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Adverse Effects of Second-Generation Antipsychotics in Children and Adolescents: A Bayesian Meta-Analysis

Cohen, David MD, PhD*†; Bonnot, Olivier MD, PhD*‡; Bodeau, Nicolas MS*; Consoli, Angèle MD, PhD*‡; Laurent, Claudine MD, PhD*‡

Journal of Clinical Psychopharmacology: June 2012 - Volume 32 - Issue 3 - p 309–316
doi: 10.1097/JCP.0b013e3182549259
Original Contributions

Abstract: In adults, second-generation antipsychotics (SGAs) have a low frequency of extrapyramidal syndrome (EPS) and a moderate frequency of metabolic adverse effects. Here we aimed to assess short-term adverse effects of SGAs in children and adolescents. We searched for relevant studies in MEDLINE and EMBASE (1996–2010), Food and Drug Administration and European Medicines Agency clinical trial registries, and reference lists of review articles. We found 41 were short-term (3–12 weeks) controlled studies that evaluated SGA adverse effects in youths. Using Bayesian meta-analysis, we analyzed odds ratios (ORs) or mean average effects. Numbers of arms (subjects) in the 41 trials were aripiprazole, 10 (n = 671); olanzapine, 14 (n = 413); quetiapine, 10 (n = 446); risperidone, 25 (n = 1040); ziprasidone, 4 (n = 228); clozapine, 5 (n = 79); and placebo/untreated, 23 (n = 1138), totaling 93 arms (4015 patients). Clozapine was assessed only for weight gain and somnolence. Compared with placebo, significant treatment-related increases were observed for weight gain with olanzapine (mean ± SD = 3.99 ± 0.42 kg; 95% credible interval, 3.17–4.84 kg), clozapine (2.38 ± 1.13 kg; 95% credible interval, 0.19–4.62 kg), risperidone (2.02 ± 0.32 kg; 95% credible interval, 1.39–2.66 kg), quetiapine (1.74 ± 0.38 kg; 95% credible interval, 0.99–2.5 kg), and aripiprazole (0.89 ± 0.32 kg; 95% credible interval, 0.26–1.51 kg); glucose levels with risperidone (3.7 ± 1.36 mg/dL; 95% credible interval, 1.08–6.42 mg/dL) and olanzapine (2.09 ± 1.08 mg/dL; 95% credible interval, 0.13–4.32 mg/dL); cholesterol levels with quetiapine (10.77 ± 2.14 mg/dL; 95% credible interval, 6.6–14.95 mg/dL) and olanzapine (4.46 ± 1.65 mg/dL; 95% credible interval, 1.24–7.73 mg/dL); triglyceride levels with olanzapine (20.18 ± 5.26 mg/dL; 95% credible interval, 9.85–30.53 mg/dL) and quetiapine (19.5 ± 3.92 mg/dL; 95% credible interval, 11.84–27.17 mg/dL); hyperprolactinemia with risperidone (OR, 38.63; 95% credible interval, 8.62–125.6), olanzapine (OR, 15.6; 95% credible interval, 4.39–41.1), and ziprasidone (OR, 9.35; 95% credible interval, 1.24–37.03); and EPS with ziprasidone (OR, 20.56; 95% credible interval, 3.53–68.94), olanzapine (OR, 6.36; 95% credible interval, 2.43–13.84), aripiprazole (OR, 3.79; 95% credible interval, 2.17–6.17), and risperidone (OR, 3.71; 95% credible interval, 2.18–6.02). All SGAs increased the risk of somnolence/sedation. We conclude that short-term metabolic effects and EPS are frequent in children treated with SGAs. Second-generation antipsychotics have distinct profiles of secondary effects, which should be considered in making treatment decisions.

From the *Department of Child and Adolescent Psychiatry, Université Pierre et Marie Curie, GH Pitié-Salpétrière; †CNRS UMR 7222, Institut des Systèmes Intelligents et Robotiques; and ‡CNRS UMR 7225, Biotechnologie et Biothérapie, CRICM, UPMC, Paris, France.

Received April 18, 2011; accepted after revision November 30, 2011.

Reprints: David Cohen, MD, PhD, Department of Child and Adolescent Psychiatry, Université Pierre et Marie Curie, Hôpital de la Pitié-Salpétrière, AP-HP, 47 bld de l’Hôpital, 75013, Paris, France (e-mail: david.cohen@psl.aphp.fr).

The current review was supported by a grant from the European Union FP7 (PERS) and the University Pierre et Marie Curie. None of these noncommercial funding organizations had any role in the design or conduct of the meta-analysis, preparation, review, or approval of the manuscript. N.B. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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© 2012 Lippincott Williams & Wilkins, Inc.