Salicylic Augmentation in Depression

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.

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