How can I dose gabapentin (GABA analog) for Alcohol Use Disorder (AUD) when a patient prefers one-time daily dosing?

Gabapentin Dosing for AUD with Once-Daily Preference

While gabapentin for AUD is traditionally dosed 600-1800 mg/day in divided doses (typically three times daily), once-daily dosing is pharmacologically problematic and not supported by current evidence for this indication. 1

The Fundamental Problem with Once-Daily Gabapentin

Gabapentin has saturable, dose-dependent absorption that makes once-daily dosing ineffective:

• Bioavailability decreases significantly as individual dose size increases—at 3600 mg/day given three times daily (1200 mg per dose), bioavailability is only 38.7%, and this drops further with larger individual doses 2
• The medication has a short half-life requiring multiple daily doses to maintain therapeutic levels 3
• Once-daily extended-release formulations (like Gralise) are FDA-approved only for post-herpetic neuralgia, not AUD, and have never been studied for alcohol use disorder 3

Evidence-Based Dosing for AUD

The established dosing from major hepatology guidelines is:

• 600-1800 mg/day in divided doses (typically three times daily) 1
• This dosing has shown efficacy specifically in patients with higher alcohol withdrawal symptoms, though benefits are modest 4
• Gabapentin may worsen drinking outcomes in patients with low withdrawal symptoms 4

Practical Approach When Patient Prefers Once-Daily Dosing

You should have a direct conversation about why once-daily dosing won't work for this medication and this indication:

1. Explain the pharmacology: The drug is simply not absorbed well enough in large single doses to be effective 2

2. Consider alternative medications that support once-daily dosing:

   • Acamprosate 666 mg three times daily (still requires multiple doses but has no hepatic metabolism and no hepatotoxicity concerns) 1
   • Naltrexone 50 mg once daily (true once-daily option, though has hepatotoxicity concerns and contraindicated in significant liver disease) 1
   • Baclofen 30-60 mg/day (can be divided into fewer doses, and is the only AUD medication actually studied in patients with cirrhosis) 1

3. If gabapentin is still preferred, negotiate for twice-daily dosing as a compromise:

   • Start with 300 mg twice daily (600 mg/day total) 1
   • Can increase to 600 mg twice daily (1200 mg/day) or 900 mg twice daily (1800 mg/day) based on response 1
   • Twice-daily dosing is more convenient than three times daily while maintaining better bioavailability than once-daily 2

Critical Safety Considerations

• Monitor closely for falls/fractures and altered mental status, especially at doses ≥600 mg/day 5
• Risk is dose-dependent, with highest risk at ≥2400 mg/day 5
• Gabapentin can cause severe physiologic dependence—one case required an 18-month taper to discontinue 6
• Adjust dose for renal dysfunction (renally excreted) 1
• Monitor for worsening mental status/sedation, particularly in patients with liver disease 1

Clinical Bottom Line

Gabapentin is a second-line agent for AUD (after naltrexone and acamprosate) and requires divided dosing to work 4. If the patient cannot accept at least twice-daily dosing, choose a different medication rather than prescribing ineffective once-daily gabapentin. The pharmacokinetics simply don't support once-daily dosing for any therapeutic effect in AUD 2.