levetiracetam and Epilepsies--Partial

Levetiracetam (LEV) is an antiseizure medication (ASM) whose mechanism of action involves the modulation of neurotransmitters release through binding to the synaptic vesicle glycoprotein 2A. It is a broad-spectrum ASM displaying favorable pharmacokinetic and tolerability profiles. Since its introduction in 1999, it has been widely prescribed, becoming the first-line treatment for numerous epilepsy syndromes and clinical scenarios. However, this might have resulted in overuse. Increasing evidence, including the recently published SANAD II trials, suggests that other ASMs are reasonable therapeutic options for generalized and focal epilepsies. Not infrequently, these ASMs show better safety and effectiveness profiles compared to LEV (partially due to the latter's well-known cognitive and behavioral adverse effects, present in up to 20% of patients). Moreover, it has been shown that the underlying etiology of epilepsy is significantly linked to ASMs response in particular scenarios, highlighting the importance of an etiology-based ASM choice. In the case of LEV, it has demonstrated an optimal effectiveness in Alzheimer's disease, Down syndrome, and PCDH19-related epilepsies whereas, in other etiologies such as malformations of cortical development, it may show negligible effects. This narrative review analyzes the current evidence related to the use of LEV for the treatment of seizures. Illustrative clinical scenarios and practical decision-making approaches are also addressed, therefore aiming to define a rational use of this ASM.

Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy; Expert Testimony; Humans; Levetiracetam; Protocadherins

To compare the efficacy and safety of Levetiracetam (LEV) and Oxcarbazepine (OXC) as monotherapy for the treatment of newly diagnosed focal epilepsy.. We searched PubMed, Cochrane Library, EMBASE, and Google Scholar from January 1, 2000 to May 11, 2022, with no language restrictions along with The ClinicalTrials.gov website and the WHO International Controlled Trials Registry platforms. We pooled the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for the efficacy and safety outcomes. The quality of included trials was assessed using the Cochrane Collaboration's tool.. Two RCTs included a total of 574 newly diagnosed focal epilepsy patients (the LEV group [282 patients] and the OXC group [292 patients]). LEV group when compared with the OXC group had no significant difference in the pooled estimate of seizure freedom at week 24. (RR: 0.81; 95% CI: 0.62-1.05, p = .11). Similarly, there was no significant difference in the pooled estimate of withdrawal due to adverse events (AEs) (RR: 0.87; 95% CI: 0.34-2.23, p = .77). The commonly reported AEs in both trials were dizziness, headache, rash, somnolence, and nasopharyngitis with zero medication-related death and few serious AEs.. LEV is noninferior to OXC in terms of seizure freedom at week 24 and treatment withdrawal rate due to AEs among adults but long-term treatment data is still missing. Future multicentric double-blinded RCTs and real-world studies are of great need.

Topics: Adult; Anticonvulsants; Epilepsies, Partial; Humans; Levetiracetam; Oxcarbazepine

To assess the efficacy and safety of levetiracetam (LEV) as adjunctive treatment in children (0-18 years) with focal-onset seizures (FOS) with a larger dataset.. A pooled analysis would be performed for prospective clinical trials and a meta-analysis for controlled studies. Retrospectives studies were also summarized using descriptive statistics.. Thirty-one articles (1763 patients) were identified, eighteen prospective self-controlled studies and thirteen retrospective studies. LEV was more effective than placebo, the pooled risk ratios (RRs) and 95% confidence intervals (CIs) for the 50% responder rate, seizure freedom rate and the median percentage reduction rate were 1.98 (1.49-2.63), 5.12 (2.09-12.51) and 3.19 (2.37-4.30), respectively. The overall response rates (ORRs) and 95% CIs were 56% (52%-60%), 14% (9%-19%) and 55% (31%-79%), respectively. For safety assessment, the pooled RRs and 95% CIs for the at least one treatment-emergent adverse events (TEAE) rate and at least one adverse drug reactions related (ADR-related) TEAE rate were 1.03 (0.94-1.13) and 1.45 (1.13-1.86) between two group. The ORRs and 95% CIs were 74% (54%-94%) and 48% (40%-55%). The adverse events significantly associated with LEV were somnolence 2.26 (95% CI 1.30-3.93) and hostility 2.33 (95% CI 1.15-4.70). The most frequency adverse events were pyrexia, headache, nervousness, upper respiratory tract and somnolence. The RRs for withdrawal rate or the ADR-related withdrawal rate were 0.77 (95% CI 0.44-1.38) and 0.91 (0.42-1.98), the ORRs were 17% (5%-28%) and 6% (4%-8%).. The meta-analysis suggested that add-on LEV can significantly reduce seizure frequency and fairly tolerated compared to placebo.

Topics: Anticonvulsants; Child; Epilepsies, Partial; Humans; Levetiracetam

Epilepsy is a common neurological disease that affects approximately 1% of the UK population. Approximately one-third of these people continue to have seizures despite drug treatment. Pregabalin is one of the newer antiepileptic drugs which have been developed to improve outcomes.This is an updated version of the Cochrane Review published in Issue 3, 2014, and includes three new studies.. To assess the efficacy and tolerability of pregabalin when used as an add-on treatment for drug-resistant focal epilepsy.. For the latest update we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), on 5 July 2018, MEDLINE (Ovid, 1946 to 5 July 2018), ClinicalTrials.gov (5 July 2018), and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 5 July 2018), and contacted Pfizer Ltd, manufacturer of pregabalin, to identify published, unpublished, and ongoing trials.. We included randomised controlled trials comparing pregabalin with placebo or an alternative antiepileptic drug as an add-on for people of any age with drug-resistant focal epilepsy. Double-blind and single-blind trials were eligible for inclusion. The primary outcome was 50% or greater reduction in seizure frequency; secondary outcomes were seizure freedom, treatment withdrawal for any reason, treatment withdrawal due to adverse effects, and proportion of individuals experiencing adverse effects.. Two review authors independently selected and assessed trials for eligibility and extracted data. Analyses were by intention-to-treat. We presented results as risk ratios (RR) and odds ratios (OR) with 95% confidence intervals (CIs). Two review authors assessed the included studies for risk of bias using the Cochrane 'Risk of bias' tool.. We included nine industry-sponsored randomised controlled trials (3327 participants) in the review. Seven trials compared pregabalin to placebo. For the primary outcome, participants randomised to pregabalin were significantly more likely to attain a 50% or greater reduction in seizure frequency compared to placebo (RR 2.28, 95% CI 1.52 to 3.42, 7 trials, 2193 participants, low-certainty evidence). The odds of response doubled with an increase in dose from 300 mg/day to 600 mg/day (OR 1.99, 95% CI 1.74 to 2.28), indicating a dose-response relationship. Pregabalin was significantly associated with seizure freedom (RR 3.94, 95% CI 1.50 to 10.37, 4 trials, 1125 participants, moderate-certainty evidence). Participants were significantly more likely to withdraw from pregabalin treatment than placebo for any reason (RR 1.35, 95% CI 1.11 to 1.65, 7 trials, 2193 participants, moderate-certainty evidence) and for adverse effects (RR 2.65, 95% CI 1.88 to 3.74, 7 trials, 2193 participants, moderate-certainty evidence).Three trials compared pregabalin to three active-control drugs: lamotrigine, levetiracetam, and gabapentin. Participants allocated to pregabalin were significantly more likely to achieve a 50% or greater reduction in seizure frequency than those allocated to lamotrigine (RR 1.47, 95% CI 1.03 to 2.12, 1 trial, 293 participants) but not those allocated to levetiracetam (RR 0.94, 95% CI 0.80 to 1.11, 1 trial, 509 participants) or gabapentin (RR 0.96, 95% CI 0.82 to 1.12, 1 trial, 484 participants). We found no significant differences between pregabalin and lamotrigine (RR 1.39, 95% CI 0.40 to 4.83) for seizure freedom, however, significantly fewer participants achieved seizure freedom with add-on pregabalin compared to levetiracetam (RR 0.50, 95% CI 0.30 to 0.85). No data were reported for this outcome for pregabalin versus gabapentin. We found no significant differences between pregabalin and lamotrigine (RR 1.07, 95% CI 0.75 to 1.52), levetiracetam (RR 1.03, 95% CI 0.71 to 1.49), or gabapentin (RR 0.78, 95% CI 0.57 to 1.07) for treatment withdrawal due to any reason or due to adverse effects (pregabalin versus lamotrigine: RR 0.89, 95% CI 0.53 to 1.48; versus levetiracetam: RR 1.29, 95% CI 0.66 to 2.54; versus gabapentin: RR 1.07, 95% CI 0.54 to 2.11). Ataxia, dizziness, somnolence, weight gain, and fatigue were significantly associated with pregabalin.We rated the overall risk of bias in the included studies as low or unclear due to the possibility of. Pregabalin, when used as an add-on drug for treatment-resistant focal epilepsy, is significantly more effective than placebo at producing a 50% or greater seizure reduction and seizure freedom. Results demonstrated efficacy for doses from 150 mg/day to 600 mg/day, with increasing effectiveness at 600 mg doses, however issues with tolerability were noted at higher doses. The trials included in this review were of short duration, and longer-term trials are needed to inform clinical decision making.

Topics: Anticonvulsants; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsies, Partial; Gabapentin; Humans; Lamotrigine; Levetiracetam; Pregabalin; Randomized Controlled Trials as Topic; Seizures

To estimate the comparative efficacy among antiepileptic drugs in the pediatric population (0-18 years).. Using the Embase and MEDLINE databases, we updated to February 2017 the search strategy of the National Institute for Health and Care Excellence guidelines for epilepsy. We only included randomized clinical trials conducted in children and mixed-age populations. According to the PRISMA network meta-analysis guideline, the study-level quality assessment was made with the Cochrane risk-of-bias tool. Three investigators independently selected articles. The efficacy outcome was considered to be seizure freedom or ≥50% seizure reduction.. We selected 46 randomized clinical trials. A total of 5652 individuals were randomized to 22 antiepileptic drugs and placebo. The point estimates of carbamazepine and lamotrigine efficacy showed their superiority with respect to all comparator antiepileptic drugs for the treatment of newly diagnosed focal epilepsy. In refractory focal epilepsy, levetiracetam (odds ratio [OR] = 3.3, 95% credible interval [CrI] = 1.3-7.6) and perampanel (OR = 2.5, 95% CrI = 1.1-5.8) were more effective compared to placebo. Ethosuximide and valproic acid were both superior to lamotrigine against absence seizures. The OR point estimate showed the superiority of adrenocorticotropic hormone over all comparators in infantile spasms. A wide heterogeneity in the length of follow-up was observed among the studies.. This network meta-analysis suggests that the quality of studies should be improved through the use of comparative designs, relevant outcomes, appropriate follow-up length, and more reliable inclusion criteria.

Topics: Adolescent; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Drug Resistant Epilepsy; Epilepsies, Partial; Epilepsy; Epilepsy, Absence; Ethosuximide; Hormones; Humans; Infant; Lamotrigine; Levetiracetam; Network Meta-Analysis; Nitriles; Odds Ratio; Piracetam; Pyridones; Spasms, Infantile; Treatment Outcome; Triazines; Valproic Acid

Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for partial onset seizures and sodium valproate for generalised onset seizures; however a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices.. To compare the time to withdrawal of allocated treatment, remission and first seizure of 10 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide) currently used as monotherapy in children and adults with partial onset seizures (simple partial, complex partial or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus).. We searched the following databases: Cochrane Epilepsy's Specialised Register, CENTRAL, MEDLINE and SCOPUS, and two clinical trials registers. We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field. The date of the most recent search was 27 July 2016.. We included randomised controlled trials of a monotherapy design in adults or children with partial onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types).. This was an individual participant data (IPD) review and network meta-analysis. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary outcomes were 'time to achieve 12-month remission', 'time to achieve six-month remission', 'time to first seizure post-randomisation', and 'occurrence of adverse events'. We presented all time-to-event outcomes as Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs). We performed pairwise meta-analysis of head-to-head comparisons between drugs within trials to obtain 'direct' treatment effect estimates and we performed frequentist network meta-analysis to combine direct evidence with indirect evidence across the treatment network of 10 drugs. We investigated inconsistency between direct estimates and network meta-analysis via node splitting. Due to variability in methods and detail of reporting adverse events, we have not performed an analysis. We have provided a narrative summary of the most commonly reported adverse events.. IPD was provided for at least one outcome of this review for 12,391 out of a total of 17,961 eligible participants (69% of total data) from 36 out of the 77 eligible trials (47% of total trials). We could not include IPD from the remaining 41 trials in analysis for a variety of reasons, such as being unable to contact an author or sponsor to request data, data being lost or no longer available, cost and resources required to prepare data being prohibitive, or local authority or country-specific restrictions.We were able to calculate direct treatment effect estimates for between half and two thirds of comparisons across the outcomes of the review, however for many of the comparisons, data were contributed by only a single trial or by a small number of participants, so confidence intervals of estimates were wide.Network meta-analysis showed that for the primary outcome 'Time to withdrawal of allocated treatment,' for individuals with partial seizures; levetiracetam performed (statistically) significantly better than both current first-line treatments carbamazepine and lamotrigine; lamotrigine performed better than all other treatments (aside from levetiracetam), and carbamazepine performed significantly better than gabapentin and phenobarbitone (high-quality evidence). For individuals with generalised onset seizures, first-line treatment sodium valproate performed significantly better than carbamazepine, topiramate and phenobarbitone (moderate- to high-quality evidence). Furthermore, for both partial and generalised onset seizures, the earliest licenced treatment, phenobarbitone seems to perform worse than all other treatments (moderate- to high-quality evidence).Network meta-analysis also showed that for secondary outcomes 'Time to 12-month remission of seizures' and 'Time to six-month remission of seizures,' few notable differences were shown for either partial or generalised seizure types (moderate- to high-quality evidence). For secondary outcome 'Time to first seizure,' for individuals with partial seizures; phenobarbitone performed significantly better than both current first-line treatments carbamazepine and lamotrigine; carbamazepine performed significantly better than sodium valproate, gabapentin and lamotrigine. Phenytoin also performed significantly better than lamotrigine (high-quality evidence). In general, the earliest licenced treatments (phenytoin and phenobarbitone) performed better than the other treatments for both seizure types (moderate. Overall, the high-quality evidence provided by this review supports current guidance (e.g. NICE) that carbamazepine and lamotrigine are suitable first-line treatments for individuals with partial onset seizures and also demonstrates that levetiracetam may be a suitable alternative. High-quality evidence from this review also supports the use of sodium valproate as the first-line treatment for individuals with generalised tonic-clonic seizures (with or without other generalised seizure types) and also demonstrates that lamotrigine and levetiracetam would be suitable alternatives to either of these first-line treatments, particularly for those of childbearing potential, for whom sodium valproate may not be an appropriate treatment option due to teratogenicity.

Topics: Adult; Amines; Anticonvulsants; Carbamazepine; Child; Cyclohexanecarboxylic Acids; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Network Meta-Analysis; Oxcarbazepine; Phenobarbital; Phenytoin; Piracetam; Remission Induction; Topiramate; Triazines; Valproic Acid; Zonisamide

Brivaracetam (BRV) is a new AED currently licensed for the adjunctive treatment of adult patients with focal epilepsies. It is a ligand of the ubiquitous synaptic vesicle glycoprotein 2A (SV2A). Areas covered: This paper covers the preclinical and subsequent clinical development of BRV focusing on the discovery of the SV2A protein as the main target for levetiracetam (LEV) and the main similarities and differences between LEV and BRV in terms of pharmacodynamic and pharmacokinetic properties. Phase II and Phase III studies are also presented and data from post-marketing phase IV studies are discussed. Expert opinion: The preclinical development of BRV is quite unique and has raised several doubts on current methodologies adopted for AED development, reinforcing the need for new approaches. The preclinical and clinical profile suggest that BRV is potentially an ideal compound in the emergency setting given the rapid onset of action associated with being water soluble and, therefore, available in intravenous formulation. In addition, data from Phase III studies have already suggested that BRV may be effective not only in focal epilepsies but also in generalised syndromes. Further data from special populations such as children and women of child bearing age are urgently needed.

Topics: Adult; Animals; Anticonvulsants; Drug Discovery; Epilepsies, Partial; Humans; Levetiracetam; Ligands; Membrane Glycoproteins; Nerve Tissue Proteins; Piracetam; Pyrrolidinones; Solubility

In 4 Phase III registration trials (3 in patients with partial seizures, N=1480; 1 in patients with PGTCS, N=163), perampanel administered to patients already receiving 1-3 concomitant antiepileptic drugs (AEDs) demonstrated statistically superior efficacy compared to placebo in reducing seizure frequency. However, use of perampanel in these studies was associated with a risk of psychiatric and behavioral adverse reactions, including aggression, hostility, irritability, anger, and homicidal ideation and threats. The present study is a post hoc analysis of pooled data from these 4 trials to determine if concomitant treatment with levetiracetam and/or topiramate increased the risk of hostility- and aggression-related AEs. Treatment-emergent AEs (TEAEs) were determined using a "Narrow & Broad" search based on the Medical Dictionary for Regulatory Activities (MedDRA) standard MedDRA query (SMQ) for hostility- and aggression-related events. The rate of hostility- and aggression-related TEAEs was observed to be similar among perampanel-treated patients: a) receiving levetiracetam (N=340) compared to those not receiving levetiracetam (N=779); b) receiving topiramate (N=223) compared to those not receiving topiramate (N=896); and c) receiving both levetiracetam and topiramate (N=47) compared to those not receiving levetiracetam and topiramate (N=1072). Severe and serious TEAEs related to hostility and aggression were rare and occurred at a similar rate regardless of concomitant levetiracetam and/or topiramate therapy. Taken together, these results suggest that concomitant treatment with levetiracetam and/or topiramate has no appreciable effect on the occurrence of hostility- or aggression-related TEAEs in patients receiving perampanel.

Topics: Adolescent; Adult; Aged; Aggression; Anticonvulsants; Child; Drug Therapy, Combination; Epilepsies, Partial; Fructose; Hostility; Humans; Levetiracetam; Middle Aged; Nitriles; Piracetam; Pyridones; Topiramate; Treatment Outcome; Young Adult

Newer antiepileptic drugs (AEDs), such as Eslicarbazepine (ESL), Lacosamide (LAC), Perampanel (PER) and Brivaracetam (BRV), have been marketed as adjunctive treatments for partial-onset seizures. Our aim was to compare the efficacy and tolerability of newer AEDs with Levetiracetam (LEV), when used as add-on treatments for uncontrolled focal epilepsy.. We conducted an online database search on PubMed, Embase, Cochrane Online Library and Clinicaltrials.gov for all available randomized controlled trials (RCTs) investigating the therapeutic effects of newer AEDs or LEV vs placebo. Indirect comparisons for clinical efficacy and tolerability at different doses between the newer AEDs and LEV were then performed using Indirect Treatment Comparison (ITC) software.. Twenty-four RCTs with a total of 8540 patients were included. Compared to LEV, ESL, LAC and BRV did not showed significant difference in efficacy at all dose level. PER showed lower 50% response rates and seizure-free rates at the highest effective recommended dosages. Treatment-emergent adverse events (TEAEs) and withdrawal rates due to adverse events (AEs) of LAC and PER were higher than LEV at the highest effective recommended dosages, and overall AE rates from ESL were higher than LEV.. Indirect comparisons suggested that ESL, LAC and BRV were not inferior to LEV in efficacy. ESL, LAC and PER may have a possible worse tolerability profile compared to LEV at high dose. But BRV may exhibit a similar tolerability to LEV. Newer AEDs cannot exceed the LEV on efficacy and tolerability.

Topics: Anticonvulsants; Epilepsies, Partial; Humans; Levetiracetam; Piracetam

Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for partial onset seizures and sodium valproate for generalised onset seizures; however a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices.. To compare the time to withdrawal of allocated treatment, remission and first seizure of 10 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide) currently used as monotherapy in children and adults with partial onset seizures (simple partial, complex partial or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus).. We searched the following databases: Cochrane Epilepsy's Specialised Register, CENTRAL, MEDLINE and SCOPUS, and two clinical trials registers. We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field. The date of the most recent search was 27 July 2016.. We included randomised controlled trials of a monotherapy design in adults or children with partial onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types).. This was an individual participant data (IPD) review and network meta-analysis. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary outcomes were 'time to achieve 12-month remission', 'time to achieve six-month remission', 'time to first seizure post-randomisation', and 'occurrence of adverse events'. We presented all time-to-event outcomes as Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs). We performed pairwise meta-analysis of head-to-head comparisons between drugs within trials to obtain 'direct' treatment effect estimates and we performed frequentist network meta-analysis to combine direct evidence with indirect evidence across the treatment network of 10 drugs. We investigated inconsistency between direct estimates and network meta-analysis via node splitting. Due to variability in methods and detail of reporting adverse events, we have not performed an analysis. We have provided a narrative summary of the most commonly reported adverse events.. IPD was provided for at least one outcome of this review for 12,391 out of a total of 17,961 eligible participants (69% of total data) from 36 out of the 77 eligible trials (47% of total trials). We could not include IPD from the remaining 41 trials in analysis for a variety of reasons, such as being unable to contact an author or sponsor to request data, data being lost or no longer available, cost and resources required to prepare data being prohibitive, or local authority or country-specific restrictions.We were able to calculate direct treatment effect estimates for between half and two thirds of comparisons across the outcomes of the review, however for many of the comparisons, data were contributed by only a single trial or by a small number of participants, so confidence intervals of estimates were wide.Network meta-analysis showed that for the primary outcome 'Time to withdrawal of allocated treatment,' for individuals with partial seizures; levetiracetam performed (statistically) significantly better than current first-line treatment carbamazepine and other current first-line treatment lamotrigine performed better than all other treatments (aside from levetiracetam); carbamazepine performed significantly better than gabapentin and phenobarbitone (high-quality evidence). For individuals with generalised onset seizures, first-line treatment sodium valproate performed significantly better than carbamazepine, topiramate and phenobarbitone (moderate- to high-quality evidence). Furthermore, for both partial and generalised onset seizures, the earliest licenced treatment, phenobarbitone seems to perform worse than all other treatments (moderate- to high-quality evidence).Network meta-analysis also showed that for secondary outcomes 'Time to 12-month remission of seizures' and 'Time to six-month remission of seizures,' few notable differences were shown for either partial or generalised seizure types (moderate- to high-quality evidence). For secondary outcome 'Time to first seizure,' for individuals with partial seizures; phenobarbitone performed significantly better than both current first-line treatments carbamazepine and lamotrigine; carbamazepine performed significantly better than sodium valproate, gabapentin and lamotrigine. Phenytoin also performed significantly better than lamotrigine (high-quality evidence). In general, the earliest licenced treatments (phenytoin and phenobarbitone) performed better than the other treatments for both seizure typ. Overall, the high-quality evidence provided by this review supports current guidance (e.g. NICE) that carbamazepine and lamotrigine are suitable first-line treatments for individuals with partial onset seizures and also demonstrates that levetiracetam may be a suitable alternative. High-quality evidence from this review also supports the use of sodium valproate as the first-line treatment for individuals with generalised tonic-clonic seizures (with or without other generalised seizure types) and also demonstrates that lamotrigine and levetiracetam would be suitable alternatives to either of these first-line treatments, particularly for those of childbearing potential, for whom sodium valproate may not be an appropriate treatment option due to teratogenicity.

Topics: Adult; Amines; Anticonvulsants; Carbamazepine; Child; Cyclohexanecarboxylic Acids; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Network Meta-Analysis; Oxcarbazepine; Phenobarbital; Phenytoin; Piracetam; Remission Induction; Topiramate; Triazines; Valproic Acid; Zonisamide

The study aimed to compare the efficacy and tolerability of levetiracetam (LEV) and brivaracetam (BRV) in adults with refractory focal seizures.. We systematically queried Medline, Embase, and the Cochrane Library. We looked for additional studies in the references of all identified publications and ClinicalTrials.gov. The cutoff day was November 6, 2015. Randomized, double-blind, placebo-controlled trials were included. The indirect comparison for 50% responder rate, seizure-free rate, and adverse effects were conducted.. Thirteen trials enrolling 1765 patients in the LEV group and 1919 patients in the BRV group were included. No statistically significant differences were found in efficacy between LEV and BRV at various dose levels. However, most risk ratios (RRs) at three dose levels and the overall RR were >1 for 50% response proportions. The majority of statistically significant differences for adverse events and withdrawal of LEV and BRV were found at high- and middle-dose levels. The indirect comparison of adverse effects (AEs) showed statistically statistical differences in dizziness.. Our results suggested that LEV might have a slightly higher efficacy with a lower probability of dizziness compared with BRV for patients with refractory focal seizures.

Topics: Adult; Anticonvulsants; Epilepsies, Partial; Humans; Levetiracetam; Outcome Assessment, Health Care; Piracetam; Pyrrolidinones

Topics: Adult; Anticonvulsants; Epilepsies, Partial; Humans; Levetiracetam; Piracetam; Pyrrolidinones

Chronic administration of antiepileptic drugs without history of unprovoked epileptic seizures are not recommended for epilepsy prophylaxis. Conversely, if the patient suffered the first unprovoked seizure, then the presence of epileptiform discharges on the EEG, focal neurological signs, and the presence of epileptogenic lesion on the MRI are risk factors for a second seizure (such as for the development of epilepsy). Without these risk factors, the chance of a second seizure is about 25-30%, while the presence of these risk factors (for example signs of previous stroke, neurotrauma, or encephalitis on the MRI) can predict >70% seizure recurrence. Thus the International League Against Epilepsy (ILAE) re-defined the term 'epilepsy' which can be diagnosed even after the first seizure, if the risk of seizure recurrence is high. According to this definition, we can start antiepileptic drug therapy after a single unprovoked seizure. There are four antiepileptic drugs which has the highest evidence (level "A") as first-line initial monotherapy for treating newly diagnosed epilepsy. These are: carbamazepine, phenytoin, levetiracetam, and zonisamide (ZNS). The present review focuses on the ZNS. Beacuse ZNS can be administrated once a day, it is an optimal drug for maintaining patient's compliance and for those patients who have a high risk for developing a non-compliance (for example teenagers and young adults). Due to the low interaction potential, ZNS treatment is safe and effective in treating epilepsy of elderly people. ZNS is an ideal drug in epilepsy accompanied by obesity, because ZNS has a weight loss effect, especially in obese patients.

