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 .
The prevalence of depression in patients with epilepsy varied also during the pandemic. Sun et al. found that the prevalence of depression among PWE increased to 42.3% during the period of the pandemic . Abokalawa et al. found that two-thirds of their sample of PWE (66.2%) reported depression during the pandemic . Van Hees et al. found that 159/399 (39.8%) PWE scored positive for depression during the pandemic .
In our study, we found that a lot of factors related to the COVID-19 pandemic are significantly associated with increased frequency of moderately severe to severe depression. Patients who were afraid of COVID-19 infection, afraid of death from COVID-19 infection, had closed people infected or dead, had financial changes during the pandemic, had sleep disturbances during the pandemic, and continuously followed the pandemic news clearly suffered from more depression during the pandemic.
So, the COVID-19 pandemic is highly associated with increased prevalence and severity of depression among PWE which in turn has a severe burden on the patients.
These findings are consistent with other studies. Van Hees et al. reported increased depression severity with low financial status in PWE during the pandemic . Sonbol et al. found that PWE who were concerned about the COVID-19 pandemic news and spent 3 h or more following the news had higher depression than the less concerned ones . Kaya et al. reported increased depression levels in PWE if they encountered a COVID-19 patient or had a relative with COVID-19 . Çilliler and Güven and Stauder et al. found that poor sleep quality was associated with higher depressive symptoms in PWE [22, 23].
In our study, there was a statistically significant association between increased depression severity and increased seizure rate, increased ER visits, decreased drug adherence, and decreased routine follow-up during the pandemic.
Our study is consistent with other studies who reported increased severity of depression in PWE is associated with decreased drug adherence in PWE during the pandemic [19, 24]. Other studies found that there was a significant relationship between increasing seizure frequency in PWE and increased depression severity during the pandemic [25, 26].
Depression itself is associated with depressed mood, lack of interest, and lack of activity that leads to decreased drug adherence which in turn leads to increased seizure frequency and increased rate of ER visits, so it is a bidirectional relationship. Our study is consistent with other studies who demonstrated a 2-way relation between a broad spectrum of psychiatric disorders (i.e., depression, anxiety, psychosis) and epilepsy [27, 28]. The bidirectional relationship suggests that common pathogenetic mechanisms are operant in both conditions, with the presence of one disorder potentially increasing the severity of the other . Also, there is a decreased routine follow-up during the pandemic which in turn leads to worse control of the epilepsy.
Inconsistent with our results about the aspect of increased ER visits in PWE during the pandemic is Bamaga et al.  who found a 24% reduction in the number of ER visits for common neurological symptoms during the pandemic time in comparison to pre-pandemic. They explained this result by the public anxiety about the pandemic.
This inconsistency with our result can be explained by the fact that in our study 15.2% of the patients are illiterate and 54.1 % are secondarily educated. This lack of education makes it hard for the patient’s caretaker to fully understand how to support the patient during acute seizures and how to perform simple life-saving maneuvers like CPR which actually can be performed by many of the public in other communities. Moreover, this lack of education and low socioeconomic levels in our sample, along with the added financial problems during the pandemic, make it hard for these patients to access telemedicine services on the internet and mobile applications.
Using binary logistic regression analysis of the predictors of depression among the studied group during the pandemic, we found that these factors are significantly associated with increased frequency of depression in PWE during the pandemic: refractory seizures (more than 14-fold increase in the risk of depression, as a bidirectional link between depression and epilepsy), sleep disturbance (more than 12-fold increase in the risk of depression), low financial status (more than 11-fold increase in the risk of depression), increased seizures’ rate (7-fold increase in the risk of depression) (bidirectional relationship), being unemployed (5.8-fold increase in the risk of depression), increased ER visits (5.7-fold increase in the risk of depression), fear of COVID-19 infection (5-fold increase in the risk of depression), fear of death by COVID-19 infection (4.9 increase in the risk of depression), lack of drug adherence during the pandemic (4.2-fold increase in the risk of depression), decreased epilepsy-related follow-up consultations (3.7 increase in the risk of depression), and closed people death by COVID-19 infection (3.6 increase in the risk of depression).
Our results are consistent with other studies. Zis et al. found in their regression analysis model that unemployment and increased seizure frequency, in turn, increase the risk of depression in PWE . Bifftu et al. found in their regression analysis model that perceived stress, seizure frequency of ≥ 1 per month, and difficulties of adherence to antiepileptic drugs were independently associated with depression in PWE . Dos Santos 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 . 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 . 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 cross-sectional 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.