767–76.

    PubMed  Google Scholar 

  27. Brown WH, Chey WD, Elta GH. Number of responses on a review of systems questionnaire predicts the diagnosis of functional gastrointestinal disorders. J Clin Gastroenterol. 2003;36:222–7.

    PubMed  Google Scholar 

  28. Wauters L, Talley NJ, Walker MM, et al. Novel concepts in the pathophysiology and treatment of functional dyspepsia. Gut. 2020;69:591–600.

    PubMed  Google Scholar 

  29. Talley NJ, Walker MM, Holtmann G. Functional dyspepsia. Curr Opin Gastroenterol. 2016;32:467–73.

    CAS  PubMed  Google Scholar 

  30. Delgado-Aros S, Camilleri M, Cremonini F, et al. Contributions of gastric volumes and gastric emptying to meal size and postmeal symptoms in functional dyspepsia. Gastroenterology. 2004;127:1685–94.

    PubMed  Google Scholar 

  31. Ardila-Hani A, Arabyan M, Waxman A, et al. Severity of dyspeptic symptoms correlates with delayed and early variables of gastric emptying. Dig Dis Sci. 2013;58:478–87.

    PubMed  Google Scholar 

  32. Park SY, Acosta A, Camilleri M, et al. Gastric motor dysfunction in patients with functional gastroduodenal symptoms. Am J Gastroenterol. 2017;112:1689–99.

    PubMed  Google Scholar 

  33. Vanheel H, Carbone F, Valvekens L, et al. Pathophysiological abnormalities in functional dyspepsia subgroups according to the Rome III criteria. Am J Gastroenterol. 2017;112:132–40.

    CAS  PubMed  Google Scholar 

  34. Tack J, Bisschops R, Sarnelli G. Pathophysiology and treatment of functional dyspepsia. Gastroenterology. 2004;127:1239–55.

    PubMed  Google Scholar 

  35. Talley NJ, Locke GR 3rd, Lahr BD, et al. Functional dyspepsia, delayed gastric emptying, and impaired quality of life. Gut. 2006;55:933–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Bisschops R, Karamanolis G, Arts J, et al. Relationship between symptoms and ingestion of a meal in functional dyspepsia. Gut. 2008;57:1495–503.

    CAS  PubMed  Google Scholar 

  37. Sarnelli G, Caenepeel P, Geypens B, et al. Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia. Am J Gastroenterol. 2003;98:783–8.

    PubMed  Google Scholar 

  38. Tack J, Piessevaux H, Coulie B, et al. Role of impaired gastric accommodation to a meal in functional dyspepsia. Gastroenterology. 1998;115:1346–52.

    CAS  PubMed  Google Scholar 

  39. Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology. 2007;132:397–414.

    CAS  PubMed  Google Scholar 

  40. Tornblom H, Holmvall P, Svenungsson B, et al. Gastrointestinal symptoms after infectious diarrhea: a 5-year follow-up in a Swedish cohort of adults. Clin Gastroenterol Hepatol. 2007;5:461–4.

    PubMed  Google Scholar 

  41. Mearin F, Perez-Oliveras M, Perello A, et al. Dyspepsia and irritable bowel syndrome after a Salmonella gastroenteritis outbreak: 1-year follow-up cohort study. Gastroenterology. 2005;129:98–104.

    PubMed  Google Scholar 

  42. Gwee KA, Leong YL, Graham C, et al. The role of psychological and biological factors in postinfective gut dysfunction. Gut. 1999;44:400–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Ohman L, Simren M. Intestinal microbiota and its role in irritable bowel syndrome (IBS). Curr Gastroenterol Rep. 2013;15:323.

    PubMed  Google Scholar 

  44. Vanheel H, Vicario M, Vanuytsel T, et al. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia. Gut. 2014;63:262–71.

    CAS  PubMed  Google Scholar 

  45. Ronkainen J, Talley NJ, Aro P, et al. Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults: the population-based Kalixanda study. Gut. 2007;56:615–20.

    PubMed  Google Scholar 

  46. Walker MM, Aggarwal KR, Shim LS, et al. Duodenal eosinophilia and early satiety in functional dyspepsia: confirmation of a positive association in an Australian cohort. J Gastroenterol Hepatol. 2014;29:474–9.

