What is the recommended treatment for a patient with non-ulcer dyspepsia?

Treatment of Non-Ulcer Dyspepsia

All patients with non-ulcer dyspepsia (functional dyspepsia) should first undergo H. pylori testing and receive eradication therapy if positive, followed by empirical proton pump inhibitor therapy if H. pylori-negative or symptoms persist, with tricyclic antidepressants reserved as second-line treatment. 1

Initial Diagnostic Approach

• Test all patients for H. pylori infection using non-invasive testing (urea breath test or stool antigen) and provide eradication therapy if positive, as this is the only treatment that may alter the natural history of the condition 1
• Perform full blood count in patients aged ≥55 years and coeliac serology in those with overlapping IBS-type symptoms 1
• Reserve urgent endoscopy only for patients aged ≥55 years with weight loss, or those aged >40 years from high gastric cancer risk areas or with family history of gastro-oesophageal cancer 1

First-Line Pharmacological Treatment

For H. pylori-Positive Patients

• Eradication therapy is highly efficacious (strong recommendation, high-quality evidence), though adverse events are more common than control therapy 1
• Confirm successful eradication only in patients at increased risk of gastric cancer 1

For H. pylori-Negative Patients or Persistent Symptoms

• Proton pump inhibitors (PPIs) are the first-line treatment (strong recommendation, high-quality evidence) 1
• Use the lowest effective dose that controls symptoms, as there is no dose-response relationship 1
• PPIs are well-tolerated and superior to H2-receptor antagonists, which have only weak evidence (weak recommendation, low-quality evidence) 1

Second-Line Treatment for Refractory Symptoms

Prokinetic Agents (for postprandial distress symptoms)

• Consider prokinetics only after H. pylori eradication and PPI trial have failed 2
• Acotiamide 100 mg three times daily is the preferred first-line prokinetic based on robust clinical trial data and long-term safety evidence 2
• Itopride is an alternative if acotiamide is unavailable or unaffordable 2
• Cintapride may be chosen for patients with overlapping GERD symptoms, but avoid combining with QT-prolonging agents 2
• Tegaserod has strong evidence (strong recommendation, moderate-quality evidence) but limited availability 1
• Note: Many prokinetics are unavailable outside Asia and the USA 1, 2

Tricyclic Antidepressants (TCAs)

• TCAs are efficacious second-line treatment (strong recommendation, moderate-quality evidence) when first-line therapies fail 1
• Start amitriptyline at 10 mg once daily at bedtime and titrate slowly to maximum 30-50 mg once daily 1
• Provide careful explanation that these are used as gut-brain neuromodulators, not for depression 1
• Counsel patients about side effect profile before initiating 1

Non-Pharmacological Management

• Advise all patients to take regular aerobic exercise (strong recommendation) 1
• Establish an empathic doctor-patient relationship with shared understanding of the condition, which may reduce healthcare utilization and improve quality of life 1
• Explain that functional dyspepsia is a disorder of gut-brain interaction with a chronic, fluctuating course affecting approximately two-thirds of patients long-term 3
• Discuss common symptom triggers and the gut-brain axis, including how diet, stress, and emotional responses impact symptoms 1
• There is insufficient evidence to recommend specific dietary therapies, including low-FODMAP diets 1

Referral Criteria

• Refer to gastroenterology when there is diagnostic doubt, severe symptoms, refractoriness to first-line treatments, or patient request for specialist opinion 1
• Ideally, manage referred patients in specialist clinics with access to dietetic support, efficacious drugs, and gut-brain behavioral therapies 1

Critical Pitfalls to Avoid

• Do not use prokinetics as first-line therapy—PPIs have stronger evidence and should be tried first 2
• Do not routinely perform gastric emptying testing or 24-hour pH monitoring in patients with typical functional dyspepsia symptoms 1
• Avoid opioids or surgery for refractory symptoms to minimize iatrogenic harm 3
• Counsel patients that prokinetics work best for meal-related symptoms (early satiety, postprandial fullness) rather than epigastric pain 2
• Involve dietitians early if food restriction develops to prevent overly restrictive diets 3