AUTHOR=De Giorgi Riccardo , Rizzo Pesci Nicola , Quinton Alice , De Crescenzo Franco , Cowen Philip J. , Harmer Catherine J. 

TITLE=Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

JOURNAL=Frontiers in Psychiatry

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.702617

DOI=10.3389/fpsyt.2021.702617

ISSN=1664-0640

ABSTRACT=<p><bold>Background:</bold> Depression is a leading cause of disability, burdened by high levels of non-response to conventional antidepressants. Novel therapeutic strategies targeting non-monoaminergic pathways are sorely needed. The widely available and safe statins have several putative mechanisms of action, especially anti-inflammatory, which make them ideal candidates for repurposing in the treatment of depression. A large number of articles has been published on this topic. The aim of this study is to assess this literature according to evidence-based medicine principles to inform clinical practise and research.</p><p><bold>Methods:</bold> We performed a systematic review of the electronic databases MEDLINE, CENTRAL, Web of Science, CINAHL, and <ext-link ext-link-type="uri" xlink:href="https://www.clinicaltrials.gov/" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link>, and an unstructured Google Scholar and manual search, until the 9th of April 2021, for all types of clinical studies assessing the effects of statins in depression.</p><p><bold>Results:</bold> Seventy-two studies were retrieved that investigated the effects of statins on the risk of developing depression or on depressive symptoms in both depressed and non-depressed populations. Fifteen studies specifically addressed the effects of statins on inflammatory-related symptoms of anhedonia, psychomotor retardation, anxiety, and sleep disturbances in depression. Most studies suggested a positive effect of statins on the occurrence and severity of depression, with fewer studies showing no effect, while a minority indicated some negative effects.</p><p><bold>Limitations:</bold> We provide a narrative report on all the included studies but did not perform any quantitative analysis, which limits the strength of our conclusions.</p><p><bold>Conclusions:</bold> Robust evidence indicates that statins are unlikely to lead to depressive symptoms in the general population. Promising data suggest a potential role for statins in the treatment of depression. Further clinical studies are needed, especially in specific subgroups of patients identified by pre-treatment assessments of inflammatory and lipid profiles.</p>