A systematic review to assess seizure risk with chloroquine therapy in persons with epilepsy

BackgroundThe goal of this systematic review is to assess the published literature for seizure risk with chloroquine therapy in persons with and without epilepsy. With the COVID-19 pandemic, there is a desperate need for therapy against the SARS CoV-2 virus. Chloroquine is one proposed medication that has received substantial public attention. However, drug labeling in the package insertion states that persons with epilepsy have the risk of chloroquine provoking seizures, and this has increased questions and anxiety in the epilepsy community. MethodsPubMed (1970 to March 27, 2020) and the Embase (1970 to March 27, 2020) were searched with the terms chloroquine and seizure or epilepsy. Selected studies were reviewed, and the adverse drug reaction was classified. ResultsOnly nine out of 27 studies were deemed eligible for systematic analysis. Out of the nine studies, only one was a prospective study (N=109), two were case series (N=6), and the remaining 6 were case reports. The dose of chloroquine ranged between 100-500 mg/day, except in one patient, the seizure was after taking 1000 mg. The strength of causality for the drug causing seizures in healthy and persons with epilepsy was mostly possible or unlikely, and none were certain. The only clinical trial that evaluated seizure risk with chloroquine failed to find any significant relation. ConclusionAlthough the drug insertion label states an increased risk of seizure, the systematic review highlights that such a statement is not supported by any class I studies but by anecdotal case reports. The only randomized clinical study revealed that seizures were not associated with an increased blood level of chloroquine or its metabolite. The present systematic review should provide reassurance to busy clinicians and persons with epilepsy that chloroquine, if prescribed to treat COVID-19, lacks any substantial evidence to suggest that the medication increases the risk of seizure.