Best Event Schizophrenia Trial--A Randomized Double-Blind Trial of Aripiprazole and Risperidone in Schizophrenia

The primary objective of the proposed research project is to identify a practical method of
predicting differential antipsychotic drug treatment response in patients with schizophrenia.
In particular, we will examine differential response to two antipsychotic drugs, aripiprazole
and risperidone, that have contrasting pharmacologic activity at D2-type dopamine receptors,
i.e., partial agonism vs. antagonism, respectively. A number of candidate predictors will be
examined, including neuroimaging parameters (regional neuroanatomical and metabolic
variations, fallypride binding to D2-like receptors), neuropsychological testing, clinical
features, laboratory measures, and genetic studies.

Secondary objectives include: (1) extension of our previous efforts to characterize
abnormalities in cortico-striato-thalamic circuits in unmedicated schizophrenics using PET
and MR imaging; and, (2) examination of the role of omega-3 fatty acid activity in
schizophrenics as a predictor of dopaminergic activity.

Inclusion Criteria:

1. Subjects will meet DSM-IV diagnostic criteria for schizophreniform disorder,
schizophrenia, schizoaffective disorder or (non-affective) psychotic disorder, NOS.
Subjects with schizophreniform disorder or psychotic disorder, NOS, will be
diagnostically reevaluated (recontacted if no longer involved in the study) after a
minimum of six months of psychotic symptoms in order to determine whether diagnostic
criteria for schizophrenia or schizoaffective disorder have been met.

2. Subjects will be between 18 and 55 years of age, inclusive.

3. Subjects will be able to fully participate in the informed consent process, or have a
legal guardian able to participate in the informed consent process.

4. Present score on at least one PANSS psychosis items (P1, P2, P3, P5 or P6) >
4(moderately severe) and CGI Severity score > 4 (moderate).

5. Female patients of childbearing potential must be using a medically accepted means of
contraception

Exclusion Criteria:

1. Current active substance use disorder diagnosis or a history of cocaine abuse or
dependence;

2. Female patients who are either pregnant or nursing;

3. Known history of mental retardation, seizure disorder, or a clinically significant
head injury (prolonged loss of consciousness, neurological sequelae, or demonstrated
structural brain injury);

4. Non-English speaking (mastery of English insufficient to participate in study
evaluation procedures);

5. Serious, unstable medical illness;

6. Known hypersensitivity to any study medication;

7. Medical contraindication to any element of the study procedure;

8. Current symptoms which present serious risk of danger to self or others;

9. Participation in a clinical trial of an investigational drug within 30 days of study
entry;

10. Current severity of psychiatric symptoms contraindicates a delay in initiation of
antipsychotic medication treatment until functional imaging studies and
neuropsychological testing have been completed;

11. Baseline QTc interval of > 450 msec.