What are the treatment options for a patient with functional dyspepsia?

Treatment of Functional Dyspepsia

First-Line Treatment Algorithm

All patients with functional dyspepsia must undergo non-invasive H. pylori testing ("test and treat") and receive eradication therapy if positive, as this is the only treatment with high-quality evidence for efficacy. 1, 2

Step 1: H. pylori Testing and Eradication

• Perform non-invasive H. pylori testing (stool antigen or urea breath test) in all patients with dyspepsia 1, 2
• If positive, provide eradication therapy (typically triple or quadruple therapy depending on local resistance patterns) 1, 2
• Eradication provides modest but meaningful symptom improvement, though adverse events are more common than control therapy 1
• Confirmation of eradication is only needed in patients at increased risk for gastric cancer 1

Step 2: Empirical Acid Suppression (H. pylori-negative or persistent symptoms)

• Proton pump inhibitors (PPIs) are the first-line pharmacological treatment for H. pylori-negative patients or those with persistent symptoms after eradication 1, 2
• Use the lowest effective dose—there is no dose-response relationship 1
• PPIs are particularly effective for epigastric pain syndrome (EPS) subtype 2, 3
• H2-receptor antagonists are an alternative option, though with weaker evidence 1

Common pitfall: Avoid long-term PPI use without reassessment due to risks of acute tubulointerstitial nephritis, C. difficile infection, bone fractures, hypomagnesemia, and vitamin B12 deficiency 4

Step 3: Lifestyle Modifications (concurrent with pharmacotherapy)

• Recommend regular aerobic exercise for all patients 1, 2
• Advise avoiding specific trigger foods while cautioning against overly restrictive diets that risk malnutrition 2, 5
• There is insufficient evidence to recommend low FODMAP or other specialized diets 1, 2

Second-Line Treatment for Refractory Symptoms

For Postprandial Distress Syndrome (PDS)

• Prokinetic agents are the rational first choice for bloating-predominant symptoms and early satiety 2
• Metoclopramide is the only available effective prokinetic in many regions, but use requires extreme caution 6, 7

Critical safety warning: Metoclopramide carries a black box warning for tardive dyskinesia (TD), which increases with duration of use and may be irreversible. Risk is highest in elderly women and diabetics. Never prescribe metoclopramide for longer than 12 weeks 6

• Alternative prokinetics include acotiamide, itopride, and mosapride where available 8, 3
• If prokinetic therapy fails, switch to full-dose PPI for 4-8 weeks, as patients may have been misclassified 2

For Epigastric Pain Syndrome (EPS) or Treatment-Resistant Cases

• Low-dose tricyclic antidepressants (TCAs) are the most effective second-line treatment, particularly for EPS 2, 5, 3
• Start with amitriptyline 10 mg once daily at bedtime, slowly titrating to 30-50 mg as tolerated 5, 8
• TCAs work by modulating visceral hypersensitivity and central pain processing 7, 3

Management of Severe or Refractory Cases

When to Refer to Gastroenterology

• Diagnostic uncertainty 1
• Severe symptoms despite first-line treatments 1
• Treatment-resistant dyspepsia in patients ≥55 years (consider non-urgent endoscopy) 1
• Patient request for specialist opinion 1

Multidisciplinary Team Approach

• Severe refractory cases require management by a team including primary care physicians, dietitians, gastroenterologists, and psychologists 2, 5
• Early dietitian referral prevents excessively restrictive diets that can lead to malnutrition or eating disorders 2, 5
• Screen patients with severe FD presenting with weight loss and food restriction for avoidant restrictive food intake disorder (ARFID) 2

Combination Therapy Options

• Consider dual therapy with different medication classes (e.g., TCA plus PPI) 5
• Behavioral therapies including cognitive behavioral therapy may benefit refractory cases 9, 10

Critical safety warning: Avoid opioids and surgery in severe or refractory functional dyspepsia to minimize iatrogenic harm 2, 5

Essential Diagnostic Considerations

Age-Based Endoscopy Thresholds

• Urgent endoscopy: Patients ≥55 years with weight loss, or >40 years from high gastric cancer risk areas or with family history of gastro-oesophageal cancer 1, 2
• Non-urgent endoscopy: Patients ≥55 years with treatment-resistant dyspepsia, raised platelet count, or persistent nausea/vomiting 1, 2
• Urgent abdominal CT: Patients ≥60 years with abdominal pain and weight loss to exclude pancreatic cancer 1, 2

Additional Testing

• Full blood count in patients ≥55 years 1, 2
• Coeliac serology in patients with overlapping IBS-type symptoms 1, 2
• Do not routinely perform gastric emptying studies or 24-hour pH monitoring in typical FD 1, 2

Patient Communication Strategy

Establish an empathic relationship and explain that functional dyspepsia is a disorder of gut-brain interaction—not a psychological condition or "all in their head" 1, 2, 5

• Discuss the underlying pathophysiology, natural history, and common symptom triggers 1, 2
• This approach reduces healthcare utilization and improves quality of life 1, 2
• Frame FD as a real physiological disorder involving altered gut motility, visceral hypersensitivity, and duodenal inflammation 9, 11