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Balancing risk and benefit in heavy drinkers treated with topiramate: implications for personalized care.

ABSTRACT: Despite topiramate's ability to reduce heavy drinking, its adverse effects may limit its clinical utility.To evaluate the risks and benefits of topiramate, we reanalyzed data from a completed trial of the medication in 138 heavy drinkers whose goal was to reduce their drinking to safe levels. We used the number of patients who had no heavy drinking days during the last 4 weeks of treatment to calculate topiramate's number needed to treat (NNT). To balance the risks and benefits of topiramate, we adjusted the NNT using 2 different levels of adverse event severity: moderate or greater (NNT-AEmod+) and severe or greater (NNT-AEsev+). This measure helps to guide the clinical use of topiramate in heavy drinkers by incorporating both its beneficial and adverse effects in a single measure. Because a polymorphism (rs2832407) in the gene encoding a kainate receptor subunit appears to moderate topiramate's effects in heavy drinkers, we repeated the analyses based on rs2832407 genotype (C-homozygote vs A-allele carrier) in the European American subsample (n = 122).Overall, the NNT for topiramate was 5.29, the NNT-AEmod+ was 7.52, and the NNT-AEsev+ was 6.12. Among European Americans with the rs2832407*CC genotype, the NNT was 2.28, the NNT-AEmod+ was 2.63, and the NNT-AEsev+ was 2.56. In contrast, for rs2832407*A-allele carriers, the NNT was 180.00, the NNT-AEmod+ was 322.16, and the NNT-AEsev+ was 217.45.In this sample of heavy drinkers, topiramate had a clinically important treatment effect that was most evident in European Americans with the rs2832407*CC genotype. In that group, in particular, it had a robust treatment effect, even when adjusted for adverse events.ClinicalTrials.gov identifier: NCT00626925.

SUBMITTER: Feinn R

PROVIDER: S-EPMC4845738 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Balancing risk and benefit in heavy drinkers treated with topiramate: implications for personalized care.

Feinn Richard R Curtis Brenda B Kranzler Henry R HR

The Journal of clinical psychiatry 20160301 3

<h4>Background</h4>Despite topiramate's ability to reduce heavy drinking, its adverse effects may limit its clinical utility.<h4>Method</h4>To evaluate the risks and benefits of topiramate, we reanalyzed data from a completed trial of the medication in 138 heavy drinkers whose goal was to reduce their drinking to safe levels. We used the number of patients who had no heavy drinking days during the last 4 weeks of treatment to calculate topiramate's number needed to treat (NNT). To balance the ri ...[more]

PMID: 26891181

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Project description:OBJECTIVE:Despite its prominence in the health communication literature, psychological reactance has rarely been considered as a factor that may undermine web-based Personalized Normative Feedback (PNF) alcohol interventions for college students. This study built on recent gamification work to examine how chance-based uncertainty, a popular game mechanic associated with motivation and attention in digital games for learning, might be leveraged to reduce the psychological reactance experienced by heavy drinking students receiving alcohol PNF, thereby leading to larger reductions in their alcohol consumption. METHOD:Psychological reactance, perceptions of norms, and drinking behaviors were assessed during a 3-week period following random assignment of binge drinking students (N = 141, 51% female) into one of four web-based PNF conditions. These conditions asked the same questions about drinking and delivered identical PNF on alcohol use but differed in whether animated slot-machine spinners appeared to select participants' question and feedback topics as well as the number of additional topics (beyond alcohol) on which questions were asked and PNF was delivered. RESULTS:All conditions similarly reduced drinking norms but differed in the degree to which they aroused cognitive reactance and reduced drinking. Relative to a no-spinner alcohol-only condition, increasing chance-based uncertainty by giving question and feedback topics the appearance of being selected by gamelike spinners substantially reduced cognitive reactance, which, in turn, reduced drinking 20 days later. Overall, participants experienced the least cognitive reactance when spinners first selected three question topics and later selected two of these topics to deliver feedback on. CONCLUSIONS:Findings suggest that introducing chance-based uncertainty through gamelike spinners, asking questions about multiple topics, and delivering feedback on additional topics unrelated to alcohol together work to reduce the degree to which the task feels like an alcohol intervention overtly aimed at reducing consumption, thereby making the alcohol PNF more effective among heavy drinking students.

Project description:Background: Alcohol-associated liver disease (ALD) is the most common disorder of prolonged drinking. Mechanisms underlying cirrhosis in such patients remain unclear. MicroRNAs play regulatory role in several diseases, are affected by alcohol and may be important players in alcohol use disorders, such as cirrhosis. Methods: We investigated serum samples from heavy chronic alcohol users (80 g/day (male) and 50 g/day (female) for ≥10 years) that were available from our previously reported GenomALC study. A subset of GenomALC drinkers with liver cirrhosis (cases, n = 24) and those without significant liver disease (drinking controls, n = 23) were included. Global microRNA profiling was performed using high-throughput real-time quantitative PCR to identify the microRNA signatures associated with cirrhosis. Ingenuity Pathway Analysis (IPA) software was utilized to identify target mRNAs of significantly altered microRNAs, and molecular pathways were analysed. Identified microRNAs were analysed for correlation with traditional liver disease biomarkers and risk gene variants previously reported from GenomALC genome-wide association study. Results: The expression of 21 microRNAs was significantly downregulated in cases compared to drinking controls (p < 0.05, ∆∆Ct > 1.5-fold). Seven microRNAs (miR-16, miR-19a, miR-27a, miR-29b, miR-101, miR-130a, and miR-191) had a highly significant correlation (p < 0.001) with INR, bilirubin and MELD score. Three microRNAs (miR-27a, miR-130a and miR-191) significantly predicted cases with AUC-ROC 0.8, 0.78 and 0.85, respectively (p < 0.020); however, INR performed best (0.97, p < 0.001). A different set of six microRNAs (miR-19a, miR-26a, miR-101, miR-151-3p, miR-221, and miR-301) showed positive correlation (ranging from 0.32 to 0.51, p < 0.05) with rs10433937:HSD17B13 gene variant, associated with the risk of cirrhosis. IPA analysis revealed mRNA targets of the significantly altered microRNAs associated with cell death/necrosis, fibrosis and increased steatosis, particularly triglyceride metabolism. Conclusions: MicroRNA signatures in drinkers distinguished those with liver cirrhosis from drinkers without liver disease. We identified mRNA targets in liver functions that were enriched for disease pathogenesis pathways.

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Balancing risk and benefit in heavy drinkers treated with topiramate: implications for personalized care.

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Balancing risk and benefit in heavy drinkers treated with topiramate: implications for personalized care.

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