Reference: September 2025 | Issue 9 | Vol 11 | Page 10
Approximately 7 per cent of individuals worldwide suffer from functional dyspepsia (FD), according to the results of the Rome Foundation Global Study, which were published in 2021. This figure rises to almost 10 per cent in people in their 20s and 30s, and is significantly more common in women.
The latest United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on FD recommends proton pump inhibitors (PPIs) as the only medical treatment. However, one of the authors of that consensus has expressed his dissatisfaction with the final recommendation.
“In terms of treatment, this is giving the clinician very little to act with,” said Prof Jan Tack, Head of the Department of Gastroenterology and Hepatology, University Hospital Leuven, Belgium, and one of the authors of the UEG-ESNM consensus statement.
“It recommends Helicobacter pylori (H pylori) eradication and a PPI. That’s about it. You can think of diet or an antidepressant, but no further support. This is where I get disappointed.”
There is more to the treatment of FD than PPIs, he said.
Subgroups
The ROME definition of FD requires one or more of the following symptoms to be present for the last three months, with symptom onset at least six months prior to diagnosis:
- Bothersome post-prandial fullness;
- Bothersome early satiation;
- Bothersome epigastric pain;
- Bothersome epigastric burning;
- No evidence of structural disease that is likely to explain the symptoms.
The condition is categorised into two subgroups: Postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Approximately two-thirds of people with FD have PDS, while an estimated 15.3 per cent have EPS alone and 18 per cent have PDS-EPS overlap.
PDS is meal-triggered and symptoms include early satiation, postprandial fullness, and other post-prandial symptoms. EPS is characterised by epigastric pain and burning and is usually not clearly related to the meal.
FD is a consequence of disordered stomach function. A third of patients show impaired gastric accommodation and a third have disordered emptying. In recent years research has also “honed in on the duodenum”, according to Prof Tack.
Low-grade duodenal inflammation has been observed in FD, and duodenal eosinophils and mast cells, together or separately, play a key role in immune activation.
Management
Although prokinetic agents provide the most pathophysiology-oriented treatment option for PDS, Prof Tack pointed out that there is a paucity of suitable agents. Other options include agents that enhance gastric accommodation such as 5-HT1A agonists, neuromodulators such as mirtazapine, and traditional medicine approaches.
The recommended approach for the management of EPS is acid suppression. Other approaches including tricyclic antidepressants, nutritional support, psychotherapy, and traditional therapies can be helpful.
Prof Tack shared his personal approach to treating patients with FD. He pointed out that H pylori eradication has been shown to be the most cost-effective treatment for FD, with efficacy rates of almost 6 per cent in some populations studied. He initiates a H pylori eradication regimen in all test-positive patients.
This has resolved the dyspepsia in approximately 7 per cent of patients. However, he remarked that the literature has shown that the number needed to treat (NNT) is in the region of 12.5 and the therapeutic gain does not reach significance for six to 12 months.
He uses PPIs frequently, both in patients without H pylori and those on H pylori eradication therapy. PPIs have demonstrated efficacy in the management of FD, with one meta-analysis finding a risk ratio of 0.87 compared to placebo.
“PPIs work in these patients, just like they do for reflux, but there are differences,” Prof Tack said. “One difference is that there’s no dose-response effect [in FD]. If you give 20, 40, or 80 milligrams of a PPI, there’s no difference, so you don’t need to escalate.”
The other important difference is that in FD, PPIs should only be used short-term, he stressed. The literature suggests that, in FD, PPIs should be prescribed for 12 months. Why?
“In functional dyspepsia, PPIs are an anti-eosinophil treatment,” Prof Tack explained. “The clinical efficacy has nothing to do with PH effects. This explains the lack of dose response, because you tackled the eosinophils at the lowest dose. It probably also explains why this gets worse because, in healthy volunteers, if you put them on a PPI, they get a leaky mucosa.”
Beyond PPIs
Prof Tack stressed that pharmacological options for the management of FD go beyond just PPIs. He highlighted itopride as an example.
Itopride has bivalent prokinetic effects on gastric motility. It is a cholinesterase inhibitor and a dopamine D2 receptor antagonist. It increases the levels of acetylcholine released from nerve endings and blocks D2, which normally dampens acetylcholine release.
The professor pointed out that several studies have demonstrated itopride’s efficacy in FD. A 2012
meta-analysis of nine randomised controlled trials comparing the drug to domperidone, mosapride, and placebo. Compared with control groups, itopride demonstrated superior benefit in global patient assessment, postprandial fullness, and early satiety. For the Leeds Dyspepsia Questionnaire (LDQ) score, the weighted mean deviation was -1.38. The incidence of adverse effects was similar in the itopride and control groups.
He acknowledged that previous studies have found little benefit from itopride, but he attributed this to the use of LDQ as an endpoint in these studies which, he said, is not an appropriate measure as only two symptoms of FD are included in the LDQ.
He highlighted the results of a double-blind, randomised, controlled trial published in 2022 in Neurogastroenterology and Motility, which found that itopride had no therapeutic benefit over placebo in PDS when using the Leuven Postprandial Distress Scale as the primary endpoint. However, in an exploratory post-hoc analysis, itopride but not placebo was associated with symptom improvement compared to baseline and this was most prominent in patients with overlapping PDS/EPS.
Antidepressants also have a role in the management of some FD cases. A multi-centre, randomised, controlled study of amitriptyline and escitalopram in FD published in Gastroenterology in 2016 found that amitriptyline, but not escitalopram, benefited some patients with FD, particularly those with ulcer-like (painful) FD. Patients with delayed gastric emptying did not respond to these drugs.
Other therapeutic approaches that Prof Tack employs in his clinical practice include prucalopride, mirtazapine, and probiotics. In a study published in the Lancet Gastroenterology and Hepatology, he and his team reported that the probiotics B coagulans MY01 and B subtilis MY02 were efficacious and safe in the treatment of FD.
He also uses nutritional interventions where appropriate and he predicts that this will be an area of growing importance in the coming years.
“I think that will be the next wave we will see – efficacious dietary interventions. That will be popping up. The studies are ongoing and I don’t think all of them are going to be negative. There will be some positive possibilities,” he predicted.
Conclusion
Prof Tack said the point he wanted to stress is that treatment options for FD are not and should not be limited to PPIs.
“I think that is the most important thing,” he said. “PPIs work short-term, but they should not be continued long-term. Alternatives are prokinetics and there are a couple of herbal medicines. For difficult patients, we use neuromodulators and they are actually well tolerated and easy to use.”
