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, and we 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.
authors.affiliation: Epilepsy Unit, West Glasgow Ambulatory Care Hospital-Yorkhill, Glasgow, Scotland (M.J.B.); East London National Health Service Foundation Trust, Bedford, United Kingdom (F.B.); University College London School of Pharmacy, London, United Kingdom (F.B.); Winthrop University Hospital, Mineola, New York (A.B.E.); Epilepsy Group, Atkinson Morley Regional Neuroscience Centre, St. George's University Hospitals National Health Service Foundation Trust, London, United Kingdom (M.M.); Institute of Medical and Biomedical Sciences, St. George's, University of London, London, United Kingdom (M.M.); Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, Canada (G.G., S.C.); McGill University Health Center, McGill University, Montreal, Quebec, Canada (G.G., S.C.); Division of Neuroscience, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy (S.C.); Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands (A.P.A.); Maastricht University Medical Centre, Maastricht, The Netherlands (A.P.A.); and Kork Epilepsy Centre, Kehl-Kork, Germany (B.J.S.) Martin.Brodie@glasgow.ac.uk.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Brodie
authors.affiliation: Epilepsy Unit, West Glasgow Ambulatory Care Hospital-Yorkhill, Glasgow, Scotland (M.J.B.); East London National Health Service Foundation Trust, Bedford, United Kingdom (F.B.); University College London School of Pharmacy, London, United Kingdom (F.B.); Winthrop University Hospital, Mineola, New York (A.B.E.); Epilepsy Group, Atkinson Morley Regional Neuroscience Centre, St. George's University Hospitals National Health Service Foundation Trust, London, United Kingdom (M.M.); Institute of Medical and Biomedical Sciences, St. George's, University of London, London, United Kingdom (M.M.); Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, Canada (G.G., S.C.); McGill University Health Center, McGill University, Montreal, Quebec, Canada (G.G., S.C.); Division of Neuroscience, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy (S.C.); Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands (A.P.A.); Maastricht University Medical Centre, Maastricht, The Netherlands (A.P.A.); and Kork Epilepsy Centre, Kehl-Kork, Germany (B.J.S.).
authors.forename: Frank
authors.initials: F
authors.lastname: Besag
authors.affiliation: Epilepsy Unit, West Glasgow Ambulatory Care Hospital-Yorkhill, Glasgow, Scotland (M.J.B.); East London National Health Service Foundation Trust, Bedford, United Kingdom (F.B.); University College London School of Pharmacy, London, United Kingdom (F.B.); Winthrop University Hospital, Mineola, New York (A.B.E.); Epilepsy Group, Atkinson Morley Regional Neuroscience Centre, St. George's University Hospitals National Health Service Foundation Trust, London, United Kingdom (M.M.); Institute of Medical and Biomedical Sciences, St. George's, University of London, London, United Kingdom (M.M.); Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, Canada (G.G., S.C.); McGill University Health Center, McGill University, Montreal, Quebec, Canada (G.G., S.C.); Division of Neuroscience, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy (S.C.); Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands (A.P.A.); Maastricht University Medical Centre, Maastricht, The Netherlands (A.P.A.); and Kork Epilepsy Centre, Kehl-Kork, Germany (B.J.S.).
authors.forename: Alan B
authors.initials: AB
authors.lastname: Ettinger
authors.affiliation: Epilepsy Unit, West Glasgow Ambulatory Care Hospital-Yorkhill, Glasgow, Scotland (M.J.B.); East London National Health Service Foundation Trust, Bedford, United Kingdom (F.B.); University College London School of Pharmacy, London, United Kingdom (F.B.); Winthrop University Hospital, Mineola, New York (A.B.E.); Epilepsy Group, Atkinson Morley Regional Neuroscience Centre, St. George's University Hospitals National Health Service Foundation Trust, London, United Kingdom (M.M.); Institute of Medical and Biomedical Sciences, St. George's, University of London, London, United Kingdom (M.M.); Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, Canada (G.G., S.C.); McGill University Health Center, McGill University, Montreal, Quebec, Canada (G.G., S.C.); Division of Neuroscience, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy (S.C.); Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands (A.P.A.); Maastricht University Medical Centre, Maastricht, The Netherlands (A.P.A.); and Kork Epilepsy Centre, Kehl-Kork, Germany (B.J.S.).
