Lifetime prevalence of epilepsy in the United States is estimated to be 1.2 to 2.9%. People with epilepsy have a significantly increased risk of injury, and a three-fold higher risk of death from any cause compared to the general population. In spite of advances in antiepileptic drugs (AEDs) and other therapies, many people with epilepsy experience negative health events (NHEs), such as accidents and emergency department (ED) visits, diminished quality of life, and poor mental health. Minorities and individuals of lower socioeconomic status may be particularly likely to have NHEs and reduced quality of life related to epilepsy [1–4].

Psychological factors and poor mental health have sustained and negative effects on people with epilepsy [5–6]. Comorbid affective disorders, in particular depression and anxiety, are major risk factors for poor quality of life in people with epilepsy [7]. Some studies found depression to be a more robust predictor of quality of life than seizure frequency, seizure duration, seizure type, number and adverse effects of AEDs [8–9]. Furthermore, the presence of depression and other psychiatric disorders may make epilepsy treatments less effective. One study of 890 patients with epilepsy found that individuals with psychiatric disorders were more than three times less likely to be seizure-free with AEDs than patients without [10]. A study of 121 patients who underwent temporal lobectomy found worse postsurgical seizure outcomes in patients with a psychiatric history than those without [11]. Given these findings, it is not surprising that depression and other mental health conditions have become an increasing focus of clinical care and research in epilepsy as well as a priority for public health and health policy recommendations [12–13].

In addition to depression and the stress of living with an unpredictable neurological condition, people with epilepsy experience social isolation and stigma [14–15]. Reports from surveys in 2010 and 2013 found that at least one out of five U.S. adults with epilepsy lives alone [16]. The stigma associated with epilepsy could be more harmful than the condition itself in that higher levels of stigma perception are associated with lower levels of self-efficacy in epilepsy management, worse treatment outcomes, less adherence to treatment regimens, and lower life satisfaction [17]. Additionally, the social disadvantages that many people with epilepsy face (e.g., unemployment, loss of income, requirement for caregiving in some cases) can further deflate self-esteem and marginalize people with epilepsy, compounding stigma [18].

This analysis, using baseline data from an ongoing randomized controlled trial (RCT) testing a novel self-management approach for epilepsy, evaluated demographic and clinical correlates of NHEs. We were particularly interested in the potential associations between factors relevant to epilepsy self-management as they relate to complications of epilepsy such as recurrent seizures, injuries or accidents, ED visits and hospitalizations. Previous work has suggested that individuals with epilepsy and serious mental illness comorbidity are more likely to experience NHEs compared with individuals that do not have mental illness comorbidity [19]. Being able to characterize factors that indicate elevated risk for NHEs may help inform care approaches that reduce epilepsy complications and burden.

The RCT from which the data for this analysis is derived is a Centers for Disease Control and Prevention (CDC) funded project testing a novel intervention “Self-management for people with epilepsy and a history of negative health events” (SMART). The SMART intervention is intended to reduce NHEs and improve health outcomes in people with epilepsy, and is specially focused on high-risk sub-groups with epilepsy who have recently experienced seizures or epilepsy-related complications. The study design is a prospective 6-month randomized comparison of SMART vs. 6-month wait-list control. Study inclusion criteria included a self-reported diagnosis of epilepsy, adults 18 years of age and older, having experienced an NHE within the last 6 months of initial contact/screen, and being able to provide written informed consent and participate in study procedures. The NHEs were defined as seizures, accidents or traumatic injury, self-harm attempts, ED visits, and hospitalizations. Participants were excluded if they were at immediate risk of self-harm, have dementia, were pregnant, and were unable to read/understand English. Recruitment was conducted in an urban setting in northeastern Ohio. All participants provided written informed consent and the study was approved by the local institutional review board (IRB).

This baseline data from a larger prospective RCT that enrolled individuals with epilepsy who experienced NHEs (seizures, ED visits, hospitalizations, self-harm attempts, accidents) within the past 6 months investigated the association between demographic and clinical variables related to frequency of NHEs and seizures. We found more frequent seizures in individuals with lower levels of education and income. Seizure-related disability can be associated with decreased ability to achieve educational and financial goals as well as more stigma [18]. However, our analysis generally found no associations between other demographic variables and epilepsy-related complications.

In contrast to the limited associations between NHEs and demographic variables, there were clear associations between NHEs and seizures vs. standardized measures of depression severity, quality of life and epilepsy-related stigma. Although the causality of associations is unclear given the cross-sectional design, findings highlight the need to consider and address social determinants of health as they relate to epilepsy outcomes. These findings also have strong clinical relevance as some of these clinical variables may themselves be a target of clinical or policy interventions (depression, perceived stigma) and thus have potential to improve health outcomes among people with poorly controlled epilepsy.

