A Study of Infliximab for Treatment Resistant Major Depression

NCT00463580 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: IRB000117341R21MH077172-01A2
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Major depression is increasingly recognized to be a chronic and highly recurrent condition, which results in significantly increased health problems. One possible mechanism that may contribute to treatment resistance is increased production and release of chemicals called proinflammatory cytokines in patients with major depression. These chemicals mediate the body's response to infectious agents like bacteria and have been shown to be increased by psychological stress. They produce the symptoms that we associate with being sick, including fever, malaise and changes in sleep and appetite. Several lines of evidence indicate that proinflammatory cytokines may contribute to the development of major depression and may thus represent a novel target for the pharmacological treatment of the disorder. The TNF-alpha antagonist, Infliximab (Remicade®), is an infusion style drug approved by the FDA for the treatment of inflammatory conditions like Crohns disease and rheumatoid arthritis. The researchers are conducting a study to see if the infliximab (Remicade®) is more effective than placebo in acutely reducing symptoms of depression in patients who have elevated proinflammatory markers and have not responded to, or been unable to tolerate, at least two previous treatments in the current depressive episode. Proinflammatory markers are measured by a simple blood test for C-Reactive Protein (CRP) levels in the body.

Conditions

Depression

Keywords

depression; TNF-alpha antagonist; infliximab; treatment resistant depression; major depressive disorder (MDD); bipolar I disorder; bipolar II disorder

Outcome Measures

Primary Outcomes (1)

• Hamilton Depression Rating Scale 17 (HDRS-17) Scores

  The HDRS is a 17-item survey asking respondents to rate the degree of depressive symptoms they are feeling on a scale of 0 to 2-4, where 0 means the symptom is absent and 2-4 means the symptom is very strong. Total scores can range from 0 to 52 where higher scores represent greater symptom severity. Scores of 0-7 are considered normal, scores of 8-16 indicates mild depression, scores of 17-23 indicate moderate depression, and scores of 24 and greater indicate severe depression.

  Baseline, Weeks 1, 2, 4, 6, 8, 10 and 12

Secondary Outcomes (9)

• Number of Participants With a 50% Reduction in Hamilton Depression Rating Scale (HDRS) Scores

  Week 12

• Number of Remitted Patients During Treatment

  Week 12

• Inventory of Depressive Symptomatology-Self-Report (IDS-SR) Scores

  Baseline, Weeks 1, 2, 4, 6, 8, 10 and 12

• Plasma Concentrations of Interleukin-6 (IL-6)

  Baseline, Week 12

• Plasma Concentrations of CRP

  Baseline, Week 12

Study Arms (2)

Infliximab

EXPERIMENTAL

Participants in this arm will receive an infusion of infliximab.

Drug: Infliximab

Placebo

PLACEBO COMPARATOR

Participants in this arm will receive an infusion of normal saline.

Drug: Placebo

Interventions

Infliximab DRUG

Participants will receive three infusions 5mg/kg of infliximab (at Baseline, Week 2 and Week 6)

Also known as: Remicade

Infliximab

Placebo DRUG

Participants will receive three infusions of a placebo (at Baseline, Week 2 and Week 6)

Also known as: Normal saline

Placebo

Eligibility Criteria

• Age: 25 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females ages 25-60. Must be able to read and understand English.
• Currently meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-IV) criteria for a major depressive episode. (History of either unipolar major depression (depressive episodes only) or bipolar I disorder (history of manias and depressions) or bipolar II disorder (hypomanias and depressions), current episode depressed acceptable).
• Must meet criteria for "treatment resistant" depression defined by failure to respond to, or intolerance of, at least 2 treatment trials (antidepressants or ECT) during the current episode.
• All subjects will be fully ambulatory and in good medical health.
• Are required to either be antidepressant free for 2 weeks prior to study entry (4 weeks for fluoxetine secondary to long half-life) or be on a fixed psychotropic medication regimen for at least 4 weeks. Subjects and their primary care providers must agree to continue their status (i.e. without antidepressant or on a fixed regimen) until the 12-week assessment is complete.
• Pre-menopausal female subjects must not be pregnant and must be willing to use adequate contraception during the study period.

You may not qualify if:

• Current or history of psychotic symptoms.
• Active suicidal ideation (defined as a score of ≥3 on Hamilton Depression Rating Scale (HDRS) suicide item).
• Prior use of a TNF-alpha antagonist (i.e. etanercept, infliximab, adalimumab) and use of any other immunosuppressant agent (i.e. systemic corticosteroids or anti-proliferative agents such as methotrexate) within one year of study entry.
• Current use of aspirin, non-steroidal anti-inflammatory agents (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors during the study. Acetaminophen will be allowed.
• History of any of the following conditions: Congestive heart failure, abnormal electrocardiogram, malignancy, schizophrenia, neurological disease, auto-immune condition (e.g. rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, lupus), chronic infection (e.g. human immunodeficiency virus, hepatitis B or C), and hematologic, renal or hepatic abnormality.
• Subjects will be excluded for a positive anti-double stranded DNA antibody test.

Sponsors & Collaborators

• Emory University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Emory Clinic, Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Related Publications (3)

• Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, Haroon E, Miller AH. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2013 Jan;70(1):31-41. doi: 10.1001/2013.jamapsychiatry.4.

  PMID: 22945416 RESULT

• Weinberger JF, Raison CL, Rye DB, Montague AR, Woolwine BJ, Felger JC, Haroon E, Miller AH. Inhibition of tumor necrosis factor improves sleep continuity in patients with treatment resistant depression and high inflammation. Brain Behav Immun. 2015 Jul;47:193-200. doi: 10.1016/j.bbi.2014.12.016. Epub 2014 Dec 18.

  PMID: 25529904 RESULT

• Mehta D, Raison CL, Woolwine BJ, Haroon E, Binder EB, Miller AH, Felger JC. Transcriptional signatures related to glucose and lipid metabolism predict treatment response to the tumor necrosis factor antagonist infliximab in patients with treatment-resistant depression. Brain Behav Immun. 2013 Jul;31:205-15. doi: 10.1016/j.bbi.2013.04.004. Epub 2013 Apr 25.

  PMID: 23624296 RESULT

MeSH Terms

Conditions

Depression; Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major; Bipolar Disorder

Interventions

Infliximab; Saline Solution

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders; Bipolar and Related Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

This study was underpowered to adequately test placebo response typically reported for treatment resistant depression. Also, no direct measures of the effect of either infliximab or placebo on the central nervous system (CNS) were obtained.

Results Point of Contact

• Title: Andrew H. Miller, MD
• Organization: Emory University

amill02@emory.edu

404-727-8260

Study Officials

• Andrew H. Miller, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 19, 2007
• First Posted: April 20, 2007
• Study Start: December 1, 2008
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: July 8, 2025
• Results First Posted: May 12, 2014

Record last verified: 2025-06

Locations

US (1)