Efficacy and tolerability of perampanel and levetiracetam as first add-on therapy in patients with epilepsy: A retrospective single center study

Liguori, Claudio; Izzi, Francesca; Manfredi, Natalia; D'Elia, Alessio; Mari, Luisa; Mercuri, Nicola Biagio; Placidi, Fabio

doi:10.1016/j.yebeh.2018.01.001

Cited by 41 publications

(40 citation statements)

References 22 publications

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“…In keeping with the results of this study, it is conceivable that PER may less frequently cause irritability at lower doses when used as first add‐on treatment. This result concords with a previous report published by our group and describing a good tolerability profile of PER when used as first adjunctive treatment . Furthermore, recent real‐life observations confirmed the tolerability and effectiveness of PER also in highly drug‐resistant patients with different epilepsy syndromes .…”

Section: Discussionsupporting

confidence: 79%

“…This result concords with a previous report published by our group and describing a good tolerability profile of PER when used as first adjunctive treatment. 20 Furthermore, recent real-life observations confirmed the tolerability and effectiveness of PER also in highly drug-resistant patients with different epilepsy syndromes. 21 In agreement with this recent evidence, serious psychiatric adverse events were usually reported by patients with psychiatric comorbidities; moreover, it appeared much more evident that PER may be more efficacious in treating symptomatic epilepsy, as previously suggested considering the mechanism of action of the drug.…”

Section: Discussionmentioning

confidence: 80%

“…Hence, since less but increasing data about the real‐life use of PER treatment, also as first add‐on, have been published in the recent past, this retrospective observational study aimed at better describing the effectiveness of PER and its psychiatric side effects, focusing on irritability. On these bases, the primary objective of the present study was to measure irritability by using the I‐EPI questionnaire in patients affected by uncontrolled seizures who start PER as first add‐on treatment at baseline and 12‐month follow‐up visits.…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2019

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Summary Aims Irritability has been described as a frequent adverse event in patients affected by epilepsy and treated with perampanel (PER), levetiracetam (LEV), and less frequently with valproic acid (VPA). Since the questionnaire for irritability (I‐EPI) is a validated instrument to measure this psychiatric manifestation in patients affected by epilepsy, in this study we aimed at investigating the effect of PER as first add‐on therapy on I‐EPI. Moreover, we compared the effectiveness and I‐EPI scores obtained at 12‐month follow‐up visits in patients treated by PER, LEV, or VPA in order to measure irritability as a consequence of these treatments. Methods We collected data from 17 patients treated by PER, 16 patients treated by LEV, and 16 patients under VPA treatment followed for 12 months. Results We did not document significant changes of I‐EPI questionnaire between baseline and follow‐up in the PER group. As concerning the comparison of I‐EPI among PER, LEV, and VPA groups, we documented lower global scores in PER than both LEV ( P < 0.05) and VPA ( P < 0.05) groups. Moreover, patients under PER treatment showed lower scores than LEV and VPA ( P < 0.05) in I‐EPI items measuring the gentle personality, anxiety of having epileptic seizures in front of others, and irritability in thinking that they can have an epileptic seizure. Conclusions This retrospective study described a stable and possibly lower degree of irritability in patients starting PER than LEV and VPA treatments, although we documented the comparable effectiveness of PER, LEV, and VPA as first add‐on treatments in patients affected by uncontrolled epileptic seizures. However, the small sample of patients included in this study and the absence of I‐EPI scores obtained at baseline visits in LEV and VPA groups require further investigations to confirm this preliminary evidence.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

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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

et al. 2019

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“…Rates of discontinuation due to AEs were lower in our cohort (12.8%) than in other observational studies with perampanel . Our lower rate could be related to use in earlier add‐on, and lower discontinuation rates (7%) have been reported with earlier use (first add‐on: 1/15; monotherapy: 4/60) . Eighty percent of our patients were maintained on 4 or 6 mg perampanel, and at 3 months, just over half of patients were being titrated in 2‐mg increments every 2 weeks, and a quarter every 4 weeks.…”

