Citalopram reduces endotoxin-induced fatigue.
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.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. jonas.hannestad@yale.edu
Jonas
J
Hannestad
Nicole
N
DellaGioia
Nyrma
N
Ortiz
Brian
B
Pittman
Zubin
Z
Bhagwagar
D000328:Adult; D001007:Anxiety / Q000523:psychology; D001519:Behavior / Q000187:drug effects; D015283:Citalopram / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D003863:Depression / Q000139:chemically induced / Q000523:psychology; D004311:Double-Blind Method; D004731:Endotoxins / Q000633:toxicity*; D005221:Fatigue / Q000139:chemically induced* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007398:Interpersonal Relations; D008297:Male; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D012919:Social Behavior
D015283:Citalopram; D016207:Cytokines; D004731:Endotoxins; D017367:Selective Serotonin Reuptake Inhibitors