Perampanel for treatment of status epilepticus in Austria, Finland, Germany, and Spain

Abstract

Objective Novel treatments are needed to control treatment‐resistant status epilepticus (SE). We report a summary of clinical cases where perampanel was used in established SE, refractory SE (RSE), or super‐refractory SE (SRSE). Methods Medical records were retrospectively reviewed for perampanel administration in SE at five European hospitals between 2011 and 2015. Results Of 1319 patients identified as experiencing SE, 52 (3.9%) received perampanel. Median latency from SE onset to perampanel initiation was 10 days. Patients with SE had previously failed benzodiazepines (when received) and a median of five other antiepileptic drugs (AEDs). Median initial perampanel dose was 6 mg/d, up‐titrated to a median maximum dose of 10 mg/d. Perampanel was the last drug added in 32/52 (61.5%) patients, with response attributed to perampanel in 19/52 (36.5%) patients. A greater proportion of perampanel non‐responders had SRSE (51.5%; 17/33) vs perampanel responders (31.6%; 6/19), and had failed a higher mean number of AEDs before initiating perampanel (5.9 vs 5.1, respectively). Most commonly reported adverse effects during perampanel treatment were dizziness (n = 1 [1.9%]) and somnolence (n = 1 [1.9%]). No serious adverse effects were documented, and none led to discontinuation of perampanel. Conclusions Perampanel was administered to patients with established SE, RSE, or SRSE at greater initial doses than those administered in clinical practice to patients with epilepsy. The SE cases reported here represent a refractory and heterogeneous population, and rate of seizure cessation attributed to perampanel treatment (36.5%) represents a notable response. These data should be confirmed in a larger patient population.

Treatment of refractory and superrefractory status epilepticus with topiramate: A cohort study of 106 patients and a review of the literature

“…Patients are separated as responders and nonresponders to topiramate, and among the latter, patients in whom topiramate was the last drug added before the cessation of status epilepticus but where other interventions precluded an unambiguous classification are indicated in light green [41][42][43] Two recent case series reported on the use of oral perampanel in patients with various stages of SE, reporting response rates between 17% 44 and 37%. 45 Use of oral oxcarbazepine in SE was reported in 13 patients with a median treatment latency of 81 hours. 46 Oxcarbazepine was the last drug in eight patients (62%); however, hyponatremia was seen in three of these individuals.…”

Oral Perampanel for the Treatment of Super-Refractory Status Epilepticus

“…This explains the resistance to those antiepileptic drugs having a GABAergic effect and a possible better response to those drugs acting on the neuroexcitatory receptors (NMDA and AMPA receptors). The effect of Perampanel, a noncompetitive AMPA receptor antagonist, as an adjunctive treatment in refractory status epilepticus has not been largely studied, with the exception of few published data demonstrating a variable range of efficacy [6–9].…”

Allopregnanolone and perampanel as adjuncts to midazolam for treating diisopropylfluorophosphate‐induced status epilepticus in rats

“…35 Studies in animal models 36 and anecdotal evidence from numerous case reports indicate utility in the treatment of SE. [37][38][39] Moreover, AMPA receptor antagonists, including PPL, can depress epileptogenesis, 40 including that caused by prolonged SE. 41 A consistent finding in studies of the neurotoxicological effects of OP nerve agents is that acute OPinduced seizures cause progressive neurodegeneration and neuroinflammation in the days to weeks following exposure.…”

“…Perampanel (PPL) is a potent, highly selective noncompetitive AMPA receptor antagonist approved for epilepsy therapy 35 . Studies in animal models 36 and anecdotal evidence from numerous case reports indicate utility in the treatment of SE 37–39 . Moreover, AMPA receptor antagonists, including PPL, can depress epileptogenesis, 40 including that caused by prolonged SE 41 …”