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Functional dyspepsia in adults

George F Longstreth, MD
Brian E Lacy, MD, PhD
Section Editor
Nicholas J Talley, MD, PhD
Deputy Editor
Shilpa Grover, MD, MPH, AGAF


Dyspepsia is a common symptom with an extensive differential diagnosis and a heterogeneous pathophysiology [1]. It occurs in approximately 25 percent of the population each year, but most affected people do not seek medical care. Approximately 25 percent of patients with dyspepsia have an underlying organic cause. However, up to 75 percent of patients have functional (idiopathic or nonulcer) dyspepsia with no underlying cause on diagnostic evaluation [2-4]. This topic review will provide an overview of the pathophysiology and treatment of functional dyspepsia.

Our recommendations for the diagnosis and management of functional dyspepsia are largely consistent with the American College of Gastroenterology and American Gastroenterological Association guidelines [5,6]. The etiology, general approach to the evaluation, and management of the patient with uninvestigated dyspepsia are presented separately. (See "Approach to the adult with dyspepsia".)


The prevalence of functional dyspepsia ranges from 5 to 11 percent worldwide [7]. The pathophysiology of functional dyspepsia is not well understood. However, several potential mechanisms have been suggested. These mechanisms may differ between subtypes of functional dyspepsia (postprandial distress syndrome and epigastric pain syndrome) [8]. (See 'Diagnostic criteria' below.)

Gastric motility and compliance – Functional dyspepsia has been associated with several motility disorders. These include mild delays in gastric emptying, rapid gastric emptying, antral hypomotility, gastric dysrhythmias, and impaired gastric accommodation in response to a meal [8-11]. However, these findings are noted in only a subset of patients with dyspepsia. As examples, delayed gastric emptying and antral hypomotility are found in approximately 25 to 35 percent of patients with dyspepsia while up to 10 percent of patients with dyspepsia have rapid gastric emptying [3,12-14]. (See "Gastroparesis: Etiology, clinical manifestations, and diagnosis".)

Visceral hypersensitivity – Visceral hypersensitivity is characterized by a lowered threshold for induction of pain in the presence of normal gastric compliance. Several studies have demonstrated visceral hypersensitivity in patients with functional dyspepsia that occurs independently of delayed gastric emptying [15-19]. Both mechanoreceptor dysfunction and aberrant processing of afferent input in the spinal cord or brain may play a role in the pathophysiology of visceral hypersensitivity [20,21]. In one study that included 270 patients with functional dyspepsia, 37 percent had hypersensitivity to gastric distension, and hypersensitive patients reported higher cumulative symptom scores as compared with normosensitive patients [8]. Patients with functional dyspepsia may also have increased chemosensitivity [17].

