Epilepsy is a chronic neurological disorder characterised not only by recurrent seizures but also by cognitive, emotional, behavioural and social consequences. Psychiatric morbidity is considerably more common among people with epilepsy than among individuals without epilepsy. A recent systematic review and meta-analysis demonstrated increased odds of depression, anxiety disorders, psychosis, bipolar disorder and several other psychiatric conditions in persons with epilepsy, emphasising that psychiatric illness represents an important component of the overall disease burden [1]. The effect of these comorbidities may extend beyond the affected individual. Epilepsy is frequently managed within the family, particularly where seizures remain unpredictable, medication regimens are complex, cognitive impairment is present or the patient requires supervision. Caregivers may need to monitor medication adherence, manage seizure-related emergencies, accompany patients for healthcare visits and assume occupational or financial sacrifices. These responsibilities can produce caregiver burden, which encompasses emotional strain, restriction of personal activities, social disruption, financial pressure and deterioration in physical and psychological well-being. Traditionally, caregiver research in epilepsy has concentrated on clinical characteristics such as seizure frequency, duration of epilepsy, drug resistance and number of antiseizure medications. However, emerging evidence suggests that behavioural and psychiatric disturbances may be equally or more important. In a study of 151 caregivers, caregivers of patients with psychiatric comorbidity had poorer psychological and social quality of life, while patient aggressiveness was independently associated with greater caregiver burden. Seizure control itself did not demonstrate a significant relationship with burden in that study [3]. Similar observations have emerged in paediatric epilepsy. Children and adolescents with epilepsy exhibit increased internalising and externalising symptoms, and parental stress is associated with these behavioural disturbances. Operto et al. found significant relationships between total parental stress and child internalising, externalising and total behavioural problem scores [6]. More recent work has shown age-specific patterns in which internalising manifestations predominate as correlates of stress in younger children, whereas externalising behaviours become particularly relevant in older children and adolescents [9]. Psychological effects may also operate within the patient-caregiver dyad. Depression in patients may coexist with anxiety and depression in caregivers, while caregiver distress can in turn influence family functioning and patient well-being. Recent adult dyadic research has demonstrated that patient depression is independently associated with anxiety and depression among caregivers, whose psychological morbidity is itself closely linked to family burden [11]. Despite increasing interest in caregiver outcomes, studies remain heterogeneous, and psychiatric factors are often examined alongside numerous neurological, socioeconomic and caregiver-related variables. A focused synthesis of evidence specifically addressing patient psychiatric and behavioural morbidity in relation to caregiver burden is therefore warranted. The present systematic review aimed to evaluate the association between psychiatric and behavioural comorbidities in patients with epilepsy and caregiver burden, parental stress, caregiver psychological distress and family impact in adult and paediatric populations.

Study Design A systematic review of observational studies was undertaken and reported according to the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. The review protocol was not prospectively registered. Review Question The review addressed the following question: Among persons with epilepsy, are psychiatric, emotional or behavioural comorbidities associated with increased caregiver burden, parental stress, caregiver psychological morbidity or family impact? Information Sources and Search Strategy Searches were conducted using PubMed/MEDLINE and a multidisciplinary peer-reviewed academic literature index up to June 2026. Search concepts included epilepsy or seizure disorder; psychiatric morbidity, depression, anxiety, aggression, internalising symptoms, externalising symptoms and other behavioural problems; and caregiver burden, parental stress, family burden, caregiver distress and caregiver quality of life. Reference lists of potentially relevant articles were additionally examined. Eligibility Criteria Original studies were eligible when they evaluated children, adolescents or adults with epilepsy; included a family, parental or informal caregiver outcome; measured psychiatric, emotional, behavioural or neuropsychiatric characteristics in the patient; assessed caregiver burden, parental stress, family burden, caregiver psychopathology or family impact; and provided an analysable relationship between patient characteristics and caregiver outcomes. Reviews, meta-analyses, editorials, case reports, conference abstracts without sufficient primary data, studies focused solely on seizure burden, and studies without an eligible caregiver outcome were excluded. Study Selection A total of 42 records were identified during structured and supplementary searching. Five duplicate records were removed, leaving 37 records for title and abstract screening. Twenty-one were excluded at this stage. Sixteen reports were assessed in full text, of which six were excluded because they were secondary reviews or non-primary studies (n=2), investigated caregiver psychopathology without an appropriate patient psychiatric exposure (n=2), did not report an eligible caregiver-burden or stress outcome (n=1), or involved an ineligible clinical population (n=1). The final qualitative synthesis included 10 studies. Data Extraction For each included study, information was extracted on publication year, population, sample size, age group, patient psychiatric or behavioural exposure, caregiver assessment, principal statistical findings and major potential confounders. Methodological Assessment The methodological characteristics of the studies were considered with emphasis on sampling, use of validated psychiatric and caregiver instruments, clarity of exposure and outcome definitions, consideration of confounding variables and appropriateness of statistical analysis. Data Synthesis A meta-analysis was considered inappropriate because the included studies used heterogeneous psychiatric constructs, caregiver-burden measures and statistical models. Results were therefore synthesised narratively and organised according to adult epilepsy, paediatric epilepsy and major psychiatric or behavioural domains.

