Pilot randomized placebo-controlled clinical trial of high-dose gabapentin for alcohol use disorder

Abstract

Background: Despite advances in the development of pharmacotherapy for alcohol use disorder (AUD), there remains a need for medications that can be administered to actively drinking outpatients to promote a reduction in harmful alcohol consumption. The primary aim of this pilot study was to determine whether high-dose gabapentin (3600 mg/daily) is more effective than placebo in reducing harmful alcohol consumption in outpatients with AUD.

Methods: Forty patients (27 men) who met DSM-IV-TR criteria for alcohol dependence and reporting at least 4 heavy drinking days (HDD) per week were recruited at a single site. Participants were actively drinking at study entry and received double-blind gabapentin (3600 mg/day; n = 19) or placebo (n = 20) for 8 weeks. Study medication was titrated over 5 days and administered in three divided doses (1200 mg three times per day). The proportion of HDD (primary outcome) and percent days abstinent (PDA; secondary outcome) were analyzed using generalized longitudinal mixed models with the predictors being study arm, week, study arm by week interaction, and corresponding baseline drinking measure.

Results: There was a significant interaction between study arm and week for the proportion of HDD per week, F (7, 215) = 3.33, p = 0.002 . There was also a significant interaction between study arm and week for PDA per week, F (7, 215) = 3.11, p = 0.004. The overall retention rate was 67.5% with no significant difference in time-to-dropout between treatment groups. There were no serious adverse events. No participants were removed from the trial due to the development of moderate-to-severe alcohol withdrawal (CIWA-Ar ≥ 13).

Conclusions: Gabapentin treatment rapidly titrated to a dosage of 3600 mg/day is associated with a reduction in the proportion of HDD per week and an increase in PDA per week in actively drinking outpatients with AUD. High-dose gabapentin is potentially a feasible approach to treating AUD and deserving of further study.

Trial registration: ClinicalTrials.gov NCT01141049.

Keywords: alcohol use disorder; gabapentin; pharmacotherapy.

© 2021 by the Research Society on Alcoholism.

Figures

Figure 1.

CONSORT Diagram

Figure 2.

Model estimated proportion of weekly heavy drinking days across treatment groups with 95% confidence intervals. P-values for tests between treatment groups at each week are reported.

Figure 3.

Model estimated proportion days abstinent per week across treatment groups with 95% confidence intervals. P-values for tests between treatment groups at each week are reported.

Figure 4.

Observed mean CIWA-Ar score across treatment groups with 95% confidence intervals

Figure 5.

Kaplan-Meier survival curves for time to dropout across treatment groups