Anticonvulsants may Help Some Heavy Drinkers Cut Alcohol Use

Treatment with the anticonvulsant topiramate may help alcohol-dependent individuals who do not want to stop drinking completely reduce their alcohol consumption, new research shows.
A randomized controlled trial of 138 adult heavy drinkers in the United States showed that those who received topiramate at a maximum daily dose of 200 mg for 12 weeks were 5 times less likely to experience a heavy drinking day compared with those who received matching placebo. In addition, participants in the topiramate group experienced significantly more abstinent days.
In further analysis, the investigators found that the effect on heavy drinking days after topiramate treatment was only shown in the participants who carried the rs2832407 genotype. They note that, if validated, this finding could help identify patients most likely to respond to this treatment.
"We had 2 main results. First, topiramate is useful to help people reduce drinking at a lower dosage, and it was well tolerated," lead author Henry R. Kranzler, MD, professor of psychiatry at the University of Pennsylvania Perelman School of Medicine in Philadelphia and director of the school's Center for Studies of Addiction, told Medscape Medical News.
"We have very complete data, which gives us confidence that the findings are real," he added.
Secondly, "it is possible with an SNP [single-nucleotide polymorphism] genotype, which is easy to get done these days, to predict who will respond better to topiramate than to placebo."
Dr. Kranzler noted that the findings also implicate the importance of the kainate receptor, and specifically its GluK1 subunit, in controlling alcohol drinking behavior.
"This means it might be possible to design a new drug to specifically block that subunit and avoid many of the side effects that topiramate has," he said.
The study was published online February 14 in the American Journal of Psychiatry.
Few Seek Treatment
Data released in 2010 showed that 23% of all US residents older than 11 years consumed 5 or more drinks in 1 setting during the previous month ― and 7% reported doing so at least 5 days per month.

Dr. Henry Kranzler

"Despite this, few heavy drinkers seek out treatment ― especially those who do not meet the clinical criteria for an alcohol use disorder but whose drinking causes substantial damage to individuals, their families, and the community," note the researchers in a release.
Previous research has shown that topiramate can reduce drinking in those who want to abstain from alcohol. But for this trial, the investigators sought to determine whether it could also help those who wanted to limit their alcohol consumption to safe levels, rather than to stop drinking altogether.
Topiramate increases γ-aminobutyric acid (GABA) while also inhibiting glutamate activity by blocking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors.
As reported by Medscape Medical News, a recent randomized controlled trial showed that adults who were dependent on both cocaine and alcohol were significantly more likely to be abstinent from cocaine after 13 weeks of treatment with 300 mg/day of topiramate plus cognitive-behavioral therapy (CBT) than those who received placebo plus CBT.
"By increasing GABAergic activity in the nucleus accumbens, topiramate may reduce the dopamine release associated with cocaine or alcohol use and reduce the reinforcing effects," the researchers wrote at the time.