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.
Keywords: ASM resistance; PWNDE; depression symptoms; fatigue; sleep quality.
Association between fatigue, sleep quality, depression symptoms, and antiseizure medication resistance in patients with newly diagnosed epilepsy Why was the study done? Complaints of fatigue and poor sleep quality are common in patients with epilepsy. A crucial problem related to fatigue is that it may precipitate a single or multiple seizures. Patients with poor sleep quality also have high seizures frequency and depression symptoms. We wondered whether patients with fatigue or poor sleep quality have higher risk of developing resistance to anti-seizure medication. We also investigate the role of depression symptoms in the relationship. What did the researchers do? The research team invited patients with newly diagnosed epilepsy to participate in this study in Northeast China. The participants were asked to complete questionnaires to assess fatigue, sleep quality and depression symptoms. Then the participants were treated with anti-seizure medications. The researchers observed how the patients responded to the anti-seizure medications over 24-month period. What did the researchers find? A total of 189 patients participated in this study. We observed that 59 patients had resistance to anti-seizure medication and 130 responded well to drugs. Patients who had fatigue were more likely to experience drug resistance. Similarly, patients who had poor sleep quality were more likely to have drug resistance. Additionally, depression symptoms play an important in the effect of fatigue and sleep quality on drug responsiveness. What do the findings mean? This study has some important findings. Patients who had fatigue or poor sleep quality were more likely to responded poorly to anti-seizure medications. We also observed the mediating role of depression severity. These findings tell us the importance of assessing fatigue, sleep quality and depression symptoms in patients with newly diagnosed epilepsy which may help identify those at greater risk of drug resistance.
© The Author(s), 2025.