Previous studies have demonstrated little efficacy for traditional tricyclic antidepressants in treating the excessive alcohol ingestion or the depressive symptoms of alcoholics. This lack of effectiveness has important public health implications because of the prevalence of alcoholism and because depression is the most common comorbid diagnosis in alcoholics. In the last several years, several lines of evidence have emerged which suggest that abnormalities in the metabolism of serotonin may play an etiologic role in alcoholism, in depression, and in suicidality. Recently, some researchers have reported that selective serotonergic agents, including fluoxetine, show promise in the treatment of the excessive alcohol ingestion of nondepressed alcoholics. To date, no studies of selective serotonergic agents have been conducted for treating the excessive alcohol ingestion or the depressive symptoms (including suicidality) of depressed alcoholics. In this proposed study, a first large scale (N=84) prospective double-blind, placebo-controlled study will be undertaken involving the selective serotonergic agent fluoxetine and placebo in the treatment of depressed alcoholics. These patients will include both females and males and all available racial and ethnic groups. The goals of this study include the following: (1) To compare the efficacy of the selective serotonin agonist fluoxetine versus placebo in the treatment of the pathological alcohol use, the depressive symptoms, and the suicidal symptoms of patients with comorbid DSM-III-R alcohol dependence and major depression. (2) To assess specific predictors of medication response for drinking, depression, and suicidality. (3) To define subtypes of depressive alcoholics.
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