    PubMed  Google Scholar 

  47. Talley NJ, Walker MM, Aro P, et al. Non-ulcer dyspepsia and duodenal eosinophilia: an adult endoscopic population-based case–control study. Clin Gastroenterol Hepatol. 2007;5:1175–83.

    PubMed  Google Scholar 

  48. Cirillo C, Bessissow T, Desmet AS, et al. Evidence for neuronal and structural changes in submucous ganglia of patients with functional dyspepsia. Am J Gastroenterol. 2015;110:1205–15.

    CAS  PubMed  Google Scholar 

  49. Liebregts T, Adam B, Bredack C, et al. Small bowel homing T cells are associated with symptoms and delayed gastric emptying in functional dyspepsia. Am J Gastroenterol. 2011;106:1089–98.

    CAS  PubMed  Google Scholar 

  50. Amieva MR, El-Omar EM. Host–bacterial interactions in Helicobacter pylori infection. Gastroenterology. 2008;134:306–23.

    CAS  PubMed  Google Scholar 

  51. Turkkan E, Uslan I, Acarturk G, et al. Does Helicobacter pylori-induced inflammation of gastric mucosa determine the severity of symptoms in functional dyspepsia? J Gastroenterol. 2009;44:66–70.

    PubMed  Google Scholar 

  52. Henningsen P, Zimmermann T, Sattel H. Medically unexplained physical symptoms, anxiety, and depression: a meta-analytic review. Psychosom Med. 2003;65:528–33.

    PubMed  Google Scholar 

  53. Van Oudenhove L, Aziz Q. The role of psychosocial factors and psychiatric disorders in functional dyspepsia. Nat Rev Gastroenterol Hepatol. 2013;10:158–67.

    PubMed  Google Scholar 

  54. Piessevaux H, De Winter B, Louis E, et al. Dyspeptic symptoms in the general population: a factor and cluster analysis of symptom groupings. Neurogastroenterol Motil. 2009;21:378–88.

    CAS  PubMed  Google Scholar 

  55. Koloski NA, Talley NJ, Boyce PM. The impact of functional gastrointestinal disorders on quality of life. Am J Gastroenterol. 2000;95:67–71.

    CAS  PubMed  Google Scholar 

  56. Kindt S, Van Oudenhove L, Mispelon L, et al. Longitudinal and cross-sectional factors associated with long-term clinical course in functional dyspepsia: a 5-year follow-up study. Am J Gastroenterol. 2011;106:340–8.

    PubMed  Google Scholar 

  57. Aro P, Talley NJ, Ronkainen J, et al. Anxiety is associated with uninvestigated and functional dyspepsia (Rome III criteria) in a Swedish population-based study. Gastroenterology. 2009;137:94–100.

    PubMed  Google Scholar 

  58. Koloski NA, Jones M, Kalantar J, et al. The brain–gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based study. Gut. 2012;61:1284–90.

    CAS  PubMed  Google Scholar 

  59. Kanuri N, Cassell B, Bruce SE, et al. The impact of abuse and mood on bowel symptoms and health-related quality of life in irritable bowel syndrome (IBS). Neurogastroenterol Motil. 2016;28:1508–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Jones MP, Coppens E, Vos R, et al. A multidimensional model of psychobiological interactions in functional dyspepsia: a structural equation modelling approach. Gut. 2013;62:1573–80.

    PubMed  Google Scholar 

  61. Kano M, Dupont P, Aziz Q, et al. Understanding neurogastroenterology from neuroimaging perspective: a comprehensive review of functional and structural brain imaging in functional gastrointestinal disorders. J Neurogastroenterol Motil. 2018;24:512–27.

    PubMed  PubMed Central  Google Scholar 

  62. Duncanson KR, Talley NJ, Walker MM, et al. Food and functional dyspepsia: a systematic review. J Hum Nutr Diet. 2018;31:390–407.

    CAS  PubMed  Google Scholar 

  63. Ferch CC, Chey WD. Irritable bowel syndrome and gluten sensitivity without celiac disease: separating the wheat from the chaff. Gastroenterology. 2012;142:664–6.

    PubMed  Google Scholar 

  64. Vazquez-Roque MI, Camilleri M, Smyrk T, et al. A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function. Gastroenterology. 2013;144(903–911):e3.

    Google Scholar 

  65. Locke GR 3rd, Zinsmeister AR, Talley NJ, et al. Familial association in adults with functional gastrointestinal disorders. Mayo Clin Proc. 2000;75:907–12.

