Fatigue, sleep quality, depression symptoms, and antiseizure medication resistance in patients with newly diagnosed epilepsy

Background: Complaints of fatigue and poor sleep quality are common in patients with epilepsy. Fatigue may precipitate seizures, and patients with poor sleep quality have higher frequency of seizures and are more likely to have symptoms of depression. Objectives: This study aims to determine the association of baseline fatigue and sleep quality with antiseizure medication (ASM) resistance in patients with newly diagnosed epilepsy (PWNDE). We also evaluate whether the association is mediated by depression symptoms. Methods: We performed a prospective cohort study of PWNDE at comprehensive epilepsy center in Northeast China between June 2020 and May 2024. Fatigue, sleep quality, and depression symptoms were assessed at baseline. All patients were followed for 24 months for ASM-resistant epilepsy. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) of ASM resistance. Models fitted with restricted cubic spline were performed to test for linear and nonlinear shapes of each association. Mediation analysis was used to estimate the mediating effects of depression severity on association between fatigue, sleep quality, and ASM resistance. Results: A total of 189 patients (59 ASM-resistant cases and 130 ASM-responsive controls) were included in the final analysis. Baseline fatigue (HR, 1.98; 95% confidence interval (CI), 1.094–3.583, p = 0.024) and poor sleep quality (HR, 2.193; 95% CI, 1.29–3.729, p = 0.004) were associated with an increased hazard of ASM resistance in PWNDE after full adjustments. There exists a nonlinear association between Fatigue Severity Scale score and the hazard of ASM resistance ( P for nonlinear = 0.012). Depression severity partly mediated the effect of fatigue and sleep quality on ASM resistance, with mediated proportions of 18.5% for the fatigue and 23.7% for the sleep quality. Conclusion: Baseline fatigue and poor sleep quality were associated with an increased risk of ASM resistance. The association between fatigue, sleep quality, and ASM resistance were partly mediated by depression severity. These findings emphasize that patients with ASM-resistant epilepsy are more likely to have fatigue, depression, and poor sleep quality at baseline and this may be unrelated to ASM intake.