Topics: Adolescent; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Carbamazepine; Drug Administration Schedule; Drug Approval; Drug Prescriptions; Electroencephalography; Encephalitis; Epilepsies, Partial; Humans; Hungary; Isoxazoles; Levetiracetam; Magnetic Resonance Imaging; Medication Adherence; Obesity; Phenytoin; Piracetam; Risk Assessment; Risk Factors; Seizures; Stroke; Weight Loss; Young Adult; Zonisamide

Epilepsy is an important neurological condition and drug resistance in epilepsy is particularly common in individuals with focal seizures. In this review, we summarise the current evidence regarding a new antiepileptic drug, levetiracetam, when used as add-on treatment for controlling drug-resistant focal epilepsy. This is an update to a Cochrane Review that was originally published in 2001.. To evaluate the effectiveness of levetiracetam, added on to usual care, in treating drug-resistant focal epilepsy.. We searched the Cochrane Epilepsy Group's Specialized Register (August 2012), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 7, 2012), and MEDLINE (1946 to August week 1, 2012). We also contacted the manufacturers of levetiracetam and researchers in the field to seek any ongoing or unpublished trials.. Randomised, placebo-controlled trials of add-on levetiracetam treatment in people with drug-resistant focal epilepsy.. Two review authors independently selected trials for inclusion, assessed trials for bias, extracted data, and evaluated the overall quality of evidence. Outcomes investigated included 50% or greater reduction in focal seizure frequency (response); less than 50% reduction in focal seizure frequency (non-response); treatment withdrawal; adverse effects (including a specific analysis of changes in behaviour); cognitive effects and quality of life (QoL). Risk ratios (RR) with 95% confidence intervals (CIs) were used as measures of effect (99% CIs for adverse effects). Primary analyses were Intention-to-Treat (ITT). Dose response and inter-trial heterogeneity were evaluated in regression models.. Eleven trials (1861 participants) were included. They predominantly possessed low risks of bias. Participants were adults in nine trials (1565 participants) and children in the remaining two trials (296 participants). The dose of levetiracetam tested was 1000 to 4000 mg/day in adults, and 60 mg/kg/day in children. Treatment ranged from 12 to 24 weeks. For the 50% or greater reduction in focal seizure frequency outcome, the RR was significantly in favour of levetiracetam at all doses. The naive estimates, ignoring dose, showed children (52% responded) as better responders than adults (39% responded) on levetiracetam. 25% of children and 16% of adults responded to placebo. The Number Needed to Treat for an additional beneficial outcome for children and adults was four (95% CI three to seven) and five (95% CI four to six), respectively. The significant levels of statistical heterogeneity between trials on adults precluded valid provision of an overall RR (ignoring dose). Results for the two trials that tested levetiracetam 2000 mg on adults were sufficiently similar to be combined to give an RR for 50% or greater reduction in focal seizure frequency of 4.91 (95% CI 2.75 to 8.77), with an RR of 0.68 (95% CI 0.60 to 0.77) for non-response. At this dose, 37% and 8% of adults were responders in the levetiracetam and placebo groups, respectively. Regression analysis demonstrated that much of the heterogeneity between adult trials was likely to be explained by different doses of levetiracetam tested and different years of trial publication. There was no evidence of statistical heterogeneity between trials on children. For these trials, the RR for 50% or greater reduction in focal seizure frequency was 1.91 (95% CI 1.38 to 2.63), with an RR of 0.68 (95% CI 0.56 to 0.81) for non-response. 27% of children responded. Participants were not significantly more likely to have levetiracetam withdrawn (RR 0.98; 95% CI 0.73 to 1.32 and RR 0.80; 95% CI 0.43 to 1.46 for adults and children, respectively). For adults, somnolence (RR 1.51; 99% CI 1.06 to 2.17) and infection (RR 1.76; 99% CI 1.03 to 3.02) were significantly associated with levetiracetam. Accidental injury was significantly associated with placebo (RR 0.60; 99% CI 0.39 to 0.92). No individual adverse effect was significantly associated with levetiracetam in children. Changes in behaviour were negligible in adults (1% affected; RR 1.79; 99% CI 0.59 to 5.41) but significant in children (23% affected; RR 1.90; 99% CI. This update adds seven more trials to the original review, which contained four trials. At every dose analysed, levetiracetam significantly reduced focal seizure frequency relative to placebo. This indicates that levetiracetam can significantly reduce focal seizure frequency when it is used as an add-on treatment for both adults and children with drug-resistant focal epilepsy. As there was evidence of significant levels of statistical heterogeneity within this positive effect it is difficult to be precise about the relative magnitude of the effect. At a dose of 2000 mg, levetiracetam may be expected to be 3.9 times more effective than placebo; with 30% of adults being responders at this dose. At a dose of 60 mg/kg/day, levetiracetam may be expected to be 0.9 times more effective than placebo; with 25% of children being responders at this dose. When dose was ignored, children were better responders than adults by around 4% to 13%. The results grossly suggest that one child or adult may respond to levetiracetam for every four or five children or adults, respectively, that have received levetiracetam rather than placebo. The drug seems to be well tolerated in both adults and children although non-specific changes in behaviour may be experienced in as high as 20% of children. This aspect of the adverse-effect profile of levetiracetam was analysed crudely and requires further investigation and validation. It seems reasonable to continue the use of levetiracetam in both adults and children with drug-resistant focal epilepsy. The results cannot be used to confirm longer-term or monotherapy effects of levetiracetam or its effects on generalised seizures. The conclusions are largely unchanged from those in the original review. The most significant contribution of this update is the addition of paediatric data into the analysis.

Topics: Adult; Anticonvulsants; Child; Drug Resistance; Drug Therapy, Combination; Epilepsies, Partial; Humans; Levetiracetam; Piracetam; Quality of Life; Randomized Controlled Trials as Topic

Levetiracetam is an antiepileptic drug (AED) approved for the adjunctive treatment of partial seizures firstly in the US in 1999. In Japan, levetiracetam was approved for the adjunctive treatment of partial seizures. Accumulated evidences and experiences in US, Europe and Asian counties have indicated clinical features of levetiracetam (i.e., rapid onset of action, high efficacy and tolerability, no drug-drug interactions). One may ask whether the known clinical features are applicable to Japanese epilepsy patients with partial seizures. This article is aimed at answering such questions by reviewing published articles on effects of races onto pharmacokinetics and on efficacy and safety profiles shown in studies conducted in the US, Europe, Taiwan, China, Korea, Asian 6 countries and Japan, which allowed to compare the profiles across the different populations. Pharmacokinetic profiles were not different between Western and Japanese, and between Chinese and Western populations. The values of efficacy variables such as percentage (%) reduction of seizure frequency from baselines, 50% responder rate and seizure free rate at dose range of 1,000 mg-3,000 mg/d were similar across 4 open studies (Korea, 6 Asian countries, US, Europe and other western; % reduction: 43.2-52.3%, 50% responder rate: 43.6-57.9%, Seizure free rate: 16.2-20.2%). In the 6 placebo-controlled double blind studies (US, 2 Europe studies, China, Taiwan and Japan), the values of the efficacy variables of the levetiracetam arms (1,000 mg/d, 2,000 mg/d, 3,000 mg/d, 1,000-2,000 mg/d, 2,000-3,000 mg/d) were at least numerically superior to those of corresponding placebo arms even though the statistical significance was not obtained for all of the variables. The degrees of difference between the values of placebo and levetiracetam arms were within comparable ranges. These comparisons suggested levetiracetam would have similar efficacy and safety profiles in Japanese patients to those in the US, Europe, and the Asian countries, thereby indicating the known clinical features applicable to Japanese patients in usual clinical settings. In the open studies, average dosages were 1,335-1,953 mg/d. The interquartile ranges of the doses of the 6-Asian country study subjects showing 100% and 75- < 100% seizure reduction were 925-1,000 mg/d and 975-1,509 mg/d, respectively. The most frequent dose was 1,000 mg/d in the US open study. The % reduction and 50% responder rates at a dose of 1,000 mg/d in Japan stu

Topics: Anticonvulsants; Asia, Eastern; Clinical Trials as Topic; Epilepsies, Partial; Europe; Humans; Japan; Levetiracetam; Piracetam; United States

Evaluate the clinical comparability of new antiepileptic drugs (AEDs) in partial refractory epilepsy.. Systematic review of randomized trials (RCTs) comparing a new AED (add-on treatment) with placebo or another AED.. responder (≥50% seizure reduction) and withdrawal (tolerability) rates. Pooled estimates of odds ratios (ORs) and number needed treat/harm (NNT/NNH) taking into account baseline risk were derived by random-effects meta-analysis. Adjusted frequentist indirect comparisons between AEDs were estimated.. Sixty-two placebo-controlled (12,902 patients) and eight head-to-head RCTs (1,370 patients) were included. Pooled ORs for responder and withdrawal rates (vs. placebo) were 3.00 [95% confidence interval (CI) 2.63-3.41] and 1.48 (1.30-1.68), respectively. Indirect comparisons of responder rate based on relative measurements of treatment effect (ORs) favored topiramate (1.52; 1.06-2.20) in comparison to all other AEDs, whereas gabapentin (0.67; 0.46-0.97) and lacosamide (0.66; 0.48-0.92) were less efficacious, without significant heterogeneity. When analyses were based on absolute estimates (NNTs), topiramate and levetiracetam were more efficacious, whereas gabapentin and tiagabine were less efficacious. Withdrawal rate was higher with oxcarbazepine (OR 1.60; 1.12-2.29) and topiramate (OR 1.68; 1.07-2.63), and lower with gabapentin (OR 0.65; 0.42-1.00) and levetiracetam (OR 0.62; 0.43-0.89).. The differences found are of relatively small magnitude to allow a definitive conclusion about which new AED(s) has superior effectiveness. This uncertainty probably reflects the limitations of conclusions based on indirect evidence. The process of pharmacologic clinical decision making in partial refractory epilepsy probably depends more on other aspects, such as individual patient characteristics and pharmacoeconomics, than on available controlled randomized evidence.

Topics: Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Epilepsies, Partial; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Levetiracetam; Nipecotic Acids; Piracetam; Randomized Controlled Trials as Topic; Tiagabine; Topiramate; Treatment Outcome

In this post hoc analysis, individual seizure counts from four double-blind trials of adjunctive treatment with levetiracetam were analyzed by non-linear mixed-effects modeling (NONMEM). First, a model was fitted to the individual count data assuming a Poisson distribution, in order to classify the patients as either improving or deteriorating from baseline. In the second stage, the dose-response relationship in improving patients was determined by fitting the data to an E(max) model including a placebo effect. The percentage of improvers was 59% on placebo and 73%, 74%, 77% and 73% on levetiracetam 1, 2, 3 and 4g/day, respectively. The ED(50) of 1408mg/day was close to the current WHO Defined Daily Dose of levetiracetam (1500mg). The maximum recommended dose of 3000mg/day was predicted to reduce seizures by >or=90% in 10% of improving patients. Age, gender, body weight, race, and number of concomitant antiepileptic drugs neither affected the percentage of responders nor the extent of change in seizure frequency from baseline.

Topics: Anticonvulsants; Clinical Trials, Phase III as Topic; Computer Simulation; Dose-Response Relationship, Drug; Double-Blind Method; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Nonlinear Dynamics; Piracetam; Seizures

Topics: Amines; Anticonvulsants; Carbamazepine; Child; Cyclohexanecarboxylic Acids; Dioxolanes; Epilepsies, Partial; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Oxcarbazepine; Piracetam; Pregabalin; Topiramate; Triazines; Vigabatrin; Zonisamide

In add-on studies of partial-onset seizures, the placebo response, defined as a 50% decrease from baseline in seizure frequency, ranges from 0-19%. Reasons for this significant difference between placebo groups in different trials are not given in the literature. This exploratory analysis was undertaken to compare the baseline characteristics of placebo responders and nonresponders, in an attempt to identify common features. The pooled statistical analysis was performed on the database for three pivotal studies of levetiracetam (n = 904). Using the 50% response definition, we found that 45.6% of placebo nonresponders were on one antiepileptic drug at baseline, compared with 69% of placebo responders. The difference in number of baseline antiepileptic drugs was almost statistically significant (p = 0.056). Placebo nonresponders also tended to have epilepsy for longer than responders. The mean age at onset of epilepsy was consistently different between placebo nonresponders and responders (15.2 versus 20.8 years, respectively; p = 0.019). These findings suggest that the placebo response is higher in patients with partial-onset seizures who are taking only one antiepileptic drug at baseline and have later onset and shorter duration of epilepsy than in patients on more than one antiepileptic drug at baseline with earlier onset and longer duration of epilepsy.

Topics: Adolescent; Adult; Age of Onset; Aged; Anticonvulsants; Databases, Factual; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Placebo Effect; Randomized Controlled Trials as Topic

To assess the advantages and disadvantages of six methodologies used in calculating seizure freedom rates in placebo-controlled, adjunctive therapy trials of new antiepileptic drugs (AEDs) in partial epilepsy, and two methodologies for long-term follow-up studies.. Data from levetiracetam trials were used to illustrate the impact of different methodologies on seizure freedom rates. Seizure-freedom data for several new AEDs were identified from the published medical literature using MEDLINE and from a recent comprehensive textbook.. Most randomized, placebo-controlled add-on clinical trials of new AEDs contain little or no information about seizure freedom. Importantly, the methodology used can profoundly affect results when calculating seizure-free rates. Seizure freedom data should be reported as well as the methodology used. The minimum duration for assessing seizure freedom should be the entire stable dose period in short-term trials and at least six months for long-term follow-up studies. It is proposed that the seizure freedom rates be calculated and reported with at least two different methodologies, one that considers patients withdrawing from treatment without having had a seizure as successes, and one that considers the same patients as failures. For an effective and well-tolerated AED, seizure freedom rates will be consistent across the two methodologies.. Seizure freedom is the ultimate goal of AED therapy and should be reported for all clinical trials. Methodological differences among the few clinical studies reporting seizure freedom rates make it difficult to compare results across trials. Improved reporting of methodologies and seizure-free rates is warranted.

Topics: Adult; Anticonvulsants; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Piracetam; Remission Induction; Research Design; Seizures

To investigate whether rapid achievement of levetiracetam (LEV) steady state is translated into an immediate measurable efficacy. The time to onset of action of LEV immediately after its initiation in adult patients with refractory partial seizures was analyzed.. Treatment effect was assessed in a pooled analysis (n=883) from three randomized, double-blind, placebo-controlled add-on trials.. The increase in the proportion of seizure-free patients over baseline was 15, 17, and 17% for the first, second, and third day, respectively, for the LEV 1,000-mg group (all differences statistically significant; McNemar p value<0.001), whereas the increase was 7, 9, and 9% for the 333-mg LEV group (differences not significant). No major changes were observed for the placebo group. For differences in proportion of seizure-free patients between groups, the probability of being seizure free in the LEV groups was twofold higher than in the placebo group. For the 1,000-mg LEV group, odds ratios were 2.3, 2.5, and 2.7 for the first, second, and third day of therapy, respectively; all differences versus placebo were statistically significant (logistic regression p values, all <0.001). The addition of LEV significantly increased the proportion of patients without a seizure as of the first day of therapy. Each of the first 3 days, seizure freedom was twice as likely to occur with LEV 1,000 mg than with placebo.. Evidence of a rapid onset of action of LEV 1,000 mg was demonstrated through a significant increase in the proportion of seizure-free patients as of the first day of therapy.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Disease-Free Survival; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Follow-Up Studies; Humans; Levetiracetam; Logistic Models; Middle Aged; Odds Ratio; Piracetam; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome

To investigate whether the efficacy of levetiracetam (LEV) is sustained in adult patients with refractory partial seizures over a 3-month period.. Treatment effect was assessed in a post hoc analysis by determining the proportion of seizure-free days during each week of a 3-month period after the initiation of treatment. Pooled data from three randomized, double-blind, placebo-controlled trials (n = 883) were analyzed.. The mean proportion of seizure-free days was greater in the LEV group than in the placebo group. The difference, which was statistically significant, was observed as early as the first week after the initiation of treatment. It was higher in the first week of treatment and subsequently was maintained for each week over the 3-month period (p < 0.001 or p = 0.002 at each time point). Patients in the LEV group had on average 74% to 81% days each week without any seizure, compared with 69% to 72% in the placebo group.. LEV is efficient in controlling seizures from the first week of drug initiation, during uptitration, and throughout the first 3 months of treatment. An interesting amplification of efficacy occurs in the first week of therapy, which is intriguing and warrants further investigation.

Topics: Adult; Anticonvulsants; Clinical Trials, Phase III as Topic; Double-Blind Method; Drug Administration Schedule; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Piracetam; Placebos; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome

Levetiracetam is a novel antiepileptic drug that has been demonstrated as being effective in the management of partial seizures. It is rapidly and completely absorbed after oral administration and it is predominantly eliminated as unchanged drug in the urine. Its metabolism is independent of the cytochrome P450 enzyme system, nor does it induce cytochrome P450 enzymes. As a result of its pharmacokinetic features, levetiracetam has not been demonstrated to interact with other drugs in either direction. In double-blind, placebo-controlled trials, all the levetiracetam dosages tested were effective, including 1000 mg/day, 2000 mg/day and 3000 mg/day. The ineffective dose is not known. Efficacy seemed to be maintained in long-term studies, with no evidence of tolerance. In major double-blind, placebo-controlled trials discontinuation rates because of adverse events were 6.9-10.9% for levetiracetam-treated patients (all doses) compared with 5.3-8.6% for placebo-treated patients. The most common adverse events that differed between treatment groups and placebo control groups were somnolence, asthenia, dizziness and, in the US study, infection. Since levetiracetam was marketed, behavioural effects have been reported, namely irritability, agitation, anger and aggressive behaviour. These adverse effects are more likely in learning disabled individuals, those with prior psychiatric history and those with symptomatic generalised epilepsy. Overall, the risk has been estimated at 12-15%. Laboratory parameters overall seem to be not significantly affected by levetiracetam, although slight trends to lower white and red blood cell counts were detected in the studies. No organ toxicity has been described so far, with patient exposures exceeding 500,000. In summary, levetiracetam exhibits a very favourable safety profile in patients with partial onset seizures. Whereas somnolence, asthenia and dizziness were the most prominent adverse effects in clinical trials, behavioural adverse effects have generally been the most common reason for drug discontinuation in clinical practice.

Topics: Adult; Aged; Anticonvulsants; Child; Clinical Trials as Topic; Dose-Response Relationship, Drug; Economics, Pharmaceutical; Epilepsies, Partial; Humans; Levetiracetam; Piracetam; Quality of Life; Risk Assessment

To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies.. A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 until September 2002, with selected manual searches up to 2003.. Evidence exists, either from comparative or dose-controlled trials, that GBP, LTG, TPM, and OXC have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. Evidence also shows that LTG is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking.. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Topics: Acetates; Adolescent; Adult; Age Factors; Amines; Antipsychotic Agents; Carbamazepine; Child; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Drug Approval; Epilepsies, Partial; Epilepsy, Absence; Epilepsy, Generalized; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Piracetam; Tiagabine; Topiramate; Triazines; United States; United States Food and Drug Administration; Zonisamide

To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) [gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS)] in the treatment of children and adults with refractory partial and generalized epilepsies.. A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 to March 2003.. All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. GBP can be effective for the treatment of mixed seizure disorders, and GBP, LTG, OXC, and TPM for the treatment of refractory partial seizures in children. Limited evidence suggests that LTG and TPM also are effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox-Gastaut syndrome.. The choice of AED depends on seizure and/or syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Topics: Acetates; Adolescent; Adult; Age Factors; Amines; Anticonvulsants; Carbamazepine; Child; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Drug Approval; Epilepsies, Partial; Epilepsy, Generalized; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Piracetam; Practice Patterns, Physicians'; Tiagabine; Topiramate; Triazines; United States; United States Food and Drug Administration; Zonisamide

To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies.. A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003.. All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome.. The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary.

Topics: Acetates; Adult; Amines; Anticonvulsants; Carbamazepine; Child; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Drug Resistance; Epilepsies, Partial; Epilepsy, Generalized; Evidence-Based Medicine; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Piracetam; Tiagabine; Topiramate; Treatment Outcome; Triazines; Zonisamide

Controlled clinical trials and routine clinical practice demon-strate that levetiracetam is effective as add-on therapy and appears to allow for withdrawal to monotherapy in patients who respond well in the add-on setting. In pivotal clinical trials of adjunctive therapy with levetiracetam 1000 to 3000 mg/day (pooled data), 40% to 54% of patients experienced a 50% or greater reduction in seizure frequency, compared with 18% to 28% of patients treated with placebo. The median percent reduction from baseline in seizure frequency ranged from 36% to 68% for levetiracetam, versus 10% to 23% for placebo. Seizure freedom was achieved by 11% to 35% of those in the levetiracetam treatment group, compared with 3% to 18% of those in the placebo group. (All comparisons statistically significant versus placebo for simple partial, complex partial, and secondarily generalized seizures except for percentage of seizure-free patients with simple partial seizures.) Clinical obser-vations are consistent with these findings.

Topics: Animals; Anticonvulsants; Clinical Trials as Topic; Dose-Response Relationship, Drug; Epilepsies, Partial; Epilepsy; Humans; Levetiracetam; Meta-Analysis as Topic; Piracetam

We examined the effect of adjunctive levetiracetam (LEV; 1,000 to 3,000 mg/day) on the number of seizure-free days gained per quarter in adult patients with refractory partial-onset epilepsy.. The treatment effect was studied in a meta-analysis using individual patient data of a subpopulation of patients (n = 846) emerging from the three randomized, double-blind, placebo-controlled, phase III trials (n = 904).. Adding LEV effectively increased the number of days without seizures by 5.19 days per quarter [95% confidence interval (CI), 3.63-6.76; p = 0.0001; titration and stable dose periods].. LEV adjunctive treatment shows a clear benefit in terms of seizure-free days gained for patients with refractory epilepsy. This gain is significant for the pooled and for each LEV dose compared with placebo.

Topics: Adult; Confidence Intervals; Dose-Response Relationship, Drug; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Randomized Controlled Trials as Topic; Seizures

To determine the effect of levetiracetam (LEV) on partial seizure subtypes (simple partial, complex partial, and secondarily generalized seizures) in patients with refractory epilepsy.. Pooled results from three placebo-controlled trials were analyzed.. A statistically significant reduction in the frequency of all partial seizures and all seizure subtypes was observed in the LEV group (p < 0.001 vs. placebo). The proportion of patients in whom secondarily generalized seizures could be prevented over and above the reduction of partial seizures was significantly greater in the LEV group as compared with placebo, with an odds ratio of 1.83 [95% confidence interval (CI), 1.10-3.05]. CONCLUSIONS; LEV reduces frequency of simple and complex partial seizures. In addition, it demonstrates a specific, independent reduction of secondarily generalized seizures.

Topics: Adult; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Complex Partial; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Female; Humans; Levetiracetam; Male; Meta-Analysis as Topic; Middle Aged; Outcome Assessment, Health Care; Piracetam; Randomized Controlled Trials as Topic

Topics: Action Potentials; Anticonvulsants; Calcium Channels; Epilepsies, Partial; Humans; Levetiracetam; Piracetam; Potassium Channels; Protein Conformation; Receptors, GABA-A

Levetiracetam is a new anticonvulsant for adjunctive treatment of partial epilepsy. It is well tolerated, with no significant risks, at a dose of 1000-3000 mg/day in adults. The efficacy (> 50% reduction in attacks) in refractory partial epilepsy is 22-40%, depending on the dose. Efficacy was also seen with levetiracetam monotherapy in more than half of the positive responders. Levetiracetam does not cause induction or inhibition of the P450 enzyme system or other enzyme systems, there is no active metabolite and it exhibits almost no protein binding. These factors mean that this drug undergoes no significant interactions with other medication and appears suitable for elderly patients and for conditions requiring complex pharmacotherapy. Compared with other recently registered anti-epilepsy drugs, levetiracetam appears promising in terms of efficacy, tolerability and pharmacokinetics. The simple dosing schedule is an additional benefit.

Topics: Anticonvulsants; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Epilepsies, Partial; Humans; Levetiracetam; Piracetam; Treatment Outcome

Levetiracetam (Keppra--UCB Pharma) is a new anti-epileptic drug, marketed in the UK since 2000. It is licensed for use as adjunctive treatment for partial seizures, with or without secondary generalisation, in people aged over 16 years. The company claims that levetiracetam is "highly effective", with a "therapeutic starting dose", "excellent tolerability", and "no known drug/drug interactions". Here, we discuss the place of levetiracetam in the treatment of patienTs with epilepsy.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Epilepsies, Partial; Humans; Levetiracetam; Middle Aged; Piracetam; Treatment Outcome

The majority of patients with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug. However, up to 30% develop refractory seizures, particularly those with partial seizures. In this review, we summarise the current evidence regarding a new antiepileptic drug, levetiracetam, when used as an add-on treatment for drug-resistant localization related (partial) epilepsy.. To evaluate the effects of levetiracetam on seizures, side effects, quality of life and cognition, when used as an add-on treatment for patients with a drug-resistant localization related (partial) epilepsy.. We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2000). In addition, we contacted UCB SA (makers of levetiracetam) and experts in the field to seek any ongoing studies or unpublished studies.. Randomized placebo controlled add-on trials of levetiracetam in patients with a drug-resistant localization related (partial) epilepsy.. Two reviewers independently selected trials for inclusion and extracted relevant data. The following outcomes were assessed: (a) 50% or greater reduction in total seizure frequency; (b) treatment withdrawal (any reason); (c) side effects; (d) cognitive effects; (e) quality of life. Primary analyses were intention to treat. Sensitivity best and worst case analyses were also undertaken. Summary odds ratios (ORs) were estimated for each outcome. Dose response was evaluated in regression models.. Four trials (1023 patients) were included. All four trials had data for treatment withdrawal and side effect outcomes. Three trials (904 patients) had data for 50% or greater reduction in seizure frequency. Three trials (595 patients) had data for quality of life and cognitive outcomes. The overall Odds Ratio (OR) (95% Confidence Interval (CI)) for 50% or greater reduction in total seizure frequency outcome was 3.81 (2.78,5.22). Dose regression analysis shows clear evidence that levetiracetam reduces seizure frequency with an increase in efficacy with increasing dose of levetiracetam. Approximately 15% of patients taking 1000 mg and 20-30% of patients taking 3000 mg levetiracetam per day have a 50% or greater reduction in seizure frequency. Patients were not significantly more likely to have levetiracetam withdrawn, OR (95% CI) 1.25 (0.87,1.80). The following side effects were significantly associated with levetiracetam: dizziness 2.36 (1.21, 4.61) and infection 1.82 (1.05, 3.14) whereas accidental injury was significantly associated with placebo 0.55 (0.32, 0.93). Quality of life and cognitive effect outcomes suggest that levetiracetam has a positive effect on cognition and some aspects of quality of life.. Levetiracetam reduces seizure frequency when used as an add-on treatment for patients with a drug-resistant localization related (partial) epilepsy, and seems well tolerated. Minimum effective and maximum tolerated doses have not been identified. The trials reviewed were of 16-24 weeks duration and results cannot be used to confirm longer term effects. Our results cannot be extrapolated to monotherapy or to patients with other seizure types or epilepsy syndromes. Great care should also be taken with any attempt to apply these results to children.

Topics: Anticonvulsants; Drug Resistance; Drug Therapy, Combination; Epilepsies, Partial; Humans; Levetiracetam; Piracetam; Quality of Life; Randomized Controlled Trials as Topic

To undertake a systematic review and meta-analysis of placebo controlled add-on trials of levetiracetam, oxcarbazepine, remacemide and zonisamide for patients with drug resistant localization related epilepsy.. We searched Medline, The Cochrane Library and contacted the relevant pharmaceutical companies. Outcomes were 50% or greater reduction in seizure frequency and treatment withdrawal for any reason. Data were synthesised in a meta-analysis. The effect of dose was explored in regression models for levetiracetam and remacemide.. We found four trials (1023 patients) of levetiracetam, two (961) of oxcarbazepine, two (388) of remacemide and three (499) of zonisamide. Ignoring dose, the relative risks (95% CI) for a 50% response were 3.78 (2.62-5.44), 2.51 (1.88-3.33), 1.59 (0.91-2.97) and 2.46 (1.61-3.79), respectively. There was evidence for increasing effect with increasing dose for levetiracetam, oxcarbazepine and remacemide. The relative risks for treatment withdrawal were 1.21 (0.88-1.66), 1.72 (1.35-2.18), 1.90 (1.00-3.60) and 1.64 (1.02-2.62), respectively.. These data suggest a useful effect for levetiracetam, oxcarbazepine and zonisamide. Levetiracetam has the more favourable 'responder-withdrawal ratio' followed by zonisamide and oxcarbazepine.

Topics: Acetamides; Anticonvulsants; Carbamazepine; Controlled Clinical Trials as Topic; Drug Resistance; Epilepsies, Partial; Humans; Isoxazoles; Levetiracetam; Linear Models; Logistic Models; Oxcarbazepine; Piracetam; Zonisamide

Levetiracetam was approved in November 1999 as add-on therapy for the treatment of partial-onset seizures in adults (age 16 years and older). This review focuses on recently published data from four well-controlled studies in patients with partial-onset seizures with or without secondary generalization. When levetiracetam was given along with other antiepileptic drugs (AEDs), the most frequently reported adverse events were central nervous system related. Adverse events were usually mild to moderate in intensity, with the most frequently reported events occurring predominantly during the first 4 weeks of treatment. No relationship was apparent between the dose of levetiracetam and the most commonly reported adverse events in well-controlled clinical trials within the recommended dose range of 1,000-3,000 mg/day. Levetiracetam is a Pregnancy Category C drug. Overall, when used in combination with other AEDs, levetiracetam was generally well tolerated as add-on treatment for partial-onset seizures.

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Central Nervous System Diseases; Controlled Clinical Trials as Topic; Death, Sudden; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Approval; Drug Overdose; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy; Female; Humans; Incidence; Infant, Newborn; Levetiracetam; Male; Piracetam; Placebos; Pregnancy

This multicenter, open-label, randomized study (Registration No. ChiCTR-OCH-14004528) aimed to compare the efficacy and effects of oxcarbazepine (OXC) with levetiracetam (LEV) as monotherapies on patient quality of life and mental health for patients with newly diagnosed focal epilepsy from China.. Patients with newly diagnosed focal epilepsy who had experienced 2 or more unprovoked seizures at greater than a 24-h interval during the previous year were recruited. Participants were randomly assigned to the OXC group or LEV group. Efficacy, safety, quality of life, and mental health were evaluated over 12-week and 24-week periods.. In total, we recruited 271 newly diagnosed patients from 23 centers. Forty-four patients were excluded before treatment for reasons. The rate of seizure freedom of OXC was significantly superior to that of LEV at 12 weeks and 24 weeks (p < 0.05). The quality of life (except for the seizure worry subsection) and anxiety scale scores also showed significant differences from before to after treatment in the OXC and LEV groups.. OXC monotherapy may be more effective than LEV monotherapy in patients with newly diagnosed focal epilepsy. Both OXC and LEV could improve the quality of life and anxiety state in adult patients with focal epilepsy.

