A recent systematic review of these cytokine inhibitors in patients without a diagnosis of MDD showed that these drugs lead to an overall improvement in depressive symptoms compared with placebo, independent of their effect on physical health.26 In RCT in patients with treatment-resistant MDD, there was no overall difference between infliximab and placebo, even when controlling for baseline level of inflammation.64 A phase II trial of an anti-IL-6 mAb (sirukumab) in patients with MDD and elevated plasma CRP (ClinicalTrials.gov Identifier: NCT02473289) is awaiting publication. Here, CRP is linked to major depressive disorder.