Review: Children and adolescents with schizophrenia spectrum disorders respond to antipsychotics, but are susceptible to adverse events

ED FROM Kumra S, Oberstar JV, Sikich L, et al. Efficacy and tolerability of second-generation antipsychotics in children and adolescents with schizophrenia. Schizophr Bull 2008;34:60–71. Correspondence to: Sanjiv Kumra, Division of Child and Adolescent Psychiatry, University of Minnesota Medical School, 2450 Riverside Avenue, F256/2B, Minneapolis, MN 55454, USA; kumra002@umn.edu Source of funding: National Institute of Mental Health, National Alliance for research in Schizophrenia and Affective Disorders, and the Mental Illness and Neuroscience Discovery Institute. c Additional references are published online only at http://ebmh.bmj. com/content/ vol11/issue3 C O M M EN TA R Y K umra and colleagues have offered a timely review on the efficacy and tolerability of second-generation antipsychotics (SGAs) for the treatment of Early Onset Schizophrenia Spectrum (EOSS) disorders. This review potentially helps clinicians analyse and critically interpret the available study results relevant to EOSS disorders. A relatively well-supported conclusion that clozapine offers superior efficacy for treatment of EOSS is offered. However, it is difficult to draw firm conclusions regarding comparative efficacy for other SGAs given the lack of differences in efficacy noted in the existing literature. Therefore, the distinction between individual medications is likely to be based on differences in adverse event profiles, an important principle for the practicing clinician. The authors allude to this issue, but readers are left to decide for themselves whether this might be the primary basis for choosing between agents. There are limited head-to-head comparisons of SGAs addressing relative risk of adverse events in children and adolescents. Having noted this limitation, the authors summarise that first generation antipsychotics probably have a higher risk of extrapyramidal side-effects (EPS) and that certain medications like olanzapine and clozapine probably have a higher risk of metabolic side-effects like weight gain, consistent with evidence from adults. The authors also note that the adverse event ‘‘stakes’’ are higher for children than adults due to the length of exposure and/or the longer opportunity to develop gradual onset, weight-related conditions like diabetes mellitus or cardiovascular disease. A brief summary of methods to avoid or attenuate antipsychotic-associated weight gain is provided, including lifestyle interventions and adjunctive pharmacotherapies such as metformin or sibutramine, although neither drug therapy has been adequately tested or approved for this use in children. However, the differential risk of weight gain rationally suggests the preferential first-line use of lower-risk medications, which is not clearly stated by the authors. These fundamentally different approaches are of great interest to clinicians and might ideally deserve equal and thorough treatment in future studies and reviews. Despite these limitations, this review offers a succinct compilation of what is known about the efficacy and risk profile of antipsychotics in EOSS disorders, usefully highlighting crucial areas where future studies on the treatment of these complex and disabling disorders are needed. Ginger Nicol, MD, John Newcomer, MD Washington University School of Medicine, Department of Psychiatry, St Louis, USA Competing interests: None. Therapeutics EBMH August 2008 Vol 11 No 3 81