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

Abstract

Increased concentrations of inflammatory biomarkers predict antidepressant nonresponse, and inflammatory cytokines can sabotage and circumvent the mechanisms of action of conventional antidepressants.Objectives: To determine whether inhibition of the inflammatory cytokine tumor necrosis factor (TNF) reduces depressive symptoms in patients with treatmentresistant depression and whether an increase in baseline plasma inflammatory biomarkers, including highsensitivity C-reactive protein (hs-CRP), TNF, and its soluble receptors, predicts treatment response.

Defective Inflammatory Pathways in Never-Treated Depressed Patients Are Associated with Poor Treatment Response

“…Our population is unique because they are treatment-naïve and many were diagnosed for the first time, thereby providing a unique group for interrogation the role of the inflammatory response in MDD patients. Surprisingly, and in contrast to recent findings proposing that only a subgroup of MDD patients exhibit increased inflammatory markers (Raison et al, 2013), we found that the majority of MDD patients have elevated inflammatory markers above the mean of the HC subjects. Moreover, this increase in the cytokine levels occurred early in the disease as 5 cytokine (IL-2, IL-10, IL-12, IL15 and IL-17A), 1 chemokine (MIP1a/CCL3) and 2 growth factor (GM-CSF, FGF) levels were elevated in MDD patients within their first episode of the disease compared to MDD patients who experienced several episodes of the disease (data not shown).…”

Prevalence and correlates of low-grade systemic inflammation in adult psychiatric inpatients: An electronic health record-based study

“…Our results are in line with previous studies reporting prevalence of low-grade inflammation (CRP >3 mg/L) in depression ( Cizza et al, 2009 ; Raison et al, 2013 ; Wium-Andersen et al, 2013 ). These studies have investigated inflammation in depression in specific contexts such as in premenopausal women, in depressed outpatients, or in the general population.…”

Elevated C-Reactive Protein Levels Modify the Effect of Magnesium on Depressive Symptoms: A Population-Based Study

“…Those individuals with higher serum magnesium showed lower ORs of depression in the subgroup with CRP levels ≥ 5 mg/L (0.14 in the crude model, 0.11 in Model 1, 0.11 in Model 2) than in the subgroup with CRP levels ≥ 3 mg/L (0.21 in the crude model, 0.21 in Model 1, 0.23 in Model 2) ( Figure 2 ). For participants taking serum magnesium as an antidepressant agent, the differences in effects with different thresholds shown in our results were compatible with a previous study [ 39 ]. Raison et al examined the antidepressant effects of Infliximab, a tumor necrosis factor antagonist, in an intervention study.…”