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Tolerability Profile of Atypical Antipsychotics in Children and Adolescents

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Abstract

Antipsychotics are frequently used in the treatment of a variety of neuropsychiatric conditions in children and adolescents. Atypical antipsychotics have come to the forefront in child psychiatry due largely to their tolerability profiles as well as their efficacy. Potential treatment options include clozapine, risperidone, olanzapine, quetiapine and ziprasidone.

A number of studies investigating the use of clozapine have been published in children; however, owing to the frequent monitoring required for agranulocytosis, the use of clozapine may be restricted to patients with treatment-refractory disease. With accumulating data on the development of glucose intolerance in adults receiving clozapine, closer monitoring of bodyweight and fasting blood glucose is imperative. Clozapine also has an increased seizure risk, therefore a baseline electroencephalogram should be performed, as well as continued vigilance for this adverse effect.

Risperidone is an atypical antipsychotic that is generally well tolerated and numerous studies have been published investigating this drug in children. Unlike clozapine, its receptor interaction profile lends itself toward increased risk of extrapyramidal symptoms (EPS) and hyperprolactinaemia. Bodyweight gain is a common adverse effect, although somewhat less than that reported with olanzapine. Baseline liver function studies prior to initiation of this medication are recommended. Risperidone-induced mania has been reported in adults and, therefore, increased caution should be used when deciding to treat children and adolescents with risperidone, particularly in those with a predisposition toward mania.

Olanzapine, like risperidone, has also been associated with onset of mania in adults. Olanzapine has a receptor profile that results in significant risk for bodyweight gain and sedation. Furthermore, this drug has been linked to the development of glucose intolerance; thus, it is important to monitor bodyweight and fasting blood glucose on a frequent basis.

Less information is known about quetiapine in children and adolescents. Reports about its efficacy and tolerability vary. Quetiapine appears to have increased risk for sedation and bodyweight gain, albeit less than that of olanzapine. The compound appears to be less likely to induce EPS.

Finally, ziprasidone has recently been approved for use in the adult population. This compound, in terms of its receptor profile, has more in common with risperidone. This suggests a potential for increased risk of EPS and hyperprolactinaemia. It also has an increased risk of QTc prolongation; thus, a baseline electrocardiogram is suggested, particularly in those patients with a history of cardiovascular illness. Lack of evidence for bodyweight gain with ziprasidone is a considerable advantage.

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Acknowledgements

Dr McDougle receives research grant support from Eli Lilly and Co., Janssen Pharmaceutica and Pfizer, Inc. He is a consultant for Eli Lilly and Co., Janssen Pharmaceutica and Pfizer, Inc. He is a member of the speaker’s bureau of Janssen Pharmaceutica and Pfizer, Inc.

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  1. Department of Psychiatry, Indiana University School of Medicine, Clinical Building Room 298, 541 Clinical Drive, Indiana, Indianapolis, 46202-5111, USA

    Kimberly A. Stigler &  Christopher J. McDougle

  2. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA

    Marc N. Potenza

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Stigler, K.A., Potenza, M.N. & McDougle, C.J. Tolerability Profile of Atypical Antipsychotics in Children and Adolescents. Paediatr Drugs 3, 927–942 (2001). https://doi.org/10.2165/00128072-200103120-00005

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