Comparative risk of lipophilic and hydrophilic statins on incident depression: A retrospective cohort study.

Objectives: To evaluate the risk of new-onset depression in a cohort of US adult patients initiating lipophilic statin therapy compared to hydrophilic statin therapy.

Design: Retrospective cohort study. Setting: Large US commercial claims database PARTICIPANTS: 1:1 propensity score matched cohort of lipophilic (atorvastatin, lovastatin and simvastatin) and hydrophilic (pravastatin and rosuvastatin) statin initiators between January 2009 to June 2015. Outcome: New onset of depression.

Results: In a propensity-score matched cohort of 299,298 statin initiators, the crude incidence of depression in the hydrophilic and lipophilic group was 136.6 and 142.8 per 10,000 person-years respectively. Compared to hydrophilic statin use, lipophilic statin use was not associated with a statistically significant increase in the risk of depression, adjusted HR 1.05 (95% CI, 1.00-1.10, p = 0.078) and excess incidence of 6.3 (95% CI, -0.7-13.7) per 10,000 person-years. Findings were consistent across the subgroups of patients with history of psychiatric conditions HR 1.05 (95% CI, 0.94-1.16, p = 0.41), and those initiating statins for primary or secondary prevention, HR 1.03 (95% CI, 0.97-1.10, p = 0.33) and 1.07 (95% CI, 0.99-1.16, p = 0.10) respectively. Within individual lipophilic statins, only simvastatin was associated with a moderate increase in the risk of depression HR 1.09 (95% CI, 1.02-1.16, p = 0.003), followed by lovastatin HR 1.07 (95% CI, 0.93-1.24, p = 0.34) and atorvastatin HR 1.05 (95% CI, 0.97-1.13, p = 0.27). Limitations: Findings are generalizable to patients with commercial insurance.

Conclusions: Lipophilic statin use was not associated with a significant increase in the risk of incident depression.