Statins as antiepileptogenic drugs: Analyzing the evidence and identifying the most promising statin

Abstract

Many brain insults and injuries are "epileptogenic": they increase the risk of developing epilepsy. It is desirable to identify treatments that are "antiepileptogenic": treatments that prevent the development of epilepsy, if administered after the occurrence of an epileptogenic insult. Current antiepileptic drugs are not antiepileptogenic, but evidence of antiepileptogenic efficacy is accumulating for a growing number of other compounds. From among these candidate compounds, statins are deserving of particular attention because statins are reported to be antiepileptogenic in more published studies and in a wider range of brain insults than any other individual or class of compounds. Although many studies report the antiepileptogenic effect of statins, it is unclear how many studies provide evidence that statins exhibit the following two essential features of a clinically viable antiepileptogenic drug: the drug must exert an antiepileptogenic effect even if it is initiated after the epileptogenic brain insult has already occurred, and the antiepileptogenic effect must endure even after the drug has been discontinued. In the current work, we interrogate published preclinical and clinical studies, to determine if statins fulfill these essential requirements. There are eight different statins in clinical use. To enable the clinical use of one of these statins for antiepileptogenesis, its antiepileptogenic effect will have to be established through future time- and resource-intensive clinical trials. Therefore, it is desirable to review the published literature to determine which of the statins emerges as the most promising candidate for antiepileptogenic therapy. Hence, in the current work, we also collate and analyze published data-clinical and pre-clinical, direct and indirect-that help to answer the question: Which statin is the most promising candidate to take forward into an antiepileptogenesis clinical trial?

Keywords: antiepileptogenesis; drug repurposing; epilepsy; epileptogenesis.