One multi-site US trial found immediate-release gabapentin reduced drinking in people with alcohol use disorder (AUD) but it has not been replicated. This multisite randomized trial tested the effect of gabapentin enacarbil extended-release (GE-XR, an FDA-approved treatment for postherpetic neuralgia and restless leg syndrome). Participants were treatment seeking, aged ≥21, with at least moderate DSM-5 AUD, drinking ≥21 drinks/week for women, ≥28/week for men plus 1 heavy drinking day/week in the last month. Participants had to be abstinent for at least 3 days before being randomized to receive 26 weeks of either GE-XR (600mg twice/day) or a matching placebo. Those who took at least 1 dose were analyzed (338 out of 346 randomized). Intervention effects were assessed in weeks 22–25 (considered the maintenance phase of the treatment).
- Medication adherence was similar in both groups (93% in intervention group, 92% in control).
- There was no significant difference in the primary outcome, the percentage of participants with no heavy drinking days (28% in intervention group versus 22% in control).
- There were no significant differences in other drinking measures, craving, or alcohol-related consequences.
Comments: In people with moderate to severe AUD, there was no effect of extended-release gabapentin on drinking or craving, contrary to hypotheses based on previous studies conducted with immediate-release gabapentin. GE-RX cannot be recommended for the treatment of AUD, especially considering the risk of misuse and accidental drug poisoning posed by gabapentin. These findings also raise doubts regarding the effectiveness of immediate-release gabapentin to treat AUD.
Nicolas Bertholet, MD, MSc
Reference: Falk DE, Ryan ML, Fertig JB, et al. Gabapentin enacarbil extended-release for alcohol use disorder: a randomized, double-blind, placebo-controlled, multisite trial assessing efficacy and safety. Alcohol Clin Exp Res. 2019;43(1):158–169.