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Literature review current through: Dec 2017. | This topic last updated: Nov 01, 2017.
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  1. Talley NJ, Ford AC. Functional Dyspepsia. N Engl J Med 2015; 373:1853.
  2. Bytzer P, Talley NJ. Dyspepsia. Ann Intern Med 2001; 134:815.
  3. Koch KL, Stern RM. Functional disorders of the stomach. Semin Gastrointest Dis 1996; 7:185.
  4. Malagelada JR. Functional dyspepsia. Insights on mechanisms and management strategies. Gastroenterol Clin North Am 1996; 25:103.
  5. Talley NJ, American Gastroenterological Association. American Gastroenterological Association medical position statement: evaluation of dyspepsia. Gastroenterology 2005; 129:1753.
  6. Moayyedi PM, Lacy BE, Andrews CN, et al. ACG and CAG Clinical Guideline: Management of Dyspepsia. Am J Gastroenterol 2017; 112:988.
  7. Ford AC, Marwaha A, Sood R, Moayyedi P. Global prevalence of, and risk factors for, uninvestigated dyspepsia: a meta-analysis. Gut 2015; 64:1049.
  8. 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.
  9. Tack J, Piessevaux H, Coulie B, et al. Role of impaired gastric accommodation to a meal in functional dyspepsia. Gastroenterology 1998; 115:1346.
  10. 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.
  11. Karamanolis G, Caenepeel P, Arts J, Tack J. Association of the predominant symptom with clinical characteristics and pathophysiological mechanisms in functional dyspepsia. Gastroenterology 2006; 130:296.
  12. Scolapio JS, Camilleri M. Nonulcer dyspepsia. Gastroenterologist 1996; 4:13.
  13. Quartero AO, de Wit NJ, Lodder AC, et al. Disturbed solid-phase gastric emptying in functional dyspepsia: a meta-analysis. Dig Dis Sci 1998; 43:2028.
  14. 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.
  15. Mearin F, Cucala M, Azpiroz F, Malagelada JR. The origin of symptoms on the brain-gut axis in functional dyspepsia. Gastroenterology 1991; 101:999.
  16. Mertz H, Fullerton S, Naliboff B, Mayer EA. Symptoms and visceral perception in severe functional and organic dyspepsia. Gut 1998; 42:814.
  17. Samsom M, Verhagen MA, vanBerge Henegouwen GP, Smout AJ. Abnormal clearance of exogenous acid and increased acid sensitivity of the proximal duodenum in dyspeptic patients. Gastroenterology 1999; 116:515.
  18. Camilleri M, Malagelada JR, Kao PC, Zinsmeister AR. Gastric and autonomic responses to stress in functional dyspepsia. Dig Dis Sci 1986; 31:1169.
  19. Farré R, Vanheel H, Vanuytsel T, et al. In functional dyspepsia, hypersensitivity to postprandial distention correlates with meal-related symptom severity. Gastroenterology 2013; 145:566.
  20. Iovino P, Azpiroz F, Domingo E, Malagelada JR. The sympathetic nervous system modulates perception and reflex responses to gut distention in humans. Gastroenterology 1995; 108:680.
  21. Van Oudenhove L, Vandenberghe J, Dupont P, et al. Abnormal regional brain activity during rest and (anticipated) gastric distension in functional dyspepsia and the role of anxiety: a H(2)(15)O-PET study. Am J Gastroenterol 2010; 105:913.
  22. Talley NJ, Hunt RH. What role does Helicobacter pylori play in dyspepsia and nonulcer dyspepsia? Arguments for and against H. pylori being associated with dyspeptic symptoms. Gastroenterology 1997; 113:S67.
  23. Bercík P, De Giorgio R, Blennerhassett P, et al. Immune-mediated neural dysfunction in a murine model of chronic Helicobacter pylori infection. Gastroenterology 2002; 123:1205.
  24. Minocha A, Mokshagundam S, Gallo SH, Rahal PS. Alterations in upper gastrointestinal motility in Helicobacter pylori-positive nonulcer dyspepsia. Am J Gastroenterol 1994; 89:1797.
  25. Mearin F, de Ribot X, Balboa A, et al. Does Helicobacter pylori infection increase gastric sensitivity in functional dyspepsia? Gut 1995; 37:47.
  26. Tack J, Demedts I, Dehondt G, et al. Clinical and pathophysiological characteristics of acute-onset functional dyspepsia. Gastroenterology 2002; 122:1738.
  27. Mearin F, Pérez-Oliveras M, Perelló A, et al. Dyspepsia and irritable bowel syndrome after a Salmonella gastroenteritis outbreak: one-year follow-up cohort study. Gastroenterology 2005; 129:98.
