title: Randomized double-blind comparison of cognitive and EEG effects of lacosamide and carbamazepine.
abstract: Differential effectiveness of antiepileptic drugs (AEDs) is more commonly determined by tolerability than efficacy. Cognitive effects of AEDs can adversely affect tolerability and quality of life. This study evaluated cognitive and EEG effects of lacosamide (LCM) compared with carbamazepine immediate-release (CBZ-IR). A randomized, double-blind, double-dummy, two-period crossover, fixed-dose study in healthy subjects compared neuropsychological and EEG effects of LCM (150mg, b.i.d.) and CBZ-IR (200mg, t.i.d.). Testing was conducted at screening, predrug baseline, the end of each treatment period (3-week titration; 3-week maintenance), and the end of each washout period (4weeks after treatment). A composite Z-score was derived for the primary outcome variable (computerized cognitive tests and traditional neuropsychological measures) and separately for the EEG measures. Other variables included individual computer, neuropsychological, and EEG scores and adverse events (AEs). Subjects included 60 healthy adults (57% female; mean age: 34.4years [SD: 10.5]); 44 completed both treatments; 41 were per protocol subjects. Carbamazepine immediate-release had worse scores compared with LCM for the primary composite neuropsychological outcome (mean difference=0.33 [SD: 1.36], p=0.011) and for the composite EEG score (mean difference=0.92 [SD: 1.77], p=0.003). Secondary analyses across the individual variables revealed that CBZ-IR was statistically worse than LCM on 36% (4/11) of the neuropsychological tests (computerized and noncomputerized) and 0% of the four EEG measures; none favored CBZ-IR. Drug-related AEs occurred more with CBZ-IR (49%) than LCM (22%). Lacosamide had fewer untoward neuropsychological and EEG effects and fewer AEs and AE-related discontinuations than CBZ-IR in healthy subjects. Lacosamide exhibits a favorable cognitive profile.
authors: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. Electronic address: kmeador@stanford.edu.
authors: Kimford J
authors: KJ
authors: Meador
authors: Department of Neurology, Emory University, Atlanta, GA, USA; Department of Pediatrics, Emory University, Atlanta, GA, USA. Electronic address: dloring@emory.edu.
authors: David W
authors: DW
authors: Loring
authors: CNS Vital Signs, Morrisville, NC, USA. Electronic address: aboyd@cnsvs.com.
authors: Alan
authors: A
authors: Boyd
authors: JE Research, Inc., Alpharetta, GA, USA. Electronic address: echauz@ieee.org.
authors: Javier
authors: J
authors: Echauz
authors: Department of Neurology, Emory University, Atlanta, GA, USA. Electronic address: Suzette.LaRoche@msj.org.
authors: Suzette
authors: S
authors: LaRoche
authors: Department of Neurology, Emory University, Atlanta, GA, USA. Electronic address: nxv146@med.miami.edu.
authors: Naymee
authors: N
authors: Velez-Ruiz
authors: Department of Neurology, University of Colorado, Denver, CO, USA. Electronic address: pearce.korb@ucdenver.edu.
authors: Pearce
authors: P
authors: Korb
authors: UCB Pharma, Raleigh, NC, USA. Electronic address: Bill.Byrnes@ucb.com.
authors: William
authors: W
authors: Byrnes
authors: UCB Pharma, Raleigh, NC, USA. Electronic address: Deanne.Dilley@ucb.com.
authors: Deanne
authors: D
authors: Dilley
authors: UCB Pharma, Slough, UK. Electronic address: Simon.Borghs@ucb.com.
authors: Simon
authors: S
authors: Borghs
authors: UCB Pharma, Brussels, Belgium. Electronic address: Marc.DeBacker@ucb.com.
authors: Marc
authors: M
authors: De Backer
authors: UCB Pharma, Atlanta, GA, USA. Electronic address: TylerJStory@gmail.com.
authors: Tyler
authors: T
authors: Story
authors: UCB Pharma, Brussels, Belgium. Electronic address: Peter.Dedeken@ucb.com.
authors: Peter
authors: P
authors: Dedeken
authors: UCB Pharma, Raleigh, NC, USA. Electronic address: Elizabeth.Webster@ucb.com.
authors: Elizabeth
authors: E
authors: Webster
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D002220:Carbamazepine / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography; D005260:Female; D006801:Humans; D000078334:Lacosamide; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D055815:Young Adult
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D002220:Carbamazepine; D000078334:Lacosamide
keywords: Carbamazepine; Cognition; EEG; Lacosamide; Neuropsychology