Cyclooxygenase-2-Inhibitor Combination Treatment for Bipolar Depression

Inclusion Criteria: * Ages 21 - 65 years old at time of screening visit. Both genders and any race will be accepted. * Diagnosis of BPD I or II without significant co-morbid secondary medical or psychiatric diagnoses; no substance abuse or dependence during preceding 12 months * A minimum score of 18 on the first 17 items of the 21-item Hamilton Depression Scale * Willingness to washout for a reasonable time (depending on the substance) from: Vitamin E and fish oils (\>600 IU/day), non-aspirin NSAIDs or aspirin (\>81 mg/day, H2 receptor antagonists, Ginko biloba, caffeine on morning of blood drawing, and to institute lights-out at 23:00 hours on the nights before blood drawings Exclusion Criteria: * Any abnormal findings on the physical exam, ECG, blood/urine or minor infections * Any pre-existing physical pain condition, including fibromyalgia * History of peptic ulcer complicated by perforation, hemorrhage, or obstruction; symptoms of peptic ulcer within 4 weeks of enrollment date * Any substance abuse or dependence during the preceding 12 months * Clinically significant hypertension, anemia, liver disease, kidney disease, arthritis, diabetes, recurrent migraines, epilepsy, stroke, gum disease, autoimmune disease * Current use of lithium * Current use of a stimulant * Certain steroids including use of hormonal birth control and any systemic or topical corticosteroids (hormone replacement therapy will be allowed) * Unwillingness to refrain from H2 receptor antagonists, non-aspirin NSAIDs, or aspirin (more than 1 mg/day). * Use of any anticoagulant agents * Use of nicotine-containing substances. Subjects who quit smoking more than 3 months prior to assessment may be considered for the study * Known sensitivity or allergy to the study medications or a need to receive agents that are contra-indicated in combination with CBX or ESC * Unwillingness to fast and abstain from caffeine on mornings of blood drawings * A sleep disorder other than insomnia or hypersomnia as a distinct symptom of major depressive disorder (MDD) * Inability to commit to the follow-up visits between 8 and 11 am