This project will attempt to enhance and augment the antidepressant efficacy of a commonly used antidepressant in poorly responding bipolar depressed patients.

This is a placebo-controlled study of patients with bipolar I disorder (BPD) utilizing a well-known antidepressant, escitalopram (ESC), in combination with the anti-inflammatory agent, celecoxib (CBX). The investigators hypothesize that combination treatment will lead to a qualitatively and quantitatively augmented response and will result in greater numbers of remitters compared to ESC monotherapy.

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

The baseline analysis population comprises all patients who were randomized and completed at least eight consecutive weeks of assigned treatment

8 weeks