key: cord-0750420-29pk69jp
authors: Katyal, Jatinder; Rashid, Haroon; Tripathi, Manjari; Sood, Mamta
title: Prevalence of depression and suicidal ideation in persons with epilepsy during the COVID-19 pandemic: A longitudinal study from India
date: 2021-09-20
journal: Epilepsy Behav
DOI: 10.1016/j.yebeh.2021.108342
sha: e35bee7a0188bb06a10cf608a3f6499bc5d60396
doc_id: 750420
cord_uid: 29pk69jp

OBJECTIVES: COVID-19 pandemic has disrupted healthcare services for chronic disorders such as epilepsy. In this study, the impact of COVID-19 pandemic on persons with epilepsy (PWE) with regard to their seizure control, depression status, and medication adherence was assessed. METHODS: After ethical clearance, 449 PWE who had been previously evaluated for depression at All India Institute of Medical Sciences (AIIMS), New Delhi, India, were telephonically revaluated using Mini International Neuropsychiatric Interview and surveyed for source of medication and medication adherence over last 6 months. The prevalence and the association of depression, suicidality and seizures during pandemic with different PWE variables were determined. RESULTS: Out of 449 PWE, 70.6% responded. 19.9% were diagnosed positive for depression as per MINI while suicidal ideation was observed in 5.4%. Seventy six (23.9%) PWE reported seizures during pandemic. The incidence being greater in females, unemployed, previously uncontrolled epilepsy, polytherapy, altered use of medications and depressed PWE. Seizure during pandemic, increased seizure frequency, previous history of depression and altered use of medications were all significantly associated with depression during COVID-19 pandemic (2.6- 95%CI, 1.45–4.73; 1.9- 95%CI, 1.01–3.57; 8.8- 95%CI, 4.54–17.21; 2.9- 95%CI, 1.19–7.24), and polytherapy (2.9- 95%CI, 0.92–9.04), seizures during pandemic (3.9- 95%CI, 1.45–10.53) and previous history of depression and suicidality, were related with suicidal ideation. CONCLUSION: COVID-19 pandemic induced disruptions can be detrimental for PWE and restoring services to the precovid levels as well as putting appropriate continuity plans in place for care of PWE should be a priority.

The COVID-19 pandemic has resulted in a massive strain on healthcare facilities leading to major disruptions and collapses all over the world [1, 2] . While wave after wave of infection spreads, the extremely high morbidity and mortality has necessitated imposition of stringent measure like curfews and lockdowns, diversion of available health care workers for COVID management, and changes in resource allocations. These changes in healthcare dynamics coupled with stress and financial hardships have invariably compromised the level of care for sick individuals particularly for chronic disorders like epilepsy [3] . It is conceivable that PWE are more likely to be affected during COVID19 pandemic because of multiple stressors i.e. disease, mobility restrictions, financial hardships, lack of routine medical access etc. In a survey conducted on 337 members of American epilepsy society, concerns were raised that PWE did not get adequate medical care. While 10% of respondents noted worsening in seizure frequency, 5% noted an improvement [4] . Epilepsy is one of the most common neurological disorder with an overall prevalence of 5-9 per 1,000 population across the globe [5] . Whereas most PWE require anti-seizure medications (ASMs), the mainstay of treatment, for many years or even lifelong, many nearly 25-30% do not respond i.e. refractory patients and may require surgical intervention [6] . Epilepsy is also associated with multiple co-morbidities and neuropsychiatric problems. Depression in particular has been reported in a sizable proportion of PWE [7] [8] [9] [10] and a bidirectional relationship between epilepsy and depression is suggested [11] . While many studies over the past one year have reported an increase in seizure frequency in PWE [3, [12] [13] [14] [15] [16] [17] [18] , however, to the best of our knowledge studies assessing the impact on depression in PWE are scarce. A few studies have evaluated the mental health of PWE i.e. anxiety, depression and psychological distress using online surveys [3, 12, [14] [15] [16] [17] [18] [19] [20] [21] but in all these studies the baseline status of PWE was not available and therefore the impact of COVID-19 cannot be assessed.

In this study, in order to determine the effect of COVID19 pandemic on depression in PWE we revaluated PWE who had been previously evaluated for depression and suicidal ideation.

This longitudinal study was conducted from September to October 2020 which corresponds to unlock 3.0 in India.

