What is the initial treatment approach for a patient with Non-Ulcer Dyspepsia (NUD)?

Initial Treatment for Non-Ulcer Dyspepsia

All patients with non-ulcer dyspepsia should first undergo H. pylori testing ("test and treat" strategy), and if positive, receive eradication therapy; if negative or symptoms persist after eradication, empirical acid suppression with proton pump inhibitors should be initiated. 1, 2

Age-Based Triage and Alarm Features

Before initiating treatment, determine if urgent investigation is needed:

• Patients ≥55 years with weight loss require urgent endoscopy 1
• Patients >40 years from high-risk areas for gastric cancer or with family history of gastro-oesophageal cancer need urgent endoscopy 1
• Patients ≥60 years with abdominal pain and weight loss require urgent abdominal CT to exclude pancreatic cancer 1
• Non-urgent endoscopy should be considered for patients ≥55 years with treatment-resistant dyspepsia, raised platelet count, or nausea/vomiting 1

First-Line Treatment Algorithm

Step 1: H. pylori Test and Treat Strategy

For all other patients without alarm features, offer non-invasive H. pylori testing (stool antigen or urea breath test) as the initial approach. 1, 2

• This strategy is more cost-effective than empirical therapy and reduces subsequent endoscopy burden 2
• If H. pylori positive: provide eradication therapy (typically triple or quadruple therapy depending on local resistance patterns) 1, 2, 3
• Eradication therapy is highly efficacious for H. pylori-positive functional dyspepsia, though adverse events are more common than control therapy 1
• Confirmation of successful eradication is only necessary in patients at increased risk of gastric cancer 1, 3

Step 2: Empirical Acid Suppression

For H. pylori-negative patients or those with persistent symptoms after successful eradication, offer empirical proton pump inhibitor therapy. 1, 3

• PPIs are highly efficacious for functional dyspepsia and well-tolerated 1
• Use the lowest dose that controls symptoms, as there is no dose-response relationship (e.g., omeprazole 20 mg once daily) 1, 3
• PPIs are particularly effective for ulcer-like dyspepsia with predominant epigastric pain 3

Adjunctive Non-Pharmacological Measures

All patients should be advised to take regular aerobic exercise. 1, 3

• Counsel patients to avoid foods that trigger their specific symptoms 3
• Establish an empathetic doctor-patient relationship and explain that functional dyspepsia is a brain-gut interaction disorder 3
• There is insufficient evidence to recommend specialized diets including low-FODMAP diets 1
• Early dietitian involvement is recommended in refractory cases to prevent overly restrictive diets that could lead to malnutrition 2, 3

Alternative First-Line Options

Histamine-2 Receptor Antagonists

H2-receptor antagonists may be efficacious and are well-tolerated, though evidence is weaker than for PPIs. 1

• These can be considered as an alternative to PPIs or for on-demand therapy 4

Prokinetic Agents

For dyspepsia with predominant bloating, distension, or early satiety, consider a prokinetic agent. 3

• Efficacy varies by drug class and availability differs by region 1
• Acotiamide, itopride, and mosapride have low-quality evidence; tegaserod has moderate-quality evidence 1
• Metoclopramide is available in the US but should be used short-term due to side effect concerns 5, 4

Common Pitfalls to Avoid

• Do not perform empirical H. pylori eradication without prior testing, as this leads to overtreatment 2
• Symptom subgrouping has limited value in predicting underlying disease but may guide treatment choices 2
• Antacids alone are no more effective than placebo and should not be used as primary therapy 6, 5
• Avoid opioids and surgery in refractory cases to minimize iatrogenic harm 3

When to Refer or Escalate

Referral to gastroenterology is appropriate when there is diagnostic doubt, severe symptoms, treatment refractoriness, or patient request for specialist opinion. 1

• Ideally, manage refractory patients in specialist clinics with access to dietetic support, efficacious drugs, and gut-brain behavioral therapies 1
• If first-line therapies fail after 4-8 weeks, consider switching between PPI and prokinetic therapy before escalating to second-line treatments 7, 4