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

University Hospitals (UH)

Status and phase: Completed; Phase 3

Conditions: Bipolar Disorder

Treatments: Drug: Divalproex; Drug: Lithium; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00194129

R01MH050165 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 31 patients

Sex: All

Ages: 16 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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31 participants in 2 patient groups, including a placebo group

Lithium plus Divalproex

Experimental group

Description:

Patients assigned to the combination group were continued on lithium and blinded divalproex.

Treatment:

Drug: Lithium

Drug: Divalproex

Lithium plus placebo

Placebo Comparator group

Description:

Patients assigned to lithium monotherapy underwent divalproex-placebo substitution at a rate of 250 mg decrements every week until discontinued.

Treatment:

Drug: Placebo

Drug: Lithium