Stress has been suggested as a trigger factor for seizures in epilepsy patients, but little is known about cortisol levels, as indicators of stress, in adults with epilepsy. This systematic review summarizes the evidence on this topic. Following PRISMA guidelines, 38 articles were selected: 14 analyzing basal cortisol levels, eight examining antiepileptic drugs (AEDs) effects, 13 focused on seizure effects, and three examining stress. Higher basal cortisol levels were found in patients than in healthy people in studies with the most homogeneous samples (45% of 38 total studies). Despite heterogeneous results associated with AEDs, seizures were related to increases in cortisol levels in 77% of 38 total studies. The only study with acute stress administration found higher cortisol reactivity in epilepsy than in healthy controls. In studies using self-reported stress, high seizure frequency was related to increased cortisol levels and lower functional brain connectivity. Findings suggest that epilepsy could be considered a chronic stress model. The potential sensitizing role of accumulative seizures and issues for future research are discussed.
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