What medication regimen should be prescribed for an adult with functional dyspepsia without alarm features?

Treatment of Functional Dyspepsia

For adults with functional dyspepsia without alarm features, initiate a test-and-treat strategy for H. pylori followed by a 4-8 week trial of proton pump inhibitor (PPI) therapy if symptoms persist. 1

Initial Management Algorithm

Step 1: H. pylori Testing and Eradication

• Test all patients under age 55 without alarm features using either 13C-urea breath test or stool antigen test (these are the optimal non-invasive methods). 1
• If H. pylori positive, provide eradication therapy first—this helps 1 in 15 patients with functional dyspepsia and may prevent future gastric adenocarcinoma. 1, 2
• After successful eradication, reassess symptoms before proceeding to acid suppression. 1

Step 2: Acid Suppression Therapy

• PPIs are the drug class of choice for functional dyspepsia, superior to H2-receptor antagonists, antacids, and placebo. 1
• Prescribe a standard-dose PPI once daily for 4-8 weeks initially. 1
• PPIs work for both epigastric pain syndrome (ulcer-like dyspepsia) and can benefit postprandial distress syndrome. 3
• If H. pylori is negative from the start, proceed directly to empirical PPI trial. 1

Second-Line Options for PPI Non-Responders

For Dysmotility-Predominant Symptoms

If patients have persistent postprandial fullness, early satiety, bloating, or upper abdominal discomfort after PPI trial, add prokinetic therapy. 4, 3

• Itopride is recommended as first-line prokinetic with excellent safety profile (adverse events only 1.5-3.1%), no cardiac toxicity or QT prolongation reported. 4
• The American College of Gastroenterology rates itopride's safety evidence as high quality. 4
• Itopride can be used as add-on therapy to PPIs when acid suppression alone is insufficient. 4
• Alternative prokinetics include cinitapride (favorable safety profile, minimal QT effects) and mosapride, though overall prokinetic effects are modest. 4, 3

For Pain-Predominant or Refractory Symptoms

Tricyclic antidepressants (TCAs) are the most evidence-based second-line therapy for functional dyspepsia. 5, 6

• Start amitriptyline 10 mg once daily at bedtime, titrate slowly to 30-50 mg once daily as tolerated. 5
• TCAs target visceral hypersensitivity and pain pathways—they have strong recommendation with moderate quality evidence from the British Society of Gastroenterology. 5, 6
• Imipramine is an alternative TCA with demonstrated efficacy. 6
• Levosulpiride (25 mg three times daily) can be combined with amitriptyline for patients with mixed pain and dysmotility symptoms, as it acts as a D2 antagonist with prokinetic activity. 5
• The combination has no significant drug-drug interactions but counsel patients about additive drowsiness and potential hyperprolactinemia. 5

When to Perform Endoscopy

Age-Based Thresholds

• Patients over age 55 with new-onset dyspepsia require endoscopy before empirical therapy due to increased gastric malignancy risk. 1
• Patients under 55 without alarm features can be managed with test-and-treat strategy without endoscopy. 1

Alarm Features Requiring Immediate Endoscopy (Any Age)

• Unintended weight loss 1, 2
• Progressive dysphagia 1, 2
• Recurrent vomiting 1
• Evidence of gastrointestinal bleeding 1, 2
• Family history of gastric cancer 1, 2

Failed Empirical Therapy

• Consider endoscopy in young patients who fail both H. pylori eradication (if positive) and PPI trial, though yield is very low and may not be cost-effective. 1
• Endoscopy may provide reassurance to some patients but evidence suggests this doesn't help those who are most anxious. 1

Important Clinical Caveats

Stop PPIs before the initial diagnostic endoscopy—PPIs can mask malignant ulcers or alter their endoscopic appearance, potentially causing misdiagnosis. 1

The quality of evidence for prokinetics is rated as low overall by major gastroenterology societies, with only modest effects demonstrated. 4 However, itopride specifically has moderate-quality evidence for dysmotility symptoms. 4

SSRIs and SNRIs have not shown benefit in functional dyspepsia and should not be used as neuromodulators for this indication. 6

Avoid repetitive or extensive testing in the absence of alarm features—this has low diagnostic yield and is not cost-effective compared to empirical management. 1, 7