Use Of Lacosamide Research Articles

Intravenous lacosamide for acute repetitive seizures and convulsive status epilepticus in critically ill children.

Acute repetitive seizures and convulsive status epilepticus are common neurological emergencies in critically ill children. The aim of the study was to evaluate the effectiveness and safety of intravenous lacosamide in critically ill children with acute repetitive seizures and convulsive status epilepticus. This retrospective study included children who received intravenous lacosamide for acute repetitive seizures or convulsive status epilepticus from October 2017 to September 2022 and were admitted to the pediatric intensive care unit at a tertiary medical center. Children who were newly started on intravenous lacosamide were included and divided into two groups: (a) previously healthy, and (b) history of epilepsy and receiving antiseizure medications. Efficacy was defined as the cessation of seizures within 72 h of administering lacosamide. Adverse effects were defined using predefined criteria, and most were evaluated during the first 7 days. Sixty-seven children were enrolled, including 25 (37.3%) girls and 42 (62.7%) boys with a mean age of 7.20 ± 5.66 years. Among them, 30 (44.8%) had acute repetitive seizures, and 37 (55.2%) had convulsive status epilepticus. The seizure types were focal onset (n = 34, 50.7%), generalized onset (n = 27, 40.3%), and mixed type (n = 6, 9.0%). In the previously healthy group, 9 patients had acute repetitive seizures and 23 had convulsive status epilepticus, and the rates of seizure cessation when lacosamide was used as the first to fourth choice of antiseizure medication were 100.0%, 85.7%, 40.0%, and 50.0%, respectively, compared to 73.7%, 54.5%, 100.0%, and 0.0% in the patients with epilepsy (21 had acute repetitive seizures and 14 had convulsive status epilepticus). Sixteen (23.9%) patients developed bradycardia and 1 (1.5%) patient developed a rash. The early use of intravenous lacosamide was effective with acceptable side effects in treating acute repetitive seizures and convulsive status epilepticus in critically ill children, including young infants and children less than 4 years old and those with different etiologies. Acute repetitive seizures and convulsive status epilepticus are common neurological emergencies in pediatric intensive care units (PICUs), traditional intravenous antiseizure medications (ASMs) include phenytoin, valproic acid, levetiracetam, and phenobarbital. In this study, we categorized patients based on their epilepsy history and different etiologies. We observed that early use of lacosamide, even in young infants, demonstrated good efficacy and safety.

Intravenous Lacosamide Therapy for Pediatric Patients With Cluster Seizures

BackgroundFew studies have investigated intravenous lacosamide use to treat cluster seizures in pediatric patients. Therefore, we aimed to investigate the efficacy and safety of intravenous lacosamide therapy in pediatric patients with cluster seizures. MethodsWe retrospectively evaluated the efficacy and safety of intravenous lacosamide therapy in 25 pediatric patients with cluster seizures at Saitama Children's Medical Center between March 2019 and June 2023. Cluster seizures were defined as a single seizure of less than five minutes duration, repeated three or more times within 12 hours, with recovery of consciousness between seizures. Response was defined as seizure freedom for at least 12 hours after lacosamide infusion. ResultsThe median age at onset of epilepsy was 1.5 (0.0 to 9.8) years. The median seizure frequency was 5 (3 to 20) times per 12 hours. The etiologies were remote (n = 17), acute (n = 4), and progressive (n = 4). The median age at which intravenous lacosamide therapy was administered was 4.2 (0.0 to 11.3) years. The median lacosamide dose was 2.6 (1.3 to 5.2) mg/kg. In total, 12 of 25 patients (48.0%) responded. Among patients treated with intravenous lacosamide as first-line therapy, nine of 17 (52.9%) had complete seizure remission. The frequency of complete seizure remission in patients with remote etiologies was 58.8% (10 of 17); among them, seven of 12 (58.3%) patients with structural abnormalities showed complete seizure remission. No adverse events were observed. ConclusionsIntravenous lacosamide therapy is a potentially useful treatment option for cluster seizures in pediatric patients.

