Quality of life in adults with refractory epilepsy in Thailand: a multicenter upcountry nationwide study

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Few studies have described the variables that impact quality of life (QoL) in patients with refractory epilepsy in developing Asian countries. Here, we sought to assess the relationship of sociodemographic factors, epilepsy-related variables, and psychiatric comorbidity with HRQoL. Methods: We consecutively recruited a sample of adult patients with confirmed refractory epilepsy in multiple centers in Thailand. Multivariable linear regression analyses were used to identify socio-demographic factors, epilepsy-related variables, and psychiatric comorbidity factors associated with quality of life using QOLIE-31 score. Regression models were based on a pre-compiled directed acyclic graph (DAG). Results: A total of 394 patients from seven centers were evaluated. The mean QOLIE-31 score was 59.3 (SD = 15.5). The subscale score for overall quality of life was the highest (65.0 ± 15.9) and that for social function was the lowest (51.6 ± 25.2). There were significant differences between age groups, gender, current working status, seizure frequency, depression, anxiety, and QOLIE-31 score in the univariate analysis. Multivariable regression analyses identified significant total effects of age and gender on quality of life, significant direct effects of depression and anxiety, and both total and direct effects of seizure frequency, current working status, depression, and anxiety, indicating that the DAG sought factors associated with quality of life. We found a statistically significant difference in QOLIE-31 scores between age groups and religion-interaction, current working status, depression, and anxiety. Conclusions: Our study included adult patients with focal refractory epilepsy. In addition to age and gender, depression, anxiety, and seizure frequency were the main determinants of QOL. Thus, improvement of QOL by screening for its factors should be one of the main goals in the treatment of refractory epilepsy. quality of life refractory epilepsy Thailand risk factors Introduction Epilepsy is a chronic neurological condition that affects approximately 50 million people worldwide [ 1 ]. Beyond the burden of recurrent seizures, individuals with epilepsy often experience a range of physical, psychological, and social difficulties that substantially impair their quality of life (QoL). In particular, refractory epilepsy, defined as the failure of adequate trials of two appropriate antiseizure medications (ASMs) to achieve sustained seizure freedom, is associated with significantly greater disability, psychiatric comorbidity, and treatment burden. Recurrent seizures can lead to physical injury, cognitive impairment, and psychiatric comorbidities—particularly anxiety and depression—are highly prevalent and further contribute to diminished QoL. Beyond clinical factors, people with epilepsy frequently face stigma, discrimination, and social exclusion, all of which can negatively impact education, employment, and interpersonal relationships [ 2 , 3 ]. Multiple clinical and psychosocial factors are known to influence the quality of life of adults with epilepsy. Previous studies showed that seizure frequency [ 3 – 6 ], age at onset [ 5 ], sex [ 5 , 7 ], epilepsy duration [ 5 , 8 ] and number of antiseizure medication [ 6 , 9 , 10 ] are significantly associated with QoL. Polytherapy and medication-related side effects have been linked to poorer physical and cognitive functioning [ 11 ]. Moreover, depression and anxiety [ 3 , 5 , 12 , 13 ] are recognized as some of the strongest predictors of reduced QoL, often outweighing seizure frequency in statistical models. Other factors such as educational level, marital status, and social support also contribute meaningfully to QoL outcomes [ 13 , 14 ]. Employment and education, as markers of social inclusion, have been positively linked to QoL in multiple studies [ 14 , 15 ] These findings underscore the multifactorial nature of QoL in epilepsy and the need for holistic, patient-centered approaches in care. While previous studies have identified various clinical and psychosocial factors influencing QoL in individuals with epilepsy, most of this research has focused on general epilepsy populations without specifically addressing those with refractory epilepsy. This subgroup experiences persistent seizures despite adequate treatment, placing them at increased risk for physical harm, psychiatric comorbidity, cognitive impairment, and social disadvantage. Their QoL is often substantially lower than that of patients with well-controlled epilepsy. Moreover, in low- and middle-income countries (LMICs) such as Thailand—where access to specialized epilepsy care, surgical options, and psychosocial support services may be limited—the burden faced by individuals with refractory epilepsy is likely to be even more severe. Despite these challenges, few studies to date have examined QoL specifically in this population, particularly within multicenter or rural settings in Southeast Asia. To address this gap, we conducted a cross-sectional, multicenter study across upcountry regions of Thailand to evaluate the potential association of QoL in multicenter study of adult with drug resistance epilepsy. Potential correlates included age, age of onset, duration of epilepsy, sex, education level, religion, marital status, current working, net income, insurance, seizure frequency, number of antiseizure medications, history of adverse drug reactions, depression and anxiety. Methods Study design and participants We used a cross-sectional association study design and a multicenter prospective cohort study. We invited subjects who consecutively visited epilepsy clinics, neurology clinics, or medical clinics from seven centers across Thailand, including the Maharaj Nakorn Chiang Mai Hospital, Sunpasitthiprasong Hospital, Songklanagarind Hospital, Hat Yai Hospital, Yala Hospital, Suratthani Hospital, and Vachiraphuket Hospital between January 2019 to May 2021. All hospitals were referral hospitals from the Northern, Northeastern, and Southern regions. Inclusion/exclusion criteria The inclusion criteria were 1) diagnosis of epilepsy by a neurologist, 2) age 16 years or above, and able to communicate in Thai. 3) Patients taking more than two antiseizure medications. Exclusion criteria were: 1) presence of dementia or cognitive impairment; 2) active psychosis or delirium; 3) developmental disorder or mental retardation; 4) presence of comorbidities including diabetes, thyroid dysfunction, stroke, coronary heart disease, respiratory disorder, renal failure, or malignancy; 5) no a history of epileptic surgery or vagus nerve stimulation; and 6) neurodegenerative disorders and genetic epilepsy syndromes such as genetic generalized epilepsy and epileptic encephalopathies. Refractory epilepsy is defined as the failure of adequate trials of two tolerated and appropriately chosen antiseizure medications [ 16 ]. We divided adverse drug reaction to 3 groups. 1) no adverse drug reaction; 2) minor adverse drug reaction: mild and no treatment; 3) major adverse drug reaction: severe and needing hospitalization; severe adverse drug reaction: life-threatening condition such as toxic epidermal necrosis, or Stevens-Johnson Syndrome. This study was conducted in accordance with the ethical principles of the Declaration of Helsinki and was approved by the Ethical Committee of the Faculty of Medicine, Prince of Songkla University. Written informed consent was obtained prior to completion of the questionnaires and without incentives. The overall response rate was 95% and ranged from 90–100%. Data collection Data were collected from the participants using a self-administered multipart structured questionnaire including basic clinical characteristics, sociodemographic, Quality of Life in Epilepsy Inventory-31 (QOLIE-31) and The Hospital Anxiety and Depression Scale (HADS). The clinical variables included age, age at onset, gender, education level, religious status, marital status, current working status, net income, insurance, duration of epilepsy, seizure frequency, number of antiseizure medications, adverse drug reaction (ADR), history of febrile convulsion, and family history of epilepsy. Questionnaires The Hospital Anxiety and Depression Scale The HADS is easy to use and appropriate for screening in situations with limited time. It has been shown to correlate significantly with other scales for depression diagnosis rating [ 17 ]. In previous studies, the HADS has been used to detect depression and anxiety in people with epilepsy [ 18 ]. The Thai version has been translated and validated by Nilchaikovit et al. [ 19 ]. It is a 14-item self-report scale that measures the presence of symptoms related to both anxiety (7 items) and depression (7 items) during the past week. Each item is scored on a 4-point (0–3) scale, with possible scores ranging from 0 to 21 for anxiety and 0 to 21 for depression. Quality of Life in Epilepsy Inventory-31 QOLIE-31 is a self-administered questionnaire designed for adult patients. This measure of QoL has been extensively applied worldwide 3 and validated in the Thai language [ 20 ]. The questionnaire contains 31 items divided into seven subscales: seizure worry, overall QoL, emotional well-being, energy/fatigue, cognitive functioning, medication effects, and social functioning, which are summed to give a total score. Raw domain scores were calculated and transformed into 0-100 linear subscales, with higher scores indicating a better QoL. The global QoL was then calculated as 0-100 scales by adding the seven subscale scores using the overall QOLIE-31 formula Higher QOLIE-31 scores indicated better QoL [ 21 ]. Statistical analysis Quality of life was compared across basic characteristics using either t-test or ANOVA. Prior to the analysis, a Directed Acyclic Graph (DAG) was compiled using the software DAGitty, version 2.3 [ 22 ] to explicitly depict the potential relationships between predictors and outcomes. Age was treated as a categorical variable by stratifying participants into tertiles based on the distribution of age within the study population. The associations between characteristics and QoL were estimated using linear regression adjusted for confounding variables (total effect) or confounding and intermediate variables (direct effect), as indicated by the DAG. The following variables were included in the DAG: QoL, age, age of onset, gender, duration of epilepsy, education, religion, marital status, current employment, net income, insurance, seizure frequency, number of antiseizure medications, history of adverse drug reactions, depression, and anxiety. The relationships between each of the variables were assigned by KP and AG based on the knowledge of these associations from the literature review. Stata statistical software Version 14.1 (Stata Corp, College Station, TX, USA) was used to analyze the data. Statistical significance was set at P < 0.05. Results We invited 394 patients with refractory epilepsy over the study period, and 13 patients refused for personal reasons. Three