Current and emerging therapeutic options for the management of functional dyspepsia

ABSTRACT

Introduction: Functional Dyspepsia (FD), defined as chronic symptoms originating from the gastroduodenal region in absence of readily identifiable organic disease, is one of the most common gastrointestinal disorders. FD is divided into two subgroups: Post-Prandial Distress Syndrome (PDS) or meal-related FD, characterized by postprandial fullness and early satiation, and Epigastric Pain Syndrome (EPS) or meal-unrelated FD, characterized by epigastric pain and burning.

Areas covered: This review summarizes the existing and off-label therapeutic options for FD.

Expert opinion: The identification of mechanisms, the Rome IV classification, the reduction of PDS/EPS overlap and pictograms for symptom identification allow a better diagnosis and a more targeted treatment choice. Acotiamide, a first-in-class prokinetic agent available only in Japan and India, is the only agent of proven efficacy for FD, but clinicians use acid-suppressive therapy, prokinetics, neuromodulators and herbal therapies for treating FD symptoms. New emerging targets are duodenal low-grade inflammation with eosinophils and duodenal or other modified luminal microbiota.

KEYWORDS:

• Functional dyspepsia
• post prandial distress syndrome
• epigastric pain syndrome
• functional dyspepsia overlap
• therapeutic gap
• prokinetics
• proton pomp inhibitors
• potassium-competitive acid blockers
• medicinal herbal preparations
• neuromodulators
• duodenal microbiota
• probiotics
• duodenal inflammation
• anti-inflammatory approach
• postprandial distress syndrome
• overlap
• acid suppressants
• histamine receptor blockers
• herbal medicines

Article highlights

• Functional dyspepsia (FD) is one of the most prevalent functional digestive diseases. Yet, there are few treatment options with established efficacy, due to a number of challenges and historical factors such as poor disease classification and lack of validated endpoints.

• The Rome IV classification, consistently taking in account the relationship of symptoms to meal, the emergence of valid endpoints for treatment trials and the development of pictograms to assist diagnosis and the elucidation of novel underlying mechanisms, are all paving the way for truely efficacious therapeutic approaches.

• The first agent with established efficacy for treating meal-related symptoms of FD, acotiamide, is now available in Japan. The EU and the US are still waiting for this drug to enter phase III evaluation. Novel dopamine-2 receptor antagonists and 5-HT4 agonists are being developed for treatment of gastric sensorimotor disorders.

• Meta-analyses attribute significant efficacy to proton pomp inhibitors (PPIs) in FD. Stronger acid suppressive therapy with potassium-competitive acid blockers is becoming available and should be studied.

• Central neuromodulators, as amitriptyline and mirtazapine, and peripherally acting neuromodulators as cannabinoids and guanylyl-cyclase agonists, have a potential to provide benefit by acting on visceral hypersensitivity.

• Also, some herbal preparations have shown efficacy in FD, and this approach benefits from the combination of several modes of action in a single treatment.

• More recent, pathophysiological insights, such as low-grade duodenal inflammation, bacterial proliferation, hypersensitivity to acid and impaired permeability, are novel targets for therapy, using for instance histamine antagonists, more powerful acid suppressants, probiotics, and antibiotics.

This box summarizes key points contained in the article.

Declaration of interest

J Tack has given Scientific advice to Alfa Wassermann, Allergan, Christian Hansen, Danone, Grünenthal, Ironwood, Janssen Pharmaceuticals, Kiowa Kirin, Menarini, Mylan, Neutec, Novartis, Noventure, Nutricia, Shionogi, Shire, Takeda, Theravance, Tramedico, Truvion, Tsumura, Zealand and Zeria Pharmaceutical Co. Ltd and has served on the Speaker’s bureau for Abbott, Allergan, AstraZeneca, Janssen, Kyowa Kirin, Menarini, Mylan, Novartis, Shire, Takeda, Truvion and Zeria Pharmaceutical Co. Ltd. A Vandenberghe has given scientific advice to Zeria Pharmaceutical Co. Ltd, Zeria Group, Tsumura, Tillots, Mylan, Menarini, AstraZeneca and Abbott. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors are supported by the University of Leuven through a Methusalem grant to Professor Jan Tack.