Gabapentin combined with naltrexone for the treatment of alcohol dependence

Abstract

Objective: Naltrexone, an efficacious medication for alcohol dependence, does not work for everyone. Symptoms such as insomnia and mood instability that are most evident during early abstinence might respond better to a different pharmacotherapy. Gabapentin may reduce these symptoms and help prevent early relapse. This clinical trial evaluated whether the combination of naltrexone and gabapentin was better than naltrexone alone and/or placebo during the early drinking cessation phase (first 6 weeks), and if so, whether this effect persisted.

Method: A total of 150 alcohol-dependent individuals were randomly assigned to a 16-week course of naltrexone alone (50 mg/day [N=50]), naltrexone (50 mg/day) with gabapentin (up to 1,200 mg/day [N=50]) added for the first 6 weeks, or double placebo (N=50). All participants received medical management.

Results: During the first 6 weeks, the naltrexone-gabapentin group had a longer interval to heavy drinking than the naltrexone-alone group, which had an interval similar to that of the placebo group; had fewer heavy drinking days than the naltrexone-alone group, which in turn had more than the placebo group; and had fewer drinks per drinking day than the naltrexone-alone group and the placebo group. These differences faded over the remaining weeks of the study. Poor sleep was associated with more drinking in the naltrexone-alone group but not in the naltrexone-gabapentin group, while a history of alcohol withdrawal was associated with better response in the naltrexone-gabapentin group.

Conclusions: The addition of gabapentin to naltrexone improved drinking outcomes over naltrexone alone during the first 6 weeks after cessation of drinking. This effect did not endure after gabapentin was discontinued.

Trial registration: ClinicalTrials.gov NCT00183196.

Figures

Figure 1

Participant flow into a randomized, double-blind placebo-controlled trial combining naltrexone and gabapentin (for the first 6 weeks) with naltrexone-alone for treatment of alcohol dependence.

Figure 2

Time to First Heavy Drinking Day Cumulative survival of participants not having a heavy drinking day over the course of the study. During the first six weeks, the naltrexone/gabapentin group had more time to a first heavy drinking day than the naltrexone-alone group (p= 0.04), which in turn was not significantly different than the placebo group. There were no significant differences in the post-gabapentin phase.

Figure 3

Percent Heavy Drinking Days Percent heavy drinking days per week during the trial (left panel) and the total over each period (right panel). During the first six weeks, those receiving naltrexone/gabapentin had less heavy drinking days than those receiving naltrexone-alone (p=0.0002) but similar to placebo (p=0.16). These effects faded after gabapentin was stopped (post-gabapentin) phase.

Figure 4

Drinks Per Drinking Day Average drinks per drinking day each week during the trial (left panel) and total over each period (right panel). During the first six weeks, those receiving naltrexone/gabapentin had less drinks/drinking day than those receiving naltrexone-alone (p=0.02) and placebo (p=0.01). There were no significant differences after gabapentin was stopped (post-gabapentin) phase.

Figure 5

Alcohol Withdrawal History and Treatment Response Cumulative survival of participants not having a heavy drinking day over the course of the study for those with or without a history of alcohol withdrawal (AW). Those with a history of AW treated with naltrexone/gabapentin had more time to a first heavy drinking day compared to those receiving placebo (p= 0.03). For those without a history of AW there was no difference between medication groups.