lithium and divalproex for the treatment of comorbid rapid cycling bipolar disorder and substance abuse disorder

Conditions: Bipolar Disorder

Summary: this study will determine the efficacy and safety of combination therapy with divalproex and lithium for treating mania in people with rapid cycling bipolar disorder and a substance abuse disorder.

longitudinal evaluation of the efficacy and safety of divalproex and lithium in dual diagnosis bipolar rapid cycling: this study recruits males and females age 18 and older who currently meet diagnostic criteria for rapid cycling bipolar disorder (type i or ii) and who have met the criteria for substance abuse or dependence of cocaine, marijuana and/or alcohol within the past six months. patients are initially stabilized on dual therapy of lithium and depakote and then randomly assigned to double-blind treatment with either lithium monotherapy or continued dual therapy. patients remain in the study for six months or until they experience a relapse. patients in this study are required to bring a friend or family member to all study visits as well as attend chemical dependency services. this study is sponsored by the nimh. subjects receive study-related care at no cost.

Eligibility criteria:
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.