Why do we limit the duration of Proton Pump Inhibitor (PPI) therapy?

Limiting PPI Duration: Evidence-Based Rationale

PPI therapy should be limited to the shortest duration necessary based on the specific indication, with regular reassessment for continued necessity, as prolonged use may lead to rebound acid hypersecretion and potential adverse effects without changing the natural history of reflux disease in most patients. 1

Rationale for Limiting PPI Duration

Physiological Concerns

• Rebound Acid Hypersecretion (RAHS): Discontinuing PPIs after prolonged use can lead to significant rebound hyperacidity due to:
  • Parietal cell hyperplasia that persists for 8 weeks to 6 months after discontinuation 1
  • Enterochromaffin-like cell hyperplasia causing increased gastrin production 1
  • This physiological response often causes symptom recurrence that may be misinterpreted as need for continued therapy

Lack of Disease-Modifying Effects

• Long-term PPI therapy does not alter the natural history of reflux disease beyond reducing the already low incidence of peptic strictures 1
• The main identifiable risk of discontinuing therapy is increased symptom burden rather than disease progression 1

Potential Adverse Effects

• While the American College of Cardiology recommends PPIs for gastrointestinal protection in high-risk patients on dual antiplatelet therapy 2, prolonged use should be regularly reassessed
• Concerns about long-term PPI use include:
  • Increased risk of gastrointestinal infections including C. difficile 1, 3
  • Community-acquired pneumonia (though not hospital-acquired) 4
  • Potential micronutrient absorption issues in specific populations 3

Appropriate Duration Based on Indication

For GERD/Esophagitis

• Initial treatment: 8-12 weeks 1
• For erosive esophagitis: Continuous therapy may be needed to maintain healed mucosa 1
• For non-erosive reflux disease: On-demand therapy is a reasonable strategy 1

For Eosinophilic Esophagitis

• Initial treatment: 8-12 weeks with twice-daily dosing 1
• Assessment of histological response while on treatment 1
• For responders: Maintenance therapy may be required long-term 1

For Extraesophageal Reflux Syndromes

• With concomitant esophageal GERD: Maintenance therapy may be warranted 1
• Without concomitant esophageal GERD: Discontinue after empirical trial if no improvement 1

De-prescribing Strategies

When to Consider De-prescribing

• Lack of clear ongoing indication for PPI use 1
• Resolution of the initial condition requiring PPI therapy
• Note: The decision to discontinue should NOT be based solely on concerns about PPI-associated adverse events 1

How to De-prescribe

• Either tapering or abrupt discontinuation can be considered 1
  • Tapering: May help manage RAHS symptoms but evidence for superiority is limited
  • Abrupt discontinuation: Equally effective in some studies but may lead to more pronounced rebound symptoms

Managing Post-Discontinuation Symptoms

• Advise patients about potential rebound symptoms lasting up to 2 months 1
• Consider alternative acid-suppression strategies:
  • On-demand PPI use 1
  • H2-receptor antagonists 1
  • Over-the-counter antacids 1
• Persistent severe symptoms beyond 2 months suggest either:
  • Continuing indication for PPI therapy
  • Non-acid-mediated cause of symptoms 1

Clinical Pearls

• Approximately 50% of patients with uncomplicated GERD can remain off PPIs 6 months after discontinuation 1
• Of those who successfully discontinue, 75% will require H2-blockers or antacids for symptom control 1
• The lowest effective PPI dose should be used when therapy is required 2
• Morning dosing (30 minutes before breakfast) provides optimal efficacy for PPIs 2

Remember that while limiting PPI duration is important, PPIs should not be withheld from patients with true indications, and concerns about poorly proven side effects should not lead to unnecessary discontinuation in patients who clearly benefit from therapy 3.