Quetiapine for Bipolar Disorder and Alcohol Dependence

Phase 4

Completed

Conditions: Bipolar Disorder
Alcohol Dependence

Interventions: Drug: Placebo
Drug: Quetiapine

Registration Number: NCT00457197

Lead Sponsor: University of Texas Southwestern Medical Center

Brief Summary: The purpose of this study is to find out whether an investigational drug called quetiapine can treat bipolar disorder, improve mood and reduce alcohol use and craving.

Detailed Description: The primary aim in the study is to determine if quetiapine treatment is associated with greater reduction in alcohol use than placebo in outpatients with bipolar disorder and alcohol dependence. We will also examine if quetiapine treatment is associated with greater reduction in alcohol craving than placebo in outpatients with bipolar disorder and alcohol dependence and if quetiapine treatment is associated with greater improvement in depressive symptoms than placebo in outpatients with bipolar disorder and alcohol dependence.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 90

Inclusion Criteria

Outpatients with a diagnosis of bipolar I or II disorder, depressed or mixed phase on the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (SCID) and confirmed by interview with PI or co-I.
Current diagnosis of alcohol dependence.
Alcohol use (by self-report) of at least 15 drinks in the 7 days prior to baseline.
Currently taking a mood stabilizer defined as lithium, divalproex/valproic acid, oxcarbazepine, or lamotrigine at a stable dose for > 14 days.
Men and women age 18-65 years old.
English or Spanish speaking.

Exclusion Criteria

Bipolar disorders other than bipolar I or II (e.g., not otherwise specified or cyclothymic disorders) based on the SCID and confirmed through clinical assessment by PI or co-I.
Baseline Young Mania Rating Scale (YMRS) score > 35 or Hamilton Depression Rating Scale (HRSD) 17 score > 35.
Current clinically significant psychotic features (hallucinations, delusions, disorganized thought processes).
Evidence of clinically significant alcohol withdrawal symptoms defined as a Clinical Institute Withdrawal Assessment (CIWA-AR) score of > 8.
History of hepatic cirrhosis or baseline AST or ALT > 3X upper limit of normal or other clinically significant findings on physical or laboratory examination.
Mental retardation or other severe cognitive impairment.
Prison or jail inmates.
Pregnant or nursing women or women of childbearing age who will not use oral contraceptives, abstinence, or other acceptable methods of birth control during the study.
Antipsychotic therapy within 14 days prior to randomization.
Current carbamazepine or benzodiazepine therapy.
Current treatment with medications shown to reduce alcohol consumption (naltrexone, acamprosate, disulfiram, or topiramate) in large randomized, controlled trials.
Initiation of antidepressants or mood stabilizers or psychotherapy within past 2 weeks.
High risk for suicide, defined as any suicide attempts in the past 3 months or current suicidal ideation with plan and intent.
Intensive outpatient treatment for substance abuse (AA, NA meetings, or other 12-step programs or weekly psychotherapy that started at least 14 days prior to randomization will be allowed).
Current treatment with ketoconazole, itraconazole, erythromycin, or nefazodone.
Severe or life-threatening medical condition (e.g., congestive heart failure, terminal cancer) or laboratory or physical examination findings consistent with serious medical illness (e.g., severe edema, atrial fibrillation, dangerously abnormal electrolytes).
Diabetes mellitus by history or suspected from baseline blood sugar.
History of cataracts or suspected cataracts on ophthalmic exam
History of seizure disorder of any etiology; if a subject develops a seizure episode, s/he will be discontinued from the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	This group will be given placebo matching quetiapine for the course of the 12 weeks in the study.
Quetiapine	Quetiapine	This group will be given 50mg Quetiapine per day baseline-week 1, 100mg Quetiapine per day week 1-week 2, 200mg Quetiapine per day week 2-week 3, 400mg Quetiapine per day week 3-week 4, and 600mg Quetiapine per day week 4 to week 12.

Primary Outcome Measures

Name	Time	Method
The Number of Standard Drinks/Day Will Serve as the Primary Outcome Measure.	12 weeks

Secondary Outcome Measures

Name	Time	Method
Percent of Heavy Drinking Days	12 weeks
Gamma-glutamyltransferase (GGT)	12 weeks	GGT is a liver enzyme measurement (IU/I)
Aspartate Aminotransferase (AST)	12 weeks	AST is a liver enzyme measurement (IU/I)
Alanine Aminotransferase (ALT)	12 weeks	ALT is a liver enzyme measurement (IU/I).
Hamilton Rating Scale for Depression (HRSD)	12 weeks	The assessment is a clinician administered rating of depression with 17 questions. The total score is indicates level of depression within the following ranges: none (0-5), mild (6-10), moderate (11-15), severe (16-20), and very severe (21+). Scale: Minimum: 0 Maximum: 50 Lower score associated with better outcome
Inventory of Depressive Symptomatology-Self Report (IDS-SR)	12 weeks	IDS-SR is a self reported 30 item assessment to diagnose a major depressive episode. Score: Minimum: 0 Maximum: 84 Lower score associated with better outcome
Young Mania Rating Scale (YMRS)	12 weeks	This is an 11-item, observer rated measure of the severity of manic symptoms on a 5 point scale. The total score indicates overall severity of mania with a minimum of zero (indicating normalcy) and a maximum of 60 (indicating very severe). Score: Minimum: 0 Maximum: 60 Lower score associated with better outcome
Penn Alcohol Craving Scale (PACS)	12 weeks	The PACS is a five-item self-administered instrument for assessing craving, frequency, intensity, and duration of thoughts about drinking are assessed along with ability to resist drinking Score: Minimum: 0 Maximum: 30 Lower score associated with better outcome.