Abstract
Objective: To examine the dose-dependent relationship of different types of statins with the occurrence of major depressive disorder (MDD) and prescription of antidepressant medication.Methods: This cross-sectional study used medical claims data for the general Austrian population (n = 7,481,168) to identify all statin-treated patients. We analyzed all patients with MDD undergoing statin treatment and calculated the average defined daily dose for six different types of statins. In a sub-analysis conducted independently of inpatient care, we investigated all patients on antidepressant medication (statin-treated patients: n = 98,913; non-statin-treated patients: n = 789,683). Multivariate logistic regression analyses were conducted to calculate the risk of diagnosed MDD and prescription of antidepressant medication in patients treated with different types of statins and dosages compared to non-statin-treated patients.Results: In this study, there was an overrepresentation of MDD in statin-treated patients when compared to non-statin-treated patients (OR: 1.22, 95% CI: 1.20–1.25). However, there was a dose dependent relationship between statins and diagnosis of MDD. Compared to controls, the ORs of MDD were lower for low-dose statin-treated patients (simvastatin>0– < =10 mg:OR: 0.59, 95% CI: 0.54–0.64; atorvastatin>0– < =10 mg:OR:0.65, 95%CI: 0.59–0.70; rosuvastatin>0– < =10 mg:OR: 0.68, 95% CI: 0.53–0.85). In higher statin dosages there was an overrepresentation of MDD (simvastatin>40– < =60 mg:OR: 2.42, 95% CI: 2.18–2.70, >60–80 mg:OR: 5.27, 95% CI: 4.21–6.60; atorvastatin>40– < =60 mg:OR: 2.71, 95% CI: 1.98–3.72, >60– < =80 mg:OR: 3.73, 95% CI: 2.22–6.28; rosuvastatin>20– < =40 mg:OR: 2.09, 95% CI: 1.31–3.34). The results were confirmed in a sex-specific analysis and in a cohort of patients taking antidepressants, prescribed independently of inpatient care.Conclusions: This study shows that it is important to carefully re-investigate the relationship between statins and MDD. High-dose statin treatment was related to an overrepresentation, low-dose statin treatment to an underrepresentation of MDD.
Highlights
Statins rank among the most-prescribed drugs worldwide and have significant lipid-lowering effects and they are usually prescribed to prevent and treat cardiovascular disease (CVD)
Statin-treated patients were more likely to have been diagnosed with MDD and were more commonly treated with antidepressants when compared to age- and sex-matched non-statin treated patients (OR: 1.54, CI: 1.53–1.56)
Sex-Specific Analysis of the Dose-Dependent Relationship Between Statins and Diagnosis of MDD. In both male and female patients, the results shown in the general population were confirmed, demonstrating that lowdose statin treatment is related to underrepresentation of diagnosed MDD whereas high-dose statin treatment is related to overrepresentation when compared to non-statin-treated patients
Summary
Statins rank among the most-prescribed drugs worldwide and have significant lipid-lowering effects and they are usually prescribed to prevent and treat cardiovascular disease (CVD). Cholesterol itself is the basic substance for the synthesis of essential hormones such as sex hormones or vitamin D. In this context, earlier studies have shown that statins can lower the concentrations of sex hormones for instance [2,3,4,5]. A connection between sex hormones and depression has been demonstrated by earlier studies. Earlier studies report associations between low levels of cholesterol and statin usage and depression, as well as related symptoms such as lowered mood, aggression and suicidality [14,15,16,17]. A potential mechanism for these associations is impaired serotonin signaling, as cholesterol is required for serotonin 1A receptor function [18,19,20] and downregulation of the serotonin 1A receptor has been linked to mood disorders such as depression [21]
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