title: Cognitive effects of adjunctive perampanel for partial-onset seizures: A randomized trial.
abstract: OBJECTIVE
  Assess cognitive effects of adjunctive perampanel in adolescents.
  
  
  METHODS
  In this double-blind study (ClinicalTrials.gov identifier: NCT01161524), patients aged 12 to <18 years with partial-onset seizures despite receiving 1-3 antiepileptic drugs were randomized (2:1) to perampanel or placebo. Perampanel was increased weekly in 2-mg increments to 8-12 mg/day (6-week titration; 13-week maintenance). Changes in neuropsychological outcomes were assessed at end of maintenance: Cognitive Drug Research (CDR) System Global Cognition Score (primary end point), five CDR System domain T-scores (secondary end points), letter fluency, category fluency, and Lafayette Grooved Pegboard Test (LGPT).
  
  
  RESULTS
  One hundred thirty-three patients were randomized. In the full analysis set, there were no differences of perampanel (n = 79) vs. placebo (n = 44) in CDR System Global Cognition Score (least squares mean change, -0.6 vs. 1.6; p = 0.145), Quality of Working Memory (1.1 vs. 2.0; p = 0.579), or Power of Attention (-6.9 vs. -2.7; p = 0.219). There were small differences with perampanel vs. placebo in other CDR System domains: improvements in Quality of Episodic Memory (3.0 vs. -1.2; p = 0.012), and worsening in Continuity of Attention (-3.3 vs. 1.6; p = 0.013) and Speed of Memory (0.3 vs. 7.0; p = 0.032). Letter fluency, category fluency, and LGPT were not significantly different between groups. The most frequent adverse events with perampanel were dizziness (30.6%) and somnolence (15.3%).
  
  
  CONCLUSIONS
  Perampanel did not differ from placebo in the global cognitive score, two of five subdomains, and four other cognitive measures. Perampanel was worse on two and better on one subdomain.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, U.S.A.
authors.forename: Kimford J
authors.initials: KJ
authors.lastname: Meador
authors.affiliation: Eisai Neuroscience and General Medicine PCU, Eisai Inc., Woodcliff Lake, New Jersey, U.S.A.
authors.forename: Haichen
authors.initials: H
authors.lastname: Yang
authors.affiliation: The Children's Hospital at TriStar Centennial, Nashville, Tennessee, U.S.A.
authors.forename: Jesus Eric
authors.initials: JE
authors.lastname: Piña-Garza
authors.affiliation: Eisai Neuroscience and General Medicine PCU, Eisai Inc., Woodcliff Lake, New Jersey, U.S.A.
authors.forename: Antonio
authors.initials: A
authors.lastname: Laurenza
authors.affiliation: Eisai Neuroscience and General Medicine PCU, Eisai Inc., Woodcliff Lake, New Jersey, U.S.A.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Wesnes Cognition, Streatley on Thames, United Kingdom.|Psychology Department, Northumbria University, Newcastle, United Kingdom.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Wesnes
mesh_terms: D000081:Acetamides / Q000627:therapeutic use; D000293:Adolescent; D000927:Anticonvulsants / Q000627:therapeutic use*; D001288:Attention; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000627:therapeutic use; D002648:Child; D003071:Cognition; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D000078334:Lacosamide; D000077213:Lamotrigine; D000077287:Levetiracetam; D008297:Male; D008570:Memory, Short-Term; D009483:Neuropsychological Tests; D009570:Nitriles; D000078330:Oxcarbazepine; D010889:Piracetam / Q000031:analogs & derivatives / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use*; D000077236:Topiramate; D016896:Treatment Outcome; D014227:Triazines / Q000627:therapeutic use; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D009570:Nitriles; D011728:Pyridones; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D002220:Carbamazepine; D000077287:Levetiracetam; D000078334:Lacosamide; D014635:Valproic Acid; C551441:perampanel; D000077213:Lamotrigine; D000078330:Oxcarbazepine; D010889:Piracetam
keywords: Adolescent; Antiepileptic drugs; Cognition; Partial seizures; Perampanel