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Epilepsy Behav. 2020 Jan;102:106687. doi: 10.1016/j.yebeh.2019.106687. Epub 2019 Dec 6.

Differential antiseizure medication sensitivity of the Affective Reactivity Index: A randomized controlled trial in new-onset pediatric focal epilepsy.

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Departments of Neurology and Pediatrics, Emory University, Atlanta, GA, United States of America. Electronic address:
Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA, United States of America.
Departments of Neurology, Pediatrics, Epidemiology & Population Health, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, United States of America.
Department of Neurology, Children's National Health System, Washington, DC, United States of America.
Department of Pediatrics, Division of Neurology, University of Tennessee Health Science Center, Le Bonheur Children's Hospital, Memphis, TN, United States of America.
Division of Neurology, Children's Hospital of Philadelphia, Departments of Neurology and Pediatrics, University of Pennsylvania, Philadelphia, PA, United States of America.
Department of Neuropsychology, Children's National Health System, Washington, DC, United States of America.
Department of Neuropsychology, Children's Healthcare of Atlanta, Atlanta, GA, United States of America.
Division of Neurology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.
Department of Psychiatry and Behavioral Science, Emory University, Atlanta, GA, United States of America.
Department of Pediatrics, George Washington University, Washington, DC, United States of America.



Irritability is a adverse effect of many antiseizure medications (ASMs), but there are no validated measures currently available to characterize this behavioral risk. We examined both child and parent/guardian versions of the Affective Reactivity Index (ARI), a validated measure developed for application in adolescent psychiatry, to determine its sensitivity to ASM-related irritability. We hypothesized irritability increases associated with levetiracetam (LEV) but not lamotrigine (LTG) or oxcarbazepine (OXC).


The ARI was administered to 71 child and parent/guardian pairs randomized to one of three common ASMs (LEV, LTG, OXC) used to treat new-onset focal (localization-related) epilepsy. Subjects were recruited as part of a prospective multicenter, randomized, open-label, parallel group design. The ARI was administered at baseline prior to treatment initiation and again at 3 months after ASM initiation.


There was a significant increase in ARI ratings for both child and parent/guardian ratings for LEV but not LTG or OXC when assessed 3 months after treatment initiation. When examined on the individual subject level using a criterion of at least a 3-point ARI increase, there was an increase associated with LEV for child ratings but not parent/guardian scores.


Both child and parent/guardian versions of the ARI appear sensitive to medication-induced irritability associated with LEV on both the group and individual levels. The findings extend the applicability of ARI from characterizing the presence of clinical irritability as a psychiatric diagnostic feature to a more modifiable aspect of behavior change related to medication management and support its use in clinical trial applications.


Affective Reactivity Index; Antiseizure medications; Irritability

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