Infliximab for Depression

Overseen By David Mischoulon, MD, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must be taking: Antidepressants

Must not be taking: Antipsychotics, Anticonvulsants, Corticosteroids, others

Disqualifiers: Infections, Cancer, Bipolar, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether infliximab, a medication typically used to reduce inflammation, can improve thinking speed and decision-making abilities in individuals with depression linked to inflammation. Participants will receive either infliximab or a placebo (a harmless substance resembling the real treatment) to compare effects. The trial seeks individuals diagnosed with major depressive disorder who have moderate symptoms and show signs of inflammation, such as elevated C-reactive protein levels detectable in some blood tests. Those who meet these criteria and have had no recent changes in antidepressant treatments might be suitable candidates. 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.

Do I need to stop taking my current medications to join the trial?

You may need to stop taking certain medications to join the trial. Specifically, you cannot use antipsychotic, anticonvulsant, or anti-inflammatory medications during the study. If you are on antidepressants, you must either be off them for at least 4 weeks before the study or continue a fixed regimen without changes.

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

Research has shown that infliximab, a treatment under study for depression, has been used safely for other conditions. Studies have found that infliximab and similar products are generally safe and effective. However, there is a higher chance of experiencing mental health side effects with infliximab, meaning some people might notice changes in their mental well-being.

Infliximab is already approved for other health issues, indicating it has passed safety checks for those uses. While this doesn't guarantee safety for treating depression, it does provide some reassurance. Always consult a healthcare provider to understand the risks and benefits before joining a trial. ^{1 2 3 4 5}

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

Unlike the standard treatments for depression, which primarily focus on neurotransmitters like serotonin, infliximab targets inflammation in the brain. Infliximab is a monoclonal antibody that blocks tumor necrosis factor-alpha (TNF-alpha), a substance in the body that can cause inflammation. Researchers are excited about infliximab because it offers a new approach by addressing the inflammatory processes that might contribute to depression. This could potentially benefit patients who do not respond well to conventional antidepressants, offering new hope for those with treatment-resistant depression.

What evidence suggests that infliximab might be an effective treatment for depression?

Research has shown that infliximab, a medication typically used for inflammatory conditions, might help with depression in certain cases. Past studies generally found that infliximab did not reduce depression symptoms. However, it appeared more effective for individuals with high levels of inflammation. Infliximab blocks a protein called tumor necrosis factor, which is associated with inflammation. In this trial, participants will receive either infliximab or a placebo. For those with depression and high inflammation, infliximab might prove more effective. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with Major Depressive Disorder and inflammation (CRP ≥ 3mg/L). Participants must have moderate depression, not be on new antidepressants for the last 4 weeks, and either be unable to become pregnant or use reliable contraception. They should agree not to change their treatment during the study.

Inclusion Criteria

I have been diagnosed with Major Depressive Disorder.

I am willing to undergo IV infusions and have my blood drawn.

Your blood has a high level of C reactive protein, which is 3mg/L or more.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive infliximab or placebo via intravenous infusion and complete daily assessments of depressive symptoms and cognitive function

2 weeks

1 visit (in-person) for infusion, daily remote assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Remote assessments and in-person visit for final evaluation

What Are the Treatments Tested in This Trial?

Interventions

• Infliximab

Trial Overview The trial tests if infliximab, given through an IV, can improve thinking speed and problem-solving in people with depression linked to inflammation. It's a randomized controlled trial comparing infliximab against a placebo.

How Is the Trial Designed?

Group I: Infliximab Experimental Treatment 1 Intervention

Participants in this arm will receive 5 mg/kg of infliximab via an in-dwelling catheter.

Group II: Placebo Placebo Group 1 Intervention

Participants in this arm will receive saline as placebo via an in-dwelling catheter.

Infliximab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in United States as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in Canada as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Approved in Japan as Remicade for:

• Ankylosing Spondylitis
• Crohn's Disease
• Ulcerative Colitis
• Psoriatic Arthritis
• Rheumatoid Arthritis
• Plaque Psoriasis

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Infliximab, an anti-inflammatory drug used for autoimmune disorders, can lead to severe psychiatric side effects, including depression and suicidal behaviors, particularly in adolescents, as demonstrated in a case involving a 16-year-old male with Crohn's disease.

