Antiinflammatory drugs achieve their therapeutic actions at least in part by regulation of cytokine formation. A “cytokine hypothesis” of depression is supported by the observation that depressed individuals have elevated plasma levels of certain cytokines compared with healthy controls. The authors found that widely used antiinflammatory drugs antagonize both biochemical and behavioral responses to selective serotonin reuptake inhibitors (SSRIs). In contrast to the levels detected in serum, they found that frontal cortical levels of certain cytokines (e.g., TNFα and IFNγ) were increased by serotonergic antidepressants and that these effects were inhibited by antiinflammatory agents. The antagonistic effect of antiinflammatory agents on antidepressant-induced behaviors was confirmed by analysis of a dataset from a large-scale real-world human study, “sequenced treatment alternatives to relieve depression” (STAR*D). The authors suggest that clinicians should carefully balance the therapeutic benefits of antiinflammatory agents versus the potentially negative consequences of antagonizing the therapeutic efficacy of antidepressant agents in patients suffering from depression.



Warner-Schmidt JL et al. Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans.

Proc. Natl. Acad. Sci. USA 108(22):9262-9267 (2011).

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