The purpose of this study is to determine whether adding the drug risperidone is more effective than placebo in treating schizophrenic patients who are taking the drug clozapine.

Clozapine is the only antipsychotic drug that has been approved for treatment resistant patients with schizophrenia. However, up to 50% of patients treated with clozapine fail to respond and continue to exhibit clinically significant residual positive and negative symptoms and cognitive impairments. An emerging trend in treatment is the addition of a second antipsychotic drug. This study will determine if risperidone when given as adjunctive treatment is more effective than placebo in treating schizophrenic patients failing clozapine therapy.

Participants are randomly assigned to add either adjunctive risperidone or placebo to their current clozapine treatment in a single, daily dose for 16 weeks. Positive and negative symptoms, cognitive impairments, side effects of the treatment, anxiety, depression, hostility symptoms, and quality of life are assessed. Neurological tests, self administered questionnaires, and interviews are used to assess patients.

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• DSM-IV criteria for schizophrenia or schizoaffective disorder
• Current clozapine treatment
• Moderate illness severity and inadequate positive symptom response to clozapine treatment
• 6 month period of clozapine treatment with documented clozapine blood level >= 350 ng/ml or clozapine and norclozapine blood level >= 450 ng/ml

Exclusion Criteria:

• Organic brain disorder
• Mental retardation
• Medical condition whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with the proposed treatment protocol
• Pregnancy
• DSM-IV criteria for current alcohol or substance dependence within the last 6 months or DSM-IV criteria for alcohol or substance abuse within the last month
• Previously received adjunctive risperidone (at doses >= 8 mg/day) with their clozapine treatment for >= 6 weeks