Adult Epilepsy Gutierrez-Angel et al. provided one of the clearest demonstrations of the relationship between patient psychiatric morbidity and caregiver burden. Among 151 caregivers, 112 patients had a psychiatric comorbidity. Caregivers of these patients had significantly poorer psychological and social quality-of-life scores. After adjustment, aggressive behaviour was associated with higher caregiver burden (p=0.008). In contrast, seizure control showed no significant correlation with burden or caregiver quality of life [3]. Yeni et al. evaluated 107 adults and their primary caregivers using the Zarit Caregiver Burden Inventory together with patient measures of anxiety, depression, cognition, stigma and quality of life. Patient anxiety (p=0.001) and depression (p=0.005) were significantly correlated with caregiver burden. Cognition, stigma and patient quality of life also demonstrated significant relationships with burden, indicating that caregiver strain occurs within a broader psychosocial context [8]. Tsamakis et al. examined 100 adult patient-caregiver dyads. Mood disorders were highly prevalent among both groups. In univariate analysis, a patient mood disorder was associated with caregiver burden as well as unemployment, frequent hospitalisation, treatment adverse effects, stigma and poorer quality of life. The findings demonstrate that patient psychiatric morbidity may interact with clinical and social disadvantage rather than acting as an isolated determinant [7]. Cui et al. examined 178 adult patient-caregiver pairs. Patient depression was independently associated with both caregiver anxiety and caregiver depression. Caregivers reported a moderate degree of family burden, with economic burden representing its largest component. Psychological symptoms in caregivers were significantly related to family burden, supporting a pathway from patient psychopathology to caregiver distress and subsequently to broader family consequences [11]. Paediatric Epilepsy Shatla et al. assessed children with epilepsy using measures of depression, anxiety, behavioural problems and cognitive performance together with the Parenting Stress Index. Although the sample was small, clinically important internalising and total behavioural problems were identified, and children with more difficult epilepsy were associated with high parenting stress [2]. Operto et al. compared 103 children and adolescents with epilepsy with 93 age- and sex-matched controls. Both emotional/behavioural symptoms and parental stress were significantly higher in the epilepsy group. Parenting Stress Index total scores were significantly associated with internalising, externalising and total Child Behavior Checklist problem scores, demonstrating that parental stress was closely related to the child psychiatric and behavioural profile [6]. Jakobsen et al. studied 162 caregivers of 140 children with severe epilepsy. Symptoms compatible with at least one psychiatric disorder were present in 43.5% of parents, while an additional 11% demonstrated subclinical post-traumatic stress symptoms. Greater parent-rated child difficulties were associated with parental PTSD, depression, anxiety and perceived stress. The authors reported that child behavioural difficulties and caregiver resources were more closely related to parental distress than epilepsy variables alone [4]. A subsequent study by Jakobsen and Elklit demonstrated that the association between child behavioural difficulties and parental outcomes was partly mediated through perceived self-control and coping responses. Their mediation model explained 64% of variance in parental stress and 42% of variance in family impact, suggesting that caregiver coping capacity modifies the consequences of patient behavioural morbidity [5]. Sirisha et al. provided evidence that age modifies which behavioural manifestations are most relevant. Among 314 children and adolescents, internalising manifestations such as withdrawal were strongly associated with parental stress in younger children, whereas externalising problems were more strongly related to stress among school-age children and adolescents. Educational difficulties and the requirement for special schooling were also associated with higher parental stress [9]. Correale et al. similarly demonstrated that clinical-range behavioural symptoms, particularly internalising problems, were associated with elevated parental stress. Cognitive impairment, polytherapy and drug-resistant epilepsy contributed additional burden. These findings suggest that neurobehavioural and developmental characteristics may account for a substantial portion of caregiver stress beyond conventional seizure-related factors [10]. Major Patterns Emerging from the Evidence Depression and anxiety: Depressive symptoms in persons with epilepsy were repeatedly associated with caregiver psychological morbidity or burden. Patient anxiety also correlated with burden in some adult studies, although its independent contribution was less consistent than that of depression. Aggression and externalising behaviour: Aggression was an independent predictor of caregiver burden in adult epilepsy. Among older children and adolescents, externalising behavioural symptoms were also strongly associated with parental stress [3,9]. Internalising symptoms: Anxiety, depressive features, withdrawal and other internalising manifestations were prominent correlates of stress among caregivers of younger children with epilepsy [6,9,10]. Cognitive and treatment complexity: Psychiatric morbidity rarely acted alone. Cognitive impairment, stigma, drug resistance, polytherapy, poorer quality of life and educational difficulties amplified caregiver stress in several studies [8,10].

