title: Issues related to symptomatic and disease-modifying treatments affecting cognitive and neuropsychiatric comorbidities of epilepsy.
abstract: 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.
authors.affiliation: Departments of Pediatrics, Neurology and Pharmaceutical Sciences, University of Colorado Schools of Medicine and Pharmacy, Children's Hospital Colorado, Aurora, Colorado, USA. Amy.brooks-kayal@childrenscolorado.org
authors.forename: Amy R
authors.initials: AR
authors.lastname: Brooks-Kayal
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Bath
authors.forename: Anne T
authors.initials: AT
authors.lastname: Berg
authors.forename: Aristea S
authors.initials: AS
authors.lastname: Galanopoulou
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Holmes
authors.forename: Frances E
authors.initials: FE
authors.lastname: Jensen
authors.forename: Andres M
authors.initials: AM
authors.lastname: Kanner
authors.forename: Terence J
authors.initials: TJ
authors.lastname: O'Brien
authors.forename: Vicky H
authors.initials: VH
authors.lastname: Whittemore
authors.forename: Melodie R
authors.initials: MR
authors.lastname: Winawer
authors.forename: Manisha
authors.initials: M
authors.lastname: Patel
authors.forename: Helen E
authors.initials: HE
authors.lastname: Scharfman
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology; D003072:Cognition Disorders / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D015897:Comorbidity; D003866:Depressive Disorder / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology; D004195:Disease Models, Animal; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use*; D004827:Epilepsy / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D008881:Migraine Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology; D019965:Neurocognitive Disorders / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D011788:Quality of Life / Q000523:psychology; D057170:Translational Research, Biomedical
chemical_list: D015507:Drugs, Investigational
keywords: Animal models; Biomarkers; Comorbidity; Epilepsy; Therapy
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