Prevalence and determinants of depression in patients with epilepsy during the COVID-19 pandemic

Background Epilepsy is one of the commonest and most serious neurological conditions. It is frequently associated with one or more medical or psychiatric comorbidities. Depression is one of the most common comorbidities. Patients with epilepsy (PWE) are expected to suffer from a high level of depression during the COVID-19 pandemic. This cross-sectional study was applied to 290 PWE. Data was collected by personal interviews with each patient using the Patient Health Questionnaire 9 (PHQ 9) scale for the diagnosis of depression and assessing its severity. We aimed to assess the prevalence and the risk factors of depression in PWE during the COVID-19 pandemic. Results We found that 70.3% of PWE suffered from depression. Low financial status, refractory seizures, fear of infection and death by COVID-19, had close relatives died by COVID-19, had a sleep disturbance, a decreased family support, increased seizure rate during the pandemic, increased ER visits during the pandemic, lack of drug adherence, and decreased epilepsy-related follow-up visits during the pandemic were significantly associated with increased risk of depression in PWE during the pandemic. Conclusions The COVID-19 pandemic has a serious effect on the psychological and physical well-being of PWE. There was an increased rate of depression during the COVID-19 pandemic in PWE with its subsequent burden on those patients. So, these patients are in a high need of care and support during the pandemic.

Page 2 of 8 Sehlo et al. Middle East Current Psychiatry (2022) 29:22 (serotonin and norepinephrine) [8], and anatomical abnormalities (prefrontal cortex and paralimbic structures) [9], also the social burden of the epilepsy itself on the patients. The COVID-19 pandemic incorporates a lot of new stressful situations: loss of employment, the death of family members and colleagues, financial insecurity, and isolation from others, especially for people who live alone [10]. That can lead to a higher level of depression in PWE.
The frequency of depressive symptoms in the general population in the USA was found to be more than 3-fold higher during COVID-19 than before the pandemic. Individuals with fewer financial resources and more stressor exposure (such as job loss) reported more depressive symptoms [11].
Patients with epilepsy are expected to suffer from a high rate of depression during the COVID-19 pandemic. It was found that the prevalence of depression among patients with epilepsy (PWE) increased to 42.3% during the period of the pandemic [12].
The aims of this study were to assess the prevalence and the risk factors of depression in PWE during the COVID-19 pandemic. To our knowledge, this is the first study that had been conducted to assess depression among PWE in Egypt.

Participants
A sample of 290 consecutive patients diagnosed with epilepsy according to the International League Against Epilepsy (ILAE) classification 2017 were included in this cross-sectional study. The patients were recruited from the outpatient clinic and the inpatient ward of the Neurology Department, Zagazig University Hospital, Zagazig, Egypt, between August 2020 and September 2021.
Both male and female patients with an age range from 19 to 60 years were included in the study.
Exclusion criteria were patients with a past history of psychiatric illness, substance abuse, intellectual disability, chronic major medical disorders other than epilepsy, and previous or current infection with COVID-19.

Sociodemographic and clinical data form
The sociodemographic and clinical data form is composed of questions related to personal and clinical characteristics of the patients and questions related to the COVID-19 pandemic. Including age, gender, marital status, employment status, number of children, educational degree, financial status, where and with whom the patient lives, family history of epilepsy, and psychiatric illness. Epilepsy-related data: type of seizures, response to antiepileptic drugs (AEDs) whether respondent or resistant, age of onset, time of seizure occurrence, number of drugs taken, rate of seizures before and during the pandemic, number of previous ER visits by a seizure, number of ER visits by a seizure during the pandemic, fear of having an uncontrolled seizure during the pandemic, drug adherence during the pandemic, routine follow-up during the pandemic. COVID-19-related data: closed people infection or death, following news about the pandemic, sleep disturbance during the pandemic, family support during the pandemic, job changes during the pandemic, financial changes during the pandemic, fear of job loss during the pandemic, fear of infection or death by COVID-19, fear of closed one's infection or death by COVID-19, and sense of the end of the world.

Patient Health Questionnaire 9
The Patient Health Questionnaire (PHQ 9) will be used to assess depressive symptoms [13]. The PHQ 9 is a widely used measure for identifying depressive symptoms and diagnosing depressive disorders and has excellent psychometric properties when used in medical and psychiatric patients. The PHQ 9 incorporates DSM-IV diagnostic criteria for major depressive disorder, assessing the presence and severity of the nine primary symptoms of major depression. This enables not only the determination of the severity of depression but also the presence of depressive disorder. Scores of 5, 10, 15, and 20 represent mild, moderate, moderately severe, and severe depression respectively [14].
The validated Arabic version of the scale was used in this study [15].