March 2020 at All India Institute of Medical Sciences (AIIMS), New Delhi, a tertiary care centre in India. Since a follow up was planned, informed consent for the same was recorded which enabled us to carry out this study. Thus the demographic data, baseline data on depression and seizure frequency for comparison were available. After taking ethical clearance from the Institute Ethics Committee at AIIMS, New Delhi, the participants of the study i.e. the PWE who had previously attended neurology OPD at AIIMS, New Delhi, India, and had given informed consent, were telephonically informed about the study, evaluated for depression, and also a short survey pertaining to seizure frequency and compliance was carried out. The inclusion criteria followed for recruiting the patients were age ≥ 18years, either gender, meet diagnostic criteria for epilepsy as per ILAE, and on ASMs. Those with any other co-morbidity were excluded.

Neuropsychiatric Interview (MINI: version 6.0.0) for evaluation of depression and suicidal ideation in these patients. The same version was reapplied. The permission for using MINI (version 6.0.0) was duly obtained. Both English and Hindi versions were used. The evaluator was naive to the previous status of PWE i.e. depressed or not depressed.

The 6-item survey questionnaire was optional for the PWE. The respondents were asked closed-ended questions relating to the source of medication and the medication adherence over the last 6 months.

Statistical analysis was performed using STATA statistical software, version 14. The categorical variables between the group with depression and the group without depression were compared using the chi-square test, while continuous variables were compared using the Student t-test. A significance level of p <0.05 (two-tailed) was adopted.

Univariate and stepwise multivariate logistic regression was applied to find independent associative factor of depression, suicidality, and seizures during follow-up, and unadjusted and adjusted odds ratio was calculated. R (version 4.1.0) was used for paired plot analysis between PWE with and without depression, and PWE with and without seizures during pandemic period.

Out of 449 PWE approached, 317 responded (response rate 70.6%) (Fig.1 (Table 1) .

Fifty percent PWE who were not taking ASMs or had altered the dose of ASM showed seizures versus 24% in the whole follow up group. Pair-wise analysis is given in fig. 2 (a).

Out of 317 PWE, 19.9% met the criteria for depression as per MINI as opposed to 40.1% that were depressed in previous assessment (Table 2 ). Thus a highly significant reduction was observed. Of these 13 PWE had new onset depression i.e.

had not screened positive previously. Among those who had undergone tapering only 1 had depression and the subject had tested positive earlier also.

The percent depressed at all the three time intervals i.e. ≥ 1 year, 1-2 years and ≥ 2 years was similar i.e. 16 .07, 20.6 and 20.8% respectively. Similarly gender also did not have any effect, the prevalence of depression being nearly 20% in both genders. A higher percentage of those on polytherapy tended to be positive for depression as opposed to those on monotherapy (21.5% vs. 17.93%). This was not statistically significant. There was however no new onset case of depression in PWE on monotherapy. The pairwise relationship between different variables is given in fig. 2 

A total of 12 PWE reported not taking the ASM at all while 9 had reduced the use of medication. The reasons cited were mostly financial difficulty or no access, although loss of interest was also cited as a reason. For nearly 96% of PWE,

procuring ASMs was an out of pocket expense (Fig 3) . Non compliance was more with monotherapy, in previously uncontrolled and female PWE. 

Although many studies are now focused on understanding seizure control in PWE in relation to various COVID19 pandemic associated factors like suspension of routine outpatient department services, non-availability of EEG facilities, inaccessible medication due to shortages and mobility restrictions, uncertainty over finances and change in societal and family dynamics, very few are focusing on impact on co-morbidities like depression. Some workers carried out online surveys across countries, but mostly through social media to determine the effect on depression and anxiety and psychological stress as a measure of depression and anxiety [12, 20, 22] . These studies have some inherent limitations like small sample size, limited and very specific reach due to use of online media and importantly lack of baseline data. Here it is worthwhile to mention that prevalence of depression in PWE up to even 88% has been reported though the range is 20-55% in most studies [23, 8, 24] . Since we had evaluated 449 PWE for depression using four different scales over the last few years before the start of pandemic in India [7] , these same patients were re-evaluated telephonically for depression. The response rate was 70%, and MINI was used.

Mini International Neuropsychiatric Interview is a semi-structured diagnostic interview recognized as gold standard for validation of diagnosis of depression [25] . It uses Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) and International

Classification of Diseases, Tenth Revision (ICD-10) criteria to diagnose depression and has been validated previously against structured clinical interview for diagnosis (SCID) in PWE [25] . Previously a number of studies have used telephonic mode for MINI to assess depression [26] [27] [28] [29] and it has been reported that telephone versus in person mode do not influence findings [26, [30] [31] [32] [33] .

