Movement Disorders in Children and Adolescents Receiving Antipsychotic Pharmacotherapy: A Population-Based Study

By Biscontri, Robert G.; Jha, Sarita et al. | Journal of Child and Adolescent Psychopharmacology, December 2017 | Go to article overview

Movement Disorders in Children and Adolescents Receiving Antipsychotic Pharmacotherapy: A Population-Based Study


Biscontri, Robert G., Jha, Sarita, Collins, David M., Bugden, Shawn, Katz, Laurence Y., Alessi-Severini, Silvia, Journal of Child and Adolescent Psychopharmacology


Address correspondence to: Silvia Alessi-Severini, PhD, College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, 750 McDermot Avenue, Winnipeg R3E 0T5, Manitoba, Canada, E-mail: silvia.alessi-severini@umanitoba.ca

Introduction

Children are particularly sensitive to drug-induced movement disorders (Campbell et al. 1983; Derinoz 2013) and risperidone has been recognized as the second-generation agent (SGA) more likely to cause movement disorders because of its higher affinity for the dopamine D2 receptor (Seeman 2006).

High rates of prescribing antipsychotics to children and adolescents have been reported in recent years (Alessi-Severini et al. 2012; Patten et al. 2012; Zito et al. 2013; Olfson et al. 2015; Bachmann et al. 2014; Hartz et al. 2016; Huskamp et al. 2016). Official indications of SGAs in pediatric populations vary across countries (Penfold et al. 2013; Bachmann et al. 2014; Huskamp et al. 2016). FDA-approved use for risperidone, olanzapine, quetiapine, and aripiprazole in children and adolescents includes schizophrenia and bipolar disorder; riperidone and aripiprazole are also approved for the treatment of aggressive behaviors in young patients diagnosed with autism spectrum disorder (Penfold et al. 2013; Huskamp et al. 2016). In Canada, only aripiprazole is indicated for adolescents diagnosed with schizophrenia or bipolar disorder (Health Canada 2015); the official product monographs of the other SGAs explicitly state that the safety and efficacy of such products have not been established in children under the age of 18 years (Health Canada 2015). As a result, the use of antipsychotics in pediatric populations has largely been off-label (Alessi-Severini et al. 2012; Murphy et al. 2013; Burcu et al. 2014; Huskamp et al. 2016).

The aims of this study were to describe incidence rates of antipsychotic use in children and adolescents (≤19 years of age) in the province of Manitoba (Canada) and to assess the risk for movement disorders in patients treated with risperidone compared with those treated with quetiapine, which is currently the second most used antipsychotic agent prescribed to children in Canada (Alessi-Severini et al. 2012; Murphy et al. 2013; Pringsheim and Gardner 2014).

Methods

This study was a population-based retrospective cohort of all children and adolescents (age 0-19 years) living in the Canadian province of Manitoba (total population ∼1.2 M) served by a universal healthcare system.

Data were obtained from the administrative healthcare databases of the Manitoba Population Health Research Data Repository housed at the Manitoba Centre for Health Policy (MCHP). The Repository is a comprehensive collection of administrative, registry, survey, and other data relating to virtually all registered residents of the province. All individual contacts with the universal provincial healthcare system, including physician visits, hospitalizations, and pharmaceutical prescriptions, are captured and linkable through the use of one 9-digit identifier, which is scrambled to protect privacy (Brownell et al. 2006; Fransoo et al. 2008). Data are suppressed (not revealed or published) when the number of persons or events involved is five or less. This process of suppressing data is conducted to avoid potential identification of individuals residing in areas of low-density population. Databases accessed and linked included the Manitoba Health Insurance Registry, Drug Program Information Network (DPIN), Hospital Abstracts, Medical Services, Statistics Canada Census, and Vital Statistics.

Incident rates of second-generation antipsychotic use between April 1, 1996, and March 31, 2011, were described. Incident users were defined as individuals ≤19 years of age at the date of their first antipsychotic prescription (no previous use of any antipsychotic in the year prior). Individuals with a pre-existing condition of a movement disorder identified by the appropriate diagnostic codes (ICD-9-332, 333, 781 and ICD-10-G20-G26) or a prescription for a medication to treat the condition were excluded, subjects who spent >25% of the year before cohort entry in hospital were also excluded from the study (as the DPIN database does not include information on prescriptions administered in hospitals). …

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