Bipolar Disorder, Cocaine Dependence
Conditions
Keywords
Bipolar Disorder, Cocaine Dependence, Dual Diagnosis
Brief summary
The purpose of this study is to determine if lamotrigine add-on therapy is associated with decreased cocaine craving and improvement in depressive symptom severity than placebo in a group of outpatients with bipolar disorder and cocaine dependence. Additionally, this study is examining whether lamotrigine add-on therapy is associated with decreased cocaine use and the improvement of manic symptom severity than placebo in a group of outpatients with bipolar disorder and cocaine dependence.
Detailed description
One hundred and twenty (120) adult outpatients with bipolar I, II, not otherwise specified, or cyclothymic disorder and current cocaine dependence will be enrolled. After obtaining informed consent baseline assessment measures will be administered including the Structured Clinical Interview for Diagnostic Statistical Manual-IV Axis I Disorders. Drug use will be assessed using the timeline-followback method to quantify days and amount of drug use, urine drug screens will also be obtained and craving will be assessed with the Cocaine Craving Questionnaire. Mood symptoms will be quantified at each weekly visit with the Hamilton Rating Scale for Depression (17-item version), Quick Inventory of Depressive Symptomatology-SR (QIDS-SR), and Young Mania Rating Scale (YMRS). Impulsivity will be assessed at weeks 0, 5 and 10 with the Barratt Impulsiveness Scale (BIS, Barratt et al 1983). Cognition will be assessed at weeks 0, 5, and 10 with the Rey Auditory Verbal Learning Test (RAVLT) and STROOP color-word task. The Addiction Severity Index (ASI) will be administered at baseline and week 10. The Psychobiology of Recovery in Depression-III Somatic Symptom Scale (PRD-III)will be administered every 2 weeks to track side effects. A study psychiatrist will assess participant-reported side effects weekly. Women of childbearing age will be given a test to rule out pregnancy. Subjects will be randomized and Lamotrigine therapy or identical appearing placebo add-on therapy in a double- blind fashion will be initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks (as outlined by Calabrese et al 2000 and following the package insert) to minimize risk of side effects such as rash. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day can be made if the medication is well tolerated and HRSD scores have decreased by ≤ 40% from baseline or Cocaine Craving Questionaire (CCQ) scores have decreased ≤ 25% from baseline or participants continue to use cocaine in past week based on either self-report or urine drug screen results. Subjects will be assessed weekly for mood and drug use/craving and every four weeks for cognition over 10 weeks. All of the assessments may be provided in Spanish, if needed. Additionally, a Spanish-speaking research assistant and study psychiatrist will be available at all times. Subjects will be paid $30 for each visit and given $2 restaurant coupons. Parking tokens ($3) or bus passes ($2) will also be provided. Concomitant medications will be managed with an algorithm that discourages but, if necessary, allows changes in other psychiatric medications. At the completion of 10 weeks of blinded therapy participants in both groups will be offered 4 weeks of open-label therapy either continuing at the week 10 dose in those on active medication or slowly titrated upward for those on placebo. Participants will be assessed with the HRSD, QIDS-SR, YMRS, CCQ and drug use quantified at biweekly appointments with the RAVLT and STROOP also administered at week 14 exit. Participants will not be paid for participation in the open-label phase but bus tokens and parking passes will be provided.