Topics: Adult; Anticonvulsants; Epilepsies, Partial; Humans; Levetiracetam; Oxcarbazepine; Quality of Life; Seizures; Treatment Outcome

In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile.. This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice.. The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure-freedom, seizure response (≥ 50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed.. A total of 1029 patients with a median age of 45 years (33-56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p < 0.001); the corresponding values for ≥ 50% seizure frequency reduction were 47.9%, 29.7%, and 42.8% (p < 0.001). There were no statistically significant differences in seizure freedom and seizure response rates by use of strong EiASMs. The rates of seizure freedom (20.0% vs. 16.6%;  p = 0.341) and seizure response (39.7% vs. 26.9%; p = 0.006) were higher in patients receiving SCBs than those not receiving SCBs; 265 (25.8%) patients discontinued BRV. AEs were reported by 30.1% of patients, and were less common in patients treated with BRV and concomitant SCBs than those not treated with SCBs (28.9% vs. 39.8%; p = 0.017).. The BRIVAFIRST provided real-world evidence on the effectiveness of BRV in patients with focal epilepsy irrespective of LEV history and concomitant ASMs, and suggested favourable therapeutic combinations.

Topics: Adult; Anticonvulsants; Chemotherapy, Adjuvant; Drug Resistant Epilepsy; Epilepsies, Partial; Female; Humans; Italy; Levetiracetam; Male; Middle Aged; Pyrrolidinones; Retrospective Studies; Treatment Outcome

Levetiracetam (Keppra. To compare the clinical effectiveness and cost-effectiveness of lamotrigine (Lamictal. Two pragmatic randomised unblinded non-inferiority trials run in parallel.. Outpatient services in NHS hospitals throughout the UK.. Those aged ≥ 5 years with two or more spontaneous seizures that require anti-seizure medication.. Participants with focal epilepsy were randomised to receive lamotrigine, levetiracetam or zonisamide. Participants with generalised or unclassifiable epilepsy were randomised to receive valproate or levetiracetam. The randomisation method was minimisation using a web-based program.. The primary outcome was time to 12-month remission from seizures. For this outcome, and all other time-to-event outcomes, we report hazard ratios for the standard treatment compared with the new treatment. For the focal epilepsy trial, the non-inferiority limit (lamotrigine vs. new treatments) was 1.329. For the generalised and unclassified epilepsy trial, the non-inferiority limit (valproate vs. new treatments) was 1.314. Secondary outcomes included time to treatment failure, time to first seizure, time to 24-month remission, adverse reactions, quality of life and cost-effectiveness.. The SANAD II trial was unblinded, which could have biased results by influencing decisions about dosing, treatment failure and the attribution of adverse reactions.. SANAD II data could now be included in an individual participant meta-analysis of similar trials, and future similar trials are required to assess the clinical effectiveness and cost-effectiveness of other new treatments, including lacosamide and perampanel.. Current Controlled Trials ISRCTN30294119 and EudraCT 2012-001884-64.. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in. The SANAD II trial was a clinical trial designed to identify the most clinically effective and cost-effective treatment for adults and children aged > 5 years with newly diagnosed epilepsy. There are two main epilepsy types: focal and generalised. In focal epilepsy, seizures start at a single place in the brain (a focus), whereas in generalised epilepsy seizures start in both sides of the brain at the same time. Anti-seizure medications are the main treatment. For people with newly diagnosed epilepsy, the first anti-seizure medication should control the seizures as quickly as possible while avoiding side effects. The first-choice treatments are lamotrigine (Lamictal. People starting treatment with levetiracetam or zonisamide were significantly less likely to have a 12-month remission from seizures than people starting treatment with lamotrigine, unless they were changed to another anti-seizure medication. Side effects that were thought to be caused by anti-seizure medications were reported by 33% of participants starting lamotrigine, 44% of those starting levetiracetam and 45% of those starting zonisamide. The cost-effectiveness analyses showed that neither levetiracetam nor zonisamide is value for money for the NHS when compared with lamotrigine. The SANAD II findings do not support the use of levetiracetam or zonisamide as first-line treatments in focal epilepsy.. People starting treatment with levetiracetam were significantly less likely to have a 12-month remission from seizures than people starting valproate, unless they were changed to another anti-seizure medication. Side effects that were thought to be caused by anti-seizure medications were reported by 37% of participants starting valproate and 42% of participants starting levetiracetam. The cost-effectiveness analyses showed that levetiracetam is not good value for money for the NHS when compared with valproate. The SANAD II findings do not support the use of levetiracetam as a first-line treatment for newly diagnosed generalised epilepsy. Importantly, our results will inform treatment decisions for women, who may choose a less effective treatment that is safer in pregnancy.

Topics: Child, Preschool; Cost-Benefit Analysis; Epilepsies, Partial; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Quality of Life; Valproic Acid; Zonisamide

Levetiracetam and zonisamide are licensed as monotherapy for patients with focal epilepsy, but there is uncertainty as to whether they should be recommended as first-line treatments because of insufficient evidence of clinical effectiveness and cost-effectiveness. We aimed to assess the long-term clinical effectiveness and cost-effectiveness of levetiracetam and zonisamide compared with lamotrigine in people with newly diagnosed focal epilepsy.. This randomised, open-label, controlled trial compared levetiracetam and zonisamide with lamotrigine as first-line treatment for patients with newly diagnosed focal epilepsy. Adult and paediatric neurology services across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked focal seizures. Participants were randomly allocated (1:1:1) using a minimisation programme with a random element utilising factor to receive lamotrigine, levetiracetam, or zonisamide. Participants and investigators were not masked and were aware of treatment allocation. SANAD II was designed to assess non-inferiority of both levetiracetam and zonisamide to lamotrigine for the primary outcome of time to 12-month remission. Anti-seizure medications were taken orally and for participants aged 12 years or older the initial advised maintenance doses were lamotrigine 50 mg (morning) and 100 mg (evening), levetiracetam 500 mg twice per day, and zonisamide 100 mg twice per day. For children aged between 5 and 12 years the initial daily maintenance doses advised were lamotrigine 1·5 mg/kg twice per day, levetiracetam 20 mg/kg twice per day, and zonisamide 2·5 mg/kg twice per day. All participants were included in the intention-to-treat (ITT) analysis. The per-protocol (PP) analysis excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analysis included all participants who received one dose of any study drug. The non-inferiority limit was a hazard ratio (HR) of 1·329, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on lamotrigine. The trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64).. 990 participants were recruited between May 2, 2013, and June 20, 2017, and followed up for a further 2 years. Patients were randomly assigned to receive lamotrigine (n=330), levetiracetam (n=332), or zonisamide (n=328). The ITT analysis included all participants and the PP analysis included 324 participants randomly assigned to lamotrigine, 320 participants randomly assigned to levetiracetam, and 315 participants randomly assigned to zonisamide. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission versus lamotrigine (HR 1·18; 97·5% CI 0·95-1·47) but zonisamide did meet the criteria for non-inferiority in the ITT analysis versus lamotrigine (1·03; 0·83-1·28). The PP analysis showed that 12-month remission was superior with lamotrigine than both levetiracetam (HR 1·32 [97·5% CI 1·05 to 1·66]) and zonisamide (HR 1·37 [1·08-1·73]). There were 37 deaths during the trial. Adverse reactions were reported by 108 (33%) participants who started lamotrigine, 144 (44%) participants who started levetiracetam, and 146 (45%) participants who started zonisamide. Lamotrigine was superior in the cost-utility analysis, with a higher net health benefit of 1·403 QALYs (97·5% central range 1·319-1·458) compared with 1·222 (1·110-1·283) for levetiracetam and 1·232 (1·112, 1·307) for zonisamide at a cost-effectiveness threshold of £20 000 per QALY. Cost-effectiveness was based on differences between treatment groups in costs and QALYs.. These findings do not support the use of levetiracetam or zonisamide as first-line treatments for patients with focal epilepsy. Lamotrigine should remain a first-line treatment for patients with focal epilepsy and should be the standard treatment in future trials.. National Institute for Health Research Health Technology Assessment programme.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticonvulsants; Child; Cost-Benefit Analysis; Epilepsies, Partial; Female; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Treatment Outcome; Young Adult; Zonisamide

Recently, a novel trial design has been proposed to overcome challenges with traditional placebo-controlled trials of antiepileptic drugs in infants and young children (≥1 month of age) (Auvin S, et al. Epilepsia Open 2019;4:537-43). The proposed time-to-event trial design involves seizure counting by caregivers and allows adjustment of the duration of the baseline period and duration of exposure to placebo or potentially ineffective treatment based on the patient's seizure burden and response. We performed post hoc analyses to mimic this trial design and evaluate its viability. As these analyses required trials with prolonged baseline and treatment periods and diary data, which is not a typical design of trials in infants and young children (1 month to <4 years of age), data from two trials in pediatric patients (4-16 years of age) were used.. We performed post hoc analyses of two randomized, double-blind, placebo-controlled trials of adjunctive levetiracetam (N159; NCT00615615) and lacosamide (SP0969; NCT01921205) in children and adolescents (4-16 years of age) with focal-onset seizures. In these analyses, patients were followed until they completed the 10-week maintenance period, discontinued during the maintenance period, or reached their "nth" seizure (n = number of seizures patient had during baseline). Efficacy was assessed by determining time to nth seizure.. In the analyses of both trials, patients on levetiracetam or lacosamide had a 34% lower risk of reaching their baseline seizure count during their 10-week maintenance period than patients on placebo. The previously published primary results of these trials also demonstrated efficacy of adjunctive levetiracetam and lacosamide.. Although these were post hoc analyses of trials in older children (4-16 years of age), our results provide supportive evidence for the utility of the novel time-to-event trial design for future trials in infants and young children (1 month to <4 years of age).

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy; Humans; Lacosamide; Levetiracetam; Seizures

Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality.. The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy.. This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day.. Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo.. Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.

Topics: Adult; Anticonvulsants; Child; Double-Blind Method; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsies, Partial; Humans; Levetiracetam; Quality of Life; Treatment Outcome

Irritability is a adverse effect of many antiseizure medications (ASMs), but there are no validated measures currently available to characterize this behavioral risk. We examined both child and parent/guardian versions of the Affective Reactivity Index (ARI), a validated measure developed for application in adolescent psychiatry, to determine its sensitivity to ASM-related irritability. We hypothesized irritability increases associated with levetiracetam (LEV) but not lamotrigine (LTG) or oxcarbazepine (OXC).. The ARI was administered to 71 child and parent/guardian pairs randomized to one of three common ASMs (LEV, LTG, OXC) used to treat new-onset focal (localization-related) epilepsy. Subjects were recruited as part of a prospective multicenter, randomized, open-label, parallel group design. The ARI was administered at baseline prior to treatment initiation and again at 3 months after ASM initiation.. There was a significant increase in ARI ratings for both child and parent/guardian ratings for LEV but not LTG or OXC when assessed 3 months after treatment initiation. When examined on the individual subject level using a criterion of at least a 3-point ARI increase, there was an increase associated with LEV for child ratings but not parent/guardian scores.. Both child and parent/guardian versions of the ARI appear sensitive to medication-induced irritability associated with LEV on both the group and individual levels. The findings extend the applicability of ARI from characterizing the presence of clinical irritability as a psychiatric diagnostic feature to a more modifiable aspect of behavior change related to medication management and support its use in clinical trial applications.

Topics: Adolescent; Anticonvulsants; Child; Dose-Response Relationship, Drug; Epilepsies, Partial; Female; Humans; Irritable Mood; Lamotrigine; Levetiracetam; Male; Oxcarbazepine; Prospective Studies

The objective of this trial was to compare the effectiveness of levetiracetam (LEV) and topiramate (TPM) as adjunctive treatment for patients with focal seizures in Korea.. In this Phase IV, open-label, multicenter trial (NCT01229735), adults were randomized to treatment with LEV (1000-3000 mg/day) or TPM (200-400 mg/day). Only patients achieving LEV ≥1000 mg/day or TPM ≥100 mg/day after a 4-week up-titration entered the 20-week dose-finding and subsequent 28-week maintenance periods. The primary outcome was the 52-week retention rate; others included safety and exploratory efficacy outcomes.. Of 343 randomized patients (LEV 177; TPM 166), 211 (61.5%) completed the trial. In the full analysis set (FAS), retention rate was 59.1% with LEV vs 56.6% with TPM (p = 0.7007), while in the prespecified sensitivity analysis, based on data from patients who received drug doses in the recommended range (LEV 176; TPM 113), it was 59.1% with LEV vs 42.5% with TPM (p = 0.0086). In the FAS, median percent reduction in seizure frequency from baseline was 74.47% with LEV and 67.86% with TPM (p = 0.0665); ≥50% responder rate was 69.0% vs 64.8% (p = 0.4205), and the 6-month seizure-freedom rate was 35.8% vs 22.3% (p = 0.0061). In the sensitivity analysis, differences between groups were greater, favoring LEV. Incidences of treatment-emergent adverse events (TEAEs) were 70.6% with LEV vs 77.1% with TPM; most frequently somnolence (20.3%), dizziness (18.1%), and nasopharyngitis (13.6%) with LEV; and decreased appetite (15.7%), dizziness (14.5%), and headache (14.5%) with TPM. Discontinuations due to TEAEs were 7.9% with LEV and 12.7% with TPM.. In this open-label trial, the 52-week retention rate was not significantly different between LEV and TPM. However, LEV was associated with a substantially higher seizure freedom rate and a more favorable safety profile than TPM in this population of Korean patients with focal seizures.

Topics: Adult; Anticonvulsants; Dizziness; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Headache; Humans; Levetiracetam; Male; Middle Aged; Republic of Korea; Seizures; Sleepiness; Topiramate

Prediction of brivaracetam effects in children was obtained by scaling an existing adult pharmacokinetic/pharmacodynamic (PK/PD) model for brivaracetam to children, using an existing population PK model for brivaracetam in children. The scaling was supported by estimating the change from adults to children in the concentration-effect relationship parameters for levetiracetam, a compound interacting with the same target protein (synaptic vesicle protein SV2A).. The existing adult PK/PD model for brivaracetam was applied to a combined adult-pediatric dataset of levetiracetam. This model was then used to predict the effective oral twice-daily dose of brivaracetam in children aged ≥4 to <16 years as adjunctive treatment for focal (partial onset) seizures. The existing model described daily seizure counts using a negative binomial distribution, taking previous-day seizure frequencies into account, and using a mixture model to separate 'placebo-like' and 'responder' subpopulations. The model was adapted to describe aggregated monthly seizure counts for adult patients in the levetiracetam studies: daily seizure counts were only available for children in the levetiracetam studies.. The levetiracetam PK/PD model successfully described both the adult and pediatric data using the same drug effect parameters, and using a model structure similar to the existing adult brivaracetam PK/PD model.. Simulation with the adult brivaracetam PK/PD model in combination with an existing pediatric brivaracetam population PK model allowed characterization of the dose-response curve, suggesting maximum response at brivaracetam 4 mg/kg/day dosing (capped at 200 mg/day, the maximum adult dose) in children aged ≥4 years.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Models, Theoretical; Pyrrolidinones; Seizures; Young Adult

To investigate the effects of antiepileptic drugs (AEDs; oxcarbazepine [OXC], levetiracetam [LEV], and lamotrigine [LTG]) on semen quality, sexual function, and sex hormones in male adults with epilepsy.. Individual treatment with OXC, LEV, or LTG was randomly assigned to 38 newly diagnosed male adult patients with epilepsy. Semen quality and sex hormones were measured before treatment and 6 months after taking the medicine. A questionnaire was administered using the International Index of Erectile Function Scale-5 and the Premature Ejaculation Diagnostic Tool Self-Assessment Scale to evaluate sexual function, followed by an analysis of the comparison between the treated patients and healthy volunteers (healthy controls) as well as the changes and differences between the patients themselves before and after treatment.. The total sperm count, fast forward movement rate (FFMR), survival rate, and normal sperm rate in the group with epilepsy were lower than those in healthy controls (P < .05). The FFMR and survival rate of sperm after OXC treatment were significantly higher than before treatment (P < .05). All semen parameters after LEV and LTG showed a possible trend for improvement, but no significant statistical difference. There was no significant difference in sexual function between patients and the control group, as well as before and after treatment with the 3 different AEDs. There was no significant difference in sex hormone levels in the epilepsy group before treatment compared with the healthy controls, or when compared after treatment with the 3 different AEDs. The marital rate and fertility rate of patients with epilepsy were significantly lower than those of healthy controls (P < .05).. The semen quality of males with epilepsy is decreased even before treatment. The AEDs (OXC, LEV, and LTG) have no significant effect on sexual function and sex hormones, and OXC can improve the sperm FFMR and survival rate.

Topics: Adult; Anticonvulsants; Epilepsies, Partial; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Fertility; Gonadal Steroid Hormones; Humans; Lamotrigine; Levetiracetam; Male; Marital Status; Oxcarbazepine; Semen Analysis

To investigate the effects of sodium channel-blocking antiepileptic drugs (AEDs) on functional magnetic resonance imaging (fMRI) language network activations in patients with focal epilepsy.. In a retrospective study, we identified patients who were treated at the time of language fMRI scanning with either carbamazepine (CBZ; n = 42) or lamotrigine (LTG; n = 42), but not another sodium channel-blocking AED. We propensity-matched 42 patients taking levetiracetam (LEV) as "patient-controls" and included further 42 age- and gender-matched healthy controls. After controlling for age, age at onset of epilepsy, gender, and antiepileptic comedications, we compared verbal fluency fMRI activations between groups and out-of-scanner psychometric measures of verbal fluency.. Patients on CBZ performed less well on a verbal fluency tests than those taking LTG or LEV. Compared to either LEV-treated patients or controls, patients taking CBZ showed decreased activations in left inferior frontal gyrus and patients on LTG showed abnormal deactivations in frontal and parietal default mode areas. All patient groups showed fewer activations in the putamen bilaterally compared to controls. In a post hoc analysis, out-of-scanner fluency scores correlated positively with left putamen activation.. Our study provides evidence of AED effects on the functional neuroanatomy of language, which might explain subtle language deficits in patients taking otherwise well-tolerated sodium channel-blocking agents. Patients on CBZ showed dysfunctional frontal activation and more pronounced impairment of performance than patients taking LTG, which was associated only with failure to deactivate task-negative networks. As previously shown for working memory, LEV treatment did not affect functional language networks.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Brain; Carbamazepine; Cognition; Dose-Response Relationship, Drug; Drug Resistant Epilepsy; Epilepsies, Partial; Female; Humans; Lamotrigine; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Net; Retrospective Studies; Young Adult

The aim of this trial was to compare the efficacy and safety of two formulations of levetiracetam in people with partial epilepsy over a 12-week treatment period.. We performed a randomized, paralleled, and multicenter trial that consisted of a 4-week single-blind placebo run-in, followed by a 12-week double-blind, double-dummy treatment phase to compare the efficacy and safety of levetiracetam extended-release (LEV-ER) and immediate-release (LEV-IR) tablets as an adjunctive treatment in adult patients with uncontrolled epilepsy.. The median partial-onset seizure (POS) frequency per week (min-max) was 0.3 (0.0, 17.4; 95% confidence interval [95% CI] 1.3, 4.8) in the LEV-ER group and 0.3 (0.0, 31.4; 95% CI - 0.1, 4.3) in the LEV-IR group. No serious adverse events occurred during the trial period. Both groups had the same responder rate (58.6%), while a higher rate of seizure freedom over the treatment period was noted in the LEV-ER group compared with the LEV-IR group (27.6% vs. 13.8%, respectively). The European Quality of Life-5 Dimensions scores significantly increased in the LEV-ER-treated group, in contrast to the scores in the LEV-IR group, which decreased (7.2 vs. - 1.5, p = 0.03).. These results suggest that LEV-ER is equivalent to LEV-IR in reducing the frequency of POS and has a similar tolerability as LEV-IR as an add-on therapy. In addition, LEV-ER treatment improved the health-related quality of life of people with uncontrolled partial epilepsy.

Topics: Adolescent; Adult; Anticonvulsants; Double-Blind Method; Drug Delivery Systems; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Quality of Life; Time Factors; Treatment Outcome; Young Adult

This open-label, multicenter, randomized phase IV trial (NCT01498822) of noninferiority design compared the long-term effectiveness, safety, and tolerability of levetiracetam (LEV) monotherapy with those of oxcarbazepine (OXC) monotherapy in adults with newly diagnosed focal epilepsy. Korean patients (16-80 years), with ≥2 unprovoked focal seizures in the year preceding the trial, who had not taken any antiepileptic drugs (AEDs) in the last 6 months, were randomized to receive LEV or OXC (1:1). Effectiveness, safety, and tolerability were assessed over a 50-week period. Treatment failure rates (per protocol set) were 15/118 (12.7%) in the LEV-treated group and 30/128 (23.4%) in the OXC-treated group, an absolute difference of -10.7% (95% confidence interval [CI] -20.2, -1.2). Because the upper 95% CI limit was less than the pre-specified noninferiority margin of 15%, LEV was considered noninferior to OXC. Twenty-four-week and 48-week seizure freedom rates were 53.8% and 34.7% for LEV vs. 58.5% and 40.9% for OXC. Both LEV and OXC were well tolerated, with 8.7% and 8.6% of patients reporting serious treatment-emergent adverse events, respectively. By comparing LEV with OXC, another newer AED, LEV can be considered a useful option as initial monotherapy for patients with newly diagnosed focal epilepsy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Carbamazepine; Dose-Response Relationship, Drug; Epilepsies, Partial; Female; Humans; Levetiracetam; Longitudinal Studies; Male; Middle Aged; Oxcarbazepine; Piracetam; Republic of Korea; Treatment Outcome; Young Adult

Patients with focal seizures recruited into adjunctive antiepileptic drug (AED) trials have become more refractory and severe over time; concurrently, placebo responses have increased. To attempt to account for heterogeneity among trials, propensity-score weighted patient-level data were used to indirectly compare placebo responses reported in brivaracetam and levetiracetam trials.. Patient-level data from randomised, placebo-controlled brivaracetam (recruited 2007-2014) and levetiracetam (1993-1998) trials were pooled. Consistent inclusion/exclusion criteria were applied and outcomes were defined consistently. Potentially confounding baseline characteristics were adjusted for using propensity score weighting. Weighting success was assessed using placebo response.. In total, 707 and 473 active drug and 399 and 253 placebo patients comprised the brivaracetam and levetiracetam groups, respectively. Before weighting, several baseline variables were significantly different between groups; after weighting, prior vagal nerve stimulation, co-morbid depression and co-morbid anxiety remained different. Before weighting, median seizure frequency reduction was 21.7 and 3.9% in the brivaracetam and levetiracetam placebo arms, respectively; after weighting, median reduction was 15.0 and 6.0%. The comparison of non-randomised groups could be biased by unobserved confounding factors and region of residence. Lifetime AED history was unavailable in the brivaracetam trials and excluded from analysis.. Placebo responses remained different between brivaracetam and levetiracetam trials after propensity score weighting, indicating the presence of residual confounding factors associated with placebo response in these trials. It therefore remains problematic to conduct reliable indirect comparisons of brivaracetam and levetiracetam given the current evidence base, which may apply to comparisons between other AED trials.

Topics: Adult; Anticonvulsants; Databases, Bibliographic; Double-Blind Method; Epilepsies, Partial; Female; Humans; Levetiracetam; Longitudinal Studies; Male; Middle Aged; Piracetam; Placebo Effect; Pyrrolidinones; Retrospective Studies; Treatment Outcome

To assess prospectively the effectiveness of lacosamide (LCM) added to levetiracetam (LEV) after down-titration of a concomitant sodium channel blocker (SCB) among patients with focal epilepsy not adequately controlled on LEV and SCB.. In this open-label trial, LCM was initiated at 100 mg/day and up-titrated to 200-600 mg/day over 9 weeks; SCB down-titration started when LCM dose reached 200 mg/day. Patients remained on stable LCM/LEV doses for 12 weeks' maintenance (21-week treatment period). The primary outcome was retention rate on LCM.. Due to recruitment challenges, fewer than the planned 300 patients participated in the trial, resulting in the trial being underpowered. Overall, 120 patients (mean age 39.7 years) started and 93 completed the trial. The most frequently used SCBs were lamotrigine (39.2%), carbamazepine (30.8%) and oxcarbazepine (27.5%). Eighty-four patients adhered to protocol and discontinued their SCB after cross-titration, but there was insufficient evidence for 36 patients. Retention rate was 73.3% (88/120) for all patients and 83.3% (70/84) for those with evidence of SCB discontinuation. Seizure freedom for patients completing maintenance was 14.0% (13/93). Discontinuation due to adverse events (6.7%) and lack of efficacy (3.3%) occurred primarily during cross-titration. Most frequently reported adverse events during treatment were dizziness (23.3%), headache (15.0%) and fatigue (8.3%).. In patients with uncontrolled seizures on LEV/SCB, the LCM/LEV combination appeared to be effective and well tolerated. A cross-titration schedule-flexible LCM up-titration, concomitant SCB down-titration and stable background LEV-could present a feasible and practical approach to initiating LCM while minimizing pharmacodynamic interactions with a SCB.

Topics: Acetamides; Adult; Anticonvulsants; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Lacosamide; Levetiracetam; Male; Middle Aged; Piracetam; Sodium Channel Blockers

This was an open-label study (N01281 [NCT00419393]) assessing the long-term safety of extended-release levetiracetam (LEV XR) in patients with partial-onset seizures (POS); the study was a follow-up to a double-blind, randomized, historical controlled, multicenter, conversion to monotherapy study (N01280 [NCT00419094]). Eligible patients initially received LEV XR 2000 mg/day; dose adjustments and the addition of other antiepileptic drugs (AEDs) were permitted. Overall, 190 patients were enrolled, 189 (99.5%) received LEV XR (safety and efficacy populations) and 166 patients (87.4%) completed the study. The study duration in completed patients was 5.5-24.6 months. Mean daily dose of LEV XR was 2131 mg/day. Treatment-emergent adverse events (TEAEs) occurred in 126 patients (66.7%); most were of mild or moderate severity. Five patients (2.6%) had a TEAE that led to treatment discontinuation. Treatment-emergent serious adverse events occurred in 22 patients (11.6%). Twenty-six patients (13.8%) experienced a psychiatric TEAE. The median 7-day normalized POS frequency was: 1.38 at N01280 study baseline; 0.50 at the first visit of N01281 (last visit of N01280); and 0.00-0.36 between all subsequent visits. Overall, 171 patients (90.5%) entered the N01281 study on LEV XR monotherapy; 65.3% (32/49) of patients remained on monotherapy for 12 months and 47.1% (8/17) for 18 months. While remaining on LEV XR monotherapy, 27/139 patients (19.4%) were seizure-free at 6 months and 8/49 (16.3%) at 12 months. In conclusion, LEV XR was well tolerated when administered as long-term monotherapy or in combination with other AEDs in patients with inadequately controlled POS.

Topics: Adult; Anticonvulsants; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Piracetam; Seizures; Treatment Outcome

Assess cognitive effects of adjunctive perampanel in adolescents.. In this double-blind study (ClinicalTrials.gov identifier: NCT01161524), patients aged 12 to <18 years with partial-onset seizures despite receiving 1-3 antiepileptic drugs were randomized (2:1) to perampanel or placebo. Perampanel was increased weekly in 2-mg increments to 8-12 mg/day (6-week titration; 13-week maintenance). Changes in neuropsychological outcomes were assessed at end of maintenance: Cognitive Drug Research (CDR) System Global Cognition Score (primary end point), five CDR System domain T-scores (secondary end points), letter fluency, category fluency, and Lafayette Grooved Pegboard Test (LGPT).. One hundred thirty-three patients were randomized. In the full analysis set, there were no differences of perampanel (n = 79) vs. placebo (n = 44) in CDR System Global Cognition Score (least squares mean change, -0.6 vs. 1.6; p = 0.145), Quality of Working Memory (1.1 vs. 2.0; p = 0.579), or Power of Attention (-6.9 vs. -2.7; p = 0.219). There were small differences with perampanel vs. placebo in other CDR System domains: improvements in Quality of Episodic Memory (3.0 vs. -1.2; p = 0.012), and worsening in Continuity of Attention (-3.3 vs. 1.6; p = 0.013) and Speed of Memory (0.3 vs. 7.0; p = 0.032). Letter fluency, category fluency, and LGPT were not significantly different between groups. The most frequent adverse events with perampanel were dizziness (30.6%) and somnolence (15.3%).. Perampanel did not differ from placebo in the global cognitive score, two of five subdomains, and four other cognitive measures. Perampanel was worse on two and better on one subdomain.