Statistical analysis
The data analysis and sample size calculations (with 80% power) were performed using the statistical package for social sciences (SPSS version 20). The categorical data were presented in the form of number and percentage. continuous data were expressed as mean ± SD (standard deviation) and median with the interquartile range (IQR). Chi-square was used as a test of significance of the differences among groups. Binary logistic regression analysis was used to assess the predictors of depression. A P value < 0.05 was considered to indicate statistical significance. Table 1 shows that the age of the studied group ranged from 18 to 60 years with a mean of 33.69 years. Regarding sex, more than half of them were male (52.4%). About 50% of them live in urban areas; 55.9% live with their spouse and siblings. 56.2% of them were married. Regarding education and occupation, 54.1% had secondary education. 40.3% of them were working. Low financial status was found among 39% of them, while financial status was satisfying among 54.1% of them. Finally, 37.6% of them had no children and 39.6% had 1 to 2 children. Table 2 shows that the median age of onset of epilepsy among the studied group was 17 years while duration was 14 years. About 21.4% of them had a positive family history of epilepsy, 2.8% had a positive family history of psychiatric disease, and 8.3% had a positive past history of psychiatric disease. The most frequent type of seizures found among the studied groups was generalized (43.4%); also 69.3% of the cases were responsive. Almost 89% of the studied group take more than one AEDs. Finally, 83.3% of the cases had seizures at any time. Table 3 shows that 28.3% of the studied group had moderately severe and 21% had severe depression according to the PHQ 9 score. Table 4 shows that there was a statistically significant increase in the frequency of moderately severe to severe depression among persons who fear COVID-19 infection, fear of death from COVID-19 infection, had close people infected, had close people dead, had financial changes during the pandemic, had sleep disturbances during the pandemic, had decreased family support during the pandemic, and continuously follow news about the pandemic. Table 5 shows that there was a statistically significant increase in the frequency of moderately severe to severe depression among patients who had increased seizure rate, increased ER visits during the pandemic, patients who reported lack of drug adherence, and patients who reported decreased follow-up visits during the pandemic. Table 6 shows that not working, low financial status, refractory seizures, fear of infection and death by

Discussion
To our knowledge, this is the first study that had been conducted to assess depression among PWE in Egypt. In our study, we assessed the prevalence and the determinants of depression in patients with epilepsy (PWE), during the COVID-19 pandemic. In our study, the prevalence of depression in patients with epilepsy during the pandemic is 70.3%. 6.2% of the participants had mild depression, 14.8% had moderate depression, and 28.3% had moderately severe depression, while 21% had severe depression. Few studies have investigated the relationship between depression and COVID-19 in PWE, and all of them are consistent with our results about the increased prevalence of depression in those patients during the COVID-19 pandemic with varying percentages and this can be explained by the severe stress of the COVID-19 pandemic added to the burden of epilepsy itself.
The prevalence of depression in patients with epilepsy varied largely across the studies. In a meta-analysis of 51 cross-sectional studies published between 1999 and 2018 with sample sizes ranging from 36 to 1763, Yang et al. found that the prevalence of depression among patients with epilepsy (PWE) ranged greatly from 5.09 to 85.5% largely depending on the used diagnostic criteria [16].
The prevalence of depression in patients with epilepsy varied also during the pandemic. Sun et al. found that Table 6 Binary logistic regression analysis of the predictors of depression among the studied group OR odds ratio, CI confidence interval; *significant (P < 0.05), **highly significant (P < 0.001) Lunardi et al. found in their regression analysis model that increased seizure frequency, difficulties to access their physicians and anti-seizure drugs, and unemployment increase the risk of depression in PWE during the pandemic [24]. Yang et al. found that the most significant factors associated with an increased risk of depression in PWE during the pandemic were unemployment and poor antiepileptic drug (AED) adherence [16]. Our study is the first to assess a lot of predictors for depression in PWE during the pandemic, while the previously mentioned studies assessed only a few predictors that were consistent with our results. The present study has some limitations; as the crosssectional design of the study prevents causal conclusions, it just proves an association between depression with its determinants and COVID-19 pandemic and opens the floor for further longitudinal studies to prove causality. There are also several strengths of this study as it is the first study in Egypt that assessed the association between depression with its determinants and the COVID-19 pandemic and also the first study that examined a lot of determinants for depression in PWE during the COVID-19 pandemic.

Conclusions
Our study revealed a high prevalence of depression in PWE during the COVID-19 pandemic. During the pandemic, patients with refractory seizures, sleep disturbance, low financial status, increased seizures' rate, being unemployed, increased ER visits, fear of COVID-19 infection, fear of death by COVID-19 infection, lack of drug adherence, decreased epilepsy-related follow-up consultations, and closed people death by COVID-19 were the most significant predictors for depression in PWE. So, these risk factors must be evaluated and adjusted as this will be reflected in the improvement of the depression which in turn will be reflected in the improvement of epilepsy and on the quality of life of PWE.

Limitations of the study
Our study has some limitations. Because the exposure and outcome are examined concurrently in a cross-sectional study, there is often no evidence of a causation link between exposure and outcome and longitudinal studies are recommended. However, we have many strengths in our study as our results are useful in focusing on PWE who are already under severe stress that increased more in the pandemic. Our study was performed by direct doctor-patient interview, not online or self-submitted questionnaires, which guarantees correct understanding of the patients to the questions and good interpretation of the results. Our study was performed in an epilepsy clinic and not in primary care clinic, allowing us to reach the medical records of the patients, which was very important to confirm the diagnosis, the type of seizures, the duration of illness, the number of anti-seizure medications, and the past medical history.

Recommendations
We recommend that PWE should be regularly screened for depression especially during unusual circumstances like the COVID-19 pandemic. Early detection of depression in PWE and early adjustment of its risk factors helps for early treatment and better outcomes that will be reflected also on better management of epilepsy and better quality of life for those patients.