We observed a highly significant decrease in prevalence of depression in PWE during the follow up during COVID 19 pandemic. Although we did not come across any comparable,

i.e. both pre-COVID and post-COVID studies, in PWE, in studies comparing PWE with normal subjects, mostly an increased depression and anxiety in PWE has been reported [3, 21] . Van Hees et al (2020) also reported a prevalence of 39.8% and 46.9% using HADS and PHQ-9 respectively in PWE [20] . These values fall in the reported range of 20-55% [8] .

However, Abokalawa et al (2021) reported prevalence of depression as high as 66.2% [22] , whereas it was 12.2% in a Spanish study [14] .

The reasons for decrease in depression prevalence are not clear.

were still screened positive for depression. A case to case analysis of previously depressed and now not-depressed PWE reveals that 17 were controlled PWE who were no longer on ASMs. Among these only one was assessed as depressed as opposed to 03 previously. A good percentage screening positive with MINI, 65% were previously assessed as mild cases using PHQ-9 and HAM-D respectively, and almost 96% were strictly adhering to their ASM schedules. Since the survey was carried out during lockdown, a probable better support structure and care with regards to ASM schedule could have contributed. The role of social capital in enhancing quality of life in PWE and mitigating neuropsychiatric problems has been proposed [34] [35] [36] .

had markedly lower depressive symptoms and depression risk [37] . Many other studies have suggested that having positive and enjoyable social experiences is linked to lower depressive symptoms [38] .The risk of underestimating however on account of telephonic interview cannot be ruled out, it has been reported that in population with low or intermediate risk of psychiatric disorder, the sensitivity of telephonic interview is low, implying that many of the cases might be missed by the telephone interview in comparison with the face-to-face interview [39] [40] [41] .

In contrast to the precovid results for factors affecting depression in PWE, no association between female gender and depression was observed. Polytherapy was however significantly associated along with seizure incidence and frequency. A similar trend was seen for suicidal ideation as well.

Polytherapy, seizure frequency and seizure incidence are well recognized risk factors for depression in PWE. Polytherapy itself would imply a more severe disorder and use of multiple ASMs further compounds the risk due to their inherent adverse effect profiles [7, 42, 43] . Occurrence of seizures on the other hand is a major stressor [11, 44] .

Another notable finding in this study was an altered seizure control in 70% PWE. The seizure frequency tended to increase in 44.7% PWE who experienced seizures. Seizure worsening during COVID-19 pandemic has been reported by other workers also [3, 12, 13, 16, 17] , but report of worsening as well as improvement are also available [4] . Fonseca et al (2020) and

Tedrus et al (2020) reported an increase in seizure frequency in almost 10% of PWE during the pandemic period [14, 15] . As for factors associated with seizure worsening, sleep disorder, polytherapy and compliance issues were found to be related. We did not delve into sleep disorders but in our study also polytherapy and altered use of medicine were associated.

Apart from these, depression was also identified as a significant contributing factor. It is conceivable that previously proposed bidirectional relationship between seizure and depression is not restricted to neuropathological changes but has some component of ASM as well [8, 11, 42] .

The altered use of medicine was implicated not just in seizure occurrence but also in depression and suicidal ideation. In the latter, it may be an outcome rather than a cause as 02 PWE described loss of interest as a reason for not taking ASMs. Nearly 50% of those not adhering to ASMs were found to be depressed. In other cases financial difficulty and inability to obtain medicine were cited as reasons for non compliance. Surveys conducted worldwide have reported that PWE experienced difficulties during the pandemic in obtaining medications [19] . Asadi-Pooya et al (2020) also reported that about one-third of PWE faced difficulties in obtaining their medicines [18] . Van Hees et al (2020) have reported the unavailability of ASMs to be majorly on account of non-availability (69.4%), mobility restrictions (12.5%), and financial problems (12.5%) [20] . However, few studies reported that no significant problem was experienced by PWE in accessing drugs [16] , and most of the patients were compliant with their ASMs. A 93% compliance rate was reported in an Italian study [3] , 93.5% in the Saudi study [12] , and 96% in Kuwaiti study [22] which is similar to this study.

One of the major limitations is that the COVID status for self and any impact on family was not determined. Besides, owing to different times to follow-up the role of progression of disease in depression cannot be accounted for.

The pandemic appears to have had a mixed effect on PWE depending on the individual profile. In view of the risks involved i.e. seizure exacerbation and precipitation of depression, it is imperative that efforts be made to restore medical care mechanisms for this highly vulnerable population and suitable continuity plans put in place to overcome any disruption in future. 

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We would like to acknowledge Dr David V. Sheehan for permission to use MINI. This work was supported in part by a research grant from All India Institute of Medical Sciences, New Delhi to JK & MT.We would also like to thank Ms Aishani Katyal for her assistance with R software.

None of the authors have any conflict of interest to declare.