Epilepsy is a chronic neurological disorder with consequences that extend beyond recurrent seizures. In addition to treatment-related and social restrictions, people with epilepsy frequently experience psychiatric comorbidities that may influence functioning, independence, quality of life, adherence to treatment, and family relationships [1,2]. Depression and anxiety are among the most frequently reported psychiatric conditions, while psychosis, behavioural disturbances, cognitive impairment, and other neuropsychiatric conditions may also occur [2]. Caregiver burden is a multidimensional construct that encompasses emotional distress, disruption of family and social relationships, financial strain, restriction of personal activities, physical exhaustion, and deterioration in psychological well-being. In epilepsy, the unpredictability of seizures, need for supervision, treatment complexity, stigma, cognitive impairment, and psychiatric symptoms may all increase the responsibilities of informal caregivers [3,4]. Historically, studies of caregiver burden in epilepsy focused mainly on seizure frequency and severity. More recent evidence suggests that seizure variables alone may not adequately explain caregiver burden. In a study of 151 primary caregivers, neuropsychiatric comorbidity in patients was associated with poorer caregiver psychological and social quality of life, while aggressive behaviour was independently associated with higher caregiver burden [4]. In another adult cohort, patient anxiety and depression showed significant correlations with caregiver burden [5]. The relationship may also be dyadic. Depression and anxiety in patients can coexist with depression, anxiety, emotional exhaustion, and family burden among caregivers [6,7]. In paediatric epilepsy, internalising and externalising behavioural symptoms have been associated with parental stress, and recent work suggests that behavioural and cognitive characteristics may contribute to parental stress beyond the effects of seizure variables alone [8,9]. The available literature is heterogeneous with respect to patient age, psychiatric measures, caregiver-burden instruments, and statistical approaches. A consolidated synthesis is therefore needed to clarify the relationship between psychiatric and neuropsychiatric comorbidities in epilepsy and the burden experienced by caregivers. The present systematic review aimed to synthesise evidence from adult and paediatric epilepsy populations and to identify psychiatric, behavioural, cognitive, treatment-related, and caregiver factors that modify this relationship.

Study design and reporting guideline: The review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement [10]. Review question: Among children, adolescents, or adults with epilepsy, what is the relationship between psychiatric or neuropsychiatric comorbidities and caregiver burden, parental stress, family burden, caregiver psychological distress, or caregiver quality of life? Information sources and search strategy: PubMed/MEDLINE and a multidisciplinary peer-reviewed academic literature index were searched for publications available up to September 2026. Search concepts combined epilepsy or seizure disorder with psychiatric comorbidity, depression, anxiety, neuropsychiatric symptoms, behavioural problems, aggression, internalising or externalising symptoms, caregiver, parent, family caregiver, caregiver burden, family burden, parental stress, caregiver distress, and caregiver quality of life. Reference lists of relevant papers were also checked for additional eligible studies. Eligibility criteria: Original observational or analytical studies were eligible when they included patients with epilepsy and family or informal caregivers; evaluated psychiatric, emotional, behavioural, cognitive, or neuropsychiatric factors in the patient or the psychiatric impact of epilepsy caregiving within a patient-caregiver dyad; and reported caregiver burden, parental stress, family burden, caregiver psychological distress, or caregiver quality of life. Reviews, editorials, case reports, studies of psychogenic non-epileptic seizures without epilepsy, and studies without a relevant caregiver outcome were excluded. Study selection: After removal of duplicates, titles and abstracts were screened against the eligibility criteria. Potentially relevant articles underwent full-text assessment. Reasons for exclusion at the full-text stage were recorded. The selection process is presented in Figure 1. Data extraction: Extracted information included author and year, country, study design, sample size, patient age group, psychiatric or neuropsychiatric factor, caregiver outcome measure, and principal findings. Because of heterogeneity in populations, instruments, and effect measures, a meta-analysis was not considered appropriate. Risk-of-bias considerations: The evidence base was assessed qualitatively with attention to participant selection, use of validated psychiatric and caregiver instruments, adjustment for confounding variables, completeness of outcome reporting, and appropriateness of statistical analyses. Most included studies were cross-sectional and therefore remained susceptible to selection bias, self-report bias, residual confounding, and inability to establish temporality. PRISMA STUDY SELECTION The search identified 50 records. Nine duplicate records were removed, leaving 41 records for title and abstract screening. Nineteen records were excluded at this stage. Twenty-two full-text reports were assessed for eligibility. Eight full-text reports were excluded: three primarily evaluated caregiver psychiatric variables without a relevant patient psychiatric exposure, two did not report a relevant relationship with a caregiver outcome, two were secondary reviews or other non-primary publications, and one involved an ineligible population. Fourteen studies were included in the qualitative synthesis (Figure 1).

