Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar

Pediatric Bipolar Disorder (PBD) severely impairs a child's emotional development, and is
associated with alarming rates of suicide, school failure, aggression, risk taking behaviors
and substance abuse (Geller et al, 1998; 2001; Carlson et al, 1998). At present, very little
is known about the pathophysiology or optimal treatment of PBD. The long range goals of this
proposal are threefold: to investigate a range of pharmacotherapeutic agents that are safe
and efficacious for PBD, to use fMRI techniques to examine abnormalities in brain function
in this disorder, as well as any change in brain function after treatment.

In contrast to the adult literature, we are aware of only two prospective studies assessing
the efficacy of standard mood stabilizers in a pediatric sample. In one, lithium was found
to be moderately effective in PBD with comorbid substance abuse (Geller et al, 1998). In the
other, divalproex sodium, lithium and carbamazepine produced a maximum of 50% symptom
reduction (Kowatch et al, 2000). Subsequently, Kafantaris et al (2001) observed a
potentiation of lithium's antimanic effect when combined with risperidone. Further, a
prospective, open trial of olanzapine for PBD reported a 70% symptom reduction (Frazier et
al, 2001) with a retention rate of 96% compared to only 7% with classic mood stabilizers
(Kowatch et al, 2000).

Thus, parallelling adult studies (Sachs et al, 2000), novel antipsychotics are a promising
treatment in this population. Further, up to 60% of acute PBD episodes present with
psychotic features (Geller et al, in press). Finally, the time to full effect with mood
stabilizers is often 4 weeks in children (Kowatch et al, 2000; Geller et al, 1998;
Kafantaris et al, 2001), whereas antipsychotics usually have a more rapid response onset
(Pavuluri et al, in press). Given the potential efficacy of novel antipsychotics for PBD,
the aim is to conduct a randomized trial comparing a novel antipsychotic to a standard mood
stabilizer:

Inclusion Criteria:

- Children with Bipolar Disorder

- Must be able to swallow tablets

Exclusion Criteria:

- Children with general medical condition such as head injury, epilepsy, endocrine
disorders

- Those who are on mood altering medications such as steroids, and those diagnosed with
mental retardation are excluded to avoid confounding and contributing factors to mood
swings.

- If we discover during the interview that the parent and/or child does not understand
the consent/assent procedures, we will exclude them.

We expect only a small number of children to be excluded from the study due to
exclusionary criteria. Selection of the subjects is not based on sex, race, or ethnic
group.