Seizure Drugs Shows Promise for Alcohol Dependence in Subjects With Genetic Polymorphism

Treatment with the drug topiramate, used to treat seizures, appears to significantly reduce heavy drinking days and increase abstinent days in alcohol-dependent individuals relative to placebo, according to the report titled "Topiramate Treatment for Heavy Drinkers: Moderation by a GRIK1 Polymorphism" in AJP in Advance. But notably, the drug’s effects were only significantly better than placebo in individuals carrying a particular single nucleotide polymorphism known as rs2832407, which is believed to be associated with alcohol dependence.

Henry R. Kranzler, M.D, of the Department of Psychiatry at the University of Pennsylvania Perelman School of Medicine, and colleagues at several other institutions randomly assigned a total of 138 individuals to receive 12 weeks of treatment with topiramate (n=67), at a maximal daily dose of 200 mg, or placebo (n=71). Both groups received brief counseling to reduce drinking and increase abstinent days. DNA was extracted from whole blood, and subjects were genotyped for the presence of rs2832407.

There was a significant main effect seen in the medication group, with topiramate patients reducing heavy drinking more than placebo patients. By the last week of treatment, the odds of experiencing a heavy drinking day in the placebo group was 5.33 times that of the topiramate treatment group, and the number of patients with no heavy drinking days during the last four weeks of treatment in the topiramate group was more than double that of the placebo group. Topiramate patients also reported more abstinent days than placebo patients.

The effect on heavy drinking days was seen only in patients with the rs2832407 polymorphism. (The effect on days of abstinence was not significant.)


“The moderator effect of rs2832407, if validated, would facilitate the identification of heavy drinkers who are likely to respond well to topiramate treatment and provide an important personalized treatment option,” the researchers stated.

For more information on topiramate’s potential effects on addiction, see the Psychiatric News article, “Seizure Drug Shows Promise as Cocaine Addiction Treatment.”

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