Background: Evidence regarding whether statin use is associated with depression is inconsistent. Therefore, we performed a meta-analysis to investigate this association. Methods: We searched PubMed, the Cochrane Library, and the EMBASE database, limiting the search to human patients and articles written in English and published by March 31, 2020. The Newcastle–Ottawa scale for observational studies was used to assess study quality. All included studies were evaluated by 2 reviewers independently; any discrepancies were resolved through discussion. Because of the heterogeneity of study populations, a random effects model was used to calculate the pooled effect size. Statistical heterogeneity across studies was assessed using the I2 statistic. All analyses were performed using RevMan5 and Comprehensive Meta-Analysis software. Results: A total of 13 observational (9 cohort, 3 case–control, and 1 cross-sectional) studies conducted in 11 countries and enrolling 5 035 070 participants were included. Substantial statistical heterogeneity was discovered (I2, 83%). Overall, use of statins was not associated with depression after trim and fill analysis (adjusted pooled odds ratio [OR], 0.87; 95% CI, 0.74-1.02). The finding was consistent in the subgroup analysis, except for studies published before 2013, showing statin use was associated with a lower risk of depression. Limitations: High heterogeneity and asymmetry funnel plot of ORs from these studies were observed. Conclusions: This meta-analysis revealed statin use was not associated with depression. However, high heterogeneity was observed between identified studies, and results were inconsistent in the subgroups of studies published before 2013.
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