hundred eighty-one patients (96.7 %) were included in the analysis. The mean age was 35.8 + 12.2 years. (range 18-77). There were 179 women (51 %) and 172 men (49 %). Two hundred sixty (68.2 %) patients had focal epilepsy, 62 (16.3 %) had generalized epilepsy, and 59 (15.5 %) had both types of epilepsy. Seventy-five percent of participants were educated below the university degree level. Almost half (44.7 %) of the participants had no current employment. Almost one third of the respondents had no income. The participants had been diagnosed with epilepsy 2 to 60 years previously. Three percent of the participants had self-pay, and 64.7 % had a universal coverage program. The sociodemographic and clinical variables of patients are summarized in Table 1. In this study, the QOLIE-31 score ranged from 18.9 to 93.9, with a mean of 59.3 (SD = 15.5). The subscale score for overall QoL was the highest (65.0 + 15.9) followed by that for emotional well-being (63.8 + 18.6); the score for social function (51.6 + 25.2) was the lowest. Among respondents, 65.2 % had no anxiety, 21.7 % had mild anxiety, and 13.1 % had severe anxiety. In the same population, 71.8 % were identified as having no depression, 20.2 % as borderline, and 8.0 % as clinically depressed. As shown in Table 2, the patients were divided into three groups: 15–29 years of age (n = 130), 30-39 years (n=98) and 40-60 years (n = 127). There were significant differences in QOLIE-31 score among age group, gender, current working status, seizure frequency, depression and anxiety in the univariate analysis (p = 0.038, p=0.01, p = 0.008, p < 0.001, p< 0.001, and p < 0.001, respectively) (Table 2). There was no significant statistical relationship between the QOLIE-31 score and age at seizure onset, duration of epilepsy, education, marital status, net income, insurance, number of antiseizure medications, or history of adverse drug reactions (p > 0.05). In linear regression models based on the DAG to identify factors influencing QoL as measured using QOLIE-31, we found significant total effects of age group (p = 0.038), and gender (p = 0.019). Depression (p < 0.001) and anxiety (p < 0.001) were shown to have significant direct effects, while seizure frequency exhibited both total (p=0.007) and direct (p=0.013) effects (Table 3).When analyzing the subscale scores of the QOLIE-31 scores and characteristics of patients, statistically significant associations were found in the following subscales: “cognitive function” and net income, depression, anxiety; “emotional well-being” and gender, history of adverse drug reaction, depression, anxiety; “energy/fatigue” and gender, depression, anxiety; “effects of medication” and age group, age of onset, current working, anxiety; “seizure worry” and age group, history of adverse drug reaction, anxiety, seizure frequency; “social function” and age group, current working, depression, anxiety, seizure frequency; “overall quality of life” and current working, anxiety (data not show). Discussion The QOLIE-31 is one of the most popular questionnaires used worldwide for identifying the QoL in epilepsy. QOLIE-31 scores differed among countries based on culture, income level, world region, and methodology. Previous studies have reported that the QOLIE-31 score in non-selected patients with epilepsy was relatively low (59.8). Based on a specific countries, the reported scores were: Malaysia 68.9 ± 15.9 [ 8 ], Northern Ethiopia 77.9 ± 20.8 [ 23 ], Australia 52.9 + 23.1 [ 24 ], Morocco 43.6 ± 10.2 [ 25 ], Nigeria 77.9 ± 13.3 [ 4 ] and Pakistan 51.6 ± 17.1 [ 14 ]. Our study was conducted in patients with refractory epilepsy and revealed that the QOLIE-31 score was 59.3 ± 15.5. Compared with results from other studies in patients with refractory epilepsy, our results reveal that QOLIE-31 was higher than in a study conducted in Portugal (54.7 ± 16.3) [ 26 ] Nevertheless, it was lower than that reported in studies conducted in Taiwan of 63.96 ± 16.1 [ 27 ] and Southeast England of 66.0 ± 14.2 [ 28 ] using QOLIE-31-P, a modified version of the QOLIE-31. The difference in results between different countries may be due to differences in methodology, questionnaires, sample size, inclusion and exclusion criteria, and study setting. It can also be due to sociocultural factors or country of origin. The relatively low QOLIE-31 score in our study reflects the complex burden experienced by patients with refractory epilepsy, who face significantly more challenges than those with well-controlled seizures. Persistent seizure activity contributes not only to physical risks, such as injury and hospitalization, but also to a chronic sense of unpredictability that limits social engagement, independence, and daily functioning [ 29 , 30 ]. This ongoing uncertainty can result in increased anxiety, reduced self-confidence, and activity avoidance, which collectively reduce quality of life. Beyond seizure burden, psychiatric comorbidities, particularly depression and anxiety, are consistently identified as dominant predictors of poor QoL in patients with epilepsy [ 31 , 32 ] These mental health conditions are often underdiagnosed and undertreated, especially in settings where clinical attention is focused primarily on seizure control. Yet, evidence shows that emotional well-being, more than seizure frequency alone, significantly determines how patients perceive and experience their illness. Stigma and social discrimination also remain major barriers to well-being for people with epilepsy, particularly for those with refractory disease who are more visibly affected by frequent seizures. In LMIC settings, epilepsy-related stigma often leads to unemployment, social isolation, and educational exclusion, which in turn exacerbate psychological distress and reinforce health disparities [ 33 , 34 ]. Our finding that nearly half of participants were unemployed and one-third had no income reflects the socioeconomic vulnerabilities of this population. Moreover, treatment burden, including polytherapy and adverse effects of antiseizure medications (ASMs), can impair cognition, increase fatigue, and negatively impact mood, further lowering QoL [ 35 ]. For patients with refractory epilepsy, the complexity of managing medication side effects alongside uncontrolled seizures often creates a cycle of disability that is difficult to break, especially in healthcare systems with limited access to advanced treatments such as epilepsy surgery or neurostimulation. These findings underscore the importance of viewing refractory epilepsy not only as a condition of persistent seizures, but also as a syndrome of multidimensional disability—psychiatric, cognitive, social, and economic. Addressing these domains is essential to improving outcomes beyond seizure control alone Psychiatric comorbidities, especially anxiety, are common in patients with epilepsy. Depression and anxiety often occur more than 2–3 times more commonly than in the general population without epilepsy [ 36 ] and the prevalence in epilepsy is high compared with other chronic disorder [ 37 ]. According to a recent meta-analysis, the prevalence of anxiety in patients with epilepsy was 20.2% and the prevalence of depressive disorders was 22.9% [ 38 ]. In our study, using the Hospital Anxiety and Depression Scale, we found that 21.2% had depression and 34.8% had anxiety. These rates are comparable to previous reports such as Gonzalez-Martinez et al. (anxiety 28.5% via GAD-7, depression 33.3% via NDDI-E) and Silva et al., who found 40% of patients with refractory epilepsy had anxiety diagnosed by a psychiatrist. We also observed that anxiety and depression were significantly associated with all subscales of the QOLIE-31, reinforcing that psychiatric symptoms are crucial determinants of QoL in epilepsy. Our findings are further supported by previous studies using the same instrument. The Hospital Anxiety and Depression Scale (HADS) has been widely validated for identifying psychiatric symptoms in epilepsy and their impact on QoL. A recent large multicenter study in Germany reported that people with epilepsy had significantly higher HADS scores than the general population, with strong inverse correlations between HADS scores and QOLIE-31 outcomes. Notably, depressive symptoms were more predictive of reduced QoL than seizure frequency [ 39 ]. Likewise, a study in Spain identified depression measured by HADS as the only independent predictor of impaired QoL, underlining the critical influence of mood disturbances in this population [ 40 ]. Also, a study in Spain by Sobregrau et al. used both HADS and QOLIE-31 to assess psychiatric symptoms and QoL in patients with drug-resistant epilepsy and psychogenic non-epileptic seizures (PNES), demonstrating a high burden of depression and anxiety and their clear association with poorer QoL outcomes [ 41 ]. These findings align with ours and support the routine use of brief, reliable screening tools such as HADS in both research and clinical care for people with epilepsy. Although depression and anxiety are well-recognized comorbidities in epilepsy, they remain frequently underdiagnosed and undertreated in clinical practice. Studies estimate that up to 50% of psychiatric symptoms in people with epilepsy go unrecognized, particularly in busy neurology clinics where attention is focused primarily on seizure control. Our findings underscore the importance of proactive screening, especially in patients with refractory epilepsy, where psychiatric comorbidities significantly worsen quality of life and may contribute to poor treatment adherence and increased seizure burden. Routine use of validated, brief screening tools such as the Hospital Anxiety and Depression Scale (HADS) or the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) can facilitate early detection of symptoms during outpatient visits. Once identified, patients should be referred for further psychiatric evaluation and evidence-based interventions, including cognitive behavioral therapy (CBT), psychotherapy, or pharmacologic treatment with selective serotonin reuptake inhibitors (SSRIs), which are generally considered safe in epilepsy when appropriately monitored. Multidisciplinary care models involving neurologists, psychiatrists, and mental health professionals have been shown to improve psychiatric outcomes and seizure control [ 42 , 43 ] Given the high burden and impact of psychiatric comorbidities, we recommend that mental health screening be integrated into routine epilepsy management, particularly for patients with refractory epilepsy. Improving clinician awareness and expanding access to psychiatric services—whether onsite or through referral networks—are essential steps toward comprehensive, patient-centered care. The frequency of seizures and seizure-related symptoms has historically been regarded as the most serious problem in patients with epilepsy. Our study also showed that seizure frequency was significantly associated with QOL-31 score and subscale “seizure worry.” Previous studies have shown a clear relationship between the severity and frequency of seizures and QoL in which people with frequent seizures had significantly poorer QoL than those with infrequent