This study is a randomized, placebo-controlled, double-blind trial of gepirone, a selective 5-HT1A agonist that is currently under investigation for use as an anxiolytic/antidepressant. We are near completion of a placebo-controlled trial of buspirone (an analog of gepirone) in combination with relapse prevention psychotherapy in anxious alcoholics. Preliminary analysis of the results of that trial have shown an advantage for buspirone, in terms of retention in treatment and on measures of alcohol consumption (the latter being particularly evident during the six months following active treatment). These effects appear to be independent of an anxiolytic effect. Given that fact, combined with a growing literature that shows 5-HT1A agonists to reduce alcohol consumption in animals and humans, we propose to expand our investigation in this area with a trial of gepirone, a more selective and pharmacologically efficacious agent. The study will employ a factorial design and will involve 120 alcohol-dependent male and female subjects. Subjects will be assigned to treatment groups using a balanced randomization procedure that employs a typologic variable to differentiate low- and high-risk/severity groups. All subjects will receive a total of 12 weeks of medication or placebo, combined with coping skills training. Followup assessments to identify delayed or persistent effects will be done at 3, 6, and 12 months after treatment is completed. Data analysis will focus on the effects of drug treatment (gepirone vs. placebo), alcoholic typology (low vs. high risk/severity), and the interactive effect of these independent variables on measures of alcohol consumption, drinking-related problems, and psychopathology. It is hypothesized that gepirone will be superior to placebo in the prevention of relapse to heavy drinking (and associated disabilities). Based on its serotonergic activity, gepirone's therapeutic advantage is expected to be most evident in the high-risk/severity alcoholics, among whom impulsivity and aggressivity (characteristics associated with abnormalities in serotonergic neurotransmission) are more common.
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