The effect of lacosamide on calcitonin gene-related peptide serum level in episodic migraine patients: a randomized, controlled trial

BackgroundMigraine affects 11–15% of people worldwide, and the calcitonin gene-related peptide (CGRP) is released during the migraine attack, producing pulsating pain of migraine. Also, lacosamide reacts with collapsin-response mediator protein 2, preventing its phosphorylation and leading to the inhibition of CGRP release in the trigeminal system.ObjectiveThe primary outcome was the difference in the serum level of CGRP-LI after three months of treatment with either lacosamide and ibuprofen or ibuprofen alone in episodic migraine patients. The secondary outcomes were assessing safety and efficacy of lacosamide in episodic migraine patients.MethodsWe conducted an open-label randomized controlled trial on episodic migraine patients aged 10–55 years diagnosed according to (ICHD-3) in Kafr El-Sheikh University Hospital, Egypt. We assessed serum levels of CGRP-LI before and three months after treatment in our two groups, the lacosamide, and the control groups. We also assessed the side effects of treatment in each group, the percentage of patients who achieved ≥ 50% reduction in the migraine monthly days (MMD) frequency and the percentage of patients who achieved pain freedom within 2 h in ≥ 4 of 5 attacks in each group.Results200 episodic migraine patients completed the study. There was a statistically significantly higher reduction in the serum CGRP-LI level in the lacosamide group compared with the control group. In addition, lacosamide was well tolerated by patients. Also, the lacosamide group had statistically significant higher percentage of patients who achieved ≥ 50% reduction in the migraine monthly days (MMD) frequency and pain freedom within two hours in ≥ 4 of 5 attacks with P-values 0.002, 0.02 respectively.ConclusionThe daily use of lacosamide 50 mg Bid for three months in episodic migraine patients was associated with a significant reduction in serum CGRP-LI, better clinical outcomes regarding frequency and duration of migraine attacks, and was well tolerated by patients. These results were derived from an open-label pilot study that needed to be thoroughly investigated by a large-scale, randomized, double-blinded, placebo-controlled study.Trial registration: We registered our trial on ClinicalTrials.gov, named after "The Lacosamide's Effect on Calcitonin Gene-related Peptide in Migraine Patients," and with a clinical trial number (NCT05632133)—August 8, 2023.

Retrospective Multicenter Cohort Study on Safety and Electroencephalographic Response to Lacosamide for Neonatal Seizures

BackgroundThere is growing evidence supporting the safety and effectiveness of lacosamide in older children. However, minimal data are available for neonates. We aimed to determine the incidence of adverse events associated with lacosamide use and explore the electroencephalographic seizure response to lacosamide in neonates. MethodsA retrospective cohort study was conducted using data from seven pediatric hospitals from January 2009 to February 2020. For safety outcomes, neonates were followed for ≤30 days from index date. Electroencephalographic response of lacosamide was evaluated based on electroencephalographic reports for ≤3 days. ResultsAmong 47 neonates, 98% received the first lacosamide dose in the intensive care units. During the median follow-up of 12 days, 19% of neonates died, and the crude incidence rate per 1000 patient-days (95% confidence interval) of the adverse events by diagnostic categories ranged from 2.8 (0.3, 10.2) for blood or lymphatic system disorders and nervous system disorders to 10.5 (4.2, 21.6) for cardiac disorders. Electroencephalographic seizures were observed in 31 of 34 patients with available electroencephalographic data on the index date. There was seizure improvement in 29% of neonates on day 1 and also in 29% of neonates on day 2. On day 3, there was no change in 50% of neonates and unknown change in 50% of neonates. ConclusionsThe results are reassuring regarding the safety of lacosamide in neonates. Although some neonates had fewer seizures after lacosamide administration, the lack of a comparator arm and reliance on qualitative statements in electroencephalographic reports limit the preliminary efficacy results.

CYP2C19 genotype and sodium channel blockers in lacosamide-treated children with epilepsy: two major determinants of trough lacosamide concentration or clinical response.