or no seizures [ 44 – 46 ] People with uncontrolled epileptic seizures will always be in an uncomfortable position of not knowing when the next seizure will occur and may take precautions and impose restrictions to avoid seizures at inappropriate times, public places, or social events. The frequency of seizures is related to fear and misunderstanding, which results in social stigma and discrimination against epilepsy. Seizure frequency also has a high prevalence of depression, anxiety, and low self-esteem [ 47 ] and the association between seizure control and poor QoL in patients with epilepsy has been consistent despite the differences in methodologies and QoL instruments used in the assessment. This emphasizes the importance of encouraging patients to avoid precipitating factors, adhere to regular intake of medication, and record symptoms of seizure, which can improve the availability of seizure reduction, avoid adverse drug reactions from inappropriate increased dosages of antiseizure medication [ 47 ]. Lower seizure frequency has been related to a greater likelihood of being employed [ 48 ]. More than half of the respondents reported being unemployed. The reasons for unemployment are multifactorial and are related to the state of seizure control. Patients with poor seizure control are also a high-risk group for poor QOL and should be evaluated thoroughly and properly managed to help them live their best lives. In our study, age was significantly associated with QOLIE-31 scores in the univariate analysis. Patients aged 30–39 years reported better QoL than those under 30. This age effect differ from several previous studies that found no independent association between age and QoL after adjusting for clinical and psychosocial factors [ 49 ]. Younger patients may report lower QoL not solely because of their age, but because they are more likely to be in educational or transitional employment phases, experience stigma, or feel socially limited compared to their peers. In contrast, older patients may have more stable life roles, fewer expectations for social participation, and better acceptance of their condition, potentially balancing out the perceived impact of epilepsy on their lives. Conversely, some studies have reported that older age is associated with poorer QoL, possibly due to cumulative seizure-related complications, longer disease duration, or age-related cognitive decline [ 50 ]. These mixed findings in the literature suggest that age itself may not be a primary driver of QoL but instead reflects an interaction of biological, social, and disease-related variables that vary across life stages. Our results highlight the importance of interpreting age-related QoL differences within a broader clinical and psychosocial context, and of focusing on modifiable mediators such as mental health, seizure control, and social participation, rather than age alone. Gender was another factor associated with QOLIE-31 score in our study; female participants had a significantly lower QoL score (57.3 ± 13.1) than males (61.2 ± 15.8). This finding aligns with several previous studies suggesting that women with epilepsy may experience a greater burden of illness [ 22 , 33 ]. Although some literature reports no significant gender-based differences in QoL among patients with refractory epilepsy [ 41 ], the disparity observed in our study may reflect a complex interaction of biological, psychological, and sociocultural factors. Biologically, women are more susceptible to hormonal fluctuations that can influence seizure frequency, mood, and medication metabolism. For example, catamenial epilepsy and reproductive hormone-related changes may exacerbate both seizure control and emotional symptoms in women. Psychologically, women with epilepsy have been shown to report higher rates of anxiety, depression, and perceived stigma, which are all strong predictors of poorer QoL. Studies also suggest that women may internalize distress differently, leading to greater emotional and cognitive burden [ 51 , 52 ]. Socioculturally, women-especially in many LMIC contexts-may face greater barriers to education, employment, and healthcare access, contributing to diminished autonomy and increased dependency. Additionally, societal expectations regarding gender roles, marriage, fertility, and caregiving responsibilities may place women under greater psychosocial stress, further impacting perceived quality of life. These dynamics suggest that gender disparities in epilepsy care and outcomes are not merely clinical but deeply embedded in broader structural and social systems. In our study, monthly income did not show a statistically significant association with overall QOLIE-31 scores. This finding contrasts with several studies that have reported a strong link between low income and reduced QoL in people with epilepsy (PWE). For instance, a study in Ethiopia found that higher income was positively associated with better QoL among PWE, suggesting that financial stability can enhance access to healthcare resources and support systems [ 53 ]. However, the lack of association in our study may reflect the mitigating effects of Thailand's Universal Coverage Scheme (UCS), which provides comprehensive healthcare services, including access to antiseizure medications, regardless of income level. Such universal healthcare access may reduce the direct impact of income disparities on treatment availability. Despite the non-significant relationship between income and QoL, our findings revealed that nearly half of the participants were unemployed, and unemployment was associated with lower scores in several QOLIE-31 subscales, particularly those related to social functioning and overall QoL. This aligns with recent research indicating that employment status significantly influences QoL in PWE. A study from the Australian Epilepsy Project reported that individuals with drug-resistant epilepsy who were employed had higher QoL scores compared to their unemployed counterparts. Similarly, research has shown that unemployed PWE report worse health-related QoL, especially in physical health domains, and greater somatic symptoms [ 30 , 54 ] The main goal of QoL measurement is to assist physicians in making treatment decisions. While 80% of patients with epilepsy live in developing countries, physicians have a heavy workload, with many patients to manage each day. The primary goals of treatment are focused on physical complications, the control of seizures, while epileptic patients suffer from several psychological challenges, such as low self-confidence and depression, and social challenges, such as driving constraints, unemployment, and social isolation. These findings suggest that comprehensive management of patients with epilepsy should be emphasized. QoL measurements in patients with epilepsy can improve clinical outcomes and lead to patient satisfaction with care. Screening is one of the most important tools for identifying QOLIE. Screening tools should be short questionnaires, not time-consuming, and friendly to use. Investigators in this study found that the QOLIE-31 is difficult to score manually due to the complex summation of subscales and total scores. This is not ideal for use in clinical practice. The QOLIE-31 uses a weighted scoring system that is difficult to perform immediately after administration, making the results unavailable for review by the clinician. In today’s situation, it is impossible to increase the workload of nurses or medical assistants to perform the administration while patients are waiting for consultation. To overcome this limitation, we suggest adapting this scoring system using applications in tablets or smartphones. We plan to investigate this in future studies. The strengths of our study are as follows: First, it focused on a multicenter study across Thailand. Second, we based the statistical analysis on an explicit causal framework to ensure appropriate covariate adjustment in regression analysis. Third, QOL was evaluated based on an assessment instrument specifically designed and validated for patients with epilepsy. The main limitations of our study are as follows: 1) The majority of participants from Southern Thailand may not truly represent the entire Thai population. This study had three limitations. 2) The study was conducted in secondary care, tertiary care, and referral centers, where service physicians are very busy. They had limited time to invite participants to participate in the study, but nearly all invited participants agreed to participate. 3) We used the HADS score, but not The Neurological Disorder Inventory for Epilepsy, for screening depression. However, previous studies have shown that both NDDI-E and HADS-D are brief and efficient screening instruments to identify depression in people with epilepsy [ 55 , 56 ]. The HADS is a screening tool for detecting depression and anxiety simultaneously. 4) This was a cross-sectional study. It cannot fully reveal causality between QOL and other variables; a longitudinal study is needed to understand these relationships. Conclusion Quality of life is an important outcome measure for people with epilepsy. Our study demonstrate that factors such as age and gender, depression, anxiety and seizure frequency are associated with the QoL in patient suffering from refractory epilepsy. While clinical care often focuses on seizure control, epilepsy-related factors such as seizure frequency were not enough. Therefore, early comprehensive psychiatric evaluation in real-life clinical practice is important to adequately diagnose and manage comorbidities and to improve QoL of these patients. Abbreviations HRQoL: Health related quality of life QoL : quality of life DAG : directed acyclic graph ASEMs : antiseizure medications QOLIE-31 : Quality of life-31 inventory HADS : The Hospital Anxiety and Depression Scale ADR : adverse drug reaction Declarations Ethics approval and consent to participate We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Consent for publication Not applicable Availability of data and materials Not applicable Competing interests None of the authors have any conflicts of interest to disclose. Funding This work was supported by a research grant from Faculty of Medicine, Prince of Songkla University, grant number 59-299-14-1. 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Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies Epilepsia. 2010;51:1069–77. Aben I, Verhey F, Lousberg R, Lodder J, Honig A. Validity of the beck depression inventory, hospital anxiety and depression scale, SCL-90, and hamilton depression rating scale as screening instruments for depression in stroke patients. Psychosomatics. 2002;43:386–93. Wiglusz MS, Landowski J, Michalak L, Cubała WJ. Validation of the Hospital Anxiety and Depression Scale in patients with epilepsy. Epilepsy Behav. 2016;58:97–101. Nilchaikovit T, Lortrakul M, Phisansutjideth U. Development of Thai version of Hospital Anxiety and Depression Scale in cancer patients. J Psychiatr Assoc Thail. 