Infliximab for Depression
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Massachusetts General Hospital
Must be taking: Antidepressants
Must not be taking: Antipsychotics, Anticonvulsants, Corticosteroids, others
Disqualifiers: Infections, Cancer, Bipolar, others
Prior Safety Data
Approved in 4 Jurisdictions
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.
12345Is 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.
678910How 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.
1261112Eligibility Criteria
This trial is for adults aged 18-65 with Major Depressive Disorder and inflammation (CRP β₯ 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.
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Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: InfliximabExperimental Treatment1 Intervention
Participants in this arm will receive 5 mg/kg of infliximab via an in-dwelling catheter.
Group II: PlaceboPlacebo Group1 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:
πͺπΊ Approved in European Union as Remicade for:
- Ankylosing Spondylitis
- Crohn's Disease
- Ulcerative Colitis
- Psoriatic Arthritis
- Rheumatoid Arthritis
- Plaque Psoriasis
πΊπΈ Approved in United States as Remicade for:
- Ankylosing Spondylitis
- Crohn's Disease
- Ulcerative Colitis
- Psoriatic Arthritis
- Rheumatoid Arthritis
- Plaque Psoriasis
π¨π¦ Approved in Canada as Remicade for:
- Ankylosing Spondylitis
- Crohn's Disease
- Ulcerative Colitis
- Psoriatic Arthritis
- Rheumatoid Arthritis
- Plaque Psoriasis
π―π΅ Approved in Japan as Remicade for:
- Ankylosing Spondylitis
- Crohn's Disease
- Ulcerative Colitis
- Psoriatic Arthritis
- Rheumatoid Arthritis
- Plaque Psoriasis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Massachusetts General HospitalBoston, MA
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Who Is Running the Clinical Trial?
Massachusetts General HospitalLead Sponsor
References
Infliximab: an updated review of its use in Crohn's disease and rheumatoid arthritis. [2022]Infliximab is a chimeric monoclonal antibody that binds to tumour necrosis factor-alpha (TNFalpha) and neutralises its effects. TNFalpha plays an important role in the development of both Crohn's disease and rheumatoid arthritis. In a large, double-blind, randomised study involving patients with active, refractory Crohn's disease, significantly more recipients of intravenous infliximab, compared with placebo, achieved a clinical response after 4 weeks' follow-up. Moreover, infliximab administration was associated with a rapid improvement in endoscopic and histological findings in clinical trials involving patients with active, refractory Crohn's disease. The results of the A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-Term Treatment Regimen (ACCENT) I study showed that maintenance infliximab therapy prolonged response and remission in patients with moderate to severe Crohn's disease. In patients with enterocutaneous fistulae associated with Crohn's disease who were involved in a double-blind, randomised study, significantly more patients who received multiple infusions of infliximab, compared with placebo, experienced a > or=50% reduction from baseline in the number of draining fistulae at > or =2 consecutive study visits. In patients with active rheumatoid arthritis refractory to treatment with methotrexate who were enrolled in a large, double-blind, randomised study [the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) study], American College of Rheumatology (ACR) 20, 50 and 70% response rates were seen in significantly more patients who received multiple infusions of infliximab plus methotrexate, compared with methotrexate plus placebo, after 30 and 54 weeks' treatment. Moreover, the ACR 20% response rate was maintained after 102 weeks' treatment. In addition, significantly less radiographic progression was seen in infliximab plus methotrexate, compared with methotrexate plus placebo, recipients after 54 weeks' treatment. Infliximab therapy was also associated with improvements in health-related quality of life in patients with Crohn's disease or rheumatoid arthritis. Infliximab was generally well tolerated in clinical trials with the most common adverse events including upper respiratory tract infection, headache, nausea, coughing, sinusitis and diarrhoea. Infliximab therapy may be associated with an increased risk of reactivation of tuberculosis in patients with latent disease. In conclusion, infliximab is an important treatment option in patients with active Crohn's disease who have not responded to conventional therapy and in patients with Crohn's disease who have fistulae. Moreover, infliximab plus methotrexate is effective in patients with active rheumatoid arthritis who have not responded adequately to traditional disease-modifying antirheumatic drugs, in terms of reducing symptoms and signs, improving physical function and delaying the progression of structural damage.