Topics: Acetamides; Adolescent; Anticonvulsants; Attention; Carbamazepine; Child; Cognition; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Lacosamide; Lamotrigine; Levetiracetam; Male; Memory, Short-Term; Neuropsychological Tests; Nitriles; Oxcarbazepine; Piracetam; Pyridones; Topiramate; Treatment Outcome; Triazines; Valproic Acid

To assess the efficacy, safety, and tolerability of adjunctive brivaracetam (BRV), a selective, high-affinity ligand for SV2A, for treatment of partial-onset (focal) seizures (POS) in adults.. Data were pooled from patients (aged 16-80 years) with POS uncontrolled by 1 to 2 antiepileptic drugs receiving BRV 50, 100, or 200 mg/d or placebo, without titration, in 3 phase III studies of BRV (NCT00490035, NCT00464269, and NCT01261325, ClinicalTrials.gov, funded by UCB Pharma). The studies had an 8-week baseline and a 12-week treatment period. Patients receiving concomitant levetiracetam were excluded from the efficacy pool.. In the efficacy population (n = 1,160), reduction over placebo (95% confidence interval) in baseline-adjusted POS frequency/28 days was 19.5% (8.0%-29.6%) for 50 mg/d (p = 0.0015), 24.4% (16.8%-31.2%) for 100 mg/d (p < 0.00001), and 24.0% (15.3%-31.8%) for 200 mg/d (p < 0.00001). The ≥50% responder rate was 34.2% (50 mg/d, p = 0.0015), 39.5% (100 mg/d, p < 0.00001), and 37.8% (200 mg/d, p = 0.00003) vs 20.3% for placebo (p < 0.01). Across the safety population groups (n = 1,262), 90.0% to 93.9% completed the studies. Treatment-emergent adverse events (TEAEs) were reported by 68.0% BRV overall (n = 803) and 62.1% placebo (n = 459). Serious TEAEs were reported by 3.0% (BRV) and 2.8% (placebo); 3 patients receiving BRV and one patient receiving placebo died. TEAEs in ≥5% patients taking BRV (vs placebo) were somnolence (15.2% vs 8.5%), dizziness (11.2% vs 7.2%), headache (9.6% vs 10.2%), and fatigue (8.7% vs 3.7%).. Adjunctive BRV was effective and generally well tolerated in adults with POS.. This analysis provides Class I evidence that adjunctive BRV is effective in reducing POS frequency in adults with epilepsy and uncontrolled seizures.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Pyrrolidinones; Seizures; Young Adult

Treatment with enzyme-inducing antiepileptic drugs (AEDs) such as carbamazepine (CBZ) can lead to changes in reproductive, endocrine, and lipid parameters, resulting in clinical symptoms for some patients. Previous studies indicate that these changes can be reversed by switching to a nonenzyme-inducing AED. Lacosamide is a newer-generation AED, not known to induce or strongly inhibit cytochrome P450 (CYP450) enzymes. In this phase IIIb, prospective, multicenter, open-label, single-arm trial (NCT01375374), the serum concentrations of CYP-related reproductive hormones, thyroid hormones, and lipids were assessed in otherwise healthy male patients with focal seizures (N=11), before and after a switch from CBZ (600-1200mg/day at baseline) to lacosamide (target dose: 400mg/day by the end of titration) as adjunctive treatment to the nonenzyme-inducing AED levetiracetam (LEV, stable dosage of >1000mg/day throughout). Cross titration took place over 4weeks, followed by an 8-week maintenance period. Serum measurements were conducted at baseline and at the end of maintenance. The median serum sex-hormone-binding globulin (SHBG) concentration was towards the higher end of the normal range at baseline and decreased following the switch (61.7 to 47.5nmol/L, N=10, p=0.027 by Wilcoxon signed-rank test). Free androgen index (100×testosterone/SHBG) and free thyroxine serum concentration increased (25.4 to 36.4 and 13.0 to 14.9pmol/L, respectively, both N=10 and p=0.002). At baseline, the median progesterone serum concentration was below the normal range (0.7nmol/L), whereas median cholesterol and low-density lipoprotein concentrations were above the normal range (5.5 and 3.6mmol/L, respectively). By the end of maintenance, all measured parameters were within the normal range. The safety and tolerability profile of lacosamide was consistent with that observed in previous studies. Furthermore, antiseizure efficacy appeared to be maintained, suggesting that deinduction of CYP enzymes following a switch from CBZ to lacosamide as adjunctive therapy to LEV is feasible within 8weeks and is associated with normalization of serum parameters.

Topics: Acetamides; Adult; Anticonvulsants; Carbamazepine; Cholesterol; Dose-Response Relationship, Drug; Drug Substitution; Drug Therapy, Combination; Epilepsies, Partial; Humans; Lacosamide; Levetiracetam; Lipids; Lipoproteins, LDL; Male; Piracetam; Progesterone; Prospective Studies; Sex Hormone-Binding Globulin; Testosterone; Thyroxine; Treatment Outcome

The aim of this study was to confirm the efficacy and safety of adjunctive levetiracetam in adult Japanese patients with uncontrolled partial-onset seizures.. In a double-blind, placebo-controlled, confirmatory trial, eligible patients were randomized to receive levetiracetam 500, 1000, 2000, or 3000 mg/day or placebo for 16 weeks. The primary end-point was percentage reduction from baseline in seizure frequency/week over a 12-week evaluation period. Tolerability assessments were also conducted. Findings of this and a previous randomized, double-blind trial were compared.. Of 401 patients screened, 352 were randomized and 316 completed the study. Median percentage reduction in seizure frequency/week from baseline was 12.92%, 18.00%, 11.11% and 31.67% in the levetiracetam 500, 1000, 2000 and 3000-mg groups, respectively, compared with 12.50% in the placebo group. Unlike the previous trial, the primary efficacy analysis between the levetiracetam 1000 and 3000-mg and placebo groups did not reach statistical significance (P = 0.067). Exploratory analyses demonstrated that the difference in seizure reduction versus placebo was 14.93% (95% confidence interval, 1.98-27.64; P = 0.025) for the levetiracetam 3000-mg group. All levetiracetam doses were well tolerated. The main difference between the two trials was a high placebo response in the present trial.. The primary efficacy analysis did not reach statistical significance, a finding that could be attributed to an unexpectedly high placebo response. Nonetheless, exploratory analysis suggests that levetiracetam at 3000 mg/day may, at least marginally, be beneficial for patients with uncontrolled partial-onset seizures.

Topics: Adolescent; Adult; Anticonvulsants; Double-Blind Method; Epilepsies, Partial; Female; Humans; Japan; Levetiracetam; Male; Middle Aged; Molecular Sequence Data; Piracetam; Placebo Effect; Treatment Outcome; Young Adult

To prospectively evaluate the neuropsychological effect of levetiracetam (LVT) in comparison with carbamazepine (CBZ) and its efficacy and tolerability as a monotherapy in children with focal epilepsy.. A total of 121 out of 135 screened children (4-16 years) were randomly assigned to LVT or CBZ groups in a multicenter, parallel-group, open-label trial. The study's primary endpoints were defined as the end of 52 weeks of treatment, followed by analysis of changes observed in a series of follow-up neurocognitive, behavioral, and emotional function tests performed during treatment in the per protocol population. Drug efficacy and tolerability were also analyzed among the intention-to-treat (ITT) population (ClinicalTrials.gov, number NCT02208492).. Eighty-one patients (41 LVT, 40 CBZ) from the randomly assigned ITT population of 121 children (57 LVT, 64 CBZ) were followed up to their last visit. No significant worsening or differences were noted between groups in neuropsychological tests, except for the Children's Depression Inventory (LVT -1.97 vs CBZ +1.43, p = 0.027, [+] improvement of function). LVT-treated patients showed an improvement (p = 0.004) in internalizing behavioral problems on the Korean Child Behavior Checklist. Seizure-free outcomes were not different between the 2 groups (CBZ 57.8% vs LVT 66.7%, p = 0.317).. Neither LVT nor CBZ adversely affected neuropsychological function in pediatric patients. Both medications were considered equally safe and effective as monotherapy in children with focal epilepsy.. This study provides Class II evidence that in patients with pediatric focal epilepsy, LVT and CBZ exhibit equivalent effects on neuropsychological function.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child Behavior; Child, Preschool; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Intelligence; Levetiracetam; Male; Piracetam; Social Skills; Treatment Outcome

To assess efficacy/tolerability of ezogabine (EZG)/retigabine (RTG) in combination with specified monotherapy antiepileptic drug (AED) treatments in adults with uncontrolled partial-onset seizures using a flexible dosing regimen.. NCT01227902 was an open-label, uncontrolled study of flexibly dosed EZG/RTG. Adults with partial-onset seizures must have been taking either carbamazepine/oxcarbazepine (CBZ/OXC), lamotrigine (LTG), levetiracetam (LEV), or valproic acid (VPA). The study comprised a screening/baseline phase, a 4-week titration phase (initiation on 150mg/day [50mg three times daily (TID)] with weekly increases of 150mg/day [50mg TID] over 4 weeks to 600mg/day), and a flexible dose evaluation (FDE) phase (optional weekly dose changes of 50-150mg/day, to an optimal daily dosage [300-1200mg/day]). The primary efficacy endpoint was percentage of patients experiencing a ≥50% reduction from baseline in partial seizure frequency (responder rate) during the treatment phase (titration and FDE phases). Safety and tolerability were also assessed.. Patients (N=203) were enrolled and received ≥1 dose of EZG/RTG. The dose of EZG/RTG prescribed most frequently during the treatment phase was 600mg/day for all AED groups. Responder rates during the treatment phase were: 40.0% (CBZ/OXC), 32.0% (LTG), 50.0% (LEV), and 56.9% (VPA). Treatment-emergent adverse events occurred in 82% (CBZ/OXC), 76% (LTG), 73% (LEV), and 67% (VPA) of patients; most were of mild-to-moderate intensity.. EZG/RTG was effective as adjunctive therapy to CBZ/OXC, LTG, LEV, and VPA, using a flexible dosing regimen, in adults with partial-onset seizures; safety and tolerability were consistent with that previously observed.

Topics: Aged; Anticonvulsants; Carbamates; Carbamazepine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Kaplan-Meier Estimate; Lamotrigine; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Phenylenediamines; Piracetam; Seizures; Treatment Outcome; Triazines; Valproic Acid

Following the first period of the multicenter, open-label, single-armed N01223 trial, the second period of the N01223 trial was conducted to evaluate long-term safety, along with the efficacy of adjunctive levetiracetam treatment (individualized dose range, 20-60 mg/kg/day or 1,000-3,000 mg/day) in Japanese pediatric patients with uncontrolled partial-onset seizures (POS). Of the 62 children who completed the first period, 55 children [age: 10.4 ± 3.4 years (mean ± standard deviation)] were elected to enter the second period for a maximum of 39 months. Twenty children were withdrawn during this second period. Frequencies of treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) were 98.2% (54/55 cases) and 27.3% (15/55 cases), respectively. The most common TEAEs were nasopharyngitis (76.4%), influenza (36.4%) and pyrexia (25.5%). The only frequent ADR (>2%) was somnolence (3.6%). Although serious TEAEs and death were reported in 8 cases and 1 case (drowning), respectively, a serious ADR was only reported in 1 case (vomiting). The median percentage reduction and 50% response rate for POS were 43.32% and 41.8%, respectively. One child showed a maximum seizure-free period of 163 days. In conclusion, levetiracetam demonstrated long-term safety and good tolerance with beneficial efficacy as an adjunctive therapy in Japanese children with uncontrolled POS. (Received June 30, 2015; Accepted July 14, 2015: Published November 1, 2015).

Topics: Adolescent; Anticonvulsants; Asian People; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Piracetam; Seizures; Time; Treatment Outcome

To assess the comparative efficacy and safety of pregabalin and levetiracetam for the reduction of seizure frequency in patients with partial seizures.. This was a randomized, double-blind, flexible-dose, parallel-group noninferiority study of pregabalin and levetiracetam (randomized 1:1) as adjunctive treatment in adult patients with refractory partial seizures. The study included a 6-week baseline phase, 4-week dose-escalation phase, and 12-week maintenance phase. The primary endpoint was the proportion of patients with a ≥ 50% reduction in 28-day seizure rate during the 12-week maintenance phase, as compared with baseline. Noninferiority of pregabalin was declared if the lower limit of the 95% confidence interval (CI) for the difference in responder rates was greater than the prespecified noninferiority margin of -12%. A key secondary endpoint was the percent change from baseline in 28-day seizure rate during the dose-escalation and maintenance phases.. Five hundred nine patients were randomized to pregabalin (n = 254) or levetiracetam (n = 255) and 418 (208 pregabalin, 210 levetiracetam) completed the maintenance phase. With both pregabalin and levetiracetam, the proportion of patients with a ≥ 50% reduction in 28-day seizure rate was 0.59 (difference between groups [95% CI], 0.00 [-0.08 to 0.09]). Because the lower bound of the 95% CI was greater than the prespecified noninferiority margin of -12%, pregabalin was not inferior to levetiracetam. There was no significant difference between pregabalin and levetiracetam in the percent change in 28-day seizure rate (median difference [95% CI], 4.1 [-2.6 to 10.9], p = 0.3571). In a post hoc analysis, the proportion of patients who were seizure-free for the maintenance phase was lower with pregabalin (8.4%) than with levetiracetam (16.2%), p = 0.0155. Safety profiles were similar and consistent with prior trials.. These results indicate that pregabalin is noninferior, and has a similar tolerability, to levetiracetam as adjunctive therapy in reducing seizure frequency in patients with partial seizures.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Female; gamma-Aminobutyric Acid; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Pregabalin; Treatment Outcome; Young Adult

Epilepsy is a common paediatric neurologic disorder that is difficult to manage in a substantial portion of children, highlighting the continued need for more effective and better tolerated drugs. A multicentric study was conducted from August, 2011 to July, 2013 using levetiracetam (LEV) in newely diagnosed epilepsy in 122 young children of 1-5 years age group to find its role in practical scenario depending upon the knowledge from prior literature available. It has been demonstrated effective as adjunctive therapy as well as monotherapy for new-onset partial seizures and generalised tonic-clonic seizures (GTCS) but it acts better as adjunctive therapy than the monotherapy. When LEV was used as adjunctive therapy 15.4% children with partial seizure were seizure-free as compared to 11.12% in GTCS and when LEV was used as monotherapy 16.17% children with partial seizure were seizure-free as compared to 15.38% in GTCS. When LEV was used as add on therapy 16.67% children < 2 years were seizure-free as compared to 17.85% in > 2 years. When LEV was used as monotherapy 25.00% children < 2 years were seizure-free as compared to 18.18% > 2 years. So, it was found more efficacious in partial group of seizures than the GTCS variety. It also shows more efficacy in older age group (> 2 years) than the younger ones (< 2 years). Somnolence and behavioural changes were noted as ad- verse effects in a few cases. So, LEV is an important addition to the treatment of paediatric epilepsy.

Topics: Age Factors; Anticonvulsants; Child, Preschool; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Tonic-Clonic; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Tertiary Care Centers

To compare the effectiveness of levetiracetam (LEV) with extended-release sodium valproate (VPA-ER) and controlled-release carbamazepine (CBZ-CR) as monotherapy in patients with newly diagnosed epilepsy.. This unblinded, randomised, 52-week superiority trial (NCT00175903) recruited patients (≥16 years of age) with ≥2 unprovoked seizures in the previous 2 years and ≥1 in the previous 6 months. The physician chose VPA or CBZ as preferred standard treatment; each patient was randomised to standard treatment or LEV. The primary outcome was time to treatment withdrawal (LEV vs standard antiepileptic drugs (AEDs)). Analyses also compared LEV with VPA-ER, and LEV with CBZ-CR.. 1688 patients (mean age 41 years; 44% female) were randomised to LEV (n=841) or standard AEDs (n=847). Time to treatment withdrawal was not significantly different between LEV and standard AEDs: HR (95% CI) 0.90 (0.74 to 1.08). Time to treatment withdrawal (HR (95% CI)) was 1.02 (0.74 to 1.41) for LEV/VPA-ER and 0.84 (0.66 to 1.07) for LEV/CBZ-CR. Time to first seizure (HR, 95% CI) was significantly longer for standard AEDs, 1.20 (1.03 to 1.39), being 1.19 (0.93 to 1.54) for LEV/VPA-ER and 1.20 (0.99 to 1.46) for LEV/CBZ-CR. Estimated 12-month seizure freedom rates from randomisation: 58.7% LEV versus 64.5% VPA-ER; 50.5% LEV versus 56.7% CBZ-CR. Similar proportions of patients within each stratum reported at least one adverse event: 66.1% LEV versus 62.0% VPA-ER; 73.4% LEV versus 72.5% CBZ-CR.. LEV monotherapy was not superior to standard AEDs for the global outcome, namely time to treatment withdrawal, in patients with newly diagnosed focal or generalised seizures.

Topics: Adult; Anticonvulsants; Carbamazepine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Electroencephalography; Epilepsies, Partial; Epilepsy, Generalized; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Levetiracetam; Male; Middle Aged; Patient Dropouts; Piracetam; Quality of Life; Signal Processing, Computer-Assisted; Valproic Acid

The objective of this study was to assess cognition and behavior in children (4-16 years; n = 103) with partial-onset seizures using the Leiter-R International Performance Scale and Achenbach Child Behavior Checklist. The study was a multicenter, open-label, noncomparative 48-week extension study (NCT00152516) of adjunctive levetiracetam (20-100 mg/kg/d, mean 50.2 mg/kg/d). Improvement from baseline in Leiter-R Memory Screen composite score at weeks 24 and 48 (mean [SD] change, +4.8 [12.6] and +4.5 [15.3]) was similar to changes observed with levetiracetam and placebo in a prior study. Child Behavior Checklist Syndrome scores improved from baseline at weeks 24 and 48 (total problems mean [SD] change, -9.3 [22.2] and -10.4 [23.4]). Adjunctive levetiracetam was well tolerated (most frequently reported central nervous system-related treatment-emergent adverse events: headache [24.3%], aggression [7.8%], irritability [7.8%]). Of the patients, 4.9% discontinued because of treatment-emergent adverse events. Levetiracetam provided good and sustained seizure control (median percentage reduction from baseline in partial-onset seizure frequency/wk during maintenance: 86.4%); 24.7% of patients had continuous seizure freedom from all seizure types for ≥40 weeks. In children, adjunctive levetiracetam was associated with long-term stability in cognitive functioning and improvement in emotional/behavioral functioning over time.

Topics: Adolescent; Age Factors; Anticonvulsants; Behavioral Symptoms; Child; Child, Preschool; Cognition Disorders; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Longitudinal Studies; Male; Neuropsychological Tests; Piracetam; Psychiatric Status Rating Scales; Treatment Outcome

This double-blind, randomised, multicentre, conversion to monotherapy, historical control study (N01280; NCT00419094) evaluated the efficacy, safety and tolerability of levetiracetam extended release (LEV XR) 2000mg/day once daily for the treatment of patients with partial-onset seizures compared with a historical control. Patients aged 12-75 years with 2-40 partial-onset seizures per 4 weeks, taking 1-2 antiepileptic drugs (AEDs) and receiving a stable dosage for ≥4 weeks prior to screening were randomised in a 3:1 ratio to LEV XR 2000 or 1000 mg/day. The study comprised baseline (8 weeks), LEV XR up-titration (2 weeks), baseline AED tapering (6 weeks), LEV XR monotherapy (10 weeks), and entry into open-label follow-up study or down-titration (1 week). The primary efficacy variable was the cumulative exit rate at Day 112 due to predefined exit criteria compared with the historical control. Of the 171 patients randomised to LEV XR 2000 mg/day and 57 randomised to 1000 mg/day, 141 (82.5%) and 50 (87.7%) completed the study. The cumulative exit rate for patients on LEV XR 2000 mg/day (0.375 [95% CI 0.297, 0.453]) was significantly lower than historical control (0.653). Both LEV doses were well tolerated. The most common adverse events during the treatment period were somnolence (21.9%), headache (19.7%) and convulsion (14.9%).

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Double-Blind Method; Epilepsies, Partial; Female; Humans; Kaplan-Meier Estimate; Levetiracetam; Male; Middle Aged; Piracetam; Sample Size; Treatment Outcome; Young Adult

The long-term safety and efficacy of levetiracetam (LEV) was evaluated as add-on therapy in focal epilepsy patients (n=491) aged at least 65 years who failed at least one monotherapy.. Patients (n=491) with focal epilepsy treated with at least one antiepileptic drug in monotherapy with insufficient seizure control were included in this prospective open-label study. The recommended LEV dose range was 1000-3000 mg per day. Follow-up visits were done approximately after 3, 6 and 12 months. Safety and efficacy was analysed based on all patients who received LEV (safety population, n=491) and all patients who were seen at all visits and completed the trial (per protocol population, n=364).. Patients (53% men, median age 71 years) had a total of 97 adverse events (AEs) reported in 53 patients. The most common AEs were fatigue and restlessness (9.7% each of all AEs). A total of 35 serious AEs occurred in 19 patients (3.9% of the safety population), all but one unrelated to the study medication. Mean monthly seizure frequency dropped significantly from 7.0 (SD 8.7, range 1-85, median 4) at baseline to 1.7 (SD 2.9, range 0-29, median 1) at 3 month, 1.2 (SD 2.6, range 0-30, median 0) at 6, and 1.4 (SD 6.6, range 0-99, median 0) at 12 months, corresponding to a reduction of 75.7%, 82.9%, and 80.0% relative to baseline. Seizure freedom was reported by 42%, 57.7%, and 58% of patients during the previous period at 3, 6 and 12 months follow-up, respectively.. Add-on treatment with LEV in elderly patients with focal epilepsy was safe and efficient. Levetiracetam might be considered as a suitable drug in the elderly.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Piracetam

This study evaluated the safety and efficacy of levetiracetam as adjunctive therapy for partial seizures in everyday clinical practice in Asian populations. Patients aged > or =16 years (N=251) with inadequately controlled partial epilepsy were recruited from 29 centers across Asia. Levetiracetam was added to existing antiepileptic medication for 16 weeks at a starting dose of 500 or 1000 mg/day and titrated to a maximum of 3000 mg/day according to clinical response. The study completion rate was 86.9%. Adverse events were reported by 73.3% of patients and were generally mild, leading to treatment withdrawal in only 7.2%. The most common adverse events were somnolence (30.3%) and dizziness (14.7%). Compared with pretreatment baseline, 44.0% of patients had a > or =50% reduction in seizure frequency, with a median reduction of 46.4%, and 17.7% became seizure free during the treatment period. Levetiracetam was well tolerated and efficacious as adjunctive therapy for partial epilepsy in clinical practice among Asian populations.

Topics: Adolescent; Adult; Anticonvulsants; Asian People; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Intention to Treat Analysis; Levetiracetam; Male; Patient Selection; Piracetam; Treatment Outcome

A randomized, double-blind, placebo-controlled study (N01103, NCT00105040) evaluated behavioral and emotional effects of adjunctive levetiracetam (LEV) treatment in children and adolescents (4-16years old) with uncontrolled partial-onset seizures. Patients received adjunctive LEV 20-60mg/kg/day (n=64) or placebo (n=34) for 12weeks. The Achenbach Child Behavior Checklist (CBCL) and portions of the Child Health Questionnaire-Parent Form 50 (CHQ-PF50) were used to assess behavioral and emotional functioning at baseline and end of the treatment period. Worsening of the mean CBCL Aggressive Behavior score occurred for LEV but not placebo, leading to similar results for Externalizing Syndromes and Total Problems (all P<0.05 vs placebo). The change in the CBCL Activities Competence score favored LEV (P<0.05). These results are in line with the known safety profile of LEV.

Topics: Adolescent; Anticonvulsants; Behavioral Symptoms; Checklist; Child; Child, Preschool; Double-Blind Method; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Mood Disorders; Piracetam; Psychiatric Status Rating Scales; Surveys and Questionnaires

We aimed to investigate the effects of levetiracetam on oxidative stress which is one of the new antiepileptic drugs in epileptic patients.. The study consisted of 21 patients with cryptogenic partial epilepsy. We determined the urinary 15F-2t-isoprostane levels of the 30 patients which is a marker of oxidative stress. Morning urine samples were collected from the patients before beginning LEV and after 3 months treatment. Of these patients 9 were excluded from the study that had seizure history in the last 1 month. Urinary levels of 15-F2t-isoprostane determined by ELISA initially and after 3 months treatment for each patient.. Mean age of the 21 patients was 29.6, of these 11 were females and 10 males. Mean urinary 15F-2t-isoprostane level of the patients was 876 ± 447 ng/mg Cr before the treatment of LEV. After 3 months treatment the mean 15F-2t-isoprostane level of the patients was 1560 ± 630. The patients had significantly higher levels of urinary 15F-2t-isoprostane when compared with initial levels (p = 0.025).. Our results showed the increase of urinary 15F-2t-isoprostane levels in epileptic patients whom were treated with LEV which may indicate that LEV induces the oxidative stress in epileptic patients.

Topics: Adult; Anticonvulsants; Biomarkers; Dinoprost; Epilepsies, Partial; Epilepsy; Female; Humans; Isoprostanes; Levetiracetam; Male; Oxidative Stress; Piracetam

One hundred and forty-three patients with partial epilepsy, aged 16-73 years, were treated with levetiracetam (keppra) during 3 years. Group 1 included 71 patients who received the drug as the first monotherapy, group 2 consisted of 72 patients who received levetiracetam as the second or the third monotherapy due to the insufficient efficacy/poor tolerability of the initial therapy with AED. Percent of retention of patients on the drug is an integral index of the total efficacy of treatment (remission or >50% decrease of seizure frequency) minus the percent of drug withdrawal due to different reasons for a certain period. In group1, the percent of retention was 90,1% for the first year, 87,3% for the second year and 83,1% for the third year; in group 2-75% for the first year, 70,8% for the second year and 69,4% - for the third year. The drug was well-tolerated. The drug withdrawals due to side effects was 5,6% in group 1 and 8,2% in group 2. The results of the study suggest high efficacy of levetiracetam in treatment of partial epilepsy.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Epilepsies, Partial; Humans; Levetiracetam; Middle Aged; Piracetam; Treatment Outcome; Withholding Treatment; Young Adult

To evaluate efficacy and tolerability of levetiracetam (LEV; Keppra) as add-on therapy in Chinese patients with refractory partial-onset seizures.. In this multicenter, double-blind, randomized, placebo-controlled trial, 206 patients aged 16-70 years with uncontrolled partial-onset seizures were randomized to receive LEV (n =103) or placebo (n =103); 202 patients (LEV, n =102; placebo, n = 100) comprised the intent-to-treat population. An 8-week historical baseline period confirmed eligibility according to seizure count. The 16-week treatment period consisted of a 4-week up-titration period (LEV, 1,000-3,000 mg/day in two equal divided doses) followed by a 12-week maintenance period. Efficacy assessments were based on weekly frequency of partial-onset seizures during the 16-week treatment period.. LEV significantly decreased weekly partial-onset seizure frequency over placebo by 26.8% (p < 0.001). Median percentage reductions in weekly partial-onset seizure frequency from historical baseline were 55.9% for LEV and 13.7% for placebo (p < 0.001). The >or=50% responder rates were 55.9% for LEV, compared with 26.0% for placebo (p < 0.001). Freedom from partial-onset seizures during treatment period was achieved by 11 LEV patients (10.8%) and 2 placebo patients (2.0%) (p = 0.012). Adverse events were reported by 65 LEV-treated patients (63.1%) and 62 placebo-treated patients (60.2%); most were of mild-to-moderate intensity. The most common adverse events were somnolence (LEV, 17.5%; placebo, 17.5%), decreased platelet count (LEV, 9.7%; placebo, 9.7%), and dizziness (LEV, 7.8%; placebo, 13.6%).. Add-on LEV was effective and well-tolerated in Chinese patients with refractory partial-onset seizures.

Topics: Adolescent; Adult; Anticonvulsants; China; Cross-Cultural Comparison; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Young Adult

To assess anger/hostility during treatment with lamotrigine adjunctive therapy versus levetiracetam adjunctive therapy in patients with partial seizures.. This randomized, double-blind, parallel-group study in adults with partial seizures included an 8-week escalation phase, during which adjunctive lamotrigine (n = 132) or adjunctive levetiracetam (n = 136) was titrated to a target dose, and a 12-week, double-blind maintenance phase, during which dosages of study medication and concomitant antiepileptic drugs were maintained. The primary endpoint was change from baseline to the end of the maintenance phase (week 20) in the Anger-Hostility subscale score of the Profile of Mood States (POMS).. Improvement with lamotrigine relative to levetiracetam was observed for mean +/- SD (standard deviation) change from baseline to the end of the maintenance phase (week 20) on the Anger-Hostility subscale (lamotrigine -2.0 +/- 8.2, levetiracetam -0.3 +/- 8.4; p = 0.024) (the primary endpoint); the Anger-Hostility subscale on weeks 5, 6, 7, 8, 9, 11, 12, 14, 16, 18, and 19; and the Total Mood Disturbance score on weeks 6, 7, 8, 9, 11, 12, 17, 19, and 20. Improvement (p < 0.05) with lamotrigine relative to levetiracetam was also observed on the POMS subscales Depression-Dejection, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment. No difference in seizure frequency was observed between groups. The most common adverse events with both medications were headache and dizziness.. Adjunctive lamotrigine significantly improved Anger-Hostility subscale scores relative to adjunctive levetiracetam in patients with partial seizures at the end of 20 weeks. This difference was consistently observed throughout the treatment period. Similar improvement with lamotrigine versus levetiracetam was observed for other mood symptoms.

