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Cited by 89Substance Abuse Treatment and OutcomesAlcohol Consumption and Health EffectsOpioid Use Disorder Treatment

Gabapentin enacarbil extended-release for alcohol use disorder: a randomized, double-blind, placebo-controlled, multisite trial assessing efficacy and safety

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Falk, Daniel E., Ryan, Megan L., Fertig, Joanne B., Devine, Eric G., Cruz, Ricardo, Brown, E. Sherwood, Burns, Heather, Salloum, Ihsan M. +21 more·2019·Alcoholism: Clinical and Experimental Research
DOI 10.1111/acer.13917PMC PMC6317996
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Abstract

Background: Several single‐site alcohol treatment clinical trials have demonstrated efficacy for immediate‐release (IR) gabapentin in reducing drinking outcomes among individuals with alcohol dependence. The purpose of this study was to conduct a large, multisite clinical trial of gabapentin enacarbil extended‐release (GE‐XR) (HORIZANT®), a gabapentin prodrug formulation, to determine its safety and efficacy in treating alcohol use disorder (AUD). Methods: Men and women (n = 346) who met DSM‐5 criteria for at least moderate AUD were recruited across 10 U.S. clinical sites. Participants received double‐blind GE‐XR (600 mg twice a day) or placebo and a computerized behavioral intervention (Take Control) for 6 months. Efficacy analyses were prespecified for the last 4 weeks of the treatment period. Results: The GE‐XR and placebo groups did not differ significantly on the primary outcome measure, percentage of subjects with no heavy drinking days (28.3 vs. 21.5, respectively, p = 0.157). Similarly, no clinical benefit was found for other drinking measures (percent subjects abstinent, percent days abstinent, percent heavy drinking days, drinks per week, drinks per drinking day), alcohol craving, alcohol‐related consequences, sleep problems, smoking, and depression/anxiety symptoms. Common side‐effects were fatigue, dizziness, and somnolence. A population pharmacokinetics analysis revealed that patients had lower gabapentin exposure levels compared with those in other studies using a similar dose but for other indications. Conclusions: Overall, GE‐XR at 600 mg twice a day did not reduce alcohol consumption or craving in individuals with AUD. It is possible that, unlike the IR formulation of gabapentin, which showed efficacy in smaller Phase 2 trials at a higher dose, GE‐XR is not effective in treating AUD, at least not at doses approved by the U.S. Food and Drug Administration for treating other medical conditions.

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  • A recent overall-negative study with a gabapentin prodrug was reported, but the consensus was that the dose was low, and secondary analyses showed some efficacy in some subgroups.

    “A recent overall-negative study with a gabapentin prodrug has been reported, but the consensus was that the dose was low, and secondary analyses showed some efficacy in some subgroups of subjects in the study (Falk et al., 2019;Laska et al., 2020).”

    From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Falk et al., 2019

    The Results report no significant overall benefit and identify statistically significant effects in some subgroups; the Discussion cautions that these subgroup findings could be spurious. The Discussion says a higher dose might have been needed, but also says the tested dose was within the range previously found efficacious for alcohol use disorder. It does not establish a consensus that the dose was low. (LLM, conf=0.88)

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  • In a 6-month RCT of 346 individuals with AUD, extended-release gabapentin (600 mg twice daily) did not significantly differ from placebo in percentage of subjects with no heavy drinking days.

    “In a different study involving 346 individuals with AUD, participants were randomly assigned to receive either extended-release gabapentin (GE-XR) at 600 mg twice a day or a placebo, along with a computerized behavioral intervention over a 6-month period. The primary outcome measure, the percentage of subjects with no heavy drinking days, did not significantly differ between the GE-XR and placebo”

    From A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder (2024) · cites this paper as [67]

  • In that same trial, no clinical benefits were observed for various drinking measures, alcohol craving, alcohol-related consequences, sleep problems, smoking, or depression/anxiety symptoms.

    “Additionally, no clinical benefits were observed for various drinking measures, alcohol craving, alcohol-related consequences, sleep problems, smoking, and depression/anxiety symptoms”

    From A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder (2024) · cites this paper as [67]

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Research works printed but not linked: 2

  1. Miller W (1995) The Drinker Inventory of Consequences (DrInC): an instrument for assessing adverse consequences of alcohol abuse, in NIAAA Project MATCH Monograph Series (Vol. 4) (Mattson M, Marshall LA eds), pp. 1– 94. National Institute on Alcohol Abuse and Alcoholism: Bethesda, MD.
  2. Singleton EG (2000) A brief version of the Alcohol Craving Questionnaire (ACQ-NOW)? Proceedings of the 60th Annual Meeting, The College on Problems of Drug Dependence, Inc. Volume II: Abstracts. NIDA Research Monograph 180. Rockville, Maryland: National Institute on Drug Abuse, p. 304.

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Authors
Falk, D. E., Ryan, M. L., Fertig, J. B., Devine, E. G., Cruz, R., Brown, E. S., Burns, H., Salloum, I. M., Newport, D. J., Mendelson, J., Galloway, G., Kampman, K., Brooks, C., Green, A. I., Brunette, M. F., Rosenthal, R. N., Dunn, K. E., Strain, E. C., Ray, L., Shoptaw, S., Ait‐Daoud Tiouririne, N., Gunderson, E. W., Ransom, J., Scott, C., Leggio, L., Caras, S., Mason, B. J., Litten, R. Z., & the National Institute on Alcohol Abuse and Alcoholism Clinical Investigations Group (NCIG) Study Group
Affiliations
  • National Institute on Alcohol Abuse and Alcoholism (US)
  • Boston University (US)
  • The University of Texas Southwestern Medical Center (US)
  • University of Miami (US)
  • Friends Research Institute (US)
  • University of Pennsylvania (US)
  • Dartmouth College (US)
  • Stony Brook University (US)
  • Johns Hopkins University (US)
  • University of California, Los Angeles (US)
  • Center for Leading Edge Addiction Research University of Virginia Charlottesville Virginia
  • University of Virginia (US)
  • Fast Track Drugs and Biologics (US)
  • National Institutes of Health (US)
  • Arbor Pharmaceuticals (United States) (US)
  • Scripps Research Institute (US)
Corresponding author
Falk, Daniel E.
ORCID
Venue
Alcoholism: Clinical and Experimental Research
Publisher
Wiley
Published
2018-12-09
Volume
43
Issue
1
Pages
158-169
ISSN
  • 0145-6008 (ISSN-L)
  • 1530-0277
DOI
10.1111/acer.13917
PMC
PMC6317996
OpenAlex
W2899873708
Cited by
89
References
45
Citations by year
2026: 7 · 2025: 7 · 2024: 14 · 2023: 7 · 2022: 18 · 2021: 9 · 2020: 13 · 2019: 12 · 2018: 2
FWCI
7.02
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Alcoholism Clinical and Experimental Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
National Institute on Alcohol Abuse and Alcoholism (HHSN275201400001l)
Topics
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
Keywords
gabapentin enacarbil, sustained-release formulation, alcoholism, alcohol craving, heavy drinking, pharmacokinetics, drug efficacy, drug safety, adverse effects, sleep disorders
MeSH terms
Adult, Alcoholism, Behavior Therapy, Carbamates, Combined Modality Therapy, Delayed-Action Preparations, Double-Blind Method, Female, gamma-Aminobutyric Acid, Humans, Male, Middle Aged, Prodrugs, Therapy, Computer-Assisted, Treatment Outcome, Young Adult

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