Two Syndromes in One
Functional dyspepsia (FD) is defined by Rome IV as bothersome symptoms originating from the gastroduodenal region, in the absence of structural disease that explains them. It is divided into two subtypes that often overlap. Postprandial distress syndrome (PDS) features early satiation and postprandial fullness — the sensation that food sits in the stomach like a brick. Epigastric pain syndrome (EPS) centres on burning or gnawing pain in the upper abdomen, not exclusively related to meals.
Global prevalence is estimated at 7 to 8 percent under Rome IV criteria. Many patients meet criteria for both subtypes simultaneously, and overlap with IBS is common — roughly 30 to 40 percent of FD patients also meet IBS criteria.
What Goes Wrong
Several mechanisms have been identified in subsets of FD patients, though no single mechanism explains all cases. Delayed gastric emptying is present in about 25 to 35 percent of PDS patients, confirmed by gastric emptying scintigraphy or breath test. Impaired gastric accommodation — the failure of the stomach fundus to relax after food intake — has been demonstrated by barostat studies in another subset.
Duodenal eosinophilia and mast cell infiltration have emerged as particularly intriguing findings. Studies show that FD patients have increased eosinophils and mast cells in the duodenal mucosa, potentially causing local nerve sensitisation. These cells release mediators (histamine, serotonin, nerve growth factor) that activate submucosal sensory neurons, contributing to visceral hypersensitivity.
Helicobacter pylori infection is found in 20 to 50 percent of FD patients depending on geographic prevalence. Rome IV classifies H. pylori-associated dyspepsia separately: if symptoms resolve after eradication and remain absent for 6 months, the diagnosis is H. pylori-associated dyspepsia rather than functional dyspepsia. This makes test-and-treat a logical first step in populations with H. pylori prevalence above 10 percent.
Treatment Approach
First-line management depends on the subtype. For EPS, a 4 to 8 week trial of proton pump inhibitors (PPIs) is recommended — not because FD involves excess acid, but because even normal acid levels can trigger pain in sensitised mucosa. Response rates are modest, around 30 to 40 percent above placebo.
For PDS, prokinetics (domperidone, itopride) that accelerate gastric emptying may help. In both subtypes, low-dose tricyclic antidepressants (amitriptyline 10-25mg) used as visceral analgesics — not as antidepressants — show benefit in randomised trials. The FDACT trial (Talley et al., Lancet 2024) demonstrated amitriptyline's superiority over placebo in FD independent of baseline anxiety or depression.
Gut-directed hypnotherapy and cognitive behavioural therapy are effective second-line options, particularly in patients with psychological comorbidity or PPI-refractory symptoms. Dietary modification — smaller, more frequent meals, low-fat content, avoiding known personal triggers — is pragmatic and low-risk.