Metabolic Effects of Antipsychotics in Children
Condition: Aggression; Attention Deficit-Hyperactivity; Oppositional Defiant Disorder; Pervasive Development Disorders; Bipolar Disorder
MeSH terms: Bipolar Disorder; Aggression; Attention Deficit and Disruptive Behavior Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder
Intervention: risperidone; olanzapine; aripiprazole
Intervention description: randomized to begin 12 week trial of risperidone; randomized to begin 12 week trial of olanzapine; randomized to 12 week trial of aripiprazole
Intervention MeSH terms: Olanzapine; Risperidone; Aripiprazole
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 144.0
Sex: All
Minimum age: 6 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Antipsychotic treatment; Insulin action/secretion; Abdominal fat mass, total body fat; Aggression; Resting metabolic rates

Summary:

      The project aims to describe and compare the outcome of 12 weeks of prospective, randomized
      treatment with olanzapine, risperidone or aripiprazole on insulin action in skeletal muscle,
      liver and adipose tissue, abdominal fat mass, total body and fat-free mass, efficacy for
      symptoms of aggression and non-metabolic adverse events. Children aged 6-18 will be studied,
      exploring effects of stimulant therapy and age-related differences in vulnerability to
      treatment-induced adverse metabolic changes. Aims are addressed by measuring glucose and
      lipid kinetics with stable isotope tracers, body composition with dual energy x-ray
      absorptiometry and magnetic resonance imaging (MRI), and standardized assessments of efficacy
      and adverse events. Relevant data are critically needed to target clinical therapy and basic
      research, identify medical risks, and guide regulatory decisions in this vulnerable
      population.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Aged 6-18 years

          -  Generally healthy and a score of ≥ 18 on the Aberrant Behavior Checklist in the
             context of one or more Axis I Diagnostic and Statistical Manual of Mental Disorders,
             Fourth Edition (DSM-IV) childhood psychiatric disorders, including conduct disorder,
             oppositional defiant disorder, disruptive behavior disorder, autism, pervasive
             developmental disorder, attention deficit disorder, schizophrenia and bipolar
             affective disorders

          -  Children's Global Assessment Scale (CGAS) score ≤ 60

          -  Not previously treated with an antipsychotic; individual subjects with remote, brief
             prior antipsychotic exposure may be considered for enrollment by the PI on a case by
             case basis

          -  Patient assent and informed consent obtained from the parent or guardian

          -  No clinically significant (based on PI determination) changes in permitted medications
             (e.g., stimulants and selective serotonin reuptake inhibitors [SSRIs]) for
             approximately 1 month prior to Baseline evaluations

        Exclusion Criteria:

          -  Active suicidality or primary dx of major depressive disorder

          -  Any lifetime use of antipsychotics or non-serotonin selective reuptake inhibitor
             (non-SSRI) anti-depressants

          -  The presence of any serious medical disorder, based on PI determination, that may
             confound the assessment of relevant biologic measures or diagnoses, including:

               -  significant organ system dysfunction;

               -  endocrine disease, including type 1 or type 2 diabetes mellitus;

               -  coagulopathy;

               -  anemia;

               -  or acute infection.

          -  Subjects regularly taking any glucose lowering agent, lipid lowering agent, exogenous
             testosterone, recombinant human growth hormone, or any other endocrine agent that
             might confound substrate metabolism, oral glucocorticoids (glucocorticoid inhalants
             and nasal sprays are permitted), antihistamines, sedating antihistamines (non-sedating
             antihistamines such as but not limited to Claritin (loratadine) and Zyrtec
             (cetirizine) are permitted), and certain mood stabilizing agents, as some medications
             may themselves worsen or otherwise alter weight gain, glucose and lipid regulation or
             otherwise make it difficult to assess the effects of the antipsychotic alone; (note
             that exposure to many psychotropic agents including stimulants and SSRI's is permitted
             in order to maintain the generalizability of the sample);

          -  Intelligence quotient (IQ) < 70 (based on school records and/or evaluation by
             clinician)

          -  current substance abuse

          -  Past history or currently has dyskinesia

          -  Stimulant dosage significantly higher (per PI judgment)than the equivalent of
             approximately 2mg/kg/day methylphenidate equivalent dose.