Antipsychotics for Children and Young Adults: A Comparative Effectiveness Review

Alberta Research Centre for Health Evidence, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
PEDIATRICS (Impact Factor: 5.3). 03/2012; 129(3):e771-84. DOI: 10.1542/peds.2011-2158
Source: PubMed

ABSTRACT Despite increasing on-label and off-label use of antipsychotics, prescribing antipsychotics to children remains controversial due to uncertainty of their relative benefits and safety. We systematically reviewed the effectiveness and safety of first- (FGA) and second-generation antipsychotics (SGA) for patients aged ≤24 years with psychiatric and behavioral conditions.
We searched 10 databases from January 1987 to February 2011, gray literature, trial registries, and reference lists. Two reviewers independently selected studies, assessed methodologic quality, and graded the evidence. One reviewer extracted, and a second verified, data. We summarized findings qualitatively and conducted meta-analyses when appropriate.
Sixty-four trials and 17 cohort studies were included. Most trials had a high risk of bias; cohort studies had moderate quality. All comparisons of FGAs versus SGAs, FGAs versus FGAs, and FGAs versus placebo had low or insufficient strength of evidence. There was moderate strength of evidence for the following comparisons. Olanzapine caused more dyslipidemia and weight gain, but fewer prolactin-related events, than risperidone. Olanzapine caused more weight gain than quetiapine. Compared with placebo, SGAs improved clinical global impressions (schizophrenia, bipolar and disruptive behavior disorders) and diminished positive and negative symptoms (schizophrenia), behavior symptoms (disruptive behavior disorders), and tics (Tourette syndrome).
This is the first comprehensive review comparing the effectiveness and safety across the range of antipsychotics for children and young adults. The evidence on the comparative benefits and harms of antipsychotics is limited. Some SGAs have a better side effect profile than other SGAs. Additional studies using head-to-head comparisons are needed.