The widespread clinical use of lacosamide (LCM) has revealed significant individual differences in clinical response, with various reported influencing factors. However, it remains unclear how genetic factors related to the disposition and clinical response of LCM, as well as drug-drug interactions (DDIs), exert their influence on pediatric patients with epilepsy. To evaluate the impact of genetic variations and DDIs on plasma LCM concentrations and clinical response. Patients with epilepsy treated with LCM from June 2021 to March 2023 in the Children's Hospital of Nanjing Medical University were included in the analysis. The demographic information and laboratory examination data were obtained from the hospital information system. For the pharmacogenetic study, the left-over blood specimens, collected for routine plasma LCM concentration monitoring, were used to perform genotyping analysis for the selected 26 single nucleotide polymorphisms from 14 genes. The trough concentration/daily dose (C 0/D) ratio and efficacy outcomes were compared. Patients achieved 90.1% and 68.9% responder rates in LCM mono- and add-on therapy, respectively. The genetic variant in the CYP2C19 *2 (rs4244285) was associated with a better responsive treatment outcome (odds ratio: 1.82; 95% confidence interval: 1.05-3.15; p = 0.031). In monotherapy, 36% of patients were CYP2C19 normal metabolizers (NMs), 49% were intermediate metabolizers (IMs), and 15% were poor metabolizers (PMs) carrying CYP2C19 *2 or *3. Of note, the C 0/D ratios of IMs and PMs were 9.1% and 39.6% higher than those of NMs, respectively. Similar results were in the add-on therapy group, and we also observed a substantial decrease in the C 0/D ratio when patients were concomitant with sodium channel blockers (SCBs). This study was the first to confirm that CYP2C19 *2 or *3 variants impact the disposition and treatment response of LCM in children with epilepsy. Moreover, concomitant with SCBs, particularly oxcarbazepine, also decreased plasma LCM concentration.

Effects of Levetiracetam and Lacosamide on survival and seizure control in IDH-wild type glioblastoma during temozolomide plus radiation adjuvant therapy

IntroductionThere are no clear indications for the best choice of anti-seizure medications to control brain tumor related epilepsy. In vitro studies have shown an antitumoral effect of Levetiracetam and Lacosamide on glioblastoma IDH-wild type. Research questionThis study investigates whether the use of levetiracetam and/or lacosamide impacts survival rates. The secondary aim was to evaluate the efficacy of both ASMs in controlling seizures. Materials and methodsIn this observational retrospective single-cohort study, patients underwent chemoradiation protocol after GBM surgery. They were grouped as follows: (1) use of levetiracetam, (2) use of lacosamide, (3) simultaneous use of levetiracetam and lacosamide, (4) no ASM usage. Survival curves were plotted using the Kaplan-Meier method coupled with a log-rank test for difference assesments. To evaluate the pharmacological efficacy of post-operative seizure control, a negative binomial regression was conducted. ResultsThe study included 272 patients, 174 of which underwent adjuvant chemoradiation treatment. Patients without ASM therapy had a non-significant longer median OS (compared to the other groups (log-rank = 0.37). The IRR of seizure relapse was 2.57 (p = 0.007) times higher in lacosamide users, and MGMT promoter methylation demonstrated a protective effect against postoperative seizure onset (p = 0.05), regardless of the aforementioned confounding factors. Discussion and conclusionsIn patients diagnosed with GBM IDH-WT undergoing chemoradiation therapy, the use of levetiracetam or lacosamide for controlling BTRE does not seem to modify survival. Lacosamide users exhibited a higher IRR of postoperative seizures compared to levetiracetam users, and MGMT promoter methylation appears to be a protective factor.

Lacosamide for the Treatment of Seizures in Neonates and Infants: A Retrospective Assessment of Efficacy and Tolerability

BackgroundA retrospective study was conducted to assess the safety and efficacy of lacosamide in children aged less than 24 months. MethodsPatients were included if they were ≤24 months when they first received lacosamide; patients were excluded if they were enrolled in research studies investigating lacosamide or if there were insufficient data in the chart. Treatment response was assessed by reviewing charts and electroencephalographic reports to determine reduction in seizure burden. ResultsIn this sample, 53 of 86 patients (61.63%) in status epilepticus had good response to lacosamide, defined by ≥50% reduction in seizure burden. In addition, patients’ charts were reviewed until age 24 months to assess for any adverse effects attributed to maintenance lacosamide therapy, with adverse effects noted in three patients (abnormal movements in two patients, worsened seizures in one patient). ConclusionsThis study is among the largest retrospective chart reviews investigating the use of lacosamide in children and the first investigating the efficacy of lacosamide in children aged ≤24 months. Lacosamide was efficacious in reducing seizure burden in status epilepticus, and it was very well-tolerated in this age group. This study should prompt further investigation into the use of lacosamide in this age group.

