Treatment of early-onset schizophrenia spectrum disorders (TEOSS): rationale, design, and methods

OBJECTIVE: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. METHOD: Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. RESULTS: From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. CONCLUSIONS: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization

Treatment of early-onset schizophrenia spectrum disorders (TEOSS): demographic and clinical characteristics

OBJECTIVE: We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders. METHOD: Youths (8-19 years) with schizophrenia (SZ) and schizoaffective disorder were recruited at four academic sites. Diagnosis was made via structured and clinical interviews. Assessments of psychiatric symptoms and social and global functioning were included. RESULTS: A total of 119 youths were enrolled. The mean age at illness onset was 11.1 +/- 3.5 years. Patients with SZ and schizoaffective disorder had similar ratings on the Positive and Negative Symptom Scale, Brief Psychiatric Rating Scale for Children, and Clinical Global Impression-Severity Scale. The overall level of functioning was similar in the two groups. A comparison to published reports of adults with SZ indicates that these youths may have more severe symptoms based on results of the Positive and Negative Symptom Scale. CONCLUSIONS: This is one of the largest samples of youths with SZ spectrum disorders studied to date and the largest assessment of youths with schizoaffective disorder. High rates of symptoms and general psychopathology were noted. There was a substantial degree of social and functional impairment. The symptom profiles are consistent with, but more severe than, those reported in the adult literature