Topics: Adult; Affect; Anger; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Hostility; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Personality Inventory; Piracetam; Psychometrics; Triazines

To evaluate the efficacy and safety of 3,000 mg daily levetiracetam (LEV; Keppra) as an adjunctive therapy for Chinese patients with refractory partial seizures.. This randomized, placebo-controlled trial consisted of an 8-week baseline period followed by a 4-week titration interval and a 12-week maintenance period, and concluded with a 4-week medication withdrawal period or entered an open-label study. LEV was compared with placebo.. The 50% responder rate (the proportion of patients with a minimum of 50% reduction in partial seizure frequency) occurred in 46.4% of the LEV group, compared with 39.3% of the placebo group (p = 0.590). The median of the absolute weekly frequency reduction from baseline of partial seizures was 0.66 per week for LEV versus 0.48 per week for placebo (p = 0.187). The most common treatment-emergent adverse events, mostly mild to moderate in severity, were somnolence, dizziness and agitation.. In this study, adjunctive therapy with LEV 3,000 mg daily was well tolerated but not as effective as expected in controlling partial seizures in this study population. Considering the lower mean weight of this study population, we suggest the dosage of LEV 3,000 mg daily may contribute to the results.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Anticonvulsants; Body Weight; Chemotherapy, Adjuvant; China; Dizziness; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Psychomotor Agitation; Seizures; Sleep Wake Disorders; Treatment Outcome; Young Adult

To evaluate the efficacy and tolerability of adjunctive levetiracetam in very young children (aged 1 month to <4 years) with partial-onset seizures inadequately controlled with one or two antiepileptic drugs.. This multicenter, double-blind, randomized, placebo-controlled study consisted of a 48-h inpatient baseline video-EEG (electroencephalography) and a 5-day inpatient treatment period (1-day up-titration; 48-h evaluation video-EEG in the last 2 days). Children who experienced at least two partial-onset seizures during the 48-h baseline video-EEG were randomized to either levetiracetam [40 mg/kg/day (age 1 to <6 months); 50 mg/kg/day (age >or=6 months to <4 years] or placebo.. Of 175 patients screened, 116 patients were randomized [60 levetiracetam; 56 placebo; intent-to-treat (ITT) population], and 111 completed the study. The responder rate in average daily partial-onset seizures frequency (48-h video-EEG monitoring; primary efficacy variable) was 43.1% for levetiracetam [modified ITT (mITT) = 58] versus 19.6% for placebo (mITT = 51; p=0.013), with odds ratio for response 3.11 [95% confidence interval (CI), 1.22-8.26]. The median percent reduction from baseline in average daily partial-onset seizure frequency was 43.6% for levetiracetam and 7.1% for placebo with a median difference between treatment groups of 39.2% (95% CI, 17.5-62.2; p < 0.001). In general, levetiracetam was well tolerated. Treatment-emergent adverse events were reported by 55.0% levetiracetam- and 44.6% placebo-treated patients (ITT population). The most frequently reported adverse events were somnolence (13.3% levetiracetam, 1.8% placebo) and irritability (11.7% levetiracetam, 0% placebo).. Adjunctive levetiracetam is an efficacious and well-tolerated treatment for partial-onset seizures in infants and young children.

Topics: Anticonvulsants; Child, Preschool; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Female; Humans; Infant; Infant, Newborn; International Cooperation; Levetiracetam; Male; Odds Ratio; Piracetam; Retrospective Studies; Time Factors; Treatment Outcome; Videotape Recording

Double-blind randomized trial to assess efficacy and tolerability of once-daily extended-release levetiracetam (LEV XR) tablets (2 x 500 mg) as add-on therapy in patients (12-70 years old) with partial-onset seizures (POS) refractory to one to three antiepileptic drugs.. After an 8-week prospective baseline-period, eligible patients were randomized (1:1) to once-daily LEV XR 1,000 mg/day or placebo for 12 weeks. Evaluations included changes from baseline in POS-frequency/week, responders (>or=50% reduction in POS-frequency/week), seizure-freedom, adverse events, laboratory tests, physical and neurologic examinations, vital signs, body-weight, and 12-lead electrocardiogram.. Of 188 patients screened, 158 were randomized (intention-to-treat population): LEV XR (n = 79) or placebo (n = 79). Seventy-one (89.9%) LEV XR and 72 (91.1%) placebo patients completed the trial. Median POS-frequency/week reduction was 46.1% on LEV XR and 33.4% on placebo. Estimated reduction with LEV XR over placebo was 14.4% (p = 0.038). Thirty-four (43%) LEV XR and 23 (29.1%) placebo patients experienced >or=50% reduction in POS-frequency/week. Eight (10.1%) patients receiving LEV XR and one (1.3%) receiving placebo were free of POS during the 12-week treatment period. Forty-one (53.2%) LEV XR and 43 (54.4%) placebo patients reported >or=1 adverse event. Adverse events reported with an incidence >5% and seen more often with LEV XR than with placebo were somnolence, influenza, irritability, nasopharyngitis, dizziness, and nausea.. Once-daily LEV XR 1,000 mg was effective and well-tolerated as adjunct therapy in patients with POS. Ten percent of patients randomized to LEV XR experienced freedom from POS. These results support the clinical value of this new LEV XR formulation.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Anticonvulsants; Delayed-Action Preparations; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Treatment Outcome; Young Adult

The safety profiles of once-daily adjunctive levetiracetam (LEV) extended release (XR) (1000mg/day) and adjunctive LEV immediate release (IR) (500mg twice daily) were compared using data from three randomized, placebo (PBO)-controlled phase III clinical trials in patients with partial-onset seizures. MedDRA 9.0 treatment-emergent adverse events (TEAEs) were indirectly compared using meta-analytic techniques, including calculation of risk difference (RD) and mixed-effects analysis. Statistical significance was set at 10% alpha risk, the normative value for these analyses. Data from 555 patients older than 16 (204 LEV IR, 70 LEV XR, 281 PBO) were analyzed. Following adjustment for incidence of placebo TEAEs, LEV XR showed statistically significantly lower rates of TEAEs than LEV IR across nervous system disorders (RD=-18%, P=0.03), psychiatric disorders (RD=-11%, P=0.08), and metabolism and nutrition disorders (RD=-3%, P=0.08). Among nervous system disorders, the RD for headache favored LEV XR (RD=-11%, P=0.08). These results suggest that adjunctive LEV XR may be associated with a lower incidence of nervous system, psychiatric, and nutritional and metabolic TEAEs as compared with LEV IR. However, this difference was observed at a broad scale and not at a specific TEAE level except for headache.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Anticonvulsants; Chemotherapy, Adjuvant; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Delivery Systems; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Meta-Analysis as Topic; Middle Aged; Piracetam; Severity of Illness Index; Treatment Outcome; Young Adult

Evaluate potential neurocognitive effects of adjunctive levetiracetam in children with inadequately controlled partial-onset seizures (POS).. Randomized, double-blind, placebo-controlled, noninferiority safety study. Children (4-16 years; IQ > or =65) with > or =1 POS during 4 weeks before screening despite taking 1-2 antiepileptic drugs (AEDs) were randomized (2:1) to levetiracetam (20-60 mg/kg/day) or placebo for 12 weeks.. Ninety-nine patients were randomized with 98 (levetiracetam 64, placebo 34) in intent-to-treat (ITT) and 73 (levetiracetam 46, placebo 27) in per protocol (PP) populations. Primary cognitive assessment was the Leiter International Performance Scale-Revised Attention and Memory Battery with the memory screen composite score change from baseline as the primary endpoint. PP Least Square Mean [LSM (standard error)] were 5.36 (1.78) for levetiracetam; 5.17 (2.33) for placebo; difference [two-sided 90% confidence interval (CI)] 0.19 (-4.69, 5.08). Levetiracetam was noninferior to placebo because the 90% CI lower bound was greater than the defined noninferiority margin (-9.0). There were no statistically significant differences between groups in Wide Range Assessment of Memory and Learning-2 indexes and Leiter-R Examiner's Rating Scale scores. Median reductions from baseline in weekly POS frequency were 91.5% versus 26.5% for levetiracetam versus placebo; > or =50% responder rates: 62.5% versus 41.2%; seizure freedom rates: 46.9% versus 8.8% (ITT). Adverse events were reported by 89.1% levetiracetam-treated and 85.3% placebo-treated patients; those reported by > or =10% levetiracetam patients and more often with levetiracetam were headache, nasopharyngitis, fatigue, vomiting, somnolence, and aggression.. Neurocognitive effects were no different in pediatric patients with POS treated with adjunctive levetiracetam or placebo. Levetiracetam was effective and well tolerated.

Topics: Adolescent; Adult; Age Distribution; Anticonvulsants; Child; Cognition; Cognition Disorders; Comorbidity; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Piracetam; Placebos; Treatment Outcome

The aim of this open label pilot study was to evaluate the efficacy and tolerability of levetiracetam (LEV) as 'de novo' monotherapy in children and adolescents with late onset childhood occipital epilepsy-Gastaut type (COE-G).. Twelve patients suffering from COE-G were enrolled in this prospective study. The age of seizures onset ranged from 6.1 to 16.2 years with a peak of frequency at mean (+/-SD) 10.54 +/- 2.77 years. Therapy with LEV was started at 10 mg/kg/day and, after titration, the final dose was generally achieved within 4 weeks and ranged from 20.7 to 45.2 mg/kg/day.. At the 6 month evaluation, 11 (91.6%) of the 12 patients studied were seizure free, and one (8.3%) showed four additional episodes. Electroencephalography (EEG) activity was normal in six (54.5%) patients, unchanged in two (18.1%) children, and in four (33.3%) patients sporadic occipital abnormalities persisted. At the 12-month evaluation all patients were completely seizure free. Four patients (33.3%) continued to show some EEG abnormalities, while eight (72.8%) patients had normal EEG. At the 18-month evaluation all patients were seizure free and 10 patients (83.3%) showed a complete normalization of EEG abnormalities.. Monotherapy with LEV was effective and well tolerated in patients with COE-G. Nevertheless, prospective, large, long-term double-blind studies are needed to confirm these findings.

Topics: Adolescent; Anticonvulsants; Child; Drug Administration Schedule; Electroencephalography; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Patient Selection; Pilot Projects; Piracetam; Prospective Studies; Seizures; Treatment Outcome

Anti-epileptic drugs (AED) may cause cognitive impairment. Because intractable epilepsy (IE) represents a distinct group, the purpose of the present study was to study the comparative cognitive effects of the two efficacious AED, levetiracetam (LEV) and topiramate (TPM), on IE.. This was a non-randomized, blinded cognitive assessment and parallel design. The cognitive effects of LEV and TPM on 79 demographically comparable patients with IE were assessed at baseline (T1) and after 1 year of treatment (T2) using the Cognitive Abilities Screening Instrument.. Forty patients took TPM and 39 took LEV. At T1, seizure frequency, number of AED, and epilepsy duration were not significantly different. There were no significant differences in cognition between the two groups at T1 or T2. T2 orientation scores were lower than T1 scores in the TPM group (P < 0.05). In the TPM subgroup with T1 cognitive abnormalities, T2 scores for recent memory improved (P < 0.05).. For patients with IE, LEV might preserve cognition, TPM's effects for patients with baseline cognitive abnormalities are worth observation.

Topics: Adolescent; Adult; Anticonvulsants; Cognition Disorders; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Complex Partial; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Piracetam; Prospective Studies; Psychometrics; Taiwan; Topiramate; Young Adult

To study the efficacy and tolerability of add-on levetiracetam in children and adolescents with refractory epilepsy.. In this prospective multi-centre, open-label, add-on study, 33 children aged 4-16 years (median 8.5 years) with epilepsy refractory to at least two antiepileptic drugs were treated with levetiracetam in addition to their present treatment regimen with a follow-up of 26 weeks. The starting dose of 10 mg/kg/day was increased with 2-week steps of 10 mg/kg/day, if necessary, up to a maximum dose of 60 mg/kg/day.. Retention rate was 69.7% after 26 weeks on a median levetiracetam dosage of 22 mg/kg/day. Four children dropped-out because levetiracetam was ineffective, four because seizure frequency increased and/or seizures became more severe, and two because they developed aggressive behaviour. Compared to their baseline seizure frequency, 13 children (39.4%) had a >50% seizure reduction 12 weeks after initiation of levetiracetam, and 17 children (51.5%) at 26 weeks. At 26 weeks, nine children (27.3%) had been seizure-free for at least the last 4 weeks, terminal remission ranged from 0 to 187 days (mean 46 days). Levetiracetam was effective in both partial and primary generalized seizures, but had most effect in partial seizures. Most reported side effects were hyperactivity (48.5%), somnolence (36.4%), irritability (33.3%) and aggressive behaviour (27.3%). Severity of most side effects was mild. Five children had a serious adverse event, which all concerned hospital admissions that were not related to levetiracetam use.. Levetiracetam proved to be an effective and well-tolerated add-on treatment in this group of children with refractory epilepsy.

Topics: Adolescent; Anticonvulsants; Child; Disorders of Excessive Somnolence; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Epilepsies, Partial; Epilepsy, Generalized; Female; Follow-Up Studies; Humans; Irritable Mood; Levetiracetam; Male; Piracetam; Prospective Studies; Seizures; Treatment Outcome

This study comprised two phases and evaluated the effects of levetiracetam (LEV), as an add-on treatment, on cognitive function and quality of life (QOL) in patients with refractory partial seizures. The short-term phase employed a randomized, double-blind, placebo-controlled design including an 8-week baseline period, 4-week titration interval, and 12-week period at the maximum LEV dose (1500 mg twice daily). The long-term phase was an open-label study in which the maximum LEV dose was administered for another 24 weeks. Neuropsychological tests and the 31-item Quality of Life in Epilepsy (QOLIE-31) inventory were administered at baseline, at the end of the short-term phase, and at the end of the long-term phase. Twenty-four eligible patients entered into the final phase. After short-term LEV treatment, performance time on the Wisconsin Card Sorting Test (WCST) and Delayed Logic Memory significantly improved for the patient group, but not the control group. Subscale scores on the QOLIE-31, including scores on Cognitive Functioning and Social Function, also improved only for the LEV group. At the end of the long-term phase, these improvements were maintained, and both groups performed better in more areas, as measured by the Trail Making Test, WCST, and Delayed Visual Memory in the neuropsychological battery and the QOLIE-31 subscales Overall QOL and Health Status. Thus, as an adjunctive therapy, LEV did not negatively affect and, in a way, improved cognitive function and QOL in patients with medically refractory partial seizures. Some of these improvements may be maintained during long-term treatment.

Topics: Adult; Anticonvulsants; Chi-Square Distribution; Cognition; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Neuropsychological Tests; Piracetam; Problem Solving; Quality of Life; Statistics, Nonparametric; Treatment Outcome

Interictal depression is common in patients with epilepsy and it significantly impacts quality of life. Some studies indicate that levetiracetam (LEV) may have mood stabilizing properties.. Twenty-five adults with uncontrolled partial seizures and concomitant depressive symptoms were treated with LEV. Patients were evaluated for depression and anxiety with several psychometric measures, including: Montgomery and Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS), Zung Self-rating Scale for Depression (Z-SDS), Hamilton Anxiety Rating Scale (HARS), Zung Self-rating Scale for Anxiety (Z-SAS).. Evaluations after 5 weeks and after 3 months of LEV treatment demonstrated significant improvement in depression and anxiety.. This uncontrolled study suggests that treatment with LEV may also improve depression and anxiety in patients with partial seizures. However, the sample of patients is limited and the possibility of a placebo effect cannot be excluded. These findings must be considered preliminary and should be replicated under placebo-controlled conditions.

Topics: Adult; Age Factors; Anticonvulsants; Anxiety Disorders; Depressive Disorder; Dizziness; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Piracetam; Placebo Effect; Psychiatric Status Rating Scales; Severity of Illness Index; Treatment Outcome

Newer antiepileptic drugs are reported to have better side-effect profiles than traditional antiepileptics, although the evidence to this effect and their efficacy is limited. We compare the efficacy and tolerability of levetiracetam and carbamazepine monotherapy in children with partial epilepsy < or = 16 years of age. We identified 86 patients (66 levetiracetam, 20 carbamazepine) treated with initial monotherapy for partial epilepsy and followed for > or = 6 months. Efficacy was based on the number of patients achieving seizure freedom of > or = 6 months. Tolerability was based on parent-and patient-reported side effects. Forty-eight (73%) subjects on levetiracetam and 13 (65%) subjects on carbamazepine achieved 6 months of seizure freedom. A total of 70% of patients on carbamazepine and 45% of those on levetiracetam had at least 1 adverse event while on monotherapy (P = .07). Levetiracetam and carbamazepine monotherapy demonstrate similar efficacy for treatment of partial epilepsy and are well tolerated in children.

Topics: Anticonvulsants; Carbamazepine; Child; Child, Preschool; Databases, Factual; Drug Evaluation; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Piracetam; Retrospective Studies

To assess the multiple-dose pharmacokinetics of levetiracetam and its major metabolite ucb L057 in children with partial-onset seizures and determine whether it is affected by adjunctive carbamazepine or valproate. To correlate levetiracetam concentrations in plasma and saliva and to assess its safety and clinical response.. Design was an open-label, multicenter study. Twenty-one children (4-12 years old) with epilepsy taking carbamazepine (13) or valproate (8) received adjunctive levetiracetam. Levetiracetam was initiated at 20 mg/(kg day) and titrated at 2-week intervals to 40 and then 60 mg/(kg day). Twelve-hour pharmacokinetics were determined at the end of each 2-week period. Efficacy was estimated from the partial seizure frequency per week and Global Evaluation Scale.. Levetiracetam was rapidly absorbed following oral dosing, with median t(max) of 0.5 h. Dose proportional increases were observed for C(max) and AUC((0-12)) over the dose range; t(1/2) was 4.9 h. Pharmacokinetics of levetiracetam and ucb L057 were not markedly different with concomitant carbamazepine or valproate; clearance was only 7-13% faster and AUC was decreased by only 15-24% in those on carbamazepine compared to valproate. Levetiracetam did not affect trough carbamazepine or valproate. Concentration in saliva and plasma were strongly correlated. Seizure frequency declined by 50% or more in 43% of subjects in the intent-to-treat population (n=21) and in 56% of those with seizures at baseline (n=16). Marked or moderate improvement occurred in 80% and 75% of patients based on Global Evaluation Scale ratings by investigators and parents/guardians, respectively. Levetiracetam was well tolerated.. Levetiracetam exhibits simple pharmacokinetics in children, with rapid absorption and dose-proportional kinetics. Small but not clinically relevant differences were observed between subjects receiving carbamazepine and valproate, suggesting significant dose adjustment is usually not necessary. This substantiates prior assessments that levetiracetam clearance is higher in children than adults, necessitating a higher dose in children on a mg/kg basis, and suggests it is useful add-on therapy for children with partial-onset seizures regardless of baseline therapy.

Topics: Anticonvulsants; Carbamazepine; Child; Child, Preschool; Drug Therapy, Combination; Epilepsies, Partial; Humans; Levetiracetam; Piracetam; Saliva; Valproic Acid

This multicenter, open-label study evaluated the short-term tolerability of intravenously (IV)-infused levetiracetam (LEV; 500-1,500 mg/100 ml, 15 min, b.i.d.) as a substitute for the same oral dose.. The study consisted of screening, 4-day IV LEV and 1-7 days of follow-up, and was conducted in 25 adults with partial-onset seizures receiving adjunctive oral LEV.. During the 4-day IV LEV, 11 (44%) subjects experienced at least one treatment-emergent adverse event (TEAE), with headache and fatigue being the most frequently reported. Five (20%) subjects experienced TEAEs considered to be related to the study drug. The tolerability profile was consistent with that of oral LEV, with all events judged mild or moderate in severity, no discontinuations, and no serious AEs or deaths reported. No AE related to seizure worsening was reported during IV LEV or brief follow-up.. LEV IV appears to be a well-tolerated, practical alternative in patients with partial-onset seizures temporarily unable to take the drug orally.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticonvulsants; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Fatigue; Female; Follow-Up Studies; Headache; Humans; Infusions, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Treatment Outcome

This prospective, open-label study evaluated the efficacy and safety of adjunctive levetiracetam (LEV) in Korean adults with uncontrolled partial epilepsy. Study patients had to have an average of at least 1 and not more than 14 partial seizures per month (averaged over a 3-month historical baseline) despite the use of one or two AEDs. Patients initially received LEV 1000 mg/day (administered bid) and could increase to 2000 mg/day after 2 weeks, and to 3000 mg/day after another 2 weeks, to obtain adequate seizure control. During the 12-week maintenance period, the dose of LEV could be increased or decreased once if seizure control was insufficient or tolerability warranted, respectively. Seizure count and adverse events (AEs) were recorded by patients. Global evaluation scale (GES) and quality of life (QOLIE-31) were also evaluated. A total of 100 patients were enrolled and 92 patients completed the study. The median percent reduction in weekly seizure frequency over the treatment period was 43.2%. The >or=50% and >or=75% responder rates were 45.4% and 36.1%, respectively. Seizure freedom throughout the 16-week treatment period was observed in 17 patients. On investigator's GES, 81 patients were considered improved, with 41 patients showing marked improvement. Most QOLIE-31 scales improved significantly. Treatment-emergent AEs were reported in 59 patients. Three most common AEs were somnolence (36%), dizziness (12%), and headache (8%). Adjunctive LEV therapy was effective and well-tolerated in Korean adults with refractory partial epilepsy.

Topics: Adult; Anticonvulsants; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Korea; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Severity of Illness Index; Treatment Outcome

The Safety of Keppra as Adjunctive Therapy in Epilepsy (SKATE) study aimed to evaluate the safety and efficacy of levetiracetam (Keppra, LEV) as add-on therapy for refractory partial seizures in clinical practice. This Phase IV, 16-week, open-label study recruited patients > or =16-year old with treatment-resistant partial seizures. LEV (1000 mg/day) was added to a stable concomitant antiepileptic drug regimen. LEV dosage was adjusted based on seizure control and tolerability to a maximum of 3000 mg/day. 1541 patients (intent-to-treat population) were recruited including 1346 (87.3%) who completed the study and 77.0% who declared further continuing on LEV after the trial. Overall, 50.5% of patients reported at least one adverse event that was considered related to LEV treatment. The most frequently reported drug-related adverse events were mild-to-moderate somnolence, fatigue, dizziness and headache. Serious adverse events considered related to LEV occurred in 1.0% of patients. 7.5% of patients reported adverse events as the most important reason for study drug discontinuation. The median reduction from baseline in the frequency of all seizures was 50.2%; 15.8% of patients were seizure free; 50.1% had seizure frequency reduction of > or =50%. At the end of the study, 60.4% of patients were considered by the investigator to show marked or moderate improvement. There was a significant improvement in health-related quality of life as assessed with the QOLIE-10-P (total score increasing from 55.6 to 61.6; p<0.001). This community-based study suggests that LEV is well tolerated and effective as add-on therapy for refractory partial seizures in adults. These data provide supportive evidence for the safety and efficacy of LEV demonstrated in the pivotal Phase III placebo-controlled studies.

Topics: Adolescent; Adult; Anticonvulsants; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Health Status; Humans; International Cooperation; Levetiracetam; Male; Middle Aged; Piracetam; Quality of Life; Residence Characteristics; Retrospective Studies; Single-Blind Method; Treatment Outcome

The goal of the work described here was to explore the efficacy, safety, and tolerability of adjunctive therapy with levetiracetam and associated changes in health-related quality of life in Australian patients with uncontrolled partial seizures.. A phase IV open-label 16-week clinical trial was undertaken. Patients received adjunctive levetiracetam, adjusted according to clinical response to a final daily dose of 1000-3000 mg. Seizure frequency and adverse events were recorded. A quality-of-life questionnaire (QOLIE-10-P) was administered at the start and end of therapy.. The intention-to-treat population (N=152) experienced a median reduction in total seizure frequency of 57.7%. The 50% responder rate was 56.6%, and 12.5% of patients were free of seizures throughout the trial. Adverse events were mostly mild or moderate, leading to discontinuation in 9.9%. The most common adverse events were somnolence, fatigue, headache, and dizziness. Behavioral adverse events occurred in approximately one-quarter of patients, including two-thirds of those who withdrew because of adverse events. There was an improvement in the QOLIE-10-P score.. Levetiracetam is effective and well tolerated when added to existing therapy in patients with uncontrolled partial seizures.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Australia; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Evaluation; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Naphthalenes; Oxepins; Piracetam; Quality of Life; Treatment Outcome

The aim of the present study is to verify whether patients with partial epilepsy receiving levetiracetam (LEV) as an add-on treatment show an improvement in cognitive function.. A neuropsychological battery of tests was administered to 35 patients with partial epilepsy before the assumption of LEV and after the achievement of the therapeutical dose of this drug, 7 weeks later. A control group of 35 patients with partial epilepsy was administered the same battery of tests twice, at the same time interval as the LEV group. The controls were administered the same pharmacological treatment, which did not include LEV in either of the two sessions.. We found a statistically significant improvement in cognitive functioning, i.e. in attention and oral fluency, in patients receiving LEV compared to the controls. The responders to LEV were 28.6%.. LEV as an add-on therapy improved attention level and verbal fluency in our sample of patients with partial epilepsy. It is reasonable to assume that LEV may influence the metabolism of attention and of language area, as already suggested for piracetam (PIR) from which LEV derives. Further studies are needed to confirm these findings.

Topics: Adult; Anticonvulsants; Attention; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Neuropsychological Tests; Nootropic Agents; Piracetam; Speech Disorders; Treatment Outcome

The objective of this observational study was to compare the efficacy of levetiracetam and topiramate during the first 15 days of add-on treatment in adults with refractory partial epilepsy. Two cohorts of patients with > or =3 simple or complex partial seizures with or without secondary generalisation per month over an 8-week baseline period received levetiracetam or topiramate in two distinct phases, in addition to standard antiepileptic treatment. During the first 15 days of the therapy, levetiracetam was added at the dosage of 250 mg b.i.d. or topiramate at 25mg o.i.d. Efficacy parameters included number of seizure-free days (SFDs), mean and percent reduction in seizure frequency (in general and by type), and number of seizure-free patients in the first 15 days of treatment compared to last 15 days of the baseline period. Sixty-one patients received levetiracetam and 61 topiramate. The general characteristics of the two treatment groups were similar. The total number of SFDs during 15 days before treatment was 637 with levetiracetam and 621 with topiramate; in the 15-day evaluation period the SFDs increased to 748 (17.4%) and 668 (7.6%), respectively (ANOVA, p<0.05). Twenty-six patients (42.6%) taking levetiracetam were seizure free compared to 10 (16.4%) receiving topiramate (chi-square, p=0.003). This open-label non-controlled study suggests an early efficacy of levetiracetam as add-on therapy in patients with refractory partial epilepsy: these results appear to confirm previous indications of a rapid onset of action and seem to suggest first evaluation of the patient at the dose of 500 mg/day before increasing to the considered minimum standard dose of 1000 mg/day, as some patients could respond to the starting dose.