Neonatal Cardiac Arrest Following Lacosamide Treatment: A Case Report

BackgroundLacosamide is an antiepileptic drug with US Food and Drug Administration approval for the treatment of partial-onset seizures in patients older than one month. Lacosamide works by selective enhancement of proteins that induce preferential slow promotion of sodium channels to the hyperpolarized inactive state. Lacosamide is generally well-tolerated; however, clinical and nonclinical studies have linked its use with cardiac side effects including PR prolongation and atrioventricular (AV) block. ResultsWe present the case of a three-week-old female neonatal patient born at 25 weeks’ gestation who developed second-degree AV heart block and cardiac arrest after initiating lacosamide therapy. The patient was being treated for neonatal seizure complicated by intraventricular hemorrhage (grade II) and electrolyte disturbances with phenobarbital, levetiracetam, and phenytoin. Before addition of lacosamide therapy, the patient had an unremarkable electrocardiogram and no known cardiac risk factors for lacosamide. After medication discontinuation, the patient experienced no reoccurring episodes or other cardiac events. ConclusionUse of lacosamide for neonatal populations is currently under evaluation. This is the first report of adverse cardiac event (AV block) in the setting of neonatal lacosamide use. Risk of future adverse cardiac events should be evaluated when determining the safety and efficacy of lacosamide in the neonatal population.

Simple and validated method to quantify lacosamide in human breast milk and plasma using UPLC/MS/MS and its application to estimate drug transfer into breast milk

BackgroundEpilepsy is a common neurological disorder. Lacosamide is a third-generation antiepileptic drug used to treat partial-onset seizures. Limited information is currently available on the transfer of lacosamide to breast milk. To facilitate studies on the safety of lacosamide use during breastfeeding, we aimed to develop a method to quantify lacosamide in human breast milk and plasma using ultra-performance liquid chromatography/tandem mass spectrometry.MethodsFifty microliters of breast milk or plasma was used, and samples were prepared by protein precipitation using methanol containing lacosamide-d3 as an internal standard (IS). Chromatography was performed using an ACQUITY HSS T3 column with an isocratic flow of 10 mM ammonium acetate solution/methanol (70:30, v/v). Lacosamide and IS were detected by multiple reaction monitoring in positive ion electrospray mode. The run time was 3.5 min.ResultsCalibration curves were linear and in the range of 0.5 to 100 ng/mL both in breast milk and plasma. The validation assessment indicated that precision, accuracy, matrix effects, selectivity, dilution integrity, and stability were acceptable. The developed method was successfully applied to quantify lacosamide in breast milk and plasma obtained from a volunteer who had been orally administered lacosamide twice a day (100 mg × 2). Relative infant dose of lacosamide was estimated to be 14.6% in breast milk at five time points.ConclusionsWe developed a simple and robust method to quantify of lacosamide in human breast milk and plasma. This method could be useful for in future studies investigating the safety of lacosamide use during breastfeeding.

Trends in Antiseizure Medication Prescribing Among Nursing Home Residents With and Without a Seizure Diagnosis.

Evaluate current prevalence and changes in prescribing of antiseizure medications (ASMs) in Virginia nursing homes for residents with and without seizures. Retrospective cohort. De-identified claims extracted from the Virginia All-Payers-Claims-Database defined annual and biennial cohorts of all insured long-stay residents with and without any claims-based seizure diagnoses. ASM prescribing prevalence rates for these cohorts were analyzed from 2011 to 2016. Multiple logistic regression compared prescribing prevalence rates within and between these 2 groups. Annual cohorts averaged 57,190. 65.6% Female, 38% white. 80% public insurance, 20% commercial secondary. Between 2011 and 2016, the claims-based prevalence of seizure diagnoses decreased (17.1% to 10.5%). However, ASM prescribing prevalence increased (10.4% to 11.6%). Increases were entirely among residents who never had any seizure-epilepsy claim, whereas ASM prescribing among residents with seizures decreased. Different drugs were used for patients with and without seizures. For residents without seizures, 85% of ASMs prescribed have alternative indications for mood or pain symptoms, and large gains in gabapentin and modest but significant increases in valproate, lamotrigine, carbamazepine, and topiramate prescribing were detected. Among residents with seizures, ASMs without alternative indications were more common (59%), with marked reductions in phenobarbital and phenytoin but significant increases in levetiracetam and lacosamide use observed. Long-stay ASM use is changing. ASM gains are unrelated to seizure-epilepsy prevalence. ASM prescribing increased only among residents without seizures, where ASMs with expanded indications were preferred. Long-stay ASM prescribing and prescribing indication should be included in mandatory CMS reporting similar to other CNS-active medications.

