What is the best approach to manage a patient with non-erosive reflux disease?

Management of Non-Erosive Reflux Disease (NERD)

Start with a 4-8 week trial of standard-dose PPI once daily (e.g., omeprazole 20 mg) taken 30-60 minutes before breakfast, combined with weight loss if BMI ≥25 kg/m² and elevation of the head of bed by 6-8 inches for nocturnal symptoms. 1

Initial Treatment Approach

First-Line Pharmacotherapy

• Begin with single-dose PPI therapy once daily for 4-8 weeks as the most effective first-line treatment for NERD, superior to H2-receptor antagonists and placebo. 1, 2
• Take the PPI 30-60 minutes before breakfast to optimize acid suppression during the postprandial period. 1, 2
• Reassess symptom response at 4-8 weeks to determine next steps. 1

Essential Lifestyle Modifications

• Weight loss is mandatory for all patients with BMI ≥25 kg/m², as this has the strongest evidence (Grade B) for reducing GERD symptoms and is the most effective lifestyle intervention. 1, 2
• Elevate the head of bed by 6-8 inches (not just using pillows) for patients with nighttime symptoms or regurgitation. 1, 2
• Avoid lying down for 2-3 hours after meals to reduce esophageal acid exposure. 1, 2
• Identify and avoid individual trigger foods (coffee, chocolate, alcohol, fatty foods, citrus, carbonated beverages) based on patient-specific symptom patterns. 1, 2

Treatment Escalation for Inadequate Response

Step-Up Therapy (After 4-8 Weeks)

If symptoms persist despite initial therapy:

• Escalate to twice-daily PPI dosing (one dose before breakfast, one before dinner) rather than switching agents initially. 1, 2
• Continue aggressive lifestyle modifications with emphasis on weight management. 1
• Consider adding alginate-containing antacids for breakthrough postprandial symptoms, as they neutralize the acid pocket. 1, 3
• Add nighttime H2-receptor antagonist (H2RA) for nocturnal breakthrough symptoms, though be aware of tachyphylaxis with prolonged use. 1, 3

Diagnostic Evaluation for Refractory Symptoms

If symptoms remain uncontrolled after 8-12 weeks of optimized twice-daily PPI therapy, perform objective testing rather than empirically increasing doses further. 1

• Upper endoscopy to exclude erosive esophagitis (Los Angeles grade B or higher), Barrett's esophagus, or peptic stricture. 1
• 96-hour wireless pH monitoring OFF PPI therapy (preferred over 24-hour monitoring) to objectively confirm GERD diagnosis and phenotype the disease. 1
• GERD is confirmed by Los Angeles grade B or greater esophagitis and/or acid exposure time (AET) ≥6.0% on 2 or more days. 1

Phenotyping NERD Based on Objective Testing

Patients with Normal Acid Exposure (AET <4.0%)

• These patients do NOT have GERD and should have PPI therapy discontinued. 1
• Consider functional heartburn or reflux hypersensitivity as alternative diagnoses. 1, 4, 5
• Refer to GI psychologist for cognitive behavioral therapy (CBT), gut-directed hypnotherapy, and/or pharmacologic neuromodulation. 1
• High-resolution manometry may identify rumination syndrome or esophageal motor disorders. 1

Patients with Confirmed GERD (AET ≥6.0% on ≥2 days)

• Continue long-term PPI therapy at the lowest effective dose that controls symptoms. 1
• Since NERD patients have no baseline erosive disease, attempt to wean to lowest effective dose or on-demand therapy with H2 blockers/antacids once symptoms are controlled. 1
• Do NOT perform routine surveillance endoscopy, as progression from NERD to severe erosive disease or Barrett's esophagus is uncommon (1.9% over 7 years). 1

Patients with Borderline GERD (AET 4.0-6.0% or Los Angeles A esophagitis)

• Titrate PPIs to the lowest dose or frequency that controls symptoms. 1
• Consider replacement with H2RAs for maintenance if symptoms allow. 1
• Emphasize aggressive lifestyle modifications and weight management. 1

Adjunctive Therapies for Specific Phenotypes

Personalize adjunctive pharmacotherapy to the GERD phenotype rather than using empirically. 1

• Alginate antacids for breakthrough postprandial symptoms, particularly in patients with hiatal hernia. 1, 3
• Baclofen (GABA-B agonist) for belch-predominant symptoms or mild regurgitation, though limited by CNS and GI side effects. 1
• Prokinetics only if coexistent gastroparesis is documented; they have no proven role in GERD alone. 1, 2
• Neuromodulators and/or CBT/hypnotherapy for patients with esophageal hypervigilance, reflux hypersensitivity, or functional heartburn. 1

Long-Term Management Considerations

PPI De-escalation Strategy

• After achieving symptom control in NERD patients without erosive disease, attempt to wean to the lowest effective dose or on-demand therapy. 1, 6
• Reassess the need for continued PPI therapy within 12 months if GERD was never objectively confirmed. 1, 6
• Do NOT use less-than-daily dosing in patients who had erosive esophagitis at baseline. 1, 6

Safety of Long-Term PPI Use

• Emphasize to patients that PPIs are safe for long-term use when appropriately indicated. 1
• While associations exist with bone fractures, C. difficile infection, hypomagnesemia, and community-acquired pneumonia, direct causality is unproven and benefits outweigh risks in confirmed GERD. 6, 2
• Titrate to the lowest effective dose to minimize theoretical long-term risks. 1, 6

Critical Pitfalls to Avoid

• Do NOT assume GERD diagnosis based solely on symptom response to PPI, as up to 50% of NERD patients have normal acid exposure and may have functional disorders. 1, 6, 4, 5, 7
• Do NOT continue long-term PPI without documented ongoing indication after 12 months without objective testing. 1, 6
• Do NOT perform routine surveillance endoscopy in NERD patients, as progression rates are very low and surveillance does not reduce cancer risk. 1
• Do NOT use metoclopramide as monotherapy or adjunctive therapy due to unfavorable risk-benefit profile including tardive dyskinesia risk. 2
• Do NOT empirically rotate PPIs in refractory symptoms without first optimizing timing, ensuring twice-daily dosing, and performing objective testing. 6

Response Expectations

• NERD patients have lower response rates to PPI therapy (approximately 50-70%) compared to erosive esophagitis patients (70-90%). 4, 5, 8, 9
• This reflects the heterogeneous pathophysiology of NERD, including visceral hypersensitivity, weakly acidic reflux, and functional disorders that do not respond to acid suppression alone. 4, 5, 7, 9
• Allow 1-3 months to assess response to optimized therapy before declaring treatment failure. 3, 2