Abstract
Objective: To study the safety and usage of atypical antipsychotic medicines in post-marketing use in a nationwide paediatric population.
Design: Prospective observational cohort study using prescription event monitoring and record linkage.
Population: New Zealand children aged ≤15 years, who were prescribed atypical antipsychotic medicines between April and July 2003.
Outcomes: Usage measures included prescription data for each medication, the diagnosis for which the patient was being treated and main target symptom. Safety outcome measures were all new clinical adverse events between the start of treatment (which could be before April 2003) and 30 November 2004.
Results: The cohort included 420 children aged 2–15 years. Total exposure to atypical antipsychotic medicines was 641.2 patient-years of treatment with most (94%) of the exposure being to risperidone. The most common diagnoses were disruptive disorders. The symptoms most frequently targeted by the atypical antipsychotic were aggression and difficult behaviour. The treatment of sleep disorders as a target symptom was reported in 3% of children. A total of 131 (31 %) children experienced an adverse event. The most frequent adverse events reported were weight gain, severe dental caries and somnolence. The incidence of diabetes mellitus was 4 (95% CI 0.5,15) cases per 1000 patient-years of treatment in this study. Four children prescribed risperidone developed symptoms of depression, giving an incidence of 8 (95% CI 2.0, 21) cases per 1000 patient-years of treatment.
Conclusions: This study provides a picture of ‘real-life’ use of atypical antipsychotics in a nationwide cohort of children. Most prescriptions were for risperidone and the most common diagnoses were disruptive disorders. Investigation of the symptoms targeted by these medicines identified unexpected use for the treatment of sleep disorders. Regarding safety, symptoms of depression were identified as a potential new signal for risperidone in the paediatric population. Further research is now required to investigate this.
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Acknowledgements
The New Zealand Ministry of Health (Medsafe) provided the majority of the funding for this study. The Intensive Medicines Monitoring Programme has also received unconditional donations (for general support of the programme) from some pharmaceutical companies, including Janssen-Cilag (manufacturer of risperidone) and Novartis (manufacturer of clozapine) in New Zealand. However, no pharmaceutical company had any role in the design, conduct or analysis of this study.
The authors have no conflicts of interest that are directly relevant to the content of this study.
We would like to acknowledge the contribution of Dr Rachael McLean, clinical research fellow at the IMMP during the time this study was performed, for assessing the majority of the clinical events identified. We are also grateful for advice provided by Professor Charlotte Paul (Chair of Preventive and Social Medicine, University of Otago) and Professor Peter Ellis (Professor of Psychiatry, University of Otago, Dunedin). Both Professors Paul and Ellis advised on the design and conduct of this study.
This study was dependent on the accuracy of data entry and data processing performed by the IMMP Team —Kaylene Crawford, Richard Weeks, Jayne Faitala and Elizabeth Watson.
Dr Mira Harrison-Woolrych conceived and designed this study, supervised the conduct of the study, is responsible for the raw data collected, supervised and checked the clinical assessments performed, designed and conducted the analyses, interpreted the findings (with the other authors) and wrote the manuscript.
Dr Juan Garcia-Quiroga advised on the design of this study, in particular the clinical aspects of the follow-up questionnaire. He has been involved with the study from its inception and helped with liaison with child and adolescent psychiatrists throughout New Zealand. He also helped perform literature searches, has reviewed all drafts of the manuscript and approved the final version.
Mrs Janelle Ashton was responsible for all data extraction from the IMMP databases for this study, performed the required analyses and contributed to interpretation of the data. She has also reviewed all drafts of the manuscript and approved the final version.
Associate Professor Peter Herbison provided biostatistical advice on the design of this study and the analyses performed. He has also reviewed the manuscripts and approved the final version.
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Harrison-Woolrych, M., Garcia-Quiroga, J., Ashton, J. et al. Safety and Usage of Atypical Antipsychotic Medicines in Children. Drug-Safety 30, 569–579 (2007). https://doi.org/10.2165/00002018-200730070-00002
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DOI: https://doi.org/10.2165/00002018-200730070-00002