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

Trial Summary

What is the purpose of this trial?

This study is a mechanistic randomized controlled trial that investigates whether inhibition of tumor necrosis factor signaling via intravenous infusion of infliximab improves psychomotor speed and executive functioning in depressed individuals who exhibit an inflammatory phenotype.

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.

What evidence supports the effectiveness of the drug infliximab for treating depression?

Infliximab has been effective in treating conditions like Crohn's disease and rheumatoid arthritis by targeting a protein called TNF-alpha, which is involved in inflammation. While this doesn't directly show its effectiveness for depression, it suggests that infliximab might help if inflammation plays a role in depression. ^{1 2 3 4 5}

Is infliximab generally safe for humans?

Infliximab has been used to treat conditions like Crohn's disease and rheumatoid arthritis, and while it has an acceptable safety profile, it can cause side effects like infections, infusion reactions (such as headache and fever), and rare psychiatric events. Serious side effects are uncommon, but some patients have experienced serious infections and rare cases of drug-induced lupus, which resolved after stopping the drug. ^{6 7 8 9 10}

How does the drug infliximab differ from other treatments for depression?

Infliximab is unique because it is an anti-inflammatory drug originally used to treat autoimmune diseases like Crohn's disease and rheumatoid arthritis by targeting TNFalpha (a protein involved in inflammation). Its use for depression is novel, as it explores the potential link between inflammation and depression, which is different from traditional antidepressants that primarily target brain chemicals. ^{1 2 6 11 12}

Eligibility Criteria

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 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.

I have been diagnosed with Major Depressive Disorder.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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 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]

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, 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. Canada pubmed.ncbi.nlm.nih.gov

The efficacy of switching from etanercept to infliximab in patients with rheumatoid arthritis. [2015]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Infliximab: a review of its use in Crohn's disease and rheumatoid arthritis. [2018]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on infliximab in Crohn disease and rheumatoid arthritis. [2018]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Infliximab: a review of its use in Crohn's disease and rheumatoid arthritis. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Psychiatric Adverse Events Associated With Infliximab: A Cohort Study From the French Nationwide Discharge Abstract Database. [2022]

7. Canada pubmed.ncbi.nlm.nih.gov

Long term safety of infliximab. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Suicide attempt in ulcerative colitis patient after 4 months of infliximab therapy--a case report. [2016]

9. United States pubmed.ncbi.nlm.nih.gov

Prescribing patterns and awareness of adverse effects of infliximab: a health survey of gastroenterologists. [2018]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Infliximab: a review of its use in the management of rheumatoid arthritis. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Infliximab-induced Depression and Suicidal Behavior in Adolescent with Crohn's Disease: Case Report and Review of Literature. [2022]

12. Japan pubmed.ncbi.nlm.nih.gov

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