Lacosamide exhibits neuroprotective effects in a rat model of Parkinson's disease

BackgroundParkinson's disease (PD) is a chronic and progressive neurodegenerative disorder that primarily affects the motor system. Although there are several treatments available to alleviate PD symptoms, there is currently no cure for the disease. Lacosamide, an anti-epileptic drug, has shown promising results in preclinical studies as a potential neuroprotective agent for PD. In this study, we aimed to investigate the neuroprotective effect of lacosamide in a murine model of PD. MethodsTwenty-one adult male rats were randomly divided into the following three groups (n = 7): 1 group received stereotaxical infusion of dimethyl sulfoxide (vehicle, group 1), and the others received stereotaxical infusion of rotenone (groups 2 and 3). The apomorphine-induced rotation test was applied to the rats after 10 days. Thereafter, group 2 was administered isotonic saline, whereas group 3 was administered lacosamide (20 mg/kg,i.p.) for 28 days. Apomorphine-induced rotation tests were performed to assess the effect of lacosamide on motor function. In addition, immunohistochemistry and biochemistry were used to assess the dopaminergic neuron loss in the substantia nigra and MDA, TNF-α and HVA levels, respectively. ResultsIn rats with Parkinson's disease induced by rotenone, levels of malondialdehyde and TNF-α significantly increased and HVA levels decreased, whereas in mice treated with lacosamide, levels of malondialdehyde and TNF-α significantly decreased and HVA levels increased. The apomorphine-induced rotation test scores of lacosamide-treated mice were lower compared with the untreated group. Furthermore, treatment with lacosamide significantly mitigated the degeneration of dopaminergic projections within the striatum originating from the substantia nigra and increased tyrosine hydroxylase (TH) immunofluorescence, indicative of preserved dopaminergic neuronal function. ConclusionIn conclusion, our study provides evidence that lacosamide has a neuroprotective effect on the rat model of PD. Further studies are required to investigate the underlying mechanisms and evaluate the potential clinical use of lacosamide as a neuroprotective agent for PD.

Real-world safety of Lacosamide: A pharmacovigilance study based on spontaneous reports in the FDA adverse event reporting system

IntroductionLacosamide is licensed for the treatment of focal seizures in both adults and children, however there is little information available on its adverse reactions. Using the FDA Adverse Event Reporting System (FAERS), we seek to assess adverse occurrences that may be related to Lacosamide. MethodsOn the basis of the FAERS database from the fourth quarter of 2008 to the second quarter of 2022, disproportionality analysis was carried out using the reporting odds ratio (ROR) method, the United Kingdom Medicines and Healthcare Products Regulatory Agency omnbius standard (MHRA) method, and the bayesian confidence propagation neural network (BCPNN) method. We extracted valuable positive signals for designated medical event (DME) screening, focused on the evaluation and comparison of safety signals appearing in DME with system organ classification (SOC) analysis. ResultsA total of 10,226 adverse reaction reports with Lacosamide as the primary suspect drug were obtained, with 30,960 reported cases, detecting 232 valuable positive signals, involving a total of 20 SOCs, of which the most frequently reported SOCs were nervous system disorders (6537 cases, 55.21%), psychiatric disorders (1530 cases, 12.92%), injury poisoning and procedural complications (1059 cases, 8.94%). According to 232 valuable positive signals with DME screening results, two signals of stevens-johnson syndrome and ventricular fibrillation were consistent with PT signals on the DME list, with the two SOCs focusing on skin and subcutaneous tissue disorders and cardiac disorders, respectively. ConclusionsOur research demonstrates that the clinical use of Lacosamide should be noticed and avoided in relation to ADRs since it raises the risk of cardiac arrest, ventricular fibrillation, stevens-johnson syndrome, and rhabdomyolysis.

