Post‐treatment effects of topiramate on alcohol‐related outcomes: A combined analysis of two placebo‐controlled trials. (25th January 2022)

• Record Type: Journal Article
• Authors: Kranzler, Henry R.; Feinn, Richard; Pond, Timothy; Hartwell, Emily; Gelernter, Joel; Crist, Richard C.; Witkiewitz, Katie
• Is Part Of: Addiction biology. Volume 27:Number 2(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-01-25
• Subjects: alcohol use disorder -- heavy drinkers -- pharmacogenetic analysis -- post‐treatment follow‐up -- topiramate; Substance abuse -- Periodicals; Substance abuse -- Physiological aspects -- Periodicals; Substance-Related Disorders -- periodicals; 616.86
• DOI: 10.1111/adb.13130
• Languages: English
• ISSNs: 1355-6215

Abstract

Abstract: Topiramate reduces drinking and alcohol‐related problems and is increasingly being used to treat alcohol use disorder (AUD). In a randomized controlled trial (RCT) of topiramate, rs2832407, a single nucleotide polymorphism (SNP) in the GRIK1 gene moderated topiramate's effects (Study 1). However, a second RCT (Study 2) did not replicate the SNP's moderating effect during treatment. The current analysis combines data from these two studies to examine topiramate's effects on alcohol‐related outcomes and on its pharmacogenetic moderation during a 6‐month post‐treatment period. This analysis includes 308 individuals with problematic alcohol use (67% male; mean age = 51.1; topiramate: 49%, placebo: 51%). It uses generalized linear mixed models to examine changes in self‐reported alcohol consumption and alcohol‐related problems and concentrations of the liver enzyme γ‐glutamyltransferase. The report combines published 3‐ and 6‐month follow‐up data from Study 1 with similar, unpublished data from Study 2. Despite robust effects of topiramate on drinking during treatment, the overall multivariate medication effects on outcomes during 3‐ and 6‐month follow‐up were not significant ( p = 0.08 and p = 0.26, respectively). The moderating effect of the SNP on primary treatment outcomes was also not significant during either follow‐up period ( p = 0.13 and p = 0.16, respectively). However, during the 3‐month post‐treatment period, drinks per day was significantly lower in the topiramate group than the placebo group in the rs2832407*CC‐genotype group. The robust effects of topiramate on alcohol‐related outcomes during treatment diminish substantially once the medication is discontinued. Research is needed both to determine the optimal treatment duration and to identify clinically useful pharmacogenetic moderators of topiramate for treating AUD. Abstract : Combining two randomized placebo controlled trials of topiramate to treat problematic alcohol use, we find strong evidence of efficacy for the drug during treatment. However, the moderating effects of a polymorphism in the GRIK1 gene were not supported. Further, the main effects of medication seen during treatment diminished substantially during a 6‐month post‐treatment follow‐up.