Preliminary evidence about irritability in patients with epilepsy treated by perampanel as first add‐on therapy compared to levetiracetam and valproic acid

Liguori, Claudio; Turner, Katherine; Izzi, Francesca; Assogna, Martina; Canevini, Maria Paola; Mercuri, Nicola Biagio; Placidi, Fabio

doi:10.1111/cns.13098

Cited by 9 publications

(6 citation statements)

References 29 publications

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“…PER did not increase depression and anxiety scores-even when scores indicated a mild level of anxiety before PER treatment. Although irritability was often reported in PER RCTs and observational studies, this study reports no increase in irritability, in line with the results of another smaller cohort (222). However, another study on 136 patients found that irritability and depression comorbidities before PER administration (as well as etiology of structural abnormalities and concomitant use of nitrazepam) were associated with psychiatric and behavioral deterioration after starting PER treatment (223).…”

Section: Overview Of Per and Psychiatric Comorbidities In Epilepsysupporting

confidence: 86%

The broad-spectrum activity of perampanel: state of the art and future perspective of AMPA antagonism beyond epilepsy

Perversi¹,

Costa²,

Labate³

et al. 2023

Front. Neurol.

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Glutamate is the brain’s main excitatory neurotransmitter. Glutamatergic neurons primarily compose basic neuronal networks, especially in the cortex. An imbalance of excitatory and inhibitory activities may result in epilepsy or other neurological and psychiatric conditions. Among glutamate receptors, AMPA receptors are the predominant mediator of glutamate-induced excitatory neurotransmission and dictate synaptic efficiency and plasticity by their numbers and/or properties. Therefore, they appear to be a major drug target for modulating several brain functions. Perampanel (PER) is a highly selective, noncompetitive AMPA antagonist approved in several countries worldwide for treating different types of seizures in various epileptic conditions. However, recent data show that PER can potentially address many other conditions within epilepsy and beyond. From this perspective, this review aims to examine the new preclinical and clinical studies—especially those produced from 2017 onwards—on AMPA antagonism and PER in conditions such as mesial temporal lobe epilepsy, idiopathic and genetic generalized epilepsy, brain tumor-related epilepsy, status epilepticus, rare epileptic syndromes, stroke, sleep, epilepsy-related migraine, cognitive impairment, autism, dementia, and other neurodegenerative diseases, as well as provide suggestions on future research agenda aimed at probing the possibility of treating these conditions with PER and/or other AMPA receptor antagonists.

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Section: Overview Of Per and Psychiatric Comorbidities In Epilepsysupporting

confidence: 86%

The broad-spectrum activity of perampanel: state of the art and future perspective of AMPA antagonism beyond epilepsy

Perversi¹,

Costa²,

Labate³

et al. 2023

Front. Neurol.

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“…6 Perampanel (PER) is a third-generation ASM, licensed for the treatment of focal and generalized epilepsies and recognized as an effective therapy in particular when used as first add-on ASM. 7-11 Consistently, long-term adjunctive treatment with PER does not have any significant overall effects on global cognition in adolescent and adult patients. 12,13 Quantitative EEG (qEEG) is a technique used to evaluate brain background activity in patients affected by epilepsy and can represent a useful tool in order to monitor cognition.…”

Section: Introductionmentioning

confidence: 84%

Perampanel Increases Cortical EEG Fast Activity in Child and Adult Patients Affected by Epilepsy: A Quantitative EEG Study

