440
Views
14
CrossRef citations to date
0
Altmetric
Review

Current and emerging therapeutic options for the management of functional dyspepsia

, , , , &
Pages 365-376 | Received 11 Sep 2019, Accepted 18 Dec 2019, Published online: 03 Jan 2020

References

  • Stanghellini V, Talley N, Chan F, et al. Functional gastroduodenal disorders. Gastroenterology. 2016 May;150(6):1380–1392.
  • Aziz I, Palsson OS, Törnblom H, et al. Epidemiology, clinical characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults in the USA, Canada, and the UK: a cross-sectional population-based study. Lancet Gastroenterol Hepatol. 2018 Apr;3(4):252–262.
  • 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 Apr;21(4):378–388.
  • Jones MP, Talley NJ, Eslick GD, et al. Community subgroups in dyspepsia and their association with weight loss. Am J Gastroenterol. 2008 Aug;103(8):2051–2056.
  • Tack J, Jones MP, Karamanolis G, et al. Symptom pattern and pathophysiological correlates of weight loss in tertiary-referred functional dyspepsia. Neurogastroenterol Motil. 2010 Jan;22(1):29–35, e4–5.
  • Ford AC, Marwaha A, Lim A, et al. What is the prevalence of clinically significant endoscopic findings in subjects with dyspepsia? Systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2010 Oct;8(10):830–7, 837.e1–2.
  • Oustamanolakis P, Tack J. Dyspepsia: organic versus functional. J Clin Gastroenterol. 2012 Mar;46(3):175–190.
  • Tack J, Talley NJ. Functional dyspepsia-symptoms, definitions and validity of the Rome III criteria. Nat Rev Gastroenterol Hepatol. 2013;10:134–141.
  • Van den Houte K, Carbone F, Tack J. Postprandial distress syndrome: stratification and management. Expert Rev Gastroenterol Hepatol. 2019 Aug;3(4):337–343.
  • Carbone F, Tack J. Gastroduodenal mechanisms underlying functional gastric disorders. Dig Dis. 2014;32(3):222–229.
  • Simrén M, Törnblom H, Palsson OS, et al. Visceral hypersensitivity is associated with GI symptom severity in functional GI disorders: consistent findings from five different patient cohorts. Gut. 2018 Feb;67(2):255–262.
  • Stanghellini V, Tack J. Gastroparesis: separate entity or just a part of dyspepsia? Gut. 2014 Dec;63(12):1972–1978.
  • Janssen P, Harris MS, Jones M, et al. The relation between symptom improvement and gastric emptying in the treatment of diabetic and idiopathic gastroparesis. Am J Gastroenterol. 2013 Sept;108(9):1382–1391.
  • Vijayvargiya P, Camilleri M, Chedid V, et al. Effects of promotility agents on gastric emptying and symptoms: a systematic review and meta-analysis. Gastroenterology. 2019 May;156(6):1650–1660.
  • Enck P, Azpiroz F, Boeckxstaens G, et al. Functional dyspepsia. Nat Rev Dis Primers. 2017 Nov;3(3):17081.
  • Camilleri M, Stanghellini V. Current management strategies and emerging treatments for functional dyspepsia. Nat Rev Gastroenterol Hepatol. 2013 Mar;10(3):187–194.
  • Moayyedi P, Lacy BE, Andrews CN, et al. ACG and CAG clinical guideline: management of dyspepsia. Am J Gastroenterol. 2017 July;112(7):988–1013.
  • Van Oudenhove L, Vandenberghe J, Geeraerts B, et al. Determinants of symptoms in functional dyspepsia: gastric sensorimotor function, psychosocial factors or somatisation? Gut. 2008 Dec;57(12):1666–1673.
  • Janssen P, Verschueren S, Ly HG, et al. Intragastric pressure during food intake: a physiological and minimally invasive method to assess gastric accommodation. Neurogastroenterol Motil. 2011 Apr;23(4):316–22, e153–4.
  • Tack J, Caenepeel P, Piessevaux H, et al. Assessment of meal-induced gastric accommodation by a satiety drinking test in health and in functional dyspepsia. Gut. 2003;52:1271–1277.
  • Sarnelli G, Vos R, Cuomo R, et al. Reproducibility of gastric barostat studies in healthy controls and in dyspeptic patients. Am J Gastroenterol. 2001;96:1047–1053.
