Activation of the inflammasome and elevated cytokines in stress and depression suggests that suppression of the inflammatory response could ameliorate depressive symptoms. Interestingly, tricyclic antidepressants (TCA) and SSRIs normalize serum levels of inflammatory cytokines in depressed patients, as well as increase the production of anti-inflammatory cytokines such as IL-10 (Kenis and Maes, 2002; Raedler, 2011). In addition, co-treatment of antidepressants with non-steroidal anti-inflammatory drugs (NSAIDs), such as celecoxib, a cyclooxygenase-2 inhibitor, significantly augments antidepressant efficacy (Muller et al., 2006). Administration of minocycline, an anti-inflammatory drug and selective microglial inhibitor, also augments the clinical efficacy of antidepressants (Pae et al., 2008). Minocycline treatment has neuroprotective effects (i.e., decreases excitotoxicity) by inhibiting microglial proliferation (Tikka et al., 2001). However, a recent study in mice reported that NSAIDs inhibit the beneficial effects of antidepressants on inflammation (Warner-Schmidt et al., 2011).
