The Need for Broad Spectrum and Safe Anti-epileptic Drugs in Childhood Epilepsy

Lagae, Lieven

doi:10.17925/enr.2006.00.02.36

Cited by 5 publications

(11 citation statements)

References 20 publications

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“…An estimated 2.4 million people are diagnosed with epilepsy each year . The standard of care for people with epilepsy is pharmacotherapy, with the aim of treatment being to preserve brain and cognitive development in infants and children and prevent morbidity and mortality through complete seizure control or reduced seizure frequency, with minimal adverse effects …”

Section: Introductionmentioning

confidence: 99%

“…The characteristic mechanisms of action that distinguish broad‐spectrum from narrow‐spectrum AEDs have not been elucidated. Until the development of the newer generations of AEDs in the 1990s, only valproate was considered to have broad‐spectrum efficacy against all seizure types . Since then, newer AEDs with a broader spectrum of activity in specific epileptic syndromes and seizure types have emerged, including zonisamide, topiramate, lamotrigine, levetiracetam, and brivaracetam .…”

Section: Introductionmentioning

confidence: 99%

“…For example, zonisamide acts by inhibiting voltage‐gated ion channels, inhibiting low‐threshold T‐type calcium currents, enhancing γ‐aminobutyric acid release, and inhibiting glutamatergic neurotransmission . On the other hand, some narrow‐spectrum AEDs may not only be ineffective for some seizures, but also harmful, by inducing or aggravating specific seizure types or seizures associated with specific epilepsy syndromes . For example, several sodium channel modulators can aggravate and induce seizures in absence epilepsy, juvenile myoclonic epilepsy, and other idiopathic generalized epilepsies …”

Section: Introductionmentioning

confidence: 99%

“…However, characterization of the seizure type at the time of diagnosis is often very difficult or even impossible, and misdiagnosis after a first seizure occurs in approximately 5%‐30% of patients . Therefore, broad‐spectrum AEDs are a logical choice for initial first‐line treatment, particularly during the diagnostic period, after which the treatment can be tailored to the epilepsy syndrome and individual patient factors …”

Section: Introductionmentioning

confidence: 99%

“…Until the development of the newer generations of AEDs in the 1990s, only valproate was considered to have broad-spectrum efficacy against all seizure types. 3,4,6 Since then, newer AEDs with a broader spectrum of activity in specific epileptic syndromes and seizure types have emerged, 3,4 including zonisamide, 9 topiramate, 10 lamotrigine, levetiracetam, 11,12 and brivaracetam. 13 Some broad-spectrum AEDs have multiple mechanisms of action.…”

mentioning

confidence: 99%

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Perampanel: Does it have broad‐spectrum potential?

Potschka

Trinka

2018

Epilepsia

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This article reviews the profile of perampanel, a novel noncompetitive α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor antagonist, and its role as a potential broad-spectrum antiepileptic drug in the treatment of epilepsy. For this narrative review, data were collected using specified search criteria. Articles reporting the evidence for perampanel's efficacy from preclinical models, phase 3 clinical studies, observational studies, and descriptive evidence were included. AMPA receptors play a key role in mediating the action of glutamate at the excitatory synapse. Preclinical research showed the AMPA receptor blockade to constitute a promising target for antiepileptic drug therapy. In animal models, perampanel proved to be protective against seizures and reduce seizure severity and duration. Four phase-3 randomized controlled trials (3 in patients with focal seizures and one in primary generalized tonic-clonic seizures in idiopathic generalized epilepsy) have been completed. In focal (partial) onset seizures, perampanel (4, 8, and 12 mg) significantly reduced seizure frequency per 28 days (23.3%-28.8% vs 12.8%; P < .01) and responder rates (≥50% reduction in seizures) (28.5%-35.3% vs 19.3%; P < .05) compared with placebo. In primary generalized tonic-clonic seizures, perampanel 8 mg resulted in greater reduction in seizure frequency per 28 days (-76.5% vs -38.4%; P < .0001) and responder rate (64.2% vs 39.5%; P = .0019) than placebo. The efficacy, safety, and tolerability of perampanel have been reproduced in real-world clinical practice, and the agent has been shown to be effective in other epilepsy syndromes. Perampanel is a potentially broad-spectrum antiepileptic drug with a novel mechanism of action that may be a useful addition for patients with epilepsy with various seizure types. The availability of novel antiepileptic drugs for epilepsy treatment enables more individualized treatment for these patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Perampanel: Does it have broad‐spectrum potential?

Potschka

Trinka

2018

Epilepsia

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Vertical gaze palsy due to medication error

Rao

Harper-Shankie

Agarwal

2017

Epilepsy & Behavior Case Reports

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Ideal characteristics of an antiepileptic drug: how do these impact treatment decisions for individual patients?

Trinka

2012

Acta Neurol Scand

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Effective management of epilepsy requires a holistic approach that takes into account the needs of the individual patient. Antiepileptic drug (AED) treatment must therefore look beyond efficacy to ensure that the patient's overall health status and quality of life (QoL) are optimized. Because the primary objective of AED treatment is to control seizures over the long term, the ideal AED should, first and foremost, demonstrate sustained efficacy and favourable tolerability. In addition, it should have a broad spectrum of activity; its pharmacokinetic profile should be stable and predictable and allow the option of once-daily dosing; and it should not interact with other medications and concomitant AEDs. Because the efficacy of first-line AEDs is broadly comparable, choice of treatment should be based on the individual patient's specific clinical characteristics. In particular, the primary and secondary prevention of comorbid conditions should be taken into consideration, because this can reduce the risk of mortality and improve health outcomes and QoL. Treatment selection must also take into account the patient's particular lifestyle and priorities, to maximize the likelihood of long-term treatment adherence. Advances in genetic testing may help inform choice of treatment - not only by elucidating a patient's underlying aetiology, but also by helping to avoid unnecessary side effects. Although certain patient populations (e.g. women of childbearing potential, adolescents, the elderly) require particular consideration when choosing the most appropriate treatment, every patient's unique clinical characteristics and personal circumstances must be taken into account to ensure treatment success and optimize their QoL.

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The Need for Broad Spectrum and Safe Anti-epileptic Drugs in Childhood Epilepsy

Cited by 5 publications

References 20 publications

Perampanel: Does it have broad‐spectrum potential?

Perampanel: Does it have broad‐spectrum potential?

Vertical gaze palsy due to medication error

Ideal characteristics of an antiepileptic drug: how do these impact treatment decisions for individual patients?

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