Study of Depakote ER for the Treatment of Mania in Children Ages 6-12 With Bipolar Disorder

Inclusion Criteria: 1. Male or female subjects, 6-12 years of age. 2. Subjects must have a DSM-IV diagnosis of bipolar I, bipolar II disorder or bipolar spectrum disorder and currently displaying manic, hypomanic, or mixed symptoms (with or without psychotic features) according to the DSM-IV based on clinical assessment and confirmed by structured diagnostic interview (Kidd Schedule of Affective Disorders and Schizophrenia Epidemiological Version)(Kaufman, Birmaher et al. 1997). Bipolar spectrum disorder (or sub-threshold bipolar disorder) is operationalized as having severe mood disturbance, which meets DSM-IV Criteria A for bipolar disorder but meet fewer elements in criteria B (only require 2 items for elation category and 3 for irritability). 3. Subjects and their legal representative must have a level of understanding sufficient to communicate intelligently with the investigator and study coordinator, and to cooperate with all tests and examinations required by the protocol. 4. Subjects and their legal representative must be considered reliable. 5. Each subject and his/her authorized legal representative must understand the nature of the study. The subject's authorized legal representative must sign an informed consent document and the subject must sign an informed assent document. 6. Subjects must have an initial score on the Y-MRS total score of at least 20. 7. Subject must be able to participate in mandatory blood draws. 8. Subject must be able to swallow pills. 9. Subjects with comorbid ADHD, ODD, CD, anxiety and depressive disorders will be allowed to participate in the study provided they do not meet for any of the exclusionary criteria. 10. For concomitant stimulant therapy used to treat ADHD, subjects must have been on a stable dose of the medication for 1 month prior to study enrollment. The dose of the stimulant therapy will not change throughout the duration of the initial phase of the study. Exclusion Criteria: 1. Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild. 2. Serious, unstable illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease. 3. Uncorrected hypothyroidism or hyperthyroidism. 4. History of severe allergies or multiple adverse drug reactions. 5. Non-febrile seizures without a clear and resolved etiology. 6. Leukopenia or history of leukopenia without a clear and resolved etiology. 7. DSM-IV substance (except nicotine or caffeine) dependence within past 6 months. 8. Judged clinically to be at serious suicidal risk. 9. Any other concomitant medication with primarily central nervous system activity other than specified in Concomitant Medication portion of the protocol. 10. A non-responder or a history of intolerance to Divalproex Sodium Extended Release to an adequate trial (2 months or more at an adequate dose) as determined by the clinician. 11. Receiving treatment with Strattera. 12. Current diagnosis of schizophrenia. 13. Pregnant or nursing females. 14. Non English speaking subjects will not be allowed into the study for the following reasons: a) the assessment instruments are not available and have not been adequately standardized in other languages; b) our clinical trials facility is located in Cambridge and not in the MGH main campus without the availability of translators; c) psychiatric questionnaires and evaluations are taxing and adding the complexity of a translator has the potential to make the patient experience even more exhausting.