This case highlights the importance of screening for preexisting psychiatric conditions in young patients before starting infliximab, as the patient developed significant depressive symptoms shortly after treatment initiation, but successfully managed these symptoms with fluoxetine and psychotherapy without recurrence during subsequent infusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab-induced Depression and Suicidal Behavior in Adolescent with Crohn's Disease: Case Report and Review of Literature. Shayowitz, M., Bressler, M., Ricardo, AP., et al.[2022]

Infliximab is an effective treatment for patients with active, refractory Crohn's disease, showing significant clinical response and improvement in endoscopic findings after 4 weeks, as well as prolonged response and remission with maintenance therapy.

In rheumatoid arthritis patients who did not respond to methotrexate, infliximab combined with methotrexate led to significantly better response rates and less radiographic progression over 54 weeks, while also improving quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab: an updated review of its use in Crohn's disease and rheumatoid arthritis. Keating, GM., Perry, CM.[2022]

Infliximab, an anti-TNF-alpha monoclonal antibody, was studied in 771 patients for Crohn's disease and rheumatoid arthritis, showing an acceptable safety profile with only 17% experiencing acute infusion reactions compared to 7% in the placebo group.

While infliximab was associated with a higher overall rate of infections (26% vs. 16% for placebo), there was no increased risk of serious infections or difference in mortality rates, indicating it is generally safe for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term safety of infliximab. Schaible, TF.[2019]

A survey of 96 gastroenterologists revealed that while 86% frequently use infliximab, only 48% prescribe immunomodulators beforehand, indicating a potential gap in optimal treatment practices.

Many gastroenterologists underestimated the risks of serious adverse effects associated with infliximab, such as serious infections and malignancies, highlighting the need for improved education on treatment protocols and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescribing patterns and awareness of adverse effects of infliximab: a health survey of gastroenterologists. Donovan, M., Lunney, K., Carter-Pokras, O., et al.[2018]

Infliximab, a monoclonal antibody targeting TNF-alpha, has been shown to significantly improve symptoms of active rheumatoid arthritis when combined with methotrexate, demonstrating clinical efficacy within just 2 weeks and sustained effects for up to 54 weeks in two large trials.

Preliminary findings suggest that infliximab can prevent joint damage, with no median progression of damage in treated patients compared to a 7-8% deterioration in those receiving placebo, although there are some safety concerns including serious adverse events and the development of antibodies against the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab: a review of its use in the management of rheumatoid arthritis. Markham, A., Lamb, HM.[2018]

A case report describes a patient with ulcerative colitis who developed depression with psychotic symptoms and attempted suicide four months after starting infliximab (IFX) therapy, highlighting a potential but unproven link between the medication and these severe psychiatric side effects.

While psychiatric side effects from infliximab are considered rare according to product guidelines, this case emphasizes the need for careful monitoring of mental health in patients undergoing IFX treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suicide attempt in ulcerative colitis patient after 4 months of infliximab therapy--a case report. Eshuis, EJ., Magnin, KM., Stokkers, PC., et al.[2016]

A study of 7,600 patients treated with infliximab (IFX) revealed a significantly higher rate of psychiatric hospital admissions (9.87%) compared to non-exposed patients (5.49%), indicating a strong association between IFX treatment and psychiatric adverse events.

The risk of specific psychiatric issues varied by underlying condition, with notably high hazard ratios for manic episodes in severe psoriasis patients (HR = 12.6) and suicide attempts in rheumatoid arthritis patients (HR = 4.45), highlighting the need for careful monitoring of mental health in patients receiving IFX.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychiatric Adverse Events Associated With Infliximab: A Cohort Study From the French Nationwide Discharge Abstract Database. Thillard, EM., Gautier, S., Babykina, E., et al.[2022]

In a study of 93 rheumatoid arthritis patients, those who switched from etanercept to infliximab showed similar clinical improvements as those who had never received TNF therapy, indicating that previous lack of response to etanercept does not predict a lack of response to infliximab.

