UNASSIGNED: Focal epilepsy constitutes the most common epilepsy in children, and medical treatment represents the first-line therapy in this condition. The main goal of medical treatment for children and adolescents with epilepsy is the achievement of seizure freedom or, in drug-resistant epilepsies, a significant seizure reduction, both minimizing antiseizure medications (ASM)-related adverse events, thus improving the patient\'s quality of life. However, up to 20-40% of pediatric epilepsies are refractory to drug treatments. New ASMs came to light in the pediatric landscape, improving the drug profile compared to that of the preexisting ones. Clinicians should consider several factors during the drug choice process, including patient and medication-specific characteristics.
UNASSIGNED: This narrative review aims to summarize the latest evidence on the effectiveness and tolerability of the newest ASMs administered as monotherapy or adjunctive therapy in pediatric epilepsies with focal onset seizures, providing a practical appraisal based on the existing evidence.
UNASSIGNED: The latest ASMs have the potential to be effective in the pharmacological management of focal onset seizures in children, and treatment choice should consider several drug- and epilepsy-related factors. Future treatments should be increasingly personalized and targeted on patient-specific pathways. Future research should focus on discovering new chemical compounds and repurposing medications used for other indications.

Despite the many therapeutic options for epilepsy available today, a third of patients still have poorly controlled epilepsy. Over the years, their transition through lines of treatment exposes them to increased risk of disease progression, mortality, morbidity, mental distress, and not least significantly impaired quality of life (QoL). The present review explores the multiple factors contributing to the impairment of health-related QoL in PWE-including both seizure-related and non seizure-related. The analysis aims to identify potential areas of intervention and strategies for a more holistic approach to epilepsy care and inform policy-makers and healthcare providers in their approach to this condition.

UNASSIGNED: Although epilepsy is a common neurological condition, there is paucity of nationwide data on treatment patterns and sociodemographic and clinical factors affecting treatment decisions in India.
UNASSIGNED: To assess clinical profiles, usage pattern of antiepileptic drugs (AEDs), and seizure control among patients with epilepsy in India.
UNASSIGNED: This was a cross-sectional, observational, multicenter study on adult patients with epilepsy who were on AEDs for at least six months before enrollment. Data were collected from patient interviews and medical records.
UNASSIGNED: Out of 800 enrolled patients, a majority (69.0%) had generalized onset seizure in the six months before enrollment. The median age at epilepsy onset was 20.0 (1.0-64.0) years; 40.0% of the patients were females, 48.5% were married, 99.1% were literate, and 67.0% belonged to the lower or upper-middle socioeconomic class. Overall, 459 patients (57.4%) received AEDs as combination therapy. Most patients received levetiracetam (37.0%), sodium valproate (18.5%), carbamazepine (17.3%), or phenytoin (13.8%) as monotherapy, and clobazam (59.7%), levetiracetam (52.9%), carbamazepine (26.4%), sodium valproate (24.8%), or phenytoin (24.0%) in combination therapy. Quality of life was comparable for first- and third-generation AEDs. Adverse drug reactions were mostly attributed to dose modification or switching between drugs. No serious adverse drug reactions or new safety concerns were identified.
UNASSIGNED: Findings from this large, cross-sectional, observational, multicenter study indicate that first-generation AEDs sodium valproate and phenytoin continued to be used in a substantial number of patients on monotherapy and combination therapy in India, even though an increasing trend toward use of second-generation AEDs was noted in clinical practice.

