Skip to main content
SpringerLink
Log in

Functional Esophageal Disorders: Pharmacological Options

  • Therapy in Practice
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Functional esophageal disorders are a group of disorders that cause esophageal symptoms, although with negative results on investigation with standard esophageal tests. Therefore, structural disorders, motility disorders with a histopathological basis and gastroesophageal reflux disease (GERD) are excluded. They are frequently encountered by clinicians, and so a systematic and evidence-based approach to investigation, diagnosis and treatment are crucial. There are four functional esophageal disorders defined by the ROME III consensus, namely functional heartburn, functional chest pain, functional dysphagia and globus. Since the advent of ROME, the specification of diagnostic criteria for functional esophageal disorders has allowed more comparable studies and clinical trials. Despite this, the evidence base for many therapies in use at present is not as robust as would be desired. In this paper, we discuss the four categories of functional esophageal disorders. We then propose diagnostic algorithms based on current evidence. Finally, we discuss current therapies for each of the four functional esophageal disorders based on current evidence.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Galmiche JP, Clouse RE, Bálint A, Cook IJ, Kahrilas PJ, Paterson WG, et al. Functional esophageal disorders. Gastroenterology. 2006;130(5):1459–65.

    Article  PubMed  Google Scholar 

  2. Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R, Group GC. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101(8):1900–20 (quiz 43).

    Article  PubMed  Google Scholar 

  3. Numans ME, Lau J, de Wit NJ, Bonis PA. Short-term treatment with proton-pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics. Ann Inter Med. 2004;140(7):518–27.

    Article  CAS  Google Scholar 

  4. Vakil N. Review article: how valuable are proton-pump inhibitors in establishing a diagnosis of gastro-oesophageal reflux disease? Aliment Pharmacol Ther. 2005;22(Suppl 1):64–9 (Epub 2005/07/27).

    Article  CAS  PubMed  Google Scholar 

  5. Drossman DA, Li Z, Andruzzi E, Temple RD, Talley NJ, Thompson WG, et al. U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact. Dig Dis Sci. 1993;38(9):1569–80.

    Article  CAS  PubMed  Google Scholar 

  6. Martinez SD, Malagon IB, Garewal HS, Cui H, Fass R. Non-erosive reflux disease (NERD)—acid reflux and symptom patterns. Aliment Pharmacol Ther. 2003;17(4):537–45.

    Article  CAS  PubMed  Google Scholar 

  7. Surdea Blaga T, Dumitrascu D, Galmiche JP, Bruley des Varannes S. Functional heartburn: clinical characteristics and outcome. Eur J Gastroenterol Hepatol. 2013;25(3):282–90 (Epub 2012/11/07).

    Article  PubMed  Google Scholar 

  8. Eslick GD, Jones MP, Talley NJ. Non-cardiac chest pain: prevalence, risk factors, impact and consulting—a population-based study. Aliment Pharmacol Ther. 2003;17(9):1115–24 (Epub 2003/05/20).

    Article  CAS  PubMed  Google Scholar 

  9. Zerbib F, Bruley des Varannes S, Simon M, Galmiche JP. Functional heartburn: definition and management strategies. Curr Gastroenterol Rep. 2012;14(3):181–8.

    Article  PubMed  Google Scholar 

  10. Sweis R, Fox M, Anggiansah A, Wong T. Prolonged, wireless pH-studies have a high diagnostic yield in patients with reflux symptoms and negative 24-h catheter-based pH-studies. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2011;23(5):419–26 (Epub 2011/01/18).

    Article  CAS  Google Scholar 

  11. Slaughter JC, Goutte M, Rymer JA, Oranu AC, Schneider JA, Garrett CG, et al. Caution about overinterpretation of symptom indexes in reflux monitoring for refractory gastroesophageal reflux disease. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2011;9(10):868–74.

    Google Scholar 

  12. Fass R, Sifrim D. Management of heartburn not responding to proton pump inhibitors. Gut. 2009;58(2):295–309.

    Article  CAS  PubMed  Google Scholar 

  13. Savarino E, Zentilin P, Mastracci L, Dulbecco P, Marabotto E, Gemignani L, et al. Microscopic esophagitis distinguishes patients with non-erosive reflux disease from those with functional heartburn. J Gastroenterol. 2013;48(4):473–82 (Epub 2012/09/25).

    Article  PubMed  Google Scholar 

  14. Miner PB Jr, Rodriguez-Stanley S, Proskin HM, Kianifard F, Bottoli I. Tegaserod in patients with mechanical sensitivity and overlapping symptoms of functional heartburn and functional dyspepsia. Curr Med Res Opin. 2008;24(8):2159–72 (Epub 2008/06/20).