It is worth mentioning that our sample had a relatively high proportion of African-Americans (close to 70%) in contrast to many epilepsy treatment RCTs. It has been reported that there are health disparities in epilepsy outcomes based upon race and ethnicity status [32]. These disparities may be the result of overall reduced level of income, reduced education or lack of access to healthcare [33–35]. Fanteneanu et al recently found higher rates of ED use for African-American patients with epilepsy in comparison to whites with epilepsy [36]. Our analysis found no association between seizure frequency or NHEs and race. It is possible that our focus on individuals with poorly controlled epilepsy or NHEs (based upon study inclusion criteria) could at least partially explain the high proportion of African-Americans in the sample. Alternatively, the multiple challenges imposed by limited financial resources and social support evident in this sample could have swamped any differences related to race or ethnicity.

Our results found that more severe depression and lower quality of life were correlated with a greater number of seizures in the last 30 days, last 6 months, and increased number of NHEs overall. This is consistent with the published literature. Depression is the most common psychiatric disorder in people with epilepsy, and nearly five times more common than in the general population and is a significant risk factor for suicide [37]. Quality of life for people with well-controlled epilepsy is comparable to the general population, but worse than the general population for people with poorly controlled seizures [38]. Furthermore, seizure control is associated with both overall quality of life and a variety of life domains including everyday activities, mental health (i.e. depression), health perceptions and social functioning [38].

Unfortunately, medication treatment for depression in people with epilepsy may pose a challenge as antidepressants may lower seizure threshold and cause adverse drug interactions, and/or undesirable side effect burden. One study found that the risk of seizures is significantly increased for all classes of antidepressants, measured in the first 5 years of follow-up compared to no treatment [39]. Given the limitation of pharmacologic treatment, clinicians might consider the use of behavioral therapies for people with epilepsy who are depressed. Cognitive behavioral therapy is one possibly efficacious approach for depression in epilepsy [40]. Other evidence-based epilepsy self-management approaches can specifically target depressive symptoms in people with epilepsy [41–42].

The other major finding in this analysis is that greater levels of perceived stigma were correlated with higher seizure frequency in the last 30 days, last 6 months, and a greater number of NHEs overall. To the best of our knowledge, the relationship between total NHE counts and stigma has not been previously reported. Investigators examining the role of seizures in the perception of stigma have noted that feelings of stigma are greater for people who are recently diagnosed, those who still have seizures as compared to those who are seizure free, and in those with more frequent seizures [18, 26, 43, 44]. A study involving 182 individuals with epilepsy treated in a comprehensive epilepsy program in Florida found no association between seizure frequency and stigma scores [45]. Another study found a significant association between perceived stigma and frequency of adverse events related to the use of AEDs, encompassing neurological, psychiatric, and non-neurological events [46]. Another relevant previous study found that stigma and seizure frequency accounted for 54% of the variability in quality of life among people with epilepsy [47].

As with other stigmatizing conditions, enhancing social support and sharing experiences may be helpful for people with epilepsy. One study noted that peer support group participation significantly decreased stigma for youth participants [48]. Fortunately, national and international patient and family organizations have well-developed initiatives to address epilepsy stigma; some of these include the U.S. Epilepsy Foundation, International Bureau of Epilepsy (IBE), World Health Organization (WHO), and the International League Against Epilepsy (ILAE) [49]. The larger study, from which this data is derived, is part of the Managing Epilepsy Well (MEW) Network, a U.S. national research collaborative that emphasizes partnerships between patient and family groups such as EF [42]. Our results suggest that individuals with frequent epilepsy-related complications may be a sub-group that has particular need for support in managing and coping with stigma. Future research might target people with epilepsy at NHE points of care such as the ED or hospital, especially when NHEs are recurrent.

This study has a number of limitations that suggest a need for cautious interpretation of results, including relatively small sample, cross-sectional design and single-site setting. Additionally, individuals who volunteer to participate in an epilepsy self-management study are not representative of the wider population of people with epilepsy. That said, the minimal exclusion criteria, robust representation of minority participants, and focus on individuals with poorly controlled epilepsy provide insight into clinical and social variables that are associated with complications and frequent seizures.

In conclusion, among people with epilepsy who have frequent epilepsy-related health complications, depression, poor quality of life and high levels of stigma are common. Care approaches that target potentially modifiable factors could improve health outcomes for this vulnerable population with epilepsy.