Lithium and Divalproex for the Treatment of Comorbid Rapid Cycling Bipolar Disorder and Substance Abuse Disorder

Inclusion Criteria: * To be included in this study, patients will be required to be either acutely hypomanic or manic as defined by the Diagnostic and Statistical Manual -IV (DSM-IV) and meet criteria for current substance abuse and/or dependence disorder within the last six months. * Must have 4 or more episodes in the immediate 12 months prior to study entry. * Males or females 16 - 65 years of age. * A score of 60 or less on the Global Assessment Scale. * Have no medical illness precluding the use of lithium or divalproex. Exclusion Criteria: * Patients who have had intolerable side effects to lithium levels 0.8 meq/L or divalproex levels of 50 ug/ml. Patients who have been completely non-responsive to lithium in the past will be excluded, whereas patients who have had partial responses to lithium will be permitted into the study. * Patients with a prior history of seizure disorder, cerebral vascular disease, structural brain damage from trauma, clinically significant focal neurological abnormalities, EEG abnormalities with frank paroxysmal activity or a previous CT/MRI scan of the brain with gross structural abnormalities. * Patients who require anticoagulant drug therapy. * Patients who have uncontrolled gastrointestinal, renal, hepatic, endocrine, cardiovascular, pulmonary, immunological or hematological disease. Patients with alcohol-related liver disease as reflected by diffuse elevations in liver functions tests exceeding the upper limits of the normal range by 50% will be excluded. * Patients who are pregnant or plan to become pregnant during the study. * Patients who have received haloperidol decanoate or fluphenazine decanoate within the last 10 weeks. * Patients who have a central nervous system (CNS) neoplasm, uncontrolled metabolic, demyelinating or progressive disorder; active CNS infection; or any progressive neurological disorder. * Patients who are taking exogenous steroids. * Patients who do not meet criteria for substance abuse or dependence.