1996;41:18–30. Kanjanasilp J, Khaewwichit S, Richards RME, Preechagoon Y. Thai Version of the Quality-of-Life in Epilepsy Inventory: Comparison Between the QOLIE-31 and the QOLIE-10. CMU J. 2004;3:35–42. Saadi A, Patenaude B, Mateen FJ. Quality of life in epilepsy-31 inventory (QOLIE-31) scores: a global comparison. Epilesy Behav. 2016;65:13–7. Textor J, Hardt J, Knüppel S. DAGitty: a graphical tool for analyzing causal diagrams. Epidemiology. 2011;5:745. Gebre AK, Haylay A, Sociodemographic. Clinical Variables, and Quality of Life in Patients with Epilepsy in Mekelle City, Northern Ethiopia. Behav Neurol. 2018;2:7593573. Welton JM, Walker C, Riney K, Ng A, Todd L, D'Souza WJ. Quality of life and its association with comorbidities and adverse events from antiepileptic medications: Online survey of patients with epilepsy in Australia. Epilepsy Behav. 2020;104(Pt A):106856. Zoulou O, Maiouak M, El Fakir S, Tachfouti N, Souirti Z. Quality of life predictors among Moroccan adults with epilepsy. Clin Neurol Neurosurg. 2024;241:108282. Silva B, Canas-Simião H, Cordeiro S, et al. Determinants of quality of life in patients with drug-resistant focal epilepsy. Epilepsy Behav. 2019;100:106525. Chen HF, Tsai YF, His MS, Chen JC. Factors affecting quality of life in adults with epilepsy in Taiwan: A cross-sectional. correlational study Epilepsy Behav. 2016;58:26–32. Ridsdale L, Wojewodka G, Robinson E, et al. Characteristics associated with quality of life among people with drug-resistant epilepsy. J Neurol. 2017;264:1174–84. Wang H, Wang W, Zhang J, Hong Z, Zhou D. Prevalence and influencing factors of anxiety and depression among people with epilepsy in China: A systematic review and meta-analysis. Epilepsy Res. 2020;159:106263. Kim JH, Lee SA. Differences in health-related quality of life and somatic symptoms in employed and unemployed people with epilepsy. Epilepsy Behav. 2023;139:11067481. Kwon HE, Mazarati A, Choi H, Moshé SL. Psychiatric comorbidities in epilepsy: Update on prevalence, mechanisms, and treatment. Epilepsy Res. 2022;183:106907. Johnson EK, Jones JE, Seidenberg M, Hermann BP. The impact of comorbid depression and anxiety on quality of life in epilepsy: a systematic review. Epilepsy Behav. 2019;98:157–64. Adotevi N, Serafini A, Caplan R. Stigma in epilepsy: a review of current knowledge and implications for neuropsychological practice. Clin Neuropsychol. 2020;34:761–85. Singh A, Trevick S, Stone J. Epilepsy and the hidden burden of stigma. Epilepsy Behav. 2021;124:108308. Kanemura H. Therapeutic Strategies in Children with Epilepsy: A Quality-of-Life-Related Perspective. J Clin Med. 2024;13:405. Josephson CB, Jetté N. Psychiatric comorbidities in epilepsy. Int Rev Psychiatry. 2017;29:409–24. Ettinger A, Reed M, Cramer J. Depression and comorbidity in community-based patients with epilepsy or asthma. Neurology. 2004;63:1008–14. Scott AJ, Sharpe L, Hunt C, Gandy M. Anxiety and depressive disorders in people with epilepsy: a meta-analysis. Epilepsia. 2017;58:973–82. Siebenbrodt K, Willems LM, von Podewils F, Mross PM, Strüber M, Langenbruch L, et al. Determinants of quality of life in adults with epilepsy: a multicenter, cross-sectional study from Germany. Neurol Res Pract. 2023;5:41. Sánchez-Gómez A, Salas-Puig J, García-Morales I, Gil-Nagel A. The mediating role of epileptic seizures, irritability, and depression on quality of life in people with epilepsy. Epilepsy Behav. 2020;112:107375. Sobregrau P, Baillès E, Carreño M, Donaire A, Boget T, Setoain X, et al. Psychiatric and psychological assessment of Spanish patients with drug-resistant epilepsy and psychogenic nonepileptic seizures (PNES) with no response to previous treatments. Epilepsy Behav. 2023;145:109329. Kanner AM, Schachter SC, Barry JJ, et al. Depression and epilepsy: epidemiologic and neurobiologic perspectives that may explain their high comorbid occurrence. Epilepsy Behav. 2020;111:107281. Michaelis R, Tang V, Goldstein LH, Reuber M, LaFrance WC Jr, Lundgren T, et al. Psychological treatments for adults and children with epilepsy: Evidence-based recommendations by the International League Against Epilepsy Psychology Task Force. Epilepsia. 2018;59:1282–302. Allain H, Schück S, Nachit-Ouinekh F, et al. Improvement in quality of life after initiation of lamotrigine therapy in patients with epilepsy in a naturalistic treatment setting. Seizure. 2007;16:173–84. Taylor RS, Sander JW, Taylor RJ, Baker GA. Predictors of health-related quality of life and costs in adults with epilepsy: a systematic review. Epilepsia. 2011;52:2168–80. Kinyanjui DW, Kathuku DM, Mburu JM. Quality of life among patients living with epilepsy attending the neurology clinic at Kenyatta National Hospital, Nairobi, Kenya: a comparative study. Health Qual Life Outcomes. 2013;18:98. Ogundare T, Adebowale TO, Borba CPC, Henderson DC. Correlates of depression and quality of life among patients with epilepsy in T Nigeria. Epilepsy Res. 2020;164:106344. Bishop M. Determinants of employment status among a community-based sample of people with epilepsy. Rehab Counsell Bull. 2004;47:112–20. Alsaadi T, Shahrour TM, Abou-Khalil B. Determinants of quality of life in patients with epilepsy in the Middle East. Epilepsy Behav. 2020;102:106715. Wirrell EC, Wood L, Hamiwka LD, Sherman EM. Quality of life in children with epilepsy: effect of diagnosis and demographic factors. Epilepsy Behav. 2020;112:107391. Asadi-Pooya AA, Sperling MR. Gender differences in epilepsy and neuropsychiatric comorbidities. Epilepsy Behav. 2020;110:107158. Josephson CB, Patten SB, Bulloch AG, Williams JV, Fiest KM, Jette N. Psychiatric comorbidity in epilepsy: A population-based analysis. Epilepsia. 2017;58:742–50. Mekuriaw B, Wondie M, Yitayih Y, Sahile AT, Abebaw G. Health-related quality of life in epilepsy and its associated factors among adult patients with epilepsy in Southwest Ethiopia. BMJ Open. 2024;14:e079165. Australian Epilepsy Project. Work productivity, quality of life, and care needs in people with epilepsy. Epilepsy Behav. 2023;140:10984321. Hagemann A, Kuramochi I, Bien CG, Brandt C. Screening for depression, anxiety, and suicidality in outpatients of a tertiary epilepsy center: How frequent are increased scores and what is recommended? Epilepsy Behav. 2025;164:110289. Martínez-Juárez IE, Gonzalez-Salido J, Colado-Martinez J, et al. Anxiety and depression in people with epilepsy during and one year after the COVID-19 pandemic. Epilepsia Open. 2025;10:186–95. Tables Tables 1 to 3 are available in the Supplementary Files section. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5926990","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":449319854,"identity":"030ca74f-52b9-417c-9041-f3cfb7740d9f","order_by":0,"name":"Kanitpong 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Arpart","middleName":"","lastName":"Nakao","suffix":""},{"id":449319862,"identity":"a08413e9-d01b-4300-887b-34e2064ac330","order_by":8,"name":"Alan Geater","email":"","orcid":"","institution":"Prince of Songkla University","correspondingAuthor":false,"prefix":"","firstName":"Alan","middleName":"","lastName":"Geater","suffix":""}],"badges":[],"createdAt":"2025-01-30 00:23:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5926990/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5926990/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12889-025-23495-5","type":"published","date":"2025-07-02T15:58:45+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":86179505,"identity":"a8ef5099-740c-4c67-b431-a6fa6680e257","added_by":"auto","created_at":"2025-07-07 16:17:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":595559,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5926990/v1/2c1faec5-70ec-4e5d-962e-39003a363ba5.pdf"},{"id":81734358,"identity":"df6e1d54-9113-412a-968b-b08ea14a576b","added_by":"auto","created_at":"2025-04-30 20:32:16","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":40127,"visible":true,"origin":"","legend":"","description":"","filename":"tableR119468.docx","url":"https://assets-eu.researchsquare.com/files/rs-5926990/v1/cfb7f148e5bad8655e852dec.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Quality of life in adults with refractory epilepsy in Thailand: a multicenter upcountry nationwide study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEpilepsy is a chronic neurological condition that affects approximately 50\u0026nbsp;million people worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Beyond the burden of recurrent seizures, individuals with epilepsy often experience a range of physical, psychological, and social difficulties that substantially impair their quality of life (QoL). In particular, refractory epilepsy, defined as the failure of adequate trials of two appropriate antiseizure medications (ASMs) to achieve sustained seizure freedom, is associated with significantly greater disability, psychiatric comorbidity, and treatment burden.\u003c/p\u003e \u003cp\u003eRecurrent seizures can lead to physical injury, cognitive impairment, and psychiatric comorbidities\u0026mdash;particularly anxiety and depression\u0026mdash;are highly prevalent and further contribute to diminished QoL. Beyond clinical factors, people with epilepsy frequently face stigma, discrimination, and social exclusion, all of which can negatively impact education, employment, and interpersonal relationships [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMultiple clinical and psychosocial factors are known to influence the quality of life of adults with epilepsy. Previous studies showed that seizure frequency [\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], age at onset [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], sex [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], epilepsy duration [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] and number of antiseizure medication [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] are significantly associated with QoL. Polytherapy and medication-related side effects have been linked to poorer physical and cognitive functioning [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Moreover, depression and anxiety [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] are recognized as some of the strongest predictors of reduced QoL, often outweighing seizure frequency in statistical models. Other factors such as educational level, marital status, and social support also contribute meaningfully to QoL outcomes [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Employment and education, as markers of social inclusion, have been positively linked to QoL in multiple studies [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] These findings underscore the multifactorial nature of QoL in epilepsy and the need for holistic, patient-centered approaches in care.