Salicylic Augmentation in Depression

Phase 2

Terminated

Conditions: Depression
Treatment Resistant Depression
Depressive Disorder
Major Depressive Disorder

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo augmentation to treatment	Placebo Oral Tablet	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.
Aspirin augmentation to treatment	Aspirin 325mg	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.

Primary Outcome Measures

Name	Time	Method
Change in Hamilton Depression Scale Score	8 weeks	Change in HDRS score in the treatment versus control groups.

Secondary Outcome Measures

Name	Time	Method
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.