Drug Resistance in Epilepsy: Which Prospect to Tame its Stubbornness?

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Doru Georg Margineanu, Ph.D.


Epilepsy is a major health problem, it being among the most common chronic neurologic pathologies. Its basic therapy is via anti-seizure drugs (ASDs), of which nearly two dozen are currently available for symptomatic treatment of epileptic seizures. But, notwithstanding the increasing ASD options, about one-third of epileptic patients remain drug-refractory, and this fraction did not diminish over decades. This paper reviews the subject of drug resistance in epilepsy (DRE), in view of exploring the prospect to overcome its persistence. The survey of various hypotheses about DRE origin and mechanisms notices that any of them alone does not fully account the DRE, their multitude deriving from the lack of solution to this bad medical need. The non-pharmacological (neurosurgical, brain stimulation, focal treatments and dietary) approaches of drug-intractable epilepsy are also surveyed, with the sober conclusion that, in a predictable future, the mainstay of epilepsy therapy will likely remain the drugs. The vast multiplicity of molecular changes associated with DRE suggests that its pharmacological resolution might arise only from integrative, systemic approaches, beyond the reductionist single-target paradigm that dominated the ASD discovery, in the last several decades. A conceivable lessening of DRE might be brought about by precision (personalized) medicine, assisted by complex systems biology description of individual epileptic pathology. In a longer run, the emergent network pharmacology might led to genuine innovative multi-potent antiepileptic drugs, able to treat distinct subpopulations of current refractory patients.

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MARGINEANU, Doru Georg. Drug Resistance in Epilepsy: Which Prospect to Tame its Stubbornness?. Medical Research Archives, [S.l.], v. 9, n. 8, aug. 2021. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2514>. Date accessed: 20 sep. 2021. doi: https://doi.org/10.18103/mra.v9i8.2514.
Research Articles


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