This is a three arm multi-center randomized double-blind study. After open label treatment with each individual being optimized with routine antipsychotic treatment for 4-6 weeks to prospectively establish lack of response to conventional antipsychotic therapy, approximately 180 patients with schizophrenia who are experiencing clinically significant psychotic symptoms will be recruited (minimum 150 enrolled) in the double-blind period of the study. All participants will sign consent forms before participating in this research study. If participants choose to enroll in the high dose quetiapine arm (period IIIb), they will sign an additional consent form before entering period IIIb.