Pharmacoresistant Epilepsy: A Current Update on Non-Conventional Pharmacological and Non-Pharmacological Interventions

Abstract

Uncontrolled seizure or epilepsy is intricately related with an increase risk of pharmacoresistant epilepsy. The failure to achieve seizure control with the first or second drug trial of an anticonvulsant medication given at the appropriate daily dosage is termed as pharmacoresistance, despite the fact that these drugs possess different modes of action. It is one of the devastating neurological disorders act as major culprit of mortality in developed as well as developing countries with towering prevalence. Indeed, the presence of several anti-epileptic drug including carbamazepine, phenytoin, valproate, gabapentin etc. But no promising therapeutic remedies available to manage pharmacoresistance in the present clinical scenario. Hence, utility of alternative strategies in management of resistance epilepsy is increased which further possible by continuing developing of promising therapeutic interventions to manage this insidious condition adequately. Strategies include add on therapy with adenosine, verapamil etc or ketogenic diet, vagus nerve stimulation, focal cooling or standard drugs in combinations have shown some promising results. In this review we will shed light on the current pharmacological and non pharmacological mediator with their potential pleiotropic action on pharmacoresistant epilepsy.

Keywords: Adenosine; Drug resistant epilepsy; Modified Atkins diet; Responsive neurostimulation; Thyrotropin releasing hormone.

Figure 1.

Representation of different mechanisms associated with resistance development in epilepsy (A) shows the normal activity of transporter protein (P-gp transporter) and sufficient concentration at target site; (B) shows the over-expression of transport protein leading reduced concentration of AEDs at target site; (C) represents the normal target protein orientation and hence good efficacy of AEDs (D) represents the modified orientation of target protein leading inefficacy of AEDs; (E) represents overall mechanisms for the development of pharmacoresistance in epilepsy.

Figure 2.

Representation of strategies to treat drug resistance in epilepsy (A) represents the inhibition of over expressed P-gp transporters; (B) represents electrical circuit for vagus nerve stimulation and (C) deep brain stimulation; (D) represent normal processing of ketone bodies in liver and (E) in brain where these metabolites further converted into product (adenosine and GABA) leading to reduction in epilepsy.