Abstract
Our study investigated the prevalence and risk factors for generalised anxiety disorder (GAD) in children with epilepsy. A clinically significant level of anxiety was observed in 8% of children with epilepsy, especially those who are older, have frequent seizures, or have been on antiepileptic drugs for extended periods.
Introduction
Epilepsy is one of the most common neurological diseases globally. An estimated 12 million people with epilepsy are in India. In a community study of epilepsy in children from North India, the prevalence rates were 6.99 for rural and 5.48 for urban areas, with 4 per 1000 population with active epilepsy. 1
The diagnosis of epilepsy requires at least two unprovoked seizures occurring more than 24 h apart. 2 Children with epilepsy are at increased risk for psychological, behavioural, cognitive, neurologic, academic, and social problems caused by their chronic neurologic condition, which may have a significant impact on their quality of life independent of the seizures.3–7
Anxiety disorders are known to be common in children with epilepsy.8–12 There are a number of epilepsy-related factors that have been linked to mood disorders and anxiety: generalised anxiety disorder (GAD) is defined as excessive worry and tension about everyday events and problems that are not controllable and are expressed on most days for at least 6 months, to the point where the person experiences distress or has marked difficulty in performing day-to-day tasks. 13 GAD is characterised by excessive and uncontrollable worry about a variety of events and is accompanied by physical symptoms such as headaches, tension, restlessness, gastrointestinal distress, and heart palpitations. 14 The seven-item generalised anxiety disorder (GAD-7) is an easy way to validate the severity of anxiety. 15 GAD-7 was therefore used in our study in Indian children.
Methods
Our cross-sectional study was conducted in the Department of Pediatrics, UPUMS Saifai, from October 2022 to July 2024 after ethical clearance from our university. All children aged 6–14 years diagnosed with epilepsy according to the International League Against Epilepsy (ILAE) 2014 guidelines were enrolled (new patients and already diagnosed patients) after written and verbal consent of the patient's attendant. Epilepsy is defined in a person if any of the following conditions are met: (a) at least two unprovoked (or reflex) seizures occurring greater than 24 h apart; (b) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures occurring over the next 10 years. The diagnosis of epilepsy syndrome was added in 2017 to classify seizures into focal, generalised, or unknown onset. 16
After establishing a proper history, a physical examination was performed. Specific treatment in the form of antiepileptic drugs (AEDs) was recorded according to age and seizure type. All significant risk factors such as age, sex, residence, religion, parents’ educational status, family member numbers, socioeconomic status (assessed by the updated BG Prasad Scale 2022), 17 duration of AEDs, name of AED, family history of seizure or of psychiatric illness, parental relationship, school performance, and substance abuse were noted on the Proforma. Relevant investigations (full blood count, glucose and electrolytes) were performed on every patient. EEG and CT or MRI brain scans were done if required.
Patients were discharged when seizure-free for 3 days and afebrile with stable vital signs. GAD on discharge was decided by the treating consultant. Patients suffering were followed every 15 days for 6 months and evaluated according to the DSM-5 initially and at 6 months of post-epilepsy treatment. 13
GAD was diagnosed if (a) excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least 6 months, about a number of events or activities (such as work or school performance); (b). The child found it difficult to control the worry; (c) the anxiety and worry were associated with one (or more) of the following six symptoms (with at least some symptoms having been present for more days than not for the past 6 months):
Restlessness or feeling keyed up or on edge Being easily fatigued Difficulty concentrating or the mind going blank Irritability Muscle tension Sleep disturbance (difficulty falling or staying asleep, or restlessness, unsatisfying sleep); (d). The anxiety, worry, or physical symptoms caused clinically significant distress or impairment in social, occupational, or other important areas of functioning; (e) the disturbance was not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition (e.g., hyperthyroidism); (f). The disturbance was not better explained by another mental disorder.
13
The diagnosis of GAD was made by taking a proper history from older children and from parents in the case of younger children. A severity measurement of anxiety was attributed according to the GAD-7 scale (Fig. 1) and further classified as none, mild, moderate and severe. 15
GAD-7 anxiety severity score.