The efficacy of switching from etanercept to infliximab in patients with rheumatoid arthritis. [2015]To describe the degree of clinical benefit in patients with rheumatoid arthritis (RA) who receive infliximab therapy after lack of efficacy with etanercept.
Infliximab: a review of its use in Crohn's disease and rheumatoid arthritis. [2018]Infliximab is a chimaeric monoclonal antibody which binds to and inhibits the activity of tumour necrosis factor-alpha (TNFalpha), a cytokine which is involved in the development of both Crohn's disease and rheumatoid arthritis. In patients with treatment-resistant Crohn's disease, infliximab was significantly more effective than placebo in the relief of symptoms. 50 to 89% of patients responded to infliximab and most of them also achieved remission. Patients showed signs of relapse 8 to 12 weeks after a single infusion but responded to additional infusions of the drug. Infliximab was also effective in closing the fistulae in 68% of patients with fistulising Crohn's disease; the response rate with placebo was 26%. Infliximab achieved a clinical response in 44 to 81% of patients with refractory rheumatoid arthritis. Following a single infusion, symptom recurrence was evident after 6 to 12 weeks, but subsequent infusions re-established a clinical response. Concurrent methotrexate appeared to prolong the effects of infliximab in this patient group. Anti-infliximab and anti-double-stranded DNA antibodies developed in some patients, particularly those who received multiple infusions of infliximab. Acute adverse events consistent with hypersensitivity occurred in some patients who received multiple infusions of infliximab. Infection occurred slightly more frequently with infliximab than with placebo.
Spotlight on infliximab in Crohn disease and rheumatoid arthritis. [2018]Infliximab (Remicade) is a chimeric monoclonal antibody against tumor necrosis factor (TNF)-alpha that has shown efficacy in Crohn disease and rheumatoid arthritis with a disease-modifying activity and rapid onset of action. It is administered intravenously, generally in a schedule with initial infusions at 0, 2, and 6 weeks, followed by administration once every 8 weeks. Infliximab is effective in the treatment of patients with moderately to severely active Crohn disease with an inadequate response to other treatment options or those with fistulizing disease. In combination with methotrexate, infliximab reduced signs and symptoms and delayed disease progression in patients with active, methotrexate-refractory rheumatoid arthritis and in those with early disease. The drug was generally well tolerated. Recrudescence of tuberculosis infection and worsening of heart failure and demyelinating disease are among some of the concerns with anti-TNFalpha therapy, requiring cautious use of these agents in high-risk patients. Current data suggest that infliximab may be cost effective, especially when long-term clinical outcomes and burden of the diseases are taken into account. More robust, prospective pharmacoeconomic studies are required to better ascertain the cost effectiveness of infliximab. Direct head-to-head comparative trials of infliximab with other biological agents are not yet available and would be helpful in determining with greater certainty the place of infliximab in the management of these diseases. Nonetheless, infliximab, like other biological agents, is a valuable treatment option in patients with moderately to severely active Crohn disease (including fistulizing disease) or rheumatoid arthritis (including early disease).
