Efficacy and safety of perampanel in Parkinson’s disease. A systematic review with meta-analysis
L-Dopa represents the mainstay of therapy of Parkinson’s disease (PD), but its effectiveness is reduced with continued treatment and disease progression. Accordingly, there remains a need to explore novel treatment strategies to manage the signs and symptoms of the later disease stages. The aim of the study was to evaluate the efficacy and safety of adjunctive perampanel (PER) in patients with PD through a meta-analysis of existing trials.
Randomized, placebo-controlled, double- or single-blind, add-on studies of PER in patients with PD were identified through a systematic literature search. The following outcomes were assessed: changes from baseline to final efficacy visit in total daily OFF time, activities of daily living during OFF time and motor function during ON time, incidence of adverse events (AEs), and treatment withdrawal.
Four trials were included involving 2266 participants, 1449 and 817 for PER and placebo treatment groups, respectively. Four PER daily doses were tested, namely 0.5, 1, 2 and 4 mg. There were no significant differences in any efficacy outcome between PER and placebo treated patients. The risk ratios (RRs) for AEs, severe AEs and treatment withdrawal were similar between placebo and PER at 0.5, 1 and 2 mg; the 4 mg daily dose was associated with an increased risk of AEs [RR 1.118 (1.047–1.193)], and withdrawal for AEs [RR 1.345 (1.034–1.749)] and for any reason [RR 1.197 (1.020–1.406)].
In PD patients experiencing motor fluctuations, adjunctive PER did not improve the motor state and was well-tolerated at the lower doses.
KeywordsParkinson’s disease Perampanel Movement disorders Dyskinesia
Compliance with ethical standards
Conflicts of interest
SL and MS declare that they have no conflict of interest. EG is an employee of Eisai s.r.l. FB has received speakers’ honoraria from Eisai and PeerVoice, payment for consultancy from Eisai, and travel support from Eisai, ITALFARMACO, and UCB Pharma.
- 1.de Lau LM, Breteler MM (2006) Epidemiology of Parkinson’s disease. Lancet Neurol 5(525):35Google Scholar
- 6.Eggert K, Squillacote D, Barone P, Dodel R, Katzenschlager R, Emre M, Lees AJ, Rascol O, Poewe W, Tolosa E, Trenkwalder C, Onofrj M, Stocchi F, Nappi G, Kostic V, Potic J, Ruzicka E, Oertel W (2010) German competence network on Parkinson’s disease. Safety and efficacy of perampanel in advanced Parkinson’s disease: a randomized, placebo-controlled study. Mov Disord 25:896–905CrossRefPubMedGoogle Scholar
- 9.Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. Higgins JPT, Green S (eds). The Cochrane Collaboration, 2011. http://handbook-5-1.cochrane.org/. Accessed June 2017
- 15.Lees A, Fahn S, Eggert KM, Jankovic J, Lang A, Micheli F, Mouradian MM, Oertel WH, Olanow CW, Poewe W, Rascol O, Tolosa E, Squillacote D, Kumar D (2012) Perampanel, an AMPA antagonist, found to have no benefit in reducing “off” time in Parkinson’s disease. Mov Disord 27:284–288CrossRefPubMedGoogle Scholar
- 29.Wiltgen BJ, Royle GA, Gray EE, Abdipranoto A, Thangthaeng N, Jacobs N, Saab F, Tonegawa S, Heinemann SF, O’Dell TJ, Fanselow MS, Vissel B (2010) A role for calcium-permeable AMPA receptors in synaptic plasticity and learning. PLoS One. https://doi.org/10.1371/journal.pone.0012818 PubMedPubMedCentralGoogle Scholar