    Article  CAS  PubMed  Google Scholar 

  15. Rodriguez-Stanley S, Zubaidi S, Proskin HM, Kralstein JR, Shetzline MA, Miner PB Jr. Effect of tegaserod on esophageal pain threshold, regurgitation, and symptom relief in patients with functional heartburn and mechanical sensitivity. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2006;4(4):442–50 (Epub 2006/04/18).

    CAS  Google Scholar 

  16. Ostovaneh MR, Saeidi B, Hajifathalian K, Farrokhi-Khajeh-Pasha Y, Fotouhi A, Mirbagheri SS, et al. Comparing omeprazole with fluoxetine for treatment of patients with heartburn and normal endoscopy who failed once daily proton pump inhibitors: double-blind placebo-controlled trial. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2014.

  17. Fass R, Achem SR. Noncardiac chest pain: epidemiology, natural course and pathogenesis. J Neurogastroenterol Motil. 2011;17(2):110–23.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Fenster PE. Evaluation of chest pain: a cardiology perspective for gastroenterologists. Gastroenterol Clin North Am. 2004;33(1):35–40.

    Article  PubMed  Google Scholar 

  19. Park SW, Lee H, Lee HJ, Park JC, Shin SK, Lee SK, et al. Low-dose amitriptyline combined with proton pump inhibitor for functional chest pain. World J Gastroenterol WJG. 2013;19(30):4958–65 (Epub 2013/08/16).

    Article  Google Scholar 

  20. Prakash C, Clouse RE. Long-term outcome from tricyclic antidepressant treatment of functional chest pain. Dig Dis Sci. 1999;44(12):2373–9.

    Article  CAS  PubMed  Google Scholar 

  21. Lee H, Kim JH, Min BH, Lee JH, Son HJ, Kim JJ, et al. Efficacy of venlafaxine for symptomatic relief in young adult patients with functional chest pain: a randomized, double-blind, placebo-controlled, crossover trial. Am J Gastroenterol. 2010;105(7):1504–12.

    Article  CAS  PubMed  Google Scholar 

  22. Cannon RO, Quyyumi AA, Mincemoyer R, Stine AM, Gracely RH, Smith WB, et al. Imipramine in patients with chest pain despite normal coronary angiograms. N Eng J Med. 1994;330(20):1411–7.

    Article  Google Scholar 

  23. Cox ID, Hann CM, Kaski JC. Low dose imipramine improves chest pain but not quality of life in patients with angina and normal coronary angiograms. Eur Heart J. 1998;19(2):250–4.

    Article  CAS  PubMed  Google Scholar 

  24. Keefe FJ, Shelby RA, Somers TJ, Varia I, Blazing M, Waters SJ, et al. Effects of coping skills training and sertraline in patients with non-cardiac chest pain: a randomized controlled study. Pain. 2011;152(4):730–41.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Doraiswamy PM, Varia I, Hellegers C, Wagner HR, Clary GL, Beyer JL, et al. A randomized controlled trial of paroxetine for noncardiac chest pain. Psychopharmacol Bull. 2006;39(1):15–24 (Epub 2006/10/27).

    PubMed  Google Scholar 

  26. Broekaert D, Fischler B, Sifrim D, Janssens J, Tack J. Influence of citalopram, a selective serotonin reuptake inhibitor, on oesophageal hypersensitivity: a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2006;23(3):365–70 (Epub 2006/01/21).

    Article  CAS  PubMed  Google Scholar 

  27. Shapiro M, Shanani R, Taback H, Abramowich D, Scapa E, Broide E. Functional chest pain responds to biofeedback treatment but functional heartburn does not: what is the difference? Eur J Gastroenterol Hepatol. 2012;24(6):708–14.

    Article  PubMed  Google Scholar 

  28. Chiarioni G, Whitehead WE. The role of biofeedback in the treatment of gastrointestinal disorders. Nat Clin Pract Gastroenterol Hepatol. 2008;5(7):371–82.

    Article  PubMed  Google Scholar 

  29. Hjelland IE, Svebak S, Berstad A, Flatabo G, Hausken T. Breathing exercises with vagal biofeedback may benefit patients with functional dyspepsia. Scand J Gastroenterol. 2007;42(9):1054–62 (Epub 2007/08/22).

    Article  PubMed  Google Scholar 

  30. Gasiorowska A, Navarro-Rodriguez T, Dickman R, Wendel C, Moty B, Powers J, et al. Clinical trial: the effect of Johrei on symptoms of patients with functional chest pain. Aliment Pharmacol Ther. 2009;29(1):126–34 (Epub 2008/10/24).

    Article  CAS  PubMed  Google Scholar 

  31. Jonsbu E, Dammen T, Morken G, Moum T, Martinsen EW. Short-term cognitive behavioral therapy for non-cardiac chest pain and benign palpitations: a randomized controlled trial. J Psychosom Res. 2011;70(2):117–23 (Epub 2011/01/26).