Focal impaired awareness seizures (FIASs) are the most common seizure type in adults and are often refractory to medication. Management of FIASs is clinically challenging, and new interventions are needed for better seizure control. The amygdala-kindling model is a preclinical model of FIASs with secondary generalization. The present study assessed the efficacy of cannabidiol (CBD), ∆9-tetrahydrocannabinol (THC), and a combination of CBD and THC in a 15:1 ratio at suppressing focal and secondarily generalized seizures in the amygdala-kindled rat.
Fully kindled, male Sprague Dawley rats, with bipolar electrodes implanted in the right amygdala, were given either CBD (0-320 mg/kg), THC (0-40 mg/kg), or a combination of CBD and THC (15:1 ratio, multiple doses) intraperitoneally. Suprathreshold kindling stimulation was administered 1 h (THC) or 2 h (CBD) after drug injection, and outcomes were assessed using focal electroencephalographic recording and the Racine seizure scale.
CBD alone produced a partial suppression of both generalized seizures (median effective dose [ED50 ] = 283 mg/kg) and focal seizures (ED40 = 320 mg/kg) at doses that did not produce ataxia. THC alone also produced partial suppression of generalized (ED50 = 10 mg/kg) and focal (ED50 = 30 mg/kg) seizures, but doses of 10 mg/kg and above produced hypolocomotion, although not ataxia. The addition of a low dose of THC to CBD (15:1) left-shifted the CBD dose-response curve, producing much lower ED50 s for both generalized (ED50 = 26 + 1.73 mg/kg) and focal (ED50 = 40 + 2.66 mg/kg) seizures. No ataxia or hypolocomotion was seen at these doses of the CBD + THC combination.
CBD and THC both have antiseizure properties in the amygdala-kindling model, although THC produces suppression of the amygdala focus only at doses that produce hypolocomotion. The addition of small amounts of THC greatly improves the effectiveness of CBD. A combination of CBD and THC might be useful for the management of FIASs.

UNASSIGNED: Epilepsy is a common neurological ailment contributing to significant disability. About one-third of all epilepsy patients would be refractory to two or more medications. Brivaracetam (BRV) is one of the newer anti-seizure medications on which extensive data is available, but its efficacy as an early add-on agent (first/second adjuvant) is unclear. The principal objective of this review is to assess the efficacy of BRV as an early add-on agent in refractory Focal Onset Seizures (FOS) and its pharmacology and usage in various clinical situations associated with seizures.
UNASSIGNED: We searched two databases, Medline and Cochrane Central, for papers on BRV and FOS, and selected six studies with randomized parallel control design to extract the data for a meta-analysis. We also did a comprehensive review of the available literature on its pharmacology and usage in various clinical scenarios associated with seizures.
UNASSIGNED: For the meta-analysis, we extracted 145 articles; six studies fulfilled the selection criteria that gave us data on 1938 patients who received Brivaracetam as an early add-on agent in FOS. The Risk Ratio (RR) (95% CI) for 50% responders across the trials was 1.88 (1.55-2.29). Similarly, the overall RR (95% CI) was 5.82 (2.15-15.70) for seizure freedom.
UNASSIGNED: Our analysis provides moderate evidence for Brivaracetam as an effective agent as an early adjuvant in FOS. Its efficacy for several other indications needs further clinical trials and evaluation.

Epilepsy is one of the most common neurological disorders, affecting approximately 50 million people worldwide. Despite a dramatic increase in treatment options over the past 30 years, it still ranks fourth in the world\'s disease burden. There are now close to 30 antiepileptic drugs (AEDs), with more than two thirds introduced to the market after carbamazepine (CBZ) and one third after its derivative, oxcarbazepine (OXC). Following the introduction of these newer AEDs, the role of CBZ and OXC in the therapeutic armamentarium for seizure control and effective epilepsy management needs to be reviewed. The main guidelines list both CBZ and OXC as first-line options or second-line alternatives for the treatment of focal-onset epilepsy and primary generalized tonic-clonic seizures. While evidence suggests that overall AEDs have similar efficacy, some newer AEDs may be better tolerated than CBZ. In line with this, there have been changes in treatment patterns, with many variations across different countries. However, CBZ remains among the two or three most prescribed drugs for focal epilepsy in many countries, and is widely used across Europe, Africa, South America, and Asia, where it represents a good compromise between cost, availability, and effectiveness. OXC is among the first-choice options for the initial treatment of focal-onset seizures in several countries, including the US and China, where the oral suspension is commonly prescribed. This review provides guidance on the optimal use of these two drugs in clinical practice, including in children, the elderly, and in pregnancy.

