Celecoxib adjunct to antidepressants for major depressive disorder: Systematic review and meta-analysis

This systematic review and meta-analysis of randomized, placebo-controlled trials evaluated the efficacy, acceptability, and tolerability of celecoxib as an adjunct to antidepressants for major depressive disorder (MDD). PubMed, Embase, the Cochrane Library, Google Scholar, and ClinicalTrials.gov were searched from inception to April 11, 2026. The primary outcome was change in depressive symptom severity. Secondary outcomes included all-cause dropouts and adverse-effect dropouts. The risk of bias in trials was assessed using the Cochrane Risk of Bias 2 tool. Standardized mean differences (SMDs) and risk ratios (RRs) were pooled using a random-effects model. Evidence certainty was rated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Seven trials were included (N = 365; 183 received celecoxib, 182 received placebo). Most trials administered celecoxib 400 mg/day for 6 weeks in patients without treatment-resistant depression. Adjunctive celecoxib significantly reduced depressive symptom severity compared with placebo (SMD = -0.63, 95% CI: -1.25 to -0.01; I ²  = 81.3%; 7 trials). All-cause dropouts (RR = 0.77; 95% CI: 0.14 to 4.07; I ²  = 57.6%; 5 trials) and adverse-effect dropouts (RR = 0.83; 95% CI: 0.19 to 3.64; I ²  = 16.9%; 5 trials) did not differ between groups. The certainty of evidence was very low for efficacy, low for acceptability, and moderate for tolerability. The antidepressant efficacy of adjunctive celecoxib remains highly uncertain due to high risk of bias in several trials, substantial heterogeneity of reported outcomes, and small sample sizes. However, celecoxib adjunctive therapy appears acceptable and likely well tolerated over the short-term treatment.