When is it appropriate to prescribe a proton pump inhibitor (PPI) permanently?

When to Prescribe a Proton Pump Inhibitor Permanently

Permanent PPI therapy is definitively indicated for Barrett's esophagus, severe erosive esophagitis (Los Angeles grade C/D), GERD-related complications (esophageal ulcer, peptic stricture), eosinophilic esophagitis responsive to PPIs, idiopathic pulmonary fibrosis, and gastroprotection in high-risk patients taking NSAIDs/aspirin with multiple bleeding risk factors. 1, 2

Definitive Indications for Long-Term PPI Use

Barrett's Esophagus

• Patients with Barrett's esophagus should never be considered for PPI discontinuation 1, 2
• PPIs reduce the risk of progression to esophageal adenocarcinoma in both observational studies and randomized controlled trials 1
• This is a non-negotiable indication regardless of symptom status 2

Severe Erosive Esophagitis

• Los Angeles Classification grade C or D erosive esophagitis requires indefinite PPI therapy 1, 2
• These patients have high recurrence rates after PPI withdrawal, with potential for complications including bleeding and stricture formation 1
• Even if esophagitis has healed, the predisposition to severe disease persists without ongoing acid suppression 1

GERD-Related Complications

• History of esophageal ulcer or peptic stricture mandates continued PPI use 1
• These complications indicate severe disease that will likely recur without ongoing therapy 1
• Benefits of continued therapy clearly outweigh potential harms in this population 1

Eosinophilic Esophagitis

• PPI-responsive eosinophilic esophagitis requires long-term therapy 1, 2
• Clinical response and histologic remission occur in 61% and 51% of patients respectively with PPI therapy 1
• Discontinuation results in high rates of symptomatic and histologic recurrence 1
• Untreated disease may lead to fibrotic strictures from uncontrolled eosinophilic inflammation 1

Idiopathic Pulmonary Fibrosis

• PPIs should be continued indefinitely in patients with idiopathic pulmonary fibrosis 1, 2
• Low-quality evidence suggests PPIs reduce disease progression 1
• Until definitive evidence proves ineffectiveness, the potential benefit justifies continued use 1

Conditional Indications for Long-Term PPI Use

High-Risk Gastroprotection

Continue PPIs indefinitely in patients taking NSAIDs/aspirin with:

• History of upper GI bleeding 1, 2
• Multiple antithrombotic agents (≥2 antiplatelet or anticoagulant drugs) 1
• Single antiplatelet/NSAID plus additional risk factors: age >60-65 years, severe comorbidity, concurrent corticosteroids, or dual antiplatelet therapy 1

PPI-Responsive Endoscopy-Negative Reflux Disease

• Long-term therapy is appropriate when symptoms consistently recur after discontinuation attempts 2, 1
• Requires documented symptom recurrence with PPI cessation to justify indefinite use 1
• If unproven GERD, perform endoscopy with 96-hour wireless pH monitoring off PPI within 12 months to establish appropriate long-term use 1

Esophageal Strictures from GERD

• Peptic strictures require ongoing PPI therapy to prevent recurrence 2, 1
• These represent a complication of severe GERD requiring indefinite acid suppression 1

Hypersecretory Conditions

• Zollinger-Ellison syndrome and other pathological hypersecretory states require lifelong PPI therapy 1, 3
• Some patients have been treated continuously for more than 5 years 3
• Dosages up to 120 mg three times daily may be required 3

When NOT to Prescribe PPIs Long-Term

Non-Erosive GERD Without Recurrence

• Most patients with non-erosive GERD should be considered for de-prescribing 1
• Attempt dose reduction to lowest effective dose or complete discontinuation 1
• Only continue if symptoms consistently recur with cessation attempts 1

Uninvestigated Dyspepsia

• Not an indication for long-term PPI use 1
• Provide 4-8 week trial, then reassess and consider discontinuation 1

Functional Dyspepsia Without Sustained Response

• Not an indication for long-term therapy 1
• If no sustained benefit, discontinue and consider alternative diagnoses 1

Critical Management Principles

Regular Indication Review

• All patients on PPIs require regular review of ongoing indications with clear documentation 1, 2
• Primary care providers should be responsible for this review 1
• Without an ongoing indication, the PPI can only cause harm through pill burden, costs, and potential adverse effects 1

Dose Optimization

• Patients on twice-daily dosing should be stepped down to once-daily unless they have documented need for higher doses 1
• Double-dose PPIs are not FDA-approved and lack RCT evidence 1
• Higher doses are associated with increased risks of pneumonia, fractures, and C. difficile infection 1

Safety Considerations

• Randomized controlled trials have not confirmed increased adverse events with long-term PPI use, despite observational associations 1, 2
• The decision to discontinue should be based solely on lack of indication, not fear of potential adverse events 1
• Presence of a PPI-associated adverse event is not an independent indication for withdrawal 1

Common Pitfalls to Avoid

Rebound Acid Hypersecretion

• Warn patients that transient upper GI symptoms may occur after discontinuation due to rebound acid hypersecretion 1, 2
• This physiologic phenomenon results from hypergastrinemia-induced parietal cell proliferation during PPI therapy 1
• Symptoms may persist for up to 8 weeks after discontinuation 1
• Either dose tapering or abrupt discontinuation can be used 1, 2

Empiric Treatment Without Documentation

• Never continue long-term PPIs without documented indication 1
• Many patients are treated empirically and may not have had endoscopy to confirm severe disease 1
• If indication is unclear, consider endoscopy with pH monitoring off PPI to establish need for continued therapy 1

Inappropriate Discontinuation in High-Risk Patients

• Never attempt de-prescribing in patients with Barrett's esophagus, severe erosive esophagitis, or documented complications 1, 2
• This can lead to serious complications including bleeding, stricture formation, or cancer progression 1