The real-world effectiveness and safety of perampanel in Europe: A scoping review.

In order to characterize the real-world effectiveness and safety of perampanel during clinical use in Europe, we conducted a structured literature search and scoping review of real-world studies conducted in Europe in adolescents (aged ≥ 12 years) or adults who were prescribed perampanel for focal epilepsy or primary generalized tonic-clonic seizures in the context of idiopathic generalized epilepsy, published between January 2016 and July 2021. We identified 29 relevant studies (20 retrospective and 9 prospective) in 3608 patients; median study duration was 12 months. Most patients (76.1%) were receiving two or more antiseizure drugs (ASDs) when perampanel was initiated. The maintenance perampanel dose ranged from 2 to 16 mg/day (most commonly 6 mg/day). Retention rate at 12 months ranged from 46% to 90.5% (median 71.1%). The proportion of patients who were free of seizures during perampanel ranged from 1.8% to 84.6%, but were consistently below 20% in studies where patients had received an average of ≥5 prior ASDs and above 20% where patients had received an average of <5 prior ASDs. The proportion of patients who achieved ≥50% reduction in seizures during perampanel ranged from 20.0% to 85.7%. Across all studies, the incidence of adverse events (AEs) ranged from 18.2% to 67.4% (median 37.1%) and discontinuation due to AEs from 6.2% to 56% (median 12.5%). Discontinuation rates tended to be higher in UK studies than in studies from Italy or Spain. The most commonly reported individual AEs were dizziness/vertigo (median incidence 13.7%), somnolence (median 11.9%), aggression (median 9.8%), irritability (median 9.1%), and cognitive deficits (median 7.0%). There was no relationship between the overall rate of AEs and perampanel dose, perampanel plasma levels, or number of concomitant medications. Our global overview of European observational studies with perampanel provides evidence that this agent is effective and safe in clinical practice in a range of countries, patients, and settings.

Efficacy and tolerability of perampanel as a first add-on therapy with different anti-seizure drugs.

PURPOSE: To investigate the efficacy and tolerability of perampanel (PER) when administered as a first add-on therapy to patients with focal epilepsy or idiopathic generalized epilepsy (IGE) taking one other antiseizure drug (ASD). METHODS: This multicentre, retrospective, one-year observational study collected data from patients (≥12 years) who initiated treatment with PER as first add-on therapy. Patients had to be experiencing inadequate seizure control on ASD monotherapy and tried ≤3 ASD monotherapies before initiating PER. Multivariate logistic regression analyses were performed, adjusted for the number and type of previous seizures, duration and aetiology of epilepsy. RESULTS: Of the 149 patients included in the study (mean age 41 years; 54.4 % male), 118 (79.2 %) were still receiving PER as first add-on treatment after 12 months. Mean PER dose was 6.2 mg/day. At 12 months, 45.6 % were seizure-free and 84.6 % responders. A significant difference in seizure freedom rate was found between patients with IGE and patients with focal epilepsy, but not in responders. Reduced seizure control was observed when PER was administered with strong enzyme-inducing ASDs; conversely, increased seizure control was seen when the same dose of PER was combined with enzyme-inhibiting ASDs. The most frequent adverse events were dizziness (15.4 %), irritability (14.1 %) and drowsiness (14.1 %); no differences in tolerance were observed among different combinations. CONCLUSION: PER demonstrated a good efficacy and safety profile when used as a first add-on therapy in patients who did not respond to monotherapy. PER dose adjustments may optimize seizure control when combined with strong enzyme-inducing or enzyme-inhibiting ASDs.

Clinical outcomes of eslicarbazepine acetate monotherapy for focal-onset seizures: A multicenter audit.

OBJECTIVE: To assess the effectiveness and tolerability of eslicarbazepine acetate (ESL) monotherapy in routine clinical practice for the treatment of focal-onset seizures. METHODS: Multicenter, retrospective, observational study conducted in patients older than 16 years treated with ESL as first-line monotherapy or converted to ESL monotherapy from polytherapy or other monotherapy. Outcomes included 1-year retention rate, seizure-free rates after 6 and 12 months of monotherapy treatment, and safety/tolerability issues. RESULTS: A total of 256 patients were included (106 first-line and 150 conversion to monotherapy; 56 patients aged >65 years). Overall, the 1-year retention rate was 79% (72.7% in the ≥65 years subgroup) and seizure-free rates at 6 and 12 months were 59.3% and 55.3% (72.2% and 67.3% in the ≥65 years subgroup), without significant differences when comparing first-line vs conversion-to-ESL monotherapy groups (P = .979). However, the conversion group was heterogeneous and included 43 (29.1%) patients that were seizure free the year prior ESL introduction. A substantially higher proportion of patients remained seizure free for the entire follow-up among those who initiated ESL due to tolerability problems compared with those treated due to inadequate seizure control (71.4% vs 37.3%). Overall, 62 of 256 (24.2%) patients reported AEs (39.3% in >65 years subgroup) and led to discontinuation in 20/256 (7.8%) patients (12.5% in >65 years subgroup). Commonly reported AEs were somnolence (6.6%), dizziness (6.3%), and headache (4.3%). Hyponatremia was recorded in five patients, the majority (4/5) of whom were older than 65 years. CONCLUSIONS: Eslicarbazepine acetate was effective and well-tolerated as first-line or conversion to monotherapy in a clinical setting in adult and elderly patients with focal-onset seizures.

