title: Topiramate's reduction of body mass index in heavy drinkers: lack of moderation by a GRIK1 polymorphism.
abstract: Topiramate, which interacts with multiple neurotransmitter and enzyme systems, is approved by the Food and Drug Administration to treat seizure disorder, prevent migraine, and (in combination with phentermine) reduce weight. Topiramate has also been shown in multiple studies to reduce heavy drinking. The authors found that topiramate 200 mg/day significantly reduced heavy drinking in heavy drinkers with a treatment goal of reduced drinking (Kranzler et al., 2014). Further, in the European American (EA) subsample (n = 122), a single nucleotide polymorphism (rs2832407) in GRIK1, which encodes the GluK1 subunit of the kainate receptor, moderated the effect on heavy drinking days. Here the authors examined the effects of topiramate on body mass index (BMI) and the moderating effect of rs2832407 in the EA subsample from Kranzler et al. (2014). Across the 12 weeks of treatment, BMI was reduced by 1.2 kg/m2 (p < .001) in the topiramate group but was unchanged in the placebo group. There was no evidence of moderation by rs2832407 of topiramate's effects on BMI. Controlling for changes in drinking and other potential confounders did not alter the findings. These results suggest that the effect of topiramate on drinking behavior, in which the GluK1-containing kainate receptor appears to play a key role, can be dissociated from its effect on weight, the specific mechanism of which remains to be determined.
authors: Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania.
authors: Henry R
authors: HR
authors: Kranzler
authors: Department of Medical Sciences, Frank Netter School of Medicine, Quinnipiac University.
authors: Richard
authors: R
authors: Feinn
authors: Department of Psychiatry, Yale University School of Medicine.
authors: Joel
authors: J
authors: Gelernter
authors: Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania.
authors: Timothy
authors: T
authors: Pond
authors: Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine.
authors: Jonathan
authors: J
authors: Covault
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D015992:Body Mass Index; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018092:Kainic Acid Receptors / Q000235:genetics*; D000077236:Topiramate
chemical_list: D019440:Anti-Obesity Agents; D005632:Fructose; D018092:Kainic Acid Receptors; D000077236:Topiramate