title: The adverse event profile of perampanel: meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  To identify adverse events (AEs) significantly associated with perampanel treatment in double-blind clinical studies (RCTs). Serious AEs, study withdrawals due to AEs and dose-effect responses of individual AEs were also investigated.
  
  
  METHODS
  All placebo controlled, double-blind RCTs investigating therapeutic effects of oral perampanel were searched. AEs were assessed for their association with perampanel after exclusion of synonyms, rare AEs and non-assessable AEs. Risk difference (RD) was used to evaluate the association of any AE (99% confidence intervals) and withdrawals or serious AEs (95% confidence intervals) with perampanel.
  
  
  RESULTS
  Nine RCTs (five in pharmacoresistant epilepsy and four in Parkinson's disease) were included in our study. Almost 4000 patients had been recruited, 2627 of whom were randomized to perampanel and treated with drug doses of 0.5 mg/day (n = 68), 1 mg/day (n = 65), 2 mg/day (n = 753), 4 mg/day (n = 1017), 8 mg/day (n = 431) or 12 mg/day (n = 293). Serious AEs were not significantly associated with perampanel treatment. The experimental drug was significantly associated with an increased risk of AE-related study withdrawals at 4 mg/day [RD (95% confidence interval) 0.03 (0.00, 0.06)] and 12 mg/day [RD (95% confidence interval) 0.13 (0.07, 0.18)]. Of 15 identified AEs, five (dizziness, ataxia, somnolence, irritability and weight increase) were found to be significantly associated with perampanel and one (seizure worsening) was significantly associated with placebo.
  
  
  CONCLUSIONS
  Vestibulocerebellar AEs (dizziness, ataxia), sedative effects (somnolence), irritability and weight increase were significantly associated with perampanel treatment.
authors.affiliation: Unit of Neurology, Department of Medicine, Florence Health Authority, Firenze, Italy. gaetano.zaccara@asf.toscana.it
authors.forename: G
authors.initials: G
authors.lastname: Zaccara
authors.forename: F
authors.initials: F
authors.lastname: Giovannelli
authors.forename: M
authors.initials: M
authors.lastname: Cincotta
authors.forename: A
authors.initials: A
authors.lastname: Verrotti
authors.forename: E
authors.initials: E
authors.lastname: Grillo
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004351:Drug Resistance; D004828:Epilepsies, Partial / Q000188:drug therapy; D004827:Epilepsy / Q000188:drug therapy; D006801:Humans; D009570:Nitriles; D010300:Parkinson Disease / Q000188:drug therapy; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012640:Seizures / Q000188:drug therapy
chemical_list: D000927:Anticonvulsants; D009570:Nitriles; D011728:Pyridones; C551441:perampanel
keywords: adverse effects; antiepileptic drugs; epilepsy; meta-analysis; perampanel; side effects