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Objectives: To compare the evidence on efficacy, safety, tolerability, and impact on short term/long functional outcome of lacosamide (LCM) and phenytoin (PHT) in patients with status epilepticus. Materials & Methods: We conducted a systematic literature search of relevant electronic databases using a suitable search strategy to identify studies directly comparing PHT and LCM, irrespective of dose and duration in patients with convulsive and/or nonconvulsive status epilepticus (SE). We used a standardized assessment form to extract information on the study design, data sources, methodologic framework, efficacy, and adverse events attributed to PHT and LCM from included studies and compared the efficacy and safety outcomes, using a fixed/random effect model. Results: Five studies were found to be eligible for inclusion out of 192 search items, enrolling a total of 115 and 166 participants (predominantly with SE) in LCM and PHT arm, respectively. Baseline characteristics were comparable between both arms. The proportion with seizure control was comparable between both arms (57.3% in LCM vs. 45.7% in PHT arm, p = 0.28) and even in the subgroup analysis separately for convulsive and non‐convulsive SE. Proportion with treatment‐emergent adverse events (TEAE) were comparable in both (17.6% vs. 12.2%, p = 0.20), but serious adverse events (SAE) were higher in PHT arm (5.1% vs. 0.8%, p = 0.049). The proportion with all‐cause mortality and survival with moderate‐severe disability were comparable between both arms (p = 0.23 and 0.37, respectively). Conclusion: LCM has comparable efficacy with fewer SAEs as compared to PHT for achieving seizure control in patients with SE. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate cutaneous allergic reactions in clinical trials of adjunctive eslicarbazepine acetate (ESL) for focal seizures. Materials and methods: Data were analyzed from three phase III randomized, double‐blind, placebo‐controlled studies of adjunctive ESL in adults (placebo, n = 426; ESL, n = 1021) and two randomized, double‐blind, placebo‐controlled studies (and open‐label extensions [OLEs]) of adjunctive ESL in children aged 4‐17 years (placebo, n = 160; ESL, n = 202; OLE, n = 337). Results: Adult studies: Rash (ESL 1.9%, placebo 0.9%) and pruritus (ESL 1.2%, placebo 0.9%) were the most frequent rash‐related treatment‐emergent adverse events (TEAEs). Most rash‐related TEAEs were mild or moderate in severity. Incidence of rash increased with increasing ESL dose, but was not higher for patients who initiated treatment with higher ESL doses. Pediatric studies: Allergic dermatitis (ESL 3.0%, placebo 0) and rash (controlled studies: ESL 1.0%, placebo 1.3%; OLE periods: ESL ≤1.2%) were the most frequent rash‐related TEAEs. There was one case of DRESS in the ESL group. Most rash‐related TEAEs were mild or moderate in severity and judged as not related to treatment with ESL. Conclusions: Serious skin rashes were rare during adult and pediatric clinical trials of ESL. Although the incidence of rash with ESL was low, it is important for patients/caregivers to be made aware of the potential signs and symptoms associated with serious skin rashes. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine the efficacy and safety of perampanel added to monotherapy in patients with focal‐onset seizures, with or without secondarily generalized tonic‐clonic seizures. Materials & Methods: In this multicentre, open‐label trial, enrolled patients were treated with perampanel monotherapy. During a 12‐week titration period, perampanel was incrementally increased by 2 mg/d over ≥2‐week intervals. Patients then entered a 24‐week maintenance period. The primary objective was to investigate the 50% responder rate in total seizure frequency, with 75% and 100% responder rates as secondary objectives. Treatment‐emergent adverse events (TEAEs) and adverse drug reactions were recorded. A post hoc analysis was performed to investigate the effect of titration speed and different concomitant AEDs on the efficacy and safety of perampanel. Results: Of the 85 patients analysed, seizure reductions of 50%, 75% and 100% were observed in 80.0% (95% confidence interval [CI]: 69.9‐87.9), 71.8% (95% CI: 61.0‐81.0) and 47.1% (95% CI: 36.1‐58.2) during the maintenance period, respectively. The 50%, 75% and 100% response rates in patients with secondarily generalized tonic‐clonic seizures were 87.5% (95% CI: 61.7‐98.5), 87.5% (95% CI: 61.7‐98.5) and 75.0% (95% CI: 47.6‐92.7), respectively. The most common TEAEs were dizziness (50.0%), somnolence (9.8%) and headache (8.8%). The efficacy outcomes and safety profile of perampanel were more favourable with slow titration and relatively consistent when stratified by concomitant AEDs. Conclusions: Perampanel was effective and well tolerated as a first add‐on to monotherapy in patients with focal‐onset seizures, with or without secondarily generalized seizures. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To assess effectiveness and tolerability of first‐line and conversion to lacosamide monotherapy for focal seizures. Materials and Methods: Retrospective, non‐interventional chart review of lacosamide monotherapy patients aged ≥16 years in Europe. Outcomes included retention rate at observational point (OP) 3 (12 ± 3 months), seizure freedom rates at OP2 (6 ± 3 months) and OP3 and adverse drug reactions (ADRs). Results: A total of 439 patients were included (98 first‐line and 341 conversion to monotherapy; 128 aged ≥65 years [25 first‐line and 103 conversion to monotherapy]). First‐line and conversion to monotherapy retention rates were 60.2% (59/98; 95% confidence interval [CI] 49.8%‐70.0%) and 62.5% (213/341; 57.1%‐67.6%), respectively. Kaplan‐Meier estimates of 12‐month retention rates were 81.2% and 91.4% for first‐line and conversion to monotherapy, respectively. First‐line and conversion to monotherapy retention rates in patients aged ≥65 years were 60.0% (38.7%‐78.9%) and 68.9% (59.1%‐77.7%), respectively. At OP2, 66.3% of first‐line and 63.0% of conversion to monotherapy patients were seizure free. At OP3, 60.2% of first‐line and 52.5% of conversion to monotherapy patients were seizure free. In the ≥65 years subgroup, seizure freedom rates at OP2 were 72.0% and 68.0% for first‐line and converted to monotherapy, respectively, and at OP3, 68.0% and 56.3%, respectively. Overall, 52 of 439 (11.8%) patients reported ADRs (16.4% in ≥65 years subgroup), most commonly dizziness (5.0%), headache (2.1%) and somnolence (1.6%). Conclusions: Lacosamide was effective and well tolerated as first‐line or conversion to monotherapy in a clinical setting in adult and elderly patients with focal seizures. [ABSTRACT FROM AUTHOR]

