A Randomized Controlled Trial of the Tumor Necrosis Factor Antagonist Infliximab for Treatment-Resistant Depression

• DOI: 10.1001/2013.jamapsychiatry.4
• Publication Date: 2012-09-03T23:02:17Z
• Authors: Charles L. Raison; Robin E. Rutherford; Bobbi J. Woolwine; Chen Shuo; Pamela Schettler; Daniel F. Drake; Ebrahim Haroon; Andrew H. Miller
• Keywords: Depression

<h3>Context</h3>Increased concentrations of inflammatory biomarkers predict antidepressant nonresponse, and cytokines can sabotage circumvent the mechanisms action conventional antidepressants.<h3>Objectives</h3>To determine whether inhibition cytokine tumor necrosis factor (TNF) reduces depressive symptoms in patients with treatment-resistant depression an increase baseline plasma biomarkers, including high-sensitivity C-reactive protein (hs-CRP), TNF, its soluble receptors, predicts treatment response.<h3>Design</h3>Double-blind, placebo-controlled, randomized clinical trial.<h3>Setting</h3>Outpatient infusion center at Emory University Atlanta, Georgia.<h3>Participants</h3>A total 60 medically stable outpatients major who were either on a consistent regimen (n = 37) or medication-free 23) for 4 weeks more moderately resistant to as determined by Massachusetts General Hospital Staging method.<h3>Interventions</h3>Three infusions TNF antagonist infliximab (5 mg/kg) 30) placebo 2 6 12-week trial.<h3>Main Outcome Measures</h3>The 17-item Hamilton Scale Depression (HAM-D) scores.<h3>Results</h3>No overall difference change HAM-D scores between groups across time was found. However, there significant interaction treatment, time, log hs-CRP concentration (P .01), (baseline week 12) favoring infliximab-treated greater than 5 mg/L placebo-treated less. Exploratory analyses focusing revealed response (≥50% reduction score any point during treatment) 62% (8 13 patients) vs 33% (3 9 .19). Baseline receptors significantly higher responders nonresponders &lt; .05), exhibited decreases from 12 compared .01). Dropouts adverse events limited did not differ groups.<h3>Conclusions</h3>This proof-of-concept study suggests that antagonism does have generalized efficacy but may improve high biomarkers.<h3>Trial Registration</h3>clinicaltrials.gov Identifier: NCT00463580.