    PubMed  Google Scholar 

  66. Gathaiya N, Locke GR 3rd, Camilleri M, et al. Novel associations with dyspepsia: a community-based study of familial aggregation, sleep dysfunction and somatization. Neurogastroenterol Motil. 2009;21:922–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Kushnir VM, Cassell B, Gyawali CP, et al. Genetic variation in the beta-2 adrenergic receptor (ADRB2) predicts functional gastrointestinal diagnoses and poorer health-related quality of life. Aliment Pharmacol Ther. 2013;38:313–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Holtmann G, Siffert W, Haag S, et al. G-protein beta 3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia. Gastroenterology. 2004;126:971–9.

    CAS  PubMed  Google Scholar 

  69. van Lelyveld N, Linde JT, Schipper M, et al. Candidate genotypes associated with functional dyspepsia. Neurogastroenterol Motil. 2008;20:767–73.

    PubMed  Google Scholar 

  70. Camilleri CE, Carlson PJ, Camilleri M, et al. A study of candidate genotypes associated with dyspepsia in a US community. Am J Gastroenterol. 2006;101:581–92.

    CAS  PubMed  Google Scholar 

  71. Klenke S, Siffert W. SNPs in genes encoding G proteins in pharmacogenetics. Pharmacogenomics. 2011;12:633–54.

    CAS  PubMed  Google Scholar 

  72. Camilleri M, Katzka DA. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Genetic epidemiology and pharmacogenetics in irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2012;302:G1075–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Tack J, Jones MP, Karamanolis G, et al. Symptom pattern and pathophysiological correlates of weight loss in tertiary-referred functional dyspepsia. Neurogastroenterol Motil. 2010;22(29–35):e4–5.

    Google Scholar 

  74. Bytzer P, Hallas J. Drug-induced symptoms of functional dyspepsia and nausea. A symmetry analysis of one million prescriptions. Aliment Pharmacol Ther. 2000;14:1479–84.

    CAS  PubMed  Google Scholar 

  75. Hallas J, Bytzer P. Screening for drug related dyspepsia: an analysis of prescription symmetry. Eur J Gastroenterol Hepatol. 1998;10:27–32.

    CAS  PubMed  Google Scholar 

  76. Talley NJ, Vakil N, Practice Parameters Committee of the American College of G. Guidelines for the management of dyspepsia. Am J Gastroenterol. 2005;100:2324–37.

    PubMed  Google Scholar 

  77. Makristathis A, Hirschl AM, Lehours P, et al. Diagnosis of Helicobacter pylori infection. Helicobacter. 2004;9(Suppl 1):7–14.

    PubMed  Google Scholar 

  78. Best LM, Takwoingi Y, Siddique S, et al. Non-invasive diagnostic tests for Helicobacter pylori infection. Cochrane Database Syst Rev 2018;3:CD012080.

  79. Moayyedi P, Lacy BE, Andrews CN, et al. ACG and CAG Clinical Guideline: management of dyspepsia. Am J Gastroenterol. 2017;112:988–1013.

    CAS  PubMed  Google Scholar 

  80. Petrarca L, Nenna R, Mastrogiorgio G, et al. Dyspepsia and celiac disease: prevalence, diagnostic tools and therapy. World J Methodol. 2014;4:189–96.

    PubMed  PubMed Central  Google Scholar 

  81. Tack J, Janssen P. Gastroduodenal motility. Curr Opin Gastroenterol. 2010;26:647–55.

    PubMed  Google Scholar 

  82. Vakil NB, Howden CW, Moayyedi P, et al. White Paper AGA: Functional Dyspepsia. Clin Gastroenterol Hepatol. 2017;15:1191–4.

    PubMed  Google Scholar 

  83. Taylor F, Higgins S, Carson RT, et al. Development of a symptom-focused patient-reported outcome measure for functional dyspepsia: the functional dyspepsia symptom diary (functional dyspepsia SD). Am J Gastroenterol. 2018;113:39–48.

    PubMed  Google Scholar 

  84. Lan L, Yu J, Chen YL, et al. Symptom-based tendencies of Helicobacter pylori eradication in patients with functional dyspepsia. World J Gastroenterol. 2011;17:3242–7.