Topics: Adolescent; Adult; Anticonvulsants; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Topiramate; Treatment Outcome

This prospective, open-label study was conducted to evaluate the effectiveness, tolerability, and safety of levetiracetam in patients with epilepsy in whom unfavorable metabolism, complex drug interactions, or direct toxic effects of antiepileptic drugs (AEDs) had caused a worsening of comorbid conditions.. Study design included the introduction of levetiracetam, discontinuation of other AEDs, and a serial assessment comprising electroencephalograms and blood tests at baseline and 2, 6, and 12 months. Of 21 patients, 16 had partial and five generalized epilepsy. Concomitant pathologies were gastroenterological (six), vascular (four), endocrinological (four), or complex conditions including hematological (four) or dermatological (three) disease. A change of regimen was necessitated by drug-drug interactions in four patients, direct real or potential toxic effects of previous AEDs in 13, and a combination of interactions/toxic effects in four.. After 12 months, 12 patients were seizure-free, nine had reductions in seizure frequency of 50-75%, and improvement in concomitant medical conditions was observed. No side effects were reported.. Levetiracetam appears to be effective, well tolerated, and safe in patients with epilepsy and other medical conditions that are difficult to manage because of drug interactions or AED-related side effects.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Generalized; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Polypharmacy; Prospective Studies; Treatment Outcome

To assess the efficacy and safety of adjunctive levetiracetam (LEV) therapy in controlling partial-onset seizures refractory to other antiepileptic drugs (AEDs) in a multicenter study in Taiwanese adults.. Ninety-four patients aged 16-60 years with refractory partial seizures were randomized to receive LEV (n = 47) or placebo (47) for 14 weeks and composed the intention-to-treat (ITT) population. After the first 2 weeks, LEV patients had their dosage increased from 500 mg twice daily to 1,000 mg twice daily. A 12-week maintenance phase followed, after which patients switched to long-term, open-label LEV therapy or entered a 4-week phase of medication discontinuation.. All patients from the ITT population, except one LEV-treated patient with missing seizure-count data, were included in the primary efficacy analysis. The least square mean of logarithmically transformed weekly partial-seizure frequency was significantly lower in the LEV than in the placebo group (0.813 vs. 1.085; p = 0.001). LEV reduced log-transformed weekly partial-seizure frequency by 23.8% (95% confidence interval, 10.4-35.2%) relative to placebo. Significantly more LEV than placebo patients (43.5% vs. 10.6%) experienced a response of a >or=50% decrease from baseline in weekly frequency of partial seizures [odds ratio, 6.5 (95% CI, 2.2-19.3); p < 0.001]. Adverse events were reported in 34 (72.3%) of 47 LEV-treated patients and 32 (68.1%) of 47 placebo patients. The three most common adverse events in the LEV and placebo groups were somnolence (40.4% and 14.9%), dizziness (14.9% and 8.5%), and headache (10.6% and 8.5%), respectively. Only four patients (three LEV-treated patients and one placebo patient) were withdrawn from the study because of adverse events.. Adjunctive LEV therapy,

Topics: Adolescent; Adult; Anticonvulsants; Asian People; Cross-Over Studies; Dizziness; Double-Blind Method; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Epilepsies, Partial; Female; Headache; Humans; Levetiracetam; Male; Middle Aged; Pharmacogenetics; Piracetam; Placebos; Sleep Wake Disorders; Taiwan; Treatment Outcome

To correlate the onset of clinical effects of add-on levetiracetam (LEV) therapy with daily serum LEV concentration, in pharmaco-resistant focal epilepsies, using the TISA method.. 25 adult patients (aged>6 years) with pharmaco-resistant focal epilepsies undergoing presurgical evaluation at the Epilepsy Center Erlangen were enrolled in the study. Eligible patients on a maximum of one other antiepileptic drug (AED) were recruited into the 48-hour baseline phase. Those who had at least two seizures during this phase were randomized into the seven-day treatment phase, when they received either LEV or placebo, under continuous day-and-night video-EEG monitoring. The starting daily dose of LEV was 500 mg bid, titrated from the second treatment day to 1,000 mg bid. The peak serum concentration of LEV was monitored daily at 8:00 am (one hour after drug administration) for every patient. The number and duration of seizures per 24h (N/24h and D/24h respectively) were investigated.. 23 patients completed the study (LEV group n=11 and placebo group n=12). Seven patients in the LEV group and two patients in the placebo group achieved seizure-freedom during the treatment phase. The intergroup comparison of the decrease in N/24h and D/24h from the baseline phase to the treatment phase was in favor of the LEV group (p<0.05). A significant effect of LEV on D/24h was seen as early as the second treatment day (p=0.013), becoming more apparent on the third treatment day (p=0.009).. The present study objectively quantified the correlation between the anticonvulsant effects of LEV in focal epilepsies and the peak serum concentration of the drug. For the first time, direct measurement was used to demonstrate the onset of action of LEV to be two days after drug initiation.

Topics: Adult; Anticonvulsants; Disease-Free Survival; Double-Blind Method; Drug Resistance; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Monitoring, Physiologic; Piracetam; Placebos; Preoperative Care; Treatment Outcome; Videotape Recording

To evaluate the efficacy and tolerability of levetiracetam (LEV) as adjunctive therapy in children (4 to 16 years) with treatment-resistant partial-onset seizures.. This multicenter, randomized, placebo-controlled trial consisted of an 8-week baseline period followed by a 14-week double-blind treatment period. During the treatment period, patients received either placebo or LEV add-on therapy and were up-titrated to a target dose of 60 mg/kg/day.. One hundred ninety-eight patients (intent-to-treat population) provided evaluable data. The reduction in partial-onset seizure frequency per week for LEV adjunctive therapy over placebo adjunctive therapy was significant (26.8%; p = 0.0002; 95% CI 14.0% to 37.6%). A 50% or greater reduction of partial seizure frequency per week was attained in 44.6% of the LEV group (45/101 patients), compared with 19.6% (19/97 patients) receiving placebo (p = 0.0002). Seven (6.9%) LEV-treated patients were seizure-free during the entire double-blind treatment period, compared with one (1.0%) placebo-treated patient. One or more adverse events were reported by 88.1% of LEV-treated patients and 91.8% of placebo patients. The most common treatment-emergent adverse events were somnolence, accidental injury, vomiting, anorexia, hostility, nervousness, rhinitis, cough, and pharyngitis. A similar number of patients in each group required a dose reduction or withdrew from the study as a result of an adverse event.. Levetiracetam adjunctive therapy administered at 60 mg/kg/day is efficacious and well tolerated in children with treatment-resistant partial seizures.

Topics: Anticonvulsants; Child; Child, Preschool; Double-Blind Method; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Pediatrics; Piracetam; Placebo Effect; Risk Assessment; Risk Factors; Treatment Outcome

Aim of the study was to assess the efficacy and safety of levetiracetam as add-on treatment in patients with partial-onset epilepsy in clinical practice.. In this observational, multi-centre study patients were treated with levetiracetam for 16 weeks. From a starting dose of 1000 mg/day, dose levels were adjusted at 2-weekly intervals in 1000-mg steps, to a maximum of 3000 mg/day, based on seizure control and tolerance. Analysis of efficacy was based on reduction in seizure frequency relative to baseline, 50% and 100% responder rates (for partial seizures and all seizure types combined) and percentage of patients using levetiracetam at the end of the study. Analysis of safety was based on occurrence of adverse events.. The present analysis concerns the results of patients recruited in Belgium and The Netherlands. Of the 251 patients included in the study, 86.9% completed 16 weeks of treatment. Reduction in frequency of partial-onset seizures was 62.2%, with 19.3% of the patients becoming seizure free and 56.6% having a reduction in seizure frequency of > or = 50%. These percentages were more or less the same when calculated for all seizure types combined. Tolerance of levetiracetam treatment was good, with most adverse events being only mild to moderate in severity, and only 10.0% of the adverse events leading to discontinuation from the study. Asthenia, somnolence, dizziness and headache were the most frequently reported adverse events.. Levetiracetam is effective and safe as add-on treatment for partial-onset seizures in clinical practice.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Belgium; Child; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Netherlands; Piracetam; Prospective Studies

The aim of this study was to evaluate the clinical effects of levetiracetam (LEV) in patients with partial epilepsy and disfluent speech.. Five consecutive patients with partial epilepsy and disfluent speech resulting from developmental or neurogenic stuttering were enrolled in a 9-week, open-label, prospective study. LEV was given in combination with carbamazepine (CBZ) or phenytoin (PHT) at dosages ranging from 500 to 1500mg twice daily. The severity of stuttering was assessed with the verbal fluency test (VFT), and with the patient global impression of improvement (PGI), at baseline and after 9weeks. Electroencephalography and serum monitoring of CBZ and PHT levels were done before and after the study. Seizure frequency was monitored.. After LEV therapy, verbal fluency for all patients, as measured by the VFT, improved from 25% at baseline to 64%, as did the speed of oral reading, from 5 to 23%. On the PGI, all patients rated themselves as better and as having less disfluent speech after LEV therapy. For four patients with incomplete control of their seizures, the seizure count decreased by more than 50% after LEV therapy. The beneficial effect of LEV on verbal disfluency demonstrated on the PGI persisted for the entire period of observation, which ranged from 7 to 11 months.. As an add-on therapy, LEV seems to improve verbal fluency in patients with partial epilepsy and disfluent speech. This effect seems unrelated to the antiepileptic activity of the drug. A placebo-controlled trial of LEV in patients with this kind of verbal disfluency is warranted.

Topics: Adult; Anticonvulsants; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Speech Disorders

To evaluate the efficacy and tolerability of levetiracetam as add-on therapy in patients with refractory partial-onset seizures in a protocol designed to reflect clinical practice.. All patients in this open-label, single-arm study entered an 8-week baseline period followed by a 4-week titration period and a 12-week maintenance period. Patients initially received levetiracetam 1000 mg/day (administered bid) and could increase to 2000 mg/day after 2 weeks, and to 3000 mg/day after another 2 weeks, to obtain adequate seizure control. During the 12-week maintenance period, the dose of levetiracetam could not be increased but could be decreased once if tolerability warranted. Seizure count and adverse events were recorded by patients in a diary. Quality of life and global evaluation of disease evolution were also evaluated.. Ninety-nine patients were enrolled and 91 completed the study. A steady dose was maintained over the last 8 weeks of treatment or longer in 84 patients, with 89.3% of these patients receiving 3000 mg/day, 9.5% receiving 2000 mg/day, and 1.2% receiving 1000 mg/day. A 35.9% median percent reduction from baseline in weekly frequency of partial-onset seizures was observed over the entire treatment period. The median partial-onset seizure count decreased from 2.3 per week during the baseline period to 1.3 per week over the treatment period. A total of 42.4% of patients were responders (> or = 50% reduction from baseline in weekly seizure frequency) over the treatment period; two patients were seizure-free from the first day of treatment throughout the treatment period. The most frequent drug-related adverse events were fatigue (27.3% of patients), somnolence (11.1%), headache (8.1%), and dizziness (8.1%).. Levetiracetam as add-on therapy at doses up to 3000 mg/day effectively reduced the frequency of partial-onset seizures in patients with refractory epilepsy and was well-tolerated in this study, bridging conditions of placebo-controlled clinical trials and clinical practice.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Cross-Over Studies; Demography; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Multicenter Studies as Topic; Piracetam; Prospective Studies; Quality of Life; Severity of Illness Index; Single-Blind Method; Time Factors; Treatment Outcome

There were analyzed efficacy of keppra (Levetiracetam) in combined therapy in 31 patients with pharmacoresistant partial epilepsy and in 2 cases with idiopathic generalized epilepsy. During the 4 months 48.4% experienced at least a 50% reduction in the frequency of partial-oncet seizures, 12.9% at least a 75% reduction, and 25.8% demonstrated a seizure free. The combined therapy was ineffective only in 12.9%. The authors emphasize a good tolerability of keppra. There was only one case with side-effect, that demand cancel of Levetiracetam. The results obtained reveal effectiveness of keppra using in epileptology, in particular, in pharmacoresistant epilepsy.

Topics: Adult; Anticonvulsants; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Generalized; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Valproic Acid; Vitamins

To obtain descriptive safety and efficacy data for long-term levetiracetam therapy and to allow patients benefiting from add-on levetiracetam to continue treatment until the drug was available commercially.. This long-term, noncomparative, open-label, follow-up study was conducted at 36 US sites. Patients with refractory partial epileptic seizures were eligible if they had benefited from add-on levetiracetam therapy in a previous study and wished to continue treatment. The levetiracetam dose was individualized over the range of 1,000-4,000 mg/day. Withdrawal of concomitant AEDs to allow levetiracetam monotherapy was permitted. Patients were evaluated every 12 weeks and followed for up to 4 years. Median total seizure frequency per week was the primary efficacy variable.. A total of 280 subjects, most of whom had refractory partial seizures with or without secondary generalization, were evaluated. Most were receiving either one (34.6%) or two (53.2%) concomitant antiepileptic drugs (AEDs) at entry. Overall, 199 (71.1%) subjects completed the study and 81 (28.9%) withdrew prematurely, most commonly due to loss or lack of efficacy or adverse events. The median total seizure frequency per week (0.7 at the selection visit) remained stable. The probability of being seizure-free during the first 12 weeks was 13.4% and 3.7% by week 216. Twenty-five (8.9%) subjects received levetiracetam monotherapy for at least 100 days. Levetiracetam was safe and well tolerated; the most common levetiracetam-related adverse events were dizziness (6.8%), convulsion (5.7%), and somnolence (5.0%).. Efficacy and safety were maintained during long-term levetiracetam treatment of refractory partial seizures.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Demography; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Levetiracetam; Longitudinal Studies; Male; Middle Aged; Piracetam; Time; Time Factors; Treatment Outcome

To evaluate the efficacy of levetiracetam (LEV) in continuous spikes and waves during slow sleep (CSWS). Despite first description dates back to 1971, no agreement exists about CSWS treatment. The condition is rare and controlled clinical trials are very difficult to perform, so the reports about efficacy of different drugs are anecdotal.. We introduced LEV in three children affected by symptomatic focal epilepsy and pharmacoresistant CSWS and evaluated clinical, neuropsychological and electroencephalographic outcome.. Two cases responded completely, one case showed only a mild reduction of spikes and waves during slow sleep.. Even if our report is anecdotal, LEV expands the spectrum of antiepileptic drugs that can be used for the treatment of CSWS. LEV efficacy should be confirmed in larger series.

Topics: Action Potentials; Anticonvulsants; Cerebral Cortex; Child; Child, Preschool; Drug Resistance; Drug Synergism; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Piracetam; Recovery of Function; Sleep; Sleep Wake Disorders; Treatment Outcome; Valproic Acid

Three randomized, placebo-controlled trials have demonstrated the safety and efficacy of levetiracetam, a new antiepileptic medication, as add-on therapy for partial-onset seizures. The purpose of this study was to gather additional safety and efficacy data on levetiracetam in the real-world setting of community-based practice.. This was a phase IV prospective, open-label, multicenter, community-based trial. A total of 1030 patients (intent-to-treat (ITT) population) at least 16 years old (mean, 42.2 years) with partial-onset seizures were enrolled by over 300 investigators. Patients whose partial-onset seizures were inadequately controlled on their current medications had levetiracetam 500 mg bid added to their regimens. The levetiracetam dose was increased by 500 mg bid at the end of weeks 2 and 4 to a maximum dose of 1500 mg bid, unless the patient had been seizure-free during the preceding 2-week period. The dose was then to remain the same for 12 weeks. The main outcome measures were reduction in seizure frequency, global evaluation scale (GES), and adverse events.. During the 16 weeks of the trial, 57.9% (542/936) experienced at least a 50% reduction in the frequency of partial-onset seizures, 40.1% (375/936) experienced at least a 75% reduction, and 20% (187/936) demonstrated a 100% seizure reduction. During the last 6 weeks of the study, 66.7% (500/750) experienced at least a 50% reduction in the frequency of partial seizures, 52.4% (393/750) experienced at least a 75% reduction, and 42.1% (316/750) demonstrated a 100% seizure reduction. On the investigator-completed clinical impression rating (GES), 74.3% (734/988) of patients were considered improved, with 37% of patients showing marked improvement. The most common adverse events were somnolence, dizziness, asthenia, and headache; these events were predominantly mild-to-moderate in nature.. These results provide further evidence regarding the efficacy and safety of levetiracetam as adjunctive treatment for partial-onset seizures.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Community Health Services; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies

Levetiracetam is a novel antiepileptic drug which has recently been released as an adjunctive treatment for partial epilepsy. In the two studies reported here we examined the objective and subjective effects of levetiracetam on sleep in 12 healthy volunteers and 17 patients [16 who could be evaluated for electroencephalogram (EEG) recordings] with a history of partial epilepsy on stable carbamazepine monotherapy. The studies were of a similar double-blind crossover placebo-controlled design with subjects' sleep being recorded in their own homes. The results from the two studies showed considerable similarities. In both, levetiracetam produced an increase in the time spent in stage 2 sleep, which in the patient study was accompanied by a decrease in the time spent in stage 4 sleep and in the volunteer study an increase in rapid eye movement (REM) latency. The subjective changes included reports that sleep was of a better quality with fewer awakenings and patients also reported that their sleep was more restful. Volunteers and patients did, however, feel less alert on waking in the morning. Therefore, both groups reported a decrease in awakenings after levetiracetam despite the finding from the EEG of no change in the actual number of awakenings. It may be concluded from both studies that levetiracetam does affect some indicators of subjective sleep perception, but does not influence objective sleep measures of sleep continuity. The results from the patient study during placebo add-on treatment also showed that patients on carbamazepine had a marked increase in SWS, an increase in stage 2 sleep and an increase in REM latency compared with healthy volunteers. Interestingly, levetiracetam also reduced bilateral epileptiform EEG activity, particularly in patients with more discharges.

Topics: Adult; Anticonvulsants; Carbamazepine; Cross-Over Studies; Double-Blind Method; Electroencephalography; Epilepsies, Partial; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Polysomnography; Severity of Illness Index; Sleep; Sleep, REM; Surveys and Questionnaires

To evaluate the efficacy, dose-response, tolerability, and withdrawal effects of levetiracetam (Keppra) as adjunctive therapy in adult patients with partial epilepsy.. In this European multicenter, double-blind, randomized, cross-over trial, levetiracetam 1000 or 2000 mg/day given in two divided doses was compared to placebo as add-on therapy in 324 patients with refractory partial seizures with or without secondary generalization. This trial consisted of six periods: an 8- or 12-week baseline, a treatment period A (4-week titration and 12-week evaluation), a treatment period B (4-week titration and 12-week evaluation), and a withdrawal period. During each evaluation period (A and B), patients received two of the three possible treatment regimens.. This study provides additional information on dose-response effects and withdrawal phenomena and confirms the responder and seizure freedom rates previously reported in the parallel part of the study (Epilepsia 41 (2000) 1179-1186). Both doses of levetiracetam significantly decreased mean partial seizure frequency compared with placebo (P<0.001), and significantly more patients receiving levetiracetam had > or = 50 and > or = 75% reductions in partial seizure frequency (1000 mg, P=0.004 and P=0.043, respectively; 2000 mg P=0.001 and P<0.001, respectively). In addition, 5.5% (10/183) of patients receiving levetiracetam 1000 mg/day and 6.3% (11/175) of patients receiving levetiracetam 2000 mg/day were seizure-free during the corresponding evaluation period, compared with 1.2% (2/172) of patients on placebo. A within-patient comparison revealed a significantly greater responder rate for the higher levetiracetam dose (P=0.018). The most commonly reported adverse effects (> or = 5% and more frequent in one of the groups with levetiracetam) were headache, asthenia, infection, somnolence, pharyngitis, dizziness, and pain. No withdrawal-related adverse events were reported during the cross-titration period.. Levetiracetam was effective and well-tolerated and decreased seizure frequency in a dose-dependent manner, with no evidence of typical withdrawal-related adverse events or rebound phenomena after withdrawal or down-titration.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Anticonvulsants; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Epilepsies, Partial; Female; Humans; Levetiracetam; Logistic Models; Male; Middle Aged; Piracetam

To assess the efficacy and safety of levetiracetam (LEV) as adjunctive therapy in children with treatment-resistant partial-onset seizures.. Children (aged 6-12 years) with treatment-resistant partial-onset seizures receiving one standard antiepileptic drug (AED) were eligible. After a 4-week baseline period, children received LEV in a 6-week titration phase (target dose, 40 mg/kg/day) followed by an 8-week evaluation phase. Seizure frequency during the evaluation period with individualized LEV doses (20-40 mg/kg/day) were compared with the 4-week baseline seizure frequency. Plasma concentrations of LEV and other AEDs were determined to evaluate potential drug interactions.. Twenty-four subjects enrolled and received LEV; 23 entered the evaluation phase, and 22 completed the evaluation phase. Compared with their baseline seizure frequency, 12 (52%) of 23 subjects entering the evaluation phase had their seizure frequency decrease by >50%. Two subjects remained seizure free during the entire evaluation period. LEV did not significantly affect plasma concentrations of any concomitant AED during this study, and no alteration of mean clinical laboratory values was observed. The most commonly reported adverse events were headache, infection, anorexia, and somnolence.. This open-label study of adjunctive LEV therapy (at 20-40 mg/kg/day) suggests that LEV is effective, safe, and well tolerated in children ages 6-12 years with treatment-resistant partial-onset seizures. A randomized, placebo-controlled, double-blind trial of LEV adjunctive therapy in children with treatment-resistant partial-onset seizures is needed and ongoing to confirm these open-label findings.

Topics: Age Factors; Age of Onset; Anorexia; Anticonvulsants; Child; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Headache; Humans; Infections; Levetiracetam; Male; Piracetam; Sleep Wake Disorders; Treatment Outcome

The effect of acute treatment with the new antiepileptic drug (AED) levetiracetam (Keppra) on the frequency of interictal epileptiform discharges (IEDs) was evaluated in a double-blind, placebo-controlled, crossover study with therapeutic drug monitoring and serial electroencephalographic (EEG) observations. Acute (500 mg twice daily) and chronic (individualized, 500-1000 mg twice daily) doses of levetiracetam were administered as an add-on to current AED treatment. Efficacy was tested by measuring the frequency of IEDs in EEG recordings and the number of seizures. A single acute dose of levetiracetam induced a reduction of IEDs in eight out of ten patients. During the acute phase, an insufficient number of seizures occurred for analysis. During chronic treatment over 8 weeks, seven patients showed a reduction in seizure frequency (responder rate), and one patient remained seizure free. No correlation was seen between levetiracetam levels and IED frequency. Doses of levetiracetam of up to 2000 mg/day were well tolerated, and no interactions were seen with concomitant AEDs.

Topics: Adolescent; Adult; Anticonvulsants; Brain; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Piracetam; Treatment Outcome

To evaluate the short-term effect of levetiracetam (LEV; UCB L059) as add-on therapy on health-related quality of life in the treatment of refractory partial-onset seizures.. Patients were enrolled in protocol UCB N132 if they had >/=12 partial-onset seizures with or without secondary generalization during the 12-week baseline period with a minimum of two seizures every 4 weeks. Randomization was made to placebo, LEV 1,000 mg, or LEV 3,000 mg, with sample size based on seizure frequency reduction. The 31-item Quality of Life in Epilepsy (QOLIE-31) questionnaire was completed by 246 patients at the end of baseline and at 18-week follow-up, or earlier if withdrawn.. Significant differences were found among the three treatment groups for Seizure Worry (p = 0. 0003), Overall Quality of Life (p = 0.04), and Cognitive Functioning domains (p = 0.01), as well as the Total Score (p = 0.009). Responders (>/=50% partial onset seizure reduction) had significant improvements in all areas, except Medication Effect, compared with nonresponders (all p > 0.006). Clinically noticeable improvement (>/=10% change from baseline to follow-up) was perceived by LEV 3, 000 mg responders in all areas, except Emotional Well-Being, by LEV 1,000 mg responders in 5 of 9 areas, and by placebo responders in 2 of 9 areas.. Addition of LEV to standard medication seems to have a positive impact on health-related quality of life, particularly among responders in this short-term study. These exploratory analyses require additional studies to evaluate long-term changes in a larger population.

Topics: Adult; Anticonvulsants; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Follow-Up Studies; Health Status Indicators; Humans; Levetiracetam; Male; Piracetam; Placebos; Quality of Life; Sickness Impact Profile; Surveys and Questionnaires; Treatment Outcome

To evaluate the efficacy and safety of 500 mg bid and 1500 mg bid levetiracetam as adjunctive therapy for refractory partial seizures in a double-blind, randomized, placebo-controlled, parallel-group, multicenter trial.. The authors studied patients with uncontrolled partial seizures (minimum 12 per 12 weeks), regardless of whether they became secondarily generalized, for 38 weeks. A 12-week baseline was followed by random assignment to adjunctive therapy with placebo (n = 95), levetiracetam 1000 mg/day (n = 98), or levetiracetam 3000 mg/day (n = 101). Upward titration over 4 weeks was followed by 14 weeks of fixed dose treatment, and concluded with an 8-week medication withdrawal period or entering a follow-up study.. Of 294 patients randomized, 268 completed the study. Partial seizure frequency during the entire evaluation period (primary efficacy variable) was lower with levetiracetam compared to placebo (p /=10%), mostly mild to moderate in severity, with incidences higher than placebo were asthenia, dizziness, flu syndrome, headache, infection, rhinitis, and somnolence.. Adjunctive therapy with levetiracetam was effective and well tolerated in controlling partial seizures.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Treatment Outcome

to determine whether the QOLIE-10, an abbreviated quality of life questionnaire, provides results similar to the more detailed QOLIE-31 instrument when the ten items are derived from the QOLIE-31.. the QOLIE-31 was completed by 246 patients participating in UCB protocol N132 at baseline and after 18 weeks of treatment with levetiracetam (LEV 1000 or 3000 mg) or placebo added to standard therapy. QOLIE-10 components and total scores were calculated from the QOLIE-31 data.. baseline QOLIE-10 components and total score correlated highly with corresponding QOLIE-31 scores, both at baseline and follow-up (range 0.70-0.95). Changes from baseline to follow-up were significantly different (ANCOVA) among treatment groups for both the QOLIE-10 and QOLIE-31 for the total score (P = 0.02, P = 0.009, respectively), seizure worry (P = 0.005, P = 0.0003) and cognitive functioning (P = 0.01, P = 0.01). One subscale (overall QOL) showed significant change with the QOLIE-31 (P = 0.04), but not with the QOLIE-10 (P = 0.07). Differences in QOLIE-10 scores were found between responders (> or = 50% partial onset seizure reduction) and non-responders for the total score (P = 0.0001) and two components (overall QOL P = 0.002, social function P = 0.0003). In the QOLIE-31, the total score and six subscale scores (all except medication effects) were significantly different. Both instruments were able to detect change over time. Responsiveness assessed by effect sizes (- 0.1 for non-responders, 0.4 for responders, 0.8 for seizure-free patients) and the Guyatt statistic (0.1, 0.6 and 1.0, respectively) was similar for both instruments.. although the QOLIE-10 was designed as a screening tool, it can be scored and used in research. The total score did discern differences among treatments in a clinical trial. Nonetheless, questionnaires with multiple, multi-item subscales provide more detailed information than abbreviated forms. The QOLIE-31 is preferred where time and resources are available.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Anticonvulsants; Anxiety; Drug Therapy, Combination; Emotions; Epilepsies, Partial; Follow-Up Studies; Humans; Levetiracetam; Middle Aged; Piracetam; Placebos; Quality of Life; Surveys and Questionnaires

To evaluate the efficacy and tolerability of levetiracetam (LEV, Keppra) as add-on therapy in patients with refractory partial seizures.. In this European multicenter, double-blind, randomized, placebo-controlled trial, LEV (500 or 1,000 mg twice daily) was compared with placebo as add-on therapy in 324 patients with uncontrolled simple or complex partial seizures, or both, with or without secondary generalization. After enrollment, three parallel groups were assessed during a baseline period of 8 or 12 weeks, followed by a 4-week titration interval and a 12-week evaluation period.. LEV significantly decreased partial seizure frequency compared with placebo. A reduction in seizure frequency of > or =50% occurred in 22.8% of patients in the 1,000-mg group and 31.6% of patients in the 2,000-mg group, compared with 10.4% of patients in the placebo group. Administration of LEV did not affect plasma concentrations of concomitant antiepileptic drugs or alter vital signs or laboratory parameters. No significant difference in the incidence of adverse events was observed between treatment groups (70.8% for the 1,000-mg group and 75.5% for the 2,000-mg group), or between the LEV and placebo groups (73.2% for placebo group). The most commonly reported adverse effects in the LEV group were asthenia, headache, and somnolence.. The antiepileptic efficacy and tolerability of LEV (1,000 mg/d and 2,000 mg/d, administered in two divided doses) as add-on therapy was established in patients with refractory partial seizures in this clinical study.

Topics: Anticonvulsants; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Humans; Levetiracetam; Piracetam; Placebos; Treatment Outcome

To evaluate the efficacy and tolerability of levetiracetam (LEV) monotherapy in selected patients with refractory partial seizures.. In this multicenter, double-blind, placebo-controlled, parallel-group, responder-selected study, patients were randomized (2:1 ratio) to receive oral LEV 1500 mg twice daily or placebo during a 12-week add-on phase. Treatment responders (patients with a reduction in partial seizure frequency of 50% or more compared with baseline) entered a monotherapy phase that included a maximum 12-week down-titration period and 12 weeks of monotherapy at 1500 mg twice daily. In both phases, responder rate, seizure frequency, and adverse events were analyzed.. A total of 286 patients (placebo, n = 105; LEV, n = 181) entered the add-on phase, and 86 patients (placebo, n = 17; LEV, n = 69) were eligible for the monotherapy phase. Thirty-six of 181 patients (19.9%) who received LEV completed the entire study compared with only 10 of 105 patients (9.5%) in the placebo group (p = 0.029). The odds of completing the study on LEV were 2.36 times (95% confidence interval, 1.08, 5.57) higher than on placebo. The responder rate during the add-on phase was significantly higher in the LEV group compared with the placebo group (42.1% vs. 16.7%, respectively; p < 0.001). In the LEV monotherapy group, the median percent reduction in partial seizure frequency compared with baseline was 73.8% (p = 0.037), with a responder rate of 59.2%. Nine patients (18.4%) remained seizure-free on LEV monotherapy.. Conversion to LEV monotherapy (1500 mg twice daily) is effective and well tolerated in patients with refractory partial seizures who responded to 3000 mg/d LEV as add-on therapy.

