Posttreatment effects of topiramate treatment for heavy drinking

Alcohol Clin Exp Res. 2014 Dec;38(12):3017-23. doi: 10.1111/acer.12578.

Abstract

Background: We examined whether the effects of topiramate and a single nucleotide polymorphism (rs2832407) in GRIK1, which encodes a kainate receptor subunit, persisted following a 12-week, placebo-controlled trial in 138 heavy drinkers with a treatment goal of reduced drinking. During treatment, topiramate 200 mg/d significantly reduced heavy drinking days and increased the frequency of abstinent days (Am J Psychiatry, 2014, 171:445). In the European-American (EA) subsample (n = 122), rs2832407 moderated the treatment effect on heavy drinking.

Methods: Patients were re-interviewed 3 and 6 months after the end of treatment. During treatment, we obtained 92.4% of drinking data, with 89.1 and 85.5% complete data at the 3- and 6-month follow-up visits, respectively. We examined 4 outcomes over time in the overall sample and the EA subsample: percent heavy drinking days (PHDD), percent days abstinent (PDA), serum γ-glutamyl transpeptidase (GGTP) concentration, and a measure of alcohol-related problems.

Results: In the full sample, the lower PHDD and higher PDA seen with topiramate treatment were no longer significant during follow-up. Nonetheless, the topiramate-treated patients had lower alcohol-related problem scores during treatment and both follow-up periods. Further, in the EA subsample, the greater reduction in PHDD seen with topiramate treatment in rs2832407*C-allele homozygotes persisted throughout follow-up, with no significant effects in A-allele carriers. A reduction in GGTP concentration was consistent with the reduction in heavy drinking, but did not reach statistical significance.

Conclusions: There are persistent therapeutic effects of topiramate in heavy drinkers, principally in rs2832407*C-allele homozygotes.

Keywords: GRIK1; Heavy Drinkers; Posttreatment Follow-Up; Topiramate; rs2832407.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alcohol Abstinence*
  • Alcohol Drinking / drug therapy*
  • Alcohol Drinking / epidemiology
  • Alcohol Drinking / genetics*
  • Alcoholic Intoxication / drug therapy*
  • Alcoholic Intoxication / epidemiology
  • Alcoholic Intoxication / genetics*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, Kainic Acid / genetics*
  • Time Factors
  • Treatment Outcome

Substances

  • Gluk1 kainate receptor
  • Receptors, Kainic Acid