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

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.