This proposal will test the efficacy of a promising pharmacological approach for the treatment of comorbid cocaine dependence and bipolar disorder. We propose a randomized, double blind, placebo controlled 12-week trial to test the efficacy of Divalproex sodium (Valproate) plus treatment as usual compared to placebo plus treatment as usual in decreasing cocaine use and stabilizing mood symptoms among patients with comorbid cocaine dependence and bipolar disorder. Treatment as usual includes the use of lithium carbonate for mood stabilization plus supportive psychosocial treatment.

Bipolar disorder has the highest rate of association with cocaine and other substance use disorders than any other major severe psychiatric syndrome. This comorbidity represents a major treatment challenge and is associated with severe disability, morbidity, and heightened risk for suicide.

The aims of this study are:

1. Examine the efficacy of valproate plus treatment as usual compared to placebo plus treatment as usual in decreasing cocaine use in patients with cocaine dependence and comorbid bipolar disorder.
2. Determine whether primary vs. secondary cocaine dependence, bipolar subtype (depressed vs. manic/mixed) and the presence of additional substance use disorders moderate the association between treatment and cocaine use outcome.
3. Assess the effects of medication compliance and mood symptoms as mediators of cocaine use outcome.

Inclusion Criteria:

• Meet DSM-IV criteria for cocaine dependence and a concurrent bipolar disorder

Exclusion Criteria:

• Schizophrenia, schizoaffective, and any non-bipolar psychotic disorder, unipolar major depression, primary anxiety disorder, mental retardation, and signs of impaired cognitive functioning.
• Current DSM-IV criteria for dependence on substances other than cocaine, alcohol, cannabis, nicotine, or caffeine
• Neurological conditions including epilepsy, history of brain injury, encephalitis, or any organic brain syndrome or documented focally abnormal EEG
• Medical conditions including severe cardiac, liver, kidney, or liver disease.
• Pregnancy
• Inability or unwillingness to use contraceptive methods
• Any medical condition or other reason that in the opinion of the investigator would prevent the subject from completing the protocol.