It is hypothesized that the atypical antipsychotic, Seroquel, will cause significant reduction in drug and alcohol cravings in patients with schizophrenia and comorbid cocaine and/methamphetamine dependence compared to the atypical antipsychotic, risperidone (Risperdal).

Patients treated with Seroquel will have less use of cocaine and/or methamphetamine as measured by the Time Line Follow-back, over a 24-week follow-up period.

Schizophrenia is a serious mental illness that afflicts approximately 1% of the population (1). Often these patients have comorbid cocaine and amphetamine dependence, which increases the severity of psychotic symptoms associated with schizophrenia, decreases treatment compliance and worsens prognosis.

The treatment of schizophrenia with comorbid cocaine and/or amphetamine dependence is complex and involves adherence to psychiatric medications, most often antipsychotic agents, along with participation in specific substance abuse treatment such as structured living, attendance at self-help group meetings, individual and group therapy and a commitment to sobriety. In the absence of specific pharmacotherapy of cocaine and amphetamine dependence, various antipsychotic medications have been compared to see if they impact comorbid cocaine and amphetamine abuse in addition to their antipsychotic effects.

The primary objective of this study is to test whether Seroquel as a mono-therapy decreases cocaine and/or methamphetamine use in patients with schizophrenia as compared to risperidone.

Inclusion Criteria:

1. Ages 19 - 65.
2. Diagnosis of schizophrenia or schizoaffective disorder with comorbid cocaine and/or amphetamine abuse/dependence as confirmed by Structured Clinical Interview for DSM-IV.
3. Comorbid diagnoses of depression, anxiety and/or personality disorders are permitted.
4. Ability to provide signed informed consent.
5. Stable general medical health.

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 bipolar disorder, primary major depressive disorder (As major Axis I diagnosis).
5. Inability to attend outpatient research clinic.
6. Medical conditions, which would preclude use of Seroquel.
7. Absolute need for ongoing treatment with antipsychotic other than Seroquel.
8. Medical instability defined as likelihood of needing to change prescription medication during the course of the study.
9. Patients currently taking quetiapine or risperidone.
10. Patients with unsuccessful treatment with quetiapine or risperidone.
11. Subjects with a HAM-D score of ≥20 at screening.