Summary
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 -y-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 γ-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 γ-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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Article info
Publication history
Published: 17 May 2003
Identification
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© 2003 Elsevier Ltd. All rights reserved.
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- Topiramate for the treatment of alcohol dependence: initiating abstinence
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The excessive consumption of alcohol is a major health problem, accounting for 1·5% of deaths worldwide and having significant social and economic costs.1 Whilst current psychosocial treatments for alcohol abuse and dependence have been useful in reducing alcohol use and alcohol-related morbidity and mortality, these treatments are not always completely successful for all patients. In the past decade, a growing understanding of the neurobiology of alcohol dependence has identified medications that could improve treatment.
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