Baricitinib for Major Depressive Disorder

Overseen By Jennifer Felger, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Antidepressants, Psychotropics, NSAIDs, others

Disqualifiers: Autoimmune, Cancer, Cardiovascular, Infections, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 11

Duration: 8 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called baricitinib to determine its effectiveness for people with major depression who also have high levels of inflammation. Researchers aim to discover if this drug can improve brain connectivity and enhance motivation and movement in those affected. Participants will receive either baricitinib or a placebo (a pill with no active medication) daily for eight weeks. This study may suit individuals diagnosed with major depression or bipolar depression, who experience low motivation or pleasure (anhedonia), have high inflammation, and are not currently on antidepressants. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

Yes, you will need to stop taking all antidepressant or other psychotropic medications (like mood stabilizers, antipsychotics, and sedative hypnotics) for at least 4 weeks before starting the trial (8 weeks for fluoxetine). Additionally, you must stop using certain anti-inflammatory medications and supplements before and during the study.

Is there any evidence suggesting that baricitinib is likely to be safe for humans?

Research has shown that baricitinib is generally well-tolerated. Most studies have examined its use for conditions like alopecia areata (a disease that causes hair loss) and rheumatoid arthritis (a disease causing joint pain and stiffness). In these studies, most side effects were mild, such as headaches, nausea, and cold-like symptoms, while serious side effects, like blood clots, were rare.

The FDA has already approved baricitinib for other conditions, indicating a documented safety record. This approval suggests a level of safety, but individual responses can vary. It is important to consult a doctor before joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for major depression?

Baricitinib is unique because it offers a novel approach to treating major depressive disorder by targeting the Janus kinase (JAK) pathway, which is different from the typical neurotransmitter-focused treatments like SSRIs or SNRIs. Most current antidepressants work by adjusting the balance of chemicals like serotonin or norepinephrine in the brain. However, baricitinib's mechanism of action involves modulating immune and inflammatory responses, which could be particularly beneficial for patients whose depression is linked to inflammation. Researchers are excited about this treatment because it opens a new avenue for managing depression, especially for those who haven't responded well to existing options.

What evidence suggests that baricitinib might be an effective treatment for major depressive disorder?

Research suggests that baricitinib might improve symptoms of major depressive disorder (MDD), particularly in patients with high inflammation levels. Baricitinib blocks certain signals in the body linked to depression. Some studies have shown that baricitinib can reduce anxiety and depression by enhancing brain functions related to motivation and movement. Over 36 weeks, related conditions showed improvements in quality of life and depression symptoms. While specific data for MDD is still being gathered, these findings suggest that baricitinib could be promising for improving depression symptoms in some patients. Participants in this trial will receive either baricitinib or a placebo to evaluate its effectiveness in treating MDD. ^{2 4 5 6 7}

Who Is on the Research Team?

Jennifer Felger, PhD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for men and women aged 25-55 with major depression or bipolar disorder in a depressive phase, who have high inflammation levels (CRP ≥3 mg/L) and significant anhedonia. Participants must not be on antidepressants or other psychotropic drugs for at least 4 weeks before the study starts (8 weeks for fluoxetine).

Inclusion Criteria

Score of >14 on the PHQ-9 from screening and HAM-D score ≥18 for study entry

CRP ≥3 mg/L

PHQ-9 anhedonia score ≥2

Exclusion Criteria

History or evidence of an autoimmune disorder

Active suicidal plan as determined by a score >3 on item #3 on the HAM-D

History of disseminated/complicated herpes zoster

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-3 weeks

1 visit (in-person or remote)

Treatment

Participants are randomly treated with either baricitinib or placebo for 8 weeks, with assessments of inflammation markers, depression symptoms, brain function, motivation, and motor speed

8 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Baricitinib

Trial Overview

The trial is testing if Baricitinib can improve brain function related to motivation and movement in patients with major depression by blocking JAK signaling, which may be linked to high inflammation. Patients will either receive Baricitinib or a placebo.

How Is the Trial Designed?

Group I: Baricitinib Arm Experimental Treatment 1 Intervention

Baricitinib at dose of 2 mg will be dispensed to be taken orally, daily for 8 weeks.

Group II: Placebo Arm Placebo Group 1 Intervention

Placebo will be dispensed to be taken orally, daily for 8 weeks.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6691861/

Efficacy and safety data based on historical or pre-existing ...

Response rates in patients with or without each comorbidity who received baricitinib were generally close to overall response rates, with the exception of ...

2.

withpower.com

withpower.com/trial/phase-2-major-depressive-disorder-mdd-7-2025-33553

Baricitinib for Major Depressive Disorder

Trial Overview The trial is testing if Baricitinib can improve brain function related to motivation and movement in patients with major depression by blocking ...

3.

link.springer.com

link.springer.com/article/10.1007/s13555-024-01208-x

Improvement in Measures of Quality of Life and Symptoms ...

Improvements in both HRQoL and levels of anxiety and depression were also observed with baricitinib through 36 weeks, with greater benefits seen ...

4.

ajmc.com

ajmc.com/view/baricitinib-shows-effectiveness-safety-for-severe-aa-with-room-for-further-exploration

Baricitinib Shows Effectiveness, Safety for Severe AA With ...

Out of 50 patients, 34 completed 16 weeks of treatment, with only 26.5% achieving a SALT score of less than or equal to 20. This percentage ...

5.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/10.1111/jdv.20312

Real‐life effectiveness and safety of baricitinib in patients ...

Data on the effectiveness and safety of baricitinib are promising and support the use of this drug in severe forms of AA, also in the early ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9443639/

A Review of Safety Outcomes from Clinical Trials ...

This narrative review summarises and discusses the safety profile of baricitinib across these diseases, with special focus on adverse events of special ...

7.

academic.oup.com

academic.oup.com/bjd/article/188/2/218/6821292

Integrated safety analysis of baricitinib in adults with severe ...

This analysis includes pooled patient-level safety data from two trials, an adaptive phase II/III trial (BRAVE-AA1) and a phase III trial (BRAVE ...