Both groups experienced significant reductions in joint swelling, pain, and inflammation markers, but switchers received a higher dose of infliximab, suggesting that dosing may play a role in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of switching from etanercept to infliximab in patients with rheumatoid arthritis. Hansen, KE., Hildebrand, JP., Genovese, MC., et al.[2015]

Infliximab, a monoclonal antibody targeting TNFalpha, has been shown to be significantly more effective than traditional therapies for various inflammatory diseases, including rheumatoid arthritis and Crohn's disease, based on clinical trials.

The combination of infliximab with methotrexate has led to substantial improvements in clinical and functional outcomes for patients with active rheumatoid arthritis who did not respond to conventional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Targeting therapy for inflammatory diseases by anti-TNFalpha biologics]. Sugita, T.[2019]

Infliximab is highly effective for patients with treatment-resistant Crohn's disease, showing a response rate of 50 to 89%, and it also significantly aids in closing fistulae, achieving a 68% success rate compared to 26% with placebo.

In patients with refractory rheumatoid arthritis, infliximab demonstrated a clinical response in 44 to 81% of cases, with concurrent methotrexate potentially enhancing its effects, although some patients experienced adverse reactions and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab: a review of its use in Crohn's disease and rheumatoid arthritis. Onrust, SV., Lamb, HM.[2018]

Infliximab is an effective treatment for moderately to severely active Crohn disease and rheumatoid arthritis, showing rapid onset of action and disease-modifying activity, particularly in patients who have not responded to other treatments.

While generally well tolerated, infliximab carries risks such as reactivation of tuberculosis and worsening of certain conditions, necessitating careful use in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on infliximab in Crohn disease and rheumatoid arthritis. Siddiqui, MA., Scott, LJ.[2018]

Infliximab is an effective treatment for moderately to severely active Crohn's disease and rheumatoid arthritis, showing rapid onset of action and disease-modifying activity, particularly in patients who have not responded to other treatments.

While generally well tolerated, infliximab carries risks such as reactivation of tuberculosis and worsening of certain conditions, necessitating careful use in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab: a review of its use in Crohn's disease and rheumatoid arthritis. Siddiqui, MA., Scott, LJ.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31837338/

Efficacy of infliximab in treatment-resistant depression Infliximab was not efficient in reducing depressive symptoms according to the HAM-D, only when the patients already had increased inflammatory genes.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7188945/

Psychiatric Adverse Events Associated With Infliximab Comparison With the Literature Data. We found that 8.93% of the IFX-exposed patients had a major depressive disorder, in agreement with the ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00463580

A Study of Infliximab for Treatment Resistant Major ... A sleep efficiency of 80% or greater is considered normal. This outcome measures examines sleep efficiency between study treatment groups. Baseline, Week 8.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0091305719303521

Efficacy of infliximab in treatment-resistant depression Infliximab was not efficient in reducing depressive symptoms according to the HAM-D, only when the patients already had increased inflammatory genes.

5. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2732872

Efficacy of Adjunctive Infliximab vs Placebo in the ... Conclusions and Relevance Infliximab did not significantly reduce depressive symptoms compared with placebo in adults with bipolar depression.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10754394/

Outcomes of the use of infliximab biosimilars in ... This study found that infliximab biosimilar products appear to be safe and effective, similar to their originator counterparts.

7. avsola.com avsola.com/hcp/totality-of-evidence

AVSOLA®(infliximab-axxq)'s Totality of Evidence AVSOLA is highly similar to Remicade based on a totality of evidence, with no clinically meaningful differences in safety and efficacy.

8. uhcprovider.com uhcprovider.com/content/dam/provider/docs/public/policies/comm-medical-drug/infliximab-remicade-inflectra.pdf

Infliximab (Avsola®, Inflectra®, Remicade®, & Renflexis®) 12 Primary outcome measures assessed were best-corrected VA (BCVA) determined by the Landolt ring, proportion of subjects without relapse of uveitis, frequency ...