The purpose of this study is to examine the safety and efficacy of Depakote ER in bipolar depression and to evaluate metabolic and GABA changes with Depakote ER administration using PET and MRI/MRS brain imaging techniques.

Mood disorders are important public health problems. Bipolar disorder is a major psychiatric disorder characterized by mood cycles alternating between mania and depression and affects approximately 1% of the population. Most patients are treated beginning in the early twenties and then embark on a course marked by multiple recurrences, hospitalizations, and encounters with legal authorities. These disorders inflict substantial morbidity which yields important deficits in occupational and interpersonal function. The risk of suicide in mood disorders may be as high as 10%.

Although the outlook for recovery from acute manic or depressive episodes is generally excellent, the long-term prognosis of the disorder varies tremendously across the patient population. The introduction of lithium, anticonvulsants and atypical antipsychotics significantly changes the outlook for bipolar disorder, with some individuals on chronic treatment attaining complete remission and indefinite prophylaxis against mood episodes. However, such optimum outcomes may be limited to as few as one-third to one-half of all treated patients. The remaining experiences various combinations of breakthrough mood episodes, including chronic mood instability, persistent depression, and rapid cycling.

Very little research has been conducted with bipolar disorder, and no medications have an FDA indication to treat bipolar depression. Previous studies suggest that Depakote is promising in the treatment of mixed and depressed episodes of bipolar disorder. This study utilizes the extended release formulation of divalproex sodium, with demonstrated increased tolerability.

We propose investigating safety, tolerability and efficacy of Depakote ER monotherapy in Bipolar I, II or NOS depression, and monitoring associated changes in brain GABA levels. In addition, we intend to evaluate and assess the differences between brain metabolic rate and GABA levels in bipolar disorder patients and healthy volunteers.

Inclusion Criteria:

• Bipolar I, II or NOS currently suffering from depression
• Both: both female and male participants are being studied
• Adults 18 years and older of any race

Exclusion Criteria:

• Schizophrenia or schizoaffective disorder and other disorders excluded at the discretion of the investigator's discretion
• Substance dependence within the past 3 months and abuse within the past 2 weeks prior to study.
• Positive screen for psychoactive drugs, stimulants or drugs of abuse (excluding marijuana, as long as dependence and abuse are ruled out according to DSM-IV)
• Significant risk harm to self or others based on history and mental status exam
• Clinically significant or unstable medical condition
• Unstable thyroid pathology and treatment initiated or altered within the past 3 months
• Clinically significant abnormal laboratory test results, vital signs, as judged by the investigators
• Women pregnant or nursing, or WOCBP who do not use adequate contraception or who are judged to be unreliable in their use of contraception
• Subjects who failed (because of inefficacy or adverse effects) an adequate trial of Depakote; eligible patient's may not have received Depakote within 30 days of screen

This trial is limited by small sample size, as well as an open-label study design with no placebo control.