ABSTRACT
Objectives: To determine the prevalence of fatigue and depression in patients with epilepsy (PWE), explore their relationship, and identify the factors associated with fatigue in this population.
Methods: This retrospective cross-sectional study involved adult PWE at King Fahad Medical City, Riyadh, Saudi Arabia, from April to July 2023. The Arabic version of the Fatigue Severity Scale questionnaire was used to estimate the presence and severity of fatigue. The Patient Health Questionnaire-9 was used for screening depression. The demographic and clinical data of the patients were analyzed.
Results: In total, 259 PWE were enrolled. Of these, 66.8% had focal epilepsy and 39.7% had controlled seizures. Fatigue was prevalent in 34.4% of PWE, of whom only 10% had no depression. Significant correlations were observed between fatigue and female sex (p=0.002), uncontrolled seizures (p<0.001), and missed medication doses (p=0.03). Additionally, a considerable positive correlation was observed between fatigue and depression scores (r=0.5, p<0.001).
Conclusion: Fatigue is prevalent among PWE. This study emphasizes the importance of assessing and managing fatigue and depression to improve the quality of life (QOL) of PWE. Further research in larger populations is recommended to identify the predictors and effective management strategies for fatigue in PWE.
Epilepsy is a common neurological disorder worldwide with an overall lifetime prevalence of 7.60 per 1,000 individuals.1 The prevalence of active epilepsy in Saudi Arabia is 6.54 per 1,000 individuals, closely aligning with the global rate.2,3,4 More recent data indicate a prevalence of 2.99–5.16 per 1,000 individuals.5 Globally, epilepsy accounted for more than 13 million disability-adjusted life-years in 2016, representing 0.5% of the total disease burden.6,7
Fatigue is a complex condition characterized by extreme and persistent tiredness, weakness, or exhaustion, mental, physical, or both.8 Fatigue is likely more prevalent in patients with epilepsy (PWE) than in the general population.9 The relationship between fatigue and seizures is complex, as fatigue is a known trigger for seizures and a consequence of them, occurring in either the interictal or postictal state, which potentially lasts for days and causes functional impairment.10,11 Fatigue negatively affects the quality of life (QOL) of PWE, necessitating the identification and management of its risk factors to improve patient outcomes.10 Studies involving 700 individuals across seven investigations reported a 43.8–50% prevalence of fatigue among PWE.12 Fatigue severity in PWE can be affected by seizures, depression, medication, and age.12.13
Fatigue is also a hallmark symptom of depression, occurring in 20–90% of individuals with depression.14,15 Furthermore, depression is prevalent in 9–37% of PWE based on variable reports.12,16 The relationship between epilepsy and depression is bidirectional, with each condition potentially exacerbating the other.
Nevertheless, research on fatigue and its association with depression in PWE, particularly in Saudi Arabia, remains limited. Therefore, this study aimed to determine the prevalence of fatigue and depression in PWE explore their relationship in this population.
Methods
Study design and data collection
This cross-sectional retrospective study was conducted from April to July 2023 using online surveillance in King Fahad Medical City (KFMC), Riyadh, Saudi Arabia. Ethical approval was obtained from the KFMC Institutional Review Board prior to the commencement of the study.
The PWE aged ≥14 years with a minimum of 1 year of history of epilepsy were included. Patients with epileptic encephalopathies or chronic disabling neurological or medical conditions were excluded. Sociodemographic and clinical data of patients, including epileptic history, seizure characterization, treatment, status epilepticus (SE)-related intensive care unit (ICU) admission, emergency department (ED) visits due to seizures, and history of epilepsy surgery, were collected from 259 patients after obtaining informed consent. Seizures were classified and localized according to the International League Against Epilepsy 2017 classification using semiology, routine scalp electroencephalography (EEG), and brain magnetic resonance imaging (MRI) findings. Additionally, fluorodeoxyglucose positron emission tomography, magnetoencephalography, and video-EEG results were evaluated when available. Seizures were categorized as either controlled or uncontrolled based on the time of occurrence of the last seizure.17-20
The Fatigue Severity Scale (FSS) questionnaire, translated and validated in Arabic, was used to determine the presence and severity of fatigue,21 wherein a total score of ≥4 and <4 indicated fatigue and no fatigue, respectively. The fatigue severity corresponded to the score, with higher scores reflecting more severe fatigue.22
A validated Arabic version of the Patient Health Questionnaire-9 (PHQ-9) was used to evaluate the prevalence and intensity of depression. The results were categorized into minimal or no depression, mild, moderate, moderately severe, and severe depression based on the corresponding total scores of 1–4, 5–9, 10–14, 15–19, and 20–27, respectively.23,24
Statistical analysis
Statistical Package for the Social Sciences program version 25 was used for data processing, and qualitative and quantitative variables were expressed as number (%) and mean (± standard deviation [SD]), respectively. Categorical data were expressed as frequencies and percentages, whereas metric data were expressed as averages, means (±SD), and medians (interquartile ranges). Statistical inference was drawn using 95% confidence intervals. The Kolmogorov–Smirnov and Shapiro–Wilk tests were used to check the normality of the metric data. Mann–Whitney U test was used for intergroup comparisons of non-normally distributed variables, whereas Student’s t-test was used for normally distributed data. The chi-square test was used to measure the association between all categorical variables and the underlying dependent variable. The Fisher test was used whenever the cell frequency was less than five. All significantly associated variables in the univariate analysis were loaded for backward-step binary regression analysis. P<0.05 was considered statistically significant.