Abstract: Epileptic seizures are refractory to treatment in approximately one‐third of patients despite the recent introduction of many newer antiepileptic drugs (AEDs). Development of novel AEDs therefore remains a high priority. Perampanel is a first‐in‐class non‐competitive selective AMPA receptor antagonist with a unique mechanism of action. Clinical efficacy and safety of perampanel as adjunctive treatment for focal seizures with/without secondary generalization (±SG) and primary generalized tonic‐clonic (PGTC) seizures have been established in five phase 3 randomized controlled trials (RCTs), and a long‐term extension study, and perampanel is approved as monotherapy for focal seizures ±SG in the USA. In patients with focal seizures ±SG, add‐on perampanel resulted in median percent reduction in seizure frequency 23.3%‐34.5% and ≥50% responder rate 28.5%‐37.6%; in PGTC seizures, these results were 76.5% and 64.2%, respectively. Efficacy among adolescents (reduction in seizure frequency 34.8%‐35.6%; ≥50% responder rate 40.9%‐45.0%) and elderly people (reduction in seizure frequency 12.5%‐16.9%; ≥50% responder rate 22.2%‐42.9%) is similar to those in adults, and results remain comparable between Asian (reduction in seizure frequency 17.3%‐38.0%) and global populations. Perampanel has been extensively studied in real‐world clinical practice, with similar efficacy and safety results to the RCTs (≥50% responder rate 12.8%‐75.0%; adverse events of somnolence/sedation, dizziness, ataxia, and behavioral changes). Real‐world observational studies suggest that perampanel tolerability can be improved by slow titration (2 mg every 2‐4 weeks), and bedtime administration can mitigate somnolence and dizziness. Counseling about the potential for behavioral changes and close monitoring are recommended. [ABSTRACT FROM AUTHOR]

Purpose Evaluate real-life experience with eslicarbazepine acetate ( ESL) after first monotherapy failure in a large series of patients with focal epilepsy. Method Multicentre, retrospective, 1-year, observational study in patients older than 18 years, with focal epilepsy, who had failed first antiepileptic drug monotherapy and who received ESL. Data from clinical records were analysed at baseline, 3, 6 and 12 months to assess effectiveness and tolerability. Results Eslicarbazepine acetate was initiated in 253 patients. The 1-year retention rate was 92.9%, and the final median dose of ESL was 800 mg. At 12 months, 62.3% of patients had been seizure free for 6 months; 37.3% had been seizure free for 1 year. During follow-up, 31.6% of the patients reported ESL-related adverse events ( AEs), most commonly somnolence (8.7%) and dizziness (5.1%), and 3.6% discontinued due to AEs. Hyponatraemia was observed in seven patients (2.8%). After starting ESL, 137 patients (54.2%) withdrew the prior monotherapy and converted to ESL monotherapy; 75.9% were seizure free, 87.6% were responders, 4.4% worsened, and 23.4% reported ESL-related AEs. Conclusion Use of ESL after first monotherapy failure was associated with an optimal seizure control and tolerability profile. Over half of patients were converted to ESL monotherapy during follow-up. [ABSTRACT FROM AUTHOR]

Objectives There are clinical situations where it might be appropriate to switch patients from immediate-release oxcarbazepine ( OXC) to eslicarbazepine acetate ( ESL). We investigated the effects of transitioning patients overnight from OXC to ESL. Materials and Methods A retrospective, single-center study was conducted in which patients with drug-resistant focal epilepsy on a stable dose of immediate-release OXC for at least 4 weeks were switched overnight to ESL. Patients were switched because they experienced persistent seizures with OXC but were unable to tolerate increased OXC dosing due to adverse events. Tolerability was assessed using the Adverse Events Profile ( AEP), quality of life was assessed using the Quality of Life in Epilepsy Inventory 10 ( QOLIE-10), and alertness was assessed as reaction time using a subtest of the Test Battery for Attention Performance version 2.3. Assessments were performed immediately prior to and 5 days after switching from OXC to ESL (days 0 and 5, respectively). Results The analysis included 21 patients (12 women, 9 men; mean age 36 years). After switching from OXC to ESL, there were significant improvements in mean scores for AEP ( P<.001), QOLIE-10 ( P=.001), and alertness ( P<.05). Adverse Events Profile total scores improved for 21/21 (100.0%) patients, QOLIE-10 total scores improved for 17/21 (81.0%) patients, and alertness scores improved for 16/21 (76.2%) patients. Conclusions In this short-term, single-center study, an overnight switch from twice-daily OXC to once-daily ESL in patients with drug-resistant focal epilepsies resulted in improvements in side effects, quality of life, and alertness. [ABSTRACT FROM AUTHOR]