Infliximab: a review of its use in Crohn's disease and rheumatoid arthritis. [2018]Infliximab (Remicade) is a chimeric monoclonal antibody against tumour necrosis factor (TNF)-alpha that has shown efficacy in Crohn's disease and rheumatoid arthritis with a disease-modifying activity and rapid onset of action. It is administered intravenously, generally in a schedule with initial infusions at 0, 2 and 6 weeks, followed by administration once every 8 weeks. Infliximab is effective in the treatment of patients with moderately to severely active Crohn's disease with an inadequate response to other treatment options or those with fistulising disease. In combination with methotrexate, infliximab reduced signs and symptoms and delayed disease progression in patients with active, methotrexate-refractory rheumatoid arthritis and in those with early disease. The drug was generally well tolerated. Recrudescence of tuberculosis infection and worsening of heart failure and demyelinating disease are among some of the concerns with anti-TNFalpha therapy, requiring cautious use of these agents in high-risk patients. Current data suggest that infliximab may be cost effective, especially when long-term clinical outcomes and burden of the diseases are taken into account. More robust, prospective pharmaco-economic studies are required to better ascertain the cost effectiveness of infliximab. Direct head-to-head comparative trials of infliximab with other biological agents are not yet available and would be helpful in determining with greater certainty the place of infliximab in the management of these diseases. Nonetheless, infliximab, like other biological agents, is a valuable treatment option in patients with moderately to severely active Crohn's disease (including fistulising disease) or rheumatoid arthritis (including early disease).
Psychiatric Adverse Events Associated With Infliximab: A Cohort Study From the French Nationwide Discharge Abstract Database. [2022]Infliximab (IFX) was the first anti-tumor necrosis factor (TNFΞ±) antibody to be used in the treatment of severe chronic inflammatory diseases, such as Crohn's disease and rheumatoid arthritis. A number of serious adverse drug reactions are known to be associated with IFX use; they include infections, malignancies, and injection site reactions. Although a few case reports have described potential psychiatric adverse events (including suicide attempts and manic episodes), the latter are barely mentioned in IFX's summary of product characteristics. The objective of the present retrospective study was to detect potential psychiatric adverse events associated with IFX treatment by analyzing a national discharge abstract database.
Long term safety of infliximab. [2019]Infliximab is a chimeric anti-tumour necrosis factor-alpha monoclonal antibody that has been studied for the treatment of Crohn's disease and rheumatoid arthritis. In several placebo controlled, randomized clinical trials and open trials, 771 patients have been given infliximab (a further 192 received placebo). Follow-up for safety has included the time of study (12 weeks after the last infusion), plus three additional years. Acute infusion reactions (headache, fever, chills, urticaria, chest pain) were seen in 17% of patients receiving infliximab compared with 7% of those receiving placebo. While infections were reported more frequently overall in the patients given infliximab (26% over 27 weeks of follow-up versus 16% of placebo-treated patients over 20 weeks of follow-up), there was no increased risk of serious infections. There was no difference in the overall mortality rate between the groups. While low titres of autoantibodies developed in less than 10% of patients, drug-induced lupus was seen in less than 1%, with these cases resolving upon discontinuation of the drug. Overall, infliximab showed an acceptable safety profile.
Suicide attempt in ulcerative colitis patient after 4 months of infliximab therapy--a case report. [2016]In the summary of product characteristics of infliximab (IFX), psychiatric side effects are reported to be rare, and in literature only limited data exist. This report presents a case of a patient with ulcerative colitis who developed a depression with psychotic symptoms during IFX therapy and made a suicide attempt 4 months after the initiation of therapy. Although the time between start of IFX therapy and onset of symptoms could suggest a correlation, this, of course, does not prove that IFX was the causative factor for his depression and suicide attempt.
Prescribing patterns and awareness of adverse effects of infliximab: a health survey of gastroenterologists. [2018]We sought to determine prescribing patterns and awareness of adverse drug reactions to infliximab among gastroenterologists. A questionnaire was developed and mailed to all gastroenterologists in Maryland and Washington, D.C. Ninety-six of 336 (28.6%) gastroenterologists responded; 86% of respondents use infliximab often or sometimes and 48% infuse infliximab on-site. Only 48% of respondents use immunomodulators prior to infusing infliximab. Thirty-three percent of respondents do not prescribe maintenance infliximab. Respondents reported that infusion reactions occur in 12.9% of infliximab infusions. Most respondents order a purified protein derivative prior to starting infliximab. Respondents underestimated the risk of serious infection, death, demyelinating diseases, and malignancy and overestimated the risk of congestive heart failure. We conclude that a substantial number of gastroenterologists underutilize immunomodulators and fail to prescribe maintenance infliximab. Further, respondents were unaware of the frequency of major adverse events associated with infliximab. Education regarding treatment algorithms in CD and infliximab-related side effects is needed.