    PubMed  PubMed Central  Google Scholar 

  85. O’Morain C. Role of Helicobacter pylori in functional dyspepsia. World J Gastroenterol. 2006;12:2677–80.

    PubMed  PubMed Central  Google Scholar 

  86. Chey WD, Leontiadis GI, Howden CW, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017;112:212–39.

    PubMed  Google Scholar 

  87. Vaezi MF, Yang YX, Howden CW. Complications of proton pump inhibitor therapy. Gastroenterology. 2017;153:35–48.

    CAS  PubMed  Google Scholar 

  88. Moayyedi P, Leontiadis GI. The risks of PPI therapy. Nat Rev Gastroenterol Hepatol. 2012;9:132–9.

    CAS  PubMed  Google Scholar 

  89. Pinto-Sanchez MI, Yuan Y, Bercik P, et al. Proton pump inhibitors for functional dyspepsia. Cochrane Database Syst Rev 2017;3:CD011194.

  90. Van Den Houte K, Carbone F, Tack J. Postprandial distress syndrome: stratification and management. Expert Rev Gastroenterol Hepatol. 2019;13:37–46.

    Google Scholar 

  91. Carbone F, Tack J. Gastroduodenal mechanisms underlying functional gastric disorders. Dig Dis. 2014;32:222–9.

    CAS  PubMed  Google Scholar 

  92. Tack J, Camilleri M. New developments in the treatment of gastroparesis and functional dyspepsia. Curr Opin Pharmacol. 2018;43:111–7.

    CAS  PubMed  Google Scholar 

  93. Pittayanon R, Yuan Y, Bollegala NP, et al. Prokinetics for functional dyspepsia: a systematic review and meta-analysis of randomized control trials. Am J Gastroenterol. 2019;114:233–43.

    PubMed  Google Scholar 

  94. Tack J, Camilleri M, Chang L, et al. Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther. 2012;35:745–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Al-Saffar A, Lennernas H, Hellstrom PM. Gastroparesis, metoclopramide, and tardive dyskinesia: risk revisited. Neurogastroenterol Motil. 2019;e13617.

  96. Nennstiel S, Bajbouj M, Schmid RM, et al. Prucalopride reduces the number of reflux episodes and improves subjective symptoms in gastroesophageal reflux disease: a case series. J Med Case Rep. 2014;8:34.

    PubMed  PubMed Central  Google Scholar 

  97. Leelakanok N, Holcombe A, Schweizer ML. Domperidone and risk of ventricular arrhythmia and cardiac death: a systematic review and meta-analysis. Clin Drug Investig. 2016;36:97–107.

    CAS  PubMed  Google Scholar 

  98. Morris AD, Chen J, Lau E, et al. Domperidone-associated QT interval prolongation in non-oncologic pediatric patients: a review of the literature. Can J Hosp Pharm. 2016;69:224–30.

    PubMed  PubMed Central  Google Scholar 

  99. Degen L, Matzinger D, Merz M, et al. Tegaserod, a 5-HT4 receptor partial agonist, accelerates gastric emptying and gastrointestinal transit in healthy male subjects. Aliment Pharmacol Ther. 2001;15:1745–51.

    CAS  PubMed  Google Scholar 

  100. Chey WD, Howden CW, Tack J, et al. Long-term tegaserod treatment for dysmotility-like functional dyspepsia: results of two identical 1-year cohort studies. Dig Dis Sci. 2010;55:684–97.

    PubMed  Google Scholar 

  101. Vakil N, Laine L, Talley NJ, et al. Tegaserod treatment for dysmotility-like functional dyspepsia: results of two randomized, controlled trials. Am J Gastroenterol. 2008;103:1906–19.

    PubMed  Google Scholar 

  102. Loughlin J, Quinn S, Rivero E, et al. Tegaserod and the risk of cardiovascular ischemic events: an observational cohort study. J Cardiovasc Pharmacol Ther. 2010;15:151–7.

    PubMed  Google Scholar 

  103. Tack J, Janssen P, Masaoka T, et al. Efficacy of buspirone, a fundus-relaxing drug, in patients with functional dyspepsia. Clin Gastroenterol Hepatol. 2012;10:1239–45.

    CAS  PubMed  Google Scholar 

  104. Altan E, Masaoka T, Farre R, et al. Acotiamide, a novel gastroprokinetic for the treatment of patients with functional dyspepsia: postprandial distress syndrome. Expert Rev Gastroenterol Hepatol. 2012;6:533–44.

