Seizure medications and interictal spiking: Implications for cognition and behavior

Interictal epileptiform discharges (IEDs) are not just biomarkers but active contributors to cognitive and behavioral dysfunction. Antiseizure medications (ASMs) not only treat seizures but can also modulate IEDs. However, their broader neurocognitive impact remains underexplored. The goal of this review is to synthesize current evidence on ASM effects on IEDs and to examine their therapeutic implications for cognitive and behavioral improvement. A comprehensive literature search was conducted, focusing on studies that reported ASM-related IED modulation and associated cognitive or behavioral measures. ASMs demonstrate variable efficacy in reducing IEDs, with broad-spectrum agents like valproate and lamotrigine showing consistent suppression of IEDs resulting in cognitive benefit, particularly in children. The use of sodium channel blockers, such as lamotrigine and oxcarbazepine, produces cognitive improvements. Additionally, γ-aminobutyric acidergic agents, including clobazam and diazepam, are effective in treating developmental epileptic encephalopathies. Emerging therapies, including cannabidiol and perampanel, show promising IED and behavioral outcomes. Animal studies confirm that ASMs can suppress IEDs, leading to enhanced memory, attention, and social behaviors. Targeted reduction of IEDs may lead to improved cognitive and behavioral outcomes. This can be achieved by testing and recognizing ASMs in carefully designed prospective trials in animals and humans.