Can gabapentin be used to treat alcohol use disorder (AUD)?

Gabapentin for Alcohol Use Disorder

Gabapentin should be considered only as a second-line or third-line option for alcohol use disorder when first-line medications (naltrexone, acamprosate, or baclofen) cannot be used, and it should NOT be used as a substitute for benzodiazepines in managing alcohol withdrawal. 1, 2

Current Guideline Recommendations

The most recent French guidelines (2022) explicitly state that gabapentin is available without marketing authorization for alcohol use disorder and requires careful assessment of the benefit-risk ratio before prescription. 1 The medication has shown "some effectiveness" but its tolerance profile is "not considered harmless." 1

European guidelines (2012) identify gabapentin as a preliminary research compound for alcohol withdrawal syndrome, but emphasize that "sufficient evidence in favor of their use is lacking." 1

Evidence for Efficacy

For Reducing Heavy Drinking

• Meta-analysis data show gabapentin has a significant but modest effect on reducing percentage of heavy drinking days (Hedges' g = 0.5478, p = 0.0441). 3
• However, gabapentin shows no significant overall benefit compared to placebo across all alcohol-related outcomes (Hedges' g = 0.0725, p = 0.6743). 3
• A large recent trial of extended-release gabapentin enacarbil found it completely ineffective for drinking outcomes in patients with alcohol use disorder. 2

For Alcohol Withdrawal

• Gabapentin demonstrates a small but significant effect on reducing alcohol withdrawal symptoms (Hedges' g = 0.2475, p = 0.0425). 3
• Critical caveat: A 2019 study found that adjunctive gabapentin with benzodiazepines actually increased benzodiazepine requirements (median 6 vs 2 doses, p = 0.01) and resulted in higher maximum CIWA-Ar scores. 4
• Benzodiazepines remain the "gold standard" and only proven treatment to prevent seizures and reduce mortality from delirium tremens. 1, 5, 6

The Symptom-Driven Controversy

One large trial suggested gabapentin might benefit patients specifically with higher alcohol withdrawal symptoms, but this finding is problematic:

• Gabapentin appeared to worsen drinking outcomes in patients with low withdrawal symptoms. 2
• The applicability of these findings to everyday clinical practice is severely limited by methodological concerns. 2
• This "symptom-driven approach" lacks sufficient validation to guide routine prescribing. 2

Safety Concerns That Must Be Monitored

Gabapentin carries dose-dependent risks that are particularly relevant in alcohol use disorder populations:

• Falls and fractures: Incidence rate ratio 1.35 (95% CI 1.28-1.44), with clear dose-response relationship reaching RR 1.90 at doses ≥2,400 mg/day. 7
• Altered mental status: Incidence rate ratio 1.12 (95% CI 1.04-1.20), especially at doses 600-2,399 mg/day. 7
• Patients with alcohol use disorder had elevated baseline incidence of these adverse events regardless of gabapentin exposure. 7
• Clinicians must actively monitor safety, especially at doses ≥600 mg/day. 7

When Gabapentin Might Be Considered

Gabapentin may have a role in specific clinical scenarios where first-line medications are contraindicated:

• Patients with alcohol use disorder who also have chronic pain, anxiety disorders, or chronic insomnia, as gabapentin may address these comorbidities. 2
• Patients who cannot use naltrexone (due to liver disease or opioid use) or acamprosate (due to renal impairment). 2
• Never as monotherapy for moderate-to-severe alcohol withdrawal where benzodiazepines are required to prevent seizures and delirium tremens. 5, 6

Practical Prescribing Algorithm

If considering gabapentin for alcohol use disorder:

1. First confirm that naltrexone, acamprosate, and baclofen are all contraindicated or have failed. 1, 2
2. Assess for comorbid chronic pain, anxiety, or insomnia that might benefit from gabapentin. 2
3. Start at 900 mg/day (the minimum dose showing efficacy in trials). 2
4. Monitor closely for falls, fractures, and altered mental status, especially if increasing dose above 600 mg/day. 7
5. Combine with evidence-based psychotherapy (CBT or another specific modality, not just "usual care"). 1

For alcohol withdrawal management:

• Use benzodiazepines as first-line (chlordiazepoxide 50-100 mg initially, then 25-100 mg every 4-6 hours). 5, 6
• Administer thiamine 100-300 mg/day BEFORE any glucose-containing fluids. 5, 6
• Do not substitute gabapentin for benzodiazepines in moderate-to-severe withdrawal. 5
• Carbamazepine 200 mg every 6-8 hours is the preferred alternative if benzodiazepines are contraindicated. 5