The findings of a study published in the Journal of Affective Disorders did not suggest a relationship between lipophilic statins and depression when compared with hydrophilic statins.

Statins are typically prescribed to individuals with diabetes or at risk for heart attack or stroke, and are intended to lower cholesterol. Research has suggested a number of possible relationships with lipophilic statins, including a protective phenomenon against depression and higher risk for dementia, although these associations remain controversial.

The authors identified lipophilic and hydrophilic statin users through the MarketScan Commercial Claims database between January 2009 and June 2015. Patients with a history of depression or antidepressant use, suicidal incidents, bipolar disorder, lithium use, or <2 visits during the study duration were not included. Characteristics were comparable between hydrophilic and lipophilic statin initiators.

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Analyses indicated statistically insignificant hazard ratios of 1.05 (95% CI, 1.00-1.10) for depression and 1.09 (95% CI, 0.57-2.10) for suicide attempts among lipophilic statin users, suggesting comparable tolerability between the 2 drugs overall. An analysis of individual lipophilic statins did find a moderate risk for depression among simvastatin users compared with hydrophilic statin users.

Simvastatin is notable for being the most lipophilic and least hepatoselective among commercially available statins. Because of this, the authors explained, “it can more easily cross the blood-brain barrier and directly influence mood.” The authors noted the association was fairly small.

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This study is notable as the first to compare lipophilic and hydrophilic statins directly. The authors noted that some relevant information was not available regarding participants, including family history of depression, socioeconomic status, and lifestyle characteristics. In addition, they stated, the findings may not generalize to individuals without commercial health insurance.


Dave C, Winterstein A, Park H, Cook R, and Hartzema A. Comparative risk of lipophilic and hydrophilic statins on incident depression: A retrospective cohort study. J Affect Disord. 2018;238:542-546.