    CAS  PubMed  Google Scholar 

  105. Matsueda K, Hongo M, Ushijima S, et al. A long-term study of acotiamide in patients with functional dyspepsia: results from an open-label phase III trial in Japan on efficacy, safety and pattern of administration. Digestion. 2011;84:261–8.

    CAS  PubMed  Google Scholar 

  106. Pasricha PJ, Yates KP, Sarosiek I, et al. Aprepitant has mixed effects on nausea and reduces other symptoms in patients with gastroparesis and related disorders. Gastroenterology. 2018;154(65–76):e11.

    Google Scholar 

  107. Spirling LI, Daniels IR. Botanical perspectives on health peppermint: more than just an after-dinner mint. J R Soc Promot Health. 2001;121:62–3.

    CAS  PubMed  Google Scholar 

  108. Li J, Lv L, Zhang J, et al. A combination of peppermint oil and caraway oil for the treatment of functional dyspepsia: a systematic review and meta-analysis. Evid Based Complement Alternat Med. 2019;2019:7654947.

    PubMed  PubMed Central  Google Scholar 

  109. Rosch W, Liebregts T, Gundermann KJ, et al. Phytotherapy for functional dyspepsia: a review of the clinical evidence for the herbal preparation STW 5. Phytomedicine. 2006;13(Suppl 5):114–21.

    PubMed  Google Scholar 

  110. Rosch W, Vinson B, Sassin I. A randomised clinical trial comparing the efficacy of a herbal preparation STW 5 with the prokinetic drug cisapride in patients with dysmotility type of functional dyspepsia. Z Gastroenterol. 2002;40:401–8.

    CAS  PubMed  Google Scholar 

  111. Pilichiewicz AN, Horowitz M, Russo A, et al. Effects of Iberogast on proximal gastric volume, antropyloroduodenal motility and gastric emptying in healthy men. Am J Gastroenterol. 2007;102:1276–83.

    CAS  PubMed  Google Scholar 

  112. von Arnim U, Peitz U, Vinson B, et al. STW 5, a phytopharmacon for patients with functional dyspepsia: results of a multicenter, placebo-controlled double-blind study. Am J Gastroenterol. 2007;102:1268–75.

    Google Scholar 

  113. Clouse RE, Prakash C, Anderson RJ. Antidepressants for functional gastrointestinal symptoms and syndromes: a meta-analysis. Gastroenterology. 2001;120:A642.

    Google Scholar 

  114. Lu Y, Chen M, Huang Z, et al. Antidepressants in the treatment of functional dyspepsia: a systematic review and meta-analysis. PLoS One. 2016;11:e0157798.

    PubMed  PubMed Central  Google Scholar 

  115. Clouse RE. Antidepressants for irritable bowel syndrome. Gut. 2003;52:598–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Morgan V, Pickens D, Gautam S, et al. Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome. Gut. 2005;54:601–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Gillman PK. Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007;151:737–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Ford AC, Luthra P, Tack J, et al. Efficacy of psychotropic drugs in functional dyspepsia: systematic review and meta-analysis. Gut. 2017;66:411–20.

    CAS  PubMed  Google Scholar 

  119. Talley NJ, Locke GR, Saito YA, et al. Effect of amitriptyline and escitalopram on functional dyspepsia: a multicenter, randomized controlled study. Gastroenterology. 2015;149(340–9):e2.

    Google Scholar 

  120. Tack J, Broekaert D, Coulie B, et al. Influence of the selective serotonin re-uptake inhibitor, paroxetine, on gastric sensorimotor function in humans. Aliment Pharmacol Ther. 2003;17:603–8.

    CAS  PubMed  Google Scholar 

  121. Chial HJ, Camilleri M, Burton D, et al. Selective effects of serotonergic psychoactive agents on gastrointestinal functions in health. Am J Physiol Gastrointest Liver Physiol. 2003;284:G130–7.

    CAS  PubMed  Google Scholar 

  122. Anttila SA, Leinonen EV. A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev. 2001;7:249–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Carbone F, Vanuytsel T, Tack J. The effect of mirtazapine on gastric accommodation, gastric sensitivity to distention, and nutrient tolerance in healthy subjects. Neurogastroenterol Motil 2017;29.

