Bipolar Depression
Conditions
Keywords
Bipolar depression, Celecoxib, Escitalopram, Inflammation
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.
Interventions
DRUGEscitalopram
Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI)
DRUGCelecoxib
Celecoxib is a nonsteroidal anti-inflammatory drug
DRUGPlacebo
Placebo is a manufactured capsule with no active ingredient
Sponsors
Stanley Medical Research Institute
Loyola University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from an outpatient psychiatric clinic
Pre-assignment details
One-hundred subjects consented to participate in this study. Among these individuals, 27 participants were screen failures and eight participants withdrew prior to randomization. The remaining 65 participants were randomized and took at least one study capsule
Participants by arm
| Arm | Count |
|---|---|
| Intervention Cohort Participants assigned to the intervention cohort receive 10mg escitalopram twice daily plus 200mg celecoxib twice daily. | 27 |
| Control Cohort Participants assigned to the control cohort receive 10mg escitalopram twice daily plus placebo administered twice daily. | 20 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 8 | 10 |
Baseline characteristics
| Characteristic | Intervention Cohort | Control Cohort | Total |
|---|---|---|---|
| Age, Continuous | 39.48 years STANDARD_DEVIATION 10.73 | 46.15 years STANDARD_DEVIATION 13.5 | 42.32 years STANDARD_DEVIATION 12.31 |
| Race/Ethnicity, Customized Self-described race non-White | 8 Participants | 7 Participants | 15 Participants |
| Race/Ethnicity, Customized Self-described race White | 19 Participants | 13 Participants | 32 Participants |
| Region of Enrollment United States | 27 participants | 20 participants | 47 participants |
| Sex: Female, Male Female | 15 Participants | 13 Participants | 28 Participants |
| Sex: Female, Male Male | 12 Participants | 7 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 30 |
| other Total, other adverse events | 0 / 35 | 0 / 30 |
| serious Total, serious adverse events | 0 / 35 | 0 / 30 |
Outcome results
Primary
Disease Remission
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.
Time frame: 8 weeks
Population: The analysis population is defined as all participants who completed at least eight weeks of treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intervention Cohort | Disease Remission | Remission | 17 Participants |
| Intervention Cohort | Disease Remission | No Remission | 10 Participants |
| Control Cohort | Disease Remission | Remission | 2 Participants |
| Control Cohort | Disease Remission | No Remission | 18 Participants |
Comparison: The null hypothesis is that there is no difference in the remission rate between patients assigned to the intervention cohort or control cohort.p-value: <0.001Chi-squared
Primary
Response to Treatment
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.
Time frame: 8 weeks
Population: The analysis population is defined as all participants who completed at least eight weeks of treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intervention Cohort | Response to Treatment | Response | 21 Participants |
| Intervention Cohort | Response to Treatment | No Response | 6 Participants |
| Control Cohort | Response to Treatment | Response | 9 Participants |
| Control Cohort | Response to Treatment | No Response | 11 Participants |
Comparison: The null hypothesis is that there is no difference in the response rate between patients assigned to the intervention cohort or control cohort.p-value: 0.02Chi-squared