Editor's Choice

Seizure 2022, Vol 103, Editor’s Choice: Psychiatric symptoms predict drug-resistant epilepsy in newly treated patients.

Markus Reuber, MD PhD, Academic Neurology Unit, University of Sheffield, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF

In 2005 the ILAE defined epilepsy as “a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures, and by the neurobiologic, cognitive, psychological, and social consequences of this condition” (1). While not fully recognising epilepsy as a complex neurobiological disorder of the brain in which the development of seizures is often preceded by cognitive, psychological or psychiatric symptoms (2), this definition of epilepsy did embrace the most important non-seizure sequelae of epilepsy which, at least for those individuals whose epileptic seizures cannot be stopped completely with treatment, have greater effects on health-related quality of life than seizure frequency or severity itself (3).

The 2014 ILAE definition of epilepsy dropped any reference to non-seizure manifestations of epilepsy. Epilepsy is currently defined as “a disease of the brain defined by … at least two unprovoked (or reflex) seizures occurring >24 h apart, …one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years … [or the] diagnosis of an epilepsy syndrome” (4).

The failure to mention the neurobiologic, cognitive, psychological, and social aspects of this multifaceted disease is particularly regrettable because (as the authors of the 2014 definition point out) “the definition of epilepsy will affect diagnosis and treatment in both resource-rich and resource-poor societies”. By not characterising epilepsy more broadly as a complex neuropsychiatric disease and by restricting the focus on seizures, the 2014 definition represents a missed opportunity for individuals with epilepsy and for clinicians interested in offering a holistic treatment service aiming to improve patients’ quality of life rather than simply reducing their seizures.

My Editor’s Choice from the current volume of Seizure is a prospective clinical study by Rui Zhong et al. exploring predictors of the development of drug resistant epilepsy – including depression and anxiety - in patients newly presenting with seizures at the time of their epilepsy diagnosis (5). Confirming the findings of a previous study (6), this paper demonstrates that the presence of depression at the point of diagnosis of epilepsy makes it three times more likely that the seizure disorder will prove drug resistant. Patients with depression and anxiety at diagnosis were five times more likely not to respond readily to antiseizure medication than patients with neither of these common “comorbidities” of epilepsy.

This paper should help to make future prediction models of drug resistant epilepsy more accurate and facilitate an earlier consideration of treatments such as epilepsy surgery. Perhaps this paper will also persuade more clinicians to assess the mental health of their patients with seizures and make it more likely that the next ILAE definition of epilepsy will recognise the fallacy of reducing epilepsy to a disease characterised by seizures, and that it will instead fully embrace all aspects of epilepsy (seizure and non-seizure), including the bidirectional relationship between seizures, mental health, cognitive and social problems. Last but not least: This paper may motivate researchers to study whether tackling depression and anxiety therapeutically at the point of epilepsy diagnosis can improve antiseizure treatment outcomes.


(1) Fisher RS, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, Engel J Jr. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. 2005;46:470-2.

(2) Hesdorffer DC, Ishihara L, Mynepalli L, Webb DJ, Weil J, Hauser WA. Epilepsy, suicidality, and psychiatric disorders: a bidirectional association. Ann Neurol. 2012;72:184-91.

(3) Rawlings GH, Brown I, Reuber M. Predictors of health-related quality of life in patients with epilepsy and psychogenic nonepileptic seizures. Epilepsy Behav. 2017;68:153-158.

(4) Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel J Jr, Forsgren L, French JA, Glynn M, Hesdorffer DC, Lee BI, Mathern GW, Moshé SL, Perucca E, Scheffer IE, Tomson T, Watanabe M, Wiebe S. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55:475-82.

(5) Zhong R, Chen Q, Li N, Zhang X, Lin W. Psychiatric symptoms predict drug-resistant epilepsy in newly treated patients. Seizure 2022, please add bibliographic details.

(6) Hitiris N, Mohanraj R, Norrie J, Sills GJ, Brodie MJ. Predictors of pharmacoresistant epilepsy. Epilepsy Res. 2007;75:192-6.