Therapeutic Advances in Drug-Resistant Epilepsy

Background: Drug-resistant epilepsy (DRE) is a condition that affects up to 40% of the total population of patients with epilepsy. Advancements in the pharmaceutical field over recent decades have facilitated a significant expansion in the range of available drug options. Nevertheless, the prevalence of DRE has remained unaltered in recent years. Areas of Uncertainty: It is not completely understood how the new antiseizure medications and therapeutic strategies will impact the current burden of patients with DRE. Data Sources: A bibliographic search was made in MEDLINE to make a content analysis of the identified studies on the management of DRE. Therapeutic Advances: The elucidation of different underlying mechanisms of DRE has helped to create therapeutic alternatives for DRE. Some current drugs under clinical studies are cenobamate (100% and ≥90% of sustained seizure reduction), padsevonil (50% of seizure reduction), radiprodil, and NRTX-1001 (good tolerability, safety, and pharmacokinetic profiles), and BL-001 (favorable safety profile and good tolerability). Preclinical studies have also shown promising results of LRP-661, a cannabidiol derivative with superior bioavailability compared with the actual formulation of cannabidiol available in the market. In addition, gene therapies such as CAMK2A-EKC have achieved good effects in the control of focal cortical dysplasia type II in animal models. However, the combination of epilepsy surgery with novel ways of antiseizure medications administration, such as intraventricular delivery of valproate, increases the possibility of therapeutic success for patients with DRE. Conclusions: The promising therapeutic advances in the pharmacologic field have still not made great changes in the prevalence of DRE. Utilizing established and widely recognized antiseizure medications continues to be a viable treatment approach, particularly when complemented by additional therapeutic modalities such as physical exercise, ketogenic diet, interventional procedures, and epilepsy surgery.