Determinants of treatment outcomes in epilepsy

Epilepsy is a serious chronic brain disorder characterized by seizures. Worldwide over 50 million people suffer from epilepsy. The impact of epilepsy on a person’s daily life can be substantial and may, apart from the seizures themselves, include psycho-social consequences such as feelings of fear, dependence or social isolation. This frequently results in a reduced quality of life. Epilepsy is mainly treated with antiepileptic drugs (AEDs) or by epilepsy surgery. Treatment choices largely depend on the type of epilepsy. Individual treatment responses, however, vary largely and are difficult to predict. AED treatment is successful only in about 70% of people with epilepsy and is frequently associated with adverse effects. It often remains a trial-and-error based search for the optimal regimen balancing efficacy and tolerability. Scientific evidence on reasons why treatment remains suboptimal in clinical practice is limited. It has been obtained mainly from clinical trials in hospitalized or specialized care settings. Such settings are not representative of persons with epilepsy in general, mainly address specific groups of people with epilepsy, and trials are frequently not designed to assess the contributive role of several determinants of treatment outcome. In this thesis, we aimed to identify determinants that could explain treatment response in people with epilepsy from both a traditional disease- and treatment-related perspective as well as the patients’ individual perspectives determining quality of life. This was assessed in both a community-based and a surgical population of people with epilepsy. We found that treatment outcomes have not improved despite increased treatment options. In our community-based (OPPEC) study, a large proportion continues to have seizures and the majority report adverse effects. These were found important contributors to a reduced quality of life. From the perspective of people with epilepsy, the ultimate goal is to maintain a normal quality of life. This is also determined by their individual perspectives on health and well-being, which are hardly assessed in clinical practice and research. Several, mainly clinical, disease related determinants, such as the type of epilepsy, have been found associated to medical intractability or surgical outcome. The evidence for their role to treatment response and quality of life is weak, lacking predictive power. This suggests that other, yet unaddressed, factors may be important in determining treatment response. These may consist of individual perspectives, needs and coping styles of people with epilepsy. Patient reports and feelings such as the perceived occurrence of seizure precipitating factors or loss of hope or fear after subsequent unsuccessful AED changes. Their influence on quality of life are frequently unacknowledged by physicians and researchers, probably due to their assumed subjectivity. These perspectives serve as red flags that may indicate a need for adaptations in epilepsy care such as life- or coping style advice. A better understanding and recognition of the scope of determinants predicting treatment response requires further assessment, preferably in a community-based setting. This is likely to facilitate clinical management decisions contributing to an improved quality of life of people with epilepsy in clinical practice.