Этанерцепт в терапии депрессии

Patients with psoriasis and generally mild depression showed improvements in depression and fatigue.

Increased concentrations of proinflammatory cytokines, such as tumor necrosis factor {alpha} (TNF-{alpha}), have been associated with major depression. Some investigators have suggested that reducing these concentrations might improve depression, but no studies exist. Improvements in fatigue and depressive symptoms were secondary endpoints in a manufacturer-funded, placebo-controlled, randomized trial that examined the effect of etanercept — a soluble TNF-{alpha} receptor that competitively inhibits TNF-{alpha} effects — among 618 patients with moderate-to-severe psoriasis.

Patients received twice-weekly injections of etanercept (50 mg) or placebo for 12 weeks. Baseline depression was minimal to mild in over 80% of patients (incidence of moderate-to-severe depression: Hamilton Rating Scale for Depression [Ham-D], 2%; Beck Depression Inventory [BDI], 15%). By 12 weeks, etanercept produced significantly greater reductions in depression than placebo, with a small effect size (0.22 and 0.25 on the BDI and the Ham-D, respectively). Response (≥50% drop in symptoms) rates were 55% for etanercept versus 39% for placebo on the BDI and 43% versus 32% on the Ham-D. Fatigue scores improved similarly with etanercept. Improvements in depression and fatigue were significantly correlated, but were unrelated to improvements in psoriasis. Etanercept was fairly well tolerated, with only infrequent serious adverse events (2%).

Comment: As expected with treatment of minimal-to-mild depression, this study shows a very modest antidepressant effect. However, the efficacy of this novel agent suggests that a unique mechanism of action targeting proinflammatory cytokines might have therapeutic potential. Testing this agent in patients with more severe and refractory depression might help to determine its viability as an antidepressant.

— Peter Roy-Byrne, MD

Published in Journal Watch Psychiatry February 8, 2006

A Novel Cytokine Inhibitor Effectively Treats Depression