  28. Ford AC, Thabane M, Collins SM, et al. Prevalence of uninvestigated dyspepsia 8 years after a large waterborne outbreak of bacterial dysentery: a cohort study. Gastroenterology 2010; 138:1727.
  29. Pike BL, Porter CK, Sorrell TJ, Riddle MS. Acute gastroenteritis and the risk of functional dyspepsia: a systematic review and meta-analysis. Am J Gastroenterol 2013; 108:1558.
  30. Moayyedi P. Helicobacter pylori eradication for functional dyspepsia: what are we treating?: comment on "Helicobacter pylori eradication in functional dyspepsia". Arch Intern Med 2011; 171:1936.
  31. Zhong L, Shanahan ER, Raj A, et al. Dyspepsia and the microbiome: time to focus on the small intestine. Gut 2017; 66:1168.
  32. 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.
  33. Walker MM, Talley NJ, Prabhakar M, et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther 2009; 29:765.
  34. Moayyedi P. Dyspepsia. Curr Opin Gastroenterol 2012; 28:602.
  35. Futagami S, Shindo T, Kawagoe T, et al. Migration of eosinophils and CCR2-/CD68-double positive cells into the duodenal mucosa of patients with postinfectious functional dyspepsia. Am J Gastroenterol 2010; 105:1835.
  36. Walker MM, Talley NJ. Clinical value of duodenal biopsies--beyond the diagnosis of coeliac disease. Pathol Res Pract 2011; 207:538.
  37. Kato M, Kephart GM, Talley NJ, et al. Eosinophil infiltration and degranulation in normal human tissue. Anat Rec 1998; 252:418.
  38. DeBrosse CW, Case JW, Putnam PE, et al. Quantity and distribution of eosinophils in the gastrointestinal tract of children. Pediatr Dev Pathol 2006; 9:210.
  39. Drossman DA, Creed FH, Olden KW, et al. Psychosocial aspects of the functional gastrointestinal disorders. Gut 1999; 45 Suppl 2:II25.
  40. 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.
  41. Goodwin RD, Cowles RA, Galea S, Jacobi F. Gastritis and mental disorders. J Psychiatr Res 2013; 47:128.
  42. Mak AD, Wu JC, Chan Y, et al. Dyspepsia is strongly associated with major depression and generalised anxiety disorder - a community study. Aliment Pharmacol Ther 2012; 36:800.
  43. 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.
  44. Drossman DA, Talley NJ, Leserman J, et al. Sexual and physical abuse and gastrointestinal illness. Review and recommendations. Ann Intern Med 1995; 123:782.
  45. Talley NJ, Fett SL, Zinsmeister AR, Melton LJ 3rd. Gastrointestinal tract symptoms and self-reported abuse: a population-based study. Gastroenterology 1994; 107:1040.
  46. Stanghellini V, Chan FK, Hasler WL, et al. Gastroduodenal Disorders. Gastroenterology 2016; 150:1380.
  47. Carbone F, Holvoet L, Tack J. Rome III functional dyspepsia subdivision in PDS and EPS: recognizing postprandial symptoms reduces overlap. Neurogastroenterol Motil 2015; 27:1069.
  48. Quigley EM, Lacy BE. Overlap of functional dyspepsia and GERD--diagnostic and treatment implications. Nat Rev Gastroenterol Hepatol 2013; 10:175.
  49. Lacy BE. Functional dyspepsia and gastroparesis: one disease or two? Am J Gastroenterol 2012; 107:1615.
  50. Lacy BE, Talley NJ, Locke GR 3rd, et al. Review article: current treatment options and management of functional dyspepsia. Aliment Pharmacol Ther 2012; 36:3.
  51. Moayyedi P, Deeks J, Talley NJ, et al. An update of the Cochrane systematic review of Helicobacter pylori eradication therapy in nonulcer dyspepsia: resolving the discrepancy between systematic reviews. Am J Gastroenterol 2003; 98:2621.
  52. Mazzoleni LE, Sander GB, Francesconi CF, et al. Helicobacter pylori eradication in functional dyspepsia: HEROES trial. Arch Intern Med 2011; 171:1929.
  53. Moayyedi P, Soo S, Deeks J, et al. Eradication of Helicobacter pylori for non-ulcer dyspepsia. Cochrane Database Syst Rev 2005; :CD002096.
  54. Wang WH, Huang JQ, Zheng GF, et al. Effects of proton-pump inhibitors on functional dyspepsia: a meta-analysis of randomized placebo-controlled trials. Clin Gastroenterol Hepatol 2007; 5:178.
  55. Moayyedi P, Delaney BC, Vakil N, et al. The efficacy of proton pump inhibitors in nonulcer dyspepsia: a systematic review and economic analysis. Gastroenterology 2004; 127:1329.
