Abstract
BACKGROUND: Statins are widely prescribed for the primary and secondary prevention of cardiovascular diseases, given their efficacy in lowering low-density lipoprotein cholesterol levels and reducing the risk of cardiovascular events. However, statins may exert effects on the central nervous system. Previous studies have hypothesized that statin use may exert protective effects against anxiety via mechanisms including anti-inflammatory activity and improved endothelial function. Conversely, observational studies have also reported associations between statin use and increased anxiety symptoms. To date, findings on the association between statin use and anxiety risk have been inconsistent. Therefore, this systematic review and meta-analysis aimed to systematically search and assess the available evidence, clarify the association between statin use and the risk of anxiety, and offer evidence-based guidance for clinical practice. METHODS: We searched PubMed, Web of Science, Embase, and the Cochrane Library for studies investigating the association between statin use and anxiety risk, with the search period ranging from the inception of each database to January 2026. Studies were screened against predefined inclusion criteria, and relevant data were extracted. The Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool was employed to assess the risk of bias in included non-randomized studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled with a random-effects model. RESULTS: A total of five studies with 1,919,059 participants were included. The meta-analysis showed that statin use was not associated with an increased risk of anxiety disorders (HR = 0.75,95% CI (0.55,1.04), P = 0.08). Subgroup analyses revealed that statin use was associated with a reduced risk of anxiety only in studies with a sample size < 10,000 (P < 0.05). No significant association was observed in other subgroups, including those stratified by region or study design, notably, studies with a sample size > 10,000 also showed no significant effect (P > 0.05). CONCLUSION: The existing evidence suggests that statin use may not be associated with the risk of developing anxiety. Given the limitations of this study, future large-scale, multi-center, and prospective cohort studies are warranted to validate these findings. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier PROSPERO CRD420261291901.