What is the recommended dose of baclofen (GABA receptor agonist) for Gastroesophageal Reflux Disease (GERD)?

Baclofen Dosing for GERD

For GERD patients with regurgitation or belch-predominant symptoms, baclofen should be dosed at 10 mg three times daily (30 mg total daily dose), though this is often limited by central nervous system and gastrointestinal side effects. 1

Indication and Patient Selection

Baclofen is not a first-line therapy for GERD but rather an adjunctive agent that should be personalized to specific GERD phenotypes 1:

• Primary indication: Regurgitation or belch-predominant symptoms 1
• Secondary indication: Mild regurgitation symptoms 1
• Mechanism: Inhibits transient lower esophageal sphincter relaxations (TLESRs) through GABA-B receptor agonism 1

Standard Dosing Regimen

The evidence-based dosing is:

• 10 mg three times daily (total 30 mg/day) 2, 3
• This represents the most commonly studied and recommended dose in clinical trials 2, 3
• Some studies have evaluated 20 mg three times daily (60 mg/day) in research settings, but this higher dose increases side effect burden 4

Alternative Formulations

Sustained-release (SR) baclofen formulations may offer improved tolerability:

• Once-daily dosing at the same total daily dose (e.g., 30 mg once daily) has shown equivalent efficacy to three-times-daily immediate release formulations 5, 6
• SR formulations demonstrated significantly reduced sedation scores compared to immediate release 6
• A 2-week trial of omeprazole plus SR baclofen showed superior symptom control compared to omeprazole alone 5

Treatment Duration and Monitoring

• Initial trial period: 2-4 weeks to assess symptomatic response 2, 5
• Longer-term use: Studies support efficacy up to 4 weeks of continuous therapy 2, 3
• Response assessment: Only patients with positive symptom association probability (SAP+) on pH-impedance monitoring experience significant clinical benefit 2

Critical Limitations and Side Effects

Central nervous system and GI side effects frequently limit baclofen use 1:

• Common side effects include drowsiness, dizziness, and muscle weakness 6
• In one controlled trial, 5 of 31 patients (16%) discontinued baclofen due to side effects 2
• These tolerability issues are the primary reason baclofen remains an adjunctive rather than primary GERD therapy 1

Efficacy Considerations

Baclofen's effectiveness varies by patient characteristics:

• Most effective in: Patients with documented non-acid reflux events and positive symptom correlation on impedance-pH monitoring 2
• Effective regardless of hiatal hernia: Baclofen reduces reflux episodes by 36% in patients without hiatal hernia and 43% in those with large (≥3 cm) hiatal hernias 4
• Mechanism of benefit: Primarily reduces total number of reflux episodes and proximal extent of reflux, rather than acid exposure time 2, 3, 4

Clinical Algorithm

Before prescribing baclofen 1:

1. Confirm patient has regurgitation or belch-predominant symptoms as the primary complaint
2. Ensure PPI therapy has been optimized (correct timing, adequate dose)
3. Consider pH-impedance monitoring to identify SAP+ patients who will benefit most 2

Prescribing approach:

• Start with 10 mg three times daily (or 30 mg once daily if SR formulation available) 2, 5, 3
• Reassess symptoms at 2-4 weeks 2, 5
• Discontinue if no benefit or intolerable side effects develop 2