  56. Moayyedi P, Soo S, Deeks J, et al. Pharmacological interventions for non-ulcer dyspepsia. Cochrane Database Syst Rev 2006; :CD001960.
  57. Abraham NS, Moayyedi P, Daniels B, Veldhuyzen Van Zanten SJ. Systematic review: the methodological quality of trials affects estimates of treatment efficacy in functional (non-ulcer) dyspepsia. Aliment Pharmacol Ther 2004; 19:631.
  58. 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.
  59. Wu JC, Cheong PK, Chan YC, et al. A randomized, double-blind, placebo-controlled trial of low dose imipramine for treatment of refractory functional dyspepsia (FD) (abstract #216). Gastroenterology 2011; 140:S50.
  60. Jackson JL, O'Malley PG, Tomkins G, et al. Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis. Am J Med 2000; 108:65.
  61. Mertz H, Fass R, Kodner A, et al. Effect of amitriptyline on symptoms, sleep, and visceral perception in patients with functional dyspepsia. Am J Gastroenterol 1998; 93:160.
  62. 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.
  63. Veldhuyzen van Zanten SJ, Jones MJ, Verlinden M, Talley NJ. Efficacy of cisapride and domperidone in functional (nonulcer) dyspepsia: a meta-analysis. Am J Gastroenterol 2001; 96:689.
  64. Seto K, Sasaki T, Katsunuma K, et al. Acotiamide hydrochloride (Z-338), a novel prokinetic agent, restores delayed gastric emptying and feeding inhibition induced by restraint stress in rats. Neurogastroenterol Motil 2008; 20:1051.
  65. Matsueda K, Hongo M, Tack J, et al. A placebo-controlled trial of acotiamide for meal-related symptoms of functional dyspepsia. Gut 2012; 61:821.
  66. Bytzer P. New hope for functional dyspepsia? Gut 2012; 61:789.
  67. Altan E, Masaoka T, Farré R, Tack J. Acotiamide, a novel gastroprokinetic for the treatment of patients with functional dyspepsia: postprandial distress syndrome. Expert Rev Gastroenterol Hepatol 2012; 6:533.
  68. Hamilton J, Guthrie E, Creed F, et al. A randomized controlled trial of psychotherapy in patients with chronic functional dyspepsia. Gastroenterology 2000; 119:661.
  69. Mine K, Kanazawa F, Hosoi M, et al. Treating nonulcer dyspepsia considering both functional disorders of the digestive system and psychiatric conditions. Dig Dis Sci 1998; 43:1241.
  70. Jones MP, Maganti K. Symptoms, gastric function, and psychosocial factors in functional dyspepsia. J Clin Gastroenterol 2004; 38:866.
  71. Calvert EL, Houghton LA, Cooper P, et al. Long-term improvement in functional dyspepsia using hypnotherapy. Gastroenterology 2002; 123:1778.
  72. 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.
  73. Stein DJ, Bruce Lydiard R, Herman BK, Mandel FS. Impact of gastrointestinal symptoms on response to pregabalin in generalized anxiety disorder: results of a six-study combined analysis. Int Clin Psychopharmacol 2009; 24:126.
  74. Gan Y, Liu H, Yang L, Yang K. Effect of banxiaxiexin tang on treatment of functional dyspepsia: a meta-analysis of randomized controlled trials. J Tradit Chin Med 2014; 34:140.
  75. Lan L, Zeng F, Liu GJ, et al. Acupuncture for functional dyspepsia. Cochrane Database Syst Rev 2014; :CD008487.
  76. Koretz RL, Rotblatt M. Complementary and alternative medicine in gastroenterology: the good, the bad, and the ugly. Clin Gastroenterol Hepatol 2004; 2:957.
  77. 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.
  78. Barbera R, Feinle C, Read NW. Nutrient-specific modulation of gastric mechanosensitivity in patients with functional dyspepsia. Dig Dis Sci 1995; 40:1636.
  79. Feinle C, Meier O, Otto B, et al. Role of duodenal lipid and cholecystokinin A receptors in the pathophysiology of functional dyspepsia. Gut 2001; 48:347.
  80. Duncanson KR, Talley NJ, Walker MM, Burrows TL. Food and functional dyspepsia: a systematic review. J Hum Nutr Diet 2017.
  81. Saito YA, Locke GR 3rd, Weaver AL, et al. Diet and functional gastrointestinal disorders: a population-based case-control study. Am J Gastroenterol 2005; 100:2743.
  82. Olafsdottir LB, Gudjonsson H, Jonsdottir HH, et al. Natural history of functional gastrointestinal disorders: comparison of two longitudinal population-based studies. Dig Liver Dis 2012; 44:211.