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Anticonvulsant Drug Topiramate Reduces Heavy Drinking

Glutamate receptor plays key role (February 14)

Researchers at the University of Pennsylvania’s Perelman School of Medicine have shown that the anticonvulsant medication topiramate, previously shown to reduce drinking in patients committed to abstinence from alcohol, can also be helpful in treating problem drinkers whose aim is to curb their alcohol consumption — particularly among a specific group of patients whose genetic makeup appears to be linked to the treatment’s efficacy.

The new findings were published online in the American Journal of Psychiatry.

The randomized double-blind trial included 138 heavy drinkers, approximately half of whom received 12 weeks of treatment with topiramate at a maximal dosage of 200 mg/day and half of whom received placebo. Both groups underwent brief counseling to reduce drinking and to increase abstinent days.

The study had three phases: a 1-week pretreatment assessment period, a 12-week treatment period, and a 9-day medication taper period.

The patients who received topiramate had fewer heavy drinking days than had those in the placebo group. By the end of treatment, the likelihood of experiencing a heavy drinking day in the placebo group was five times greater than that in the topiramate group; and the number of patients who experienced no heavy drinking days during the last 4 weeks of treatment in the topirmate group was more than double that in the placebo group. In addition, topiramate-treated patients reported more abstinent days than did placebo patients.

The study has important implications for the personalized treatment of heavy drinking, according to the authors. An analysis showed that only individuals with a specific genotype found in 40% of European–Americans benefited from treatment with topiramate. The genotype involves two copies of a variant in the gene that encodes a subunit of the receptor for an excitatory amino acid neurotransmitter, glutamate.

By showing that only individuals with a certain form of the kainate (glutamate) receptor reduced drinking with topiramate treatment, the study indicated that this receptor plays a key role in topiramate’s effects on drinking. Because topiramate interacts with multiple neurotransmitter and enzyme systems, this finding provides a specific target for the development of medications to reduce heavy drinking, the authors say.

Source: Penn Medicine; February 14, 2014.

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