Lamotrigine add-on Therapy for Bipolar Disorder and Cocaine Dependency

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Trial of Lamotrigine add-on Therapy in Outpatients With Bipolar Disorder, Depressed or Mixed Phase and Cocaine Dependence

Conditions
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Bipolar Disorder, Cocaine Dependence

Intervention / Treatment
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* Drug: Lamotrigine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: 1<br>Placebo | Drug: Placebo<br>* Placebo<br>|
| Active Comparator: 2<br>LAmotrigine | Drug: Lamotrigine<br>* Lamotrigine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 10 weeks | 
| 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. | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 10 weeks | 
| 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. | 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar Disorder, Cocaine Dependence, Dual Diagnosis