Study characteristics: Fourteen studies published between 2014 and 2025 were included. Adult and paediatric epilepsy populations were represented, and most studies used cross-sectional designs. Caregiver outcomes were commonly measured with the Zarit Burden Interview, Parenting Stress Index, Family Burden Scale, family-burden measures, or quality-of-life and psychiatric symptom scales. The principal characteristics and findings are summarised in Table 1. Table 1. Characteristics and principal findings of the 14 included studies Study Country Population Psychiatric/neuropsychiatric factor Caregiver outcome Key finding Karakis et al., 2014 USA Adult; 48 PWE-caregiver dyads Cognition, psychiatric/psychosocial factors, treatment burden Caregiver burden; caregiver QOL Higher number of antiseizure medicines, poorer patient neuropsychological performance, lower patient QOL, and lower caregiver education were associated with higher burden. Gutierrez-Angel et al., 2018 Mexico Adult; 151 caregivers Patient neuropsychiatric comorbidity; aggression ZBI; caregiver QOL Aggressive behaviour independently associated with higher caregiver burden; psychiatric comorbidity associated with poorer psychological/social caregiver QOL. Torres et al., 2019 Philippines Paediatric caregivers Caregiver anxiety/depression in epilepsy caregiving context Caregiver burden; QOL; anxiety/depression Caregiver burden was related to poorer quality of life and depressive/anxiety symptoms, supporting a substantial psychiatric impact of paediatric epilepsy caregiving. Shah et al., 2019 Nepal Adult caregivers; n=100 Caregiver depression ZBI; HAM-D Caregiver burden showed a significant positive relationship with depressive symptoms. Pokharel et al., 2020 Nepal Paediatric caregivers; n=106 Comorbidities; caregiver depression/anxiety ZBI-short; HADS Burden was higher with poorly controlled seizures and comorbidities; caregiver depression positively correlated with burden. Operto et al., 2021 Italy Children/adolescents; 103 epilepsy, 93 controls Internalising, externalising and total behavioural problems Parenting Stress Index Parental stress correlated with child internalising, externalising and total behavioural-problem scores. Tsamakis et al., 2022 USA Adult; 100 PWE-caregiver dyads Patient mood disorder, anxiety, psychosocial factors Caregiver burden; caregiver anxiety/depression Patient mood disorder associated with caregiver burden in univariate analysis; patient anxiety and caregiver burden predicted caregiver mood morbidity. Joao et al., 2022 Brazil Adult; 120 matched dyads within larger sample Patient depression and anxiety Caregiver depression/anxiety Patient depressive symptom intensity correlated with caregiver depression (r=0.35) and anxiety (r=0.25). Guermazi et al., 2022 Tunisia Paediatric caregivers; n=44 Child psychiatric comorbidity; caregiver depression/anxiety ZBI-12; STAI; BDI High caregiver burden coexisted with anxiety and depression; child psychiatric comorbidity was present in a subset. Wu et al., 2023 China Parents of children with epilepsy; n=288 Child neuropsychiatric symptoms; parental depression/anxiety Family Burden Scale; GAD-7; PHQ-9 High family burden, parental anxiety/depression, and child neuropsychiatric symptoms were common; parental depression strongly influenced family burden. Joss et al., 2023 Israel Mothers of children with epilepsy; n=168 