Epilepsy, antiepileptic drugs, and aggression: An evidence-based review

Martin J. Brodie, Frank Besag, Alan B. Ettinger, Marco Mula, Gabriella Gobbi, Stefano Comai, Albert P. Aldenkamp, Bernhard J. Steinhoff

Research output: Contribution to journalReview article

Abstract

Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, andwe present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases.
Original languageEnglish
Pages (from-to)563 - 602
Number of pages40
JournalPharmacological Reviews
Volume68
Issue number3
DOIs
Publication statusPublished - Jul 1 2016

Fingerprint

Aggression
Anticonvulsants
Epilepsy
Psychiatry
Gyrus Cinguli
Anger
Temporal Lobe
Amygdala
Prefrontal Cortex
gamma-Aminobutyric Acid
Caregivers
Observational Studies
Neurotransmitter Agents
Publications
Comorbidity
Glutamic Acid
Hippocampus
Dopamine
Serotonin
Norepinephrine

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Brodie, M. J., Besag, F., Ettinger, A. B., Mula, M., Gobbi, G., Comai, S., ... Steinhoff, B. J. (2016). Epilepsy, antiepileptic drugs, and aggression: An evidence-based review. Pharmacological Reviews, 68(3), 563 - 602. https://doi.org/10.1124/pr.115.012021

Epilepsy, antiepileptic drugs, and aggression: An evidence-based review. / Brodie, Martin J.; Besag, Frank; Ettinger, Alan B.; Mula, Marco; Gobbi, Gabriella; Comai, Stefano; Aldenkamp, Albert P.; Steinhoff, Bernhard J.

In: Pharmacological Reviews, Vol. 68, No. 3, 01.07.2016, p. 563 - 602.

Research output: Contribution to journalReview article

Brodie, MJ, Besag, F, Ettinger, AB, Mula, M, Gobbi, G, Comai, S, Aldenkamp, AP & Steinhoff, BJ 2016, 'Epilepsy, antiepileptic drugs, and aggression: An evidence-based review', Pharmacological Reviews, vol. 68, no. 3, pp. 563 - 602. https://doi.org/10.1124/pr.115.012021
Brodie MJ, Besag F, Ettinger AB, Mula M, Gobbi G, Comai S et al. Epilepsy, antiepileptic drugs, and aggression: An evidence-based review. Pharmacological Reviews. 2016 Jul 1;68(3):563 - 602. https://doi.org/10.1124/pr.115.012021
Brodie, Martin J. ; Besag, Frank ; Ettinger, Alan B. ; Mula, Marco ; Gobbi, Gabriella ; Comai, Stefano ; Aldenkamp, Albert P. ; Steinhoff, Bernhard J. / Epilepsy, antiepileptic drugs, and aggression: An evidence-based review. In: Pharmacological Reviews. 2016 ; Vol. 68, No. 3. pp. 563 - 602.
@article{5a57b060ab59493e824d2e31af9f5e4c,
title = "Epilepsy, antiepileptic drugs, and aggression: An evidence-based review",
abstract = "Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, andwe present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases.",
author = "Brodie, {Martin J.} and Frank Besag and Ettinger, {Alan B.} and Marco Mula and Gabriella Gobbi and Stefano Comai and Aldenkamp, {Albert P.} and Steinhoff, {Bernhard J.}",
year = "2016",
month = "7",
day = "1",
doi = "10.1124/pr.115.012021",
language = "English",
volume = "68",
pages = "563 -- 602",
journal = "Pharmacological Reviews",
issn = "0031-6997",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "3",

}

TY - JOUR

T1 - Epilepsy, antiepileptic drugs, and aggression: An evidence-based review

AU - Brodie, Martin J.

AU - Besag, Frank

AU - Ettinger, Alan B.

AU - Mula, Marco

AU - Gobbi, Gabriella

AU - Comai, Stefano

AU - Aldenkamp, Albert P.

AU - Steinhoff, Bernhard J.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, andwe present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases.

AB - Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, andwe present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases.

UR - http://www.scopus.com/inward/record.url?scp=84968547876&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84968547876&partnerID=8YFLogxK

U2 - 10.1124/pr.115.012021

DO - 10.1124/pr.115.012021

M3 - Review article

VL - 68

SP - 563

EP - 602

JO - Pharmacological Reviews

JF - Pharmacological Reviews

SN - 0031-6997

IS - 3

ER -