Optimizing Pharmacotherapy for Bipolar Alcoholics

Bipolar disorder has the highest rate of association with alcohol and other substance use
disorders. This complex clinical presentation is asociated with severe
disabilities,morbidity and heightened risk for suicide. There is a significant gap in our
knowledge regarding effective treatment interventions for this high risk clinical
population. This proposal will test the efficacy of a promising pharmacological approach for
the treatment of comorbid alcohol dependence and bipolar disorder. We propose a randomized,
double blind, placebo controlled 12-week trial to test the efficacy of valproate plus
naltrexone vs. valproate alone in decreasing alcohol use and stabilizing mood symptoms among
patients with comorbid alcohol dependence and bipolar disorder. All participants receive
supportive psychosocial treatment.

Inclusion Criteria:

- Subjects will meet Diagnostic and Statistical Manual-IV (DSM-IV) criteria for current
alcohol dependence and a concurrent bipolar disorder

Exclusion Criteria:

- 1) Schizophrenia, schizoaffective and any nonbipolar psychotic disorder, unipolar
major depression, primary anxiety disorder,mental retardation and signs of impaired
cognitive functioning.

- 2) Opiate dependence, abuse, or on opioid maintenance treatment for any reason and
those with positive urine screen for opiate.

- 3)Current DSM-IV criteria for dependence on substances other that alcohol,
cannabis,nicotine or caffeine.

- 4) Neurological conditions including epilepsy, history of brain injury,encephalitis
or any organic brain syndrome or documented focally abnormal EEG.

- 5)Medical conditions including severe cardiac, liver, kidney, endocrine, hematologic,
or other impairing medical conditions, or impending surgery

- 6)Pregnancy

- 7)Inability or unwillingness to use contraceptive methods

- 8)Any medical condition or other reason that in the opinion of the investigator would
prevent the subject from completing the protocol