Treatment resistance is common in depression ie in up to one-third. Presence of inflammatory biomarkers is associated with resistance.Inflammatory process can negatively affect some of the mechanisms by which antidepressants try to lift the mood. (for example: they could inhibit neuronogenesis, reduce coenzyme availability for mono amine synthesis). Tumor necrosis factor (TNF), one of the inflammatory cytokines, has been shown to be elevated in depressed patients .CRP has been shown to be elevated in depressed patients with antidepressant non response.
TNF antagonist is reported to lift mood in disorders like Psoriasis and Crohn’s disease.This study investigated whether a peripherally active cytokine antagonist, Infliximab, would improve mood in treatment resistant depression (TRD). This was a parallel-group, randomized, double blind trial of Infliximab vs placebo .Participants were on consistent antidepressant regimen for at least 4 weeks.They had moderately severe depression and had experienced moderate resistance to treatment. All those with physical disorders with immune dysfunction were excluded. Group assignment was stratified by sex and high sensitivity CRP concentration ( to achieve similar representation in each group). Infliximab 5mg/kg IVwas given baseline, 2 weeks and at 6 weeks.
60 patients were randomised. Both groups were comparable at baseline. HAM-D scores disd not show any differences over time between groups.Treatment response rates did not differ between the main groups. Both groups showed reduction in scores.Among those who had higher inflammatory marker concentration, a greater reduction in depression was observed (ie in subgroup analysis).No clinical or socio-demographic variables differed between them. The medication infusion was well tolerated.Elevated concentrations of hs-CRP prior to treatment were associated with a reduced response to placebo.
Limitations: The study was not powered for subgroup analysis and hence the response in higher CRP concentration group could include false positives. the treatment response in placebo group of 50% is interesting. participants were ‘interested’ patients and may be a motivated group.
Comment: This is proof of concept study. It shows that TNF antagonism do not translate in to improvement in TRD. Results indicate that a subgroup of TRD may have increased inflammation and they may respond to anti TNF strategy.
A Randomized Controlled Trial of the Tumor Necrosis Factor Antagonist Infliximab for Treatment-Resistant Depression: The Role of Baseline Inflammatory Biomarkers. Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, Haroon E, Miller AH. Arch Gen Psychiatry (JAMA Psych). 2013.