Physical exercise as an adjunct to the pharmacological treatment of epilepsy: a priority for future research

Medication adherence is a major determinant of seizure control in people with epilepsy, yet nonadherence remains frequent and is associated with breakthrough seizures, increased healthcare utilization, and higher mortality. Despite the central role of antiseizure medications (ASMs), adherence is a multifactorial behavior shaped by routine stability, health beliefs, self-efficacy, mood, and social support, and it cannot be improved by prescription alone. Physical exercise has emerged as a promising complementary strategy in the management of chronic diseases, with benefits that extend beyond general health. This short communication examines the potential of regular physical exercise to act as an adjunct to the pharmacological treatment of epilepsy, with particular emphasis on how it may favor medication adherence. At the behavioral level, physical exercise may stabilize daily routines, improve mood and self-efficacy, and reinforce treatment engagement factors that plausibly support consistent medication taking. At the physiological level, physical exercise modulates hemodynamic, metabolic, and neurobiological pathways, although direct evidence of clinically relevant effects on ASM disposition remains scarce. Nonetheless, exercise-induced pharmacokinetic alterations depend on the type, intensity, and duration of exertion-ranging from sustained aerobic exercise to high-intensity resistance training-which differentially modulate hemodynamics, metabolic pathways, and plasma protein binding, with the greatest potential relevance for antiseizure medications with a narrow therapeutic index. Barriers to physical exercise participation, including fear of seizures, stigma, and limited professional counseling, parallel those that compromise adherence and deserve systematic attention. We conclude that physical exercise should be regarded as a safe, low-cost, complementary component of epilepsy care, and that prospective studies examining its effects on medication adherence and pharmacological outcomes represent a research priority.