What is the recommended dose of baclofen (GABA (Gamma-Aminobutyric Acid) receptor agonist) for the treatment of Gastroesophageal Reflux Disease (GERD)?

Baclofen Dosing for GERD Treatment

For patients with GERD, particularly those with regurgitation or belching-predominant symptoms, baclofen should be dosed at 10 mg three times daily, with potential titration up to 20 mg three times daily as needed for symptom control. 1

Indications for Baclofen in GERD Management

Baclofen is not a first-line therapy for GERD but serves as an adjunctive treatment in specific clinical scenarios:

• Primary indications:
  • Regurgitation-predominant GERD 1
  • Belching-predominant symptoms 1
  • Refractory GERD symptoms despite PPI therapy 1, 2
  • Non-acid reflux that persists during PPI therapy 2

Dosing Protocol

• Starting dose: 5 mg three times daily 2
• Titration: Increase by 5 mg every fourth day 2
• Target maintenance dose: 10-20 mg three times daily 3, 2, 4
• Duration: Efficacy has been demonstrated in studies ranging from 2-8 weeks 3, 4

Mechanism of Action

Baclofen works differently than traditional GERD medications:

• As a GABA-B receptor agonist, it reduces transient lower esophageal sphincter relaxations (TLESRs) 5, 2
• Decreases both acid and non-acid reflux episodes 2, 6
• Particularly effective for reflux events with high proximal extent 6

Patient Selection for Baclofen Therapy

Baclofen is most appropriate for:

• Patients with documented GERD who remain symptomatic despite PPI therapy 1
• Those with confirmed non-acid reflux on pH-impedance monitoring 2, 6
• Patients with a positive symptom association probability (SAP+) on reflux testing 6

Monitoring and Expected Response

• Symptom improvement may begin as early as 2 weeks after initiation 4
• Maximum benefit typically observed after 6-8 weeks of therapy 4
• Objective measures of improvement include:
  • Decreased duodenal reflux exposure (from 13.8% to 6.1% of time) 2
  • Reduction in reflux episodes, particularly those lasting >5 minutes 2
  • Increased cough threshold to capsaicin in patients with reflux-induced cough 4

Common Side Effects and Management

• Most common adverse effects:
  • Somnolence/drowsiness
  • Dizziness
  • Fatigue
  • Nausea 5, 2, 4
• Side effects are generally mild but may lead to discontinuation in some patients (approximately 16% in clinical trials) 6
• Consider starting at lower doses and titrating more slowly in elderly patients or those sensitive to CNS side effects

Combination Therapy

• Baclofen is typically used as add-on therapy to PPIs rather than monotherapy 1, 3
• The combination of baclofen plus PPI has shown superior efficacy compared to PPI alone for heartburn and regurgitation symptoms 3
• Consider baclofen as part of a personalized approach to GERD management based on predominant symptoms 1, 7

Clinical Pearls

• Diagnostic testing (pH or impedance monitoring) is recommended before initiating baclofen to confirm reflux as the cause of symptoms 7, 6
• Baclofen is particularly effective for patients with objective evidence of reflux (SAP+) but less effective in those without documented reflux 6
• The medication should be continued for at least 4 weeks to properly assess efficacy 6
• Consider baclofen particularly in patients with regurgitation, which tends to be less responsive to acid suppression alone 1