Do statins have antidepressant effects?

Statins are used widely in primary and secondary prevention of cardiovascular disease; a treatment effect that has long been thought to be due to their cholesterol-lowering properties. However, statins also have a wide range of anti-inflammatory effects independent of their lipid-lowering mechanisms. In depression, low-grade inflammation is a replicated finding, and several studies have shown antidepressant properties of diverse anti-inflammatory drugs. Large observational studies have suggested reduced risks of depression amongst those taking statins, an effect that is thought to be explained by the anti-inflammatory properties of this class of drugs. Also, preliminary randomized controlled trials (RCTs) have indicated that statins may have adjunctive antidepressant effects when used as add-on treatment to selective serotonin reuptake inhibitors (SSRIs). However, the RCTs were small and limited by low generalizability, and some early observational studies have pointed towards potential neuropsychiatric adverse effects of statin treatment. Nevertheless, based on the good tolerability and general safety of the statins, researchers are currently investigating the potential antidepressant properties of these agents. The present review aims to give an overview on the potential antidepressant effects of statins based on their anti-inflammatory properties, covering topics such as safety versus treatment effects, potential mechanisms of action and the possibility of targeted treatment (precision medicine).