Efficacy of Gabapentin for the Treatment of Alcohol Use Disorder in Patients With Alcohol Withdrawal Symptoms: A Randomized Clinical Trial

Abstract

Importance: Although an estimated 30 million people meet criteria for alcohol use disorder (AUD), few receive appropriate pharmacotherapy. A more personalized, symptom-specific, approach might improve efficacy and acceptance.

Objective: To examine whether gabapentin would be useful in the treatment of AUD, especially in those with the most alcohol withdrawal symptoms.

Design, setting, and participants: This double-blind randomized clinical trial conducted between November 2014 and June 2018 evaluated gabapentin vs placebo in community-recruited participants screened and treated in an academic outpatient setting over a 16-week treatment period. A total of 145 treatment-seeking individuals who met Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for AUD and were not receiving other AUD intervention were screened, and 96 who also met recent alcohol withdrawal criteria were randomized to treatment after 3 abstinent days. Daily drinking was recorded, and percentage of disialo carbohydrate-deficient transferrin in the blood, a heavy drinking marker, was collected at baseline and monthly during treatment.

Interventions: Gabapentin up to 1200 mg/d, orally, vs placebo along with 9 medical management visits (20 minutes each).

Main outcomes and measures: The percentage of individuals with no heavy drinking days and those with total abstinence were compared between treatment groups and further evaluated based on prestudy alcohol withdrawal symptoms.

Results: Of 96 randomized individuals, 90 were evaluable (44 in the gabapentin arm and 46 in the placebo arm), with a mean (SD) age of 49.6 (10.1) years; 69 were men (77%) and 85 were white (94%). The evaluable participants had 83% baseline heavy drinking days (4 or more drinks/day for women, 5 or more for men) and met 4.5 alcohol withdrawal criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). More gabapentin-treated individuals had no heavy drinking days (12 of 44 participants [27%]) compared with placebo (4 of 46 participants [9%]), a difference of 18.6% (95% CI, 3.1-34.1; P = .02; number needed to treat [NNT], 5.4), and more total abstinence (8 of 44 [18%]) compared with placebo (2 of 46 [4%]), a difference of 13.8% (95% CI, 1.0-26.7; P = .04; NNT, 6.2). The prestudy high-alcohol withdrawal group had positive gabapentin effects on no heavy drinking days (P < .02; NNT, 3.1) and total abstinence (P = .003; NNT, 2.7) compared with placebo, while within the low-alcohol withdrawal group, there were no significant differences. These findings were similar for other drinking variables, where gabapentin was more efficacious than placebo in the high-alcohol withdrawal group only. Gabapentin caused more dizziness, but this did not affect efficacy.

Conclusions and relevance: These data, combined with others, suggest gabapentin might be most efficacious in people with AUD and a history of alcohol withdrawal symptoms. Future studies should evaluate sleep changes and mood during early recovery as mediators of gabapentin efficacy.

Trial registration: ClinicalTrials.gov Identifier: NCT02349477.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Anton reported receiving grants from the National Institute on Alcohol Abuse and Alcoholism during the conduct of the study; receiving grants and consulting fees from Laboratorio Farmaceutico CT; receiving consulting fees from Alkermes, Allergan, Indivior, Insys, Life Epigenetics, XenoPort (Arbor Pharmaceuticals), and Alcohol Clinical Trials Initiative (ACTIVE) outside the submitted work; and serving as a member and chair of ACTIVE, which was partially supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. Dr Book reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Prisciandaro reported receiving grants and consulting fees from Farmaceutico Italiano and consulting fees from Laboratorio Farmaceutico CT outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. CONSORT Diagram

CONSORT indicates Consolidated Standards of Reporting Trials; PCP, primary care physician.

Figure 2.. Percentage of Individuals With Heavy Drinking or No Drinking Days During the Study

Percentage of individuals with either (A) no heavy drinking days or (B) no drinking days (complete abstinence) over the course of the study by medication and alcohol withdrawal level (AWS low or high). At baseline (data not shown), all study participants had drinking days and heavy drinking days, so in this depiction they would start at 0%. AWS indicates alcohol withdrawal symptoms.