Treatment With Acamprosate in Patients With Schizophrenia and Comorbid Alcoholism

Alcohol use disorders (AUD) are common comorbid conditions in patients with schizophrenia,
and they cause a negative impact on the expression and course of schizophrenia. Improvements
have been reported after attaining abstinence from alcohol, suggesting that effective
treatments for AUD lead to clinically meaningful results. Acamprosate is a recently approved
treatment for alcoholism, and it may be advantageous over other treatments since is not
metabolized in the liver, and it has been used safely with other psychotropic medications.
Therefore, acamprosate would be a promising treatment in schizophrenia patients. However,
there are only few reports in the current literature evaluating the efficacy of medications
available for the treatment of alcoholism in patients with schizophrenia, and the efficacy
and safety of acamprosate have never been studied in this vulnerable group of patients.

Research Design:

This is a 12-week, randomized, double blind, placebo controlled trial of acamprosate (666 mg
tid) in addition to neuroleptics in 30 recently abstinent (>5 days) schizophrenia patients
with comorbid alcohol dependence.

Methods:

The study will be conducted at the West Haven, CT VA with support from Forest Laboratories.
Patients who are between 21 and 65, with a diagnosis of schizophrenia spectrum disorder, (on
stable psychotropic treatment > 2 weeks) and with current alcohol dependence (>1 recent
episode of heavy drinking) will be included. Patients will be willing to undergo
detoxification or self discontinuation >2weeks prior to the randomization. Main outcome
variables include the TLFB method to document the degree of daily alcohol consumption, and
PANSS, to assess the psychotic symptoms.

Inclusion Criteria

1. Men and women between 21 and 65 years of age.

2. Patients with a diagnosis of schizophrenia, schizoaffective disorder, or psychotic
disorder NOS as determined by the Structured Clinical Interview for DSM-IV Axis I
Disorders (SCID) [22].

3. Patients who are on stable treatment with psychotropic medication > 2 weeks prior to
randomization.

4. Patients with current alcohol dependence, with at least one recent episode of heavy
drinking (defined as 5 or more drinks per drinking episode) over the past 21 days,
and willing to undergo detoxification or self discontinuation (for at least 5 days).

5. Patients, who are able to comprehend and satisfactorily comply with protocol
requirements.

6. Patients who have capacity to provide informed consent prior to entering any study
procedure.

Exclusion Criteria

1. Patients with dementia, amnestic and other cognitive disorders.

2. Patients who have unstable medical disease or a medical condition that, in the
Investigator's opinion, would expose them to an increased risk of a significant
adverse event or interfere with assessments of safety and efficacy during the course
of the trial

3. Patients with a history of opioid dependence within the past month.

4. Patients with a history of intolerance or hypersensitivity to acamprosate.

5. Patients who are currently taking disulfiram or naltrexone.

6. Patients who based on history or mental status examination are at a significant risk
for suicide.

7. Patients who are homicidal or violent and who are in the Investigator's opinion in
significant imminent risk of hurting others.

8. Women who are pregnant or nursing, or women of childbearing potential who are
sexually active and who do not use adequate contraception, or who are judged to be
unreliable in their use of contraception.