What is the initial treatment for functional dyspepsia?

Initial Treatment for Functional Dyspepsia

All patients with functional dyspepsia should first undergo H. pylori testing and receive eradication therapy if positive, followed by proton pump inhibitor (PPI) therapy as the cornerstone of initial pharmacological management. 1, 2

Diagnostic Prerequisites Before Treatment

• Test all patients for H. pylori infection using non-invasive methods (stool antigen test or urea breath test) before initiating treatment 1, 2
• Perform full blood count in patients ≥55 years and coeliac serology in those with overlapping IBS-type symptoms 2
• Consider urgent endoscopy in patients ≥55 years with weight loss, or those >40 years from high-risk areas for gastric cancer or with family history of gastro-oesophageal cancer 2

First-Line Treatment Algorithm

Step 1: H. pylori Eradication (If Positive)

• Eradication therapy is the mandatory first intervention for all H. pylori-positive patients, regardless of symptom subtype 1, 2
• This provides modest but meaningful symptom improvement and eliminates ulcer risk and mortality 1, 3
• Adverse events are more common than with control therapy, but the benefit outweighs risks 1

Step 2: Lifestyle Modifications (For All Patients)

• Recommend regular aerobic exercise to all patients with functional dyspepsia 1, 2
• Advise patients to avoid specific foods that trigger their symptoms 4, 2
• Critically important: Avoid prescribing overly restrictive diets that may lead to malnutrition or abnormal eating habits 4, 2
• There is insufficient evidence to recommend low FODMAP diets or other specialized dietary therapies 1, 2

Step 3: Empirical Acid Suppression Therapy

For patients without H. pylori or after eradication:

• PPIs are the first-line pharmacological treatment, particularly effective for epigastric pain syndrome (EPS) subtype 1, 2, 3
• Use the lowest dose that controls symptoms (e.g., omeprazole 20 mg once daily) as there is no dose-response relationship 1, 3
• PPIs are well tolerated with high-quality evidence supporting their efficacy 1
• H2-receptor antagonists (H2RAs) are an alternative option when PPIs are not tolerated or available, though evidence is weaker 1, 3

Step 4: Prokinetic Agents (Symptom-Specific)

• For postprandial distress syndrome (PDS) with predominant fullness, bloating, and early satiety, consider prokinetic agents 2, 3
• Efficacy varies by drug class and geographic availability 1
• Most prokinetics are unavailable outside Asia and the USA 1
• Available options include acotiamide, itopride, mosapride (weak recommendation, low evidence), and tegaserod (strong recommendation, moderate evidence) 1

Treatment Strategy for Non-Responders

• If no response to initial PPI therapy, switch to a prokinetic agent (or vice versa) as symptom misclassification is possible 3
• Consider a treatment withdrawal trial after initial symptom control, with re-treatment justified if symptoms recur 3
• Never use acid suppression without H. pylori eradication in H. pylori-positive patients, as this represents inadequate treatment of possible ulcer disease 3

When to Escalate to Second-Line Treatment

• If symptoms remain refractory after H. pylori eradication (if applicable) and trials of both PPI and prokinetic therapy 1, 2
• Tricyclic antidepressants (TCAs) are the evidence-based second-line treatment 1, 4, 3
• Start with low dose (e.g., amitriptyline 10 mg once daily) and titrate slowly to maximum 30-50 mg once daily 1, 4
• Provide careful explanation that TCAs function as "gut-brain neuromodulators" affecting visceral hypersensitivity, not as antidepressants 3
• Counsel patients that symptom improvement may take 4-8 weeks and is unrelated to mood effects 3

Critical Pitfalls to Avoid

• Never prescribe overly restrictive diets that could lead to malnutrition or trigger eating disorders, including avoidant restrictive food intake disorder (ARFID) 4, 2
• Do not routinely perform gastric emptying testing or 24-hour pH monitoring in patients with typical functional dyspepsia symptoms 1, 2
• Avoid combining prokinetic agents like cinitaprida with other medications that prolong the QT interval 4, 2
• In severe or refractory cases, avoid opioids and surgery to minimize iatrogenic harm 1, 2

Referral Indications

• Refer to gastroenterology when there is diagnostic doubt, symptoms are severe or refractory to first-line treatments, or the patient requests specialist opinion 1, 2
• Severe refractory symptoms require management by a multidisciplinary team including primary care physicians, dietitians, gastroenterologists, and psychologists 4, 2
• Early dietitian involvement is essential in refractory cases to prevent overly restrictive diets 1, 2