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Objective: Bipolar disorder is associated with the highest rates of substance abuse of any psychiatric illness. Therefore, treatments that stabilize mood and decrease drug use or cravings are of great interest. Atypical antipsychotics are in widespread use in patients with bipolar disorder. However, minimal data are available on their use in bipolar patients with comorbid substance abuse., Methods: Open-label, add-on, quetiapine therapy was examined for 12 weeks in 17 outpatients with bipolar disorder and cocaine dependence. Subjects were evaluated with a structured clinical interview; Hamilton Depression Rating (HDRS), Young Mania Rating (YMRS), Brief Psychiatric Rating (BPRS) scales; and Cocaine Craving Questionnaire (CCQ). Urine samples and self-reported drug use were also obtained. Data were analyzed using a last observation carried forward method on all subjects given medication at baseline., Results: Significant improvement from baseline to exit was observed in HDRS, YMRS, BPRS and CCQ scores (p < or = 0.05). Dollars spent on cocaine and days/week of cocaine use decreased non-significantly, and urine drug screens did not change significantly from baseline to exit. Quetiapine was well tolerated, with no subjects to our knowledge discontinuing because of side-effects., Conclusions: The use of quetiapine was associated with substantial improvement in psychiatric symptoms and cocaine cravings. The findings are promising and suggest larger controlled trials of quetiapine are needed in this population.