Abstract
BACKGROUND AND AIMS: Previous findings have been equivocal as to whether a single-nucleotide polymorphism (rs2832407) in GRIK1, which encodes a glutamate receptor subunit, moderates the effects of topiramate treatment for drinking reduction. We leveraged intensive longitudinal data to provide greater precision and allow an examination of intermediate outcomes addressing this question. We used data from a randomized controlled trial (RCT) to test the hypotheses that topiramate treatment reduces daily heavy drinking, desire to drink and positive alcohol expectancies and that these effects are stronger in rs2832407*C-allele homozygotes. DESIGN: Secondary data analysis of a randomized controlled trial. SETTING: University of Pennsylvania Treatment Research Center in the United States. PARTICIPANTS/CASES: Participants were 164 individuals (70.1% male, mean age = 51.42, 36.0% rs2832407*C-allele homozygotes) who sought to reduce or stop drinking. INTERVENTION AND COMPARATOR: Participants were assigned to medication (topiramate or placebo), with stratification by genotype group (CC versus AA/AC) and treatment goal (reduce versus abstain). MEASUREMENTS: During the 12-week treatment period, participants completed daily interactive voice response (IVR) surveys. FINDINGS: On any given day during treatment, participants who received topiramate had lower odds of IVR-reported heavy drinking [odds ratio (OR) = 0.259, b (standard error, SE) = -1.351 (0.334), P < 0.001] and lower levels of desire to drink [b (SE) = -0.323 (0.122), P = 0.009] and positive alcohol expectancies [b (SE) = -0.347 (0.138), P = 0.013] than those who received placebo. Participants who received topiramate also reported greater reductions in positive alcohol expectancies during the first 2 weeks of treatment than those who received placebo [b (SE) = -0.028 (0.008), P = 0.001], but topiramate did not impact the daily rate of change in heavy drinking or desire to drink. Genotype did not moderate the effects of topiramate on any outcomes examined (P > 0.05). CONCLUSIONS: Topiramate is an effective medication for individuals seeking to reduce heavy drinking. The effects are not moderated by the single-nucleotide polymorphism rs2832407.