authors.forename: Marco
authors.initials: M
authors.lastname: Mula
authors.affiliation: Epilepsy Unit, West Glasgow Ambulatory Care Hospital-Yorkhill, Glasgow, Scotland (M.J.B.); East London National Health Service Foundation Trust, Bedford, United Kingdom (F.B.); University College London School of Pharmacy, London, United Kingdom (F.B.); Winthrop University Hospital, Mineola, New York (A.B.E.); Epilepsy Group, Atkinson Morley Regional Neuroscience Centre, St. George's University Hospitals National Health Service Foundation Trust, London, United Kingdom (M.M.); Institute of Medical and Biomedical Sciences, St. George's, University of London, London, United Kingdom (M.M.); Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, Canada (G.G., S.C.); McGill University Health Center, McGill University, Montreal, Quebec, Canada (G.G., S.C.); Division of Neuroscience, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy (S.C.); Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands (A.P.A.); Maastricht University Medical Centre, Maastricht, The Netherlands (A.P.A.); and Kork Epilepsy Centre, Kehl-Kork, Germany (B.J.S.).
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gobbi
authors.affiliation: Epilepsy Unit, West Glasgow Ambulatory Care Hospital-Yorkhill, Glasgow, Scotland (M.J.B.); East London National Health Service Foundation Trust, Bedford, United Kingdom (F.B.); University College London School of Pharmacy, London, United Kingdom (F.B.); Winthrop University Hospital, Mineola, New York (A.B.E.); Epilepsy Group, Atkinson Morley Regional Neuroscience Centre, St. George's University Hospitals National Health Service Foundation Trust, London, United Kingdom (M.M.); Institute of Medical and Biomedical Sciences, St. George's, University of London, London, United Kingdom (M.M.); Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, Canada (G.G., S.C.); McGill University Health Center, McGill University, Montreal, Quebec, Canada (G.G., S.C.); Division of Neuroscience, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy (S.C.); Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands (A.P.A.); Maastricht University Medical Centre, Maastricht, The Netherlands (A.P.A.); and Kork Epilepsy Centre, Kehl-Kork, Germany (B.J.S.).
authors.forename: Stefano
authors.initials: S
authors.lastname: Comai
authors.affiliation: Epilepsy Unit, West Glasgow Ambulatory Care Hospital-Yorkhill, Glasgow, Scotland (M.J.B.); East London National Health Service Foundation Trust, Bedford, United Kingdom (F.B.); University College London School of Pharmacy, London, United Kingdom (F.B.); Winthrop University Hospital, Mineola, New York (A.B.E.); Epilepsy Group, Atkinson Morley Regional Neuroscience Centre, St. George's University Hospitals National Health Service Foundation Trust, London, United Kingdom (M.M.); Institute of Medical and Biomedical Sciences, St. George's, University of London, London, United Kingdom (M.M.); Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, Canada (G.G., S.C.); McGill University Health Center, McGill University, Montreal, Quebec, Canada (G.G., S.C.); Division of Neuroscience, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy (S.C.); Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands (A.P.A.); Maastricht University Medical Centre, Maastricht, The Netherlands (A.P.A.); and Kork Epilepsy Centre, Kehl-Kork, Germany (B.J.S.).
authors.forename: Albert P
authors.initials: AP
authors.lastname: Aldenkamp
authors.affiliation: Epilepsy Unit, West Glasgow Ambulatory Care Hospital-Yorkhill, Glasgow, Scotland (M.J.B.); East London National Health Service Foundation Trust, Bedford, United Kingdom (F.B.); University College London School of Pharmacy, London, United Kingdom (F.B.); Winthrop University Hospital, Mineola, New York (A.B.E.); Epilepsy Group, Atkinson Morley Regional Neuroscience Centre, St. George's University Hospitals National Health Service Foundation Trust, London, United Kingdom (M.M.); Institute of Medical and Biomedical Sciences, St. George's, University of London, London, United Kingdom (M.M.); Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, Canada (G.G., S.C.); McGill University Health Center, McGill University, Montreal, Quebec, Canada (G.G., S.C.); Division of Neuroscience, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy (S.C.); Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands (A.P.A.); Maastricht University Medical Centre, Maastricht, The Netherlands (A.P.A.); and Kork Epilepsy Centre, Kehl-Kork, Germany (B.J.S.).
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Steinhoff
mesh_terms: D000374:Aggression / Q000187:drug effects* / Q000502:physiology*; D000927:Anticonvulsants / Q000009:adverse effects*; D001921:Brain / Q000187:drug effects / Q000502:physiology; D004827:Epilepsy / Q000503:physiopathology* / Q000523:psychology*; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D018377:Neurotransmitter Agents