Improving metabolic parameters of antipsychotic child treatment (IMPACT) study: Rationale, design, and methods

Child and Adolescent Psychiatry and Mental Health 08/2013; 7(1):31. DOI: 10.1186/1753-2000-7-31
Source: PubMed


Youth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) study, a federally funded, randomized trial comparing two pharmacologic strategies against a control condition to manage SGA-related weight gain.
The design and methodology considerations of the IMPACT trial are described and embedded in a description of health risks associated with antipsychotic-related weight gain and the limitations of currently available research.
The IMPACT study is a 4-site, six month, randomized, open-label, clinical trial of overweight/obese youth ages 8--19 years with pediatric schizophrenia-spectrum and bipolar-spectrum disorders, psychotic or non-psychotic major depressive disorder, or irritability associated with autistic disorder. Youth who have experienced clinically significant weight gain during antipsychotic treatment in the past 3 years are randomized to either (1) switch antipsychotic plus healthy lifestyle education (HLE); (2) add metformin plus HLE; or (3) HLE with no medication change. The primary aim is to compare weight change (body mass index z-scores) for each pharmacologic intervention with the control condition. Key secondary assessments include percentage body fat, insulin resistance, lipid profile, psychiatric symptom stability (monitored independently by the pharmacotherapist and a blinded evaluator), and all-cause and specific cause discontinuation. This study is ongoing, and the targeted sample size is 132 youth.
Antipsychotic-related weight gain is an important public health issue for youth requiring ongoing antipsychotic treatment to maintain psychiatric stability. The IMPACT study provides a model for pediatric research on adverse event management using state-of-the art methods. The results of this study will provide needed data on risks and benefits of two pharmacologic interventions that are already being used in pediatric clinical settings but that have not yet been compared directly in randomized trials.Trial registration: Clinical NCT00806234.

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    • "Although some guidelines have been developed for the monitoring of these adverse events, adherence to these guidelines by practitioners has been suboptimal.6 In addition, there have been few evidence-based approaches developed to manage these side effects.7 However, in response to the alarming increase in antipsychotic prescriptions for youth in Canada, a panel entitled Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) was formed to review systematically the side-effect burden of the most common SGAs.8 "
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    Adolescent Health, Medicine and Therapeutics 09/2014; 5:171-82. DOI:10.2147/AHMT.S49807
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    ABSTRACT: Introduction: Typical and atypical antipsychotics are efficacious treatments for early-onset schizophrenia (EOS) with very subtle differences in their efficacy. Therefore, when choosing an antipsychotic, the side-effect profile of the individual antipsychotic needs to be taken into account. There is a growing body of neurobiological and genetic evidence for early-onset patients, but these findings have not yet translated into the clinic. Areas covered: The authors summarize the current treatment options for EOS and discuss the novel treatment options that are under evaluation. The authors focus specifically on Phase II and Phase III clinical trials. Expert opinion: Currently, there are no truly groundbreaking pharmacological treatment options emerging in EOS. There are several newer antipsychotic agents (iloperidone, lurasidone, asenapine, blonanserin) that are currently in clinical trials. It is unclear whether therapeutic efficacy of any of these agents will be superior or even similar to the existing treatment and the main differentiating factor between individual drugs remains to be their side-effect profile. Beyond these antipsychotics, oxytocin and N-acetylcysteine are the only new pharmacological treatment options that are being evaluated in EOS. Therefore, a major change in the treatment development paradigm is necessary to identify novel and efficacious drugs.
    Expert Opinion on Investigational Drugs 06/2014; 23(11):1-10. DOI:10.1517/13543784.2014.933806 · 5.53 Impact Factor
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    ABSTRACT: Background While studies have suggested an increased prevalence of Obstructive Sleep Apnea (OSA) in adults with Bipolar Disorder (BPD), little is published about children with BPD. Behavioral difficulties including emotional liability, depression and poor school performance are commonly reported in children with either BPD or OSA. Comorbid medical disorders may exacerbate the course of BPD. We reviewed demographic and polysomnogram characteristics of children with BPD to help outpatient identification of OSA. Methods A single center retrospective chart review of children with BPD referred for a polysomnogram (PSG) over a ten-year period was conducted. There were 27 children identified whose diagnosis of BPD was independently verified by a child psychiatrist using DSM-IV standard criteria. Results Six (22%) children had OSA with a median apnea–hyponea index of 7.5 events per hour. Variables that were significantly different between the OSA and non-OSA groups were: median BMI (47 vs 30 kg/m2, p=0.001); sleep efficiency (78.2% vs 91%, p=0.009); and oxygen saturation nadir (82% vs 92%, p=0.0003). There was no difference found in snoring percentage on PSG between the two groups. Limitations The retrospective design from a single tertiary center limited the cohort size. Only secondary verification of the diagnosis of BPD from the available medical record was possible. Conclusions Our findings suggest that extreme obesity (BMI >40 kg/m2), oxygen desaturation during sleep and frequent nocturnal awakenings are associated with OSA in children with BPD. Traditional clinical parameters for obesity and snoring, per se, are poor predictors of OSA in children with BPD.
    Journal of Affective Disorders 10/2014; 167:20–24. DOI:10.1016/j.jad.2014.05.037 · 3.38 Impact Factor
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