Journal of Neurology

, Volume 265, Issue 4, pp 733–740 | Cite as

Efficacy and safety of perampanel in Parkinson’s disease. A systematic review with meta-analysis

  • Simona Lattanzi
  • Elisabetta Grillo
  • Francesco Brigo
  • Mauro Silvestrini
Review

Abstract

Background

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.

Methods

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.

Results

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)].

Conclusions

In PD patients experiencing motor fluctuations, adjunctive PER did not improve the motor state and was well-tolerated at the lower doses.

Keywords

Parkinson’s disease Perampanel Movement disorders Dyskinesia 

Notes

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.

Supplementary material

415_2017_8681_MOESM1_ESM.pdf (229 kb)
Supplementary material 1 (PDF 228 kb)
415_2017_8681_MOESM2_ESM.pdf (197 kb)
Supplementary material 2 (PDF 197 kb)

References

  1. 1.
    de Lau LM, Breteler MM (2006) Epidemiology of Parkinson’s disease. Lancet Neurol 5(525):35Google Scholar
  2. 2.
    Jankovic J, Stacy M (2007) Medical management of levodopa-associated motor complications in patients with Parkinson’s disease. CNS Drugs 21:677–692CrossRefPubMedGoogle Scholar
  3. 3.
    Klockgether T, Turski L, Honoré T, Zhang ZM, Gash DM, Kurlan R, Greenamyre JT (1991) The AMPA receptor antagonist NBQX has antiparkinsonian effects in monoamine-depleted rats and MPTP-treated monkeys. Ann Neurol 30:717–723CrossRefPubMedGoogle Scholar
  4. 4.
    Marin C, Jiménez A, Bonastre M, Vila M, Agid Y, Hirsch EC, Tolosa E (2001) LY293558, an AMPA glutamate receptor antagonist, prevents and reverses levodopa-induced motor alterations in Parkinsonian rats. Synapse 42:40–47CrossRefPubMedGoogle Scholar
  5. 5.
    Konitsiotis S, Blanchet PJ, Verhagen L, Lamers E, Chase TN (2000) AMPA receptor blockade improves levodopa-induced dyskinesia in MPTP monkeys. Neurology 54:1589–1595CrossRefPubMedGoogle Scholar
  6. 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
  7. 7.
    Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184CrossRefPubMedPubMedCentralGoogle Scholar
  9. 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
  10. 10.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558CrossRefPubMedGoogle Scholar
  12. 12.
    Lattanzi S, Cagnetti C, Foschi N, Provinciali L, Silvestrini M (2016) Brivaracetam add-on for refractory focal epilepsy: a systematic review and meta-analysis. Neurology 86:1344–1352CrossRefPubMedGoogle Scholar
  13. 13.
    Lattanzi S, Cagnetti C, Provinciali L, Silvestrini M (2017) How should we lower blood pressure after cerebral hemorrhage? A systematic review and meta-analysis. Cerebrovasc Dis 43:207–213CrossRefPubMedGoogle Scholar
  14. 14.
    Lattanzi S, Cagnetti C, Danni M, Provinciali L, Silvestrini M (2017) Oral and intravenous steroids for multiple sclerosis relapse: a systematic review and meta-analysis. J Neurol 264:1697–1704CrossRefPubMedGoogle Scholar
  15. 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
  16. 16.
    Rascol O, Barone P, Behari M, Emre M, Giladi N, Olanow CW, Ruzicka E, Bibbiani F, Squillacote D, Patten A, Tolosa E (2012) Perampanel in Parkinson disease fluctuations: a double-blind randomized trial with placebo and entacapone. Clin Neuropharmacol 35:15–20CrossRefPubMedGoogle Scholar
  17. 17.
    Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909CrossRefPubMedGoogle Scholar
  18. 18.
    Galvan A, Wichmann T (2008) Pathophysiology of parkinsonism. Clin Neurophysiol 119:1459–1474CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Stayte S, Vissel B (2014) Advances in non-dopaminergic treatments for Parkinson’s disease. Front Neurosci 8:113PubMedPubMedCentralGoogle Scholar
