An Add-On Trial of Quetiapine in Patients With Bipolar Disorder and Cocaine Dependence

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if quetiapine add-on therapy is associated with a decrease in cocaine use and craving and a greater improvement in mood.

Detailed Description
-----------------
One Hundred (100) outpatients with a diagnosis of bipolar I disorder and cocaine abuse/dependence, established by a structured clinical interview and confirmed by a psychiatrist, will participate. Eligible participants will be given a physical exam, including an eye exam with an ophthalmoscope to rule out serious medical illnesses and cataracts. Additionally, medical and psychiatric histories and baseline labs, including CBC and a liver panel will be obtained. Blood will be drawn for routine laboratory analyses including a complete blood count (CBC) and SMA-20 at baseline and exit. Women of childbearing potential will be given a urine pregnancy test. Baseline measures of psychiatric symptoms will be assessed with the Hamilton Rating Scale for Depression HRSD, Young Mania Rating Scale (YMRS), Inventory of Depression Symptomatology-Self-Report 30-item version (IDS-SR30), and the Psychobiology of Recovery in Depression III - Somatic Symptom Scale (PRD-III). Cocaine craving will be assessed with Cocaine Craving Questionnaire (CCQ). Drug use will be assessed by self-report, with the Addiction Severity Index (ASI) and a urine drug screen (UDS). Two UDSs are performed at baseline. Cocaine use in the past week (dollar amount spent/week and days used/week) will be assessed by patient self-report. Use of and craving for other substances (benzodiazepines, barbiturates, alcohol, opiates, phencyclidine, and cannabis) will also be assessed by self-report of dollar amount and days used in the past week, UDSs, and with 100-mm single item visual analog craving scales. Side effects will be assessed with the Abnormal Involuntary Movement Scale (AIMS), the Simpson-Angus Scale (SAS), and the Barnes Akathesia Rating Scale (BARS). Subjects will be randomized and be titrated up to 400 mg/day with additional flexible titration after that time to a maximum of 800 mg/day of Quetiapine or identical appearing placebo add-on therapy in a double- blind fashion for 12 weeks. At each weekly assessment subjects will be evaluated with the HRSD17, IDS-R30, YMRS, CCQ, and a UDS, and receive an upward titration of the study drug. The ASI will be repeated every four weeks. Further, participants will return one additional time each week for a UDS. At the end of the study an unblinded psychiatrist will provide standard open label treatment with Quetiapine until the participants can be transferred back to their usual treatment facility. Follow up and after care arrangements will be made for each participant near completion of the study.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled Add-On Trial of Quetiapine in Patients With Bipolar Disorder and Cocaine Dependence

Conditions
-----------------
Bipolar Disorder, Cocaine Dependence

Intervention / Treatment
-----------------
* Drug: Quetiapine
* Drug: PLacebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Bipolar Disorder, type I; Cocaine Dependence with use in the past 7 days; Currently taking a mood stabilizer; Meets criteria for a hypomanic or manic episode Exclusion Criteria: Bipolar Disorder, type II, NOS; Cyclothymia; Other substance dependence; Diabetes; Initiated therapy in the past 2 weeks; History of cataracts or likely cataracts; Current active suicidal or homicidal ideation; Life threatening medical condition; Mental retardation, dementia or severe cognitive impairment; Pregnant or nursing womenon; antipsychotic within 7 days of beginning Quetiapine therapy or have initiated antidepressants or mood stabilizers or psychotherapy within the past two weeks.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Quetiapine<br> | Drug: Quetiapine<br>* Active Quetiapine<br>* Other names: Active Quetiapine;|
| Placebo Comparator: Placebo<br>Inactive ingredient matching the active medication in appearance | Drug: PLacebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A random regression analysis will be done with treatment group as the between-subjects factor, time as the within-subjects factor, and a group by time interaction. |  | Study Exit | 
| Within-group differences between pre- and post- treatment of the study drug will be compared using Wilcoxon rank sum tests, if the sample is not normally distributed between-group differences will be compared using the Mann-Whitney test. |  | Study Exit | 
| To identify response versus non-response, logistic regression, assuming linearity, will be used. |  | Study Exit | 
| We will utilize the urine drug screen repeatedly and cocaine use/cravings as the primary outcome measure. |  | Study Exit | 
| Changes from base line to exit for all patients finishing at-least one follow up of active Quetiapine therapy, will be calculated, using the last observation carried forward (LOCF). |  | Study Exit | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
bipolar disorder, cocaine dependence, quetiapine