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

Abstract

BackgroundYouth 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.MethodsThe 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.ResultsThe 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.ConclusionAntipsychotic-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 registrationClinical Trials.gov NCT00806234

BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment

“…Some of the questions that cannot be answered adequately from current data may be resolved on the completion of a currently running, 6-month, open-label, randomised trial of metformin and healthy lifestyle education in antipsychotic-treated children and young people (aged 8-19 years), with significant weight gain, in the USA (Reeves et al, 2013).…”

Practical pharmacotherapy in child psychiatry: an update

“…Medicines are effective, but findings from research trials show the effects sizes, with the notable exception of stimulants for ADHD, to be low to medium. Furthermore, medicines can have considerable side-effects; indeed, the weight gain with second-generation antipsychotics has been described as a potential public health crisis (Reeves 2013). In our experience, despite these reservations, clinical practice, especially with the more ill patients, shows that medicines are a vital component of child psychiatry.…”

Metformin add‐on vs. antipsychotic switch vs. continued antipsychotic treatment plus healthy lifestyle education in overweight or obese youth with severe mental illness: results from the IMPACT trial

“…The Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) was a randomized, unmasked parallel group clinical trial, approved and monitored by the Institutional Review Boards at Zucker/Hillside Hospital, Johns Hopkins University, University of Maryland, and University of North Carolina at Chapel Hill. It was funded by the US National Institute of Mental Health (NIMH).…”