Barbara J. Mason, PhD, Susan Quello, BA, BS, Vivian Goodell, MPH, Farhad Shadan, MD, Mark Kyle, MD, and Adnan Begovic, MD
Abstract
Importance
Approved medications for alcohol dependence are prescribed for fewer than 9% of US alcoholics.
Objective
To determine if gabapentin, a widely-prescribed generic calcium channel/GABA modulating medication, increases rates of sustained abstinence and no heavy drinking, and decreases alcohol-related insomnia, dysphoria and craving, in a dose-dependent manner.
Design, Participants and Setting
A 12-week, double-blind, placebo-controlled, randomized dose-ranging trial of 150 men and women over 18 years of age with current alcohol dependence, conducted 2004–2010 at a single-site outpatient clinical research facility adjoining a general medical hospital.
Interventions
Oral gabapentin (0, 900, 1800 mg/d) and concomitant manual-guided counseling.
Main Outcome Measures
Rates of complete abstinence and no heavy drinking (co-primary) and changes in mood, sleep and craving (secondary) over the 12-week study.
Results
Gabapentin significantly improved the rates of abstinence and no heavy drinking. The abstinence rate was 4.1% (95% CI, 1.1 to 13.7) in the placebo group, 11.1% (95% CI, 5.2 to 22.2) in the 900 mg group, and 17.0% (95% CI, 8.9 to 30.1) in the 1800 mg group (p = 0.04 for linear dose effect, NNT = 8 for 1800 mg). The no heavy drinking rate was 22.5% (95% CI, 13.6 to 37.2) in the placebo group, 29.6% (95% CI, 19.1 to 42.8) in the 900 mg group, and 44.7% (95% CI, 31.4 to 58.8) in the 1800 mg group (p = 0.02 for linear dose effect, NNT = 5 for 1800 mg). Similar linear dose effects were obtained with measures of mood (F=7.37, df=2, p=0.001), sleep (F=136, df=2, p<0.001), and craving (F=3.56, df=2, p=0.029). There were no serious drug-related adverse events, and terminations from adverse-events (9 of 150 participants), time on study (9.1 [3.8] weeks) and rate of study completion (85 of 150 participants) did not differ between groups.
Conclusions and Relevance
Gabapentin (particularly the 1800 mg dosage) was effective in treating alcohol dependence and relapse-related symptoms of insomnia, dysphoria and craving, with a favorable safety profile. Increased implementation of pharmacological treatment of alcohol dependence in primary care may be a major benefit of gabapentin as a treatment option for alcohol dependence.