Side Effect Study of Antipsychotic Medicines to Treat Childhood Bipolar Disorder

This protocol is a six month, randomized, open label trial of risperidone versus aripiprazole
in antipsychotic naive youth (7 - 12 years old) who have been identified by their clinical
treatment provider as needing antipsychotic treatment of a bipolar disorder.

This study proposes to monitor changes in metabolic parameters (body mass index percentile, %
body fat, insulin resistance, and lipid levels) over the course of six months treatment with
aripiprazole or risperidone in youth with a bipolar spectrum disorder. We will also assess
possible mechanisms of second generation antipsychotic induced weight gain by monitoring
physical activity and hunger/appetite changes over the course of treatment.

Inclusion Criteria:

- We will include children, ages 7 - 12 years old, male and female with diagnosis of a
bipolar spectrum disorder.

- Specific diagnoses included are as follows:

- Bipolar I disorder,

- Bipolar II disorder,

- Bipolar Disorder Not Otherwise Specified,

- Mood Disorder Not otherwise specified.

- The inclusion of a spectrum of bipolar diagnosis is because children with moderate to
severe impairment from mood symptoms often still do not meet criteria for Bipolar I
disorder since young children tend to have more chronic (non-episodic) course of
symptoms and diagnostic criteria for Bipolar I disorder are more difficult to apply to
adults than young children (e.g. symptoms of grandiosity and euphoria).

- No prior treatment with an antipsychotic medication for >30 days. This criteria was
added because weight loss on an assigned treatment may be due to discontinuing a prior
antipsychotic medication rather than due to the current treatment.

- Recommendation from a current psychiatric treatment provider for treatment with an
antipsychotic medication.

- This inclusion criteria provides an added layer of safety in that youth who have
referred for the study have already been deemed by their independent provider to need
an antipsychotic medication, so we are only exposing children to antipsychotic
treatment who would have been treated with this type of medication regardless of
whether or not there care was provided in a research or clinical program.

Exclusion Criteria:

- Medications: We will exclude children who are on current treatment with

- oral steroids,

- lithium,

- depakote since these medications will have a confounding effect on weight.

- We will allow children on stimulant medication to participate, because ADHD
comorbidity is very high in prepubertal bipolar disorder (unlike adolescent or adult
onset bipolar disorder).

- We are including ADHD children to thus increase generalizability of the study, and it
would be inappropriate to withhold stimulant treatment from these children for a six
month period.

- Recruitment will be stratified to make sure there are equal numbers of patients on
stimulants in each group.

- Somatic Conditions: We will exclude children with diabetes (type I or type II), and
those with physical disability that would interfere with physical activity (will
specifically exclude children whose guardian reports that the child has been medically
excused from physical education at their school program because of physical
disability) since insulin sensitivity and activity levels are outcome measures being
assessed in this protocol.

- We will exclude youth with mental retardation, by parent report. Cognitive screening
will be done with the Wechsler Abbreviated Scale of Intelligence (WASI).

- Youth with an IQ less than 70 will be excluded because they may have difficulty with
self report measures.

- We will exclude children who have a history of treatment of an antipsychotic
medication for >30 days, as explained above.