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.