OBJECTIVE: Severe drinking can cause serious morbidity and death. Because the serotonin transporter (5-HTT) is an important regulator of neuronal 5-HT function, allelic differences at that gene may modulate the severity of alcohol consumption and predict therapeutic response to the 5-HT(3) receptor antagonist, ondansetron. METHOD: The authors randomized 283 alcoholics by genotype in the 5'-regulatory region of the 5-HTT gene (LL/LS/SS), with additional genotyping for another functional single-nucleotide polymorphism (T/G), rs1042173, in the 3'-untranslated region, in a double-blind controlled trial. Participants received either ondansetron (4 μg/kg twice daily) or placebo for 11 weeks, plus standardized cognitive-behavioral therapy. RESULTS:Individuals with the LL genotype who receivedondansetron had a lower mean number of drinks per drinking day (-1.62) and a higher percentage of days abstinent (11.27%) than those who received placebo. Among ondansetron recipients, the number of drinks per drinking day was lower (-1.53) and the percentage of days abstinent higher (9.73%) in LL compared with LS/SS individuals. LL individuals in the ondansetron group also had a lower number of drinks per drinking day (-1.45) and a higher percentage of days abstinent (9.65%) than all other genotype and treatment groups combined. For both number of drinks per drinking day and percentage of days abstinent, 5'-HTTLPR and rs1042173 variants interacted significantly. LL/TT individuals in the ondansetron group had a lower number of drinks per drinking day (-2.63) and a higher percentage of days abstinent (16.99%) than all other genotype and treatment groups combined. CONCLUSIONS: The authors propose a new pharmacogenetic approach using ondansetron to treat severe drinking and improve abstinence in alcoholics.
RCT Entities:
OBJECTIVE: Severe drinking can cause serious morbidity and death. Because the serotonin transporter (5-HTT) is an important regulator of neuronal 5-HT function, allelic differences at that gene may modulate the severity of alcohol consumption and predict therapeutic response to the 5-HT(3) receptor antagonist, ondansetron. METHOD: The authors randomized 283 alcoholics by genotype in the 5'-regulatory region of the 5-HTT gene (LL/LS/SS), with additional genotyping for another functional single-nucleotide polymorphism (T/G), rs1042173, in the 3'-untranslated region, in a double-blind controlled trial. Participants received either ondansetron (4 μg/kg twice daily) or placebo for 11 weeks, plus standardized cognitive-behavioral therapy. RESULTS: Individuals with the LL genotype who received ondansetron had a lower mean number of drinks per drinking day (-1.62) and a higher percentage of days abstinent (11.27%) than those who received placebo. Among ondansetron recipients, the number of drinks per drinking day was lower (-1.53) and the percentage of days abstinent higher (9.73%) in LL compared with LS/SS individuals. LL individuals in the ondansetron group also had a lower number of drinks per drinking day (-1.45) and a higher percentage of days abstinent (9.65%) than all other genotype and treatment groups combined. For both number of drinks per drinking day and percentage of days abstinent, 5'-HTTLPR and rs1042173 variants interacted significantly. LL/TT individuals in the ondansetron group had a lower number of drinks per drinking day (-2.63) and a higher percentage of days abstinent (16.99%) than all other genotype and treatment groups combined. CONCLUSIONS: The authors propose a new pharmacogenetic approach using ondansetron to treat severe drinking and improve abstinence in alcoholics.
Authors: Nassima Ait-Daoud; John D Roache; Michael A Dawes; Lei Liu; Xin-Qun Wang; Martin A Javors; Chamindi Seneviratne; Bankole A Johnson Journal: Alcohol Clin Exp Res Date: 2009-05-04 Impact factor: 3.455
Authors: A Heinz; D W Jones; C Mazzanti; D Goldman; P Ragan; D Hommer; M Linnoila; D R Weinberger Journal: Biol Psychiatry Date: 2000-04-01 Impact factor: 13.382
Authors: B A Johnson; J D Roache; M A Javors; C C DiClemente; C R Cloninger; T J Prihoda; P S Bordnick; N Ait-Daoud; J Hensler Journal: JAMA Date: 2000 Aug 23-30 Impact factor: 56.272
Authors: George A Kenna; William H Zywiak; Robert M Swift; John E McGeary; James S Clifford; Jessica R Shoaff; Cynthia Vuittonet; Samuel Fricchione; Michael Brickley; Kayla Beaucage; Carolina L Haass-Koffler; Lorenzo Leggio Journal: Alcohol Clin Exp Res Date: 2014-04-28 Impact factor: 3.455
Authors: Andrzej Jakubczyk; Anna Klimkiewicz; Maciej Kopera; Aleksandra Krasowska; Małgorzata Wrzosek; Halina Matsumoto; Margit Burmeister; Kirk J Brower; Marcin Wojnar Journal: J Psychiatr Res Date: 2013-01-12 Impact factor: 4.791
Authors: Henry R Kranzler; Jonathan Covault; Richard Feinn; Stephen Armeli; Howard Tennen; Albert J Arias; Joel Gelernter; Timothy Pond; Cheryl Oncken; Kyle M Kampman Journal: Am J Psychiatry Date: 2014-04 Impact factor: 18.112
Authors: Henry R Kranzler; Rachel V Smith; Robert Schnoll; Afaf Moustafa; Emma Greenstreet-Akman Journal: Addiction Date: 2017-04-21 Impact factor: 6.526
Authors: Richard L Bell; Helen J K Sable; Giancarlo Colombo; Petri Hyytia; Zachary A Rodd; Lawrence Lumeng Journal: Pharmacol Biochem Behav Date: 2012-07-25 Impact factor: 3.533