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    • "In turn, these abnormalities are risk factors for later adult obesity, metabolic syndrome, cardiovascular morbidity, and malignancy (Correll et al. 2009). Olfson et al. (2010) pointed out that this risk is an especially important one to consider when making prescribing decisions for children and adolescents, as empirical support for the efficacy of atypical antipsychotics in this population is only now emerging and long-term safety studies are lacking (Seida et al. 2012). "
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    ABSTRACT: To alert professionals and consumers about safety risks associated with approved drugs, the U.S. Food and Drug Administration (FDA) periodically issues Drug Safety Communications, or DSCs (previously known as advisories, warnings, and health care professional letters). This review consolidates balanced information from 22 DSCs issued over the last 15 years by the FDA for drugs with pediatric indications (for any disorder) that are used to treat pediatric emotional and behavioral disorders (ADHD drugs, antipsychotics, antidepressants, and antiepileptics/anticonvulsants). A single-source document of pediatric DSCs for these drugs was needed because none existed previously; finding DSC information on the FDA website can be challenging; and other information sources (e.g., manufacturer or advocacy websites, blogs, other media reports) may lack the objectivity or accuracy that the FDA is charged to maintain. This consolidation is intended to enable better informed risk-benefit analysis around treatment selection and drug safety monitoring. For the 22 DSCs, we summarize the safety concerns, the populations affected, and when available from the FDA, the incidence of the adverse events, precursors, and factors that may increase or mitigate the risk of these very serious (e.g., sudden death, life-threatening rash, liver failure), but typically low incidence (<1 %) adverse events (cardiometabolic complications with atypical antipsychotics and suicidality with antidepressants are more common). This review does not address the far more common, but usually less serious, side effects that also accompany these drugs. Implications of this review for research and practice are discussed.
    Journal of Child and Family Studies 05/2014; 23(4). DOI:10.1007/s10826-012-9706-x · 1.42 Impact Factor
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    • "before as long as they can be tracked, regardless of age, and even after the discontinuation of antipsychotic treatment and, if possible, into adulthood. The selection of the systematically collected biological and physical safety parameters and scales was based on a literature review of possible adverse effects of antipsychotics in pediatric populations and on the recommendations of several scientific associations and expert groups dealing with children and adolescents treated with antipsychotics (Panagiotopoulos et al. 2010; Seida et al. 2012; Correll et al. 2006). We defined an adverse reaction as a response to a medicinal product which is noxious and unintended. "
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    ABSTRACT: Despite drastic increases in antipsychotic prescribing in youth, data are still limited regarding their safety in this vulnerable population, necessitating additional tools for capturing long-term, real world data. We present SENTIA (SafEty of NeurolepTics in Infancy and Adolescence;, an online registry created in 2010 to track antipsychotic adverse effects in Spanish youth <18 years old currently taking or initiating with any antipsychotic treatment. SENTIA collects information on sociodemographic, diagnostic and treatment characteristics, past personal medical/psychiatric history, healthy lifestyle habits and treatment adherence. Additionally, efficacy and adverse effect data are recorded including the Children's Global Assessment Scale; Clinical Global Impressions scale for Severity and Improvement, the Safety Monitoring Uniform Report Form, Simpson-Angus Scale, Abnormal Involuntary Movement Scale, vital signs, blood pressure, and EKG. Finally, fasting blood is drawn for hematology, electrolytes, renal, liver and thyroid function, glucose, insulin, lipid, prolactin and sex hormone levels. Initially, a diagnostic interview and several psychopathology scales were also included. Patients are assessed regularly and followed even beyond stopping antipsychotics. Since 01/17/2011, 85 youth (11.5 ± 2.9 (range = 4-17) years old, 70.6% male) have been included at one inaugural center. After a mean duration of 17 ± 11 (range = 1-34) months, 78.8% are still actively followed. For feasibility reasons, the diagnostic interview and detailed psychopathology scales were dropped. The remaining data can be entered in <30 minutes. Several additional centers are currently being added to SENTIA. Implementation of a systematic online pharmacovigilance system for antipsychotic adverse effects in youth is feasible and promises to generate important information.
    SpringerPlus 04/2014; 3:187. DOI:10.1186/2193-1801-3-187
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    • "Second generation antipsychotic prescribing to young people under 25 years of age is increasing internationally [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]. The rise in prescription trends has generated controversy given available pediatric evidence for second generation antipsychotic effectiveness and safety data and the unknown longterm consequences with intermittent or continuous exposure [13] [14] [15] [16]. Antipsychotic-related weight gain and changes in the metabolic profile (e.g., glucose and lipid homeostasis) that occur following, or in concert with, weight gain are frequently discussed as significant treatment-related issues. "
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    ABSTRACT: Objectives . To explore the lived experience of youth, caregivers, and prescribers with antipsychotic medications. Design . We conducted a qualitative interpretive phenomenology study. Youth aged 11 to 25 with recent experience taking antipsychotics, the caregivers of youth taking antipsychotics, and the prescribers of antipsychotics were recruited. Subjects . Eighteen youth, 10 caregivers (parents), and 11 prescribers participated. Results . Eleven of 18 youth, six of ten parents, and all prescribers discussed antipsychotic-related weight gain. Participants were attuned to the numeric weight changes usually measured in pounds. Significant discussions occurred around weight changes in the context of body image, adherence and persistence, managing weight increases, and metabolic effects. These concepts were often inextricably linked but maintained the significance as separate issues. Participants discussed tradeoffs regarding the perceived benefits and risks of weight gain, often with uncertainty and inadequate information regarding the short- and long-term consequences. Conclusion . Antipsychotic-related weight gain in youth influences body image and weight management strategies and impacts treatment courses with respect to adherence and persistence. In our study, the experience of monitoring for weight and metabolic changes was primarily reactive in nature. Participants expressed ambiguity regarding the short- and long-term consequences of weight and metabolic changes.
    11/2013; 2013(1):390130. DOI:10.1155/2013/390130
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