Valproate Efficacy in Cocaine-Bipolar Comorbidity

Study Overview
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Brief Summary
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This proposal will test the efficacy of a promising pharmacological approach for the treatment of comorbid cocaine dependence and bipolar disorder. We propose a randomized, double blind, placebo controlled 12-week trial to test the efficacy of Divalproex sodium (Valproate) plus treatment as usual compared to placebo plus treatment as usual in decreasing cocaine use and stabilizing mood symptoms among patients with comorbid cocaine dependence and bipolar disorder. Treatment as usual includes the use of lithium carbonate for mood stabilization plus supportive psychosocial treatment.

Detailed Description
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Bipolar disorder has the highest rate of association with cocaine and other substance use disorders than any other major severe psychiatric syndrome. This comorbidity represents a major treatment challenge and is associated with severe disability, morbidity, and heightened risk for suicide. The aims of this study are: Examine the efficacy of valproate plus treatment as usual compared to placebo plus treatment as usual in decreasing cocaine use in patients with cocaine dependence and comorbid bipolar disorder. Determine whether primary vs. secondary cocaine dependence, bipolar subtype (depressed vs. manic/mixed) and the presence of additional substance use disorders moderate the association between treatment and cocaine use outcome. Assess the effects of medication compliance and mood symptoms as mediators of cocaine use outcome.

Official Title
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Valproate Efficacy in Cocaine-Bipolar Comorbidity

Conditions
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Bipolar Disorder, Cocaine Dependence

Intervention / Treatment
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* Drug: Valproate
* Drug: Placebo
* Drug: Lithium Carbonate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet DSM-IV criteria for cocaine dependence and a concurrent bipolar disorder Exclusion Criteria: Schizophrenia, schizoaffective, and any non-bipolar psychotic disorder, unipolar major depression, primary anxiety disorder, mental retardation, and signs of impaired cognitive functioning. Current DSM-IV criteria for dependence on substances other than cocaine, alcohol, cannabis, nicotine, or caffeine Neurological conditions including epilepsy, history of brain injury, encephalitis, or any organic brain syndrome or documented focally abnormal EEG Medical conditions including severe cardiac, liver, kidney, or liver disease. Pregnancy Inability or unwillingness to use contraceptive methods Any medical condition or other reason that in the opinion of the investigator would prevent the subject from completing the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Lithium carbonate add on Placebo<br>Lithium carbonate started and stabilized then participants randomized to placebo | Drug: Placebo<br>* Control arm<br>* Other names: Placebo control;Drug: Lithium Carbonate<br>* All participants were started and stabilized on lithium carbonate as a standard treatment for bipolar disorder<br>* Other names: Standard treatment;|
| Experimental: Lithium carbonate add on Valproate<br>Lithium carbonate started and stabilized then participants randomized to Valproate | Drug: Valproate<br>* Valproate with dose titration to achieve blood levels within the therapeutic range<br>* Other names: Divalproex sodium;Drug: Lithium Carbonate<br>* All participants were started and stabilized on lithium carbonate as a standard treatment for bipolar disorder<br>* Other names: Standard treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Percentage of Cocaine-abstinent Days | Change from baseline in percentage of self-report cocaine-abstinent (non-use) days (difference in base percent values) | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Percentage of Money Spent on Cocaine | Change from baseline in percentage of the amount of money spent on cocaine | week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar, Cocaine, Comorbidity