Results
Demographics
In total, 259 PWE were enrolled, with the largest proportion (110 [42.5%]) of individuals aged 21–30 years. Notably, 128 (49.4%) PWE were male and 131 (50.6%) were female. Furthermore, 232 (89.6%) PWE were right-handed, and 136 (52.5%) were graduates. Less than half of PWE were married (126 [48.6%]), more than half were employed (155 [59.8%]), and most reported working only during the daytime (130 [83.8%]) (Table 1).
- Sociodemographic characteristics of participants.
Clinical characteristics: Table 2 presents the clinical profiles of PWE. A substantial proportion of PWE (86 [33.2%]) reported having epilepsy for 10–20 years. Specifically, 173 (66.8%) PWE had focal epilepsy, 74 (28.6%) had generalized epilepsy, and 12 (4.6%) had unclassified seizures. Among the patients with focal epilepsy, temporal lobe epilepsy was the most common subtype (81 [46.8%]). MRI identified lesions as the cause of epilepsy in 123 (47.5%) patients, whereas 136 (52.5%) patients exhibited normal MRI findings.
- Clinical characteristics of participants.
Uncontrolled seizures were reported by 156 (60.2%) PWE, with 77 (49.3%) experiencing seizures once every 3–6 months and 15 (9.6%) experiencing seizures daily. Drug-resistant epilepsy (DRE) was reported in 65 (25.1%) PWE who were taking three or more antiseizure medications (ASMs). Notably, 94 (36.3%) and 100 (38.6%) PWE were taking two or one ASM, respectively. Furthermore, 228 (88%) PWE reported good medication compliance, and among those with poor compliance, 13 (41.9%) missed doses almost daily.
Epilepsy surgery was performed in 27 (10.4%) PWE. ED visits due to breakthrough seizures were reported by 126 (48.6%) PWE, whereas 47 (18.1%) PWE had previous ICU admissions due to SE. Eighty participants (31.1%) had a history of seizure-related trauma.
Fatigue
Fatigue was reported by 89 (34.4%) PWE, whereas the remaining 170 (65.6%) reported no fatigue (Figure 1).
- Prevalence of fatigue in PWE. *PWE = Patients with epilepsy
A significant association was found between fatigue and sex (p=0.002), with females experiencing fatigue more frequently than males (Table 3).
- Relationship between fatigue and demographic factors.
Analysis of epilepsy characteristics (Table 4) showed significant associations between fatigue and seizure control status (p<0.001) as well as the frequency of missing ASM doses in the noncompliant subgroup (P = 0.03). However, no significant association was observed between fatigue prevalence and epilepsy classification.
- Prevalence of fatigue according to epilepsy characteristics.
Depression
Depression was highly prevalent, affecting 57.2% of PWE with variable severity. Of these, the largest proportion of patients had mild depression (68 [26.3%]) followed by those with moderate depression (50 [19.3%]), then by those with moderately severe depression (25 [9.7%]), whereas only some experienced severe depression (5 [1.9%]) (Figure 2a).
- Correlation between FSS and PHQ-9 scores.
Fatigue and depression
A significant association was observed between fatigue and depression severity (p=0.001), with patients with fatigue demonstrating higher depression severity. Furthermore, a significant positive correlation was observed between the FSS and PHQ-9 scores (r=0.5, p<0.001) (Figure 2b).
Discussion
Fatigue in PWE
This study revealed a 34.4% prevalence of fatigue in PWE, accounting for approximately one-third of the sample. Previous studies on fatigue in PWE have reported variable rates. Our findings indicate a slightly higher prevalence of fatigue in PWE than the 29.5% prevalence reported in one previous study.25 However, another previous study reported a 34% prevalence of fatigue in PWE,26 aligning with our results. Nevertheless, several other studies have also reported higher prevalence rates, such as 45.8%.27 In contrast, Anand et al. found that 83% of PWE were fatigue-free,28 a higher proportion than that observed in our study (65.6%). Early research by Yan et al29 in 2006 demonstrated a high frequency of fatigue among PWE.29 Additionally, a systematic review by Kwon et al. highlighted the significant prevalence of fatigue among PWE, with an overall rate of 47.1%.12 A study from Nigeria comparing PWE to healthy individuals reported similar fatigue severity among the two groups, although PWE reported a greater impact on their lives.30 However, this study did not include a control group for comparison.
