title: Balancing risk and benefit in heavy drinkers treated with topiramate: implications for personalized care.
abstract: BACKGROUND
  Despite topiramate's ability to reduce heavy drinking, its adverse effects may limit its clinical utility.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00626925.
authors.affiliation: Department of Medical Sciences, Frank Netter School of Medicine, Quinnipiac University, Hamden, Connecticut.
authors.forename: Richard
authors.initials: R
authors.lastname: Feinn
authors.forename: Brenda
authors.initials: B
authors.lastname: Curtis
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics*; D000927:Anticonvulsants / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008297:Male; D061366:Numbers Needed To Treat; D011110:Polymorphism, Genetic / Q000235:genetics; D057285:Precision Medicine; D018092:Kainic Acid Receptors / Q000235:genetics; D018570:Risk Assessment; D000077236:Topiramate; D044465:White People / Q000235:genetics / Q000523:psychology
chemical_list: D000927:Anticonvulsants; D005632:Fructose; D018092:Kainic Acid Receptors; D000077236:Topiramate