Efficacy and Tolerability of Second-Generation Antipsychotics in Children and Adolescents With Schizophrenia
Open Access
- 27 October 2007
- journal article
- review article
- Published by Oxford University Press (OUP) in Schizophrenia Bulletin
- Vol. 34 (1), 60-71
- https://doi.org/10.1093/schbul/sbm109
Abstract
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 D(2) 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
This publication has 88 references indexed in Scilit:
- Aripiprazole acts as a selective dopamine D2receptor partial agonistExpert Opinion on Investigational Drugs, 2007
- Antipsychotic drug-induced weight gain mediated by histamine H1receptor-linked activation of hypothalamic AMP-kinaseProceedings of the National Academy of Sciences of the United States of America, 2007
- High rates of comorbidity are found in childhood-onset schizophreniaSchizophrenia Research, 2006
- Antipsychotics in early onset SchizophreniaEuropean Child & Adolescent Psychiatry, 2006
- Clozapine, Diabetes Mellitus, Hyperlipidemia, and Cardiovascular Risks and MortalityThe Journal of Clinical Psychiatry, 2005
- Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugsMolecular Psychiatry, 2004
- Catching Up on SchizophreniaNeuron, 2000
- Long-Term Stability of Diagnosis and Symptom Dimensions in a Systematic Sample of Patients with Onset of Schizophrenia in Childhood and Early Adolescence. I: Nosology, Sex and Age of OnsetThe British Journal of Psychiatry, 1996
- Risperidone in the Treatment of Children and Adolescents with Schizophrenia: A Retrospective StudyJournal of Child and Adolescent Psychopharmacology, 1996
- The Effects of Clozapine on Tardive DyskinesiaThe British Journal of Psychiatry, 1991