Statin treatment and the risk of depression

The effect of statin treatment on the risk of developing depression remains unclear. Therefore, we assessed the association between statin treatment and depression in a nationwide register-based cohort study with up to 20 years of follow up.

We identified all statin users in the period from 1996 to 2013 among individuals born in Denmark between 1920 and 1983. One non-user was matched to each statin user based on age, sex and a propensity score taking several potential confounders into account. Using Cox regression we investigated the association between statin use and: (I) redemption of prescriptions for antidepressants, (II) redemption of prescriptions for any other drug, (III) depression diagnosed at psychiatric hospitals, (IV) cardiovascular mortality and (V) all-cause mortality.

A total of 193,977 statin users and 193,977 non-users were followed for 2,621,282 person-years. Statin use was associated with (I) increased risk of antidepressant use (hazard rate ratio (HRR) = 1.33; 95% confidence interval (95%-CI) = 1.31-1.36), (II) increased risk of any other prescription drug use (HRR = 1.33; 95%-CI = 1.31-1.35), (III) increased risk of receiving a depression diagnosis (HRR = 1.22, 95%-CI = 1.12-1.32) - but not after adjusting for antidepressant use (HRR = 1.07, 95%-CI = 0.99-1.15), (IV) reduced cardiovascular mortality (HRR = 0.92, 95%-CI = 0.87-0.97) and (V) reduced all-cause mortality (HRR = 0.90, 95%-CI = 0.88-0.92).

These results suggest that the association between statin treatment and antidepressant use is unspecific (equivalent association between statins and most other drugs) and that the association between statin use and depression diagnoses is mediated by residual confounding, bias or by downstream effects of the statin prescription (seeing a physician more often).