Real-Life Efficacy and Tolerability of Lacosamide in Pediatric Patients Aged 4 Years or Older with Drug-Resistant Epilepsy

Purpose: The aim of this study was to evaluate the efficacy and safety of adjunctive lacosamide therapy in pediatric patients aged ≥4 years with drug-resistant epilepsy (DRE).Methods: Medical records of children aged 4 to 19 years treated with lacosamide as adjunctive therapy for DRE were retrospectively reviewed. The patients were divided into two groups according to their age at the start of lacosamide treatment: group A (aged 4–15 years) and group B (aged 16–19 years). Changes in seizure frequency from baseline, adverse events, and the retention rate were evaluated at each follow-up visit.Results: Sixty-two patients (33 males and 29 females) with a mean age of 11.4 years (range, 4 to 19) were included. The mean duration of follow-up was 20.1±12.9 months. The mean maintenance dose of lacosamide was 6.7±4.8 mg/kg/day. Forty-two patients (67.7%) were responders (≥50% reduction in seizures) with 19.4% (12/62) achieving freedom from seizures. The response rate did not differ significantly between groups A and B (67.6% vs. 68.0%, <i>P</i>=0.795) and was not affected by the concomitant use of sodium channel blockers. Significant independent factors associated with a good response to lacosamide treatment were a shorter duration of epilepsy (<i>P</i>=0.035) and fewer concomitant anti-seizure medications (<i>P</i>=0.002). Mild transient adverse events were observed in 20 patients (32.3%).Conclusion: Lacosamide adjunctive therapy was efficacious and tolerated in children aged ≥4 years with DRE. Early use of lacosamide may be helpful for a good response to drug-resistant seizures.

Risk of delirium with antiepileptic drug use: a study based on the Japanese Adverse Drug Event Report database.

Antiepileptic drugs may cause delirium, and the risk may vary with each drug. However, related studies have provided inconsistent results. The aim of this study was to investigate whether the use of antiepileptic drugs is a risk factor for delirium development. Using the Japanese Adverse Drug Event Report database, we analysed 573,316 reports pertaining to the period from 2004 to 2020. Reporting odds ratios and 95% confidence intervals of delirium associated with use of antiepileptic drugs were calculated after adjusting for potential confounders. Furthermore, for each antiepileptic drug, we performed an analysis stratified based on older age and benzodiazepine receptor agonist usage. There were 27,439 reports of antiepileptic drug-related adverse events. Of these, 191 reports were associated with antiepileptic drugs and delirium (crude reporting odds ratio [cROR], 1.66; 95% confidence interval [CI], 1.43-1.93). The use of lacosamide (adjusted reporting odds ratio [aROR], 2.44; 95% CI, 1.24-4.80), lamotrigine (aROR, 1.54; 95% CI, 1.05-2.26), levetiracetam (aROR, 1.91; 95% CI, 1.35-2.71), and valproic acid (aROR, 1.49; 95% CI, 1.16-1.91) was related to a significantly higher reporting odds ratio for delirium, even after adjustment for possible confounding factors. However, when used in combination with benzodiazepine receptor agonists, none of the antiepileptic drugs were found to be associated with delirium. Our study's findings suggest that antiepileptic drug usage may be associated with delirium development.

Tolerability and Safety of Lacosamide in Neonatal Population.

Lacosamide is a newer antiepileptic medication used in refractory neonatal seizures with limited safety and efficacy data. This case series spans 4 years and includes 38 neonates cared for in the neonatal, pediatric, and cardiovascular intensive care units, who received lacosamide for refractory seizures. Because lacosamide affects atrioventricular node function in adults, among other metrics, electrocardiogram (ECG) changes were monitored closely in these neonates. Within this cohort, 2 neonates were found to have atrial bigeminy on ECG and telemetry. Otherwise, lacosamide was generally well tolerated with sleepiness being the most common symptom noted. This case series reports data on the tolerability of lacosamide and emphasizes the importance of monitoring key cardiac intervals with ECG before and after the use of lacosamide in this population.

Use of lacosamide in children: experience of a tertiary medical care center in Brazil.

