Placebo Controlled Trial of Valproate and Risperidone in Young Children With Bipolar Disorders

It is now recognized that pediatric bipolar disorders are highly prevalent and that they seriously disrupt the lives of children and adolescents, with studies showing poorer academic performance, disturbed interpersonal relationships, increased rates of substance abuse, legal difficulties, multiple hospitalizations, and increased rates of both suicide attempts and completions (Akiskal, Downs et al. 1985; Lewinsohn, Klein et al. 1995; Strober, Schmidt-Lackner et al. 1995). We are seeing an increasing number of very young children, ages 3-7 years, with either frank symptoms of BP I disorder. Over 50% of these young patients have a first-degree relative with a bipolar disorder and all of these patient's families are significantly impacted by their BP symptoms. Many of these young BP patients have been treated with stimulants or antidepressants and few have been treated with mood stabilizing agents. Therefore, it is necessary to provide controlled studies of psychotropics in this younger bipolar population to provide clinical practice with an appropriate evidence-base.

Several major questions exist about these very young bipolar patients:

• What is the response of these very young bipolar patients to mood stabilizers and or atypical antipsychotics?
• Will non-responders to mono-therapy with either valproate or risperidone respond to treatment with both agents?
• How can we best characterize these patients clinically?
• What is the long-term outcome of these patients?
• Will earlier treatment lead to better outcomes?

The clinical use of mood stabilizers and atypical antipsychotic agents in children and adolescents with bipolar disorders has increased significantly over the past few years, despite the fact that only limited research has suggested that these agents are effective in this population. Common clinical practice is to have patients continue on medications for some time following remission, although the length of continuation treatment varies and available guidelines are based on consensus, not controlled trials. The increased number of medications prescribed has led to concern about over prescribing of psychotropics in children and adolescents (Zito, Safer et al. 2000; Zito, Safer et al. 2003). Therefore, it is necessary to provide additional controlled studies of mood stabilizing agents in this younger bipolar population to guide clinical practice.

There is an overwhelming need for controlled trials of the various mood stabilizers and atypical antipsychotics that are now available and being used in the community with these young bipolar patients. Currently, we have the most experience with valproate and risperidone in bipolar children, ages 8 - 17 yr. and based on clinical experience, believe that these two agents are the safest and most likely to be efficacious in children ages 3-7 years. These agents are widely used in the community and controlled data are desperately needed regarding the effectiveness of these agents in bipolar children, ages 3-7 years. There are no specific behavioral treatments or psychotherapies that have been shown to be efficacious for these patients.