Perampanel in achieving status epilepticus cessation: A systematic review

Status epilepticus (SE) is a neurological emergency necessitating rapid seizure control to prevent long-term consequences. Perampanel (PER) is a novel selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor antagonist that demonstrated efficacy and safety in lithium-pilocarpine models of SE; however, data in humans are limited. This systematic review was performed to assess the efficacy and safety of PER in patients with SE, RSE, and SRSE.

We searched MEDLINE (accessed through PubMed), Embase, Scopus, Cochrane Library, and ClinicalTrials.gov from inception until May 30, 2021 to identify all human studies on PER for the treatment of SE of any type and etiology. An additional search was performed on DANS Easy Archive, in which OpenGrey data were stored, from inception until January 10, 2022 and conference proceedings by the International League Against Epilepsy from 2011 onward. The GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach was used to assess the overall certainty of the body of evidence.

Twenty-one studies (7 case reports, 9 case series, and 5 retrospective cohort studies) were included with a total of 369 cases of SE in 368 patients aged 11 months to 99 years, of which 56.2% were female. Seizures of the majority were refractory (n = 220), super refractory SE (n = 70), or either (n = 81) with prominent motor symptoms (n = 284) and are associated with a structural etiology (n = 218). The number of antiseizure medications and/or anesthetics used prior to PER ranged from 1 to 13. PER was administered in 324 cases and was initiated at a dose of 2-36 mg between 30 min to 59 days from SE onset. SE cessation ranged from 1 h to 4 weeks from PER initiation. A total of 119 cases (36.6%) were considered PER responders. According to the GRADE approach, there is very low certainty of evidence for all outcomes.

The real-world data of PER as a possible therapeutic option in SE of any type are increasing. However, there is very low certainty of evidence for its use and this requires further clinical studies to establish the appropriate timing, dosing, and titration that are efficacious and safe for SE cessation.