Bipolar Depression and Inflammation

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

Detailed Description
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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.

Official Title
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Cyclooxygenase-2-Inhibitor Combination Treatment for Bipolar Depression: Role of Inflammation and Kynurenine Pathway Biomarkers

Conditions
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Bipolar Depression

Intervention / Treatment
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* Drug: ESC + CBX
* Drug: ESC + PBO.
* Drug: ESC+CBX


Participation Criteria
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Eligibility Criteria
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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 (mor 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 MDD Inability to commit to the follow-up visits between 8 and 11 am

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ESC + CBX<br>Escitalopram 10 mg twice day plus Celecoxib 200 mg twice daily. | Drug: ESC + CBX<br>* Escitalopram (ESC) 10 mg twice day given orally twice a day plus Celecoxib (CBX) 200 mg twice daily.<br>Drug: ESC+CBX<br>* • Escitalopram 10 mg given twice day plus Celecoxib 200 mg twice daily.<br>|
| Placebo Comparator: ESC + PBO.<br>Escitalopram 10 mg twice day plus placebo administered twice daily. | Drug: ESC + PBO.<br>* • Escitalopram (ESC) 10 mg twice per day plus Placebo (PBO)administered twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improved affective responses | combined pharmacotherapy of ESC + CBX will result in earlier and/or improved affective responses compared to ESC + placebo measured by rating three levels of assessment of clinical improvement: (a) time of onset of mood response, (b) magnitude of mood response, and (c) prevalence and time point of symptom remission | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety profile of combined ESC/CBX therapy | Determine whether combined pharmacotherapy of ESC + CBX poses safety or tolerability issues, particularly in terms of gastrointestinal bleeding or cardiovascular health over a 8-week course of treatment. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar depression, Celecoxib, Escitalopram, Inflammation