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

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.

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.

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).

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.