Determinants of fatigue among adults with epilepsy: Should we focus solely on antiseizure medication effects?

Abstract

Introduction: Fatigue is a frequent, albeit underexplored symptom among people with epilepsy (PWE). We aimed to investigate factors associated with fatigue among PWE with a special focus on antiseizure medication (ASM) use.

Methods: We conducted an anonymous cross-sectional survey among adult outpatients asking them to complete instruments assessing fatigue (the Fatigue Severity Scale, FSS), symptoms of anxiety (Generalized Anxiety Disorder-7, GAD-7), depression (Neurological Disorders Depression Inventory for Epilepsy, NDDI-E) as well as provide data on adverse ASM effects (Liverpool Adverse Events Profile, LAEP), medication type, number, adherence and self-reported treatment efficacy. Independent-samples t-test and Mann-Whitney U test (two groups) or analysis of variance and Kruskal-Wallis tests (more than two groups) were used for between-group comparisons. Correlation and linear multiple regression analysis was done in search of factors associated with fatigue. Multiple imputation was used for sensitivity analysis to account for missing data.

Results: The study sample comprised 232 PWE (130 (56.0 %) female, average age 39.1 ± 14.7 years) with 190 (81.9 %) PWE having completed the FSS and 40.5 % among them reporting clinically significant fatigue (FSS score ≥ 4). Higher FSS scores were associated with female sex (t = -2.086, p = 0.038), higher seizure frequency (r = 0.183, p = 0.020), missing at least one dose of ASMs in the past month (t = 2.491, p = 0.014), symptoms of anxiety (GAD-7, r = 0.510, p < 0.001), depression (NDDI-E, r = 0.453, p < 0.001) and adverse ASM profile (LAEP, r = 0.565, p < 0.001). The FSS score was inversely related to self-reported efficacy of epilepsy treatment (r = -0.277, p < 0.001) and independent of the ASM count, duration of use, recent changes in ASM regimen, frequency of non-adherence or the use of concomitant medications (p > 0.05). FSS scores also did not differ across subgroups based on specific ASM use. Adverse ASM effects (LAEP), symptoms of anxiety (GAD-7) and the subjectively perceived efficacy of current treatment were independent factors associated with results of the FSS in a multiple regression model (F(3, 130) = 27.310, p < 0.001, R_adj² = 0.372).

Conclusion: Our data suggests that fatigue among PWE is mostly associated with symptoms of anxiety, adverse ASM effects and self-reported treatment efficacy. Regardless of the type and count of ASMs, special attention to self-reported tolerability and efficacy, alongside psychological symptomatology, could help to reduce fatigue among PWE when adjusting treatment.

Keywords: Antiseizure medication; Anxiety; Depression; Pharmacotherapy; Seizure frequency.