\u003c/p\u003e \u003cp\u003eWhile previous studies have identified various clinical and psychosocial factors influencing QoL in individuals with epilepsy, most of this research has focused on general epilepsy populations without specifically addressing those with refractory epilepsy. This subgroup experiences persistent seizures despite adequate treatment, placing them at increased risk for physical harm, psychiatric comorbidity, cognitive impairment, and social disadvantage. Their QoL is often substantially lower than that of patients with well-controlled epilepsy. Moreover, in low- and middle-income countries (LMICs) such as Thailand\u0026mdash;where access to specialized epilepsy care, surgical options, and psychosocial support services may be limited\u0026mdash;the burden faced by individuals with refractory epilepsy is likely to be even more severe. Despite these challenges, few studies to date have examined QoL specifically in this population, particularly within multicenter or rural settings in Southeast Asia. To address this gap, we conducted a cross-sectional, multicenter study across upcountry regions of Thailand to evaluate the potential association of QoL in multicenter study of adult with drug resistance epilepsy. Potential correlates included age, age of onset, duration of epilepsy, sex, education level, religion, marital status, current working, net income, insurance, seizure frequency, number of antiseizure medications, history of adverse drug reactions, depression and anxiety.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eWe used a cross-sectional association study design and a multicenter prospective cohort study. We invited subjects who consecutively visited epilepsy clinics, neurology clinics, or medical clinics from seven centers across Thailand, including the Maharaj Nakorn Chiang Mai Hospital, Sunpasitthiprasong Hospital, Songklanagarind Hospital, Hat Yai Hospital, Yala Hospital, Suratthani Hospital, and Vachiraphuket Hospital between January 2019 to May 2021. All hospitals were referral hospitals from the Northern, Northeastern, and Southern regions.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInclusion/exclusion criteria\u003c/h3\u003e\n\u003cp\u003eThe inclusion criteria were 1) diagnosis of epilepsy by a neurologist, 2) age 16 years or above, and able to communicate in Thai. 3) Patients taking more than two antiseizure medications. Exclusion criteria were: 1) presence of dementia or cognitive impairment; 2) active psychosis or delirium; 3) developmental disorder or mental retardation; 4) presence of comorbidities including diabetes, thyroid dysfunction, stroke, coronary heart disease, respiratory disorder, renal failure, or malignancy; 5) no a history of epileptic surgery or vagus nerve stimulation; and 6) neurodegenerative disorders and genetic epilepsy syndromes such as genetic generalized epilepsy and epileptic encephalopathies. Refractory epilepsy is defined as the failure of adequate trials of two tolerated and appropriately chosen antiseizure medications [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. We divided adverse drug reaction to 3 groups. 1) no adverse drug reaction; 2) minor adverse drug reaction: mild and no treatment; 3) major adverse drug reaction: severe and needing hospitalization; severe adverse drug reaction: life-threatening condition such as toxic epidermal necrosis, or Stevens-Johnson Syndrome.\u003c/p\u003e \u003cp\u003e This study was conducted in accordance with the ethical principles of the Declaration of Helsinki and was approved by the Ethical Committee of the Faculty of Medicine, Prince of Songkla University. Written informed consent was obtained prior to completion of the questionnaires and without incentives. The overall response rate was 95% and ranged from 90\u0026ndash;100%.\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eData were collected from the participants using a self-administered multipart structured questionnaire including basic clinical characteristics, sociodemographic, Quality of Life in Epilepsy Inventory-31 (QOLIE-31) and The Hospital Anxiety and Depression Scale (HADS).\u003c/p\u003e \u003cp\u003eThe clinical variables included age, age at onset, gender, education level, religious status, marital status, current working status, net income, insurance, duration of epilepsy, seizure frequency, number of antiseizure medications, adverse drug reaction (ADR), history of febrile convulsion, and family history of epilepsy.\u003c/p\u003e\n\u003ch3\u003eQuestionnaires\u003c/h3\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eThe Hospital Anxiety and Depression Scale\u003c/h2\u003e \u003cp\u003eThe HADS is easy to use and appropriate for screening in situations with limited time. It has been shown to correlate significantly with other scales for depression diagnosis rating [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In previous studies, the HADS has been used to detect depression and anxiety in people with epilepsy [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The Thai version has been translated and validated by Nilchaikovit et al. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. It is a 14-item self-report scale that measures the presence of symptoms related to both anxiety (7 items) and depression (7 items) during the past week. Each item is scored on a 4-point (0\u0026ndash;3) scale, with possible scores ranging from 0 to 21 for anxiety and 0 to 21 for depression.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eQuality of Life in Epilepsy Inventory-31\u003c/h2\u003e \u003cp\u003eQOLIE-31 is a self-administered questionnaire designed for adult patients. This measure of QoL has been extensively applied worldwide\u003csup\u003e3\u003c/sup\u003e and validated in the Thai language [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The questionnaire contains 31 items divided into seven subscales: seizure worry, overall QoL, emotional well-being, energy/fatigue, cognitive functioning, medication effects, and social functioning, which are summed to give a total score. Raw domain scores were calculated and transformed into 0-100 linear subscales, with higher scores indicating a better QoL. The global QoL was then calculated as 0-100 scales by adding the seven subscale scores using the overall QOLIE-31 formula Higher QOLIE-31 scores indicated better QoL [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eQuality of life was compared across basic characteristics using either t-test or ANOVA. Prior to the analysis, a Directed Acyclic Graph (DAG) was compiled using the software DAGitty, version 2.3 [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] to explicitly depict the potential relationships between predictors and outcomes. Age was treated as a categorical variable by stratifying participants into tertiles based on the distribution of age within the study population. The associations between characteristics and QoL were estimated using linear regression adjusted for confounding variables (total effect) or confounding and intermediate variables (direct effect), as indicated by the DAG. The following variables were included in the DAG: QoL, age, age of onset, gender, duration of epilepsy, education, religion, marital status, current employment, net income, insurance, seizure frequency, number of antiseizure medications, history of adverse drug reactions, depression, and anxiety. The relationships between each of the variables were assigned by KP and AG based on the knowledge of these associations from the literature review. Stata statistical software Version 14.1 (Stata Corp, College Station, TX, USA) was used to analyze the data. Statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eWe invited 394 patients with refractory epilepsy over the study period, and 13 patients refused for personal reasons. Three hundred eighty-one patients (96.7 %) were included in the analysis. The mean age was 35.8 \u003cu\u003e+\u003c/u\u003e 12.2 years. (range 18-77). There were 179 women (51 %) and 172 men (49 %). Two hundred sixty (68.2 %) patients had focal epilepsy, 62 (16.3 %) had generalized epilepsy, and 59 (15.5 %) had both types of epilepsy. Seventy-five percent of participants were educated below the university degree level. Almost half (44.7 %) of the participants had no current employment. Almost one third of the respondents had no income. The participants had been diagnosed with epilepsy 2 to 60 years previously. Three percent of the participants had self-pay, and 64.7 % had a universal coverage program. The sociodemographic and clinical variables of patients are summarized in Table 1.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;In this study, the QOLIE-31 score ranged from 18.9 to 93.9, with a mean of 59.3 (SD = 15.5). The subscale score for overall QoL was the highest (65.0 \u003cu\u003e+\u003c/u\u003e 15.9) followed by that for emotional well-being (63.8 + 18.6); the score for social function (51.6 \u003cu\u003e+\u003c/u\u003e 25.2) was the lowest. Among respondents, 65.2 % had no anxiety, 21.7 % had mild anxiety, and 13.1 % had severe anxiety. In the same population, 71.8 % were identified as having no depression, 20.2 % as borderline, and 8.0 % as clinically depressed. As shown in Table 2, the patients were divided into three groups: 15–29 years of age (n = 130), 30-39 years (n=98) and 40-60 years (n = 127). There were significant differences in QOLIE-31 score among age group, gender, current working status, seizure frequency, depression and anxiety in the univariate analysis (p = 0.038, p=0.01, p = 0.008, p \u0026lt; 0.001, p\u0026lt; 0.001, and p \u0026lt; 0.001, respectively) (Table 2). There was no significant statistical relationship between the QOLIE-31 score and age at seizure onset, duration of epilepsy, education, marital status, net income, insurance, number of antiseizure medications, or history of adverse drug reactions (p \u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003eIn linear regression models based on the DAG to identify factors influencing QoL as measured using QOLIE-31, we found significant total effects of age group (p = 0.038), and gender (p = 0.019). Depression (p \u0026lt; 0.001) and anxiety (p \u0026lt; 0.001) were shown to have significant direct effects, while seizure frequency exhibited both total (p=0.007) and direct (p=0.013) effects (Table 3).When analyzing the subscale scores of the QOLIE-31 scores and characteristics of patients, statistically significant associations were found in the following subscales: “cognitive function” and net income, depression, anxiety; “emotional well-being” and gender, history of adverse drug reaction, depression, anxiety; “energy/fatigue” and gender, depression, anxiety; “effects of medication” and age group, age of onset, current working, anxiety; “seizure worry” and age group, history of adverse drug reaction, \u0026nbsp; anxiety, seizure frequency; “social function” and age group, current working, depression, anxiety, seizure frequency; “overall quality of life” and current working, anxiety (data not show).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe QOLIE-31 is one of the most popular questionnaires used worldwide for identifying the QoL in epilepsy. QOLIE-31 scores differed among countries based on culture, income level, world region, and methodology. Previous studies have reported that the QOLIE-31 score in non-selected patients with epilepsy was relatively low (59.8). Based on a specific countries, the reported scores were: Malaysia 68.9\u0026thinsp;\u0026plusmn;\u0026thinsp;15.9 [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], Northern Ethiopia 77.9\u0026thinsp;\u0026plusmn;\u0026thinsp;20.8 [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], Australia 52.9\u0026thinsp;+\u0026thinsp;23.1 [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], Morocco 43.