What is the protocol for Helicobacter pylori (H. pylori) eradication and acid suppression therapeutics, including proton pump inhibitor (PPI) dosing, frequency, and duration, as well as step-up and step-down treatment approaches for patients with dyspepsia?

PPI Step-Up and Step-Down Protocol, H. Pylori Eradication, and Acid Suppression Therapeutics

Initial PPI Therapy

Begin with standard-dose PPI once daily, taken 30-60 minutes before a meal, for 4-8 weeks as first-line therapy for acid peptic disease and dyspepsia. 1, 2

• Standard dosing: Omeprazole 20 mg once daily, lansoprazole 30 mg once daily, or equivalent PPI 2, 3
• All commercially available PPIs have similar efficacy for symptom control 1
• PPIs are superior to H2-receptor antagonists, which are superior to placebo 1
• Take before meals for optimal effect; antacids may be used concomitantly 2, 3

PPI Step-Up Protocol

If symptoms persist after 4-8 weeks of once-daily PPI therapy, increase to twice-daily dosing (morning and evening) before meals. 4, 1

Step-Up Dosing:

• Omeprazole: Increase from 20 mg once daily to 20 mg twice daily 2
• Lansoprazole: Increase from 30 mg once daily to 30 mg twice daily 3
• Continue twice-daily dosing for an additional 4-8 weeks 1

Additional Step-Up Measures:

• For dysmotility-like symptoms (bloating, fullness, early satiety): Add prokinetic agent 5, 4
• For breakthrough symptoms: Add alginate-containing antacids for rapid relief 4, 1
• For persistent symptoms despite twice-daily PPI: Consider endoscopy to rule out structural causes 4, 1

PPI Step-Down Protocol

Once symptoms are controlled, taper PPI to the lowest effective dose to minimize long-term exposure. 1

Step-Down Approach:

• After symptom resolution: Attempt trial withdrawal of therapy 5
• If symptoms recur: Resume therapy at the lowest effective dose 5
• On-demand therapy: Use PPI only when symptoms occur, which is effective for maintenance 5
• For maintenance of healed erosive esophagitis: Reduce to omeprazole 10 mg once daily in patients with hepatic impairment or Asian patients 2
• Duodenal ulcer maintenance: Lansoprazole 15 mg once daily 3

Important Caveats:

• PPIs should be taken 30-60 minutes before meals for optimal effect 4
• H2-receptor antagonists may develop tolerance within 6 weeks, limiting long-term effectiveness 4
• If symptoms persist despite optimized PPI therapy (twice daily for 8 weeks), endoscopy is indicated 1

H. Pylori Eradication Protocols

Test for H. pylori using urea breath test or stool antigen test in patients <60 years with dyspepsia; eradicate if positive. 5, 6, 7

First-Line Eradication Regimens:

Bismuth Quadruple Therapy or Concomitant Therapy (Preferred due to clarithromycin resistance):

Triple Therapy (if clarithromycin resistance is low): 2, 7

• Omeprazole 20 mg twice daily
• Amoxicillin 1000 mg twice daily
• Clarithromycin 500 mg twice daily
• Duration: 10 days 2
• If ulcer present at initiation: Continue omeprazole 20 mg once daily for additional 18 days for ulcer healing 2

Dual Therapy (Alternative): 2

• Omeprazole 40 mg once daily
• Clarithromycin 500 mg three times daily
• Duration: 14 days 2
• If ulcer present: Add omeprazole 20 mg once daily for additional 14 days 2

Post-Eradication Management:

• Repeat testing to confirm eradication is NOT recommended in primary care patients with functional dyspepsia 5
• For residual symptoms after successful eradication: Treat the same as H. pylori-negative patients with symptom-based therapy 5
• H. pylori eradication eliminates peptic ulcer mortality risk but may not resolve all dyspeptic symptoms 5

Acid Suppression Therapeutics by Indication

Duodenal Ulcer:

• Treatment: Omeprazole 20 mg once daily for 4 weeks (may extend to 8 weeks if not healed) 2
• Maintenance: Lansoprazole 15 mg once daily 3

Gastric Ulcer:

• Treatment: Omeprazole 40 mg once daily for 4-8 weeks 2
• NSAID-associated gastric ulcer healing: Lansoprazole 30 mg once daily for 8 weeks 3
• NSAID-associated gastric ulcer risk reduction: Lansoprazole 15 mg once daily for up to 12 weeks 3

Erosive Esophagitis:

• Treatment: Omeprazole 20 mg once daily for 4-8 weeks 2
• Maintenance: Omeprazole 20 mg once daily (controlled studies do not extend beyond 12 months) 2
• Pediatric (2-16 years):
  • 10-20 kg: 10 mg once daily for 4-8 weeks 2
  • ≥20 kg: 20 mg once daily for 4-8 weeks 2

Symptomatic GERD:

• Adults: Omeprazole 20 mg once daily for up to 4 weeks 2
• Pediatric (2-16 years):
  • 10-20 kg: 10 mg once daily for up to 4 weeks 2
  • ≥20 kg: 20 mg once daily for up to 4 weeks 2

Pathological Hypersecretory Conditions (Zollinger-Ellison):

• Starting dose: Omeprazole 60 mg once daily, adjust to patient needs 2
• Dosages >80 mg daily: Administer in divided doses 2
• Maximum: Up to 120 mg three times daily has been administered 2
• Duration: As long as clinically indicated; some patients treated continuously for >5 years 2

Algorithm for Uninvestigated Dyspepsia

Age <60 Years Without Alarm Symptoms:

1. Test for H. pylori (urea breath test or stool antigen preferred) 5, 6, 7
2. If positive: Eradicate with triple or quadruple therapy 2, 7
3. If negative or symptoms persist after eradication: Trial of PPI (omeprazole 20 mg once daily for 4-8 weeks) 5, 1, 6
4. If PPI ineffective: Consider tricyclic antidepressants or prokinetic therapy 6

Age ≥60 Years or Alarm Symptoms Present:

• Proceed directly to endoscopy to exclude organic pathology 5, 6
• Alarm symptoms include dysphagia, bleeding, anemia, weight loss, recurrent vomiting 1

Symptom-Based Therapy After H. Pylori Eradication or Negative Testing:

For ulcer-like dyspepsia (epigastric pain predominant): 5

• Full-dose PPI (omeprazole 20 mg once daily) as first choice 5
• Response confirms acid-related nature of symptoms 5

For dysmotility-like dyspepsia (fullness, bloating, early satiety predominant): 5

• Prokinetic agent as first choice 5
• Avoid cisapride due to cardiac toxicity 5

If misclassification suspected: 5

• Switch therapy (e.g., from prokinetic to PPI or vice versa) 5
• Consider high-dose PPI trial to confirm acid-related symptoms 5

Common Pitfalls to Avoid

• Not taking PPI 30-60 minutes before meals reduces efficacy significantly 4, 1
• Continuing empiric PPI long-term without confirming diagnosis in non-responders 1
• Using H. pylori serology instead of urea breath test or stool antigen (lower specificity) 5
• Failing to assess for alarm symptoms that warrant immediate endoscopy 1
• Not considering non-acid reflux as cause of persistent regurgitation despite PPI therapy 1