Increased levels of inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-6 (IL-6) may play a role in depression. Mild depressive-like symptoms can be induced in humans through activation of the innate immune system with endotoxin. Whether preventive treatment with antidepressants can reduce endotoxin-induced symptoms has never been tested. In a double-blind, randomized, placebo-controlled, cross-over study, we administered intravenous low-dose endotoxin (0.8. ng/kg) or placebo to 11 healthy subjects who had received oral pre-treatment with citalopram (10. mg twice a day) or placebo for 5. days. The Montgomery-Åsberg Depression Rating Scale, the State and Trait Anxiety Inventory, and a visual analog scale were used to measure depressive and anxiety symptoms and social anhedonia. Serum levels of TNF and IL-6 were measured with immunoassays. Compared to placebo, endotoxin administration increased serum levels of TNF and IL-6, and caused mild depressive-like symptoms, in particular lassitude and social anhedonia. While citalopram pre-treatment had no effect on the innate immune response to endotoxin, it reduced the endotoxin-induced MADRS total score by 50%, with a moderate effect size (Cohen's d= 0.5). Most of the MADRS total score was due to the lassitude item, and citalopram pre-treatment specifically reduced endotoxin-induced lassitude with a large effect size (Cohen's d= 0.9). These results suggest that subchronic pre-treatment with the serotonin-reuptake inhibitor citalopram blunts mood symptoms induced by acute immune system activation with endotoxin without inhibiting the peripheral immune response. © 2010 Elsevier Inc.
Hannestad, J., DellaGioia, N., Ortiz, N., Pittman, B., & Bhagwagar, Z. (2011). Citalopram reduces endotoxin-induced fatigue. Brain, Behavior, and Immunity, 25(2), 256–259. https://doi.org/10.1016/j.bbi.2010.10.013