Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel: A Systematic Review of Clinical Data in Generalised Seizures

Abstract

Background The effectiveness of adjunctive perampanel has not been systematically assessed in seizure types other than its approved indications of focal seizures and primary generalised tonic-clonic seizures (PGTCS) in idiopathic generalised epilepsies (IGEs). Objective We aimed to identify and review available evidence on outcomes with perampanel in generalised seizures and epilepsies to examine its potential as a broad-spectrum anti-seizure medication. Methods Bibliographic databases of publications, clinical trials, and conference abstracts were searched up to August 2020 to identify studies reporting seizure or safety outcomes in patients of any age, with any type of epilepsy-associated generalised seizures treated with perampanel. Data extracted from selected records were tabulated by seizure type and syndrome, and analysed qualitatively (PROSPERO protocol CRD42020201564). Results Ninety-one reports met inclusion criteria and were selected: 15 reports of 1 randomised controlled trial (RCT), 8 reports of 4 non-randomised interventional studies, 37 reports of observational studies, 21 case reports and 10 systematic reviews and meta-analyses. Extracted data included 359 patients with PGTCS of any aetiology, 251 with myoclonic seizures, 112 with absence seizures, 50 with tonic seizures and 32 children with epileptic spasms. The most commonly reported epilepsy type was IGE (N = 378) and the most common syndromes were juvenile myoclonic epilepsy (N = 92), progressive myoclonic epilepsies (N = 59) and absence epilepsies (N = 43). The RCT provided Class I evidence of the efficacy and tolerability of adjunctive perampanel for PGTCS in patients aged ≥ 12 years with IGE. Data from other studies provides weaker (observational) evidence of its effectiveness in multiple generalised seizure types, including myoclonic, absence and tonic seizures. There were no patterns suggesting seizure worsening or aggravation in any seizure or epilepsy type. Conclusions The identified studies suggest the potential of perampanel as a broad-spectrum antiseizure medication. Much of the available data, however, come from non-randomised, non-controlled studies and are open to high risk of bias. Further studies are warranted to provide more robust evidence.

Patient-Reported Outcome Measures in Adult Patients Diagnosed with Epilepsy Being Treated with Perampanel

“…[29][30][31][32] A recent literature review by Trinka et al found that based on the published evidence, perampanel has the potential to be used a broad-spectrum ASM. 33 Many of the real-world results observed in the current study are consistent with those reported in these randomized controlled trials, [29][30][31][32] including a noted reduction in seizures and a tolerable side-effect profile.…”

Successful use of perampanel in GABRA1-related myoclonic epilepsy with photosensitivity

“…We considered adjunctive therapy with PER in view of the evidence of its effectiveness in children and adolescents with drug-resistant epilepsy [5] , [6] , [7] . A review by Trinka et al (2021), which included randomized controlled trials, observational cohort studies, and case reports highlights conflicting results on the effectiveness of PER on myoclonic seizures.…”

“…Case studies including patients with progressive myoclonus epilepsies such as Unverricht-Lundborg and Lafora disease reported considerable improvements in myoclonic seizure frequency or severity [5] , [8] , [9] , [10] .…”

Therapeutic Options for Childhood Absence Epilepsy

“…The pharmaco-resistance of up to 30% of treated children with CAE and the detection of neuropsychiatric conditions on follow up, along with the adverse effects reported for many of the current antiepileptic drugs, require scientific research to focus on novel treatments [59]. Recent studies have underlined that adjunctive Perampanel can be useful in the treatment of absence seizures in the context of idiopathic generalized epilepsies [60] but extensive data are still missing. Concerning new frontier therapies there is a new drug (EpidiolexVR), an oral form of phytocannabinoid that is currently in phase 2 trials in children with pharmaco-resistant absence seizures; however there are no publicly reported data on the use of this drug for absence animal models and its possible neuropsychological effects in children and adolescents remains unclear [59,61].…”

“…Perampanel; EpidiolexVR Perampanel as adjunctive therapy in idiopathic generalized epilepsy with absences, no evidence yet for treatment of CAE [60]. Epidiolex VR only in animal models [59].…”