PTGS2 and major depressive disorder: By contrast, adjunctive treatment with non-selective COX-inhibitors (that is, non-steroidal antiinflammatory drugs (NSAIDs)) may reduce the efficacy of SSRIs [249,250]; two large trials reported that exposure to NSAIDs (but not to either selective COX-2 inhibitors or salicylates) was associated with a significant worsening of depression among a subset of study participants [249,250].