What is the recommended dosing regimen for gabapentin (Neurontin) in a case series of 5-10 patients with moderate alcohol use disorder (AUD) for a duration of 28-45 days?

Gabapentin Dosing Regimen for Alcohol Use Disorder Case Series

For a 28-45 day case series of 5-10 patients with moderate alcohol use disorder, gabapentin should be administered at a dosage of 600-1800 mg/day, with optimal results likely at the 1800 mg/day dosage, divided into three daily doses. 1, 2

Study Design Framework

Patient Selection Criteria

• Adults (>18 years) with moderate alcohol use disorder (AUD) based on DSM-V criteria (4-5 criteria)
• Exclude patients with:
  • Severe hepatic impairment
  • Renal dysfunction (adjust dose if GFR <60 mL/min)
  • History of gabapentin misuse
  • Severe psychiatric comorbidities
  • Concurrent use of other AUD medications

Dosing Protocol

1. Initiation Phase (Days 1-3):

   • Day 1: 300 mg at bedtime
   • Day 2: 300 mg twice daily
   • Day 3: 300 mg three times daily

2. Titration Phase (Days 4-7):

   • Increase by 300 mg/day every 1-2 days as tolerated
   • Target dose: 1800 mg/day (600 mg three times daily)

3. Maintenance Phase (Days 8-28/45):

   • Continue at 1800 mg/day (600 mg three times daily)
   • If intolerable side effects occur, reduce to 1200 mg/day (400 mg three times daily)

Outcome Measures

1. Primary Outcomes:

   • Percentage of days abstinent
   • Percentage of heavy drinking days
   • Time to first heavy drinking day

2. Secondary Outcomes:

   • Alcohol craving (measured by Penn Alcohol Craving Scale)
   • Sleep quality (measured by Pittsburgh Sleep Quality Index)
   • Mood symptoms (measured by Beck Depression Inventory)
   • Anxiety symptoms (measured by Hamilton Anxiety Rating Scale)

Safety Monitoring

• Weekly assessments for:
  • Adverse events (particularly falls, fractures, altered mental status) 3
  • Vital signs
  • Medication adherence
  • Alcohol consumption (timeline follow-back method)
  • Laboratory tests: liver function, renal function at baseline and study conclusion

Evidence-Based Rationale

Gabapentin has shown efficacy for AUD in several clinical trials, with the following key findings:

• The 1800 mg/day dosage has demonstrated superior outcomes compared to lower doses, with a number needed to treat (NNT) of 8 for complete abstinence and 5 for no heavy drinking 4
• At 1800 mg/day, gabapentin achieved 17% complete abstinence (vs. 4.1% with placebo) and 44.7% no heavy drinking (vs. 22.5% with placebo) 4
• Gabapentin has shown benefits in reducing alcohol craving, improving sleep quality, and reducing dysphoria 4, 5

Safety Considerations

• Monitor for adverse events, particularly falls/fractures and altered mental status, which occur more frequently with gabapentin doses ≥600 mg/day 3
• Gabapentin is primarily excreted renally (75%) with no hepatic metabolism, making it potentially safer than other AUD medications in patients with liver concerns 1, 2
• Dose adjustment is required in patients with renal impairment
• Sedation and dizziness are common side effects that may affect compliance

Clinical Pearls

• Gabapentin's efficacy may be particularly pronounced in patients with:
  • Alcohol withdrawal symptoms 6
  • Insomnia
  • Anxiety or dysphoria
• The three-times-daily dosing schedule is important for maintaining therapeutic blood levels
• Patient education about potential side effects is crucial for adherence
• Combining gabapentin with brief behavioral interventions may enhance outcomes

Follow-up Protocol

• Weekly in-person assessments during the 28-45 day study period
• Phone check-ins between visits to monitor adherence and adverse events
• Final assessment at day 28 or 45 with comprehensive evaluation of all outcome measures

This protocol aligns with the American Association for the Study of Liver Diseases guidance on pharmacotherapy for AUD 1 and builds on the successful methodology used in previous gabapentin trials for AUD 4, 5.