Understanding Functional Dyspepsia (FD)
Functional dyspepsia is a chronic disorder of the upper gastrointestinal tract [1.5.3]. The diagnosis, based on the Rome IV criteria, requires having one or more of the following symptoms for at least three months: bothersome postprandial (after-meal) fullness, early satiation (feeling full quickly), epigastric pain, or epigastric burning, without any evidence of structural disease that could explain the symptoms [1.8.1].
FD is generally categorized into two main subtypes [1.8.2]:
- Postprandial Distress Syndrome (PDS): Characterized by symptoms induced by meals, such as uncomfortable fullness or the inability to finish a normal-sized meal [1.8.2].
- Epigastric Pain Syndrome (EPS): Defined by upper abdominal pain or burning that is not exclusively meal-related [1.8.2].
The causes of FD are considered multifactorial and are not fully understood. Potential mechanisms include delayed gastric emptying, impaired gastric accommodation (the stomach's ability to relax and expand for food), visceral hypersensitivity (increased sensitivity to pain in the digestive tract), and low-grade inflammation in the duodenum [1.8.1, 1.8.2]. Infection with Helicobacter pylori is also considered a risk factor [1.7.2].
Limitations of Traditional Treatments
For years, the management of functional dyspepsia has relied on a few classes of medications, often with unsatisfactory results for many patients [1.9.3].
Acid Suppressants
Proton Pump Inhibitors (PPIs) and H2-receptor antagonists are commonly used as a first-line treatment, especially for patients with epigastric pain [1.7.2, 1.9.1]. While they can be effective for some, particularly those with overlapping heartburn symptoms, a significant number of patients do not experience adequate relief [1.9.3]. Long-term use of PPIs also carries potential risks, although experts believe these are not likely causal in most cases [1.3.4].
Neuromodulators
Low-dose tricyclic antidepressants (TCAs) and other psychotropic agents are used to modulate the perception of visceral pain [1.3.5]. They can be effective, especially for epigastric pain syndrome, but their use can be limited by side effects like sedation [1.7.2].
A New Era in Treatment: What is the new drug for functional dyspepsia?
The most significant recent advancements in FD treatment involve a class of drugs called prokinetics, which are designed to improve gastrointestinal motility. While some older prokinetics like metoclopramide have been used, their application is limited due to significant side effects [1.7.2]. Newer agents offer a better safety profile and more targeted action.
Acotiamide: A First-in-Class Prokinetic
Acotiamide is considered a first-in-class drug developed specifically for functional dyspepsia [1.5.4]. It works by enhancing the release of acetylcholine in the gut, which in turn improves gastric accommodation and gastric emptying [1.5.3].
- Efficacy: Clinical trials have shown that acotiamide is particularly effective for the symptoms of Postprandial Distress Syndrome (PDS), such as postprandial fullness, early satiation, and upper abdominal bloating [1.5.3, 1.5.6]. It has been shown to be superior to a placebo in improving these meal-related symptoms [1.5.6].
- Approval Status: Acotiamide is the world's first approved treatment for FD diagnosed by Rome III criteria, with its initial approval in Japan [1.5.4]. It is also approved in other countries in Europe and Asia [1.2.5]. While it has undergone trials in the US and Europe, it is not yet approved by the FDA in the United States [1.5.4, 1.7.2].
Itopride: Another Promising Prokinetic
Itopride is another prokinetic that acts as both a dopamine D2 receptor antagonist and an acetylcholinesterase inhibitor [1.2.5]. Like acotiamide, it helps improve gut motility. It is approved for FD in several countries, including Japan, Mexico, and some in Europe [1.2.5]. Long-term studies have found it to be generally safe and effective for maintaining symptom benefit for up to a year [1.2.5, 1.2.6].
Other Emerging Therapies
- Prucalopride (Motegrity): While primarily approved for chronic idiopathic constipation, this highly selective 5-HT4 receptor agonist also accelerates gastric emptying [1.6.1, 1.6.2]. Studies suggest it could be effective for patients with functional dyspepsia, particularly those with overlapping constipation symptoms, though more research is needed [1.6.1, 1.6.6].
- IB-Stim™: In May 2025, the FDA cleared a non-pharmacological device called IB-Stim™ for treating functional dyspepsia in pediatric patients (ages 8-21) [1.2.1, 1.4.4]. This device uses percutaneous electrical nerve field stimulation (PENFS) to target nerve branches in the ear, offering a non-drug option for this population [1.2.2].
Comparison of Functional Dyspepsia Medications
| Medication Class | Mechanism of Action | Primary Target Symptoms | Common Side Effects | Example(s) |
|---|---|---|---|---|
| Traditional: PPIs | Reduces stomach acid production [1.3.5] | Epigastric burning, heartburn, acid-related pain [1.3.4] | Headache, diarrhea; potential long-term risks debated [1.3.4] | Omeprazole, Esomeprazole [1.3.5] |
| Traditional: TCAs | Modulates nerve signals to reduce visceral pain perception [1.3.5] | Epigastric pain [1.7.2] | Drowsiness, dry mouth, constipation [1.7.2] | Amitriptyline, Nortriptyline [1.7.2] |
| New: Prokinetics | Enhances gastrointestinal motility and accommodation [1.5.3] | Postprandial fullness, early satiety, bloating [1.5.3] | Generally well-tolerated; may include diarrhea or headache [1.2.5, 1.5.5] | Acotiamide, Itopride [1.5.3, 1.2.5] |
| Emerging: 5-HT4 Agonists | Stimulates serotonin receptors to increase gut motility [1.6.2] | Primarily constipation, but shows promise for gastric emptying [1.6.1] | Headache, abdominal pain, nausea, diarrhea [1.6.4] | Prucalopride [1.6.3] |
Conclusion
The landscape of treatment for functional dyspepsia is evolving, moving beyond simple acid suppression to address the underlying motility issues that plague many patients. While traditional therapies remain a first step, the development of targeted prokinetics like acotiamide and itopride marks a significant advancement, especially for those suffering from postprandial distress syndrome. Although acotiamide is not yet available in the US, its success abroad provides a promising outlook. Additionally, emerging options like prucalopride and novel non-drug therapies like IB-Stim for younger patients indicate a future with more personalized and effective strategies for managing this challenging condition.
For more information on clinical trials, you can visit the U.S. National Library of Medicine's database at https://www.clinicaltrials.gov.
