Treatment of cytokine-induced depression.
A high proportion of cancer and hepatitis C patients who receive cytokine immunotherapy develop symptoms of depression that are indistinguishable from those found in major depressive disorders. These symptoms are alleviated by anti-depressant treatment. Moreover, preventive treatment with anti-depressants, in particular selective serotonin reuptake inhibitors (SSRIs) attenuates IFN-alpha-associated symptoms of depression, anxiety, and neurotoxicity. The intermediate mechanisms of these effects are still unclear. Studies suggest that the state of depression is associated with an increase in plasma levels of various cytokines and soluble cytokine receptors. Furthermore, anti-depressants have been shown to shift the cytokine network towards a decreased production of pro-inflammatory cytokines and an increased production of anti-inflammatory cytokines. Other studies suggest that anti-depressants can also modify immune reactivity by acting on neural structures involved in neuroimmunomodulation. It is possible that anti-depressants could help to normalize the serotoninergic neurotransmission that is likely disrupted during immunotherapy due to the potent effects of cytokines on the metabolism of the amino acid precursor tryptophan. Further work is needed to optimize strategies for preventing neuropsychiatric side effects of cytokine immunotherapy, to clarify the mechanisms involved in the alleviating effects of anti-depressants on cytokine-induced depression, as well as to assess the possible consequences of anti-depressant therapy on the efficacy of immunotherapy on the disease process.
Capuron
Lucile
L
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1639 Pierce Drive, Suite 4000, Atlanta, GA 30322, USA.
Hauser
Peter
P
Hinze-Selch
Dunja
D
Miller
Andrew H
AH
Neveu
Pierre J
PJ
D000928:Antidepressive Agents / Q000494:pharmacology*; D016207:Cytokines / Q000009:adverse effects* / Q000187:drug effects*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D018121:Receptors, Cytokine / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D012890:Sleep / Q000187:drug effects; D014364:Tryptophan / Q000187:drug effects
D000928:Antidepressive Agents; D016207:Cytokines; D018121:Receptors, Cytokine; D012701:Serotonin; D014364:Tryptophan