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2 [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], Nigeria 77.9\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;13.3 [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] and Pakistan 51.6\u0026thinsp;\u0026plusmn;\u0026thinsp;17.1 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Our study was conducted in patients with refractory epilepsy and revealed that the QOLIE-31 score was 59.3\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;15.5. Compared with results from other studies in patients with refractory epilepsy, our results reveal that QOLIE-31 was higher than in a study conducted in Portugal (54.7\u0026thinsp;\u0026plusmn;\u0026thinsp;16.3) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] Nevertheless, it was lower than that reported in studies conducted in Taiwan of 63.96\u0026thinsp;\u0026plusmn;\u0026thinsp;16.1 [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] and Southeast England of 66.0\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;14.2 [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] using QOLIE-31-P, a modified version of the QOLIE-31. The difference in results between different countries may be due to differences in methodology, questionnaires, sample size, inclusion and exclusion criteria, and study setting. It can also be due to sociocultural factors or country of origin.\u003c/p\u003e \u003cp\u003eThe relatively low QOLIE-31 score in our study reflects the complex burden experienced by patients with refractory epilepsy, who face significantly more challenges than those with well-controlled seizures. Persistent seizure activity contributes not only to physical risks, such as injury and hospitalization, but also to a chronic sense of unpredictability that limits social engagement, independence, and daily functioning [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. This ongoing uncertainty can result in increased anxiety, reduced self-confidence, and activity avoidance, which collectively reduce quality of life.\u003c/p\u003e \u003cp\u003eBeyond seizure burden, psychiatric comorbidities, particularly depression and anxiety, are consistently identified as dominant predictors of poor QoL in patients with epilepsy [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] These mental health conditions are often underdiagnosed and undertreated, especially in settings where clinical attention is focused primarily on seizure control. Yet, evidence shows that emotional well-being, more than seizure frequency alone, significantly determines how patients perceive and experience their illness.\u003c/p\u003e \u003cp\u003eStigma and social discrimination also remain major barriers to well-being for people with epilepsy, particularly for those with refractory disease who are more visibly affected by frequent seizures. In LMIC settings, epilepsy-related stigma often leads to unemployment, social isolation, and educational exclusion, which in turn exacerbate psychological distress and reinforce health disparities [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Our finding that nearly half of participants were unemployed and one-third had no income reflects the socioeconomic vulnerabilities of this population. Moreover, treatment burden, including polytherapy and adverse effects of antiseizure medications (ASMs), can impair cognition, increase fatigue, and negatively impact mood, further lowering QoL [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. For patients with refractory epilepsy, the complexity of managing medication side effects alongside uncontrolled seizures often creates a cycle of disability that is difficult to break, especially in healthcare systems with limited access to advanced treatments such as epilepsy surgery or neurostimulation. These findings underscore the importance of viewing refractory epilepsy not only as a condition of persistent seizures, but also as a syndrome of multidimensional disability\u0026mdash;psychiatric, cognitive, social, and economic. Addressing these domains is essential to improving outcomes beyond seizure control alone\u003c/p\u003e \u003cp\u003ePsychiatric comorbidities, especially anxiety, are common in patients with epilepsy. Depression and anxiety often occur more than 2\u0026ndash;3 times more commonly than in the general population without epilepsy [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e] and the prevalence in epilepsy is high compared with other chronic disorder [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. According to a recent meta-analysis, the prevalence of anxiety in patients with epilepsy was 20.2% and the prevalence of depressive disorders was 22.9% [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. In our study, using the Hospital Anxiety and Depression Scale, we found that 21.2% had depression and 34.8% had anxiety. These rates are comparable to previous reports such as Gonzalez-Martinez et al. (anxiety 28.5% via GAD-7, depression 33.3% via NDDI-E) and Silva et al., who found 40% of patients with refractory epilepsy had anxiety diagnosed by a psychiatrist. We also observed that anxiety and depression were significantly associated with all subscales of the QOLIE-31, reinforcing that psychiatric symptoms are crucial determinants of QoL in epilepsy. Our findings are further supported by previous studies using the same instrument. The Hospital Anxiety and Depression Scale (HADS) has been widely validated for identifying psychiatric symptoms in epilepsy and their impact on QoL. A recent large multicenter study in Germany reported that people with epilepsy had significantly higher HADS scores than the general population, with strong inverse correlations between HADS scores and QOLIE-31 outcomes. Notably, depressive symptoms were more predictive of reduced QoL than seizure frequency [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Likewise, a study in Spain identified depression measured by HADS as the only independent predictor of impaired QoL, underlining the critical influence of mood disturbances in this population [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Also, a study in Spain by Sobregrau et al. used both HADS and QOLIE-31 to assess psychiatric symptoms and QoL in patients with drug-resistant epilepsy and psychogenic non-epileptic seizures (PNES), demonstrating a high burden of depression and anxiety and their clear association with poorer QoL outcomes [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. These findings align with ours and support the routine use of brief, reliable screening tools such as HADS in both research and clinical care for people with epilepsy. Although depression and anxiety are well-recognized comorbidities in epilepsy, they remain frequently underdiagnosed and undertreated in clinical practice. Studies estimate that up to 50% of psychiatric symptoms in people with epilepsy go unrecognized, particularly in busy neurology clinics where attention is focused primarily on seizure control. Our findings underscore the importance of proactive screening, especially in patients with refractory epilepsy, where psychiatric comorbidities significantly worsen quality of life and may contribute to poor treatment adherence and increased seizure burden.\u003c/p\u003e \u003cp\u003eRoutine use of validated, brief screening tools such as the Hospital Anxiety and Depression Scale (HADS) or the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) can facilitate early detection of symptoms during outpatient visits. Once identified, patients should be referred for further psychiatric evaluation and evidence-based interventions, including cognitive behavioral therapy (CBT), psychotherapy, or pharmacologic treatment with selective serotonin reuptake inhibitors (SSRIs), which are generally considered safe in epilepsy when appropriately monitored. Multidisciplinary care models involving neurologists, psychiatrists, and mental health professionals have been shown to improve psychiatric outcomes and seizure control [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e] Given the high burden and impact of psychiatric comorbidities, we recommend that mental health screening be integrated into routine epilepsy management, particularly for patients with refractory epilepsy. Improving clinician awareness and expanding access to psychiatric services\u0026mdash;whether onsite or through referral networks\u0026mdash;are essential steps toward comprehensive, patient-centered care.\u003c/p\u003e \u003cp\u003eThe frequency of seizures and seizure-related symptoms has historically been regarded as the most serious problem in patients with epilepsy. Our study also showed that seizure frequency was significantly associated with QOL-31 score and subscale \u0026ldquo;seizure worry.\u0026rdquo; Previous studies have shown a clear relationship between the severity and frequency of seizures and QoL in which people with frequent seizures had significantly poorer QoL than those with infrequent or no seizures [\u003cspan additionalcitationids=\"CR45\" citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e] People with uncontrolled epileptic seizures will always be in an uncomfortable position of not knowing when the next seizure will occur and may take precautions and impose restrictions to avoid seizures at inappropriate times, public places, or social events. The frequency of seizures is related to fear and misunderstanding, which results in social stigma and discrimination against epilepsy. Seizure frequency also has a high prevalence of depression, anxiety, and low self-esteem [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e] and the association between seizure control and poor QoL in patients with epilepsy has been consistent despite the differences in methodologies and QoL instruments used in the assessment. This emphasizes the importance of encouraging patients to avoid precipitating factors, adhere to regular intake of medication, and record symptoms of seizure, which can improve the availability of seizure reduction, avoid adverse drug reactions from inappropriate increased dosages of antiseizure medication [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. Lower seizure frequency has been related to a greater likelihood of being employed [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. More than half of the respondents reported being unemployed. The reasons for unemployment are multifactorial and are related to the state of seizure control. Patients with poor seizure control are also a high-risk group for poor QOL and should be evaluated thoroughly and properly managed to help them live their best lives.