Overview

The goal of this clinical trial is to learn if the anti-inflammatory medication adalimumab improves depressive symptoms in adults with Major Depressive Disorder (MDD) who are already taking the anti-depressant medication Lexapro (escitalopram).

The main questions it aims to answer are:

1. Does adalimumab improve the symptoms of some patients with MDD who are already taking an anti-depressant?
2. What characteristics predict for whom adalimumab has anti-depressant properties.

Researchers will compare adalimumab to a placebo (a look-alike substance that contains no drug) to see if adalimumab works to improve depressive symptoms as an add-on drug to the anti-depressant Lexapro (escitalopram).

For these primary aims the participants will:

1. Visit the clinic once every 2 weeks for a checkups and injection of adalimumab or placebo from the study psychiatrist (Day 1, 15, 29, and 43 for injections)
2. Complete short (\<5 min) daily surveys for the 57 day duration of the study.

Eligibility

Inclusion Criteria:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18+ years
• Meet DSM-5 criteria for Major Depressive Disorder
• baseline serum TNF-alpha (average of two samples in the same week) greater than 1.5 pg/mL
• Taking a steady dose of Lexapro (escitalopram) for at least 4 weeks
• Ability to take oral medication and physician-administered subcutaneous injection and be willing to adhere to the study protocol
• For females of reproductive potential: use of highly effective contraception for at least 1 month
• Access to a phone or computer with a camera

Exclusion Criteria:

1. Pregnant or breastfeeding
2. Active, chronic or recurrent infection
3. Known malignancy
4. Current use of immune modulating medications
5. Immunocompromised, current autoimmune condition or history of severe immune condition (e.g., history of cancer, HIV/AIDS)
6. History of, or positive test for, Hepatitis B surface antigen or core antibody positivity or tuberculosis (TB)
7. Congestive heart failure
8. History of demyelinating disease (multiple sclerosis (MS), optic neuritis, Guillain-Barre syndrome)
9. History of seizure disorder
10. Symptomatic hyponatremia
11. Monoamine oxidase inhibitors (MAOI) use within 14 days
12. Recent use of Rituxan (rituximab)
13. Concomitant use of:
    1. Immunosuppressants
    2. Kineret (anakinra)
    3. Orencia (abatacept)
    4. Remicade (infliximab)
    5. Enbrel (etanercept)
    6. Cimzia (certolizumab pegol)
    7. Simponi (golimumab)
    8. Imuran (azathioprine)
    9. Purinethol (6-mercaptopurine)
    10. Linezolid
    11. IV methylene blue
    12. Pimozide
    13. Antiplatelet agents
    14. Strong anticoagulants (e.g. warfarin, large doses of NSAIDs)
    15. Other SSRIs, SNRIs, tryptophan
14. Clinically relevant substance use disorder
15. Known allergic reactions to components of adalimumab and/or escitalopram
16. Treatment with another investigational drug or other intervention while participating in the study