ucb-34714 and Cognition-Disorders

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.. 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).. 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.. 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.

Topics: Adolescent; Adult; Anticonvulsants; Blood Cell Count; Cognition; Cognition Disorders; Cross-Over Studies; Double-Blind Method; Electroencephalography; Evoked Potentials; Female; Humans; Levetiracetam; Lorazepam; Male; Memory, Short-Term; Mental Recall; Middle Aged; Neuropsychological Tests; Piracetam; Pyrrolidinones; Sample Size; Treatment Outcome; Young Adult

To assess short-term and longer-term effects of brivaracetam (BRV) on cognition and behavior in a naturalistic clinical setting.. Analyses were based on 43 patients with epilepsy who had undergone a neuropsychological screening before adjunctive treatment with BRV and a follow-up evaluation either after 5 days or 25 weeks. The standard assessment focused on reaction times (Neurocog FX), attention and executive functions (EpiTrack), and verbal memory (short version of the VLMT). Self-perceived cognition and behavior was evaluated by an extended version of the Adverse Events Profile. In addition, health-related quality of life (QOLIE-10) was reassessed at the longer-term interval.. Repeated measures analysis of variance revealed a significant improvement under BRV with regard to attention and executive functions (p = .03) without an interaction with the length of the observation interval. A statistical trend in the same direction was also seen for the reaction times (p = .07), but not for the unchanged verbal memory performance. Subjective measures indicated improvements in concentration (p = .02) and especially in comprehension (p < .001), and health-related quality of life (p = .002). Mood and aggression scores were unchanged. At the longer-term follow-up, an at least 50 percent reduction in seizure frequency was observed in 53% of the patients, 21% were seizure free.. These preliminary data point to a favorable cognitive profile of BRV similar to its precursor levetiracetam. Objective gains in attention and executive functions were accompanied by self-reported improvements in concentration and comprehension. Future studies with larger sample sizes and better control conditions are needed to confirm these findings.

Topics: Adult; Anticonvulsants; Attention; Cognition Disorders; Epilepsy; Executive Function; Female; Follow-Up Studies; Humans; Male; Mental Disorders; Middle Aged; Neuropsychological Tests; Photic Stimulation; Pyrrolidinones; Quality of Life; Reaction Time; Retrospective Studies; Time Factors; Treatment Outcome; Young Adult