title: Systematic review and meta-analysis of the efficacy and safety of perampanel in the treatment of partial-onset epilepsy.
abstract: BACKGROUND
  Perampanel is a first-in-class antiepileptic drug approved for adjunctive treatment of partial-onset seizure in patients aged 12 years or older. Published randomised controlled trials (RCTs) had small sample sizes, and meta-analyses have included too few studies to draw conclusive results for the assessment of tolerability, efficacy and safety of perampanel. There is a need to conduct a meta-analysis with a larger dataset and an appropriate study design.
  
  
  OBJECTIVE
  The aim of this study was to systematically review the efficacy and safety of perampanel in the treatment of partial-onset epilepsy.
  
  
  METHODS
  Electronic and clinical trials databases were searched for RCTs of perampanel published up to March 2013. Outcomes of interest were 50 % responder rates, seizure freedom, treatment-emergent adverse events (TEAEs) and incidence of withdrawal. Meta-analysis was performed to investigate the outcomes of interest.
  
  
  RESULTS
  Five RCTs with a total of 1,678 subjects were included. The 50 % responder rates were significantly greater in patients receiving 4, 8 and 12 mg perampanel versus placebo, with risk ratios of 1.54 (95 % CI 1.11-2.13), 1.80 (95 % CI 1.38-2.35) and 1.72 (95 % CI 1.17-2.52), respectively. There was no statistical evidence of a difference in seizure freedom between 8 or 12 mg perampanel and placebo. Of the five commonly reported TEAEs included, both dizziness and somnolence were statistically associated with 8 mg perampanel, whilst dizziness was statistically associated with 12 mg perampanel. Incidences of withdrawal due to adverse events were significantly higher in the 8 mg and 12 mg perampanel groups versus placebo.
  
  
  CONCLUSIONS
  The use of perampanel resulted in a statistically significant reduction of seizure frequency with respect to the 50 % responder rate in patients with partial-onset epilepsy. Perampanel is well tolerated at 4 mg and reasonably tolerated at 8 and 12 mg. Further clinical and pharmacovigilance studies are required to investigate the long-term efficacy and safety of perampanel in the management of other types of epilepsy.
authors.affiliation: Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, Li Ka Shing Faculty of Medicine, University of Hong Kong, 2/F Laboratory Block, 21 Sassoon Road, Hong Kong SAR, China, warhsu@hku.hk.
authors.forename: Warrington W Q
authors.initials: WW
authors.lastname: Hsu
authors.forename: C W
authors.initials: CW
authors.lastname: Sing
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Worsley
authors.forename: Ian C K
authors.initials: IC
authors.lastname: Wong
authors.forename: Esther W
authors.initials: EW
authors.lastname: Chan
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D004828:Epilepsies, Partial / Q000188:drug therapy*; D006801:Humans; D009570:Nitriles; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000706:statistics & numerical data; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D009570:Nitriles; D011728:Pyridones; C551441:perampanel
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