To evaluate the efficacy and safety of pregabalin as adjunctive treatment for children (aged 1 month-<4 years) with focal onset seizures (FOS) using video-electroencephalography (V-EEG).
This randomized, placebo-controlled, international study included V-EEG seizure monitoring (48-72 hours) at baseline and over the last 3 days of 14-day (5-day dose escalation; 9-day fixed dose) double-blind pregabalin treatment (7 or 14 mg/kg/d in three divided doses). This was followed by a double-blind 1-week taper. The primary efficacy endpoint was log-transformed seizure rate (loge [24-hour seizure rate + 1]) for all FOS recorded during the double-blind V-EEG monitoring, evaluated in subjects who took ≥1 dose of study medication, experienced ≥1 baseline seizure(s), and had a treatment phase V-EEG. Safety and tolerability were assessed by adverse events (AEs), clinical laboratory data, physical/neurological examinations, vital signs, and electrocardiograms.
Overall, 175 patients were randomized (mean age = 28.2 months; 59% male, 69% white, 30% Asian) in a 2:1:2 ratio to pregabalin 7 or 14 mg/kg/d (n = 71 or n = 34, respectively), or placebo (n = 70). Pregabalin 14 mg/kg/d (n = 28) resulted in a statistically significant 35% reduction of loge (24-hour seizure rate + 1) versus placebo (n = 53; P = .022), an effect that was not observed with pregabalin 7 mg/kg/d (n = 59; P = .461). The most frequently reported treatment-emergent AEs for pregabalin 7 mg/kg/d, 14 mg/kg/d, and placebo, respectively, were somnolence (11.3%, 17.6%, and 5.7%) and upper respiratory tract infection (7.0%, 11.8%, and 11.4%). All AEs were mild to moderate in severity.
Pregabalin 14 mg/kg/d (but not 7 mg/kg/d) significantly reduced seizure rate in children with FOS, when assessed using V-EEG, compared with placebo. Both pregabalin dosages were generally safe and well tolerated in children 1 month to <4 years of age with FOS. Safety and tolerability were consistent with the known profile of pregabalin in older children with epilepsy.

Introduction: Zonisamide is a benzisoxazole with 3-methanesulfonamide side chain, chemically unrelated with other anticonvulsants, and approved as mono-therapy of newly diagnosed focal epilepsy with or without secondary generalization in adults or adjunctive therapy in the treatment of partial seizures, with or without secondary generalization, in adults, adolescents, and children aged 6 years and above.Areas covered: Pharmacokinetics, clinical efficacy, and the adverse effects of zonisamide are discussed in the article. The discussion is based on data from published preclinical studies, clinical trials, observational studies, systematic reviews, and approved summary of product characteristics.Expert opinion: Zonisamide is an anticonvulsant with multiple mechanisms of action on neuronal tissue, which achieves seizure freedom in more than 80% of patients with newly-onset focal epilepsy and in 6.2 to 18.1% of patients with focal onset seizures inadequately controlled by first-line anticonvulsants. Within the recommended dose range, it follows linear kinetic of elimination; it is metabolized in the liver by two cytochrome isoforms, so pharmacokinetic interactions are rare and with little clinical significance. Up to 10% of patients taking zonisamide will have problems with weight loss and more than 10% with irritability, confusion or depression, and long-lasting therapy may cause renal calculi in 1.2% of patients.

