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.
Hannestad
Jonas
J
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. jonas.hannestad@yale.edu
DellaGioia
Nicole
N
Ortiz
Nyrma
N
Pittman
Brian
B
Bhagwagar
Zubin
Z
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