Cardiovascular autonomic effects of vagus nerve stimulation.

The vagus nerve is responsible for the parasympathetic innervation of the major thoracic and abdominal organs. It also carries sensory afferent fibres from these viscera and reaches different brain structures. These connections have proven useful in the treatment of different diseases. Afferent stimulation of the left vagus nerve is used to treat epilepsy and major depression, and stimulation of the right vagus nerve is being tried for the treatment of heart failure. The device used for the therapy delivers intermittent stimuli. It is indicated worldwide for the treatment of drug-resistant epilepsy in patients who are not appropriate candidates for respective surgery. It has also received approval for the treatment of major depression, obesity and episodic cluster headache by the Food and Drug Administration. Randomised controlled trials and prospective studies have confirmed the efficacy and safety of this therapy in epilepsy. Nevertheless, sporadic cases of ventricular asystole have been reported. To evaluate the effect of vagus nerve stimulation therapy on the autonomic nervous system, different studies that assess heart function and blood pressure changes have been conducted, although the methods employed were not homogeneous. These studies have found subtle or no significant changes in heart rate variability and blood pressure in epileptic patients. Moreover, this therapy may reduce the risk of one of the most lethal conditions in epilepsy-sudden unexpected death.

One-year clinical experience of perampanel in Spain: a multicentre study of efficacy and tolerability.

Perampanel, a non-competitive antagonist of the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors, is the most recent antiepileptic drug available in Spain, marketed in January 2014. It was initially approved by the European Medicines Agency as adjunctive treatment for partial-onset seizures in patients 12 years and older, but recently also for primary generalized tonic-clonic seizures. Although clinical trials provide essential information about the drug, they do not reflect daily clinical practice. This retrospective study shows the initial experience with perampanel in 11 Spanish hospitals during its first year post-commercialisation. All patients who started perampanel treatment were included, but efficacy and tolerability were only assessed in those patients with a minimum follow-up period of six months. In total, 256 patients were treated with perampanel before September 2014, and 253 had an observational period of one year. After six months, 216/256 patients (84%) continued on perampanel and 180/253 (71.1%) completed one year of treatment. The mean number of previous antiepileptic drugs used was 6.83 and the median number of concomitant antiepileptic drugs was 2. The mean perampanel dose was 7.06 mg and 8.26 mg at six and 12 months, respectively. The responder rate was 39.5% and 35.9% at both follow-up points, respectively. Adverse events were experienced by 91/253 (35.5%) and resulted in withdrawal in 37 (14.6%). The most common adverse events were somnolence, dizziness, and irritability. We found no significant differences between concomitant use of enzyme-inducing and non-inducing antiepileptic drugs, regarding efficacy, adverse effects, or withdrawals. Irritability was not influenced by concomitant use of levetiracetam, relative to other drugs, but was more frequently observed in patients with a history of psychiatric problems or learning disabilities.

Predictive factors for a good prognosis following surgery for temporal lobe epilepsy: a cohort study in Spain.

To investigate the outcome of temporal lobe epilepsy surgery and identify the variables which predict a good prognosis with respect to seizures in postoperative follow-up after two and four years. This retrospective study included 115 selected patients who underwent surgery for temporal lobe epilepsy between 1996 and 2007. In the second year after surgery 86.1% of patients had a good prognosis for seizure control (73.9% Engel class I and 12.2% Engel class II) and 89.2% (76.3% Engel class I and 12.9% Engel class II) in the fourth year. Sixty-four of 93 (68.8%) patients were free of disabling seizures (Engel class I) during the entire period and 78 (83.8%) had good prognosis (Engel class I and II). For the second year, logistic regression analysis revealed the following variables to be independently predictive of good seizure control: absence of two or more seizure episodes in the first year after surgery, normal postoperative video-EEG, and age at surgery of less than 35 years. In the fourth year, mesial temporal sclerosis, female sex and normal postoperative video-EEG were the predictive factors. For the group with a good prognosis in both the second and the fourth year, the predictive variables were: absence of two or more seizure episodes in the first year after surgery (OR: 13.762, CI 95%: 2.566-73.808, p<0.002) and normal postoperative video-EEG (OR: 16.301, CI 95%: 3.704-71.740, p<0.001). This study illustrates the sustained benefit of temporal lobe epilepsy surgery. The multivariate logistic regression analysis failed to identify a good predictive model composed of preoperative variables alone, although it was possible to build such a model with either pre- and postoperative variables or only postoperative variables.