Topics: Anticonvulsants; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Humans; Levetiracetam; Piracetam; Placebos; Treatment Outcome

The high seizure burden seen in World Health Association (WHO) grade 2 gliomas is well documented. This study aims to identify factors that influence the probability of seizure freedom (12 months of seizure remission) and treatment failure (antiseizure medication [ASM] cessation or introduction of an alternative) in patients with WHO grade 2 glioma.. This is a retrospective observational analysis of patients from a regional UK neurosurgical center with histologically proven (n = 146) WHO grade 2 glioma and brain tumor related epilepsy. Statistical analyses using both Kaplan-Meier and Cox proportional hazards models were undertaken, with a particular focus on treatment outcomes when the commonly prescribed ASM levetiracetam (n = 101) is used as first line.. Treatment with levetiracetam as a first-line ASM resulted in a significant increase in the probability of seizure freedom (p < .05) at 2 years compared with treatment with an alternative ASM. Individuals presenting with focal seizures without bilateral tonic-clonic progression were between 39% and 42% significantly less likely to reach seizure freedom within 10 years (p < .05) and 132% more likely to fail treatment by 5 years (p < .01) when compared to individuals who had seizures with progression to bilateral tonic-clonic activity. ASM choice did not significantly affect treatment failure rates.. More than two-thirds of patients with WHO grade 2 glioma related epilepsy treated with levetiracetam first line achieve seizure freedom within 2 years and it is a reasonable first-choice agent. Experiencing mainly focal seizures without progression infers a significant long-term reduction in the chance of seizure freedom. Further studies are needed to inform ASM selection.

Topics: Anticonvulsants; Carbamazepine; Epilepsies, Partial; Epilepsy; Freedom; Glioma; Humans; Levetiracetam; Seizures; Treatment Failure; World Health Organization

To elucidate the incidence and risk factors for paradoxical effects (i.e., increased seizure frequency, increased seizure severity, or onset of new seizure types) of levetiracetam (LEV) in people with epilepsy (PWE) and identify the usefulness of electroencephalography (EEG) in predicting these effects.. We examined data for consecutive PWE treated with LEV. All PWE underwent EEG and magnetic resonance imaging (MRI) before LEV administration. We also evaluated the incidence of paradoxical LEV effects and conducted multivariate logistic regression analyses to identify the associated factors.. In total, 210 (66.2%) of 317 PWEs treated in our department had a history of LEV use. The incidence of paradoxical LEV effects was 5.2% (n = 11) and was significantly associated with a high LEV dose (p = 0.029), high seizure frequency (p = 0.005), temporal lobe epilepsy (p = 0.004), focal awareness seizure (p = 0.004), focal impaired awareness seizure (p = 0.007), spike (p = 0.015), rhythmic epileptiform discharges (REDs; p = 0.003), and MRI-identified focal cortical dysplasia (FCD; p < 0.0001). Multivariate analyses revealed that REDs (odds ratio [OR] = 5.35, p = 0.048, 95% confidence interval [CI]: 1.01-28.21) were independently associated with paradoxical LEV effects.. Paradoxical LEV effects occurred in PWE, particularly in those with drug-resistant focal epilepsy. Furthermore, the occurrence of REDs in EEG was an independent factor associated with the paradoxical effects of LEV in PWE.

Topics: Anticonvulsants; Drug Resistant Epilepsy; Electroencephalography; Epilepsies, Partial; Epilepsy; Humans; Levetiracetam; Seizures; Treatment Outcome

To gather real-world evidence on antiseizure medications (ASMs) treatment patterns and related outcomes in patients with drug-resistant focal epilepsy.. Medical insurance claims from the start of 2014 till the end of 2019 were used. Patient selection criteria included International Classification of Diseases (ICD) codes followed by documented ASM use. Baseline patient demographics along with ASM and rescue medication use patterns and related patient outcome were documented for first (index) ASM regimen. Patients who failed the first regimen and then failed the second regimen were considered drug resistant. Multivariate analyses were performed to identify risks and other characteristics for positive or negative treatment outcomes.. Study cohort consisted of 46 474 patients with a mean age of 47.23 (SD: 16.94). Levetiracetam was the most first-encountered ASM (37.94%). At baseline, 87.14% were treated with ASMs prior to having study-confirmed diagnoses. Mental comorbidities were present in 37.86% of patients. After first-year ASM treatment, 34.61% of patients persisted on their index regimen and 5.91% were seizure-free. Patients failing first ASM regimen numbered 12 868 (27.69%). Drug-resistant patients who failed first and then second ASM regimens numbered 6335 (49.23%). Percentages of patients who had successful second treatment and seizure-free were 21.32 and 3.65, respectively. Initiating patients on lamotrigine or carbamazepine (relative to levetiracetam), baseline use of index ASM, rescue medications, and older age or male gender all lowered the risk for treatment failure. Having higher comorbidity, comorbid mental illness, headache, or neoplasty increased such a risk. Baseline use of index ASM, depressive episode, or anxiety disorder all entailed higher risk of failing second ASM treatment.. Overall, reported findings indicated that patient history at baseline and the early selection of an ASM all influenced treatment outcomes. Findings pointed to the complex nature of ASM treatment in drug-resistant focal epilepsy patients calling for additional research to identify the optimal treatment to achieve beneficial patient outcomes.

Topics: Anxiety Disorders; Drug Resistant Epilepsy; Epilepsies, Partial; Humans; Levetiracetam; Male; Middle Aged; Treatment Failure; Treatment Outcome

The aim of the current study was to investigate the seizure outcome and also factors associated with that in patients with epilepsy [i.e., idiopathic generalized epilepsies (IGEs), symptomatic generalized epilepsies (SGEs), and focal epilepsies], who received either lamotrigine (LTG) or levetiracetam (LEV). This was a retrospective longitudinal study. All patients with a diagnosis of IGE, focal epilepsy, or SGE, who received either LTG or LEV, were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran from 2008 until 2020. All patients had to be followed at our center for at least 14 months. Two hundred and thirty-six patients were studied (101 IGE, 98 focal epilepsy, and 37 SGE). At the first visit, LTG was prescribed for 159 patients; 40 people (25.2%) became seizure-free, and LEV was prescribed for 77 people; 23 persons (29.9%) became seizure-free (p = 0.438). Patients who were not taking any drug at the time of their first visit, or were receiving fewer drugs, and those who had received fewer drugs in their drug history were more likely to enjoy a seizure-free state at the follow-up. Among the patients, who received LTG at the first visit, taking any Na-channel blocking drug (e.g., carbamazepine) in the drug history was associated with a poor seizure outcome; this was not the case for LEV. Implementation of appropriate personalized treatment plans in patients with epilepsy is of paramount significance. Rational selection of appropriate drug(s) is the mainstay of this process.

Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Humans; Immunoglobulin E; Lamotrigine; Levetiracetam; Longitudinal Studies; Retrospective Studies; Seizures; Treatment Outcome; Triazines

In newly diagnosed neurocysticercosis (NCC) with seizures, the choice of anti-seizure medication (ASM) seems to be arbitrary due to a lack of comparative studies. Although oxcarbazepine (OXC) is often considered efficacious for focal seizures in NCC, due to adverse effects, newer ASMs like levetiracetam (LCM) and lacosamide are also being explored.. This study was performed by case record review of children with newly diagnosed solitary viable parenchymal NCC aged 4-18years who received lacosamide and OXC at least for 12 weeks between August 2019 and April 2021, from a prospective registry of a tertiary care teaching hospital in north India. Seizure control, electroencephalographic abnormalities, resolution of inflammatory granulomas and adverse effects were compared between two arms at 12 and 24 weeks.. Total 31 (8.3 ± 4.7 years, 19 boys) and 72 (8.6 ± 4.2 years, 43 boys) completed at least 12 weeks follow-up in LCM and OXC groups, out of which 2 and 51 completed at least 24 weeks follow-up in LCM and OXC groups, respectively. The occurrence of breakthrough seizure was comparable in both arms at 12 and 24 weeks (1/31 and 2/22 in lacosamide group vs. 2/72 and 4/51 in OXC group, p = 0.66 and 0.59, respectively). Patients receiving OXC had more frequent treatment-emergent adverse events (p = 0.0001) and four patients required discontinuation due to severe adverse events (SAEs), while none in the lacosamide group had SAEs.. Lacosamide appears to be efficacious and safe for achieving seizure freedom in patients with solitary viable parenchymal neurocysticercosis.

Topics: Anticonvulsants; Child; Epilepsies, Partial; Female; Humans; Lacosamide; Levetiracetam; Male; Neurocysticercosis; Oxcarbazepine; Seizures; Treatment Outcome

Specific antiseizure medications (ASM) would improve the outcome in post-stroke epilepsy (PSE). The aim of this multicenter observational study was to compare different antiseizure monotherapies in PSE.. We collected the data from 207 patients with PSE who did not change their initial antiseizure monotherapy during the period of 12 months. Efficacy was assessed by a standardized three month seizure frequency and seizure freedom. Safety was estimated by the reported side effects.. The mean three month seizure frequency was 1.9 ± 3.1 on eslicarbazepine, 2.1 ± 3.2 on lacosamide, 3.4 ± 4.4 on levetiracetam, 4.3 ± 6.8 on lamotrigine, and 5.1 ± 7.3 on valproate (p < 0.05 for eslicarbazepine or lacosamide in comparison with levetiracetam, lamotrigine and valproate, respectively). The lowest seizure frequency and the highest seizure freedom was observed on ASMs acting via the slow inactivation of sodium channels in comparison to other mechanisms of action (0.7 ± 0.9 vs 2.2 ± 2.4, p < 0.01). Among side effects, the most frequently reported were vertigo (25%) and tiredness (15.9%). They were similar in all investigated groups of ASM. The independent factors increasing seizure frequency that were identified in multiple regression analyses were increased size of infarction, cortical involvement, hemorrhagic transformation, neurological deficits at admission and functional impairment. Administration of ASM with the mechanism of action via the slow inactivation of sodium channels was an independent factor decreasing the seizure frequency.. Our data show that antiseizure medications acting via the slow inactivation of sodium channels, such as lacosamide and eslicarbazepine, are well tolerated and might be associated with better seizure control in PSE.

Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy; Humans; Lacosamide; Lamotrigine; Levetiracetam; Seizures; Sodium Channels; Stroke; Valproic Acid

Brivaracetam (BRV) is licensed as an adjunctive treatment for focal epilepsy. We describe our clinical experience with BRV at a large UK tertiary center.. Adults initiated on BRV between July 2015 and July 2020 were followed up until they discontinued BRV or September 2021. Data on epilepsy syndrome, duration, seizure types, concomitant and previous antiseizure medication (ASM) use, BRV dosing, efficacy, and side effects were recorded. Efficacy was categorized as temporary (minimum three months) or ongoing (at last follow-up) seizure freedom, ≥50% seizure reduction, or other benefits (e.g., no convulsions or daytime seizures). Brivaracetam retention was estimated using Kaplan-Meier survival analysis.. Two-hundred people were treated with BRV, of whom 81% had focal epilepsy. The mean (interquartile range [IQR]) follow-up time was 707 (688) days, and the dose range was 50-600 mg daily. The mean (IQR) of the previous number of used ASMs was 6.9 (6.0), and concomitant use was 2.2 (1.0). One-hundred and eighty-eight people (94%) had previously discontinued levetiracetam (LEV), mainly due to side effects. 13/200 (6.5%) were seizure free for a minimum of six months during treatment, and 46/200 (23%) had a ≥50% reduction in seizure frequency for six months or more. Retention rates were 83% at six months, 71% at 12 months, and 57% at 36 months. Brivaracetam was mostly discontinued due to side effects (38/75, 51%) or lack of efficacy (28/75, 37%). Concomitant use of carbamazepine significantly increased the hazard ratio of discontinuing BRV due to side effects (p = 0.006). The most commonly reported side effects were low mood (20.5%), fatigue (18%) and aggressive behavior (8.5%). These side effects were less prevalent than when the same individuals took LEV (low mood, 59%; aggressive behavior, 43%). Intellectual disability was a risk factor for behavioral side effects (p = 0.004), and a pre-existing mood disorder significantly increased the likelihood of further episodes of low mood (p = 0.019).. Brivaracetam was effective at a broad range of doses in managing drug-resistant epilepsy across various phenotypes, but less effective than LEV in those who switched due to poor tolerability on LEV. There were no new tolerability issues, but 77% of the individuals experiencing side effects on BRV also experienced similar side effects on LEV.

Topics: Anticonvulsants; Carbamazepine; Drug Resistant Epilepsy; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Epilepsies, Partial; Humans; Levetiracetam; Pyrrolidinones; Seizures; Tertiary Care Centers; Treatment Outcome

This study aimed to examine prescription patterns of antiepileptic drugs (AEDs) for adult patients with newly diagnosed focal epilepsy in Japan and whether these patterns adhere to the 2010 Japanese Society of Neurology Guidelines of Epilepsy Treatment.. Data from the JMDC Claims Database were obtained for patients aged between 20 and 65 years with newly diagnosed focal epilepsy who were prescribed AEDs between 2006 and 2017. Available prescription information up to the patient's first year was recorded and longitudinal descriptive statistics, Cochran Armitage Trend (CAT) tests, and annual percentage change (APC) were used to analyze AED trends and overall guideline adherence. In addition, logistic regression analyses were used to compare these results across different health facilities.. A total of 6024 adult patients with newly diagnosed focal epilepsy were enrolled. The prescription of new AEDs increased significantly (CAT, p < 0.001, APC = 28.74 %) up to 36.8 % of all prescriptions in 2017 when compared to 2006. Among new AEDs, prescriptions for levetiracetam increased most rapidly and were followed by lamotrigine. In contrast, prescriptions for older AEDs, especially valproate, decreased over this same time period. The average guideline adherence rate from 2010 to 2017 was 75.3 %, and was not significantly different over time (CAT, p = 0.55). Health facilities with either more than 500 beds or between 20-499 beds had higher odds of prescribing new AEDs and improved guideline adherence when compared to facilities with 0-19 beds.. Prescription patterns of AEDs for adult patients with newly diagnosed focal epilepsy exhibited a trend from older to new AED classes between 2006 and 2017, with consistent, high guideline adherence from 2010 to 2017. Health facilities with 0-19 beds were less likely to prescribe new AEDs and completely adhere to proposed guidelines.

Topics: Adult; Anticonvulsants; Drug Prescriptions; Epilepsies, Partial; Humans; Japan; Levetiracetam

The study assessed the clinical response to add-on brivaracetam (BRV) in real-world practice by means of time-to-baseline seizure count methodology. Patients with focal epilepsy who were prescribed add-on BRV were identified. Primary endpoint was the time-to-baseline seizure count defined as the number of days until each patient experienced the number of focal seizures that occurred in the 90 days before BRV initiation. Subgroup analysis was performed according to levetiracetam (LEV) status (naive vs prior use). Three-hundred eighty-seven patients were included. The overall median time-to-baseline seizure count was 150 (95% confidence interval [CI] = 130-175) days. The median time-to-baseline seizure count was 198 (lower limit of 95% CI = 168) days for LEV-naive patients, 126 (95% CI = 105-150) days for patients with prior LEV use and withdrawal due to insufficient efficacy, and 170 (95% CI = 128-291) days for patients who discontinued LEV due to adverse events (P = .002). The number of prior antiseizure medications (adjusted hazard ratio [

Topics: Adult; Anticonvulsants; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Proportional Hazards Models; Pyrrolidinones; Treatment Outcome

There are only a few reports on Go-induced epilepsy. We hereby report a case of Go-induced epilepsy and its ictal electroencephalography (EEG) findings, and treatment. A 71-year-old man reported to our hospital for seizures that lasted for several minutes after he had played Go for approximately an hour. Ictal EEG showed focal to bilateral tonic-clonic seizures of right parietal origin. He was administered levetiracetam 500 mg before the games, and he participated without seizures for more than a year. Go-induced epilepsy is considered to have a focal onset, and it may be controlled with antiepileptic drugs before the games.

Topics: Aged; Electroencephalography; Epilepsies, Partial; Games, Recreational; Humans; Levetiracetam; Male; Parietal Lobe; Seizures; Time Factors

This case report will provide further evidence for the fact that breach rhythm is not the effect of a bone abnormality only. We present the case of an 84-year-old woman, who had a craniotomy 14 month before admission to our emergency department with a focal inhibitory status epilepticus. Even after clinical recovery, electroencephalography revealed frequent subclinical seizure patterns. When seizure activity was suppressed by anticonvulsive medication with levetiracetam, breach rhythm appeared. Breach rhythm develops usually some months after craniotomy and therefore should have been established in our patient at the time of admission. Therefore, it is reasonable to assume that it was in some way suppressed by the seizure activity in our primary EEG recordings. The appearance of the breach rhythm after the complete suppression of seizure activity by antiepileptic drug treatment shows that breach rhythm is not purely the result of a skull defect but is related to the functional state of the brain tissue beneath.

Topics: Aged, 80 and over; Anticonvulsants; Brain; Craniotomy; Electroencephalography; Epilepsies, Partial; Female; Humans; Levetiracetam; Paralysis; Seizures

The aim of this study was to gather the expert opinions of Korean epileptologists regarding the treatment of adult patients with epilepsy.. A total of 42 neurologists who specialized in epilepsy were surveyed. They completed an online questionnaire describing multiple patient scenarios. Using these scenarios, they evaluated treatment strategies and gave their preference for specific antiepileptic drugs (AEDs) used to treat genetically mediated generalized epilepsy and focal epilepsy.. Initial AED monotherapy, followed by a second form of alternative monotherapy or an add-on combination therapy, was the preferred treatment strategy. The experts reached consensus for 87.2% of the items. The most commonly selected AEDs for the initial monotherapy for patients with generalized epilepsy were levetiracetam or valproate. For those with focal epilepsy, levetiracetam, oxcarbazepine, or lamotrigine were the most popular selections. Ethosuximide was the treatment of choice only for patients with generalized epilepsy with prominent absence seizures. Levetiracetam was preferred as an add-on therapy for both generalized and focal epilepsy. For special populations of patients, such as elderly adults or those with comorbid diseases, levetiracetam or lamotrigine was selected as the treatment of choice.. Most of the survey results were in accordance with the US expert opinion survey published in 2016. This survey can assist clinicians in making clinical decisions when treating individual adult patients with epilepsy.

Topics: Adult; Aged; Anticonvulsants; Epilepsies, Partial; Epilepsy, Absence; Epilepsy, Generalized; Expert Testimony; Female; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Republic of Korea; Surveys and Questionnaires; Treatment Outcome; Valproic Acid; Young Adult

The primary objective of the study was to analyze the efficacy of brivaracetam (BRV) in pediatric patients 12 months after starting treatment. The secondary objective was to establish safety 3, 6, and 12 months after starting treatment.. This was an observational and retrospective study. Data were collected from the electronic medical record. Inclusion criteria were as follows: patients under 18 years of age, diagnosis of focal or generalized epilepsy, treatment as an added therapy, initiation of treatment with BRV between June and September 2017, and at least one unprovoked seizure in the year prior to the start of treatment.. Forty-six patients were included. The response rate was 65%, including 30% seizure-free patients. The rate of adverse effects was 43.5%, resulting in withdrawal in 16 patients (34.7%). The most common adverse effects were drowsiness (17.3%) and irritability (17.3%).. Brivaracetam is effective in very diverse childhood epilepsies, including some that present with primarily generalized seizures. Given the characteristics of the population studied, we have not been able to confirm a better tolerability of BRV compared with levetiracetam (LEV).

Topics: Adolescent; Anticonvulsants; Child; Epilepsies, Partial; Epilepsy, Generalized; Female; Humans; Irritable Mood; Levetiracetam; Male; Pyrrolidinones; Retrospective Studies; Treatment Outcome; Wakefulness

Topics: Administration, Intravenous; Anticonvulsants; Child, Preschool; Contrast Media; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Gadolinium; Hamartoma; Humans; Hypothalamic Diseases; Laughter; Levetiracetam; Magnetic Resonance Imaging; Male; Topiramate; Treatment Outcome

We performed observational cohort study to compare the long-term efficacy, tolerability, and safety of oxcarbazepine (OXC), lamotrigine (LTG), and levetiracetam (LEV) monotherapy for newly diagnosed focal epilepsy patients.. Three hundred and eighty eight newly diagnosed focal epilepsy patients aged 1-70 years were enrolled in this study between June 2009 and March 2016. Among the patients, 191 were treated with OXC, 98 were treated with LTG, and 99 were treated with LEV monotherapy. The study was performed in a real-world setting and the primary outcomes were the one-year and three-year seizure-free rates. The secondary outcomes were the one-year and three-year withdrawal rates, the time to treatment withdrawal, the time to the first seizure, and the time to achieve one-year remission.. The three-year seizure-free rates with LTG (39.8 %) and LEV (41.4 %) were significantly better than that with OXC (26.2 %) (both P < 0.05). However, no significant difference was observed among the three drugs for the one-year seizure-free rate. The three-year withdrawal rate was 50.8 %, 46.9 %, and 43.4 % for OXC, LTG, and LEV, respectively (all P > 0.05). The one-year withdrawal rate for OXC (31.7 %) was higher than those for LTG (30.6 %) and LEV (26.3 %) (all P > 0.05). LEV [Relative Risk (RR) = 0.69, 95 % CI: 0.49∼0.99] and LTG (RR = 0.63, 95 % CI: 0.44∼0.9) were significantly better than OXC in preventing first seizure. LEV appears to be the superior option with regard to the time to achieve one-year remission.. The results of the study showed that LEV and LTG are significantly more effective than OXC for the treatment of newly diagnosed focal epilepsy. LEV has milder adverse events than OXC and LTG in clinical practice.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Child, Preschool; Cohort Studies; Dizziness; Drug Administration Schedule; Epilepsies, Partial; Exanthema; Female; Humans; Infant; Lamotrigine; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Time Factors; Treatment Outcome; Young Adult

Long-term treatment with certain antiepileptic drugs may lead to thyroid function disturbances or alterations in bone metabolism; the data on the effects of new antiepileptic drugs on this are limited and conflicting, especially in children with epilepsy. Therefore, the aim of this study was to investigate the effects of levetiracetam and oxcarbazepine on thyroid hormone levels and bone metabolism in children with epilepsy.. A total of 51 children with new-onset partial epilepsy were selected. They were randomly treated with either levetiracetam (n = 25), or oxcarbazepine (n = 26) monotherapy. Eight of the 51 patients were excluded for failing to take the drug continuously or failing to undergo a regular review. Thus, 43 patients were finally included (levetiracetam: 23 patients, oxcarbazepine: 20 patients). A control group consisting of age- and sex-matched healthy subjects (n = 20) was included for comparison. Serum triiodothyronine, tetraiodothyronine, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, calcium, phosphorus, alkaline phosphatase, osteocalcin, parathyroid hormone, and 25-hydroxyvitamin D levels and bone mineral density values were measured before and at 6 and 12 months after therapy in all groups.. At baseline, thyroid hormone levels, bone metabolism index, and bone mineral density values did not differ between the control group and the drug-treated groups. Levetiracetam-treated patients showed no significant changes in thyroid hormone levels, bone metabolism, and bone mineral density during the 12-month follow-up period compared with baseline values. In the oxcarbazepine group, compared to baseline values, serum free thyroxine levels decreased after 12 months of treatment (Z = -3.115, p = 0.002), and after 6 and 12 months of treatment, calcium levels decreased (Z = -3.705, p < 0.001 and Z = -3.884, p < 0.001, respectively) and parathyroid hormone levels increased (Z = -3.698, p < 0.001 and Z = -3.921, p < 0.001, respectively); however, all other parameters did not differ from baseline values.. Our data show that levetiracetam treatment has no significant effect on thyroid function and bone metabolism in children with epilepsy. Long-term use of oxcarbazepine may reduce serum free thyroxine levels, resulting in impaired thyroid function, and may reduce serum calcium and increase parathyroid hormone levels, leading to bone metabolism disorders.

Topics: Anticonvulsants; Bone Density; Carbamazepine; Child; Epilepsies, Partial; Female; Humans; Levetiracetam; Longitudinal Studies; Male; Oxcarbazepine; Parathyroid Hormone; Prospective Studies; Thyroid Hormones; Thyrotropin

Kaiser Permanente advocates using single-source generics for brand-name drugs. We compared the effectiveness of 3 different-generation generic antiepileptic drugs (AEDs) in patients with focal epilepsies.. To compare the effectiveness of the 3 most commonly used AEDs (carbamazepine [CBZ], lamotrigine [LTG], and levetiracetam [LEV]) after 24-month monotherapy.. This is a retrospective data analysis of 646 consecutive AED-naive patients aged 1-88 years treated with CBZ, LTG, or LEV between 2006 and 2012 with dosing adjustments permitted during the first 6 months. Chi-squared test with p < 0.05 was used to calculate seizure-freedom and tolerability rates.. At the end of the 24-month study period, 65.69% patients in the CBZ group continued to remain seizure free, 25.98% were drug failures, and 8.33% dropped out due to adverse events, with the corresponding numbers being 66.49%, 23.94%, and 9.57% in the LTG group and 72.44%, 12.99%, and 14.57% in the LEV group. Rash was the most common adverse event for CBZ (3.43%) and LTG (6.38%), and mood changes were the most commen adverse event for LEV (7.87%). Among the 3 groups (n = 646), AED tolerance rates and AED retention rates showed no significant difference (p = 0.08 and p = 0.23, respectively). Seizure-freedom rate difference among the 3 groups (n = 574) was significant (p = 0.003), and seizure-freedom rate for LEV was superior to CBZ (p = 0.001) and to LTG (p = 0.006).. At the end of the 24-month study period, in a head-to-head comparison of single-source bioequivalent generic formulations, superior seizure-freedom rate and comparable tolerability and retention rates for LEV were observed when compared with CBZ and LTG.

Topics: Anticonvulsants; Carbamazepine; Epilepsies, Partial; Humans; Lamotrigine; Levetiracetam; Retrospective Studies

Clinical studies suggest that the antiepileptic drug (AED) brivaracetam (BRV) is associated with fewer behavioral and psychiatric adverse events (AEs) compared with levetiracetam (LEV) in treating epilepsy. There are, however, few comparative studies of treatment-emergent AEs between patients on BRV with preexisting psychiatric or behavioral comorbidities to those without. Our study compared longer-term tolerability over a 26-month period between these patient groups and assessed the overall efficacy of BRV as add-on therapy. Patients with intellectual disabilities in whom the prevalence of epilepsy is higher, are often excluded from randomized controlled trials, and our study further assessed comparative effectiveness between this patient group and those with normal range intellect. We collected prospective data on 134 patients prescribed add-on BRV for epilepsy at a tertiary UK center over a 26-month period. All patients had previously received LEV. Sixty-three patients were on LEV at the start of the data collection period. Levetiracetam was withdrawn and switched to BRV in 39 patients because of inefficacy and 24 patients because of behavioral or psychiatric side effects. Seventy-three patients (54%) had a preexisting psychiatric or behavioral disorder compared with 64 patients (46%) without. The retention rate at last follow-up [mean: 11 months (0.5-26 months)] was 60% in the psychiatric/behavioral disorders group versus 67% in those without (p = 0.68). Forty-one patients had diagnosed intellectual disabilities. The retention rate was 66% in this group versus 62% in patients without intellectual disabilities (p = 0.36). The commonest treatment-emergent AEs were somnolence (26%), aggression (23%), and depression (9%). There were similar frequencies reported for these specific events across the groups. The proportion with a 50% responder rate was 29% in patients with focal epilepsy and 47% in patients with generalized and combined focal and generalized epilepsies. However, fifteen patients (11%) reported increased seizure activity leading to withdrawal of treatment. This study showed evidence that BRV may be an effective adjunctive therapy in patients with drug-resistant focal or generalized epilepsies whose seizures have previously not responded or tolerated LEV therapy. We demonstrated a higher incidence of treatment-emergent AEs leading to lower retention rates compared with previous studies across all patient groups. There were, however, no signifi

Topics: Adolescent; Adult; Aged; Anticonvulsants; Behavioral Symptoms; Comorbidity; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Generalized; Female; Humans; Intellectual Disability; Levetiracetam; Male; Mental Disorders; Middle Aged; Prospective Studies; Pyrrolidinones; Treatment Outcome; Young Adult

Limited population-based data are available on antiepileptic drug (AED) treatment patterns in women of childbearing age with epilepsy; the current population risk is not clear.. To examine the AED treatment patterns and identify differences in use of valproate sodium and topiramate by comorbidities among women of childbearing age with epilepsy.. A retrospective cohort study used a nationwide commercial database and supplemental Medicare as well as Medicaid insurance claims data to identify 46 767 women with epilepsy aged 15 to 44 years. The eligible study cohort was enrolled between January 1, 2009, and December 31, 2013. Data analysis was conducted from January 1, 2017, to February 22, 2018.. Cases required an International Classification of Diseases, Ninth Revision, Clinical Modification-coded epilepsy diagnosis with continuous medical and pharmacy enrollment. Incident cases required a baseline of 2 or more years without an epilepsy diagnosis or AED prescription before the index date. For both incident and prevalent cases, focal and generalized epilepsy cohorts were matched by age, payer type, and enrollment period and then compared.. Antiepileptic drug treatment pattern according to seizure type and comorbidities.. Of the 46 767 patients identified, there were 8003 incident cases (mean [SD] age, 27.3 [9.4] years) and 38 764 prevalent cases (mean [SD] age, 29.7 [9.0] years). Among 3219 women in the incident epilepsy group who received AEDs for 90 days or more, 3173 (98.6%) received monotherapy as first-line treatment; among 28 239 treated prevalent cases, 18 987 (67.2%) received monotherapy. In 3544 (44.3%) incident cases and 9480 (24.5%) prevalent cases, AED treatment was not documented during 180 days or more of follow-up after diagnosis. Valproate (incident: 35 [5.81%]; prevalent: 514 [13.1%]) and phenytoin (incident: 33 [5.48%]; prevalent: 178 [4.53%]) were more commonly used for generalized epilepsy and oxcarbazepine (incident: 53 [8.03%]; prevalent: 386 [9.89%]) was more often used for focal epilepsy. Levetiracetam (incident: focal, 267 [40.5%]; generalized, 271 [45.0%]; prevalent: focal, 794 [20.3%]; generalized, 871 [22.2%]), lamotrigine (incident: focal, 123 [18.6%]; generalized, 106 [17.6%]; prevalent: focal, 968 [24.8%]; generalized, 871 [22.2%]), and topiramate (incident: focal, 102 [15.5%]; generalized, 64 [10.6%]; prevalent: focal, 499 [12.8%]; generalized, 470 [12.0%]) were leading AEDs prescribed for both focal and generalized epilepsy. Valproate was more commonly prescribed for women with comorbid headache or migraine (incident: 53 of 1251 [4.2%]; prevalent: 839 of 8046 [10.4%]), mood disorder (incident: 63 of 860 [7.3%]; prevalent: 1110 of 6995 [15.9%]), and anxiety and dissociative disorders (incident: 57 of 881 [6.5%]; prevalent: 798 of 5912 [13.5%]). Topiramate was more likely prescribed for those with comorbid headache or migraine (incident: 335 of 1251 [26.8%]; prevalent: 2322 of 8046 [28.9%]).. Many women appear to be treated with valproate and topiramate despite known teratogenicity risks. Comorbidities may affect selecting certain AEDs despite their teratogenicity risks.

