TABLE 2

AED targets and effect on aggression in patients without epilepsy

Missing data do not necessarily imply that there is no action on a specific target. In particular, research on the effects of novel and recent AEDs on epigenetic regulation and/or gene expression is still ongoing. Unless otherwise specified, mechanism-of-action details may be found in the text of this review, in review articles (Rogawski and Löscher, 2004; Brodie, 2010; Comai et al., 2012b), and/or in the summary of product characteristics for each individual AED.

AED	Main System Targeted	Other Possible Systems Targeted	Epigenetic Mechanisms/ Gene Expression	Antiaggressive in  Psychiatric Patients^{^f}
Carbamazepine	Na⁺ channels		X	X
Eslicarbazepine acetate	Na⁺ channels		X^{^b}
Lacosamide	Na⁺ channels
Lamotrigine	Na⁺ channels	Glutamate (AMPA receptors)	X	X
Oxcarbazepine	Na⁺ channels			X
Phenytoin	Na⁺ channels		X^{^c}	X
Rufinamide	Na⁺ channels
Zonisamide	Na⁺ and Ca²⁺ channels	GABA	X^{^d}
Ethosuximide	T-type Ca²⁺ channels
Gabapentin	Ca²⁺ channels	GABA, glutamate (NMDA receptors)		X
Pregabalin	Ca²⁺ channels	GABA
Retigabine	K⁺ channels	GABA^{^a}
Felbamate	Mixed	Ca²⁺ channels, NMDA receptors, GABA receptors
Topiramate	Mixed	GABA_A receptors, AMPA/kainate receptors, Na⁺/Ca²⁺ channels	X	X
Phenobarbital	GABA
Clobazam/clonazepam	GABA (GABA_A receptor)			X
Vigabatrin	GABA		X^{^e}
Tiagabine	GABA			X
Stiripentol	GABA
Levetiracetam	Neurotransmitter release (via SV2A)		X	X
Brivaracetam	Neurotransmitter release (via SV2A)
Perampanel	Glutamate (AMPA receptors)
Valproic acid	Mixed	GABA, glutamate (NMDA, AMPA, and kainate receptors), Na⁺ channels	X	X

↵^a Treven et al. (2015).
↵^b Dezsi et al. (2013).
↵^c Hassel et al. (2010).
↵^d Ueda et al. (2012).
↵^e Tran et al. (1999).
↵^f Comai et al. (2012b), Gallagher and Herrmann (2014), and Huband et al. (2010).