Citalopram reduces endotoxin-induced fatigue

• Published in: Brain, behavior, and immunity Vol. 25; no. 2; pp. 256 - 259
• Main Authors: Hannestad, Jonas, DellaGioia, Nicole, Ortiz, Nyrma, Pittman, Brian, Bhagwagar, Zubin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.02.2011
• Subjects: Adult; Allergy and Immunology; Antidepressant; Anxiety - psychology; Behavior - drug effects; Citalopram; Citalopram - therapeutic use; Cytokines; Cytokines - blood; Depression; Depression - chemically induced; Depression - psychology; Double-Blind Method; Endotoxin; Endotoxins - toxicity; Fatigue; Fatigue - chemically induced; Fatigue - prevention & control; Female; Humans; Interpersonal Relations; Male; Psychiatric Status Rating Scales; Psychiatry; Selective Serotonin Reuptake Inhibitors - therapeutic use; Social Behavior; Antidepressant; Fatigue; Depression; Cytokines; Endotoxin; Citalopram
• ISSN: 0889-1591; 1090-2139; 1090-2139
• DOI: 10.1016/j.bbi.2010.10.013

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.