Self‐efficacy mediates the effects of topiramate and GRIK1 genotype on drinking

Abstract

Previous studies indicate that topiramate reduces alcohol use among problem drinkers, with one study showing that the effect was moderated by a polymorphism (rs2832407) in GRIK1, the gene encoding the GluK1 kainate subunit. We examined whether the interactive effect of medication and genotype (a) altered the association between daily self-efficacy and later day drinking and (b) had an indirect effect on drinking via self-efficacy. Methods In a 12-week, placebo-controlled trial of topiramate, we used daily interactive voice response technology to measure self-efficacy (i.e., confidence in avoiding heavy drinking later in the day) and drinking behavior in 122 European-American heavy drinkers. Results Topiramate’s effects on both self-efficacy and drinking level were moderated by rs2832407. C-allele homozygotes treated with topiramate showed higher levels of self-efficacy and lower levels of nighttime drinking across the 12-week trial. Further, the interactive effect of topiramate and genotype on mean nighttime drinking levels was mediated by mean levels of self-efficacy. Conclusion By modeling topiramate’s effects on nighttime drinking across multiple levels of analysis, we found that self-efficacy, a key psychological construct, mediated the effect of topiramate, which was moderated by rs2832407 genotype. Thus, it may be possible to use an individualized assessment (i.e., genotype) to select treatment (i.e., topiramate or psychotherapy aimed at enhancing self-efficacy) to optimize the reduction in heavy drinking to provide a personalized treatment approach.

Type A/Type B Alcoholism Predicts Differential Response to Topiramate in a Smoking Cessation Trial in Dually Diagnosed Men

“…Specifically, the impact of topiramate on cigarette craving was greater for the Type B group, which at least partially explains its enhanced efficacy on smoking over time in this subtype. A similar mediated moderation was demonstrated in a study by Kranzler et al (2014), in which mean daily selfefficacy to resist heavy drinking mediated the Topiramate × Genotype interaction. Although our data did not support an expected baseline difference between typology groups in negative reinforcement smoking expectancies, the mediated moderation results suggest that stronger effects of topiramate on relief-related craving for the Type B group were implicated in suppressing their long-term increases in smoking.…”

Differential potassium channel gene regulation in BXD mice reveals novel targets for pharmacogenetic therapies to reduce heavy alcohol drinking

“…For example, individuals with SNPs in OPRM1 , HTR3A/B , or GRIK1 genes moderate the reduction in heavy drinking by naltrexone, ondansetron, and topiramate treatment, respectively (Anton et al, 2008; Johnson, Seneviratne, Wang, Ait-Daoud, & Li, 2013; Kranzler, Armeli, et al, 2014; Kranzler, Covault, et al, 2014; Oslin et al, 2003). There is evidence that SNPs in KCNB1 , KCND2 , KCNJ6 , KCNMA1 , and KCNQ1/5 are associated with alcohol dependence or increased risk for developing an alcohol use disorder (Buhler et al, 2015; Clarke et al, 2011; Edenberg et al, 2010; Kendler et al, 2011; Namkung, Kim, & Park, 2005; Pan et al, 2013; Zuo et al, 2012).…”

Active Ingredients of Treatment and Client Mechanisms of Change in Behavioral Treatments for Alcohol Use Disorders: Progress 10 Years Later

“…Kiluk et al, 2011) as well as investigate the role of specific genotypes as moderators of mediated effects ( conditional process model, e.g. Kranzler et al, 2014). …”