What is the dosing regimen for baclofen (GABA receptor agonist) in the treatment of Alcohol Use Disorder (AUD)?

Baclofen Dosing Regimen for Alcohol Use Disorder (AUD)

For treating Alcohol Use Disorder, baclofen should be initiated at 5 mg three times daily and gradually titrated upward to an effective dose, typically between 40-80 mg daily, with a maximum recommended dose of 80 mg per day. 1

Initial Dosing and Titration Schedule

The FDA-approved titration schedule for baclofen in AUD is as follows:

• Start with 5 mg three times daily for 3 days
• Increase to 10 mg three times daily for 3 days
• Increase to 15 mg three times daily for 3 days
• Increase to 20 mg three times daily for 3 days 1

After this initial 12-day titration period, the standard maintenance dose is 60 mg daily (20 mg three times daily). The total daily dose should not exceed 80 mg (20 mg four times daily) according to FDA labeling. 1

Dosing Considerations Based on Evidence

Standard vs. High-Dose Approaches

• Standard dosing (30-80 mg/day): Most clinical evidence supports the safety and efficacy of baclofen at doses between 30-80 mg daily for AUD. 2

• Higher dosing: While some European practices (particularly French) have used higher doses up to 300 mg/day, the evidence for high-dose baclofen is mixed:

  • The French ANSM has issued a temporary recommendation not to exceed 80 mg/day for AUD treatment 2
  • High-dose regimens show increased risk of adverse events, particularly in women 3

Patient-Specific Factors

• Liver disease: Baclofen is particularly valuable for AUD patients with liver disease as it has limited hepatic metabolism. Standard dosing can be used in this population. 2, 4

• Sex differences: Evidence suggests differential response and tolerability by sex:

  • Women may respond better to lower doses (30 mg/day) 3
  • Men may require higher doses (90 mg/day) for efficacy 3
  • Women experience more sedative side effects at higher doses (59% vs 5% in men at 90 mg/day) 3

• Renal impairment: Dose reduction is necessary in patients with moderate renal impairment (eGFR 30-60mL/min/1.73m²) and baclofen should be avoided in severe renal impairment (eGFR <30mL/min/1.73m²) 5

Monitoring and Safety

• Monitor for common adverse effects including:

  • Fatigue
  • Dizziness
  • Somnolence/sedation
  • Dry mouth
  • Paraesthesia
  • Muscle spasms/rigidity 6

• Baclofen has a half-life of approximately 4.4 hours, requiring multiple daily dosing 7

• Important warning: Never discontinue baclofen abruptly as this can lead to severe, potentially life-threatening withdrawal symptoms including visual/auditory hallucinations, anxiety, and seizures 5

Clinical Efficacy Expectations

Patients should be informed that baclofen:

• Likely reduces risk of relapse to any drinking 6
• Increases percentage of abstinent days 6
• May not significantly reduce heavy drinking days or drinks per drinking day 6

Discontinuation

When discontinuing baclofen, implement a slow tapering schedule to prevent withdrawal symptoms. This is particularly important as abrupt discontinuation can lead to severe withdrawal including seizures, especially in patients with pre-existing seizure disorders. 5

Practical Clinical Algorithm

1. Initial assessment: Evaluate for contraindications (severe renal impairment, seizure disorders)
2. Initiate therapy: Start at 5 mg TID for 3 days
3. Titration: Follow the standard 12-day titration schedule to reach 20 mg TID
4. Maintenance: Continue at effective dose (typically 40-80 mg daily)
5. Monitoring: Assess for adverse effects and clinical response at each dose increase
6. Adjustment: Consider sex-specific dosing (lower doses for women, potentially higher doses for men if needed and tolerated)
7. Maximum dose: Do not exceed 80 mg daily without specialist consultation

Remember that baclofen should be used as part of a comprehensive treatment approach for AUD that includes appropriate psychosocial interventions.