Phase 4
N=60
A Study of Infliximab for Treatment Resistant Major Depression
Depression
Bottom Line
View on ClinicalTrials.gov: NCT00463580 ↗Enrolled (actual)
60
Serious AEs
0.0%
Results posted
May 2014
Primary outcome: Primary: Hamilton Depression Rating Scale 17 (HDRS-17) Scores — 24.1; 23.6; 20.8; 20.4 scores on a scale
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Infliximab (Drug); Placebo (Drug)
- Age
- Adult · 25+ yrs
- Sex
- All
- Sponsor
- Emory University
- Primary completion
- Jun 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Hamilton Depression Rating Scale 17 (HDRS-17) Scores |
24.1; 23.6; 20.8; 20.4; 18.8; 18.3 | — |
| SECONDARY Number of Participants With a 50% Reduction in Hamilton Depression Rating Scale (HDRS) Scores |
15; 15 | — |
| SECONDARY Number of Remitted Patients During Treatment |
9; 8 | — |
| SECONDARY Inventory of Depressive Symptomatology-Self-Report (IDS-SR) Scores |
43.5; 43.9; 37.0; 38; 35.0; 36 | — |
| SECONDARY Plasma Concentrations of Interleukin-6 (IL-6) |
2.04; 2.13; 1.88; 1.89 | — |
| SECONDARY Plasma Concentrations of CRP |
6.21; 5.69; 3.91; 6.31 | — |
| SECONDARY Plasma Concentrations of Tumor Necrosis Factor (TNF)-Alpha |
— | — |
| SECONDARY Sleep Efficiency |
89.2; 87.9; 91.5; 90.2 | — |
| SECONDARY Sleep Efficiency in High (CRP>5mg/L) Versus Low (CRP < or =5mg/L) Infliximab-treated Patients |
89.8; 88.6; 94.5; 88.7 | — |
| SECONDARY Change in Hamilton Depression Rating Scale 17 (HDRS-17) Scores Subgrouped by Baseline Hs-CRP |
2.1; 0.3; -1.8; -3.1 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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.
Exclusion Criteria
- 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.
Data sourced from ClinicalTrials.gov (NCT00463580). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.