Section: Discussioncontrasting

confidence: 56%

“…This pattern is seen for AEDs in general—as fewer prior AEDs is a proxy for less refractory epilepsy—and has been shown with perampanel in focal seizures in the phase III trials and in observational studies . In a study of first add‐on use in 15 patients with uncontrolled secondarily generalized seizures, 80% of patients were free of these seizures 1 year after addition of perampanel . Perampanel has also been studied as monotherapy—Gil‐Nagel et al reported a responder rate of 80% and a seizure‐free rate of 45% during the first 3 months of perampanel monotherapy, in an observational study in 60 patients with focal and generalized seizures.…”

Section: Discussionmentioning

confidence: 86%

Perampanel in routine clinical use in idiopathic generalized epilepsy: The 12‐month GENERAL study

et al. 2018

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Summary Objective To analyze the effectiveness and tolerability of perampanel across different seizure types in routine clinical care of patients with idiopathic generalized epilepsy (IGE). Methods This multicenter, retrospective, 1‐year observational study collected data from patient records at 21 specialist epilepsy units in Spain. All patients who were aged ≥12 years, prescribed perampanel before December 2016, and had a confirmed diagnosis of IGE were included. Results The population comprised 149 patients with IGE (60 with juvenile myoclonic epilepsy, 51 generalized tonic–clonic seizures [GTCS] only, 21 juvenile absence epilepsy, 10 childhood absence epilepsy, 6 adulthood absence epilepsy, and one Jeavons syndrome). Mean age was 36 years. The retention rate at 12 months was 83% (124/149), and 4 mg was the most common dose. At 12 months, the seizure‐free rate was 59% for all seizures (88/149); 63% for GTCS (72/115), 65% for myoclonic seizures (31/48), and 51% for absence seizures (24/47). Seizure frequency was reduced significantly at 12 months relative to baseline for GTCS (78%), myoclonic (65%), and absence seizures (48%). Increase from baseline seizure frequency was seen in 5.2% of patients with GTCS seizures, 6.3% with myoclonic, and 4.3% with absence seizures. Perampanel was effective regardless of epilepsy syndrome, concomitant antiepileptic drugs (AEDs), and prior AEDs, but retention and seizure freedom were significantly higher when used as early add‐on (after ≤2 prior AEDs) than late (≥3 prior AEDs). Adverse events were reported in 50% of patients over 12 months, mostly mild or moderate, and irritability (23%), somnolence (15%), and dizziness (14%) were most frequent. Significance In routine clinical care of patients with IGE, perampanel improved seizure outcomes for GTCS, myoclonic seizures, and absence seizures, with few discontinuations due to adverse events. This is the first real‐world evidence with perampanel across different seizure types in IGE.

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PERMIT study: a global pooled analysis study of the effectiveness and tolerability of perampanel in routine clinical practice

et al. 2021

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The PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study was a pooled analysis of data from 44 real-world studies from 17 countries, in which people with epilepsy (PWE; focal and generalized) were treated with perampanel (PER). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness assessments included 50% responder rate (≥ 50% reduction in seizure frequency from baseline) and seizure freedom rate (no seizures since at least the prior visit); in PWE with status epilepticus, response was defined as seizures under control. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. The Full Analysis Set included 5193 PWE. Retention, effectiveness and safety/tolerability were assessed in 4721, 4392 and 4617, respectively. Retention on PER treatment at 3, 6, and 12 months was 90.5%, 79.8%, and 64.2%, respectively. Mean retention time on PER treatment was 10.8 months. The 50% responder rate was 58.3% at 12 months and 50.0% at the last visit, and the corresponding seizure freedom rates were 23.2% and 20.5%, respectively; 52.7% of PWE with status epilepticus responded to PER treatment. Overall, 49.9% of PWE reported AEs and the most frequently reported AEs (≥ 5% of PWE) were dizziness/vertigo (15.2%), somnolence (10.6%), irritability (8.4%), and behavioral disorders (5.4%). At 12 months, 17.6% of PWEs had discontinued due to AEs. PERMIT demonstrated that PER is effective and generally well tolerated when used to treat people with focal and/or generalized epilepsy in everyday clinical practice.

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Efficacy and tolerability of perampanel and levetiracetam as first add-on therapy in patients with epilepsy: A retrospective single center study

Cited by 41 publications

References 22 publications

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

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

Perampanel in routine clinical use in idiopathic generalized epilepsy: The 12‐month GENERAL study

PERMIT study: a global pooled analysis study of the effectiveness and tolerability of perampanel in routine clinical practice

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