• The primary efficacy endpoint will be the change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment in the PANSS (Positive and Negative Symptoms of Schizophrenia) total score. [ Time Frame: The primary efficacy endpoint will be the change from baseline to week 6 or the last post-randomization assessment during double-blind treatment in the PANSS total score. ] [ Designated as safety issue: No ]
  

• Secondary analyses include change from baseline to endpoint scores on: Clinical Global Impression of Severity (CGI-S), Clinical Global Impression of Change (CGI-C), PANSS factor scores for anxiety/depression and hostility/excitement, YMRS and HAM-D. [ Time Frame: Secondary analysis include change from baseline to endpoint scores on: Clinical Global Impression of Severity, Clinical Global Impression of Change, PANSS factor scores for anxiety/depression and hostility/excitement, YMRS, and HAM-D. ] [ Designated as safety issue: No ]
  

Schizophrenia and schizoaffective disorder are closely related in terms of symptoms, coexisting conditions, and genetic risk. In previous studies in patients with schizophrenia, treatment with paliperidone extended-release (ER) improved psychotic symptoms, as well as mood symptoms evaluated by anxiety/depression and hostility/excitement Positive and Negative Symptoms of Schizophrenia (PANSS) factor scores. Therefore, paliperidone ER may also be effective in treating symptoms of schizoaffective disorder. Paliperidone's limited potential for drug-drug interaction is particularly important in this patient population, in which multiple drug therapy is relatively common. This multicenter, double-blind (neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage), randomized (patients are assigned different treatments based on chance), placebo-controlled, parallel-group study is designed to examine the effectiveness and safety of paliperidone ER in adult patients with schizoaffective disorder who are experiencing an acute episode of this disorder. Patients in the study will be randomly assigned to 1 of 3 groups to receive 6 weeks of oral treatment with 1 of 2 dosages of paliperidone ER or placebo. The primary efficacy outcome will be the change from baseline to Week 6, or the last post-randomization assessment during double-blind treatment (endpoint), in the PANSS total score. Safety will be assessed by monitoring adverse events, clinical laboratory testing, pregnancy testing, vital signs measurements, physical examination, administration of a 12-lead ECG, movement disorders side effect scales, and the InterSePT Scale for Suicidal Thinking. Patients may also choose to participate in a pharmacogenomic (DNA) analysis. The primary study hypotheses are that at least one of the two dosages of paliperidone ER is better than placebo on the change from baseline in the PANSS total score in acutely ill patients with schizoaffective disorder at the end of 6 weeks of treatment.

Patients will receive study drug by mouth for a total of 43 days. Beginning on Day 1, patients will take either placebo or 1 of 2 doses of paliperidone: 6 mg/day (low randomized dosage) or 12 mg/day (high randomized dosage). During the first 2 weeks, dosages may be adjusted.

Inclusion Criteria:

• Diagnostic and Statistical Manual - Fourth Edition (DSM-IV) diagnosis of schizoaffective disorder
• A total Positive and Negative Symptoms of Schizophrenia (PANSS) score of >= 60
• A score of >= 16 on Young Mania Rating Scale (YMRS) or a score of >= 16 on the Hamilton Depression Rating Scale (HAM-D 21)

Exclusion Criteria:

• A primary active mental illness diagnosis other than schizoaffective disorder
• Patients with first episode psychosis
• Active substance dependence within previous 6 months
• Treatment with clozapine within 6 months of randomization
• A history of treatment resistance, defined by failure to respond to 2 adequate trials of antipsychotic medication
• Pregnancy, breast-feeding, or planning to become pregnant