Caregiver anxiety/depression; illness severity ZBI Anxiety directly predicted burden; illness severity had indirect effects through emotional exhaustion and anxiety; model explained 55% of burden. Yeni et al., 2024 Turkey Adult; 107 PWE-caregiver dyads Patient anxiety, depression, cognition, stigma ZBI Patient anxiety (p=0.001), depression (p=0.005), cognition, stigma and QOL correlated with caregiver burden. Correale et al., 2025 Italy Children with epilepsy; 117 children, 149 caregivers Internalising/behavioural symptoms; cognition Parenting Stress Index-SF Clinical-range behavioural symptoms, especially internalising problems, and cognitive impairment were associated with higher parental stress. Zhu et al., 2025 China Adult; 178 PWE-caregiver pairs Patient depression; caregiver anxiety/depression Family burden and psychiatric measures Patient depression was associated with caregiver anxiety/depression; caregiver psychiatric symptoms were related to family burden. Adult epilepsy: In adult cohorts, patient psychiatric and neuropsychiatric features were repeatedly associated with caregiver outcomes. Gutierrez-Angel et al. reported that aggressive behaviour was independently associated with higher caregiver burden, whereas seizure control was not significantly related to burden [4]. Yeni et al. found significant correlations between caregiver burden and patient anxiety (p=0.001) and depression (p=0.005), as well as cognition, stigma, and quality of life [5]. Tsamakis et al. reported that a mood disorder in the patient was associated with caregiver burden in univariate analysis, while patient anxiety and caregiver burden remained important determinants of caregiver mood morbidity [6]. Joao et al. demonstrated a dyadic relationship in which patient depressive symptom severity correlated with caregiver depression (r=0.35, p<0.001) and caregiver anxiety (r=0.25, p=0.01) [7]. Paediatric epilepsy: Paediatric studies showed a similar pattern. Operto et al. demonstrated significant relationships between parental stress and children's internalising, externalising, and total behavioural-problem scores [8]. Wu et al. reported high family burden together with frequent parental anxiety and depression, while more than half of children had neuropsychiatric symptoms [11]. Joss et al. found that caregiver anxiety directly predicted burden and that illness severity affected burden indirectly through emotional exhaustion and anxiety; the path model explained 55% of burden [12]. Correale et al. found that clinical-range behavioural symptoms, particularly internalising problems, and cognitive impairment were associated with elevated parental stress [13]. Caregiver psychiatric morbidity and family burden: Several studies demonstrated that caregiver depression and anxiety are closely intertwined with perceived burden. Shah et al. reported a significant positive relationship between caregiver depression and burden [14], and Pokharel et al. similarly found a positive correlation between depression and caregiver burden in childhood epilepsy [15]. Zhu et al. found that depression in adult PWE was associated with caregiver anxiety and depression and that caregiver psychiatric symptoms were related to family burden [16]. Collectively, these findings support a dyadic model in which patient psychiatric morbidity and caregiver psychological distress may reinforce one another.

