Treatment Study of Bipolar Depression

Inclusion Criteria: 1. Male or female patients, 21-70 years; 2. Primary diagnosis of bipolar I or II disorder as assessed by the SCID-P and confirmed by a study psychiatrist; 3. Current depressive episode ≥ 8 weeks duration; 4. History of a failure to respond to at least three (3) adequate pharmacotherapy trials in the current depressive episode (see above for definition for adequate trials); 5. Subjects must be on a stable dose of divalproex ER with serum levels greater than 55 mcg/ml prior to enrollment; 6. Subjects must be free of psychotropic medication for at least 2 weeks (4 weeks for fluoxetine) prior to enrollment (with the exception of divalproex ER as above); 7. Subjects must have scored ≥ 32 on the IDS-C30 at both Screening and Infusion Day #1 and #2; Exclusion Criteria: 1. Women who plan to become pregnant, are pregnant or are breast-feeding; 2. Any unstable medical illness including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease; 3. Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG; 4. Lifetime history of schizophrenia, schizoaffective disorder, OCD, mental retardation, pervasive developmental disorders, or Tourette's syndrome; 5. Current presence of psychotic, mixed or manic symptoms; 6. Lifetime history of antidepressant-induced switch to a manic episode; 7. History of rapid cycling bipolar subtype; 8. Drug or alcohol abuse within the preceding 3 months or dependence within the preceding 5 years; 9. Lifetime exposure to ketamine or phencyclidine; 10. Patients judged by study investigator to be at high risk for suicide.