In our study, fatigue was significantly associated with female sex, uncontrolled seizures, and frequently missed ASM doses. However, no significant associations were observed between fatigue and age, marital status, education level, or occupation. These findings partially align with the results of previous studies, reporting associations between fatigue and being unmarried but not with sex or seizure-related factors.26 These differences highlight the variability in risk factors across populations.
Seizure control was determined by timing of the last seizure, those who had one or more seizure attack within one year, considered uncontrolled.17-20 We found that uncontrolled seizures were associated with fatigue in 42% (p<0.001).
Achieving seizure freedom with considerable tolerability to ASM and improving the QOL of the patients remain the main objectives of the medical management of seizures.31 Effective seizure control and improving adherence to ASM remain critical for minimizing fatigue in PWE.31 Poor compliance with ASM is a major barrier to achieving seizure remission, with some studies reporting that up to one-third of patients being non-compliant.32 Although no direct association was observed between fatigue and compliance status in our study, missed ASM doses either on daily, weekly or monthly basis were significantly correlated with fatigue prevalence (p=0.03), likely because of their impact on seizure control. Missing a dose of ASM weekly and monthly was associated with fatigue in 58.3 % and 50% respectively.
Depression in PWE
Psychiatric comorbidities, particularly depression, are more common in PWE than in the general population.33,34 Depression is a frequently under-recognized condition in PWE.35 In this study, depression was highly prevalent, affecting 57.2% of participants. Most patients, reported mild to moderate depression. Similar results have been reported in other studies in Saudi Arabia, with the prevalence of depression being 73.7–76.7%.36,37 Severe and moderately severe depression was observed in 1.9% and 9.7% of our sample, respectively, which is lower than the previously reported rates.
Association between fatigue and depression in PWE
This study revealed a significant association between fatigue and depression. Patients with fatigue had higher depression severity, ranging from moderate to severe. Furthermore, a positive correlation was observed between the FSS and PHQ-9 scores. These findings are consistent with those of previous studies, reporting moderate positive correlation between fatigue and depression among PWE.27 A systematic review also identified depression as a significant risk factor for fatigue in PWE, with 7 of 12 studies reporting a strong association.12 Similarly, Ettinger et al38 demonstrated a strong correlation between depression and fatigue in PWE, with the prevalence of depression reaching 52% in this population.38 Our findings suggests that screening for fatigue in PWE is considerably reasonable and potentially revealing of undiagnosed depression. Similarly, in PWE who exhibits depressive features, symptomatic fatigue may need to be addressed. Ultimately, targeting either comorbidity with pharmacological or non-pharmacological treatment modalities may significantly improve the QOL of PWE.
Our study further revealed no significant association between epilepsy classification and fatigue or depression, which is consistent with previous findings,36 underscoring the complexity of these comorbidities. This indicates that factors other than the epilepsy classification may contribute to their prevalence.
Clinical implications, limitations and future directions: This study provides valuable insights into the prevalence and interplay of fatigue and depression among PWE in Saudi Arabia. However, this study also has some limitations. First, it was conducted at a tertiary care center with specialized epilepsy services, which may have introduced a selection bias, particularly toward patients with DRE. Second, the short data-collection period and relatively small sample size further limit the generalizability of the results. Including a healthy control group would have enhanced the robustness of the findings.
Conclusion
Fatigue was prevalent in approximately one-third of PWE, irrespective of epilepsy duration or classification. Fatigue was also significantly associated with female sex, poorly controlled seizures, and non-compliance with ASM. Additionally, fatigue was positively correlated with depression severity. Screening and management of fatigue in PWE may significantly improve their QOL. Nevertheless, larger studies are warranted to explore the predictors, risk factors, and management strategies for fatigue in PWE.
Acknowledgment
We would like to thank Elsevier (webshop.elsevier.com) for English language editing.
Footnotes
Disclosure. Authors have no conflict of interests, and the work was not supported or funded by any drug company.
- Received January 30, 2025.
- Accepted July 29, 2025.
- Copyright: © Neurosciences
Neurosciences is an Open Access journal and articles published are distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC). Readers may copy, distribute, and display the work for non-commercial purposes with the proper citation of the original work.
References
In this issue
Jump to section
Related Articles
Cited By...
- No citing articles found.