Brivaracetam

Surface-engineered mesoporous silica nanoparticles (MSN) as carrier system for controlled release of Brivaracetam (BVM) for targeted brain delivery in epilepsy were developed and evaluated. Modified sol-gel process employed to synthesize MSN using tetraethylorthosilicate (TEOS) as silica source and cetyltrimethylammonium bromide (CTAB) as structure-directing agent, followed by calcination. Surface functionalization was achieved by grafting aminopropyl triethoxysilane (APTES) to introduce amine groups. Surface modification was carried out by amination, followed by the conjugation of D-mannose. Physical adsorption method was used to incorporate BVM into MSN. In-vitro studies revealed that BVM solution released 96.11% of drug within 5 h, while MSN formulation extended release upto 98.13% over 24 h. 94.25% of the drug release was observed from mannose-conjugated amine MSN over 48 h, aligning with Korsmeyer-Peppas model. Maximal Electroshock seizures (MES) model used for In-vivo pharmacodynamic evaluation, indicated that untreated group experienced 16.25 ± 1.11 seizure episodes (absence of treatment). BVM loaded MSN treatment reduced to 13.25 ± 1.11 episodes (69.63% antiepileptic effect), while mannose-conjugated BVM-loaded MSN group further decreased to 12.5 ± 1.32 episodes (71.42% antiepileptic activity). These results suggest that surface functionalized MSN are promising for sustained drug delivery for improved seizure control.

Levetiracetam and brivaracetam (BRV) are antiseizure medications that exert effects by binding to synaptic vesicle protein 2A (SV2A). BRV exhibits higher affinity and selectivity for SV2A and is generally considered to have a favorable psychiatric tolerability profile. However, reports on serious psychiatric adverse events remain scarce.

We herein report a 60‐year‐old man with a history of bipolar disorder who had remained psychiatrically stable for many years under aripiprazole treatment. He was diagnosed with focal epilepsy based on stereotyped focal seizures with impaired awareness and right temporal epileptiform discharges observed on electroencephalography. BRV was initiated at a dose of 50 mg/day and later increased to 100 mg/day. Several weeks after initiation, he developed elevated mood, marked irritability, emotional dysregulation, and delusion‐like ideation, progressing to a manic episode with psychotic features requiring inpatient psychiatric care. BRV was discontinued and replaced with lacosamide, coupled with intensification of a mood‐stabilizing treatment, which resulted in the gradual resolution of manic symptoms. No epileptic seizures occurred during BRV treatment or after the medication switch.

This case suggests that, despite its generally favorable psychiatric tolerability, BRV may be associated with the emergence of symptoms in patients with bipolar disorder. These findings highlight the importance of careful psychiatric risk assessment and close monitoring when initiating BRV in individuals with underlying mood vulnerability.