\u003c/p\u003e \u003cp\u003eIn our study, age was significantly associated with QOLIE-31 scores in the univariate analysis. Patients aged 30\u0026ndash;39 years reported better QoL than those under 30. This age effect differ from several previous studies that found no independent association between age and QoL after adjusting for clinical and psychosocial factors [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. Younger patients may report lower QoL not solely because of their age, but because they are more likely to be in educational or transitional employment phases, experience stigma, or feel socially limited compared to their peers. In contrast, older patients may have more stable life roles, fewer expectations for social participation, and better acceptance of their condition, potentially balancing out the perceived impact of epilepsy on their lives. Conversely, some studies have reported that older age is associated with poorer QoL, possibly due to cumulative seizure-related complications, longer disease duration, or age-related cognitive decline [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. These mixed findings in the literature suggest that age itself may not be a primary driver of QoL but instead reflects an interaction of biological, social, and disease-related variables that vary across life stages. Our results highlight the importance of interpreting age-related QoL differences within a broader clinical and psychosocial context, and of focusing on modifiable mediators such as mental health, seizure control, and social participation, rather than age alone.\u003c/p\u003e \u003cp\u003eGender was another factor associated with QOLIE-31 score in our study; female participants had a significantly lower QoL score (57.3\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;13.1) than males (61.2\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;15.8). This finding aligns with several previous studies suggesting that women with epilepsy may experience a greater burden of illness [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Although some literature reports no significant gender-based differences in QoL among patients with refractory epilepsy [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e], the disparity observed in our study may reflect a complex interaction of biological, psychological, and sociocultural factors. Biologically, women are more susceptible to hormonal fluctuations that can influence seizure frequency, mood, and medication metabolism. For example, catamenial epilepsy and reproductive hormone-related changes may exacerbate both seizure control and emotional symptoms in women. Psychologically, women with epilepsy have been shown to report higher rates of anxiety, depression, and perceived stigma, which are all strong predictors of poorer QoL. Studies also suggest that women may internalize distress differently, leading to greater emotional and cognitive burden [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. Socioculturally, women-especially in many LMIC contexts-may face greater barriers to education, employment, and healthcare access, contributing to diminished autonomy and increased dependency. Additionally, societal expectations regarding gender roles, marriage, fertility, and caregiving responsibilities may place women under greater psychosocial stress, further impacting perceived quality of life. These dynamics suggest that gender disparities in epilepsy care and outcomes are not merely clinical but deeply embedded in broader structural and social systems.\u003c/p\u003e \u003cp\u003eIn our study, monthly income did not show a statistically significant association with overall QOLIE-31 scores. This finding contrasts with several studies that have reported a strong link between low income and reduced QoL in people with epilepsy (PWE). For instance, a study in Ethiopia found that higher income was positively associated with better QoL among PWE, suggesting that financial stability can enhance access to healthcare resources and support systems [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. However, the lack of association in our study may reflect the mitigating effects of Thailand's Universal Coverage Scheme (UCS), which provides comprehensive healthcare services, including access to antiseizure medications, regardless of income level. Such universal healthcare access may reduce the direct impact of income disparities on treatment availability. Despite the non-significant relationship between income and QoL, our findings revealed that nearly half of the participants were unemployed, and unemployment was associated with lower scores in several QOLIE-31 subscales, particularly those related to social functioning and overall QoL. This aligns with recent research indicating that employment status significantly influences QoL in PWE. A study from the Australian Epilepsy Project reported that individuals with drug-resistant epilepsy who were employed had higher QoL scores compared to their unemployed counterparts. Similarly, research has shown that unemployed PWE report worse health-related QoL, especially in physical health domains, and greater somatic symptoms [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe main goal of QoL measurement is to assist physicians in making treatment decisions. While 80% of patients with epilepsy live in developing countries, physicians have a heavy workload, with many patients to manage each day. The primary goals of treatment are focused on physical complications, the control of seizures, while epileptic patients suffer from several psychological challenges, such as low self-confidence and depression, and social challenges, such as driving constraints, unemployment, and social isolation. These findings suggest that comprehensive management of patients with epilepsy should be emphasized. QoL measurements in patients with epilepsy can improve clinical outcomes and lead to patient satisfaction with care. Screening is one of the most important tools for identifying QOLIE. Screening tools should be short questionnaires, not time-consuming, and friendly to use. Investigators in this study found that the QOLIE-31 is difficult to score manually due to the complex summation of subscales and total scores. This is not ideal for use in clinical practice. The QOLIE-31 uses a weighted scoring system that is difficult to perform immediately after administration, making the results unavailable for review by the clinician. In today\u0026rsquo;s situation, it is impossible to increase the workload of nurses or medical assistants to perform the administration while patients are waiting for consultation. To overcome this limitation, we suggest adapting this scoring system using applications in tablets or smartphones. We plan to investigate this in future studies.\u003c/p\u003e \u003cp\u003eThe strengths of our study are as follows: First, it focused on a multicenter study across Thailand. Second, we based the statistical analysis on an explicit causal framework to ensure appropriate covariate adjustment in regression analysis. Third, QOL was evaluated based on an assessment instrument specifically designed and validated for patients with epilepsy. The main limitations of our study are as follows: 1) The majority of participants from Southern Thailand may not truly represent the entire Thai population. This study had three limitations. 2) The study was conducted in secondary care, tertiary care, and referral centers, where service physicians are very busy. They had limited time to invite participants to participate in the study, but nearly all invited participants agreed to participate. 3) We used the HADS score, but not The Neurological Disorder Inventory for Epilepsy, for screening depression. However, previous studies have shown that both NDDI-E and HADS-D are brief and efficient screening instruments to identify depression in people with epilepsy [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e]. The HADS is a screening tool for detecting depression and anxiety simultaneously. 4) This was a cross-sectional study. It cannot fully reveal causality between QOL and other variables; a longitudinal study is needed to understand these relationships.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eQuality of life is an important outcome measure for people with epilepsy. Our study demonstrate that factors such as age and gender, depression, anxiety and seizure frequency are associated with the QoL in patient suffering from refractory epilepsy. While clinical care often focuses on seizure control, epilepsy-related factors such as seizure frequency were not enough. Therefore, early comprehensive psychiatric evaluation in real-life clinical practice is important to adequately diagnose and manage comorbidities and to improve QoL of these patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eHRQoL: Health related quality of life\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eQoL : quality of life\u003c/p\u003e\n\u003cp\u003eDAG : directed acyclic graph\u003c/p\u003e\n\u003cp\u003eASEMs : antiseizure medications\u003c/p\u003e\n\u003cp\u003eQOLIE-31 : Quality of life-31 inventory\u003c/p\u003e\n\u003cp\u003eHADS : The Hospital Anxiety and Depression Scale\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eADR : adverse drug reaction\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone of the authors have any conflicts of interest to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by a research grant from Faculty of Medicine, Prince of Songkla University, grant number 59-299-14-1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKanitpong Phabphal: \u0026nbsp;participated in study design, formal analysis, methodology, writing-original draft, writing-review \u0026amp; editing\u003c/p\u003e\n\u003cp\u003eNunthamon wonghirundecha: writing-original draft\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Tabtim Chongsuvivatwong, Arpiwat Soontornpun, Pichai Rochanapithayakorn, Arkhom \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eArayawichanont, Thuspaween Wasiwat, Arpart Nakao: participated in Investigation, Resources.\u003c/p\u003e\n\u003cp\u003eAlan Geater: participated in study design formal analysis, methodology, \u0026nbsp;editing and reviewing manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe appreciate the patients’ cooperation.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWorld Health Organization. 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Epilepsy Behav. 2020;104(Pt A):106856.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZoulou O, Maiouak M, El Fakir S, Tachfouti N, Souirti Z. Quality of life predictors among Moroccan adults with epilepsy. Clin Neurol Neurosurg. 2024;241:108282.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSilva B, Canas-Simi\u0026atilde;o H, Cordeiro S, et al. Determinants of quality of life in patients with drug-resistant focal epilepsy. Epilepsy Behav. 2019;100:106525.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen HF, Tsai YF, His MS, Chen JC. Factors affecting quality of life in adults with epilepsy in Taiwan: A cross-sectional. correlational study Epilepsy Behav. 2016;58:26\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRidsdale L, Wojewodka G, Robinson E, et al. Characteristics associated with quality of life among people with drug-resistant epilepsy. J Neurol. 2017;264:1174\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang H, Wang W, Zhang J, Hong Z, Zhou D. Prevalence and influencing factors of anxiety and depression among people with epilepsy in China: A systematic review and meta-analysis. Epilepsy Res. 2020;159:106263.