What is the initial treatment for dyspepsia?

Initial Treatment for Dyspepsia

For patients with uninvestigated dyspepsia who are under age 55 without alarm symptoms and have had symptoms for 4 weeks or longer, test for H. pylori using a validated non-invasive test (13C urea breath test or stool antigen test) and eradicate if positive; if H. pylori negative or symptoms persist after successful eradication, initiate full-dose PPI therapy with omeprazole 20 mg once daily for 4-8 weeks. 1, 2, 3

Age-Based Stratification and Alarm Features

• Patients ≥55 years with dyspepsia or those with alarm symptoms (weight loss, vomiting, dysphagia, gastrointestinal bleeding) require prompt endoscopy before empirical treatment. 2, 3
• Patients ≥60 years with abdominal pain and weight loss need urgent abdominal CT to exclude pancreatic cancer. 1, 2
• For patients under 55 without alarm features, endoscopy is not mandatory as diagnostic yield is low. 2, 4

Short-Duration Symptoms (Less Than 4 Weeks)

• Patients without alarm symptoms who have had symptoms for less than 4 weeks can be managed with reassurance, over-the-counter medications, and watchful waiting. 5

First-Line Treatment Algorithm for Symptoms ≥4 Weeks

Step 1: H. pylori Testing Strategy

• Test all patients for H. pylori using a 13C urea breath test or stool antigen test (or locally validated serology with ≥90% sensitivity and specificity if breath/stool tests unavailable). 5, 2
• Most whole blood tests lack adequate sensitivity and should be avoided. 5
• If H. pylori positive, provide eradication therapy as first-line treatment—this eliminates peptic ulcer mortality risk even if dyspeptic symptoms persist. 5, 2
• Confirm successful eradication only in patients at higher risk of gastric cancer. 1, 2

Step 2: Empirical Acid Suppression

For H. pylori-negative patients or those with persistent symptoms after successful eradication:

• Start omeprazole 20 mg once daily taken 30-60 minutes before breakfast for 4-8 weeks. 1, 2, 3
• This full-dose PPI therapy is particularly effective for ulcer-like dyspepsia where epigastric pain is the predominant symptom. 5, 1
• H2-receptor antagonists (like famotidine) may be used as an alternative first-line option, though evidence is weaker than for PPIs. 2, 6

Alternative Approach in Low H. pylori Prevalence Areas

• In populations with H. pylori prevalence <10%, empirical PPI therapy without testing is a reasonable initial option. 3, 7
• The test-and-treat strategy is preferable when H. pylori prevalence is ≥10%. 3

Symptom-Based Treatment Selection

After H. pylori testing/treatment:

• Ulcer-like dyspepsia (epigastric pain predominant): Full-dose PPI is first choice—omeprazole 20 mg once daily confirms acid-related nature of symptoms. 5, 1
• Dysmotility-like dyspepsia (fullness, bloating, early satiety predominant): Consider prokinetic agents, though cisapride is contraindicated due to cardiac toxicity. 5
• Patients with predominant heartburn should be treated as GERD rather than functional dyspepsia. 5

Management of Treatment Response

If Symptoms Improve

• Attempt therapy withdrawal after 4-8 weeks of successful treatment. 5, 1, 2
• If symptoms recur, restart the same effective treatment. 5, 2
• On-demand therapy with the successful agent is a valid long-term strategy. 5, 1, 2
• Taper to the lowest effective dose that controls symptoms. 1, 2

If Symptoms Persist After Initial Therapy

• If no response after 4 weeks on once-daily PPI, escalate to twice-daily dosing (omeprazole 20 mg before breakfast and dinner). 1, 2
• If the patient was misclassified (e.g., dysmotility symptoms on PPI), switch treatment class from PPI to prokinetic or vice versa. 5
• Reassess at 4-8 weeks after escalation. 1, 2

Second-Line Treatment for Refractory Symptoms

• Low-dose tricyclic antidepressants are the preferred second-line treatment: start amitriptyline 10 mg once daily and titrate slowly to maximum 30-50 mg once daily. 1, 2, 3
• Some antipsychotics like sulpiride 100 mg four times daily or levosulpiride 25 mg three times daily may be effective as second-line options. 1
• Acotiamide may be considered if TCAs are not tolerated, as it has a superior safety profile compared to other prokinetics. 2

Important Considerations and Pitfalls

• Do not continue H2-receptor antagonists indefinitely hoping for delayed response—9 weeks is well beyond the timeframe where additional benefit would be expected; switch to PPI instead. 1
• PPIs are safe for dyspepsia treatment, and concerns about PPI-associated adverse events should not drive treatment decisions when there is a clear indication. 1
• Regular aerobic exercise is recommended for all patients with functional dyspepsia. 1, 2
• Do not prescribe opioids for chronic dyspepsia as they cause harm without benefit. 2
• Avoid domperidone due to cardiac safety concerns including QT prolongation. 2
• 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 before further escalation. 1, 2