New possibilities of overcoming pharmacoresistance in epilepsy

Abstract

Despite the presence of antiepileptic drugs with different mechanisms of action and application points, almost a third of patients still remain resistant to drug therapy. In such patients, the risk of physical and mental injuries, depression, premature death increases, and the quality and standard of living decreases.Objective. To study the mechanisms of formation of pharmacoresistance in epilepsy and to evaluate possible ways to overcome it based on the analysis of current scientific publications containing information on this topic.Results. The proposed pathophysiological mechanisms of the formation of drug resistance reflect the target hypothesis, the carrier hypothesis, pharmacokinetic theory and neural network theory. However, they are based on preclinical studies and do not have a comprehensive explanation for the appearance of this phenomenon. Surgical treatment remains the most studied and most commonly used approach. Both the usual resection of the epileptogenic part of the brain and new less crippling interventions are used: laser ablation and stereotactic radiosurgery. As an alternative, polytherapy schemes, invasive and non-invasive neurostimulation techniques, and diet therapy can be considered.Conclusions. Insensitivity to antiepileptic drugs remains a major problem in epileptology, and to overcome it, new methods are being sought and developed to influence the presumed pathogenetic targets of pharmacoresistant epileptogenesis. Vagus, deep, transcranial neurostimulation, stereotactic surgery, and laser ablation should be considered as new safe and potentially effective techniques.