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Summary   Objective  To evaluate acute and long‐term effects of intravenous brivaracetam ( BRV ) and  BRV  + diazepam ( DZP ) combination treatment in a rat model of self‐sustaining status epilepticus ( SSSE ).    Methods  Rats were treated with  BRV  (10 mg/kg) 10 min after initiation of perforant path stimulation ( PPS ) as early treatment; or  BRV  (10–300 mg/kg),  DZP  (1 mg/kg), or  BRV  (0.3–10 mg/kg) +  DZP  (1 mg/kg) 10 min after the end of  PPS  (established  SSSE ). Seizure activity was recorded electrographically for 24 h posttreatment (acute effects), and for 1 week at 6–8 weeks or 12 months' posttreatment (long‐term effects). All treatments were compared with control rats using one‐way analysis of variance (ANOVA) and Bonferroni's test, or Kruskal‐–Wallis and Dunn's multiple comparison tests, when appropriate.    Results  Treatment of established  SSSE  with  BRV  (10–300 mg/kg) resulted in dose‐dependent reduction in  SSSE  duration and cumulative seizure time, achieving statistical significance at doses ≥100 mg/kg. Lower doses of  BRV  (0.3–10 mg/kg) + low‐dose  DZP  (1 mg/kg) significantly reduced  SSSE  duration and number of seizures. All control rats developed spontaneous recurrent seizures ( SRS ) 6–8 weeks after  SSSE , whereas seizure freedom was noted in 2/10, 5/10, and 6/10 rats treated with  BRV  200 mg/kg, 300 mg/kg, and  BRV  10 mg/kg +  DZP , respectively.  BRV  (10–300 mg/kg) showed a dose‐dependent trend toward reduction of  SRS  frequency, cumulative seizure time, and spike frequency, achieving statistical significance at 300 mg/kg. Combination of  BRV  (10 mg/kg) +  DZP  significantly reduced  SRS  frequency, cumulative seizure time, and spike frequency. In the 12‐month follow‐up study,  BRV  (0.3–10 mg/kg) + low‐dose  DZP  markedly reduced  SRS  frequency, cumulative seizure time, and spike frequency, achieving statistical significance at some doses. Early treatment of  SSSE  with  BRV  10 mg/kg significantly reduced long‐term  SRS  frequency.    Significance  These findings support clinical evaluation of  BRV  for treatment of status epilepticus or acute repetitive seizures.

Acute and long‐term effects of brivaracetam and brivaracetam–diazepam combinations in an experimental model of status epilepticus