What is the relationship between HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, commonly referred to as statins, and depression?

From the Guidelines

Statins are not conclusively linked to depression, and the cardiovascular benefits of statin therapy outweigh the potential risks of depression. When considering the relationship between statins and depression, it's essential to weigh the benefits of statin therapy against potential side effects. The most recent and highest quality study, 1, found that the safety profile of statins is acceptable, and earlier observations suggesting a link between lipid-lowering treatment and depression have not been confirmed. Some key points to consider include:

• Statins reduce the probability of cardiovascular disease events and mortality by at least a moderate amount in adults with one or more cardiovascular disease risk factors 1.
• The risk of myopathy associated with statin use can be minimized by identifying vulnerable patients and avoiding statin interactions with specific drugs 1.
• While some research suggests that statins might affect brain chemistry and potentially impact mood regulation, the relationship between statins and depression is not definitively established.
• If you're taking statins and experiencing new or worsening depression symptoms, discuss this with your healthcare provider, as they can evaluate whether your depression symptoms are related to your statin and consider alternative treatments if necessary. It's crucial to prioritize the cardiovascular benefits of statin therapy while monitoring for potential side effects, including depression, and adjusting treatment plans as needed to maintain necessary cardiovascular protection.

From the Research

Statins and Depression: An Overview

• Statins have been studied for their potential effects on depression, with some studies suggesting a positive effect on the occurrence and severity of depression 2.
• A systematic review and meta-analysis found that statin use was associated with a lower risk of depression, with statin users being 32% less likely to develop depression than non-users 3.
• However, another study found that statin use was associated with an increased risk of antidepressant use, but this association was deemed unspecific and may be mediated by residual confounding or bias 4.

Mechanisms and Clinical Studies

• Statins have anti-inflammatory properties, which may contribute to their potential antidepressant effects 2.
• The relationship between statins and depression is complex, and research findings have been mixed, with some studies suggesting that statins may lead to depression by lowering cholesterol 5.
• A review of the literature found that statins could lead to depression by lowering cholesterol, and that clinicians should be aware of this potential risk, especially in patients with depressive symptoms or low serum cholesterol levels 5.

Co-Prescription of Statins and Antidepressants

• The co-prescription of statins and antidepressants is common, especially in patients with cardiovascular disease and depressive symptoms 6.
• A comprehensive review found that the co-prescription of statins and selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) was generally safe and may have synergistic effects in patients with cardiovascular disease and major depression 6.
• However, caution is advised when co-prescribing statins with other classes of antidepressants, and further research is needed to fully understand the potential risks and benefits of this combination 6.