Depression, Depressive Disorder, Major Depressive Disorder, Treatment Resistant Depression
Conditions
Keywords
Aspirin, Treatment, Salicylic acid, anti-inflammatory
Brief summary
The investigators are doing this research study to find out if using aspirin along with antidepressant treatment can lessen symptoms of depression. This study also aims to find out if some people improve more from taking aspirin than others. The investigators also want to see if it is possible to predict which participants will do better based on a blood test. Aspirin is approved by the U.S. Food and Drug Administration (FDA) as an over-the-counter pain medication. But, aspirin is not approved by the FDA to make antidepressant treatment better. This research study will compare aspirin to placebo.
Detailed description
This study is a randomized, double-blind, placebo-control trial. The primary aims of this study are: Aim 1: To evaluate the clinical effect of aspirin augmentation on depression. Aim 2: To assess the inflammatory profile of the blood of the aspirin augmentation responders compared with the non-responders. Aim 3: To evaluate whether immune gene expression patterns are associated with antidepressant response to aspirin. Aim 4: To collect samples for later, more detailed immunologic characterization.
Interventions
DRUGAspirin 325mg
Participants will take intervention drug dose once a day in combination with their existing antidepressant treatment regimen.
DRUGPlacebo Oral Tablet
Participants will take a placebo tablet of the same size, shape, and color as the aspirin tablet.
Sponsors
Columbia University
Jessica Harder
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Study team will be blinded to participant condition. Pharmacy will be responsible for providing study drug versus identical placebo to participants.
Intervention model description
Randomized control trial with about half of all participants receiving placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Current diagnosis of major depressive disorder * Hamilton Depression Rating Scale (HDRS) score of \>19 * Stable treatment regimen (no medication changes or changes in psychotherapy treatment in past 8 weeks, and no participation in stepped treatments, such as completion of a course of cognitive behavioral therapy, during the trial) * Failed to remit with at least 1 antidepressant trial, or combination of 1 antidepressant and 1 augmentation agent * Women of childbearing age must agree to use an approved method of contraception for the duration of the study
Exclusion criteria
* Active suicidal ideation * History of manic episodes or psychosis * Alcohol or substance use disorder up to one month prior to first testing session * Comorbid neurologic condition affecting the central nervous system * Comorbid autoimmune condition * Uncorrected thyroid disease or a current abnormal thyroid-stimulating hormone (TSH) * Active or recent (within the past month) infection (such as otitis, pneumonia, urinary tract infection); temperature \> 100.3 or white blood cell (WBC) count \> 11 K/microL will be considered evidence of active infection even in the absence of other symptoms * History of GI bleed * History of stroke * History of a bleeding disorder * Platelet count \< 150,000/mm3 on initial screening * On a blood-thinning agent or taking NSAIDs daily * Current use of oral steroids or other immunomodulating medications * Salicylate sensitivity * Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hamilton Depression Scale Score | 8 weeks | Change in HDRS score in the treatment versus control groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response of Inflammatory Biomarkers | 2 years | Response of inflammatory biomarkers in treatment responders versus treatment non-responders at 8 weeks. |
| Biomarker Association With Antidepressant Response | 2 years | Ability to observe the degree of biomarker association with antidepressant response. |
Countries
United States
Participant flow
Pre-assignment details
After completing informed consent, participants who agreed to participate in the study began study procedures; those with a positive pregnancy test, significant abnormalities in blood counts, electrolytes, kidney function, or thyroid stimulating hormone levels, major psychiatric comorbidities, severe current active suicidality, or certain medical conditions were not eligible to be randomized and were excluded prior to group assignment.
Participants by arm
| Arm | Count |
|---|---|
| Aspirin Augmentation to Treatment Daily dose of aspirin 325 mg in combination with their existing antidepressant treatment regimen. | 6 |
| Placebo Augmentation to Treatment Daily dose of placebo in combination with their existing antidepressant treatment regimen. | 5 |
| Total | 11 |
Baseline characteristics
| Characteristic | Aspirin Augmentation to Treatment | Total | Placebo Augmentation to Treatment |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 11 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 10 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hamilton Depression Rating Scale (HDRS) Score | 20.5 units on a scale | 20.9 units on a scale | 21.4 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 6 Participants | 8 Participants | 2 Participants |
| Region of Enrollment United States | 6 participants | 11 participants | 5 participants |
| Sex: Female, Male Female | 5 Participants | 9 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 |
| other Total, other adverse events | 2 / 6 | 3 / 5 |
| serious Total, serious adverse events | 3 / 6 | 2 / 5 |
Outcome results
Primary
Change in Hamilton Depression Scale Score
Change in HDRS score in the treatment versus control groups.
Time frame: 8 weeks
Population: Analysis population consisted of study completers for whom HDRS scores from final study visit were available.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Aspirin Augmentation to Treatment | Change in Hamilton Depression Scale Score | -9.75 units on a scale |
| Placebo Augmentation to Treatment | Change in Hamilton Depression Scale Score | -11.67 units on a scale |
Secondary
Biomarker Association With Antidepressant Response
Ability to observe the degree of biomarker association with antidepressant response.
Time frame: 2 years
Population: Unable to analyze biomarker association with antidepressant response as there was no biomarker data to analyze (study was terminated due to insufficient resources to continue, and biomarker assays were thus never completed).
Secondary
Response of Inflammatory Biomarkers
Response of inflammatory biomarkers in treatment responders versus treatment non-responders at 8 weeks.
Time frame: 2 years
Population: No participant inflammatory data were collected. Although blood samples were collected for planned inflammatory assays, the samples were frozen and assays were never performed. Once study was terminated prematurely (due to lack of resources) no further funds were allocated to the study. Thus inflammatory assays could not be funded and inflammatory data analysis could not proceed.