Excluded were those with severe illness, including severe respiratory distress needing artificial ventilation, disseminated intravascular coagulation, shock needing vasopressor support, asphyxia, neurological disorder, head injury, acute psychosis, pre-existing psychiatric illness, unstable vital signs, hearing problems, severe visual impairment, mental retardation, or a history of neurological, psychiatric, or severe medical problems. Likewise, having seizures for other reasons and having serious social issues obliged the patient's exclusion.
The sample size was calculated as 100 patients were enrolled.
Sample size formula: n = Z² × p × (1–p)/d2, where n is the sample size, Z is the Z-score (1.96 for 95% confidence), p is the expected prevalence, and d is the precision.
Results
A total of 100 children were included, being 60 boys and 40 girls. Their mean age was 8.9 ± 2.7 years, with sixty-seven <10 years old. A total of 88 had GAD scores between 0 and 4, indicating no anxiety. The remaining children were equally divided (as boys and girls) as mild anxiety (scores 5–9), moderate (scores 10–14), and severe (scores ≥15), all being over the age of 10 years (p < 0.05), and all but two living in rural areas, though this was not (p = 0.762). A minority came from lower-class families, again not statistically significant, as was school attendance (Table 1).
GAD score in various demographic variables.
Higher frequencies of seizure episodes were linked to elevated levels of anxiety, a not surprising significant finding, with severity related to the numbers of seizures, though this was not statistically significant (p = 0.84).
Patients who had been on AEDs for >6 months exhibited higher anxiety scores compared to those taking them for <6 months, again not statistically significant (p = 0.21); likewise, patients with poor medication compliance (Table 2).
GAD score on seizure episodes, AED duration and compliance.
Patients on polytherapy significantly experienced higher levels of anxiety compared to those on monotherapy (Table 3).
GAD score on various AEDs (polytherapy and monotherapy).
Among patients with >4 siblings, exhibited varying levels of anxiety; this was statistically significant (p = 0.02). Various other factors were not found to be significantly associated with different GAD scores (Table 4).
GAD scores and associated factors.
Regression analysis of various variables showed no significant variables (Table 5).
Regression analysis of various variables with GAD in univariate and multivariate models.
Discussion
GAD has been recognised as a distinct clinical entity in adults for decades, but its recognition and understanding in children have evolved more recently. Diagnosing GAD in children involves a comprehensive assessment that includes clinical interviews, behavioural observations, and standardised questionnaires. Its diagnostic reliability is today known as the most widely used anxiety measure in clinical practice and research. 18
There is a large variation in the prevalence of anxiety in various studies, ranging from 2% to 40%.19–22 In our study, significant anxiety in children with epilepsy was found in 8%, implying epilepsy may not be a contributory factor. However, differences in study populations, diagnostic criteria, the methodology used to assess GAD, contextual differences, sample size and severity of epilepsy may be responsible. Furthermore, prevalence rates remain highly dependent on the training and experience of interviewers.
Females had higher odds of having GAD, but this difference was not statistically significant. Though females are generally thought to be at higher risk for anxiety disorders, the difference may not always be significant.22,23
However, almost a quarter of the children in the 11- to 14-year old age group were diagnosed with GAD, but none of the children of 6–10 years: a significant difference (p < 0.0001). It is suggested that GAD generally increases with age,22,24 probably due to their increased cognitive awareness of their condition and its potential implications.
Seizure duration and frequency, particularly >7, and polytherapy may be associated with GAD,25,26
As the psychological burden of managing multiple medications, combined with the stress of epilepsy itself, can significantly contribute, but we found no such statistical significance.
However, different patterns were observed in the number of siblings and GAD scores, but more evidence is needed to draw a definitive conclusion on this relationship. Rural setting was likewise fraught with interpretational difficulty.
Generally, studies on children and GAD are few and far between; evaluation of psychological interventions (e.g., cognitive-behavioral therapy) and potential biomarkers (e.g., neuroimaging, genetic markers, EEG patterns) and genetic markers that could predict the development of GAD in childhood epilepsy are worth pursuing.
Footnotes
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
