The purpose of this study is to assess the efficacy and safety of continued combination therapy using Depakote plus olanzapine, vs. Depakote monotherapy and olanzapine monotherapy in stable subjects during the maintenance phase of bipolar illness.

Inclusion Criteria:

• DSM-IV-TR primary diagnosis of Bipolar I Disorder as confirmed by the SCID
• Outpatient receiving treatment with a combination of Depakote plus olanzapine for their bipolar illness and considered clinically stable (e.g., no more than minimal symptoms, no psychiatric hospitalizations, no increase in intensity of clinical interventions) for the preceding 4 months
• Identified at Screening a most bothersome side effect listed in the UKU which makes switching to monotherapy desirable
• MRS total score < 12 on two consecutive ratings, separated by at least 5 days (Screening and Day 1)
• DSS score < 13 on two consecutive ratings, separated by at least five days (Screening and Day 1)
• CGI-S score < 3 on two consecutive ratings, separated by at least five days (Screening and Day 1)
• Serum valproate level > 45 mcg/mL, and a maximum allowable dose of Depakote of 3000 mg/day at Screening
• Olanzapine dose between 5 and 20 mg/day at Screening

Exclusion Criteria:

• History of schizophrenia or schizoaffective disorder
• Axis I (e.g., anxiety disorder) or Axis II (e.g., personality disorder) that would interfere with compliance or confound interpretation of study results
• Has taken antipsychotics, mood stabilizers, or anticonvulsants (unless specifically for seizure control) other than Depakote or olanzapine in the four months prior to randomization. Other psychotropics (e.g., antidepressants, anxiolytics) with the exception of stimulants, that have been used routinely to maintain stability in the preceding four months may be continued, but not increased or decreased
• Has first manic episode after age 60
• Has ever taken clozapine
• Has received depot neuroleptic medication within six months of randomization
• Urine toxicology screen is positive for phencyclidine (PCP), opiates, cocaine or amphetamines
• History of active alcohol or substance abuse/dependence within 90 days prior to Screening
• Known history of non-response to either Depakote or olanzapine monotherapy for the treatment of bipolar disorder