What is the appropriate next step in management for a 71‑year‑old woman with hyperlipidemia who has persistent gastro‑esophageal reflux disease symptoms despite two months of omeprazole 40 mg daily?

Management of PPI-Refractory GERD

For this 71-year-old woman with persistent GERD symptoms after 2 months of omeprazole 40 mg daily, escalate to twice-daily dosing (omeprazole 20 mg twice daily, taken 30-60 minutes before breakfast and dinner) for an additional 4-8 weeks before pursuing endoscopy. 1

Rationale for Dose Escalation

The most recent AGA guidelines (2022) provide clear direction for PPI non-responders: when symptoms persist after a 4-8 week trial of once-daily PPI, dosing can be increased to twice daily or switched to a more potent acid suppressive agent before proceeding to invasive testing. 1 This patient has completed 2 months (8 weeks) on what appears to be double the standard starting dose (40 mg vs. the FDA-approved 20 mg once daily for symptomatic GERD), but this was likely given as a single daily dose rather than divided dosing. 2

Key Dosing Considerations:

• Standard initial therapy is omeprazole 20 mg once daily, not 40 mg 2
• The patient may have been on 40 mg once daily, which is less effective than 20 mg twice daily due to PPI pharmacokinetics 3
• PPIs must be taken 30-60 minutes before meals for optimal acid suppression 3
• Twice-daily dosing achieves 93-99% normalization of esophageal acid exposure 1

Immediate Action Steps

1. Verify current dosing schedule: Confirm whether the patient has been taking omeprazole 40 mg as a single morning dose or divided. 3

2. Optimize administration timing: Ensure the patient understands PPIs must be taken 30-60 minutes before meals, not at bedtime or with food. 3 This is a common pitfall that significantly reduces efficacy.

3. Switch to twice-daily dosing: Prescribe omeprazole 20 mg twice daily (before breakfast and dinner) for 4-8 weeks. 1, 3

4. Reinforce lifestyle modifications: While not a substitute for medication adjustment, ensure the patient has addressed weight management, dietary triggers, and head-of-bed elevation. 1

When to Pursue Endoscopy

If symptoms persist despite optimized twice-daily PPI therapy for 4-8 weeks, endoscopy is warranted to evaluate for:

• Erosive esophagitis (LA grade B or greater) 1
• Barrett's esophagus 1
• Alternative diagnoses (eosinophilic esophagitis, stricture, malignancy) 1

The 2022 AGA guidelines specifically state that objective testing with upper GI endoscopy is warranted in PPI non-response. 1 At age 71, this patient also meets criteria for Barrett's esophagus screening if she has additional risk factors. 1

If Endoscopy Shows No Erosive Disease

Should endoscopy reveal no erosive esophagitis or Barrett's esophagus, prolonged wireless pH monitoring off PPI therapy (96-hour preferred) should be performed to confirm GERD versus functional esophageal disorder. 1 Patients without erosive disease on endoscopy and with physiologic acid exposure often have functional heartburn or reflux hypersensitivity rather than true GERD, and may benefit from neuromodulation or behavioral interventions instead of continued PPI escalation. 1

Common Pitfalls to Avoid

• Do not add an H2-receptor antagonist (like famotidine) at bedtime without first optimizing PPI dosing and timing—this combination lacks evidence for routine GERD management and H2RAs develop tachyphylaxis within 6 weeks. 3, 4

• Do not continue empiric therapy indefinitely without objective testing: The 2022 AGA guidelines emphasize that if PPI therapy continues beyond 12 months without proven GERD, appropriateness should be evaluated with endoscopy and pH monitoring. 1, 3

• Do not assume treatment failure means GERD is absent: Research shows omeprazole converts acid reflux to weakly acidic reflux but does not reduce total reflux episodes, which may explain persistent symptoms despite adequate acid suppression. 5 This supports the need for objective testing in non-responders.

Alternative Considerations

If twice-daily omeprazole fails after 4-8 weeks, consider switching to a different PPI (such as esomeprazole or dexlansoprazole) rather than further dose escalation, as individual response varies. 3 However, endoscopy should not be delayed beyond 8 weeks of optimized twice-daily therapy in a 71-year-old patient, given the need to exclude serious pathology. 1