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim JH, Lee SA. Differences in health-related quality of life and somatic symptoms in employed and unemployed people with epilepsy. Epilepsy Behav. 2023;139:11067481.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKwon HE, Mazarati A, Choi H, Mosh\u0026eacute; SL. Psychiatric comorbidities in epilepsy: Update on prevalence, mechanisms, and treatment. Epilepsy Res. 2022;183:106907.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJohnson EK, Jones JE, Seidenberg M, Hermann BP. The impact of comorbid depression and anxiety on quality of life in epilepsy: a systematic review. Epilepsy Behav. 2019;98:157\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAdotevi N, Serafini A, Caplan R. Stigma in epilepsy: a review of current knowledge and implications for neuropsychological practice. Clin Neuropsychol. 2020;34:761\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh A, Trevick S, Stone J. Epilepsy and the hidden burden of stigma. Epilepsy Behav. 2021;124:108308.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKanemura H. Therapeutic Strategies in Children with Epilepsy: A Quality-of-Life-Related Perspective. J Clin Med. 2024;13:405.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJosephson CB, Jett\u0026eacute; N. Psychiatric comorbidities in epilepsy. Int Rev Psychiatry. 2017;29:409\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEttinger A, Reed M, Cramer J. Depression and comorbidity in community-based patients with epilepsy or asthma. Neurology. 2004;63:1008\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScott AJ, Sharpe L, Hunt C, Gandy M. Anxiety and depressive disorders in people with epilepsy: a meta-analysis. Epilepsia. 2017;58:973\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSiebenbrodt K, Willems LM, von Podewils F, Mross PM, Str\u0026uuml;ber M, Langenbruch L, et al. Determinants of quality of life in adults with epilepsy: a multicenter, cross-sectional study from Germany. Neurol Res Pract. 2023;5:41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS\u0026aacute;nchez-G\u0026oacute;mez A, Salas-Puig J, Garc\u0026iacute;a-Morales I, Gil-Nagel A. The mediating role of epileptic seizures, irritability, and depression on quality of life in people with epilepsy. Epilepsy Behav. 2020;112:107375.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSobregrau P, Baill\u0026egrave;s E, Carre\u0026ntilde;o M, Donaire A, Boget T, Setoain X, et al. Psychiatric and psychological assessment of Spanish patients with drug-resistant epilepsy and psychogenic nonepileptic seizures (PNES) with no response to previous treatments. Epilepsy Behav. 2023;145:109329.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKanner AM, Schachter SC, Barry JJ, et al. Depression and epilepsy: epidemiologic and neurobiologic perspectives that may explain their high comorbid occurrence. Epilepsy Behav. 2020;111:107281.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMichaelis R, Tang V, Goldstein LH, Reuber M, LaFrance WC Jr, Lundgren T, et al. Psychological treatments for adults and children with epilepsy: Evidence-based recommendations by the International League Against Epilepsy Psychology Task Force. Epilepsia. 2018;59:1282\u0026ndash;302.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAllain H, Sch\u0026uuml;ck S, Nachit-Ouinekh F, et al. Improvement in quality of life after initiation of lamotrigine therapy in patients with epilepsy in a naturalistic treatment setting. Seizure. 2007;16:173\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaylor RS, Sander JW, Taylor RJ, Baker GA. Predictors of health-related quality of life and costs in adults with epilepsy: a systematic review. Epilepsia. 2011;52:2168\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKinyanjui DW, Kathuku DM, Mburu JM. Quality of life among patients living with epilepsy attending the neurology clinic at Kenyatta National Hospital, Nairobi, Kenya: a comparative study. Health Qual Life Outcomes. 2013;18:98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOgundare T, Adebowale TO, Borba CPC, Henderson DC. Correlates of depression and quality of life among patients with epilepsy in T Nigeria. Epilepsy Res. 2020;164:106344.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBishop M. Determinants of employment status among a community-based sample of people with epilepsy. Rehab Counsell Bull. 2004;47:112\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlsaadi T, Shahrour TM, Abou-Khalil B. Determinants of quality of life in patients with epilepsy in the Middle East. Epilepsy Behav. 2020;102:106715.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWirrell EC, Wood L, Hamiwka LD, Sherman EM. Quality of life in children with epilepsy: effect of diagnosis and demographic factors. Epilepsy Behav. 2020;112:107391.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAsadi-Pooya AA, Sperling MR. Gender differences in epilepsy and neuropsychiatric comorbidities. Epilepsy Behav. 2020;110:107158.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJosephson CB, Patten SB, Bulloch AG, Williams JV, Fiest KM, Jette N. Psychiatric comorbidity in epilepsy: A population-based analysis. Epilepsia. 2017;58:742\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMekuriaw B, Wondie M, Yitayih Y, Sahile AT, Abebaw G. Health-related quality of life in epilepsy and its associated factors among adult patients with epilepsy in Southwest Ethiopia. BMJ Open. 2024;14:e079165.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAustralian Epilepsy Project. Work productivity, quality of life, and care needs in people with epilepsy. Epilepsy Behav. 2023;140:10984321.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHagemann A, Kuramochi I, Bien CG, Brandt C. Screening for depression, anxiety, and suicidality in outpatients of a tertiary epilepsy center: How frequent are increased scores and what is recommended? Epilepsy Behav. 2025;164:110289.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMart\u0026iacute;nez-Ju\u0026aacute;rez IE, Gonzalez-Salido J, Colado-Martinez J, et al. Anxiety and depression in people with epilepsy during and one year after the COVID-19 pandemic. Epilepsia Open. 2025;10:186\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-public-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pubh","sideBox":"Learn more about [BMC Public Health](http://bmcpublichealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pubh/default.aspx","title":"BMC Public Health","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"quality of life, refractory epilepsy, Thailand, risk factors","lastPublishedDoi":"10.21203/rs.3.rs-5926990/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5926990/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction: Health related quality of life (HRQoL) has become a pivotal outcome parameter for epilepsy management. Few studies have described the variables that impact quality of life (QoL) in patients with refractory epilepsy in developing Asian countries. Here, we sought to assess the relationship of sociodemographic factors, epilepsy-related variables, and psychiatric comorbidity with HRQoL.\u003c/p\u003e \u003cp\u003eMethods: We consecutively recruited a sample of adult patients with confirmed refractory epilepsy in multiple centers in Thailand. Multivariable linear regression analyses were used to identify socio-demographic factors, epilepsy-related variables, and psychiatric comorbidity factors associated with quality of life using QOLIE-31 score. Regression models were based on a pre-compiled directed acyclic graph (DAG).\u003c/p\u003e \u003cp\u003eResults: A total of 394 patients from seven centers were evaluated. The mean QOLIE-31 score was 59.3 (SD\u0026thinsp;=\u0026thinsp;15.5). The subscale score for overall quality of life was the highest (65.0\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;15.9) and that for social function was the lowest (51.6\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;25.2). There were significant differences between age groups, gender, current working status, seizure frequency, depression, anxiety, and QOLIE-31 score in the univariate analysis. Multivariable regression analyses identified significant total effects of age and gender on quality of life, significant direct effects of depression and anxiety, and both total and direct effects of seizure frequency, current working status, depression, and anxiety, indicating that the DAG sought factors associated with quality of life. We found a statistically significant difference in QOLIE-31 scores between age groups and religion-interaction, current working status, depression, and anxiety.\u003c/p\u003e \u003cp\u003eConclusions: Our study included adult patients with focal refractory epilepsy. In addition to age and gender, depression, anxiety, and seizure frequency were the main determinants of QOL. Thus, improvement of QOL by screening for its factors should be one of the main goals in the treatment of refractory epilepsy.\u003c/p\u003e","manuscriptTitle":"Quality of life in adults with refractory epilepsy in Thailand: a multicenter upcountry nationwide study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-30 20:32:12","doi":"10.21203/rs.3.rs-5926990/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-26T12:16:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-26T12:14:06+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-05T07:43:19+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-01T10:49:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"104270657102374922354762812297032955101","date":"2025-04-28T20:58:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"319497473861566365130342255917159697778","date":"2025-04-28T16:48:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-28T14:37:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-24T01:25:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Public Health","date":"2025-04-22T08:01:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-public-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pubh","sideBox":"Learn more about [BMC Public Health](http://bmcpublichealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pubh/default.aspx","title":"BMC Public Health","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a790a3dc-e776-4f22-9418-a76c61fdecdf","owner":[],"postedDate":"April 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-07T16:08:32+00:00","versionOfRecord":{"articleIdentity":"rs-5926990","link":"https://doi.org/10.1186/s12889-025-23495-5","journal":{"identity":"bmc-public-health","isVorOnly":false,"title":"BMC Public Health"},"publishedOn":"2025-07-02 15:58:45","publishedOnDateReadable":"July 2nd, 2025"},"versionCreatedAt":"2025-04-30 20:32:12","video":"","vorDoi":"10.1186/s12889-025-23495-5","vorDoiUrl":"https://doi.org/10.1186/s12889-025-23495-5","workflowStages":[]},"version":"v1","identity":"rs-5926990","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5926990","identity":"rs-5926990","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}