Perampanel for the treatment of primary generalized tonic-clonic seizures in idiopathic generalized epilepsy.
BACKGROUND
The non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) - receptor antagonist perampanel (PER) was approved in 2015 for treatment of primary generalized tonic-clonic seizures (pGTCS). The aim of this narrative review is to summarize available data on pharmacological properties, efficacy and tolerability of PER in pGTCs.


METHODS
Data sources included MEDLINE, EMBASE, Google Scholar and ClinicalTrials.gov, conference proceedings of the ILAE congresses and the most recent conference proceedings of the American Epilepsy Society (2013 to 2015).


CONCLUSIONS
A placebo-controlled clinical phase III study including 164 patients (≥ 12 years) with pGTCS in idiopathic generalized epilepsies (IGE) demonstrated efficacy of PER in reducing pGTCS with good tolerability profile, and without aggravating absence seizures or myoclonic seizures. Dizziness, the main adverse event (AE), can be avoided by bedtime administration. Psychiatric AEs ranging from mild depression to aggression and suicidal attempts should be especially monitored in patients with a history of psychiatric disorders. Co-administration of enzyme inducing antiepileptic drugs (AEDs) might decrease PER plasma levels and make dose adjustment necessary. A reduced efficacy of progesterone-containing oral contraceptives should be considered when administering PER to young women. There is lack of evidence on PER treatment in pregnancy. Although no teratogenic effects were observed in animal models, PER is not recommended for women of childbearing age without contraception.
a Department of Neurology , Paracelsus Medical University Salzburg, and Christian Doppler Medical Centre , Salzburg , Austria.|c Centre for Cognitive Neurosciences Salzburg , Salzburg , Austria.
Alexandra
A
Rohracher
b Department of Neurological, Biomedical, and Movement Sciences , University of Verona , Verona , Italy.
Francesco
F
Brigo
a Department of Neurology , Paracelsus Medical University Salzburg, and Christian Doppler Medical Centre , Salzburg , Austria.|c Centre for Cognitive Neurosciences Salzburg , Salzburg , Austria.
Julia
J
Höfler
a Department of Neurology , Paracelsus Medical University Salzburg, and Christian Doppler Medical Centre , Salzburg , Austria.|c Centre for Cognitive Neurosciences Salzburg , Salzburg , Austria.
Gudrun
G
Kalss
a Department of Neurology , Paracelsus Medical University Salzburg, and Christian Doppler Medical Centre , Salzburg , Austria.|c Centre for Cognitive Neurosciences Salzburg , Salzburg , Austria.
Caroline
C
Neuray
a Department of Neurology , Paracelsus Medical University Salzburg, and Christian Doppler Medical Centre , Salzburg , Austria.|c Centre for Cognitive Neurosciences Salzburg , Salzburg , Austria.
Judith
J
Dobesberger
a Department of Neurology , Paracelsus Medical University Salzburg, and Christian Doppler Medical Centre , Salzburg , Austria.|c Centre for Cognitive Neurosciences Salzburg , Salzburg , Austria.
Giorgi
G
Kuchukhidze
a Department of Neurology , Paracelsus Medical University Salzburg, and Christian Doppler Medical Centre , Salzburg , Austria.|c Centre for Cognitive Neurosciences Salzburg , Salzburg , Austria.
Markus
M
Leitinger
a Department of Neurology , Paracelsus Medical University Salzburg, and Christian Doppler Medical Centre , Salzburg , Austria.|c Centre for Cognitive Neurosciences Salzburg , Salzburg , Austria.|d Department of Public Health, Health Services Research and Health Technology Assessment , University for Medical Informatics and Health Technology, UMIT , Hall in Tirol , Austria.
Eugen
E
Trinka
D000927:Anticonvulsants / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004829:Epilepsy, Generalized / Q000188:drug therapy*; D004830:Epilepsy, Tonic-Clonic / Q000188:drug therapy; D006801:Humans; D001523:Mental Disorders / Q000150:complications; D009570:Nitriles; D011728:Pyridones / Q000627:therapeutic use*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D012640:Seizures / Q000188:drug therapy; D016896:Treatment Outcome
D000927:Anticonvulsants; D009570:Nitriles; D011728:Pyridones; D018091:Receptors, AMPA; C551441:perampanel
Idiopathic generalized epilepsy; perampanel; primary generalized tonic clonic seizures