Lacosamide (LCM) is a third-generation anti-seizure drug approved in Europe and the United States, either as a monotherapy or adjunctive therapy, to treat partial-onset seizures in adults, adolescents, and children. In Brazil, LCM is licensed for treatment only in patients older than 16 years of age. To evaluate a cohort of children presenting with refractory epilepsy who received LCM as an add-on therapy and observe the response and tolerability to the LCM treatment. A retrospective cohort study conducted in a tertiary health care facility, which included 26 children, aged up to 16 years, who presented with refractory epilepsy and received LCM as an add-on treatment. The follow-up visits were scheduled every 3 months until 9 months of treatment with LCM. After 3 months of LCM administration, in 73.1% of the children, there was a reduction of > 50% in the frequency of seizures, and this clinical improvement was maintained in most patients (73.9%) for the following 9 months. Mild (such as, somnolence and behavioral changes) or severe (seizure worsening) adverse effects were observed in two and three children respectively. Among responders to LCM, there was a higher prevalence of males, fewer concomitant anti-seizure drugs, and lower percentage of patients using sodium channel blockers. Lacosamide should be considered as an early treatment option in pediatric patients with refractory epilepsy, mainly focal seizures.

Lacosamide decreases neonatal seizures without increasing apoptosis.

Many seizing neonates fail to respond to first-line anticonvulsant medications. Phenobarbital, an allosteric modulator of γ-aminobutyric acid type A (GABAA ) receptors, has low efficacy in treating neonatal seizures and causes neuronal apoptosis. Nonetheless, it is one of the most used anticonvulsants in this age group. In neonatal mice, phenobarbital's poor effectiveness is due in part to high intraneuronal chloride concentration, which causes GABA to exert depolarizing actions. Therefore, another approach to treat neonatal seizures could be to use anticonvulsants that do not rely on GABAergic modulation. We evaluated whether lacosamide decreases seizures in neonatal mice and whether it increases apoptosis in vitro and in vivo. In vitro, we measured the effect of different lacosamide concentrations on seizure-like activity induced by the pro-convulsant drug 4-aminopyridine in neocortical brain slices (layer IV/V) from neonatal (postnatal day 8-11) and adult (1-1.6 months old) C57BL/6J mice. In vivo, we recorded the effect of different lacosamide concentrations on neonatal behavioral seizures induced by kainic acid. We studied neocortical apoptosis in vitro and in vivo, measuring terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling signal and cleaved-caspase 3. Lacosamide reduced epileptiform activity in neocortical brain slices of neonates and adults in a concentration-dependent manner. In vivo, lacosamide reduced the duration and number of behavioral seizures. Lacosamide did not increase total or neuronal apoptosis in the neocortex in vitro or in vivo. Lacosamide reduces neocortical seizure-like activity in neonatal mice in vitro and in vivo without an acute increase in apoptosis. Our results support the use of lacosamide to treat neonatal seizures, with the advantage of not increasing apoptosis acutely.

Changes in the Use of Brand Name and Generic Medications and Total Prescription Cost Among Medicare Beneficiaries With Epilepsy.

To characterize trends in antiseizure medication (ASM) fills and total prescription costs in people with epilepsy. This was a retrospective cohort study of beneficiaries with epilepsy (ASM, plus ICD codes) in a 20% random Medicare sample, with continuous Fee-For-Service coverage (Parts A, B, and D) in 2008-2018. We summed the number of pill days and costs (adjusted to 2018 dollars) per person-year for each ASM. ASMs were categorized into brand vs generic, first vs newer generation, and enzyme inducers vs noninducers. There were 77,000-133,000 beneficiaries with epilepsy per year. The most common ASM was phenytoin in 2008, which shifted to levetiracetam in 2018 (2008: phenytoin 25%, levetiracetam 14%; 2018: phenytoin 9%, levetiracetam 27%). Brand name (2008: 56%; 2018: 14%), first-generation (2008: 55%; 2018: 32%), and enzyme-inducing ASMs (2008: 44%; 2018: 24%) each decreased over time as a proportion of pill days. The number of brand pill days per person-year initially decreased (e.g., 2008: 250; 2009: 121; 2010: 96) but then plateaued (2013-2018: between 66 and 69) given a notable increase in lacosamide pill days per person (2008: 0; 2018: 20). Total brand name costs per year initially decreased 2008-2010 (2008: $150 million; 2010: $72 million) but then increased after 2010 (2018: $256 million). In 2018, brand name ASMs represented 79% of costs despite representing only 14% of pill days, a 1-year pill supply became 277% more expensive for brand name medications but 42% less expensive for generic medications over time (2008: brand ∼$2,800 vs generic ∼$800; 2018: brand ∼$10,700 vs generic ∼$460), and many common brand name ASMs cost approximately 10-fold more per pill day than their generic equivalents. First-generation and enzyme-inducing ASMs waned from 2008 to 2018. Although brand name ASMs initially waned translating into lower costs and potentially higher value care, after 2010, brand name costs markedly increased because of increasing use of lacosamide plus a 277% increase in per-pill cost of brand name ASMs. Brand name ASMs represented a minority of prescriptions, but the majority of costs.

