This study will evaluate the safety and efficacy of risperidone (Risperdal®), olanzapine (Zyprexa®), and molindone (Moban®) for the treatment of children and adolescents with schizophrenia or schizoaffective disorder.

Little research has been conducted on the use of psychotropic agents in children and adolescents with early onset schizophrenia spectrum disorders. This study will compare antipsychotic agents with different mechanisms of action in children and adolescents who have schizophrenia or schizoaffective disorder with active psychotic symptoms.

Participants are randomly assigned to receive risperidone (Risperdal), olanzapine (Zyprexa), or molindone (Moban) for 8 weeks. After 11/2005, no additional patients will be assigned to olanzapine treatment. Patients with significant improvement and without side effects continue maintenance therapy for another 44 weeks. Participants who show significant negative symptoms after 8 weeks may be started on a mood stabilizer or antidepressant. Weight gain, metabolic changes, neurocognition, functional outcome, psychotic symptoms, extrapyramidal side effects, and the ability to sustain effective therapy over time are assessed.

• Drug: Risperidone
• Drug: Olanzapine (enrollment closed in this treatment)
• Drug: Molindone

Inclusion Criteria:

• Schizophrenia, schizophreniform disorder, or schizoaffective disorder with psychotic symptoms
• Free of depot antipsychotic medication for at least 6 months. Oral antipsychotic medication at entry into the study is allowed, provided the participant has not had an adequate trial during the present episode of psychosis.
• If taking antidepressant or mood stabilizing medication, stable dosing for at least 30 days prior to entry.
• Good physical health

Exclusion Criteria:

• Risperidone (RIS), olanzapine (OLA)*, or molindone (MOL) for 8 weeks or more during THIS episode, with 2 weeks at the maximal dose (6 mg/day of RIS, 20 mg/day of OLA, or 140 mg/day of MOL)
• If using antidepressant and/or mood stabilizing medications, treatment for fewer than 30 days immediately before entry
• Intolerance or nonresponse to RIS, OLA*, or MOL during any previous treatment
• Bipolar affective disorder,post traumatic stress disorder, personality disorder, or psychosis not otherwise specified
• Currently meeting DSM IV criteria for major depression episode
• DSM IV criteria for substance abuse or dependence with intention to continue illicit substance abuse
• Endocrinological or neurological conditions which confound the diagnosis or are a contraindication to treatment with antipsychotics
• Mental retardation
• Risk of suicide or homicide that is not adequately controlled in the current setting
• Pregnancy or refusal to practice contraception during the study

"*" OLA exclusion not applicable after 11/2005