  124. Tack J, Ly HG, Carbone F, et al. Efficacy of mirtazapine in patients with functional dyspepsia and weight loss. Clin Gastroenterol Hepatol. 2016;14(385–392):e4.

    Google Scholar 

  125. Grover M, Camilleri M. Effects on gastrointestinal functions and symptoms of serotonergic psychoactive agents used in functional gastrointestinal diseases. J Gastroenterol. 2013;48:177–81.

    CAS  PubMed  Google Scholar 

  126. Preve M, Nisita C, Bellini M, et al. Duloxetine in panic disorder with somatic gastric pain. Neuropsychiatr Dis Treat. 2013;9:1811–3.

    PubMed  PubMed Central  Google Scholar 

  127. van Kerkhoven LA, Laheij RJ, Aparicio N, et al. Effect of the antidepressant venlafaxine in functional dyspepsia: a randomized, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol. 2008;6:746–52 (quiz 718).

    PubMed  Google Scholar 

  128. Maj J, Rogoz Z. Pharmacological effects of venlafaxine, a new antidepressant, given repeatedly, on the alpha 1-adrenergic, dopamine and serotonin systems. J Neural Transm (Vienna). 1999;106:197–211.

    CAS  Google Scholar 

  129. Igarashi M, Nakae H, Matsuoka T, et al. Alteration in the gastric microbiota and its restoration by probiotics in patients with functional dyspepsia. BMJ Open Gastroenterol. 2017;4:e000144.

    PubMed  PubMed Central  Google Scholar 

  130. Zhang J, Wu HM, Wang X, et al. Efficacy of prebiotics and probiotics for functional dyspepsia: a systematic review and meta-analysis. Medicine (Baltimore). 2020;99:e19107.

    Google Scholar 

  131. 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.

    CAS  PubMed  Google Scholar 

  132. Tan VP, Liu KS, Lam FY, et al. Randomised clinical trial: rifaximin versus placebo for the treatment of functional dyspepsia. Aliment Pharmacol Ther. 2017;45:767–76.

    CAS  PubMed  Google Scholar 

  133. Calvert EL, Houghton LA, Cooper P, et al. Long-term improvement in functional dyspepsia using hypnotherapy. Gastroenterology. 2002;123:1778–85.

    PubMed  Google Scholar 

  134. Cheng C, Yang FC, Jun S, et al. Flexible coping psychotherapy for functional dyspeptic patients: a randomized, controlled trial. Psychosom Med. 2007;69:81–8.

    PubMed  Google Scholar 

  135. Orive M, Barrio I, Orive VM, et al. A randomized controlled trial of a 10 week group psychotherapeutic treatment added to standard medical treatment in patients with functional dyspepsia. J Psychosom Res. 2015;78:563–8.

    CAS  PubMed  Google Scholar 

  136. Haag S, Senf W, Tagay S, et al. Is there a benefit from intensified medical and psychological interventions in patients with functional dyspepsia not responding to conventional therapy? Aliment Pharmacol Ther. 2007;25:973–86.

    CAS  PubMed  Google Scholar 

  137. Hamilton J, Guthrie E, Creed F, et al. A randomized controlled trial of psychotherapy in patients with chronic functional dyspepsia. Gastroenterology. 2000;119:661–9.

    CAS  PubMed  Google Scholar 

  138. Haug TT, Wilhelmsen I, Svebak S, et al. Psychotherapy in functional dyspepsia. J Psychosom Res. 1994;38:735–44.

    CAS  PubMed  Google Scholar 

  139. Faramarzi M, Azadfallah P, Book HE, et al. The effect of psychotherapy in improving physical and psychiatric symptoms in patients with functional dyspepsia. Iran J Psychiatry. 2015;10:43–9.

    PubMed  PubMed Central  Google Scholar 

  140. 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.

    PubMed  Google Scholar 

  141. Palsson OS, Whitehead WE. Psychological treatments in functional gastrointestinal disorders: a primer for the gastroenterologist. Clin Gastroenterol Hepatol. 2013;11:208–16 (quiz e22–3).

    PubMed  Google Scholar 

  142. Popa SL, Chiarioni G, David L, et al. The efficacy of hypnotherapy in the treatment of functional dyspepsia. Am J Ther. 2019;26:e704–13.

    PubMed  Google Scholar 

  143. Lindfors P, Unge P, Nyhlin H, et al. Long-term effects of hypnotherapy in patients with refractory irritable bowel syndrome. Scand J Gastroenterol. 2012;47:414–20.