Antiseizure medication treatment pathways for US Medicare beneficiaries with newly treated epilepsy.

ObjectiveThis study was undertaken to characterize antiseizure medication (ASM) treatment pathways in Medicare beneficiaries with newly treated epilepsy.MethodsThis was a retrospective cohort study using Medicare claims. Medicare is the United States' federal health insurance program for people aged 65 years and older plus younger people with disabilities or end‐stage renal disease. We included beneficiaries with newly treated epilepsy (International Classification of Diseases codes for epilepsy/convulsions 2014–2017, no ASM in the previous 2 years). We displayed the sequence of ASM fills using sunburst plots overall, then stratified by mood disorder, age, and neurologist prescriber. We tabulated drug costs for each pathway.ResultsWe included 21 458 beneficiaries. Levetiracetam comprised the greatest number of pill days (56%), followed by gabapentin (11%) and valproate (8%). There were 22 288 unique treatment pathways. The most common pathways were levetiracetam monotherapy (43%), gabapentin monotherapy (10%), and valproate monotherapy (5%). Gabapentin was the most common second‐ and third‐line ASM. Whereas only 2% of pathways involved first‐line lacosamide, those pathways accounted for 19% of cost. Gabapentin and valproate use was increased and levetiracetam use was decreased in beneficiaries with mood disorders compared to beneficiaries without mood disorders. Levetiracetam use was increased and gabapentin, valproate, lamotrigine, and topiramate use was decreased in beneficiaries aged >65 years compared with those aged 65 years or less. Lamotrigine, levetiracetam, and lacosamide use was increased and gabapentin use was decreased in beneficiaries whose initial prescriber was a neurologist compared to those whose prescriber was not a neurologist.SignificanceLevetiracetam monotherapy was the most common pathway, although substantial heterogeneity existed. Lacosamide accounted for a small percentage of ASMs but a disproportionately large share of cost. Neurologists were more likely to prescribe lamotrigine compared with nonneurologists, and lamotrigine was prescribed far less frequently than may be endorsed by guidelines. Future work may explore patient‐ and physician‐driven factors underlying ASM choices.

Efficacy and Tolerability of Lacosamide in Lennox-Gastaut Syndrome: A Systematic Review and Meta-analysis.

Purpose Lennox–Gastaut syndrome (LGS) is one of the most difficult to treat childhood-onset epileptic encephalopathies. There is growing evidence that lacosamide is safe and efficacious in patients and adults with refractory epilepsy. However, the evidence regarding the efficacy of lacosamide in LGS is controversial so far. We aimed to evaluate the efficacy and tolerability of lacosamide in patients with LGS. Methods We conducted a systematic review on MEDLINE, EMBASE, COCHRANE CENTRAL, Google Scholar, and Web of Science, collating all available literature till July 31, 2020. The qualitative review included case reports, case series, and both controlled/uncontrolled trials as well as retrospective studies, but for determining pooled estimates, we only included studies with a sample size of 5 or more. The primary outcome was the efficacy of lacosamide in patients with LGS. Clinical variables related to efficacy and adverse events attributed to lacosamide were extracted from each publication. The pooled estimate of variables related to these parameters was performed using a random-effect model. Results Of the 68 items identified by the search, 14 were reviewed as full-text. Eleven articles including two prospective and six retrospective studies fulfilled eligibility criteria and described outcomes in 81 patients (42 adults, 39 children, 60% male, range—1.4–61 years). On average, 35.2%, 27.9%, 7.3%, and 29.4% patients had > 50% reduction, < 50% reduction, no change, and worsening of seizure frequency, respectively. Although 36% of patients had adverse events like somnolence, behavioral abnormalities including irritability, aggressiveness, nausea, tremor, memory problems, dizziness, gastrointestinal discomfort, vomiting, and weight loss, no serious adverse events were noted. Conclusion The evidence available in the current literature is not sufficient to support or refute the use of lacosamide in patients with LGS. Although it is one of the possible therapeutic options worth exploring in patients with LGS, caution is still necessary, as there are reports of worsening of seizure frequency in some patients.