期刊
AMERICAN JOURNAL OF PSYCHIATRY
卷 168, 期 3, 页码 265-275出版社
AMER PSYCHIATRIC PUBLISHING, INC
DOI: 10.1176/appi.ajp.2010.10050755
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资金
- National Institute on Alcohol Abuse and Alcoholism [7 U10 AA011776-10, 7 R01 AA010522-12, 2 R01 AA010522-13, 5 R01 AA013964-05, 5 R01 AA014628-04, 5 R01 AA012964-06, 5 K23 AA000329-06, RC1 AA019274]
- National Institute on Drug Abuse [DA012844, DA013783]
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-HT3 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 mu g/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. (Am J Psychiatry 2011; 168:265-275)
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