The present systematic review demonstrates that psychiatric and behavioural manifestations in epilepsy are meaningfully associated with caregiver burden and psychological distress. Importantly, this association was identified in both adult and paediatric populations despite substantial variation in clinical setting, psychiatric measurements and caregiver instruments. Aggressive and disruptive behaviour appears particularly relevant because it directly changes the nature of caregiving. Gutierrez-Angel et al. found that aggressiveness remained associated with burden after adjustment, whereas seizure control did not [3]. This finding challenges the assumption that frequency or severity of seizures necessarily represents the principal determinant of family burden. A patient with reasonable seizure control but severe irritability, aggression or behavioural dysregulation may still require intensive family supervision and generate substantial interpersonal stress. Affective morbidity represents a second major pathway. Yeni et al. demonstrated significant relationships between patient anxiety, depression and caregiver burden, while Tsamakis et al. identified patient mood disorder as a correlate of caregiver burden [7,8]. More recent dyadic evidence indicates that depression in persons with epilepsy is independently associated with anxiety and depression among their caregivers, whose mental health is subsequently related to broader family burden [11]. These observations suggest that patient and caregiver mental health should not be conceptualised as independent clinical domains. The relationship appears particularly pronounced in childhood epilepsy. Emotional and behavioural abnormalities are frequent in paediatric epilepsy, and several studies demonstrated direct correlations between child behaviour and parental stress. Operto et al. identified relationships involving total, internalising and externalising symptoms, whereas Sirisha et al. demonstrated that the pattern varied according to developmental age [6,9]. These age-specific differences are clinically relevant because the challenges generated by anxiety and withdrawal in a preschool child differ from those associated with aggression, school failure or externalising behaviour in an adolescent. Studies of severe childhood epilepsy add an important family-process perspective. Jakobsen and colleagues showed that child behavioural difficulties were related not only to parental stress but also to depression, anxiety and post-traumatic stress symptoms. Furthermore, perceived control and coping responses mediated part of this relationship [4,5]. Thus, equivalent behavioural difficulties may produce markedly different caregiver outcomes depending on coping resources, psychological resilience and available social support. These findings support a conceptual model in which caregiver burden develops through the interaction of several domains. Psychiatric or behavioural morbidity increases day-to-day care demands; cognitive impairment and treatment complexity further increase dependence; stigma and social disadvantage restrict access to support; and inadequate coping resources increase the psychological consequences of these demands. The clinical implications extend beyond improving caregiver well-being. Persistent caregiver depression, anxiety or exhaustion may compromise medication supervision, attendance at follow-up, communication with healthcare providers and family functioning. Epilepsy management should therefore incorporate a family-centred approach rather than treating psychiatric comorbidity as an isolated complication of the patient. CLINICAL IMPLICATIONS Patients with epilepsy should be routinely screened for depression, anxiety, behavioural dysregulation and aggression, particularly when caregivers report disproportionate difficulty despite acceptable seizure control. In paediatric practice, validated behavioural screening should form part of epilepsy follow-up when parental stress is evident. Caregiver assessment should include psychological distress, perceived burden, financial strain, social isolation and coping resources. Where significant burden is detected, interventions may include psychoeducation, family counselling, psychiatric treatment of the patient, caregiver psychological support, social-work involvement, structured coping interventions and referral to peer-support programmes. STRENGTHS This review specifically focused on patient psychiatric and behavioural morbidity as a contributor to caregiver outcomes, rather than combining all neurological and socioeconomic predictors of burden. Both adult and paediatric populations were included, enabling identification of developmental differences in the psychiatric manifestations associated with caregiver stress. The review also distinguished direct caregiver burden from related outcomes such as family impact and caregiver psychological morbidity. LIMITATIONS Several limitations should be considered. Most included studies were cross-sectional, preventing firm conclusions regarding temporal sequence or causality. Sample sizes varied substantially, and several studies originated from tertiary epilepsy centres, potentially over-representing severe or treatment-resistant disease. Definitions of psychiatric comorbidity were heterogeneous. Some studies used formal psychiatric histories, whereas others used symptom scales such as the Child Behavior Checklist or Hospital Anxiety and Depression Scale. Caregiver outcomes were similarly diverse and included Zarit burden scores, parenting stress, family impact, caregiver quality of life and caregiver psychopathology. Adult and paediatric caregiving also represent fundamentally different contexts. Parents of young children often provide developmentally expected supervision in addition to epilepsy-related care, whereas caregivers of adults may experience different occupational, financial and dependency-related pressures. These populations could therefore not be combined quantitatively. Finally, heterogeneity in exposure definitions and effect measures precluded a meaningful meta-analysis.