  • Kuiken SD, Samsom M, Camilleri M, et al. Development of a test to measure gastric accommodation in humans. Am J Physiol. 1999 Dec;277(6):G1217–21.
  • Carbone F, Vandenberghe A, Holvoet L, et al. Validation of the leuven postprandial distress scale, a questionnaire for symptom assessment in the functional dyspepsia/postprandial distress syndrome. Aliment Pharmacol Ther. 2016 Nov;44(9):989–1001.
  • Tack J, Carbone F, Holvoet L, et al. The use of pictograms improves symptom evaluation by patients with functional dyspepsia. Aliment Pharmacol Ther. 2014 July–Sept 22;40(5):523–530.
  • Tack J, Masuy I, Van Den Houte K, et al. Drugs under development for the treatment of functional dyspepsia and related disorders. Expert Opin Investig Drugs. 2019;28(10):871–889.
  • Goelen N, Carbone F, Holvoet L, et al. The waiting room questionnaire: validation of a novel patient reported outcome questionnaire for the diagnosis of functional gastrointestinal disorders. Gastroenterology. 2017 Apr;152(5 Supplement 1):S744–S745.
  • Tack J, Pokrotnieks J, Urbonas G, et al. Long-term safety and efficacy of acotiamide in functional dyspepsia (postprandial distress syndrome)-results from the European phase 3 open-label safety trial. Neurogastroenterol Motil. 2018 June;30(6):e13284.
  • Masuy I, Carbone F 2, Holvoet L 2, et al. The effect of rikkunshito on gastrointestinal symptoms and gastric motor function: the first study in a Belgian functional dyspepsia population. Neurogastroenterol Motil. 2019 Oct 14:e13739.
  • Tack J, Piessevaux H, Coulie B, et al. Role of impaired gastric accommodation to a meal in functional dyspepsia. Gastroenterology. 1998 Dec;115(6):1346–1352.
  • 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 Apr;98(4):783–788.
  • Tack J, Camilleri M. New developments in the treatment of gastroparesis and functional dyspepsia. Curr Opin Pharmacol. 2018 Dec;43:111–117.
  • Masuy I, Van Oudenhove L, Tack J. Review article: treatment options for functional dyspepsia. Aliment Pharmacol Ther. 2019 May;49(9):1134–1172.
  • Altan E, Masaoka T, Farré R, et al. Acotiamide, a novel gastroprokinetic for the treatment of patients with functional dyspepsia: postprandial distress syndrome. Expert Rev Gastroenterol Hepatol. 2012 Sept 6;6(5):533–544. Therap Adv Gastroenterol. 2017 Sep; 10(9): 689–699.
  • Matsueda K, Hongo M, Tack J, et al. A placebo-controlled trial of acotiamide for meal-related symptoms of functional dyspepsia. Gut. 2012 June;61(6):821–828.
  • 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(4):261–268.
  • Bor S, Demir M, Ozdemir O, et al. A meta-analysis on the cardiac safety profile of domperidone compared to metoclopramide. United European Gastroenterol J. 2018 Nov;6(9):1331–1346.
  • Tack J, Camilleri M, Chang L, et al. Systematic review: cardiovascular safety profile of 5-HT agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther. 2012 Apr;35(7):745–767.
  • Cuena Boy R, Maciá Martínez MA. Extrapyramidal toxicity caused by metoclopramide and clebopride: study of voluntary notifications of adverse effects to the Spanish drug surveillance system. Aten Primaria. 1998 Mar 31;21(5):289–295. Spanish.
  • Kim K-S, Shin W-H, Park SJ, et al. Effect of clebopride, antidopaminergic gastrointestinal prokinetics, on cardiac repolarization. Int J Toxicol. 2007 Jan–Feb;26(1):25–31.
  • 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(5):959–967.
  • Tack J, Van den Houte K, Carbone F. The unfulfilled promise of prokinetics for functional dyspepsia/postprandial distress syndrome. Am J Gastroenterol. 2019 Feb;114(2):204–206.
  • Bang CS, Kim JH, Baik GH, et al. Mosapride treatment for functional dyspepsia: a meta-analysis. J Gastroenterol Hepatol. 2015 Jan;30(1):28–42.
  • Du Y, Su T, Song X, et al. Efficacy and safety of cinitapride in the treatment of mild to moderate postprandial distress syndrome-predominant functional dyspepsia. J Clin Gastroenterol. 2014 Apr;48(4):328–335.
