Pharmacological Treatment of Functional Dyspepsia
First-Line Treatment Algorithm
All patients with functional dyspepsia should first undergo non-invasive H. pylori testing and receive eradication therapy if positive, followed by empirical acid suppression with proton pump inhibitors (PPIs) if symptoms persist. 1, 2
H. pylori Eradication (If Positive)
- Triple therapy regimen: Omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg, all twice daily for 10 days 3
- This provides modest but meaningful symptom improvement in 24-82% of infected patients 4
Acid Suppression Therapy (First-Line for H. pylori-Negative or Persistent Symptoms)
For Epigastric Pain Syndrome (EPS) subtype:
- PPI therapy: Lansoprazole 15-30 mg once daily taken 30-60 minutes before breakfast for 4-8 weeks 2, 5
- Alternative: Omeprazole 20 mg once daily before breakfast for 4-8 weeks 3
- PPIs are particularly effective for EPS, with 30-70% responder rates 4
- H2-receptor antagonists (alternative): Famotidine 20 mg twice daily (morning and bedtime) for up to 6 weeks 2, 6
For Postprandial Distress Syndrome (PDS) subtype:
- Prokinetic agents are the rational first choice after H. pylori management 2
- Acotiamide (if available) has superior safety profile with no cardiac concerns 7
- Avoid domperidone due to QT prolongation and cardiac arrhythmia risk 7
Second-Line Treatment
Tricyclic antidepressants (TCAs) are the most effective second-line therapy, particularly for refractory EPS. 1, 2, 7
Amitriptyline Regimen
- Starting dose: 10 mg once daily at bedtime 1, 7
- Titration: Increase slowly to 30-50 mg once daily based on response and tolerability 1, 7, 3
- Duration: Use as gut-brain neuromodulator, not as antidepressant 1, 7
Patient Counseling for Amitriptyline
- Explain this is being used as a "gut-brain neuromodulator" rather than for depression to improve adherence 7
- Counsel about common side effects: dry mouth (25%), somnolence (54%), constipation (13%), weight gain (12%) 7
- Exercise caution in patients with cardiac conditions due to anticholinergic effects and potential QT prolongation 7
Alternative Second-Line Agents (If TCAs Contraindicated)
- Antipsychotics: Sulpiride 100 mg four times daily or levosulpiride 25 mg three times daily 1
- Requires careful explanation of rationale and counseling about side effects 1
Treatment Algorithm by Symptom Subtype
For EPS (Predominant Epigastric Pain/Burning):
- Test and treat H. pylori if positive 2
- PPI therapy: Lansoprazole 15-30 mg once daily or omeprazole 20 mg once daily for 4-8 weeks 2, 5
- If inadequate response: Amitriptyline 10 mg at bedtime, titrate to 30-50 mg daily 1, 7
For PDS (Predominant Fullness/Bloating/Early Satiety):
- Test and treat H. pylori if positive 2
- Prokinetic agent as first-line symptomatic therapy 2
- If prokinetic fails: Switch to full-dose PPI therapy (patient may have been misclassified) 2
- If symptoms persist: Amitriptyline 10 mg at bedtime, titrate to 30-50 mg daily 1, 7
Management of Refractory or Severe Cases
A multidisciplinary team including primary care physicians, dietitians, gastroenterologists, and psychologists is mandatory for severe or refractory functional dyspepsia. 1, 2, 3
Key Interventions:
- Screen for eating disorders including avoidant restrictive food intake disorder (ARFID) in patients with weight loss and food restriction 1, 2
- Early dietitian referral to prevent overly restrictive diets that lead to malnutrition 1, 2, 3
- Consider combination therapies (e.g., TCA + PPI) for augmentation effects 1
- Regular aerobic exercise is recommended for all patients 2, 3
Critical Safety Warnings and Pitfalls
Absolute Contraindications:
- Never prescribe opioids for functional dyspepsia—they cause iatrogenic harm without benefit 1, 2, 3
- Avoid surgery in severe or refractory cases to minimize harm 1, 2
- Avoid cisapride due to fatal cardiac arrhythmias and QT prolongation 1, 2
Common Pitfalls:
- Do not skip first-line therapy (H. pylori eradication and PPI trial) before using amitriptyline 7
- Do not start amitriptyline at high doses—begin at 10 mg to minimize side effects 7
- Avoid overly restrictive diets that may lead to malnutrition or eating disorders 2, 3
- Do not routinely perform gastric emptying studies or 24-hour pH monitoring in typical functional dyspepsia 2, 3
Dosage Adjustments:
- Severe hepatic impairment (Child-Pugh C): Reduce lansoprazole to 15 mg daily 5
- Renal impairment (CrCl <60 mL/min): Reduce famotidine to 20 mg once daily or 40 mg every other day 6
Patient Education and Communication
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." 2, 3