Cyclooxygenase-2-Inhibitor Combination Treatment for Bipolar Depression

Phase 4

Completed

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

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Control cohort	Escitalopram	Participants assigned to the control cohort receive 10mg escitalopram twice daily plus placebo administered twice daily.
Intervention cohort	Escitalopram	Participants assigned to the intervention cohort receive 10mg escitalopram twice daily plus 200mg celecoxib twice daily.
Intervention cohort	Celecoxib	Participants assigned to the intervention cohort receive 10mg escitalopram twice daily plus 200mg celecoxib twice daily.
Control cohort	Placebo	Participants assigned to the control cohort receive 10mg escitalopram twice daily plus placebo administered twice daily.

Primary Outcome Measures

Name	Time	Method
Response to Treatment	8 weeks	Participants complete the Hamilton Depression Rating Scale (HDRS-17). The HDRS-17 is a clinician-administered assessment scale measuring the melancholic and physical symptoms of depression. Possible scores range from 0 to 54 (i.e., where higher scores indicate worse depression). In this study, response to treatment is defined as a reduction in the HDRS-17 score of at least 50% after 8 weeks of treatment.
Disease Remission	8 weeks	Participants complete the Hamilton Depression Rating Scale (HDRS-17). The HDRS-17 is a clinician-administered assessment scale measuring the melancholic and physical symptoms of depression. Possible scores range from 0 to 54 (i.e., where higher scores indicate worse depression). In this study, diisease remission is defined as an HDRS-17 score less than 8 points after 8 weeks of treatment.

Secondary Outcome Measures