Study of Outcome and Safety of Lithium, Divalproex and Risperidone for Mania in Children and Adolescents

Study Overview
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Brief Summary
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This study will evaluate the effectiveness of the medications, lithium (Eskalith®), valproate (Depakote®), and risperidone (Risperdal®) in treating children and adolescents with bipolar disorder or symptoms of mania.

Detailed Description
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Patients are randomly assigned to receive lithium (Eskalith), valproate (Depakote), or risperidone (Risperdal) for 8 to 16 weeks. They will have weekly visits to monitor their response to the medication. When the study is complete, care will be transferred to the child's treating psychiatrist.

Official Title
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Treatment of Early Age Mania (TEAM) Study

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Drug: Lithium carbonate
* Drug: Valproate
* Drug: Risperidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DSM-IV criteria for bipolar I (manic or mixed) or mania for at least 4 weeks CGAS less than or equal to 60 Good physical health Exclusion Criteria: Schizophrenia or any pervasive developmental disorder Major medical or neurological disease History of addiction to illicit substances or alcohol or drug abuse within the last 4 weeks IQ less than 70 Pregnancy or breast-feeding Unacceptable methods of contraception In-patient care at baseline

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Participants will receive treatment with lithium for 8 to 16 weeks | Drug: Lithium carbonate<br>* Titrated until blood level is 1.1 to 1.3 mEq/L<br>|
| Experimental: 2<br>Participants will receive treatment with valproate for 8 to 16 weeks | Drug: Valproate<br>* Titrated until blood level is 111 to 125 ug/mL<br>* Other names: Depakote;|
| Experimental: 3<br>Participants will receive treatment with risperidone for 8 to 16 weeks | Drug: Risperidone<br>* Titrated by weight until dose is 2.0 mg BID to 3.0 mg BID<br>* Other names: Risperdal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impressions-Bipolar Mania Improvement | The Clinical Global Impressions-Bipolar (CGI-BP) assessment instrument measured improvement in mania, depression, and overall bipolar illness. The primary outcome measure was mania improvement, which measured the change in mania from baseline. Scores were 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse. | Measured at Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Side Effects Form for Children and Adolescents | The Modified Side Effects Form for Children and Adolescents includes 62 potential side effects, with measures of frequency and severity for each item. Frequencies are 0=not present, 1=1-2 days, 2=3-4 days, 3=5-7 days. Severity scores are 0=not present, 1=mild (does not interfere with functioning), 2=moderate (some interference with functioning), 3=severe (functioning is significantly impaired because of side effects). Items for cardiovascular, gastrointestinal, central nervous system, ocular, mouth and nose, genito urinary, dermatology, musculo-skeletal, and other side effects are included. For analyses, side effects that were reported at any frequency and a severity of 2 or greater were considered present. | Measured at Week 8 | 
| K-SADS Mania Rating Scale | The K-SADS Mania Rating Scale (KMRS) is comprised of 15 items modified from WASH-U-KSADS items. The individual items are scored on a 1-6 severity scale and then these item scores are summed to create an overall KMRS score. Guidelines for interpretation are as follows: 0-11 = no or minimal mania, 12-17 = mild mania, 18-25 = moderate mania, 26+ = marked or worse mania. The maximum possible score is 64. | Measured at Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mania