This study will examine depressed alcoholic outpatients to assess whether combining
naltrexone (Revia) and sertraline (Zoloft) will result in greater reductions in both
drinking and depression over either medication alone or placebo. A secondary aim is to
determine whether certain patient features will predict response to sertraline, naltrexone
or the combination of the two drugs. Subjects will be randomized into treatment groups for
14 weeks. The followup phase includes two visits at 6 and 9 months after treatment.
The proposed study will examine managing relapse in patients with alcohol dependence and
depression using a 14-week double-blind, placebo-controlled, combination of 100 mg/day of
naltrexone, 200 mg/day of sertraline, and individual, cognitive behavioral therapy (CBT).
For testing the medication, the design will be 2x2, consisting of four groups:
naltrexone/sertraline, naltrexone only, sertraline only, placebo. All four groups will
receive once weekly sessions of CBT given by therapists experienced in working with patients
with substance disorders and trained in the principles of CBT.
- Male and female outpatients 18 75 years of age.
- Patients must have met DSM-IV criteria for (primary or substance-induced) major
depressive episode prior to randomization.
- Patients must have a current DSM-IV diagnosis of alcohol dependence.
- Patients must have a total score of 10 or higher on the Hamilton Depression Scaleat
the day of randomization. Also, item 1 on the scale must be > 1.
- Patients must have drank sufficient alcohol in the month prior to coming for
treatment so that a practical assessment in reductions in drinking during and after
treatment can be performed. The guidelines we will follow for this study as to what
we think is sufficient will be that the patient in the month prior to coming to
treatment will have drank on 40% or more of the days or drank more than 40 standard
drinks (an average of 10 drinks per week).
- Patients must have successfully completed medical detoxification for alcohol (are
abstinent for 4 consecutive days) or if medical detoxification is not indicated, have
been abstinent for 4 consecutive days since coming to treatment but before initiating
the study medication/placebo.
- Females of childbearing potential must have a negative pregnancy test and not
contemplating pregnancy within the next 6 months. They must also use a contraceptive
method judged by the investigator to be effective.
- Patients with evidence of opiate use in the past 30 days as assessed by self-report
and intake urine drug screens (only one repeat testing permitted). Patients with a
history of treatment for opiate dependence will be excluded.
- Patients who, within the past year, met DSM IV criteria for dependence on any
psychoactive substance other than alcohol or nicotine. Patients who test positive on
the urine drug screen (with the exception of THC) at the initial visit (only one
repeat testing permitted).
- Patients who meet DSM-IV criteria for past history or current disorder of
schizophrenia or any psychotic disorder, or bipolar disorder.
- Patients with evidence or history of significant hematological, pulmonary, endocrine,
cardiovascular, renal or gastrointestinal disease. (If there is a history of such
disease but the condition has been stable for more than one year and is judged by the
investigator not to interfere with the patient's participation in the study, the
patient may be included.)
- Patients with abnormal liver function tests (AST or ALT) (more than 3.5 times the
upper level of the normal value) or patients with any abnormal elevation in
- Patients requiring concomitant therapy with any psychotropic drug (with the exception
of benadryl used sparingly if necessary for sleep or oxeazepam for detoxification or
nicotine replacement therapy).
- Patients who have taken fluoxetine (Prozac) during the 6 weeks prior to randomization
--due to its long half-life.
- Patients who have taken monoamine oxidase inhibitors (MAOI) during the 2 weeks prior
to randomization -- due to the potential toxicity of combining MAOI medications with
serotonin-specific ones. (Patients will also be instructed not to take MAOI for 2
weeks after completing the study.)
- Past use of antidepressants or other psychotropic medications (except as specified
above) within 7 days of randomization.
- Patients on concomitant therapy with an investigational drug, or patients who have
been in an investigational drug study within one month prior to entering this study.
- Patients who are unable to read or print in English.