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Schizophrenia Bulletin Advance Access originally published online on October 8, 2007
Schizophrenia Bulletin 2008 34(1):60-71; doi:10.1093/schbul/sbm109
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© 2007 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Efficacy and Tolerability of Second-Generation Antipsychotics in Children and Adolescents With Schizophrenia

Sanjiv Kumra1,2, Joel V. Oberstar2, Linmarie Sikich3, Robert L. Findling4, Jon M. McClellan5, Sophia Vinogradov6 and S. Charles Schulz2
2 University of Minnesota, Minneapolis, MN
3 University of North Carolina, Chapel Hill, NC
4 Case Western Reserve University, Cleveland, OH
5 University of Washington, Seattle, WA
6 Department of Veterans Affairs Medical Center and University of California San Francisco, San Francisco, CA

1 To whom correspondence should be addressed; Division of Child and Adolescent Psychiatry, University of Minnesota Medical School, 2450 Riverside Avenue, F256/2B, Minneapolis, MN 55454; tel: 612-273-9775, fax: 612-273-9779, e-mail: kumra002{at}umn.edu.

Early-onset schizophrenia-spectrum (EOSS) disorders (onset of psychotic symptoms before 18 years of age) represent a severe variant associated with significant chronic functional impairment and poor response to antipsychotic treatment. All drugs with proven antipsychotic effects block dopamine D2 receptors to some degree. The ongoing development of the dopamine and other neurotransmitter receptor systems during childhood and adolescence may affect clinical response and susceptibility to side effects in youth. A literature search was conducted of clinical trials of antipsychotics in children and adolescents with EOSS disorders between 1980 and 2007 from the Medline database, reference lists, and conference proceedings. Trials were limited to double-blind studies of duration of 4 or more weeks that included 15 or more patients. Ten clinical trials were identified. Antipsychotic medications were consistently found to reduce the severity of psychotic symptoms in children and adolescents when compared with placebo. The superiority of clozapine has been now demonstrated relative to haloperidol, standard-dose olanzapine, and "high-dose" olanzapine for EOSS disorders. However, limited comparative data are available regarding whether there are differences among the remaining second-generation antipsychotics (SGAs) in clinical effectiveness. The available data from short-term studies suggest that youth might be more sensitive than adults to developing antipsychotic-related adverse side effects (eg, extrapyramidal side effects, sedation, prolactin elevation, weight gain). In addition, preliminary data suggest that SGA use can lead to the development of diabetes in some youth, a disease which itself carries with it significant morbidity and mortality. Such a substantial risk points to the urgent need to develop therapeutic strategies to prevent and/or mitigate weight gain and diabetes early in the course of treatment in this population.

Keywords: psychosis / atypical antipsychotic / weight management / metabolic syndrome / cognitive deficits / double-blind treatment trial


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