Efficacy and safety of celecoxib in schizophrenia: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: The hypothesis of immune and inflammatory dysregulation has been supported in the pathogenesis of schizophrenia; this systematic review and meta-analysis aims to evaluate the efficacy and safety of celecoxib, which is a COX-2 inhibitor with anti-inflammatory effects, in the management of schizophrenia. METHODS: A comprehensive search of electronic databases, including PubMed, Scopus, Cochrane, and Web of Science, was performed in February 2025. We included only randomized controlled trials (RCTs) comparing celecoxib alone or as an adjunct to antipsychotics to placebo. Risk of bias was assessed using the ROB-2 tool, and the data of included studies were extracted and analyzed using RevMan 5.4 software. The primary outcome was the change in PANSS (Positive and Negative Syndrome Scale) total score. RESULTS: Seven RCT studies comprising 438 patients with schizophrenia were included in this study. The risk of bias was low in most of the included studies. Celecoxib showed statistically significant improvement in PANSS total score (MD = - 8.45, 95% CI [- 13.62, -3.28], p value = 0.001), PANSS-positive scale (MD = - 3.34, 95% CI [- 4.67, - 2.02], P < 0.00001), PANSS-negative sub-scales (MD = - 2.47, 95% CI [- 3.75, - 1.19], P = 0.00002), and general psychopathology (MD = - 4.47, 95% CI [8.10, - 0.85], P = 0.02). No publication bias was detected based on the DOI plot. CONCLUSION: This study's findings provide insights into the potential anti-inflammatory benefits of celecoxib in schizophrenia treatment. However, study limitations warrant cautious interpretation, highlighting the need for larger, well-designed trials to identify patient subgroups that may benefit most from this approach.