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Cited by 743Substance Abuse Treatment and OutcomesAlcohol Consumption and Health EffectsAlcoholism and Thiamine Deficiency

Oral topiramate for treatment of alcohol dependence: A randomised controlled trial

Johnson, Bankole A, Ait-Daoud, Nassima, Bowden, Charles L, DiClemente, Carlo C, Roache, John D, Lawson, Kevin, Javors, Martin A, Ma, Jennie Z·2003·The Lancet
DOI 10.1016/s0140-6736(03)13370-3
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Abstract

Background Topiramate, a sulphamate fructopyranose derivative, might antagonise alcohol's rewarding effects associated with abuse liability by inhibiting mesocorticolimbic dopamine release via the contemporaneous facilitation of gamma-amino-butyric acid activity and inhibition of glutamate function. We aimed to see whether topiramate was more effective than placebo as a treatment for alcohol dependence.Methods We did a double-blind randomised controlled 12-week clinical trial comparing oral topiramate and placebo for treatment of 150 individuals with alcohol dependence. Of these 150 individuals, 75 were assigned to receive topiramate (escalating dose of 25-300 mg per day) and 75 had placebo as an adjunct to weekly standardised medication compliance management. Primary efficacy variables were: self-reported drinking (drinks per day, drinks per drinking day, percentage of heavy drinking days, percentage of days abstinent) and plasma gamma-glutamyl transferase, an objective index of alcohol consumption. The secondary efficacy variable was self-reported craving.Findings At study end, participants on topiramate, compared with those on placebo, had 2.88 (95% CI -4.50 to -1.27) fewer drinks per day (p=0.0006), 3.10 (-4.88 to -1.31) fewer drinks per drinking day (p=0.0009), 27.6% fewer heavy drinking days (p=0.0003), 26.2% more days abstinent (p=0.0003), and a log plasma gamma-glutamyl transferase ratio of 0.07 (-0.11 to -0.02) less (p=0.0046). Topiramate-induced differences in craving were also significantly greater than those of placebo, of similar magnitude to the self-reported drinking changes, and highly correlated with them.Interpretation Topiramate (up to 300 mg per day) is more efficacious than placebo as an adjunct to standardised medication compliance management in treatment of alcohol dependence.

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  • Topiramate inhibits voltage-dependent sodium channels, enhances the inhibitory activity of GABA, and is believed to decrease dopaminergic activity in reward circuits in the brain, ultimately reducing cravings.

    “Topiramate inhibits voltage-dependent sodium channels, enhances the inhibitory activity of GABA, and is believed to decrease dopaminergic activity in reward circuits in the brain, ultimately reducing cravings [62].”

    From A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder (2024) · cites this paper as [62]

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Authors
Johnson, B. A., Ait-Daoud, N., Bowden, C. L., DiClemente, C. C., Roache, J. D., Lawson, K., Javors, M. A., & Ma, J. Z.
Affiliations
The University of Texas at San Antonio Health Science Center (US)
Corresponding author
Johnson, Bankole A
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2003-05
Volume
361
Issue
9370
Pages
1677-1685
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(03)13370-3
OpenAlex
W2108740579
Cited by
743
References
32
Citations by year
2026: 7 · 2025: 11 · 2024: 15 · 2023: 35 · 2022: 15 · 2021: 15 · 2020: 23 · 2019: 23 · 2018: 21 · 2017: 23 · 2016: 23 · 2015: 25 · 2014: 38 · 2013: 31 · 2012: 38
FWCI
42.33
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • U.S. Public Health Service (12964-01)
  • National Institute on Alcohol Abuse and Alcoholism (K23AA000329, R01AA010522, AA 10522-08, K23 AA00329-01)
  • National Institute of Mental Health
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 › Neurology › Alcoholism and Thiamine Deficiency
Keywords
topiramate, alcoholism, alcoholism treatment, adjunct pharmacotherapy, alcohol craving, heavy drinking, alcohol abstinence
MeSH terms
Topiramate, Administration, Oral, Adult, Aged, Alcohol Drinking, Alcoholism, Double-Blind Method, Drug Administration Schedule, Female, Fructose, gamma-Glutamyltransferase, Humans, Male, Middle Aged, Substance Abuse Detection, Dopamine Antagonists

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