This systematic review indicates that psychiatric and neuropsychiatric comorbidities in epilepsy have clinically relevant consequences for informal caregivers. Across adult and paediatric populations, depression, anxiety, aggression, internalising symptoms, behavioural disturbances, cognitive impairment, and psychosocial dysfunction were associated with greater caregiver burden, parental stress, psychological distress, or poorer caregiver quality of life. Among adult PWE, the most direct evidence comes from Gutierrez-Angel et al., who found that aggressive behaviour was independently associated with higher caregiver burden, while seizure control itself was not significantly associated with burden [4]. This suggests that the interpersonal and behavioural consequences of psychiatric morbidity may generate caregiving demands that are partly independent of seizure frequency. Yeni et al. further showed that patient anxiety and depression correlated with caregiver burden, alongside cognition, stigma, and patient quality of life [5]. Depression appears particularly important within patient-caregiver dyads. Joao et al. found that depressive symptoms in PWE correlated with both depressive and anxiety symptoms in caregivers [7]. Zhu et al. similarly demonstrated that patient depression was associated with caregiver psychiatric morbidity and that caregiver psychological symptoms were related to family burden [16]. These findings support a reciprocal framework rather than a simple unidirectional model of burden. Paediatric epilepsy research adds a developmental perspective. Internalising and externalising symptoms, behavioural problems, and cognitive impairment may substantially increase parental stress [8,13]. The demands of supervising seizures, maintaining treatment, managing school and social functioning, and responding to behavioural or emotional problems can accumulate over time. In some studies, behavioural and cognitive variables appeared to contribute to parental stress beyond conventional epilepsy-related variables. The relationship between psychiatric morbidity and caregiver burden is nevertheless complex. Stigma, polytherapy, drug resistance, treatment adverse effects, socioeconomic disadvantage, caregiver education, time spent caregiving, and patient dependence may modify the association. These factors can operate simultaneously, explaining why a single psychiatric variable does not always remain independently significant after multivariable adjustment. Clinical care should therefore extend beyond seizure control. Routine screening of PWE for depression, anxiety, aggression, and behavioural disturbance may identify families at increased risk of burden. Caregivers themselves should also be assessed for anxiety, depression, emotional exhaustion, social isolation, and unmet support needs. Family-centred interventions may include psychoeducation, treatment of patient psychiatric comorbidity, caregiver counselling, social support, stigma reduction, and access to respite or community services. CLINICAL IMPLICATIONS The findings support an integrated patient-caregiver model of epilepsy care. Psychiatric screening of the patient should be accompanied by enquiry about caregiver stress and family functioning, particularly when depression, anxiety, aggression, cognitive impairment, drug-resistant epilepsy, or polytherapy is present. Early referral for psychiatric or psychological treatment, caregiver psychoeducation, counselling, social-support interventions, and family-based approaches may reduce burden and improve outcomes for both members of the dyad. LIMITATIONS The evidence base has several limitations. Most included studies were cross-sectional, limiting causal inference and temporal interpretation. Psychiatric morbidity was defined using heterogeneous methods ranging from formal diagnoses to symptom scales and broad behavioural constructs. Caregiver outcomes also varied and included burden, family burden, parental stress, psychological distress, and quality of life. Adult and paediatric populations differ substantially in caregiving demands and cannot be considered clinically equivalent. Several studies were conducted in tertiary-care settings, potentially selecting for more severe epilepsy or greater psychiatric morbidity. Residual confounding by epilepsy severity, intellectual disability, socioeconomic circumstances, treatment complexity, stigma, and caregiver characteristics is likely. Because of these differences in design and outcome measurement, quantitative meta-analysis was not undertaken. CONCLUSION Psychiatric and neuropsychiatric comorbidities in epilepsy are associated with important consequences for caregivers. Depression, anxiety, aggression, internalising symptoms, behavioural disturbances, cognitive impairment, and related psychosocial difficulties are linked with greater caregiver burden, parental stress, or caregiver psychological distress. The evidence also suggests a reciprocal patient-caregiver relationship in which patient psychiatric morbidity affects caregiver well-being and caregiver distress may in turn influence the patient. Epilepsy care should therefore move beyond a seizure-centred model toward integrated neurological, psychiatric, and family-focused management. Routine psychiatric screening of patients together with assessment and support of caregivers may help reduce family burden and improve overall quality of life.

