Mood Stabilizer (MS)+ Antidepressant vs MS + Placebo in Maintenance of Bipolar Disorder.

Inclusion Criteria: OPEN-LABEL ACUTE TREATMENT PHASE 1. Diagnosed with BD, current episode depressed, with a MADRS score ≥ 20 at both the screening and baseline assessments 2. The duration of the current depressive episode is ≥ 2 weeks but ≤ 52 weeks 3. Taking or initiating treatment with an anti-manic medication at a therapeutic dose. Anti-manic medications and therapeutic doses are: lithium, serum level 0.6-1.4 mEq/L; divalproex, serum level 350-700 mM; risperidone 1-6 mg/day; olanzapine 5-30 mg/day; quetiapine IR or XR 300-900 mg/day; aripiprazole 10-30 mg/day; and ziprasidone 80-160 mg/day. Combinations of these medications as outlined above, or the combination of any of them with lamotrigine 100-400 mg daily, or the combination of a mood stabilizer plus asenapine 5-20 mg/day, are also permitted. 4. If taking any other psychoactive medication (other than lorazepam ≤ 4 mg/day or equivalent), is agreeable to tapering and discontinuing it over a period of ≤ 4 weeks 5. If female and of childbearing potential, is using an adequate method of contraception. 6. Aged 18-70 years, inclusive 7. Fluent in English and capable of providing informed consent DOUBLE-BLIND MAINTENANCE TREATMENT PHASE • Patients meeting all of the following criteria will be eligible to be included in the double-blind study phase: 1. Taking escitalopram 10-30 mg/day or bupropion XL 150-450 mg/day, in addition to their anti-manic medication. 2. Has adequately tolerated the combination of antidepressant plus mood stabilizer, and is currently in remission for ≥ 2 weeks and ≤ 8 weeks 3. If female and of childbearing potential, is using an adequate method of contraception Exclusion Criteria: OPEN-LABEL ACUTE TREATMENT PHASE 1. Has a history of rapid cycling, defined as ≥ 4 mood episodes in the preceding 12 months 2. Has current manic, hypomanic, or subsyndromal hypomanic symptoms, defined as a Young Mania Rating Scale (YMRS) score ≥ 8 at the screening or baseline visits 3. Has previously been refractory to treatment with both escitalopram and bupropion XL, or has been unable to tolerate both medications due to intolerable side effects or an allergic reaction 4. Is taking monoamine oxidase inhibitors, such as phenelzine or tranylcypromine 5. Escitalopram is contraindicated in patients taking pimozide or ziprasidone. Patients on pimozide or ziprasidone can participate in the study and will be prescribed bupropion XL 6. Bupropion XL is contraindicated in patients taking other preparations containing bupropion, in patients with active eating disorders, including anorexia nervosa and bulimia nervosa; and in patients with seizure disorders. Patients with any of these can still participate in the study and will be prescribed Escitalopram 7. Has active substance dependence, other than caffeine or nicotine dependence, in the preceding 3 months. Otherwise, patients with comorbid substance abuse or other comorbid psychiatric illnesses will be eligible to participate in the study 8. Is at high risk for suicide, as defined by a score of ≥ 4 on the suicide item of the MADRS, or in the opinion of the investigator 9. Has an unstable medical illness, as defined by a change in medication or other treatment in the past 4 weeks, or in the opinion of the investigator 10. Has significant abnormalities on an electrocardiogram 11. Is pregnant or lactating DOUBLE-BLIND MAINTENANCE TREATMENT PHASE 1. Has a history of rapid cycling, defined as ≥ 4 mood episodes in the preceding 12 months 2. Has current manic, hypomanic, or subsyndromal hypomanic symptoms, defined as a YMRS score ≥ 8 at the screening or baseline visits 3. Has active substance dependence, other than caffeine or nicotine dependence, in the preceding 3 months. Otherwise, patients with comorbid substance abuse or other comorbid psychiatric illnesses will be eligible to participate in the study 4. Is at high risk for suicide, as defined by a score of ≥ 4 on the suicide item of the MADRS, or in the opinion of the investigator 5. Has an unstable medical illness, as defined by a change in medication or other treatment in the past 4 weeks, or in the opinion of the investigator. 6. Has significant abnormalities on an electrocardiogram 7. Is pregnant or lactating 8. Has experienced an episode of mania, hypomania, or a mixed episode during antidepressant treatment of the acute depression, defined as a YMRS score of ≥ 16 at any open-label study visit, or in the opinion of the study psychiatrist