This study seeks to investigate whether tranylcypromine (Parnate®) might be an effective treatment of bipolar depression. New treatments are needed, as there is little evidence that standard antidepressants are effective in treating this condition, and the two antipsychotic medications that have indications for bipolar depression can cause substantial side effects. This study will focus specifically on currently depressed outpatients having a bipolar history for whom at least one standard antidepressant medication was ineffective. Patients will be treated openly with tranylcypromine for 8-10 months, depending on treatment response.

Inclusion Criteria:

1. History of Bipolar I, II
2. Currently depressed (major depressive episode or depression NOS)
3. Physically healthy or physically stable (i.e.,No changes in medical interventions in past three months or likely for the next three months)
4. On stable and effective mood stabilizer or hypomania deemed sufficiently mild to not require a mood stabilizer.
5. Prior adequate trial on at least one antidepressant.
6. Able to follow a tyramine-free diet
7. Must speak English

Exclusion Criteria:

1. Current psychosis
2. past psychosis not occurring during an episode of mania or depression
3. prior nonremission to tranylcypromine 60 mg/d (or greater)
4. currently taking effective medication precluded while taking a Monoamine Oxidase Inhibitor (e.g., a psychostimulant or a serotonin re-uptake inhibitor)
5. current (last six months) drug or alcohol abuse or dependence
6. significant suicide risk
7. significant cardiovascular risk