In a 25-year-old male with morning nausea, early satiety, and intermittent epigastric discomfort consistent with functional dyspepsia and negative laboratory work‑up including comprehensive metabolic panel, complete blood count, and Helicobacter pylori stool antigen test, which initial oral medication is most appropriate?

Oral Omeprazole is the Most Appropriate Initial Pharmacologic Agent

For this 25-year-old H. pylori-negative patient with functional dyspepsia, oral omeprazole (or any PPI) is the most appropriate initial pharmacologic treatment while awaiting endoscopy. 1, 2, 3

Rationale for PPI Therapy

First-Line Evidence

• PPIs are strongly recommended as first-line empirical therapy for H. pylori-negative patients with dyspepsia, with high-quality evidence demonstrating superiority over placebo, H2-receptor antagonists, and antacid-alginate combinations 1, 4
• The British Society of Gastroenterology (2022) provides a strong recommendation with high-quality evidence that patients without H. pylori infection should be offered empirical acid suppression therapy 1
• All commercially available PPIs have functionally equivalent efficacy when dosed appropriately, so omeprazole is an appropriate choice 2, 3

Dosing Protocol

• Start with standard-dose PPI (omeprazole 20 mg) once daily, taken 30-60 minutes before a meal, for 4-8 weeks 2, 3
• If symptoms persist after 4-8 weeks, escalate to twice-daily dosing (morning and evening before meals) for an additional 4-8 weeks 2, 5
• For this patient's ulcer-like symptoms (epigastric discomfort), full-dose PPI is the first choice, with symptom response confirming the acid-related nature 2, 3

Why Not the Other Options

Topical Capsaicin

• No evidence supports capsaicin for functional dyspepsia management 1
• Not mentioned in any major dyspepsia guidelines as a treatment option

Oral Amitriptyline

• Tricyclic antidepressants are second-line therapy, not first-line 1
• Reserved for patients who fail initial PPI therapy, with strong recommendation but only moderate-quality evidence 1
• Should be initiated at low dose (10 mg once daily) and titrated slowly to maximum 30-50 mg once daily, requiring careful explanation about rationale and side effects 1

Oral Gabapentin

• No evidence supports gabapentin for functional dyspepsia 1
• Not recommended in any dyspepsia management guidelines

Oral Sucralfate

• Not recommended as first-line therapy for functional dyspepsia 1
• No evidence of efficacy in this population

Clinical Pathway

Immediate Management

• Initiate omeprazole 20 mg once daily, 30-60 minutes before breakfast 2, 3
• Advise regular aerobic exercise (strong recommendation) 1
• Proceed with scheduled upper endoscopy to rule out structural disease 1

If Symptoms Persist

• After 4-8 weeks of once-daily PPI without adequate response, increase to twice-daily dosing 2, 5
• For dysmotility-like symptoms (early satiety, bloating), consider adding a prokinetic agent 2, 5
• If symptoms persist despite twice-daily PPI for 8 weeks total, endoscopy becomes more urgent 2, 3

After Endoscopy

• If endoscopy confirms functional dyspepsia and PPI fails, then consider amitriptyline as second-line therapy 1
• Taper PPI to lowest effective dose once symptoms resolve 3

Important Caveats

• Timing is critical: PPIs must be taken 30-60 minutes before meals for optimal effect 2, 5
• The patient's negative H. pylori test eliminates the need for eradication therapy, making empirical PPI the clear first choice 1, 3
• While prokinetics may be considered for dysmotility-like symptoms, PPIs remain first-line even in this scenario 1, 4
• The number needed to treat (NNTB) for PPIs versus placebo is 11, indicating clinically meaningful benefit 4