Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar

• All subjects along with their parents will undergo
  
• semi-structured interviews, and assessments for side effects. The following rating scales will be administered: the Young Mania Rating Scale (YMRS),
  
• Bipolar Clinical Global Impression Scale (BP-CGI),
  
• Overt Aggression Scale (OAS) ,
  
• Child Depression Rating Scale-Revised (CDRS-R),
  
• Brief Psychiatric Rating Scale in Children (BPRS-C),
  
• Child Bipolar Rating Scale- Parent version (subscales: Child Mania Rating Scale,
  
• Child Bipolar Depression Rating Scale,
  
• Child Bipolar Cycling Rating Scale) and
  
• Teacher version (subscales: Child Mania Rating Scale, Child Bipolar Depression Rating Scale)(CBRS-P/T),
  
• Abnormal Involuntary Movements Scale (AIMS),
  
• Adverse Events Rating Scale for Bipolar Disorder (AERS-BP) at the initial Screen, and every week for 6 weeks after starting the medication treatment.
  

• Teachers will be asked to complete the Child Bipolar Rating Scale every week for 6 weeks
  

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: