Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Matching Genotypes and Serotonergic Medications for Alcoholism
Brief Summary: Sertraline, a serotonin-specific reuptake inhibitor (SSRI) that increases basal serotonin levels, was shown to reduce alcohol consumption in lower risk/severity and later onset (LOA) but not higher risk/severity earlier onset alcoholic individuals (EOA). By contrast, ondansetron, a 5-HT3 receptor reduced alcohol consumption in EOAs but not LOAs. To explain this contrast in clinical efficacy, one approach suggests that differential serotonergic response is based on a functional polymorphism of the 5-HTTLPR promoter region of the serotonin re-uptake transporter (SERT). These alleles have typically been classified as biallelic genotypes: LL, SS and SL. The LL variant is postulated to be associated with EOA and the SS/SL variants associated with LOA. To test this hypothesis the investigators therefore propose to match and mismatch serotonergic treatments to genetic polymorphic variants [in 132 non-treatment seeking alcohol dependent volunteers] in a double-blind placebo controlled 2 x 2 design human laboratory study. The investigators propose to randomize non-treatment-seeking alcohol dependent persons based on their 5'-HTTLPR variant genotype (LL or SS/SL) into one of two counterbalanced arms: participants in the first arm (LL) will first receive one drug (either 200mg/day of sertraline or ondansetron 0.5mg/day) for three weeks followed by an alcohol self-administration experiment (ASAE), [with a 1 week down-titration period if sertraline received first, during the first week of the "placebo period"] then receive placebo for two more weeks (this will be a single-blind portion to use as a comparison group and to wash out the pharmacodynamic effects of the first drug) followed by a second ASAE. Participants will then receive the second drug for three weeks followed by a third ASAE [all will receive medication for an additional 1 week period and those receiving sertraline last will be down-titrated]. Participants in the second arm (SS/SL) will receive the same m