The International Journal of Neuropsychopharmacology

Research Article

GRIK1 Genotype moderates topiramate's effects on daily drinking level, expectations of alcohol's positive effects and desire to drink

Henry R. Kranzlera1 c1, Stephen Armelia2, Richard Feinna3, Howard Tennena4a5, Joel Gelerntera6 and Jonathan Covaulta5

a1 Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania and VISN4 MIRECC, Philadelphia VAMC, Philadelphia, PA, USA

a2 Department of Psychology, Fairleigh Dickinson University, Teaneck, NJ, USA

a3 Frank Netter School of Medicine, Quinnipiac University, Hamden, CT, USA

a4 Department of Community Medicine and Healthcare, University of Connecticut School of Medicine, Farmington, CT, USA

a5 Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA

a6 Department of Psychiatry, Yale University School of Medicine, New Haven, CT and VA Connecticut Healthcare, West Haven, CT, USA

Abstract

We (Kranzler et al., 2014) reported that topiramate 200 mg/day reduced heavy drinking days and increased abstinent days in 138 heavy drinkers whose treatment goal was to reduce drinking to safe levels. In that 12-week, placebo-controlled study, we measured drinking using the Timeline Follow-back method at each treatment visit. In addition to the intent-to-treat effects of topiramate, we found that a single nucleotide polymorphism (rs2832407) in GRIK1, encoding the GluK1 subunit of the kainate receptor, moderated the treatment effect in European Americans (EAs; n = 122). Topiramate reduced heavy drinking only in rs2832407*C allele homozygotes. Here, we augment those analyses by using patients’ daily reports obtained using interactive voice response technology; (a) to validate the interactive effects of GRIK1 and topiramate as predictors of drinking level; and, (b) to examine changes in expected positive effects of drinking (i.e. positive outcome expectancies) and desire to drink. We found that rs2832407*C allele homozygotes treated with topiramate drank less overall during treatment than those receiving placebo, validating our earlier findings for heavy drinking days (Kranzler et al., 2014). There was also a study day × medication group × genotype group interaction that predicted both positive alcohol expectancies and desire to drink, with rs2832407*C-allele homozygotes treated with topiramate showing the largest decreases in these outcomes during the study period. Changes in positive alcohol expectancies or desire to drink did not mediate the effects on drinking. These findings validate and extend our previous pharmacogenetic findings with topiramate.

(Received January 31 2014)

(Reviewed March 04 2014)

(Revised March 06 2014)

(Accepted March 14 2014)

(Online publication April 30 2014)

Key words

  • GRIK1;
  • heavy drinking;
  • pharmacogenetics;
  • subjective effects;
  • topiramate

Correspondence

c1 Address for correspondence: Dr Kranzler, Treatment Research Center, University of Pennsylvania Perelman School of Medicine, 3900 Chestnut Street, Philadelphia, PA 19104, USA. Tel.: 215-386-6662 Fax: 215-386-6770 Email: kranzler@mail.med.upenn.edu