Bipolar Disorder, Cocaine Dependence
Conditions
Keywords
Bipolar, Cocaine, Comorbidity
Brief summary
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
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: 1. 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. 2. 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. 3. Assess the effects of medication compliance and mood symptoms as mediators of cocaine use outcome.
Interventions
DRUGValproate
Valproate with dose titration to achieve blood levels within the therapeutic range
DRUGPlacebo
Control arm
DRUGLithium Carbonate
All participants were started and stabilized on lithium carbonate as a standard treatment for bipolar disorder
Sponsors
National Institute on Drug Abuse (NIDA)
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percentage of Cocaine-abstinent Days | Week 12 | Change from baseline in percentage of self-report cocaine-abstinent (non-use) days (difference in base percent values) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percentage of Money Spent on Cocaine | week 12 | Change from baseline in percentage of the amount of money spent on cocaine |
Countries
United States
Participant flow
Pre-assignment details
High screen failure for not meeting inclusion/exclusion criteria and for lost to follow-up during screening
Participants by arm
| Arm | Count |
|---|---|
| Lithium Carbonate Add on Placebo Lithium carbonate started with titration to achieve blood levels within the therapeutic range and then participants randomized to placebo | 13 |
| Lithium Carbonate Add on Valproate Lithium carbonate started with titration to achieve blood levels within the therapeutic range and then participants randomized to valproate | 13 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 6 | 7 |
Baseline characteristics
| Characteristic | Lithium Carbonate Add on Placebo | Lithium Carbonate Add on Valproate | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 13 Participants | 26 Participants |
| Age, Continuous | 46.7 years STANDARD_DEVIATION 7.4 | 44 years STANDARD_DEVIATION 7.7 | 45.4 years STANDARD_DEVIATION 7.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 9 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 7 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 13 | 10 / 13 |
| serious Total, serious adverse events | 0 / 13 | 1 / 13 |
Outcome results
Primary
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)
Time frame: Week 12
Population: All subjects with available data after assignment to study medications
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lithium Carbonate Add on Placebo | Change From Baseline in Percentage of Cocaine-abstinent Days | 16.4 percentage of days cocaine abstinent | Standard Deviation 29.7 |
| Lithium Carbonate Add on Valproate | Change From Baseline in Percentage of Cocaine-abstinent Days | 14.5 percentage of days cocaine abstinent | Standard Deviation 20.3 |
Secondary
Change From Baseline in Percentage of Money Spent on Cocaine
Change from baseline in percentage of the amount of money spent on cocaine
Time frame: week 12
Population: All subjects with available data after assignment to study medications
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lithium Carbonate Add on Placebo | Change From Baseline in Percentage of Money Spent on Cocaine | -43.6 Percentage of Money Spent on Cocaine | Standard Deviation 58.4 |
| Lithium Carbonate Add on Valproate | Change From Baseline in Percentage of Money Spent on Cocaine | -34.9 Percentage of Money Spent on Cocaine | Standard Deviation 56.1 |