Psychiatric and behavioural comorbidities in people with epilepsy are closely associated with caregiver burden and family psychological distress. Depression, anxiety, aggression, internalising symptoms, externalising behaviour and broader behavioural difficulties emerged as recurring correlates of adverse caregiver outcomes. In paediatric epilepsy, behavioural manifestations may contribute to parental stress as strongly as or more strongly than traditional seizure-related characteristics. In adults, patient depression, anxiety, aggression and psychosocial impairment are associated with caregiver burden and emotional morbidity. These findings support an integrated model of epilepsy care in which seizure management, psychiatric assessment and caregiver well-being are addressed simultaneously. Screening and treating psychiatric comorbidity may therefore offer benefits not only to patients but also to the families who provide their continuing care.

1. Kwon CS, Rafati A, Ottman R, Christensen J, Kanner AM, Jetté N, Newton CR. 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. 2. Shatla R, Sayyah HES, Azzam H, Elsayed RM. Correlates of parental stress and psychopathology in pediatric epilepsy. Ann Indian Acad Neurol. 2011;14(4):252-256. doi:10.4103/0972-2327.91938. 3. 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. 4. Jakobsen AV, Møller RS, Nikanorova M, Elklit A. The impact of severe pediatric epilepsy on experienced stress and psychopathology in parents. Epilepsy Behav. 2020;113:107538. doi:10.1016/j.yebeh.2020.107538. 5. Jakobsen AV, Elklit A. Self-control and coping responses are mediating factors between child behavior difficulties and parental stress and family impact in caregivers of children with severe epilepsy. Epilepsy Behav. 2021;122:108224. doi:10.1016/j.yebeh.2021.108224. 6. Operto FF, Pastorino GMG, Pippa F, Padovano C, Vivenzio V, Scuoppo C, Pistola I, Coppola G. Psychiatric symptoms and parental stress in children and adolescents with epilepsy. Front Neurol. 2021;12:778410. doi:10.3389/fneur.2021.778410. 7. Tsamakis K, Teagarden DL, Villarreal HK, Morton ML, Janocko NJ, Groover O, Loring DW, Drane DL, Karakis I. 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. 8. Yeni K, Tulek Z, Cavusoglu A, Polat Dunya C, Ozturk Erden S, Bostan NS, Bebek N, Baykan B. Caregiver burden and its predictors in adult epilepsy patients. Epilepsy Behav. 2024;153:109685. doi:10.1016/j.yebeh.2024.109685. 9. Sirisha S, Jala S, Vooturi S, Patil A, Somayajula S, Jayalakshmi S. Association between behavioral problems and parental stress in children and adolescents with epilepsy. Epilepsy Behav. 2025;163:110229. doi:10.1016/j.yebeh.2024.110229. 10. Correale C, Mercier M, Cappelletti S, Pietrafusa N, Falamesca C, Collalti E, et al. Neurocognitive, behavioral, and treatment burden as key predictors of parental stress in pediatric epilepsy. Epilepsia. 2025;66(12):4960-4971. doi:10.1111/epi.18580. 11. Cui X, Qi C, Ren Z, Wang B, Sun L, Chen Y, 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.