What medications are used to treat Gastroesophageal Reflux Disease (GERD)?

Medications for Gastroesophageal Reflux Disease (GERD)

Proton pump inhibitors (PPIs) are the most effective medication class for treating GERD, with higher healing rates than other medications, especially for moderate to severe cases. 1

First-Line Pharmacological Treatment

Proton Pump Inhibitors (PPIs)

• PPIs are the cornerstone of GERD treatment, providing superior acid suppression compared to other medication classes 1
• Examples include omeprazole, lansoprazole, pantoprazole, esomeprazole 2, 3
• Indicated for treatment of heartburn and other symptoms associated with GERD for up to 4 weeks in patients 2 years and older 2
• Also indicated for healing of erosive esophagitis due to acid-mediated GERD 2, 3
• Optimization includes:
  • Ensuring adequate timing (30-60 minutes before meals) 4
  • Considering dose escalation to twice daily if symptoms persist 1
  • Switching to a different PPI if response is inadequate 1
• When symptoms are controlled, acid suppression should be weaned to the lowest effective dose, except in patients with:
  • Los Angeles grade B or greater erosive esophagitis
  • Biopsy-proven Barrett's esophagus
  • Peptic stricture 1

H2 Receptor Antagonists (H2RAs)

• Effective in relieving reflux symptoms in approximately 50% of patients 5
• Primarily effective for mild GERD (grades I and II) 5, 6
• Examples include cimetidine, ranitidine, famotidine, and nizatidine 1
• Particularly useful as:
  • Adjunct to PPI therapy for nighttime symptoms 4
  • Treatment for breakthrough symptoms 1
  • Step-down therapy when PPIs can be discontinued 1
• Limitation: effectiveness may decrease over time due to tachyphylaxis 1, 6

Antacids

• Provide rapid but short-duration symptom relief 6, 7
• Best used for on-demand treatment of breakthrough symptoms 4
• Alginate-containing antacids are particularly useful for:
  • Post-prandial symptoms
  • Nighttime symptoms
  • Patients with hiatal hernia 1
  • Extraesophageal reflux symptoms 4

Adjunctive Pharmacotherapy

• Should be personalized to the specific GERD phenotype rather than used empirically 1
• Options include:
  • Baclofen (GABA-B agonist): May be effective for belch-predominant symptoms and mild regurgitation, though limited by CNS and GI side effects 1
  • Prokinetics: Limited utility in GERD but may help patients with concomitant gastroparesis 1
  • Low-dose antidepressants: For neuromodulation in patients with esophageal hypervigilance and visceral hypersensitivity 1

Treatment Algorithm Based on GERD Severity

Non-Severe GERD

1. Start with lifestyle modifications and PPI therapy 1
2. If symptoms persist, optimize PPI therapy (timing, dose, or switch to different PPI) 1
3. Add adjunctive therapy based on symptom pattern:
   • Alginate antacids for breakthrough symptoms 1
   • H2RAs for nighttime symptoms 1, 4
   • Baclofen for regurgitation/belching 1
4. When symptoms are controlled, wean to lowest effective PPI dose or switch to H2RAs/antacids 1

Severe GERD (Los Angeles C/D esophagitis, extreme acid exposure, large hiatal hernia)

1. Start with PPI therapy (may require higher doses) 1
2. Maintain indefinite long-term PPI therapy 1
3. Consider anti-reflux procedure if symptoms persist despite optimization 1

Special Considerations and Pitfalls

• PPI safety concerns: Potential side effects include kidney problems (tubulointerstitial nephritis), C. difficile diarrhea, bone fractures with long-term use, and certain types of lupus erythematosus 2
• Avoid empiric use of adjunctive agents without tailoring to specific symptoms 1
• If symptoms persist despite optimized therapy, consider:
  • Esophageal function testing (high-resolution manometry)
  • Gastric emptying testing if gastroparesis is suspected
  • 24-hour pH-impedance monitoring on PPI 1
• Patients with functional heartburn or reflux hypersensitivity may benefit from neuromodulators or behavioral therapy 1
• Sucralfate is not included in primary recommendations for GERD management due to insufficient evidence compared to standard acid-suppressive therapies 8

Non-Pharmacological Approaches

• Weight loss if overweight or obese 4
• Elevating head of bed for nighttime symptoms 4
• Avoiding meals within 3 hours of bedtime 4
• Avoiding specific trigger foods (alcohol, coffee, spicy foods) 4
• Diaphragmatic breathing exercises may strengthen the anti-reflux barrier 4