What is the recommended treatment approach for a typical adult patient with dyspepsia?

Treatment of Dyspepsia

All patients with dyspepsia should first undergo non-invasive testing for Helicobacter pylori and receive eradication therapy if positive; if H. pylori is negative or symptoms persist after eradication, start omeprazole 20 mg once daily taken 30-60 minutes before breakfast for 4-8 weeks. 1, 2, 3

Initial Risk Stratification and Red Flags

Before initiating empiric therapy, identify patients requiring urgent evaluation:

• Perform non-urgent endoscopy in patients ≥55 years with treatment-resistant dyspepsia, elevated platelet count, nausea, or vomiting 1
• Perform urgent abdominal CT in patients ≥60 years with abdominal pain and weight loss to exclude pancreatic cancer 1
• Perform prompt endoscopy in patients with alarm features (dysphagia, persistent vomiting, gastrointestinal bleeding) or regular NSAID users 2, 4

First-Line Treatment Algorithm

Step 1: Test for H. pylori

• Test all patients using a validated non-invasive test (urea breath test or stool antigen test) 1, 2, 4
• If H. pylori positive, provide eradication therapy with triple therapy: omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg, all twice daily for 10 days 1, 3
• If ulcer is present at therapy initiation, continue omeprazole 20 mg once daily for an additional 18 days 3
• Confirm successful eradication only in patients at increased risk of gastric cancer 1

Step 2: Empiric Acid Suppression (if H. pylori negative or symptoms persist after eradication)

• Start omeprazole 20 mg once daily taken 30-60 minutes before breakfast for 4-8 weeks 1, 5, 3
• This represents full-dose PPI therapy and is the FDA-approved starting dose for symptomatic GERD and dyspepsia 5, 3
• PPIs are superior to H2-receptor antagonists (famotidine) for dyspepsia treatment 1, 5
• Use the lowest dose that controls symptoms—there is no dose-response relationship with PPIs 1

Managing Treatment Response

If Symptoms Improve After 4-8 Weeks

• Attempt therapy withdrawal to assess ongoing need 5, 2
• If symptoms recur, restart the same treatment that was effective 1, 5
• On-demand therapy is a valid long-term strategy rather than continuous daily use 1, 5
• Taper to the lowest effective dose that controls symptoms 5

If Symptoms Persist on Once-Daily PPI

• Escalate to twice-daily dosing: omeprazole 20 mg before breakfast and dinner 5
• Assess response at 4-8 weeks after escalation 5
• If the patient was on H2-receptor antagonist (famotidine) for 9 weeks without adequate response, switch to full-dose PPI rather than continuing the H2RA indefinitely 5

Second-Line Treatment for Refractory Symptoms

Tricyclic Antidepressants (Preferred Second-Line)

• Start amitriptyline 10 mg once daily at bedtime as the most effective second-line treatment 1, 6, 2
• Titrate slowly to a maximum of 30-50 mg once daily based on response and tolerability 1, 6
• TCAs have moderate-quality evidence supporting their use in functional dyspepsia 1, 7
• Provide careful explanation about the rationale for use as a gut-brain neuromodulator, not as an antidepressant 1
• Counsel patients about side effects (dry mouth, sedation, constipation) 1

Alternative Second-Line Options

• Prokinetic agents may be considered if TCAs are not tolerated, though availability varies by region 1
• Acotiamide has a superior safety profile compared to other prokinetics 6, 7
• Avoid domperidone due to cardiac safety concerns (QT prolongation, arrhythmias) 6
• Metoclopramide should only be used short-term with discussion of side effects 8

Management of Severe or Refractory Dyspepsia

When to Refer to Gastroenterology

• Diagnostic doubt, severe symptoms, or refractory to first-line treatments 1
• Patient requests specialist opinion 1
• Ideally manage in a specialist clinic with access to interested clinician, dietetic support, and gut-brain behavioral therapies 1

Multidisciplinary Approach for Severe Cases

• Involve multidisciplinary team including primary care, dietitians, gastroenterologists, and psychologists 6, 2
• Arrange early dietitian involvement to prevent overly restrictive diets that worsen nutritional status 6
• Assess for eating disorders (including avoidant restrictive food intake disorder) in patients with weight loss and food restriction 6, 2
• Consider behavioral therapies or psychotherapy in patients with psychological comorbidity 1

Further Diagnostic Testing (Only if Refractory to Twice-Daily PPI)

• If symptoms persist despite twice-daily PPI after 4-8 weeks, consider prolonged wireless pH monitoring off PPI (96-hour preferred) to confirm acid reflux mechanism 5
• Do not routinely perform gastric emptying testing or 24-hour pH monitoring in patients with typical FD symptoms 1

Adjunctive Lifestyle Measures

• Recommend regular aerobic exercise for all patients with functional dyspepsia 1, 6
• Dietary changes (frequent small meals, low-fat diet, avoiding aggravating foods) may improve symptoms 8
• Cessation of smoking, avoiding excess alcohol, and minimizing coffee intake 8
• Antacids may be used concomitantly with omeprazole 3

Critical Safety Warnings and Treatments to Avoid

• Do not prescribe opioids for chronic dyspepsia—they cause harm without benefit 6, 2
• Do not refer for surgery—there is no surgical treatment for functional dyspepsia 6, 2
• Do not pursue additional endoscopy unless new alarm features develop 5, 6
• Emphasize PPI safety and do not let concerns about PPI-associated adverse events drive treatment decisions when there is clear indication 5
• Do not continue H2-receptor antagonists indefinitely hoping for delayed response after 9 weeks—escalate to PPI instead 5

Patient Communication Strategy

• Explain that functional dyspepsia is a disorder of gut-brain interaction, not a psychological condition or "all in their head" 2
• Discuss underlying pathophysiology, natural history, and common symptom triggers to improve quality of life and reduce healthcare utilization 2
• Set realistic expectations—functional dyspepsia is chronic with fluctuating symptoms in most patients 9