Rationale:
The current primary treatment for status epilepticus involves the administration of benzodiazepines (e.g., lorazepam) as the first-line therapy. Once status epilepticus is established, inhibitory γ-aminobutyric acid (GABA)-A receptors, which mediate the primary action of benzodiazepines, become internalized and deactivated within the cells. The translocations of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate receptors from intracellular compartments to the synaptic cleft as well as the alterations in their functionality are considered the crucial mechanism in the pathophysiology of refractory status epilepticus. Perampanel is the first non-competitive selective AMPA receptor antagonist, which can be a candidate for status epilepticus treatment. This study aims to demonstrate the effficacy of perampanel adjunctive therapy in lorazepam-resistant status epilepticus.
Methods:
This study is a single-center, randomized, positive-controlled trial to compare the adjunctive therapeutic effects between perampanel and levetiracetamin lorazepam-resistant status epileptics. Patients with status epilepticus were sequentially enrolled in the study. The first-line therapy was lorazepam, followed by either a perampanel loading dose (12 mg, administered orally or via an enteral tube) or a levetiracetam loading dose (50 mg/kg, intravenous) as the second-line therapy. The use of further adjunctive therapies, excluding perampanel and levetiracetam, was determined based on the clinical judgment of the attending neurologist. This study was approved by the Institutional Review Board of Keimyung University Dongsan Medical Center (No. 2020-12-041).
Results:
A total of 24 patients with status epilepticus were analyzed. The perampanel and levetiracetam groups consisted of 13 (54.2%) and 11 (45.8%) patients, including 3 (23.1%) and 8 (82.7%) females in the groups (p=0.038). Their mean age was 47.67 ± 13.45, without a difference between the groups (47.92 ± 13.15 versus 47.36 ± 14.44, p=0.898). The majority (87.5%) had generalized convulsive status epilepticus. The most common etiology of status epilepticus was unknown (41.7%), followed by CNS infection (16.7%). The mean Status Epilepticus Severity Score was 2.17 ± 0.76, 2.38 ± 0.65, and 1.91 ± 0.83 in groups (p=0.167), respectively. The average time from initial treatment (i.e., intravenous lorazepam) to seizure termination was 2:06 ± 4:10 (hh:mm), without significant difference (1:57
±3:14 vs. 2:18±5:14, p=0.700). Six patients (25.0%) had additional seizures after the administration of second-line therapy, either perampanel or levetiracetam loading. The mean length of hospital stay was 16.08 ± 21.37 days (18.15±24.31 vs 13.64±18.13, p=0.966). Three (12.5%) of the total had intensive care unit admission. The number of antiseizure medications on discharge was 3.67±1.34 on average (4.00±1.35 vs. 3.27±1.27, p=0.197). Two (8.3%) died within 30 days.Conclusions:
This study demonstrated the non-inferiority of perampanel loading compared to levetiracetam loading, which may widen the treatment options for status epilepticus. Future studies with large population will be necessary to verify the findings in this study.
Funding: None.