12- Week Open Label Treatment of Refractory Bipolar Depression

)Determine the change in symptomatology and function in refractory bipolar depression, when
treated with combination of DEP+AZP for a period of 12 weeks

2) Determine the tolerability and safety of AZP added to DEP in the treatment of refractory
bipolar depression

Inclusion Criteria:

- diagnosis of bipolar disorder I or II according to MINI

- patient has signed informed consent

- male, or female who is using effective birth control if of child bearing age

- age 18 and above

- currently in a depressed phase, with or without psychotic features, of the illness
based on DSM-IV/MINI criteria

- score of 19 on the MADRS

- history of treatment refractory bipolar depression as defined by failure of the
depressive episode to respond to a mood stabilizer alone or a combination of 2 or
more mood stabilizers or a combination of a mood stabilizer and an antidepressant

Exclusion Criteria:

- current liver disease,

- illness precluding the use of DEP

- patients who have been treated with a DEP and AZP combination in the past

- Alcohol/drug dependence in the past one month

- CNS neoplasms, demyelinating diseases, degenerative neurological condition or active
CNS infection

- history of seizure, known EEG with frank paroxysmal activity, known CT of brain
showing gross structural abnormalities, cerebral vascular disease by history or
structural brain damage from trauma

- thyroid dysfunction

- unstable general medical condition

- require antipsychotic other than AZP