BACKGROUND: Atypical antipsychotics may be useful in the treatment of alcohol dependence. Human trials suggest that atypical antipsychotics may reduce alcohol craving and consumption, especially among patients with comorbid psychopathology. Therefore, these medications may be more useful for treating more severely affected alcoholics, such as patients with Type B alcoholism. Type B alcoholics are characterized by an early age of onset of problem drinking, high severity of alcohol dependence, increased psychopathology, and treatment-resistance. Quetiapine is an atypical antipsychotic with a favorable side effect profile, and may be a promising medication for the treatment of alcohol dependence, particularly Type B alcoholism. METHODS: Male and female alcoholics (33 Type A and 28 Type B) were included in a 12-week, double-blind, placebo-controlled trial. After detoxification, patients were randomized to receive quetiapine (n = 29), 400 mg/d at bedtime, or placebo (n = 32). The primary outcome measure was the quantity and frequency of alcohol consumption, measured by the timeline follow back. RESULTS: Forty-seven patients (77%) completed the trial, with no significant between-group differences in treatment retention. Nine quetiapine-treated patients (31%) maintained complete abstinence compared with 2 placebo-treated patients (6%) (chi(2) = 6.3, P = 0.012). There was a significant interaction between quetiapine and alcoholic subtype. As predicted, quetiapine- versus placebo-treated Type B alcoholics had significantly fewer days of drinking and fewer days of heavy drinking. Alcohol craving was also significantly reduced in quetiapine-treated compared with placebo-treated Type B alcoholics. Among Type A alcoholics, quetiapine provided no advantage over placebo in improving drinking outcomes. CONCLUSIONS: Quetiapine may be effective for the treatment of alcohol dependence, particularly in the more complicated Type B, early-onset alcoholics.