Background
Numerous studies have reported that inflammation is closely associated with depression, and adjunctive non-steroidal anti-inflammatory drug (NSAID) treatment has been suggested as a novel therapeutic approach for depression.

Methods
We searched electronic databases including Medline, Embase, and the Cochrane Central Register of Controlled Trials. We only included randomized controlled trials comparing adjunctive NSAIDs with placebos for treating depressive episodes.

Results
Of the 654 retrieved entries, we identified four relevant studies with a total of 150 patients (75 NSAID patients and 75 placebo patients) with depressive episodes. All four studies used celecoxib as the NSAID. The patients receiving adjunctive celecoxib had significantly higher mean changes in the Hamilton Rating Scale for Depression scores between baseline and endpoint measurements compared with those receiving placebo (weighted mean difference = 3.26, 95% confidence interval; CI = 1.81 to 4.71). The adjunctive celecoxib group also showed better remission (odds ratio; OR = 6.58, 95% CI = 2.55 to 17.00) and response rates (OR = 6.49, 95% CI = 2.89 to 14.55) than the placebo group. The all-cause drop-out rate was more favorable for the celecoxib group than for the placebo group (OR = 0.45, 95% CI = 0.18 to 1.13), although the statistical significance was not statistically significant (p = 0.09).

Conclusion
Adjunctive treatment with NSAIDs, particularly celecoxib, can be a promising strategy for patients with depressive disorder. Future studies with a larger sample size and longer study duration are needed to confirm the efficacy and tolerability of NSAIDs for depression.