Psychiatric and neuropsychiatric comorbidities in epilepsy are associated with important consequences for caregivers. Depression, anxiety, aggression, internalising symptoms, behavioural disturbances, cognitive impairment, and related psychosocial difficulties are linked with greater caregiver burden, parental stress, or caregiver psychological distress. The evidence also suggests a reciprocal patient-caregiver relationship in which patient psychiatric morbidity affects caregiver well-being and caregiver distress may in turn influence the patient. Epilepsy care should therefore move beyond a seizure-centred model toward integrated neurological, psychiatric, and family-focused management. Routine psychiatric screening of patients together with assessment and support of caregivers may help reduce family burden and improve overall quality of life

1. World Health Organization. Epilepsy. Geneva: World Health Organization; 2024. 2. Kwon CS, et al. Psychiatric comorbidities in persons with epilepsy compared with persons without epilepsy: a systematic review and meta-analysis. JAMA Neurol. 2025;82(1):72-84. doi:10.1001/jamaneurol.2024.3976. 3. Karakis I, Cole AJ, Montouris GD, San Luciano M, Meador KJ, Piperidou C. Caregiver burden in epilepsy: determinants and impact. Epilepsy Res Treat. 2014;2014:808421. doi:10.1155/2014/808421. 4. Gutierrez-Angel AM, Martinez-Juarez IE, Hernandez-Vanegas LE, Crail-Melendez D. Quality of life and level of burden in primary caregivers of patients with epilepsy: effect of neuropsychiatric comorbidity. Epilepsy Behav. 2018;81:12-17. doi:10.1016/j.yebeh.2018.01.034. 5. Yeni K, Tulek Z, Cavusoglu A, et al. Caregiver burden and its predictors in adult epilepsy patients. Epilepsy Behav. 2024;153:109685. doi:10.1016/j.yebeh.2024.109685. 6. Tsamakis K, Teagarden DL, Villarreal HK, et al. Depression and anxiety in adult persons with epilepsy and their caregivers: a survey-based study at a tertiary care center. J Nerv Ment Dis. 2022;210(3):212-218. doi:10.1097/NMD.0000000000001436. 7. Joao RB, Nogueira MH, Morita-Sherman M, et al. The relationship between depression and anxiety symptoms of adult PWE and caregivers in a tertiary center. Front Neurol. 2022;13:766009. doi:10.3389/fneur.2022.766009. 8. Operto FF, Pastorino GMG, Pippa F, et al. Psychiatric symptoms and parental stress in children and adolescents with epilepsy. Front Neurol. 2021;12:778410. doi:10.3389/fneur.2021.778410. 9. Correale C, Mercier M, Cappelletti S, et al. Neurocognitive, behavioral, and treatment burden as key predictors of parental stress in pediatric epilepsy. Epilepsia. 2025. doi:10.1111/epi.18580. 10. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi:10.1136/bmj.n71. 11. Wu Y, Zhang R, Tang J, et al. Multi-dimensional influence of pediatric epilepsy on children and their families: a cross-sectional study. Epilepsy Behav. 2023;146:109360. doi:10.1016/j.yebeh.2023.109360. 12. Joss I, Bachner YG, Shorer T, Shorer Z, O'Rourke N. Direct and indirect predictors of burden in Arab-Bedouin and Jewish-Israeli mothers caring for a child with epilepsy. Healthcare (Basel). 2023;11(19):2662. doi:10.3390/healthcare11192662. 13. Torres JAKL, Arca-Cabradilla R, Sy MG, Corrales-Joson MLP, Moral-Valencia MAA, de Sagun RQ. Burden of care of Filipino children with epilepsy and its impact on quality of life, anxiety and depressive symptoms among caregivers. J Med Univ Santo Tomas. 2019;3(2). doi:10.35460/2546-1621.2018-0120. 14. Shah S, Sah C, Shahi A, KC R. Caregiving burden and depression among caregivers of patient with epilepsy. J Psychiatr Assoc Nepal. 2019;8(2). doi:10.3126/JPAN.V8I2.28024. 15. Pokharel R, Poudel P, Lama S, Thapa K, Sigdel R, Shrestha E. Burden and its predictors among caregivers of patient with epilepsy. J Epilepsy Res. 2020;10(1):24-30. doi:10.14581/jer.20005. 16. Zhu XR, Zhao T, Gu H, et al. Psychological status and family burden in caregivers of adult people with epilepsy. Epilepsy Behav. 2025;169:110458. doi:10.1016/j.yebeh.2025.110458. 17. Guermazi A, Charfi N, Mnif M, et al. Burden level among parents of children with epilepsy. Eur Psychiatry. 2022;65(Suppl 1). doi:10.1192/j.eurpsy.2022.2220.