Background:We examined relapse after response to a first episode of schizophrenia or schizoaffective disorder.

Clozapine therapy demonstrated superiority to olanzapine therapy in preventing suicide attempts in patients with schizophrenia and schizoaffective disorder at high risk for suicide. Use of clozapine in this population should lead to a significant reduction in suicidal behavior.

Objective The primary aim was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first episode psychosis designed for implementation in the U.S. healthcare system, to Community Care on quality of life. Methods Thirty-four clinics in 21 states were randomly assigned to NAVIGATE or Community Care. Diagnosis, duration of untreated psychosis and clinical outcomes were assessed via live, two-way video by remote, centralized raters masked to study design and treatment. Participants (mean age 23) with schizophrenia and related disorders and ≤6 months antipsychotic treatment (N=404) were enrolled and followed for ≥2 years. The primary outcome was the Total Score of the Heinrichs-Carpenter Quality of Life Scale, a measure that includes sense of purpose, motivation, emotional and social interactions, role functioning and engagement in regular activities. Results 223 NAVIGATE recipients remained in treatment longer, experienced greater improvement in quality of life, psychopathology and involvement in work/school compared to 181 Community Care participants. The median duration of untreated psychosis=74 weeks. NAVIGATE participants with duration of untreated psychosis <74 weeks had greater improvement in quality of life and psychopathology compared with those with longer duration of untreated psychosis and those in Community Care. Rates of hospitalization were relatively low compared to other first episode psychosis clinical trials and did not differ between groups. Conclusions Comprehensive care for first episode psychosis can be implemented in U.S. community clinics. and improves functional and clinical outcomes. Effects are more pronounced for those with shorter duration of untreated psychosis.

The results document a large generalized deficit, and more subtle differential deficits, in clinically stabilized first-episode patients. Learning/memory deficits were observed even in patients with less severe generalized deficit, but the pattern was unlike the amnestic syndrome and probably reflects different mechanisms. Executive and attentional deficits marked the more severely disabled patients, and may portend relatively poor outcome. Failure to develop typical patterns of cerebral dominance may increase the risk for greater generalized deficit.

In early-phase psychosis, EIS are superior to TAU across all meta-analyzable outcomes. These results support the need for funding and use of EIS in patients with early-phase psychosis.