In a 25-year-old man with morning nausea, early satiety, intermittent epigastric discomfort, normal laboratory studies (including comprehensive metabolic panel, complete blood count, and Helicobacter pylori stool test) and pending upper endoscopy, which is the most appropriate initial pharmacologic agent for symptom management?

Oral Omeprazole is the Most Appropriate Initial Pharmacologic Agent

For this 25-year-old H. pylori-negative patient with functional dyspepsia symptoms (morning nausea, early satiety, epigastric discomfort), oral omeprazole 20 mg once daily taken 30–60 minutes before a meal is the most appropriate initial pharmacologic therapy while awaiting upper endoscopy. 1, 2

Rationale for PPI as First-Line Therapy

• PPIs are strongly recommended as first-line empirical therapy for H. pylori-negative dyspepsia, demonstrating superiority over placebo, H₂-receptor antagonists, and antacid-alginate combinations. 1

• The British Society of Gastroenterology issues a strong recommendation, based on high-quality evidence, that patients without H. pylori infection should receive empirical acid-suppression therapy. 1

• Any commercially available PPI can be used (omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole, dexlansoprazole) as absolute differences in efficacy for symptom control are small. 2

• In patients with symptomatic GERD without erosive esophagitis, omeprazole 20 mg once daily provides early and sustained resolution of heartburn and other troublesome symptoms, with 48% achieving complete resolution by week 4. 3

Dosing Protocol

• Start omeprazole 20 mg once daily, taken 30–60 minutes before a meal, for 4–8 weeks. 1, 4

• If symptoms persist after 4–8 weeks of once-daily therapy, escalate to twice-daily dosing (morning and evening before meals) for an additional 4–8 weeks. 5, 1, 2

• Morning administration is optimal for acid suppression compared to evening dosing. 6

Why Other Options Are Inappropriate

• Topical capsaicin, oral gabapentin, and oral sucralfate have no evidence of benefit for functional dyspepsia and are not recommended. 1

• Amitriptyline is reserved as second-line therapy only after PPI failure, initiated at low dose (10 mg once daily) and titrated slowly to 30–50 mg daily with thorough patient counseling. 1

• Tricyclic antidepressants like amitriptyline should not be used as first-line therapy when a patient is H. pylori-negative and has not yet failed empirical PPI treatment. 1

Clinical Pathway

• Even when dysmotility-like symptoms (early satiety, bloating) are present—as in this patient—PPIs remain the first-line treatment. 1

• Prokinetics may be added only after an adequate PPI trial if dysmotility symptoms persist. 1, 2

• If symptoms persist despite optimized PPI therapy (twice daily for 8 weeks), proceed with upper endoscopy and consider prolonged wireless pH monitoring off medication to confirm or rule out GERD. 5, 2

Important Considerations

• A negative H. pylori test eliminates the need for eradication therapy, reinforcing empirical PPI as the clear first choice. 1

• The absence of alarm symptoms (dysphagia, bleeding, anemia, weight loss, recurrent vomiting) supports empirical therapy rather than immediate endoscopy. 5, 2

• Regular aerobic exercise should be advised as an adjunctive measure. 1

• Antacids may be used concomitantly with omeprazole for breakthrough symptoms. 4

Common Pitfalls to Avoid

• Do not start with amitriptyline or other neuromodulators as first-line therapy—these are reserved for PPI-refractory functional dyspepsia. 1

• Ensure proper PPI administration timing (30–60 minutes before meals) to optimize efficacy; failure to do so is a common reason for apparent treatment failure. 2, 4

• Do not use sucralfate, which has no established role in functional dyspepsia management. 1