Efficacy and safety of pregabalin as adjunctive treatment for children (aged 4-16 years) with partial-onset seizures, hereafter termed focal onset seizures for this study, was evaluated. This double-blind, randomized, placebo-controlled, international study had 3 phases: 8-week baseline, 12-week double-blind treatment (2-week dose escalation; 10-week fixed dose), and 1-week taper. Selection criteria included experiencing focal onset seizures and receiving a stable regimen of 1 to 3 antiepileptic drugs. Study treatments were pregabalin 2.5 mg/kg/d, 10 mg/kg/d, or placebo; doses were increased to 3.5 or 14 mg/kg/d for subjects weighing <30 kg. The key endpoints were change in loge(28-day seizure rate), achieving a ≥50% seizure responder rate, safety, and tolerability during double-blind treatment. Subjects (n = 295; mean age 10.2 years, 55% male, 69% white) were randomized to pregabalin 2.5 mg/kg/d (n = 104), 10 mg/kg/d (n = 97), or placebo (n = 94). A statistically significant reduction in loge(28-day seizure rate) was demonstrated with pregabalin 10 mg/kg/d (a 19.9% improvement over placebo; P = .0185). Seizure frequency was numerically improved (statistically nonsignificant) with pregabalin 2.5 mg/kg/d ( P = .2577). Responder rate significantly favored pregabalin 10 mg/kg/d (40.6%, P = .0068) compared with placebo (22.6%) and was numerically improved with pregabalin 2.5 mg/kg/d (29.1%, P = .2600). Common adverse events (≥10% of any group) in 10 mg/kg/d, 2.5 mg/kg/d, and placebo groups, respectively, included somnolence (25.8%, 17.3%, 13.8%), increased weight (13.4%, 3.8%, 4.3%), and increased appetite (10.3%, 6.7%, 4.3%). Pregabalin 10 mg/kg/d demonstrated efficacy in seizure frequency reduction in children with focal onset seizures compared with placebo, and both pregabalin doses were generally safe and well tolerated. www.clinicialtrials.gov identifier NCT01389596; EudraCT #2010-020852-79.

We assessed the efficacy and safety of once-daily eslicarbazepine acetate in comparison with twice-daily (BID) controlled-release carbamazepine (carbamazepine-CR) monotherapy in newly diagnosed focal epilepsy patients.
This randomized, double-blind, noninferiority trial (NCT01162460) utilized a stepwise design with 3 dose levels. Patients who remained seizure-free for the 26-week evaluation period (level A: eslicarbazepine acetate 800 mg/carbamazepine-CR 200 mg BID) entered a 6-month maintenance period. If a seizure occurred during the evaluation period, patients were titrated to the next target level (level B: eslicarbazepine acetate 1200 mg/carbamazepine-CR 400 mg BID, level C: eslicarbazepine acetate 1600 mg/carbamazepine-CR 600 mg BID) and the evaluation period began again. The primary endpoint was the proportion of seizure-free patients for 6 months after stabilization in the per protocol set. The predefined noninferiority criteria were -12% absolute and -20% relative difference between treatment groups.
Eight hundred fifteen patients were randomly assigned; 785 (388 in the eslicarbazepine acetate group and 397 in the carbamazepine-CR group) were included in the per protocol set, and 813 (401 in the eslicarbazepine acetate group and 412 in the carbamazepine-CR group) were included in the full analysis set for the primary analysis. Overall, 71.1% of eslicarbazepine acetate-treated patients and 75.6% of carbamazepine-CR-treated patients were seizure-free for ≥6 months at the last evaluated dose (average risk difference = -4.28%, 95% confidence interval [CI] = -10.30 to 1.74; relative risk difference = -5.87%, 95% CI = -13.50 to 2.44) in the per protocol set. Rates of treatment-emergent adverse events were similar between groups for patients in the safety set. Noninferiority was also demonstrated in the full analysis set, as 70.8% of patients with eslicarbazepine acetate and 74.0% with carbamazepine-CR were seizure-free at the last evaluated dose (average risk difference = -3.07, 95% CI = -9.04 to 2.89).
Treatment with eslicarbazepine acetate was noninferior to BID carbamazepine-CR. With its once-daily formulation, eslicarbazepine acetate provides a useful option for first-line monotherapy for adults with newly diagnosed epilepsy and focal onset seizures.