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

Condition(s) targeted: Bipolar Disorder

Intervention: Lithium (Drug); Divalproex (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: National Institute of Mental Health (NIMH)

Official(s) and/or principal investigator(s):
Joseph R Calabrese, MD, Principal Investigator, Affiliation: Case Western Reserve University / University Hospitals of Cleveland

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.

Official title: A Randomized, Double Blind Comparison of Lithium Monotherapy Versus Lithium Plus Divalproex for the Outpatient Management of Hypomania/Mania in Patients With Rapid Cycling Bipolar Disorder Comorbid With Substance Abuse/Dependence

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment

Detailed description: 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.

Minimum age: 16 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- To be included in this study, patients will be required to be either acutely hypomanic

or manic as defined by the 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 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.

University Hospitals of Cleveland, Cleveland, Ohio 44106, United States

Starting date: November 1997
Ending date: September 2006
Last updated: February 8, 2008