Interventions
DRUGLamotrigine
Lamotrigine
DRUGPlacebo
Placebo
Sponsors
University of Texas Southwestern Medical Center
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 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of bipolar I, II, not otherwise specified or cyclothymic disorders * Currently depressed or mixed mood state * Ages 18-70 years * Men or women * Self-reported cocaine use within 14 days prior to randomization * English or Spanish speaking * Baseline Hamilton Depression Rating Scale (HRSD17) score ≥ 10
Exclusion criteria
* Currently taking an enzyme inducing or inhibiting anticonvulsant (e.g. valproic acid, carbamazepine) * Current severe psychotic features (e.g. daily auditory hallucinations, fixed delusions, severely disorganized thought processes) that require antipsychotic therapy, and that do not appear to be secondary to cocaine use * Active suicidal ideation (plan and intent) or ≥2 attempts in past 12 months or any attempt in the past month * Highly unstable medical condition * Change in concomitant psychiatric medications (e.g. initiated antipsychotic) or in other substance abuse treatment (e.g. began intensive outpatient treatment) within 7 days prior to study entry * Vulnerable populations (e.g. pregnant or nursing women, prisoners, mentally retarded)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Days of Cocaine Use | 10 weeks | Number of days of cocaine use during the 7 days that comprise week 10 of the protocol, by self report, or at last assessment if participant withdrew early, as assessed by the Timeline Followback method. |
| Positive Urine Drug Screens | 10 weeks | Percentage of participants with a positive urine drug screen for cocaine at the week 10 visit or at last assessment if participant withdrew early. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depression Score on the Hamilton Rating Scale For Depression | 10 weeks | Total score on the Hamilton Rating Scale for Depression at week 10 visit or at last assessment if participant withdrew early(total score values range 0 - 52. A higher score indicates more severe depression. |
| Dollars Spent | 10 weeks | Dollars spent on cocaine during the 7 days of week 10, or at last assessment if participant withdrew early, based on self report. |
Countries
United States
Participant flow
Recruitment details
112 participants with at least one post-baseline visit were recruited between 2006 and 2010 at our research clinic in Dallas, TX and included for analysis.
Pre-assignment details
Participants with a diagnosis of bipolar I, II or NOS disorders currently depressed or mixed mood with current cocaine dependence and self-reported use within 14 days were included. The study drug was added to existing psychiatric medications or given as monotherapy when participants were not taking other medications at baseline.
Participants by arm
| Arm | Count |
|---|---|
| Lamotrigine Lamotrigine therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted. | 55 |
| Placebo Placebo group received medication in identical color/sizes as the lamotrigine group. Placebo therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted. | 57 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Incarceration/Legal Reasons | 1 | 1 |
| Overall Study | Lost to Follow-up | 14 | 12 |
| Overall Study | Physician Decision | 5 | 4 |
| Overall Study | Protocol Violation | 3 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | Total | Lamotrigine | Placebo |
|---|---|---|---|
| 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 | 112 Participants | 55 Participants | 57 Participants |
| Age Continuous | 44.3 years STANDARD_DEVIATION 8.8 | 45.1 years STANDARD_DEVIATION 7.3 | 43.5 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 112 participants | 55 participants | 57 participants |
| Sex: Female, Male Female | 45 Participants | 23 Participants | 22 Participants |
| Sex: Female, Male Male | 67 Participants | 32 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 55 | 4 / 57 |
| serious Total, serious adverse events | 5 / 55 | 4 / 57 |
Outcome results
Primary
Days of Cocaine Use
Number of days of cocaine use during the 7 days that comprise week 10 of the protocol, by self report, or at last assessment if participant withdrew early, as assessed by the Timeline Followback method.
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lamotrigine | Days of Cocaine Use | 1.8 days | Standard Deviation 2 |
| Placebo | Days of Cocaine Use | 2.8 days | Standard Deviation 4 |
Primary
Positive Urine Drug Screens
Percentage of participants with a positive urine drug screen for cocaine at the week 10 visit or at last assessment if participant withdrew early.
Time frame: 10 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lamotrigine | Positive Urine Drug Screens | 67.3 percentage of participants |
| Placebo | Positive Urine Drug Screens | 73.6 percentage of participants |
Secondary
Depression Score on the Hamilton Rating Scale For Depression
Total score on the Hamilton Rating Scale for Depression at week 10 visit or at last assessment if participant withdrew early(total score values range 0 - 52. A higher score indicates more severe depression.
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lamotrigine | Depression Score on the Hamilton Rating Scale For Depression | 13.4 units on a scale | Standard Deviation 8.5 |
| Placebo | Depression Score on the Hamilton Rating Scale For Depression | 13.6 units on a scale | Standard Deviation 8.2 |
Secondary
Dollars Spent
Dollars spent on cocaine during the 7 days of week 10, or at last assessment if participant withdrew early, based on self report.
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lamotrigine | Dollars Spent | 68.6 Dollars | Standard Deviation 121.1 |
| Placebo | Dollars Spent | 155.4 Dollars | Standard Deviation 355.5 |