    Article  PubMed  Google Scholar 

  32. Rao SS, Mudipalli RS, Mujica V, Utech CL, Zhao X, Conklin JL. An open-label trial of theophylline for functional chest pain. Dig Dis Sci. 2002;47(12):2763–8.

    Article  CAS  PubMed  Google Scholar 

  33. Jones H, Cooper P, Miller V, Brooks N, Whorwell PJ. Treatment of non-cardiac chest pain: a controlled trial of hypnotherapy. Gut. 2006;55(10):1403–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Clouse RE, Lustman PJ, Eckert TC, Ferney DM, Griffith LS. Low-dose trazodone for symptomatic patients with esophageal contraction abnormalities. A double-blind, placebo-controlled trial. Gastroenterology. 1987;92(4):1027–36.

    CAS  PubMed  Google Scholar 

  35. Cook IJ, Dent J, Shannon S, Collins SM. Measurement of upper esophageal sphincter pressure. Effect of acute emotional stress. Gastroenterology. 1987;93(3):526–32 (Epub 1987/09/01).

    CAS  PubMed  Google Scholar 

  36. Kumar AR, Katz PO. Functional esophageal disorders: a review of diagnosis and management. Expert Rev Gastroenterol Hepatol. 2013;7(5):453–61 (Epub 2013/08/01).

    Article  CAS  PubMed  Google Scholar 

  37. Selleslagh M, van Oudenhove L, Pauwels A, Tack J, Rommel N. The complexity of globus: a multidisciplinary perspective. Nat Rev Gastroenterol Hepatol. 2013.

  38. Jeon HK, Kim GH, Choi MK, Cheong JH, Baek DH, Lee GJ, et al. Clinical predictors for response to proton pump inhibitor treatment in patients with globus. J Neurogastroenterol Motil. 2013;19(1):47–53.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Kirch S, Gegg R, Johns MM, Rubin AD. Globus pharyngeus: effectiveness of treatment with proton pump inhibitors and gabapentin. Ann Otol Rhinol Laryngol. 2013;122(8):492–5.

    PubMed  Google Scholar 

  40. Kiebles JL, Kwiatek MA, Pandolfino JE, Kahrilas PJ, Keefer L. Do patients with globus sensation respond to hypnotically assisted relaxation therapy? A case series report. Dis Esophagus. 2010;23(7):545–53 (Epub 2010/05/13).

    Article  CAS  PubMed  Google Scholar 

  41. You LQ, Liu J, Jia L, Jiang SM, Wang GQ. Effect of low-dose amitriptyline on globus pharyngeus and its side effects. World J Gastroenterol WJG. 2013;19(42):7455–60.

    Article  Google Scholar 

  42. Deary IJ, Wilson JA. Problems in treating globus pharyngis. Clin Otolaryngol Allied Sci. 1994;19(1):55–60 (Epub 1994/02/01).

    Article  CAS  PubMed  Google Scholar 

  43. Tokashiki R, Okamoto I, Funato N, Suzuki M. Rikkunshito improves globus sensation in patients with proton-pump inhibitor-refractory laryngopharyngeal reflux. World J Gastroenterol WJG. 2013;19(31):5118–24.

    Article  Google Scholar 

  44. Nahata M, Muto S, Oridate N, Ohnishi S, Nakagawa K, Sadakane C, et al. Impaired ghrelin signaling is associated with gastrointestinal dysmotility in rats with gastroesophageal reflux disease. Am J Physiol Gastrointest liver Physiol. 2012;303(1):G42–53 (Epub 2012/04/21).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Khalil HS, Reddy VM, Bos-Clark M, Dowley A, Pierce MH, Morris CP, et al. Speech therapy in the treatment of globus pharyngeus: how we do it. Clin Otolaryngol Off J ENT-UK Off J Neth Soc Oto-Rhino-Laryngol Cerv-Fac Surg. 2011;36(4):388–92 (Epub 2011/08/19).

    CAS  Google Scholar 

  46. Millichap F, Lee M, Pring T. A lump in the throat: should speech and language therapists treat globus pharyngeus? Disabil Rehabil. 2005;27(3):124–30 (Epub 2005/04/13).

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

Gehanjali Amarasinghe has no conflict of interest. Daniel Sifrim received research grants from Sandhill Scientific US and Reckitt Benckiser UK.

Author information

Authors and Affiliations

  1. Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

    Gehanjali Amarasinghe & Daniel Sifrim

  2. Wingate Institute of Neurogastroenterology, 26 Ashfield Street, London, E1 1AJ, UK

    Daniel Sifrim

Authors
  1. Gehanjali Amarasinghe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel Sifrim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel Sifrim.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Amarasinghe, G., Sifrim, D. Functional Esophageal Disorders: Pharmacological Options. Drugs 74, 1335–1344 (2014). https://doi.org/10.1007/s40265-014-0272-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-014-0272-y

Keywords

Search

Navigation