    PubMed  Google Scholar 

  144. 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.

    PubMed  PubMed Central  Google Scholar 

  145. Andersson E, Ljotsson B, Smit F, et al. Cost-effectiveness of internet-based cognitive behavior therapy for irritable bowel syndrome: results from a randomized controlled trial. BMC Public Health. 2011;11:215.

    PubMed  PubMed Central  Google Scholar 

  146. Lindfors P, Ljotsson B, Bjornsson E, et al. Patient satisfaction after gut-directed hypnotherapy in irritable bowel syndrome. Neurogastroenterol Motil. 2013;25:169–86.

    CAS  PubMed  Google Scholar 

  147. Ljotsson B, Hedman E, Andersson E, et al. Internet-delivered exposure-based treatment vs stress management for irritable bowel syndrome: a randomized trial. Am J Gastroenterol. 2011;106:1481–91.

    PubMed  Google Scholar 

  148. Kim KN, Chung SY, Cho SH. Efficacy of acupuncture treatment for functional dyspepsia: a systematic review and meta-analysis. Complement Ther Med. 2015;23:759–66.

    PubMed  Google Scholar 

  149. Zhou W, Su J, Zhang H. Efficacy and safety of acupuncture for the treatment of functional dyspepsia: meta-analysis. J Altern Complement Med. 2016;22:380–9.

    PubMed  Google Scholar 

  150. Zeng F, Qin W, Ma T, et al. Influence of acupuncture treatment on cerebral activity in functional dyspepsia patients and its relationship with efficacy. Am J Gastroenterol. 2012;107:1236–47.

    PubMed  Google Scholar 

  151. Mahadeva S, Chia YC, Vinothini A, et al. Cost-effectiveness of and satisfaction with a Helicobacter pylori “test and treat” strategy compared with prompt endoscopy in young Asians with dyspepsia. Gut. 2008;57:1214–20.

    CAS  PubMed  Google Scholar 

  152. Moayyedi P, Soo S, Deeks J, et al. Eradication of Helicobacter pylori for non-ulcer dyspepsia. Cochrane Database Syst Rev 2006:CD002096.

  153. Mazzoleni LE, Sander GB, Francesconi CF, et al. Helicobacter pylori eradication in functional dyspepsia: HEROES trial. Arch Intern Med. 2011;171:1929–36.

    PubMed  Google Scholar 

  154. Talley NJ, Janssens J, Lauritsen K, et al. 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;318:833–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Suzuki H, Nishizawa T, Hibi T. Can Helicobacter pylori-associated dyspepsia be categorized as functional dyspepsia? J Gastroenterol Hepatol. 2011;26(Suppl 3):42–5.

    PubMed  Google Scholar 

  156. Sugano K, Tack J, Kuipers EJ, et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015;64:1353–67.

    PubMed  PubMed Central  Google Scholar 

  157. Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. In: (NICE) NIfHaCE, ed. Volume CG 184, September 2014 (Revised October 2019).

  158. Kurlander JE, Drossman DA. Diagnosis and treatment of narcotic bowel syndrome. Nat Rev Gastroenterol Hepatol. 2014;11:410–8.

    CAS  PubMed  Google Scholar 

  159. Sayuk GS, Kanuri N, Gyawali CP, et al. Opioid medication use in patients with gastrointestinal diagnoses vs unexplained gastrointestinal symptoms in the US Veterans Health Administration. Aliment Pharmacol Ther. 2018;47:784–91.

    CAS  PubMed  Google Scholar 

  160. Drossman DA, Morris CB, Edwards H, et al. Diagnosis, characterization, and 3-month outcome after detoxification of 39 patients with narcotic bowel syndrome. Am J Gastroenterol. 2012;107:1426–40.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gregory S. Sayuk.

Ethics declarations

Funding

No funding was received for the preparation of this manuscript.

Conflict of interest

Gregory Sayuk has given scientific advice to Allergan, Ironwood, Abbvie, and Salix. He has served on the Speaker Bureau for Allergan, Ironwood, Salix, and Alnylam.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sayuk, G.S., Gyawali, C.P. Functional Dyspepsia: Diagnostic and Therapeutic Approaches. Drugs 80, 1319–1336 (2020). https://doi.org/10.1007/s40265-020-01362-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-020-01362-4

Navigation