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Anti-inflammatory Drug Improves Depression in Treatment-Resistant Patients
Researchers at Emory University in Atlanta, Ga., found that infliximab, a tumor necrosis factor (TNF) antagonist, improved symptoms in patients with difficult-to-treat depression. The study was published on September 3 in the online edition of Archives of General Psychiatry.
Infliximab is a biologic drug used to treat autoimmune and inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease.
Inflammation is the body's natural response to infection or injury. However, when prolonged or excessive, inflammation can damage many parts of the body, including the brain. Moreover, inflammatory cytokines can sabotage the mechanisms of action of conventional antidepressants.
The researchers investigated whether the inhibition of TNF, an inflammatory cytokine, reduces depressive symptoms in patients with treatment-resistant depression and whether an increase in baseline plasma inflammatory biomarkers, including high-sensitivity C-reactive protein (hs-CRP) and TNF, predicts a treatment response.
The study involved 60 medically stable outpatients with major depression who were either receiving a consistent antidepressant regimen (n = 37) or were medication-free (n = 23) for 4 weeks or more and who were moderately resistant to treatment. The patients received three infusions of infliximab 5 mg/kg (n = 30) or placebo (n = 30) at baseline and at weeks 2 and 6 of the 12-week trial.
Inflammation in this study was measured using a simple blood test that detects CRP and that is readily available in most clinics and hospitals. The higher the CRP, the greater the inflammation, and the greater the likelihood that the patients would respond to infliximab.
Infliximab-treated patients with a baseline hs-CRP concentration of greater than 5 mg/L had a treatment response rate of 62% versus a response rate of 33% for placebo-treated patients (P = 0.19). Baseline concentrations of TNF and its soluble receptors were significantly higher in infliximab-treated responders versus nonresponders (P P
The researchers concluded that TNF antagonism may improve depressive symptoms in patients with high baseline inflammatory biomarkers.
This study marked the first successful application of a biologic therapy to depression.
For more information, visit the Archives of General Psychiatry Web site.