Naltrexone for Bipolar Disorder and Alcohol Dependence
Naltrexone for Bipolar Disorder and Alcohol Dependence
The abuse of alcohol is especially common in people with bipolar disorder. However, very
 little is known about how to treat people with both bipolar disorder and alcohol
 abuse/dependence. The purpose of this research is to determine whether naltrexone add-on
 therapy is associated with a greater reduction in alcohol use and alcohol craving than with
 placebo (an inactive substance) therapy.
A 12-week, randomized, double-blind, parallel-group, placebo-controlled trial of naltrexone
 will be conducted in 50 English- or Spanish-speaking outpatients with bipolar I disorder or
 II disorder and current alcohol dependence. At the baseline appointment, informed consent
 will be obtained, and assessment procedures, including a review of inclusion and exclusion
 criteria, will be performed. The SCID (Structured Clinical Interview for DMS-IV Axis I
 Disorders will be performed to establish the diagnoses of bipolar I or II disorder and
 alcohol dependence. A psychiatrist will confirm the SCID diagnoses obtained by the RA.
 Eligible participants will then be given the Hamilton Rating Scale for Depression 17-item
 version (HRSD17), Inventory of Depressive Symptomatology-Self-Report 30-item version
 (IDS-SR30), Young Mania Rating Scale (YMRS), Penn Alcohol Craving Scale (PACS), Addiction
 Severity Index (ASI), Psychobiology of Recovery in Depression III Somatic Symptom Scale
 (PRD-III), and a urine drug screen. Recent alcohol use (and if present other substance use)
 will be assessed using the Timeline Followback (TLFB) method, with a drink defined as 13.6g
 of absolute alcohol (approximately 12 oz (341 mL) of beer, 5 oz of wine, 3 oz of fortified
 wine, or 1.5 oz of 80 proof liquor). Length of problem alcohol use will be assessed by
 asking, "When did alcohol first start causing you problems?" Blood will be drawn for routine
 laboratory analyses including a complete blood count (CBC) and SMA-20 (includes a liver panel
 with GGT, AST, ALT, Billirubin) at baseline (week 0) and completion (week 12). Blood will
 also be drawn at weeks 4 and 8 for repeat testing of GGT levels. A physical examination will
 be performed at baseline. Women of childbearing potential will receive a urine pregnancy test
 and will be counseled about effective contraceptive methods. A psychiatrist will assess the
 participants at baseline and weekly follow-up visits, and will participate in the informed
 consent process. Study medication will be given at a second appointment after results of the
 liver function tests have been received (generally 1-2 days after the first appointment). At
 each weekly assessment the HRSD17, IDS-R30, YMRS, an assessment of alcohol use in the past
 week, and a urine drug screen will again be obtained. Urine drug screen will be obtained only
 from the newly enrolled subjects. We will not obtain urine drug screens from subjects who are
 already active in the study. In addition, all participants will receive a total of 16
 one-hour/week sessions of manual-driven CBT specifically designed for persons with bipolar
 disorder and substance abuse, provided by a bilingual psychologist with experience in CBT.
 Patients will discontinue study medication at week 12, but continue their CBT therapy until
 week 16. Pill counts will be conducted at each weekly assessment visit. In addition, during
 weekly assessments, participants will be asked about adherence with other psychotropic
 medications using a modified version of an assessment developed by Weiss et al., and the
 estimated percent of prescribed medication actually taken will be recorded.
INCLUSION CRITERIA:

 -  English or Spanish-speaking

 -  Age 18-70

 -  Diagnosis of bipolar I or II.

 -  Current mood state of depressed or mixed.

 -  Alcohol use of at least 5 drinks in the past 7 days.

 -  Current diagnosis of alcohol dependence.

 EXCLUSION CRITERIA:

 -  Bipolar disorders other than bipolar I or II disorders (e.g., bipolar NOS, or
 cyclothymic disorders, schizophrenia, schizoaffective disorder, or unipolar).

 -  Lifetime opiate abuse or dependence or any current use (including prescription drugs).

 -  Diagnosis of current dependence on substances other than alcohol (participants with
 only abuse of other substances are included. Dependence on caffeine and/or nicotine is
 allowed.)

 -  Severe or life-threatening medical illness (e.g., hepatic cirrhosis, congestive heart
 failure, terminal cancer) or labs consistent with serious medical illness (e.g.,
 severe edema, atrial fibrillation, dangerously abnormal electrolytes).

 -  Pregnant or nursing female

 -  High risk for suicide defined as ≥2 suicide attempts in the past 12 months that
 required medical attention, or current suicidal ideation with plan and intent.

 -  Prior therapy with naltrexone and/or allergic reaction to naltrexone.

 -  Current therapy with acamprosate or disulfiram.

 -  Member of a vulnerable population (Dementia, cognitively impaired, mental retardation,
 prisoner)

 -  Baseline YMRS or HRSD17 scores ≥ 30.

 -  AST, ALT, or bilirubin > 3 times upper limit of normal.