Similar results have been shown for low testosterone levels in men ( 11– 13). Low levels of estrogen have been associated with depression in women ( 6– 10) and withdrawal of hormone therapy for remitted perimenopausal depression has been linked to recurrence of depressive symptoms ( 7). In this context, earlier studies have shown that statins can lower the concentrations of sex hormones for instance ( 2– 5).Ī connection between sex hormones and depression has also been demonstrated by earlier studies. Cholesterol itself is the basic substance for the synthesis of essential hormones such as sex hormones or vitamin D. The main mechanism of statins is inhibition of 3-hydroxy-3-methyl-glutaryl-coenenzyme A reductase (HMG-CoA reductase), which in turn inhibits synthesis of mevalonic acid, the main substrate for the synthesis of cholesterol. Recently published guidelines of the European Society of Cardiology (ESC/EAS) recommend that high-risk patients, such as patients with type-2 diabetes with organ damage or patients with CVD, should have low-density lipoprotein cholesterol (LDL-cholesterol) levels lower than 55 mg/dl ( 1). Statins rank among the most-prescribed drugs worldwide and have significant lipid-lowering effects and hence they are usually prescribed to prevent and treat cardiovascular disease (CVD). High-dose statin treatment was related to an overrepresentation, low-dose statin treatment to an underrepresentation of MDD. The results were confirmed in a sex-specific analysis and in a cohort of patients taking antidepressants, prescribed independently of inpatient care.Ĭonclusions: This study shows that it is important to carefully re-investigate the relationship between statins and MDD. However, there was a dose dependent relationship between statins and diagnosis of MDD. 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). 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. 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). We analyzed all patients with MDD undergoing statin treatment and calculated the average defined daily dose for six different types of statins. Methods: This cross-sectional study used medical claims data for the general Austrian population ( n = 7,481,168) to identify all statin-treated patients. 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. 7Gender Institute, Gars am Kamp, Austria.6Institute for Applied Systems Analysis (IIASA), Laxenburg, Austria.5Santa Fe Institute, Santa Fe, NM, United States.4Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria. ![]() 3Complexity Science Hub Vienna, Vienna, Austria.2Section for Science of Complex Systems, Center for Medical Statistics, Informatics, and Intelligent Systems (CeMSIIS), Medical University of Vienna, Vienna, Austria.1Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.Michael Leutner 1, Caspar Matzhold 2,3, Alexander Kautzky 4, Michaela Kaleta 2,3, Stefan Thurner 2,3,5,6, Peter Klimek 2,3 and Alexandra Kautzky-Willer 1,7 *
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