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Pro-inflammatory proteins such as C-reactive protein (CRP) and tumor necrosis factor (TNF) are associated with depression (JW Psychiatry Mar 29 2010) and with poor response to antidepressants. To determine whether a monoclonal antibody against TNF (infliximab) would be useful in refractory depression, researchers conducted a double-blind, randomized, industry-supported trial of three infusions of infliximab or placebo given during 6 weeks. Participants were 60 patients with a major depressive episode (mean age, 43; mean episode duration: infliximab group, 184 months; placebo group, 239 months; mean antidepressant trials, 5 and 4, respectively; bipolar disorder, 10% and 20%, respectively). Antidepressants, used by 37 patients, were stably dosed.
Six weeks after treatment ended, infliximab was no better than placebo in reducing depressive symptoms overall, but was significantly better in the subgroup of patients who had baseline CRP levels above 5 mg/L, with a moderate effect size (0.41). In contrast, placebo was superior to infliximab (effect size, –0.82) in reducing depression scores in patients with lower CRP levels. Markers of TNF and TNF receptors were significantly higher in infliximab responders than nonresponders.
Raison CL et al. 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; 70:31. (http://dx.doi.org/10.1001/2013.jamapsychiatry.4)
Comment
In the high-CRP patients, infliximab improved specific depressive symptoms (depressed mood, psychomotor retardation, anhedonia, psychic anxiety, and suicidal ideation) that are consistent with symptoms produced by inflammation, suggesting that the apparent benefit was related to an anti-inflammatory effect. Measuring inflammatory markers may identify patients with refractory depression who would benefit from addition of an anti-inflammatory drug. The overlapping association of CRP and TNF markers with treatment response may indicate some nonspecificity of anti-inflammatory strategies in depression treatment. Conversely, the superiority of placebo in some low-CRP patients demonstrates that such strategies are not beneficial to all patients and may even be harmful to some.