Salicylic Augmentation in Depression

Study Overview
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Brief Summary
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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
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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.

Official Title
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Salicylic Augmentation in Depression

Conditions
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Depression, Depressive Disorder, Major Depressive Disorder, Treatment Resistant Depression

Intervention / Treatment
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* Drug: Aspirin 325mg
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Randomized control trial with about half of all participants receiving placebo.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aspirin augmentation to treatment<br>Participants who meet inclusion criteria for the study and are randomized to the active treatment arm will be given pills for the ensuing 8 weeks, consisting of a daily dose of aspirin 325 mg to be taken every evening before bed. | Drug: Aspirin 325mg<br>* Participants will take intervention drug dose once a day in combination with their existing antidepressant treatment regimen.<br>* Other names: Salicylic acid;|
| Placebo Comparator: Placebo augmentation to treatment<br>Participants randomized to the placebo arm will receive a placebo oral tablet of the same size, shape, and color as the aspirin tablet. Participants will be instructed to take their pills in the evening before bed. | Drug: Placebo Oral Tablet<br>* Participants will take a placebo tablet of the same size, shape, and color as the aspirin tablet.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hamilton Depression Scale score | Change in HDRS score in the treatment versus control groups. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response of inflammatory biomarkers | Response of inflammatory biomarkers in treatment responders versus treatment non-responders at 8 weeks. | 2 years | 
| Biomarker association with antidepressant response | Ability to observe the degree of biomarker association with antidepressant response. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aspirin, Treatment, Salicylic acid, anti-inflammatory