The purpose of this study is to ascertain whether Depakote ER (Divalproex ER) has efficacy in the treatment of patients with bipolar disorder in the manic phase, who also have comorbid substance abuse diagnoses. It is proposed that Depakote ER will decrease scores on the Young Mania Rating Scale and the Substance Abuse Time Line Follow Back.

This study will be performed in male and female subjects with a diagnosis of bipolar disorder in the manic phase of the illness who also have a comorbid diagnosis of substance abuse. This population is selected so the efficacy of Depakote ER in this population can be tested.

Inclusion Criteria:

1. Ages 19 - 65.
2. Diagnosis of mania with comorbid substance confirmed by Structured Clinical Interview for DSM-IV.
3. Comorbid diagnoses of anxiety and/or personality disorders are permitted.
4. Ability to provide signed informed consent.
5. Stable general medical health.
6. Ability to attend outpatient research clinic.

Exclusion Criteria:

1. Dangerous to self or others.
2. Pregnancy, inability or unwillingness to use approved methods of birth control.
3. Inability or unwillingness to provide signed informed consent.
4. Diagnosis of schizophrenia, major depressive disorder.
5. Inability to attend outpatient research clinic.
6. Medical conditions, which would preclude use of Depakote.
7. Need for ongoing treatment with medication other than Depakote ER, such as antipsychotic medication.
8. Medical instability defined as likelihood of needing to change prescription medication during the course of the study.