Read | new drug options for anti-epileptic seizures

The PERMIT study showed a significant reduction in monthly seizure frequency (P<0.
001) with different types of focal seizure epilepsy (eg, focal seizures, focal perceptual seizures, and focal progression to bilateral tonic-clonic seizures) from baseline to last visit, and the safety profile was good [8] (Figure 1).

。

Fig.
1 Perampanel is effective and well tolerated against different types of FOS

▌ Generalized seizures

Perampanel has been shown to be effective and well
tolerated in generalized seizures in several clinical studies.

One study included patients with myoclonus and/or absence seizures at baseline in the 322 study with a maximum dose of 8 mg/day during perampanel titration and maintenance during the double-blind phase and 12 mg/day
during OLEx maintenance.
Analysis of studies has found that long-term (> 104 weeks) addition of perampanel does not aggravate absence and myoclonic seizures, and that both 50 percent and 75 percent of response rates are stable during long-term treatment [9] (Figure 2).

Fig.
2 Long-term application of perampanel does not lead to aggravation of absence and myoclonic seizures

▌ Refractory epilepsy

Perampanel is effective and safe
for all types of refractory status epilepticus.
A retrospective analysis of information from 81 patients in intensive care with perampanel treated with refractory status epilepticus epilepticus (RSE) and ultra-refractory status epilepticus epilepticus (SRSE) found that perampanel was 33.
3 percent and 29.
3 percent effective in patients with focal seizure SE and generalized tonic-clonic SE, respectively, and 50 percent effective for SE secondary to central nervous system tumors and hypoxic encephalopathy [10].

。

▌ Seizures in children

In growing and developing children, perampanel is also effective in controlling various seizure types
in children with epilepsy, including refractory epilepsy.
In a retrospective study (44 children with epilepsy aged 6 to 12 years, with a mean maximum dose of 5.
3 mg and a median maximum dose of 5.
5 mg per perampanel, all patients received more than two AEDs from initial treatment to last visit with perampanel, and were observed for more than 6 months) showed a 50% response rate of 52.
3% to perampanel, with complete seizure control in 4 patients [ 11] (Figure 3).

Fig.
3 Efficacy of perampanel on various seizure types in children

▌ Epilepsy syndrome

In addition, in patients with Lennox-Gastaut syndrome (LGS) and Dravet syndrome, perampanel also has corresponding clinical data
.
In patients with poorly controlled LGS, perampanel is effective by about 65%; The median duration of treatment was 14.
3 months, with a retention rate of 62 percent at last follow-up [12].

Perampanel is effective for a variety of seizure types in Dravet syndrome, including generalized tonic-clonic seizures, unilateral clonic seizures, myoclonic seizures, atypical absence seizures, and focal perception disorder seizures [13].

In addition, perampanel has shown wide application prospects
in secondary epilepsy such as brain tumor-related epilepsy [14], focal brain injury-related epilepsy [15], encephalitis-related epilepsy [16], and GABRB3 variant related [17].

Based on the above research data, it may also suggest that for patients with epilepsy with unclear seizure types, complex etiology, and possible disease evolution, the "broad-spectrum" antiepileptic drug perampanel may be a better choice
.

Perampanel is approved in China for the treatment
of adults and children 4 years of age and older with partial seizures (with or without secondary generalized seizures).

Special note: Based on the analysis and interpretation of literature, it is only used for academic communication and discussion, and cannot replace the specific plan
for diagnosis and treatment in the hospital.
For drug application, please comply with the drug instructions and relevant regulations
approved by the state.

References:

[1] Expert Collaboration Group on Long-term Management of Adult Patients with Epilepsy.
Expert consensus on long-term management of adult patients with epilepsy[J] .
Chinese Journal of Neurology.
2013; 46 (7): 496-499.

[2] Chinese Anti-Epilepsy Association.
Clinical Guidelines for Epilepsy (2015 Revised Edition).

[3] Trinka E, Lattanzi S, Carpenter K, et al.
Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel: A Systematic Review of Clinical Data in Generalised Seizures[J].
CNS Drugs.
2021 Aug; 35(8):821-837.

[4] Potschka H, Trinka E.
Perampanel: Does it have broad-spectrum potential? [J].
Epilepsia.
2019 Mar; 60 Suppl 1:22-36.

[5] Rogawski MA.
AMPA receptors as a molecular target in epilepsy therapy[J].
Acta Neurol Scand Suppl.
2013;(197):9-18.

[6] Hanada T.
Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors[J].
Biomolecules.
2020 Mar 18; 10(3):464.

[7] Du Lingling, Xu Jiajun, Cui Lan.
Overview of the selective AMPA receptor antagonist perampanel[J].
Chinese pharmacist.
2013; 16(8): 1245-1247.

[8] Villanueva V, D'Souza W, Goji H, et al.
PERMIT study: a global pooled analysis study of the effectiveness and tolerability of perampanel in routine clinical practice[J].
J Neurol.
2022 Apr; 269(4):1957-1977.

[9] Brandt C, Wechsler RT, O'Brien TJ, et al.
Adjunctive perampanel and myoclonic and absence seizures: Post hoc analysis of data from study 332 in patients with idiopathic generalized epilepsy[J].
Seizure.
2020 Aug; 80:115-123.

[10] Lim SN, Wu T, Tseng WJ, et al.
Efficacy and safety of perampanel in refractory and super-refractory status epilepticus: cohort study of 81 patients and literature review[J].
J Neurol.
2021 Oct; 268(10):3744-3757.

[11]Ishikawa N, Tateishi Y, Tani H, et al.
Clinical profiles associated with serum perampanel concentrations in children with refractory epilepsy[J].
Epilepsy Behav.
2019 May; 94:82-86.

[12] Crespel A, Tang NPL, Macorig G, et al.
Open-label, uncontrolled retrospective study of perampanel in adults with Lennox-Gastaut syndrome[J].
Seizure.
2020 Feb; 75:66-69.

[13] Yoshitomi S, Takahashi Y, Yamaguchi T, et al.
Efficacy and tolerability of perampanel in pediatric patients with Dravet syndrome[J].
Epilepsy Res.
2019 Aug; 154:34-38.

[14] Coppola A, Zarabla A, Maialetti A, et al.
Perampanel Confirms to Be Effective and Well-Tolerated as an Add-On Treatment in Patients With Brain Tumor-Related Epilepsy (PERADET Study)[J].
Front Neurol.
2020 Jun 25; 11:592.

[15] Nilo A, Pauletto G, Gili GL, et al.
Perampanel as add-on therapy in epilepsies with known etiology: A single center experience with long-term follow-up[J].
Epilepsy Behav Rep.
2020 Oct 26; 15: 100393.

[16] Wang T, Wen B, Chi Z, et al.
The well responsiveness of drug-resistant focal seizures in anti-AMPA2 receptor encephalitis to perampanel treatment[J].
Neurol Sci.
2022 Jan; 43(1): 525-532.

[17] Yang Y, Zeng Q, Cheng M, et al.
GABRB3-related epilepsy: novel variants, clinical features and therapeutic implications[J].
J Neurol.
2022 May; 269(5): 2649-2665.

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