  • Robert M, Salvà M, Segarra R, et al. The prokinetic cinitapride has no clinically relevant pharmacokinetic interaction and effect on QT during coadministration with ketoconazole. Drug Metab Dispos. 2007 July;35(7):1149–1156.
  • Fernández AG, Massingham R. Peripheral receptor populations involved in the regulation of gastrointestinal motility and the pharmacological actions of metoclopramide-like drugs. Life Sci. 1985 Jan;36(1):1–14.
  • Holtmann G, Talley NJ, Liebregts T, et al. A placebo-controlled trial of itopride in functional dyspepsia. N Engl J Med. 2006;354(8):832–840.
  • Carbone F, Vandenberghe A, Holvoet L, et al. 383 - The therapeutic outcome of itopride in functional dyspepsia postprandial distress syndrome: a double-blind randomized, multicenter, placebo-controlled study. Gastroenterology. 2018;154(6):S–91.
  • Talley NJ, Tack J, Ptak T, et al. Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials. Gut. 2008;57(6):740–746.
  • Tack J. A phase II placebo controlled randomized trial with tegaserod (T) in functional dyspepsia (FD) patients with normal gastric emptying (NGE). Gastroenterology. 2002;122:154.
  • 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 Aug;103(8):1906–1919.
  • Ahn A, Barnes C, Shaywitz D, et al. Velusetrag improves gastric emptying time in subjects with diabetic or idiopathic gastroparesis. Gastroenterology. 2015;148(4): S–507. (abstract).
  • Abell T, Kuo B, Esfandyari T, et al. Velusetrag improves gastroparesis both in symptoms and gastric emptying in patients with diabetic or idiopathic gastroparesis in a 12-week global phase 2B study. Gastroenterology. 2019;156(6): S164. (abstract).
  • Carbone F, Van den Houte K, Clevers E, et al. Prucalopride in gastroparesis: a randomized placebo-controlled crossover study. Am J Gastroenterol. in press, 2019;114:1265–1274.
  • Dukes GE, Scimia C, Kuo B, et al. Safety, tolerability, and pharmacodynamics of TAK-906, A dopamine 2,3 antagonist, in patients with diabetic or idiopathic gastroparesis. Neurogastroenterol Motil. 2019;31(S3), 6 (abstract).
  • 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(1):65–76 e11.
  • Jacob D, Busciglio I, Burton D, et al. Effects of NK1 receptors on gastric motor functions and satiation in healthy humans: results from a controlled trial with the NK1 antagonist aprepitant. Am J Physiol Gastrointest Liver Physiol. 2017 Nov 1;313(5):G505–G510.
  • Van Oudenhove L, Kindt S, Vos R, et al. Influence of buspirone on gastric sensorimotor function in man. Aliment Pharmacol Ther. 2008 Dec 1;28(11–12):1326–1333.
  • Tack J, Janssen P, Masaoka T, et al. Efficacy of buspirone, a fundus-relaxing drug, in patients with functional dyspepsia. Clin Gastroenterol Hepatol. 2012 Nov;10(11):1239–1245.
  • Miwa H, Nagahara A, Tominaga K, et al. Efficacy of the 5-HT1A agonist tandospirone citrate in improving symptoms of patients with functional dyspepsia: a randomized controlled trial. Am J Gastroenterol. 2009 Nov;104(11):2779–2787.
  • Tack J, Van Den Elzen B, Tytgat G, et al. A placebo-controlled trial of the 5-HT1A agonist R-137696 on symptoms, visceral hypersensitivity and on impaired accommodation in functional dyspepsia. Neurogastroenterol Motil. 2009 June;21(6):619–626.
  • Suzuki H, Matsuzaki J, Fukushima Y, et al. Rikkunshito study group. Randomized clinical trial: rikkunshito in the treatment of functional dyspepsia–a multicenter, double-blind, randomized, placebo-controlled study. Neurogastroenterol Motil. 2014 July;26(7):950–961.
  • Tominaga K, Sakata Y, Kusunoki H, et al. Rikkunshito simultaneously improves dyspepsia correlated with anxiety in patients with functional dyspepsia: a randomized clinical trial (the DREAM study). Neurogastroenterol Motil. 2018 July;30(7):e13319.
  • Papathanasopoulos A, Rotondo A, Janssen P, et al. Effect of acute peppermint oil administration on gastric sensorimotor function and nutrient tolerance in health. Neurogastroenterol Motil. 2013;25(4):e263–271.
