Possible association of statin use with the risk of depression: An up-to-date systematic review and meta-analysis

Although the potential effect of statins on depression has been investigated, the evidence remains inconsistent. We conducted a meta-analysis to determine whether statin use is associated with depression.

A systematic search was performed in PubMed, the Cochrane Library, and EMBASE and by reviewing the reference lists of included articles. Papers published up to Sep 11, 2025, were identified, and no language restrictions were applied. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were estimated using a random-effects model.

Fifteen studies (10 countries, 5,403,692 participants) met the inclusion criteria. Statin use was associated with significantly lower depression risk than was statin nonuse (pooled OR = 0.84, 95 % CI: 0.74-0.96, p = 0.009), although the interstudy heterogeneity was discovered to be substantial (I² = 85 %). Sensitivity analyses confirmed the robustness of the results. Subgroup analyses revealed significant associations in cohort studies (OR = 0.86, 95 % CI: 0.76-0.98, p = 0.02), studies using a validated questionnaire or scale (OR = 0.71, 95 % CI: 0.54-0.94, p = 0.02), individuals with comorbidities (OR = 0.74, 95 % CI: 0.55-0.98, p = 0.04), and those concurrently using an anti-inflammatory or antidepressant drug (OR = 0.82, 95 % CI: 0.71-0.95, p = 0.009). Preventive effects were discovered for North American populations (OR = 0.63, 95 % CI: 0.51-0.78, p < 0.001) and among individuals adhering to a Western (OR = 0.61, 95 % CI: 0.45-0.81, p < 0.001) or Asian (OR = 0.75, 95 % CI: 0.64-0.89, p = 0.001) dietary pattern.

Statin use appears to be associated with a lower depression risk, particularly in specific populations and under certain clinical or lifestyle conditions. However, the substantial heterogeneity observed across studies highlights the need for cautious interpretation. Further research is needed to clarify the causal relationship and to identify factors that may affect this association.