Issues related to symptomatic and disease‐modifying treatments affecting cognitive and neuropsychiatric comorbidities of epilepsy

Abstract

Summary Many symptoms of neurologic or psychiatric illness—such as cognitive impairment, depression, anxiety, attention deficits, and migraine—occur more frequently in people with epilepsy than in the general population. These diverse comorbidities present an underappreciated problem for people with epilepsy and their caregivers because they decrease quality of life, complicate treatment, and increase mortality. In fact, it has been suggested that comorbidities can have a greater effect on quality of life in people with epilepsy than the seizures themselves. There is increasing recognition of the frequency and impact of cognitive and behavioral comorbidities of epilepsy, highlighted in the 2012 Institute of Medicine report on epilepsy. Comorbidities have also been acknowledged, as a National Institutes of Health (NIH) Benchmark area for research in epilepsy. However, relatively little progress has been made in developing new therapies directed specifically at comorbidities. On the other hand, there have been many advances in understanding underlying mechanisms. These advances have made it possible to identify novel targets for therapy and prevention. As part of the International League Against Epilepsy/American Epilepsy Society workshop on preclinical therapy development for epilepsy, our working group considered the current state of understanding related to terminology, models, and strategies for therapy development for the comorbidities of epilepsy. Herein we summarize our findings and suggest ways to accelerate development of new therapies. We also consider important issues to improve research including those related to methodology, nonpharmacologic therapies, biomarkers, and infrastructure.

Psychiatric morbidity in children with epilepsy

“…Some authors mentioned depression as the most common psychiatric co-morbidity in epilepsy. 7 Many hypotheses have been proposed to explain the relationship between depression and epilepsy. Some researchers found that seizures lead to increased susceptibility to depression by reducing expression of serotonin receptors.…”

“…Some researchers found that seizures lead to increased susceptibility to depression by reducing expression of serotonin receptors. 7 Other studies revealed that the common psychiatric co-morbidities found among patients with epilepsy were depression, neuroses (non-psychotic anxiety disorders) and psychoses. 3 It has been observed that 25%-40% of individuals with certain neurological conditions such as epilepsy will develop a marked depressive disturbance and psychotic symptoms at some point during the course of illness.…”

“…Fortunately, a number of recent efforts are increasing the attention to co-morbidities. 7 Epilepsy has long been considered to be a risk factor for psychosis. 8 There are also increased risks for developing other psychiatric co-morbidities.…”

Fingolimod Exerts only Temporary Antiepileptogenic Effects but Longer-Lasting Positive Effects on Behavior in the WAG/Rij Rat Absence Epilepsy Model

“…In conclusion, fingolimod might be considered a promising antiepileptogenic treatment on the basis of the current view of the several unmet needs in this field [4,5,85]; however, further experiments are needed in order to clarify the exact mechanism(s) by which fingolimod exerts these potentially beneficial effects in this neurological disorder …”

“…Therefore, a good antiepileptogenic treatment should not only counteract seizure onset and/or their course but it should also improve comorbidities related to epilepsy [3,4]. "Repurposing" drugs already approved for other diseases could however, lead to new insights into the epileptogenic process [1].…”