Jon McCLELLAN1, Linmarie Sikich2, Robert L Findling2, Jean A Frazier2, Benedetto Vitiello2, Stefanie A Hlastala2, Emily Williams2, Denisse Ambler2, Tyehimba Hunt-Harrison2, Ann E Maloney2, Louise Ritz2, Robert Anderson2, Robert M Hamer2, Jeffrey A Lieberman2. 1. Drs. McClellan and Hlastala are with the University of Washington, Seattle; Mr. Anderson, Ms. Williams, and Drs. Sikich, Ambler, Hunt-Harrison, and Hamer are with the University of North Carolina, Chapel Hill; Dr. Findling is with Case Western Reserve University, Cleveland; Dr. Frazier is with Cambridge Health Alliance, Harvard Medical School, Cambridge, MA; Dr. Maloney is with the Maine Medical Center, Portland; Ms. Ritz and Dr. Vitiello are with the NIMH, Bethesda, MD; and Dr. Lieberman is with Columbia University, New York.. Electronic address: drjack@u.washington.edu. 2. Drs. McClellan and Hlastala are with the University of Washington, Seattle; Mr. Anderson, Ms. Williams, and Drs. Sikich, Ambler, Hunt-Harrison, and Hamer are with the University of North Carolina, Chapel Hill; Dr. Findling is with Case Western Reserve University, Cleveland; Dr. Frazier is with Cambridge Health Alliance, Harvard Medical School, Cambridge, MA; Dr. Maloney is with the Maine Medical Center, Portland; Ms. Ritz and Dr. Vitiello are with the NIMH, Bethesda, MD; and Dr. Lieberman is with Columbia University, New York.
Abstract
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.
RCT Entities:
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.
Authors: Jessica A Hellings; Gregory Reed; Sharon E Cain; Xinghua Zhou; Francis X Barth; Michael G Aman; Gladys I Palaguachi; Dmytro Mikhnev; Rujia Teng; Rebecca Andridge; Marilyn Logan; Merlin G Butler; Joan C Han Journal: J Child Adolesc Psychopharmacol Date: 2015-03 Impact factor: 2.576
Authors: Jean A Frazier; Anthony J Giuliano; Jacqueline L Johnson; Lauren Yakutis; Eric A Youngstrom; David Breiger; Linmarie Sikich; Robert L Findling; Jon McClellan; Robert M Hamer; Benedetto Vitiello; Jeffrey A Lieberman; Stephen R Hooper Journal: J Am Acad Child Adolesc Psychiatry Date: 2012-03-13 Impact factor: 8.829