Perampanel: What is its Place in the Management of Partial Onset Epilepsy?

INTRODUCTION: Current pathways for treatment of partial onset epilepsy are diverse and include 14 new antiepileptic drugs (AEDs) licensed for use as either monotherapy or adjunctive therapy. However, the impact of these new AEDs on the treatment of partial epilepsy has so far been disappointing and there persists a need for additional drugs. Recently, perampanel, a first-in-class AED was licensed as an adjunct for the management of refractory partial onset seizures with or without secondary generalization in patients 12 years and older. This review highlights the current management of partial epilepsy and analyses the published clinical and preclinical data of perampanel to consider its potential role in the treatment of partial epilepsy.

METHODS: A literature review of Embase, Medline and PubMed was conducted in April 2013 using the search terms 'perampanel' and 'AMPA receptor antagonist/blocker'. Publications were included if they discussed perampanel in the context of preclinical or clinical epilepsy.

RESULTS: Perampanel acts on the glutamate pathway. It is a novel highly selective non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist. This is a previously untargeted post-synaptic glutamate receptor. It is responsible for mediating rapid trans-synaptic signal transduction and hence believed to play a major role in seizure propagation. The three pivotal placebo-controlled trials of adjunctive perampanel demonstrated that the effective dosing range is 4-12 mg/day. The drug can be prescribed once daily, and its adverse effect profile is minimal with dizziness, fatigue, headache, and somnolence being the most commonly reported.

CONCLUSIONS: Perampanel is a welcome addition as it represents an alternative approach in the management of epilepsy with potential to have a significant impact on the prognosis of intractable epilepsy. However, it has only recently been licensed for clinical use in Europe, the USA, and Canada, and there are no data directly comparing it with other AEDs; hence, it remains far too early to ascertain its place in the treatment of patients with partial epilepsy.