They found that NSAID exposure was associated with a greater likelihood of depression classified as treatment resistant compared with depression classified as responsive to selective serotonin reuptake inhibitors. The association was apparent in the NSAIDs-only group but not in those using other agents with NSAID-like mechanisms (cyclooxygenase-2 inhibitors and salicylates). However, inclusion of age, sex, ethnicity, and measures of comorbidity and health care utilization indicated there may have been confounding, leading the researchers to conclude that some of the observed effect may be due to this confounding. In light of the “modest effect” observed, the researchers cautioned that additional investigation in large cohorts or randomized studies is warranted before clinicians can be advised to avoid NSAID treatment in depressed patients receiving antidepressants. 