What is the recommended treatment for indigestion?

Treatment for Indigestion

All patients with indigestion should first be tested for H. pylori infection and receive eradication therapy if positive, followed by proton pump inhibitors (PPIs) as first-line pharmacological treatment if symptoms persist. 1

Initial Assessment and Testing

Test all patients for H. pylori infection using either a stool antigen test or breath test, as this is the only treatment proven to change the natural history of functional dyspepsia and eliminate ulcer risk. 1

• If H. pylori positive, provide eradication therapy with antibiotics immediately—this provides modest but meaningful symptom improvement even in functional dyspepsia. 1, 2
• Adverse events are more common with eradication therapy than placebo, but the benefit of eliminating ulcer risk and mortality justifies treatment. 1, 2

Consider urgent evaluation in specific high-risk scenarios:

• Patients ≥55 years with weight loss require urgent endoscopy. 3
• Patients >40 years from high-risk areas for gastric cancer or with family history of gastro-esophageal cancer need endoscopy. 3
• Patients ≥60 years with abdominal pain and weight loss should undergo urgent abdominal CT to exclude pancreatic cancer. 3

First-Line Pharmacological Treatment

After H. pylori testing (and eradication if positive), offer empirical acid suppression with PPIs as the primary pharmacological intervention. 1

• PPIs are highly efficacious for functional dyspepsia, particularly for epigastric pain syndrome, with strong evidence quality. 1, 2
• Use the lowest dose that controls symptoms—there is no dose-response relationship, so starting with standard dose (e.g., omeprazole 20 mg once daily) is appropriate. 1
• PPIs are well-tolerated with minimal adverse effects in short-term use. 1

H2-receptor antagonists (H2RAs) are an alternative when PPIs are not tolerated or available, though evidence is weaker. 1, 2

• H2RAs may be efficacious and are well-tolerated. 1
• Consider for breakthrough or nighttime symptoms, though tachyphylaxis limits long-term use. 1

Lifestyle Modifications

Recommend regular aerobic exercise to all patients with indigestion, as this has demonstrated benefit despite limited evidence quality. 1, 3, 4

Advise patients to avoid specific foods that trigger their symptoms, but caution against overly restrictive diets that could lead to malnutrition or abnormal eating habits. 1, 3

• Common trigger foods include spicy foods, chocolate, pizza, tomato, fried foods, fatty foods, and carbonated beverages. 5
• There is insufficient evidence to recommend specialized diets, including low FODMAP diets, for functional dyspepsia. 1, 3

Second-Line Treatment for Refractory Symptoms

Tricyclic antidepressants (TCAs) are the evidence-based second-line therapy when first-line treatments fail. 1, 2

• Start with low-dose amitriptyline 10 mg once daily and titrate slowly to a maximum of 30-50 mg once daily. 1, 2
• TCAs function as "gut-brain neuromodulators" affecting visceral hypersensitivity through peripheral and central nervous system actions. 2
• Counsel patients carefully about the rationale for use (not treating depression) and side effect profile including dry mouth, constipation, drowsiness, and sedation. 1, 2
• Therapeutic effect takes several weeks to manifest and is independent of antidepressant effects on mood. 2
• Consider switching to secondary amine TCAs (desipramine, nortriptyline) if poorly tolerated, as these have lower anticholinergic effects. 2

Prokinetic agents may be considered if available, though efficacy varies by drug class and many are unavailable outside Asia and the USA. 1, 3

• Tegaserod has moderate evidence quality, while acotiamide, itopride, and mosapride have low evidence quality. 1

Treatment Algorithm Based on Symptom Pattern

For epigastric pain syndrome (predominant burning or pain):

• First-line: PPI or H2-receptor antagonist 3
• Second-line: Tricyclic antidepressant 3

For postprandial distress syndrome (predominant fullness, bloating, early satiety):

• First-line: Prokinetic agent (if available) 3
• Alternative: PPI trial 3

Management of Severe or Refractory Cases

Refer to gastroenterology when symptoms are severe, refractory to first-line treatments, or when diagnostic doubt exists. 1, 3, 4

Severe refractory symptoms require multidisciplinary management including primary care physicians, dietitians, gastroenterologists, and psychologists. 1, 3, 4

• Screen patients with weight loss and food restriction for eating disorders, including avoidant restrictive food intake disorder (ARFID). 1, 3
• Involve dietitian early to prevent overly restrictive diets. 1, 3

Critical Pitfalls to Avoid

Do not routinely perform gastric emptying studies or 24-hour pH monitoring in patients with typical indigestion symptoms. 1, 4

Avoid opioids and surgery in patients with severe or refractory functional dyspepsia to minimize iatrogenic harm. 1, 3

Do not use acid suppression without H. pylori eradication in H. pylori-positive patients, as this represents inadequate treatment of possible ulcer disease. 2

Be aware of PPI long-term risks when used beyond medically indicated duration, including increased risk of fundic gland polyps (especially beyond one year), potential hypomagnesemia (after 3+ months), vitamin B-12 deficiency (after 3+ years), and increased risk of Clostridium difficile infection. 6

Avoid combining omeprazole with clopidogrel, as omeprazole reduces clopidogrel's antiplatelet activity even when dosed 12 hours apart. 6

Long-Term Management Strategy

Consider treatment withdrawal trials after initial symptom control, with re-treatment using the successful medication if symptoms recur. 2

Switch between PPI and prokinetic if non-responsive to first-line therapy, as symptom misclassification is possible. 2

Wean acid suppression to the lowest effective dose or switch to H2RAs once symptoms are controlled, except in patients with erosive esophagitis (Los Angeles B or greater), Barrett's esophagus, or peptic stricture who require long-term PPI therapy. 1