  • Micklefield G, Jung O, Greving I, et al. Effects of intraduodenal application of peppermint oil (WS(R) 1340) and caraway oil (WS(R) 1520) on gastroduodenal motility in healthy volunteers. Phytother Res. 2003;17(2):135–140.
  • 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. 2000;14(12):1671–1677.
  • Rich G 1,2, Shah A 1,2, Koloski N 1,2,3, et al. A randomized placebo-controlled trial on the effects of Menthacarin, a proprietary peppermint- and caraway-oil-preparation, on symptoms and quality of life in patients with functional dyspepsia. Neurogastroenterol Motil. 2017 Nov;29(11):e13132.
  • Chey WD, Lacy BE, Cash BD, et al. Sa1619 - efficacy of caraway oil/L-menthol plus usual care vs placebo plus usual care, in functional dyspepsia patients with post-prandial distress (PDS) or epigastric pain (EPS) syndromes: results from a us RCT. Gastroenterology. 2017;152(5): S307. (abstract).
  • Ottilinger B, Storr M, Malfertheiner P, et al. STW5 - a safe and effective standard in the treatment for functional gastrointestinal disorders. Wien Med Wochenschr. 2013 Feb;163(3–4):65–72.
  • Madisch A, Holtmann G, Mayr G, et al. Treatment of functional dyspepsia with a herbal preparation. A double-blind, randomized, placebo-controlled, multicenter trial. Digestion. 2004;69:45–52.
  • 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;102:1268–1275.
  • Madisch A, Vinson BR, Abdel-Aziz H, et al. Modulation of gastrointestinal motility beyond metoclopramide and domperidone: pharmacological and clinical evidence for phytotherapy in functional gastrointestinal disorders. Wien Med Wochenschr. 2017 May;167(7–8):160–168.
  • Gerhardt F, Benesic A, Tillmann HL, et al. Iberogast-induced acute liver failure-reexposure and in vitro assay support causality. Am J Gastroenterol. 2019 Aug;114(8):1358–1359.
  • Quigley EM, Lacy BE. Overlap of functional dyspepsia and GERD–diagnostic and treatment implications. Nat Rev Gastroenterol Hepatol. 2013 Mar;10(3):175–186.
  • 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(5):1329–1337.
  • Asaoka D, Nagahara A, Hojo M, et al. Efficacy of a potassium-competitive acid blocker for improving symptoms in patients with reflux esophagitis, non-erosive reflux disease, and functional dyspepsia. Biomed Rep. 2017 Feb;6(2):175–180.
  • Tack J, Caenepeel P, Fischler B, et al. Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia. Gastroenterology. 2001 Sept;121(3):526–535.
  • Van Oudenhove L, Vandenberghe J, Geeraerts B, et al. Relationship between anxiety and gastric sensorimotor function in functional dyspepsia. Psychosom Med. 2007 June;69(5):455–463.
  • Farré R, Vanheel H, Vanuytsel T, et al. In functional dyspepsia, hypersensitivity to postprandial distention correlates with meal-related symptom severity. Gastroenterology. 2013 Sept;145(3):566–573.
  • Talley NJ, Locke GR, Saito YA, et al. Effect of amitriptyline and escitalopram on functional dyspepsia: a multicenter, randomized controlled study. Gastroenterology. 2015;149(2):340–349.e342.
  • Lacy B, Saito Y, Camilleri M, et al. Effects of antidepressants on gastric function in patients with functional dyspepsia. Am J Gastroenterol. 2018;113:216–224.
  • Tack J, Broekaert D, Coulie B, et al. Influence of the selective serotonin reuptake inhibitor paroxetine on gastric sensorimotor function in man. Aliment Pharmacol Ther. 2003 Feb 15;17(4):603–608.
  • 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 Jan;284(1):G130–7.
  • Tack J, Ly HG, Carbone F, et al. Efficacy of mirtazapine in patients with functional dyspepsia and weight loss. Clin Gastroenterol Hepatol. 2016;14(3):385–392.e384.
  • 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(12):e13146.
  • Corsetti M, Tack J. Linaclotide: a new drug for the treatment of chronic constipation and irritable bowel syndrome with constipation. United European Gastroenterol J. 2013 Feb;1(1):7–20.
