The Effect of Statins in Epilepsy: A Systematic Review

Abstract

ABSTRACT Background and Objectives: Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, used for the management of hypercholesterolemia and related atherosclerotic diseases. Several studies have indicated the neuroprotective effects of statins on several neuropathological conditions. However, the role of these medications in epilepsy is still unclear. The purpose is to evaluate and summarize the level of evidence on the efficacy of statins in neuronal hyperexcitability and the neuroinflammatory processes of epilepsy. Methods: A systematic review was performed. Eligibility Criteria: This review involved studies conducted in humans and nonhuman experimental models, covering the use of an inhibitor of HMG-CoA reductase, alone or accompanied by another medication, in epilepsy. Information Sources: A systematic literature search was performed in PubMed, Embase, Ebsco Host, Scopus, Science Direct, Medline, and LILACS. Risk of Bias: It was evaluated with the Newcastle–Ottawa Scale and the experimental studies were evaluated using the GRADE tool. Results: Twenty articles of the 183 evaluated were included. Sixteen studies were conducted in animal models and four studies in humans. Most studies in mice reported a reduction in epileptiform activity and reduction in systemic inflammation with the treatment of statins, potentially influencing epilepsy control. Few studies in humans were performed in the geriatric population with variable results (neuroinflammation, seizure prevention, cell death, prevention of kindling, increase in convulsive threshold, increase in latency, decrease in frequency of crisis, and reduction in mortality) related to reduction in the rate of hospitalizations, mortality, and prevention of epilepsy. Studies in mice found a decrease in interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha and an increase in IL-10 and endothelial nitric oxide synthase. Conclusions: The possible antiepileptic mechanism of statins may be related to the reduction in neuroinflammation mediated by a decrease in pro-inflammatory cytokines and action in the nitrergic system. Further studies evaluating the impact of statins on seizure control are necessary.