  20. 20.
    Oh JD, Chase TN (2002) Glutamate-mediated striatal dysregulation and the pathogenesis of motor response complications in Parkinson’s disease. Amino Acids 23:133–139CrossRefPubMedGoogle Scholar
  21. 21.
    Koutsilieri E, Riederer P (2007) Excitotoxicity and new antiglutamatergic strategies in Parkinson’s disease and Alzheimer’s disease. Parkinsonism Relat Disord 13(Suppl. 3):S329–S331CrossRefPubMedGoogle Scholar
  22. 22.
    Engber TM, Papa SM, Boldry RC, Chase TN (1994) NMDA receptor blockade reverses motor response alterations induced by levodopa. NeuroReport 5:2586–2588CrossRefPubMedGoogle Scholar
  23. 23.
    Blanchet PJ, Konitsiotis S, Whittemore ER, Zhou ZL, Woodward RM, Chase TN (1999) Differing effects of N-methyl-d-aspartate receptor subtype selective antagonists on dyskinesias in levodopa-treated 1-methyl-4-phenyl-tetrahydropyridine monkeys. J Pharmacol Exp Ther 290:1034–1040PubMedGoogle Scholar
  24. 24.
    Marin C, Papa S, Engber TM, Bonastre M, Tolosa E, Chase TN (1996) MK-801 prevents levodopa-induced motor response alterations in parkinsonian rats. Brain Res 736:202–205CrossRefPubMedGoogle Scholar
  25. 25.
    Chase TN, Oh JD, Konitsiotis S (2000) Antiparkinsonian and antidyskinetic activity of drugs targeting central glutamatergic mechanisms. J Neurol 247(Suppl 2):II36–II42PubMedGoogle Scholar
  26. 26.
    Varanese S, Howard J, Di Rocco A (2010) NMDA antagonist memantine improves levodopa-induced dyskinesias and “on-off” phenomena in Parkinson’s disease. Mov Disord 25:508–510CrossRefPubMedGoogle Scholar
  27. 27.
    Blair HA, Dhillon S (2017) Safinamide: a review in parkinson’s disease. CNS Drugs 31:169–176CrossRefPubMedGoogle Scholar
  28. 28.
    Dingledine R, Borges K, Bowie D, Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7–61PubMedGoogle Scholar
  29. 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
  30. 30.
    Johnson KA, Conn PJ, Niswender CM (2009) Glutamate receptors as therapeutic targets for Parkinson’s disease. CNS Neurol Disord Drug Targ 8:475–491CrossRefGoogle Scholar
  31. 31.
    Marin C, Jimenez A, Bonastre M, Chase TN, Tolosa E (2000) Non-NMDA receptor-mediated mechanisms are involved in levodopa-induced motor response alterations in Parkinsonian rats. Synapse 36:267–274CrossRefPubMedGoogle Scholar
  32. 32.
    Matsunaga S, Kishi T, Iwata N (2017) Combination therapy with zonisamide and antiparkinson drugs for parkinson’s disease: a meta-analysis. J Alzheimer’s Dis 56:1229–1239CrossRefGoogle Scholar
  33. 33.
    Hirsch EC, Hunot S (2009) Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol 8:382–397CrossRefPubMedGoogle Scholar
  34. 34.
    Lattanzi S, Silvestrini M, Verbeek MM, Mollenhauer B, Lindqvist D, Janelidze S, Hansson O (2016) Increased CSF biomarkers of angiogenesis in Parkinson disease. Neurology 86:1747–1748CrossRefPubMedGoogle Scholar
  35. 35.
    Dias V, Junn E, Mouradian MM (2013) The role of oxidative stress in Parkinson’s disease. J Parkinsons Dis 3:461–491PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Simona Lattanzi
    • 1
  • Elisabetta Grillo
    • 2
  • Francesco Brigo
    • 3
    • 4
  • Mauro Silvestrini
    • 1
  1. 1.Neurological Clinic, Department of Experimental and Clinical MedicineMarche Polytechnic UniversityAnconaItaly
  2. 2.Medical Department Eisai s.r.lSan Donato MilaneseItaly
  3. 3.Department of Neuroscience, Biomedicine and Movement ScienceUniversity of VeronaVeronaItaly
  4. 4.Division of Neurology“Franz Tappeiner” HospitalMeranoItaly

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