The treatment of alcoholism is often complex and problematic. There is growing recognition that no single treatment is effective for all individuals and that treatment matching may be vital. Thus optimum treatment should include vigorous psychosocial interventions, and whether indicated, specific biological therapies targeted to underlying pathophysiology. There is considerable evidence for a role for the monamine neurotransmitter serotonin (5-HT) in both the regulation of alcohol intake and as a biological selective serotonin reuptake inhibitors (SSRI) in the reduction of alcohol intake and maintenance of abstinence in alcoholics. However, little is known about the clinical or biological characteristics that would identify those alcoholic patients who might benefit from SSRI treatment. Thus, treatment matching is still not possible. Furthermore, nothing is known about those relationship in older alcoholics, a population which might benefit greatly from a safe, effective medical therapy. The long-term objectives of this project are to gain new information on the role of alterations in serotonin (5-HT) function in the pathophysiology, clinical features and pharmacotherapy of alcoholism.
The specific aims are: (1) characterization of serotonin function in alcoholic patients, (2) a controlled trial of the efficacy of serotonergic treatment with the SSRI fluoxetine in reducing alcohol intake in alcoholic patients, (3) correlation of serotonergic measures with clinical response to fluoxetine treatment, and (4) examination of the effects of aging on serotonin function and clinical response to fluoxetine in alcoholic patients. It is proposed to measure cerebrospinal fluid (CSF) 5-hydroxyindoleacetic (5-HIAA, the major serotonin metabolite) levels in newly detoxified alcoholics and age- and sex-matched normal controls, as well as plasma prolactin, cortisol, vital signs, and behavioral state after a single intravenous infusion (""""""""challenge"""""""" strategy) of m-chlorophenylpiperazine (m--CPP, a serotonin agonist) in detoxified alcoholics and age- and sex-matched normal controls. Patients will then undergo a trial comparing the efficacy of fluoxetine, with placebo, in decreasing alcohol intake in a twelve-week, double-blind, parallel design, randomized controlled trial, during which alcohol craving, use, and other related variables will be monitored. Serotonin function measures at baseline will then be correlated with clinical response in those alcoholic patients receiving fluoxetine treatment. A sub-analysis will examine these correlations in older (>age 55) vs. younger (
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