Infliximab: a review of its use in the management of rheumatoid arthritis. [2018]Infliximab is a chimaeric monoclonal antibody to human tumour necrosis factor-alpha (TNFalpha). It binds to both soluble and transmembrane forms of TNFalpha at picomolar concentrations in vitro. Secondary to inhibition of TNFalpha, infliximab reduces serum levels of inflammatory mediators and vascular endothelial growth factor, decreases the expression of chemokines in the synovial tissue and reduces lymphocyte migration into the joints of patients with rheumatoid arthritis. In 2 multicentre randomised double-blind trials conducted over 26 and 30 weeks, infliximab plus methotrexate was significantly more effective than placebo plus methotrexate according to American College of Rheumatology response criteria in patients with active rheumatoid arthritis. A substantial response to infliximab-containing regimens was evident within 2 weeks. Extension phases of these studies indicate sustained clinical efficacy for up to 54 weeks. Of considerable importance are preliminary 1-year radiographic findings that show zero median progression of joint damage in infliximab plus methotrexate recipients compared with a 7 to 8% deterioration in placebo plus methotrexate recipients. Headache, nausea, upper respiratory tract infection and infusion-related reactions are the most commonly reported adverse events with infliximab. Serious events occurred in 4.4% of infliximab versus 1.8% of placebo recipients. In the largest clinical trial, 2 patients died from disseminated infection and 3 developed new or recurrent malignancies, although the exact relationship between infliximab and these events is unknown. To date, 2 patients with rheumatoid arthritis have developed drug-induced lupus. About 10% of patients may develop antibodies to infliximab, although the clinical significance of these is presently unknown.
Infliximab-induced Depression and Suicidal Behavior in Adolescent with Crohn's Disease: Case Report and Review of Literature. [2022]Infliximab, an anti-inflammatory agent, is used to treat various autoimmune disorders. There are at least 3 reports of severe psychiatric adverse effects of the drug, including suicidal behaviors in adults and psychosis in adult and adolescent patients. We report a case of an adolescent who developed depression and suicidal behaviors shortly after beginning infliximab. Although there have been reports of adolescents developing acute psychosis shortly after starting infliximab, this is, to our knowledge, the first report of adolescent suicidal behavior in the setting of infliximab treatment.
[Targeting therapy for inflammatory diseases by anti-TNFalpha biologics]. [2019]TNFalpha (tumor necrosis factor-alpha) plays a critical role in the pathogenesis of inflammatory diseases including rheumatoid arthritis and Crohn's disease. Infliximab is a monoclonal antibody that recognizes human TNFalpha. Clinical trials have been persuasive that infliximab is effective and far superior to the conventional drug therapy in various inflammatory diseases. Combination of infliximab plus methotrexate is effective in patients with active rheumatoid arthritis who have not responded adequately to traditional disease-modifying anti-rheumatic drugs, and has produced significant improvement in clinical, radiographic, and functional outcomes. Infliximab is also an important treatment option in patients with active Crohn's disease who have not responded to conventional therapy and in those with this disease who have fistulae. Moreover, infliximab treatment has resulted in effective suppression of ankylosing spondylitis, psoriasis and ocular inflammation in patients with refractory uveoretinitis due to Behçet's disease. Thus, biologics targeting TNFalpha have revolutionized the therapy of inflammatory diseases. Here, the current status of clinical application of anti-TNFalpha biologics is reviewed by describing the clinical outcome of infliximab and future prospects of biologics are discussed.