  • Kessler M, Solinga R, Zimmer D, et al. IW-9179, a phosphopeptide designed to target the upper gastrointestinal tract, is more potent at acidic pH and is rapidly metabolized in vitro in rodent intestinal fluid. Gastroenterology. 2015;148(4 Supplement 1): S–823. (abstract).
  • Tack J, Fitch D, Shao J, et al. Evaluation of daily GI symptoms in a Phase 2a study of IW-9179 in functional dyspepsia (abstract #P1637). Am J Gastroenterol. 2014;109:S637–S638.
  • Ironwood pharmaceuticals reports top-line data from exploratory Phase IIa study of IW-9179 in diabetic gastroparesis. (Ironwood press release); 2016 Apr.
  • Ameloot K, Janssen P, Scarpellini E, et al. Endocannabinoid control of gastric sensorimotor function in man. Aliment Pharmacol Ther. 2010 May;31(10):1123–1131.
  • Ly HG, Ceccarini J, Weltens N, et al. Increased cerebral cannabinoid-1 receptor availability is a stable feature of functional dyspepsia: a [F]MK-9470 PET study. Psychother Psychosom. 2015;84(3):149–158.
  • Higgins P, Ginsburg D, Gilder K, et al. P418 Safety and efficacy of olorinab, a peripherally restricted, highly-selective, cannabinoid receptor 2 agonist in a phase 2A study in chronic abdominal pain associated with Crohn’s disease. Ecco. 2019;P418.
  • Sugano K, Tack J, Kuipers EJ, et al., faculty members of Kyoto Global Consensus Conference. Kyoto global consensus report on helicobacter pylori gastritis. Gut. 2015;64:1353–1367.
  • Zhong L, Shanahan ER, Raj A, et al. Dyspepsia and the microbiome: time to focus on the small intestine. Gut. 2017 June;66(6):1168–1169.
  • 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 Gastro. 2017;3:e000144.
  • Lembo A, Pimentel M, Rao SS, et al. Repeat treatment with rifaximin is safe and effective in patients with diarrhea-predominant irritable bowel syndrome. Gastroenterology. 2016 Dec;151(6):1113–1121.
  • Kimer N, Krag A, Møller S, et al. Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther. 2014 July;40(2):123–132.
  • Tan VP, Liu KS, Lam FY, et al. Randomised clinical trial: rifaximin versus placebo for the treatment of functional dyspepsia. Aliment Pharmacol Ther. 2017 Mar;45(6):767–776.
  • Wauters L, Walker MM, Tack J, et al. Duodenal implications in the pathophysiology and treatment of functional dyspepsia. Submitted for publication; 2019.
  • Potter MDE, Goodsall TM, Walker MM, et al. Dual histamine blockade for the treatment of adult functional dyspepsia: a single centre experience. Gut. 2019 Apr 30. pii: gutjnl-2019-318412. doi: 10.1136/gutjnl-2019-318412. [Epub ahead of print]
  • Friesen CA, Sandridge L, Andre L, et al. Mucosal eosinophilia and response to H1/H2 antagonist and cromolyn therapy in pediatric dyspepsia. Clin Pediatr (Phila). 2006;45:143–147.
  • Friesen CA, Kearns GL, Andre L, et al. Clinical efficacy and pharmacokinetics of montelukast in dyspeptic children with duodenal eosinophilia. J Pediatr Gastroenterol Nutr. 2004;38:343–351.
  • Potter MDE, Wood NK, Walker MM, et al. Proton pump inhibitors and suppression of duodenal eosinophilia in functional dyspepsia. Gut. 2018;gutjnl-2018-316878. DOI:10.1136/gutjnl-2018-316878
  • Wauters L, Ceulemans M, Lambaerts M, et al. Duodenal hyperpermeability, eosinophilia and symptoms in functional dyspepsia patients are reduced by proton pump inhibitors. Neurogastroenterol Motil. 2019;31(S4):22–23.
  • Van den Houte K, Carbone F, Goelen N, et al. The impact of the Rome IV definitions on functional dyspepsia subgroups in secondary care. Submitted for publication; 2019.
  • Carbone F, Vanuytsel T, Tack J. Analysis of postprandial symptom patterns in subgroups of patients with Rome III or Rome IV functional dyspepsia. Clin Gastroenterol Hepatol. 2019 Aug 5. pii: S1542-3565(19)30842-0. doi: 10.1016/j.cgh.2019.07.053. [Epub ahead of print]

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.