et al. 2020

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Objective Quantitative EEG (qEEG) is an established technique used as objective measure for evaluating the effect of antiseizure medications (ASMs) on EEG background activity and monitoring cognitive effects of ASMs. Perampanel (PER) has been associated with relatively more tolerable cognitive effects in patients with epilepsy. The primary aim of the present study was to verify the effect of PER as first add-on ASM on qEEG in child and adult patients affected by epilepsy. The secondary aim of this study was to verify the effectiveness of the drug as first add-on treatment in both child and adult patients with epilepsy. Methods We collected data from 17 adults and 10 children treated with PER as first add-on treatment, who underwent qEEG analysis before starting PER and at 3-month follow-up under stable treatment. Results PER resulted with significant effectiveness in reducing seizures in both children and adults. Considering qEEG analysis, we observed at follow-up the significant increase in beta1 and beta total bands both in children and adult patients. In particular, children showed the significant increase of beta band frequencies predominantly in the occipital regions, whereas adults showed a widespread increase of beta activity. Moreover, we documented in both child and adult patients the global reduction of delta bands activity. Conclusions This qEEG study documented the relative increase of cortical EEG fast activity in both children and adult patients affected by epilepsy and treated by PER. This result may suggest a potential less negative impact of PER on cognition in patients affected by epilepsy, other than demonstrating effectiveness of the drug when used as first add-on treatment in both children and adult patients.

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“…Several studies investigating PER as an early or first add-on therapy in clinical practice were included in the PERMIT study ( 40 – 48 ). However, since the PERMIT study was conducted, several other studies of PER as first add-on therapy have been conducted, in both the clinical trial and clinical practice settings.…”

Section: Discussionmentioning

confidence: 99%

Perampanel outcomes at different stages of treatment in people with focal and generalized epilepsy treated in clinical practice: Evidence from the PERMIT study

et al. 2023

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IntroductionThe PERMIT study is the largest pooled analysis of perampanel (PER) clinical practice data conducted to date.MethodsThis post-hoc analysis of PERMIT investigated the effectiveness, safety and tolerability of PER when used as early add-on therapy (after failure of one or two previous antiseizure medications) in comparison with late add-on therapy (after failure of three or more previous antiseizure medications). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (total seizures, focal seizures, generalized tonic-clonic seizures [GTCS]) and assessments included seizure freedom rate and responder rate. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs.ResultsThe Full Analysis Set included 1184 and 2861 PWE treated with PER as early and late add-on therapy, respectively. Compared to the late add-on subgroup, the early add-on subgroup was characterized by later mean age at epilepsy onset, shorter mean duration of epilepsy, lower rates of intellectual disability and psychiatric comorbidity, and lower frequency of seizures per month, suggesting a less severe form of epilepsy in this subgroup. After 12 months, retention was significantly higher in the early versus late add-on subgroup (67.7% vs. 62.4%; p = 0.004). At the last visit, responder rates in the early versus late add-on subgroup were significantly higher for total seizures (68.2% vs. 39.3%; p < 0.001), focal seizures (65.0% vs. 36.8%; p < 0.001) and GTCS (83.7% vs. 67.2%; p < 0.001), as were seizure freedom rates (total seizures, 35.9% vs. 11.9% [p < 0.001]; focal seizures, 29.4% vs. 8.7% [p < 0.001]; GTCS, 69.0% vs. 48.1% [p < 0.001]). Incidence of AEs was significantly lower in the early versus late add-on subgroup (42.1% vs. 54.7%; p < 0.001), as was the rate of discontinuation due to AEs over 12 months (15.0% vs. 18.1%; p = 0.031).DiscussionThis study demonstrated that PER was effective and generally well tolerated when initiated as early or late add-on therapy, but it was significantly more effective and better tolerated when initiated early. These findings support PER's use as a broad-spectrum, early add-on therapy for use in PWE with focal and generalized seizures.

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Preliminary evidence about irritability in patients with epilepsy treated by perampanel as first add‐on therapy compared to levetiracetam and valproic acid

Cited by 9 publications

References 29 publications

The broad-spectrum activity of perampanel: state of the art and future perspective of AMPA antagonism beyond epilepsy

The broad-spectrum activity of perampanel: state of the art and future perspective of AMPA antagonism beyond epilepsy

Perampanel Increases Cortical EEG Fast Activity in Child and Adult Patients Affected by Epilepsy: A Quantitative EEG Study

Perampanel outcomes at different stages of treatment in people with focal and generalized epilepsy treated in clinical practice: Evidence from the PERMIT study

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