Neurocognitive effects of brivaracetam, levetiracetam, and lorazepam.
OBJECTIVE
Brivaracetam (BRV) is a new anticonvulsant under development. Although BRV is an analog of levetiracetam (LEV), in addition to being an SV2A ligand, it also inhibits sodium channels in a voltage-dependent manner. The cognitive effects of BRV are uncertain.


METHODS
A randomized, double-blind, placebo-controlled, four-way cross-over design was employed in 16 healthy volunteers comparing acute dosing (i.e., two doses) of BRV 10 mg, LEV 500 mg, lorazepam (LZP) 2 mg, and placebo. The primary outcome was the summary score from the cognitive neurophysiologic test (CNT), which combines electrophysiologic and performance measures. Secondary outcomes included CNT cognitive and electrophysiologic subscores, traditional neuropsychological measures, and treatment-emergent adverse events (TEAEs).


RESULTS
Compared to BRV, LEV, and placebo, LZP adversely affected the CNT summary score and the majority of CNT subscores and neuropsychological measures. In contrast, BRV did not differ from placebo or LEV on any measure. More TEAEs occurred with LZP compared to each of the other treatment conditions.


CONCLUSIONS
The differential pattern of drug effects was consistent across multiple electrophysiologic, cognitive, and subjective measures. The profile of cognitive, subjective, and electrophysiologic effects for BRV was similar to the analog compound LEV and to placebo. The findings suggest that BRV should be tolerated well from a neuropsychological perspective, but additional studies are needed.
Meador
Kimford J
KJ
Department of Neurology, Emory University, Atlanta, Georgia 30322, USA. kimford.meador@emory.edu
Gevins
Alan
A
Leese
Philip T
PT
Otoul
Christian
C
Loring
David W
DW
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D001772:Blood Cell Count; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000523:psychology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008140:Lorazepam / Q000009:adverse effects*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D011939:Mental Recall / Q000187:drug effects; D008875:Middle Aged; D009483:Neuropsychological Tests; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives*; D011760:Pyrrolidinones / Q000009:adverse effects*; D018401:Sample Size; D016896:Treatment Outcome; D055815:Young Adult
D000927:Anticonvulsants; D011760:Pyrrolidinones; D000077287:Levetiracetam; D008140:Lorazepam; C482793:brivaracetam; D010889:Piracetam