Topics: Adolescent; Adult; Anticonvulsants; Anxiety Disorders; Comorbidity; Dissociative Disorders; Epilepsies, Partial; Epilepsy, Generalized; Female; Headache Disorders; Humans; Lamotrigine; Levetiracetam; Mental Disorders; Migraine Disorders; Mood Disorders; Oxcarbazepine; Phenytoin; Retrospective Studies; Risk; Teratogens; Topiramate; Valproic Acid; Young Adult

Epilepsy management in elderly patients is often complex because of several concomitant comorbidities that may limit the use of some antiepileptic drugs (AEDs). Levetiracetam (LEV) is a second-generation AED widely used in elderly patients with epilepsy while lacosamide (LCM), which has been recently approved in European Union (EU) as monotherapy for the treatment of focal onset seizures, is affected by a scarcity of data in such frail population. This study is aimed at assessing the efficacy and the tolerability of LCM as monotherapy in elderly patients affected by focal onset epilepsy compared with those receiving LEV.. A retrospective chart review of patients aged ≥65 years suffering from focal onset seizures, with or without secondary generalization on LCM monotherapy or LEV monotherapy, was performed. Data regarding demographic characteristics, seizure type and etiology, LCM and LEV daily dose, number of lifetime AEDs, seizure frequency at baseline and at 12 months of follow-up, and seizure freedom rates were reported.. In this observational retrospective study, 22 patients on LCM (10 males, 12 females, mean age: 76.23 ± 7.5) and 24 patients on LEV (10 males, 14 females, mean age: 73.58 ± 6.39) were enrolled. Mean LCM daily dose was 204.51 ± 88.51 mg and mean LEV daily dose was 1281.25 ± 378.15 mg. All patients had comorbidities on chronic treatment. At 12 months of follow-up, mean monthly seizure frequency reduced from 4.23 ± 8.53 to 0.33 ± 0.9 (p < .001) in LCM group and from 2.29 ± 6.11 to 0.2 ± 0.81 (p < .001) in LEV group. Furthermore, 16/22 (72.7%) LCM patients were seizure-free at 12 months of follow-up while seizure freedom was achieved by 17/24 (70.8%) patients in LEV group.. Epilepsy management in elderly patients is often challenging. In this retrospective real-life study, the efficacy and the tolerability of LCM as monotherapy was favorable even at low doses in older patients and comparable with LEV with a high rate of long-term seizure freedom. Considering the frequent comorbidities and the risk of drug-drug interactions, LCM monotherapy may be a valuable option in elderly patients with focal onset epilepsy because of its favorable pharmacokinetic profile.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Comorbidity; Drug Interactions; Epilepsies, Partial; European Union; Female; Frail Elderly; Humans; Lacosamide; Levetiracetam; Male; Retrospective Studies; Treatment Outcome

Topics: Animals; Anticonvulsants; Chromosomes, Human, Pair 9; Drug Substitution; Electroencephalography; Epilepsies, Partial; GABA Agonists; Humans; Infant; Levetiracetam; Male; Models, Animal; Motor Skills; Neurodevelopmental Disorders; Phenobarbital; Polymorphism, Single Nucleotide; Receptors, GABA-B; Spasms, Infantile; Vigabatrin

Postoperative blindness is a devastating surgical complication. Although usually associated with prolonged cardiac and prone spinal operations, it may follow other procedures as well. Postoperative blindness is most commonly caused by a vascular etiology, but it can more rarely be caused by status epilepticus. We have previously reported a case of this phenomenon following a staged spinal deformity surgery.. Here we report 2 additional cases following a skull base procedure and a single stage lumbar spine surgery. In all instances, rapid recognition that the patients' blindness was due to occipital seizures resulted in acute antiepileptiform treatment and full restoration of vision.. Although a rare phenomenon, this syndrome, first recognized and described by Tarik F. Ibrahim, should be considered in any patient with postoperative visual impairment.

Topics: Aged; Anticonvulsants; Blindness; Brain Neoplasms; Electroencephalography; Epilepsies, Partial; Female; Humans; Levetiracetam; Lumbar Vertebrae; Occipital Lobe; Postoperative Complications; Skull Base; Spinal Stenosis; Status Epilepticus

This article compares the efficacy and tolerability of carbamazepine (CBZ) and levetiracetam (LEV) when used as initial monotherapy in children with nonlesional focal epilepsy. Patients with nonlesional focal epilepsy were subdivided into two groups according to the initial monotherapy: a LEV group administered LEV at an initial dose of 5 mg/kg/day and a CBZ group. Seizure response, adverse events, medication dose, reasons for discontinuing medication, adherence, and random serum levels were recorded. The overall percentage of patients who failed initial treatment and reasons for each treatment failure were determined. Data were analyzed from 183 children who received CBZ monotherapy and 46 children who received LEV monotherapy for ≥12 months. Overall, 126 patients (68.9%) became seizure-free with CBZ, compared with 37 patients (80.4%) with LEV. Moreover, four patients in CBZ and four patients in LEV groups showed a >50% reduction in seizure frequency. The efficacy rate was significantly higher and the adverse event rate was significantly lower in the LEV group than in the CBZ group (

Topics: Anticonvulsants; Child; Child, Preschool; Electroencephalography; Epilepsies, Partial; Epilepsy, Rolandic; Female; Follow-Up Studies; Humans; Infant; Levetiracetam; Male; Retrospective Studies; Treatment Outcome

Progressive myoclonic epilepsy (PME) is rare epilepsy syndrome. Although EEG is a useful neurophysiological technique in the evaluation of epilepsy, few EEG abnormalities have been described in PME. So, how to use EEG hints to establish the suspected diagnosis of PME as soon as possible should be addressed.. We presented a case with refractory myoclonic seizures, and progressive neurological deterioration, diagnosed as PME and neuronal ceroid lipofuscinosis disease by gene testing. The patient manifested with a significant regression in her speech ability and motor balance. The mini-mental state examination showed poor scores of 15/30. The magnetic resonance imaging showed diffused atrophy. Her EEG showed slow background with continuous occipital small spikes and photosensitivity. The following genetic testing with mutation in CLN6 confirmed the diagnosis and excluded the occipital epilepsy.. Our case showed rare manifestations and special EEG features of PME, which may be confused with occipital epilepsy or photosensitive epilepsy. Thus, if the continuous occipital spikes and photosensitivity were presented in a patient with refractory seizures and developmental regression, PME should be considered.

Topics: Anticonvulsants; Atrophy; Cerebral Cortex; Diagnosis, Differential; Disease Progression; Electroencephalography; Epilepsies, Partial; Female; Humans; Levetiracetam; Magnetic Resonance Imaging; Membrane Proteins; Mental Status and Dementia Tests; Mutation; Myoclonic Epilepsies, Progressive; Neuronal Ceroid-Lipofuscinoses; Occipital Lobe; Photosensitivity Disorders; Piracetam; Valproic Acid; Young Adult

The study aims to retrospectively compare the efficacy of lacosamide (LCS) and levetiracetam (LEV) in add-on treatment in patients with partial-onset epilepsy.. Patients who have been followed-up for at least one year due to diagnosis of partial epilepsy between September 2014 and December 2017 and who had no seizure control, despite using at least two antiepileptic monotherapies, and therefore undergone LEV or LCS add-on treatment were retrospectively reviewed. Of the patients, total number of seizures and seizure control rates 6 months before and 3 and 6 months after the add-on treatment were compared.. There was no statistically significant difference between the 30 patients in the LEV group (12 females, 18 males, mean age 29.7±6.6) and 28 patients in the LCS group (12 females, 16 males, mean age 28.2±6.4) in terms of age, gender and the duration of illness. When the LEV and LCS groups were evaluated separately, the mean number of seizures within 3 and 6 months after the add- on treatment were significantly lower than the mean number of seizures in the last 6 months before the add-on treatment (p<0.005 and p<0.005 respectively). There was no statistically significant difference between the two groups when compared with each other in terms of the rate of decrease in number of seizures and seizure control before and after the add-on treatment (p=0.445 and p=0.238, respectively).. LCS appears to be as effective as the currently well-established LEV in the treatment of partial onset seizures. No comparative study was found in the literature similar to this subject matter. There is a need for prospective studies for the comparison of the efficacies of these two drugs.. A vizsgálat célja a lacosamid (LCS) és a levetiracetam (LEV) kiegészítő kezelés hatékonyságának retrospektív összehasonlítása parciális kezdetű epilepsziában szenvedő betegek esetén.. Olyan betegek szerepeltek a vizsgálatban, akik parciális kezdetű epilepszia diagnózisát 2014 szeptembere és 2017 decembere között állapították meg, és utánkövetésük legalább egy évig zajlott, továbbá akiknél nem lehetett rohamkontrollt elérni legalább két epilepsziaellenes monoterápia alkalmazásával, ezért vagy LEV, vagy LCS kiegészítő kezelésben részesültek. Összehasonlítottuk a betegek hat hónappal a kiegészítő kezelés előtt mért összes rohamszámát és rohamkontrollarányaikat a kiegészítő kezelés után három, illetve hat hónappal mért értékekkel.. A LEV-csoportba 30 beteg (12 nő, 18 férfi, átlagéletkor 29,7±6,6 év), az LCS-csoportba 28 beteg került (12 nő, 16 férfi, átlagéletkor 28,2±6,4 év); a két csoport között nem volt statisztikailag szignifikáns különbség az életkor, a nem és a betegség fennállásának időtartama szempontjából. A LEV- és az LCS-csoport önálló értékelése esetén a kiegészítő kezelés után három és hat hónappal mért átlagos rohamszám szignifikánsan alacsonyabb volt, mint a kiegészítő kezelés előtt hat hónappal (p<0,005 és p<0,005). A két csoport eredményeit egymással összehasonlítva nem volt szignifikáns különbség a rohamszám csökkenésében és a rohamkontroll kiegészítő kezelés előtti, illetve utáni értékében (p=0,445 és p=0,238).. Az LCS ugyanolyan hatékonynak bizonyult a parciális kezdetű epilepszia kiegészítő kezelésében, mint a jelenleg leginkább használatos LEV. A szakirodalomban nem találtunk hasonló összehasonlító vizsgálatot. A jövőben prospektív vizsgálatokban kell összehasonlítani a két szer hatékonyságát.

Topics: Adult; Anticonvulsants; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Lacosamide; Levetiracetam; Male; Retrospective Studies; Seizures; Treatment Outcome

Lacosamide (LCM) due to no known drug interaction and the absence of metabolic enzyme induction is a good candidate for an add-on medication, especially in combination with lamotrigine, levetiracetam (LEV), oxcarbazepine, topiramate, and valproic acid (VPA). Here we report for the first time, to our knowledge, that LCM can lower VPA and LEV serum levels. At present, there are no known explicable mechanisms of action of LCM, which lowers VPA and LEV. Here observed drug interaction of LCM is of clinical significance, which might be useful for other colleagues in the field.

Topics: Acetamides; Adolescent; Anticonvulsants; Brain Neoplasms; Drug Interactions; Epilepsies, Partial; Humans; Lacosamide; Levetiracetam; Neoplasms, Neuroepithelial; Piracetam; Seizures; Valproic Acid

Brain tumor-related epilepsy (BTRE) is often drug resistant and patients can be forced to take polytherapy that can adversely affect their quality of life (QoL). Lacosamide (LCM) is a new antiepileptic drug (AED) used as adjunctive therapy in patients with partial seizures with or without secondary generalization, with a favorable pharmacokinetic profile that seems to be effective and well tolerated. Therefore it represents a possible therapeutic choice for patients with BTRE. We propose a prospective study with a historical control group to evaluate the effect of LCM as add-on therapy on seizure control and quality of life in patients with BTRE. This study has been designed to test the superiority of Lacosamide over Levetiracetam as an add-on. We compared a prospective cohort of 25 patients treated with Lacosamide with a historical control group (n=19) treated with Levetiracetam as an add-on.. We recruited 25 adult patients (M 18, F 7; mean age 41.9) affected by BTRE with uncontrolled partial-onset seizures treated with AED polytherapy. We added LCM as an add-on. Patients were evaluated at baseline, after 3months and at 6months. This population has been compared with a historical control group of 19 BTRE adult patients (M 13, F 6; median age 48.0, range: 28-70) with uncontrolled partial-onset seizures treated with LEV as add-on. The patients underwent QoL, mood and adverse events tests (Adverse Event Profile-AEP) and evaluation of seizure frequency.. Twelve patients had high grade gliomas, and thirteen had low grade gliomas. During follow-up, thirteen patients underwent chemotherapy, three radiotherapy and five patients had disease progression. Nine patients had simple partial seizures, eight had complex partial seizures, and eight had secondary generalized seizures. Fifteen patients were in monotherapy and ten in polytherapy with AEDs. LCM was added up to reach the maximum dosage of 400mg/die (mean final dose 300mg/die). Four patients dropped out due to poor compliance and 1 for inefficacy. In the historical control group treated with LEV (mean final dose 2000mg/die) 12 patients had high-grade gliomas, and 7 had low grade gliomas. Thirteen patients were in monotherapy and 6 in polytherapy with AEDs. In the 22 patients evaluable of 25 patients treated with LCM, we observed at final follow-up 7 patients seizure free, 12 with a significant reduction of seizures≥50%, 2 stable and 1 patient with number of seizures increased. Mean seizure frequency at baseline compared with baseline period: the mean number of seizures significantly decreased from baseline (9.4) to final follow-up (1.2) (P=0.005). The Responder Rate was 86.4%. Comparing responder rate of 22 evaluable patients with LCM with responder rate of 19 patients with LEV we didn't observe significant differences (p=0.31). In our patients treated with LCM we didn't observe significant difference at 3 and 6months in QoL tests results; we observe a significant reduction in the mean score of Karnofsky Performance Status (KPS) and Barthel Index (BI) between baseline and 6months of follow-up (KPS p=0.003; BI p=0.007). No clinical side effects were observed.. Comparing the LCM with the historical group treated with LEV in add-on, we observed that LCM seems to have a higher clinical efficacy than LEV. In our patients, we did not observe any significant changes in QoL tests, indicating stability in all quality of life domains explored, despite the objective worsening in their functional status. Although this is a small series with a relatively short follow-up, our data indicates that LCM in add-on in patients with BTRE appears to be as effective as LEV in add-on, without impact on mood and quality of life.

Topics: Acetamides; Adult; Affect; Aged; Anticonvulsants; Brain Neoplasms; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy; Female; Historically Controlled Study; Humans; Lacosamide; Levetiracetam; Male; Middle Aged; Outcome Assessment, Health Care; Piracetam; Prospective Studies; Quality of Life

Awake surgery is currently considered the best method to tailor intraparenchymatous resections according to functional boundaries. However, the exact mechanisms by which electrical stimulation disturbs behavior remain largely unknown. In this case report, we describe a new method to explore the propagation toward cortical sites of a brief pulse applied to an eloquent white matter pathway. We present a patient, operated on in awake condition for removal of a cavernoma of the left ventral premotor cortex. At the end of the resection, the application of 60Hz stimulation in the white matter of the operculum induced anomia. Stimulating the same site at a frequency of 1Hz during 70seconds allowed to record responses on electrodes put over Broca's area and around the inferior part of central sulcus. Axono-cortical evoked potentials were then obtained by averaging unitary responses, time-locked to the stimulus. We then discuss the origin of these evoked axono-cortical potentials and the likely pathway connecting the stimulation site to the recorded cortical sites.

Topics: Adult; Anomia; Anticonvulsants; Axons; Broca Area; Electrodiagnosis; Epilepsies, Partial; Evoked Potentials; Hemangioma, Cavernous, Central Nervous System; Hematoma; Humans; Language Tests; Levetiracetam; Magnetic Resonance Imaging; Male; Motor Cortex; Piracetam; Supratentorial Neoplasms; Temporal Lobe; Wakefulness; White Matter

This noninterventional, observational, postauthorization safety study (SP0942, NCT00771927) evaluated the incidence of predefined cardiovascular- (CV) and psychiatric-related treatment-emergent adverse events (TEAEs), in patients with epilepsy and uncontrolled partial-onset seizures, when initiating adjunctive therapy with lacosamide or another approved antiepileptic drug (AED) according to standard medical practice. Active recording of predefined TEAEs of interest took place at three-monthly recommended visits for up to 12months. Of 1004 patients who received at least one dose of adjunctive AEDs, 511 initially added lacosamide therapy, 493 added another AED, 69 were ≥65years of age, and 72 took concomitant antiarrhythmic drugs. Patients in the lacosamide cohort had a higher median frequency of partial-onset seizures (6.0 versus 3.5 per 28days) despite taking more concomitant AEDs (84.9% versus 66.9% took ≥2) at baseline. Patients who added lacosamide took a modal dose of 200mg/day over the treatment period (n=501), and 50.1% (256/511) completed 12months of treatment. Fifty-one point nine percent (256/493) of patients who added another AED completed the study, with the most commonly added AED being levetiracetam (28.4%). Four patients (0.8%) in each cohort, all <65years of age, reported predefined CV-related TEAEs. None were considered serious or led to discontinuation. One event each of sinus bradycardia (lacosamide), atrioventricular block first degree (lacosamide), and syncope (other AED) were judged to be treatment-related. Another patient in the other AED cohort reported bradycardia while taking concomitant antiarrhythmic drugs. Predefined psychiatric-related TEAEs were reported by 21 patients (4.1%) in the lacosamide cohort and 27 patients (5.5%) in the other AED cohort. Depression was the most common to be treatment-related (7/11 and 12/18 of patients reporting treatment-related psychiatric TEAEs, respectively). Serious psychiatric-related TEAEs were reported by four patients who added lacosamide (two cases of depression, two of suicide attempt) and one who added another AED (depression). Seven deaths occurred, all of which were considered unrelated/unlikely related to study medication. This thorough evaluation revealed a low incidence of predefined CV- and psychiatric-related TEAEs in patients taking adjunctive AED therapy according to standard medical practice. No specific safety concerns related to adjunctive lacosamide therapy were noted.

Topics: Acetamides; Adult; Aged; Anticonvulsants; Combined Modality Therapy; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Lacosamide; Levetiracetam; Longitudinal Studies; Male; Middle Aged; Piracetam; Seizures; Treatment Outcome

Prior studies have shown that switching patients from inducing antiepileptic drugs (AEDs) to lamotrigine, levetiracetam, or topiramate reduces serum lipids and C-reactive protein (CRP). These studies were all of short duration, and some drugs, such as zonisamide, have not been investigated.. We recruited 41 patients taking phenytoin or carbamazepine who were being switched to zonisamide, lamotrigine, or levetiracetam. We measured serum lipids and CRP before the switch, >6weeks after, and >6months after. An untreated control group (n=14) underwent similar measurement. We combined these data with those of our previous investigation (n=34 patients and 16 controls) of a very similar design.. There were no differences in outcome measures between the two inducing AEDs nor among the three noninducing AEDs. Total cholesterol (TC), atherogenic lipids, and CRP were higher under inducer treatment than in controls. All measures were elevated under inducer treatment relative to noninducer treatment, including TC (24mg/dL higher, 95% CI: 17.5-29.9, p<0.001) and CRP (72% higher, 95% CI: 41%-111%, p<0.001). The difference between drug treatments was clinically meaningful for atherogenic lipids (16%, 95% CI: 11%-20%, p<0.001) but small for high-density lipoprotein cholesterol (5%, 95% CI: 1%-9%, p<0.05). All measures were stable between 6weeks and 6months after drug switch.. We demonstrate that switching from inducing to noninducing AEDs produces an enduring reduction in serum lipids and CRP. These results provide further evidence that inducing AEDs may be associated with elevated vascular disease risk. These are the first vascular risk marker data in patients taking zonisamide, which shows a profile similar to that of other noninducing AEDs.

Topics: Anticonvulsants; Biomarkers; C-Reactive Protein; Carbamazepine; Drug Substitution; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Lipids; Male; Middle Aged; Phenytoin; Piracetam; Time Factors; Topiramate; Treatment Outcome; Triazines; Zonisamide

In this study we analyzed the effects of transcranial magnetic stimulation (TMS) on sleep and on the self-perceived quality of life in epileptic patients.. A total of 24 male patients diagnosed with focal epilepsy were included in the study. Pharmacological treatment with levetiracetam was standardized at 2 g daily. Before TMS onset, all-night polysomnographic recording (PSG) was performed, and the Quality of Life in Epilepsy Inventory (QOLIE-31) was administered. Thereafter, patients underwent low-frequency repetitive TMS (1000 pulses/1 Hz) daily for 10 days. After the end of the treatment, a second polysomnographic study was performed, and the QOLIE-31 questionnaire was administered again.. TMS induced a significant increase in sleep efficiency and in total sleep time, along with a decrease in sleep latency and the number of awakenings. In addition, the number of interictal discharges during sleep decreased significantly. Concerning the QOLIE-31 scale values, the patients showed great improvement in the self-perceived quality of life.. The present results indicate that TMS may mediate therapeutic effects in the treatment of patients with focal epilepsy, and that TMS treatment is accompanied by improvement of sleep patterns as well as improvement in self-perceived quality of life. However, a study that includes a control group undergoing sham stimulation is needed to confirm these findings.

Topics: Adult; Anticonvulsants; Electroencephalography; Epilepsies, Partial; Humans; Levetiracetam; Male; Piracetam; Polysomnography; Quality of Life; Sleep Stages; Surveys and Questionnaires; Transcranial Magnetic Stimulation

To examine the implementation of the clinical practice guideline "first epileptic seizure and epilepsy in adulthood" published in 2008 to patients with newly diagnosed epilepsy between 2008 and 2014.. This retrospective, population-based analysis was performed on patient data of 4.1 million insurants from the German statutory health insurance. Prevalent and incident cases in adults were identified based on ICD-10 codes, using a hierarchical diagnosis selection algorithm. The first anticonvulsive agent in a newly diagnosed epilepsy patient was validated against the clinical practice guideline.. We determined an annual crude prevalence rate in adults between 0.946% and 1.090% and incidence rates of at least 156 per 100,000. A significant increase in guideline compliant monotherapy was found in patients with a focal epilepsy syndrome, while, among patients with idiopathic generalised epilepsies, the share of guideline noncompliant monotherapy increased. Both changes are likely due to the overall increase in prescription of levetiracetam from 19.6% in 2008 to 58.9% in 2014 in all newly treated patients. Overall, the proportion of enzyme-inducing anticonvulsants fell significantly from 20.7% in 2008 to 4.3% in 2014 (p<0.001). The likelihood to receive non-enzyme-inducing antiepileptic drugs was 5.82 (95% CI 4.62-7.33) higher in 2014 than in 2008.. Initial monotherapy for focal epilepsy is in line with current clinical practice guidelines and mainly implemented by prescription of levetiracetam. Further evaluations should address the question of whether patients treated in line with the guidelines have a favorable outcome, compared to patients not treated in line with current guidelines.

Topics: Anticonvulsants; Epilepsies, Partial; Female; Germany; Guidelines as Topic; Humans; Levetiracetam; Male; National Health Programs; Piracetam; Retrospective Studies

Traumatic brain injury (TBI) is a major cause of pediatric morbidity and mortality. Secondary injury that occurs as a result of a direct impact plays a crucial role in patient prognosis. The guidelines for the management of severe TBI target treatment of secondary injury. Posttraumatic seizure, one of the secondary injury sequelae, contributes to further damage to the injured brain. Continuous electroencephalography (cEEG) helps detect both clinical and subclinical seizure, which aids early detection and prompt treatment.. The aim of this study was to examine the relationship between cEEG findings in pediatric traumatic brain injury and neurocognitive/functional outcomes.. This study focuses on a subgroup of a larger prospective parent study that examined children admitted to a level-1 trauma hospital. The subgroup included sixteen children admitted to the pediatric intensive care unit (PICU) who received cEEG monitoring. Characteristics included demographics, cEEG reports, and antiseizure medication. We also examined outcome scores at the time of discharge and 4-6weeks postdischarge using the Glasgow Outcome Scale - Extended Pediatrics and center-based speech pathology neurocognitive/functional evaluation scores.. Sixteen patients were included in this study. Patients with severe TBI made up the majority of those that received cEEG monitoring. Nonaccidental trauma was the most frequent TBI etiology (75%), and subdural hematoma was the most common lesion diagnosed by CT scan (75%). Fifteen patients received antiseizure medication, and levetiracetam was the medication of choice. Four patients (25%) developed seizures during PICU admission, and 3 patients had subclinical seizures that were detected by cEEG. One of these patients also had both a clinical and subclinical seizure. Nonaccidental trauma was an etiology of TBI in all patients with seizures. Characteristics of a nonreactive pattern, severe/burst suppression, and lack of sleep architecture, on cEEG, were associated with poor neurocognitive/functional outcome.. Continuous electroencephalography demonstrated a pattern that associated seizures and poor outcomes in patients with moderate to severe traumatic brain injury, particularly in a subgroup of patients with nonaccidental trauma. Best practice should include institution-based TBI cEEG protocols, which may detect seizure activity early and promote outcomes. Future studies should include examination of individual cEEG characteristics to help improve outcomes in pediatric TBI.

Topics: Adolescent; Brain; Brain Injuries, Traumatic; Child; Child, Preschool; Electroencephalography; Epilepsies, Partial; Female; Glasgow Outcome Scale; Humans; Infant; Infant, Newborn; Levetiracetam; Longitudinal Studies; Male; Piracetam; Prognosis; Prospective Studies; Seizures; Sleep

Since the 1970s, racetams have been in use as cognitive enhancers. Levetiracetam was discovered to have antiseizure activity in animal models and was then found to bind to SV2A in synaptic and endocrine vesicles. Brivaracetam, an analog of levetiracetam, was identified in a medicinal chemistry campaign with the objective of discovering analogs with higher affinity at racetam-binding sites and greater antiseizure potency.

Topics: Animals; Anticonvulsants; Binding Sites; Epilepsies, Partial; Epilepsy, Generalized; Humans; Levetiracetam; Ligands; Membrane Glycoproteins; Nerve Tissue Proteins; Piracetam; Protein Binding; Protein Conformation; Pyrrolidinones

Topics: Adult; Anticonvulsants; Carbamazepine; Celiac Disease; Diagnosis, Differential; Drug Substitution; Duodenal Diseases; Epilepsies, Partial; Humans; Levetiracetam; Male; Oxcarbazepine; Piracetam

This work aimed to evaluate the metabolic and atherogenic effects of long-term antiepileptic drugs in a group of Egyptian epileptic patients. Sixty-nine epileptic patients on antiepileptic drug monotherapy for at least 2 years and 34 control subjects were recruited in this study. Patients were divided into 5 subgroups according to antiepileptic drugs used (valproate, carbamazepine, lamotrigine, topiramate, and levetiracetam). Fasting lipid profile (total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), lipoprotein(a), homocysteine, free thyroxine, thyroid-stimulating hormone, and common carotid artery intima-media thickness were measured for all subjects. Significant higher mean values of low-density lipoprotein cholesterol, low-density lipoprotein / high-density lipoprotein ratio, lipoprotein(a), homocysteine, significantly lower mean value of high-density lipoprotein cholesterol, and significantly larger diameter of common carotid artery intima-media thickness were observed in each drug-treated group versus control group. Our study supports that long-term monotherapy treatment with valproate, carbamazepine, lamotrigine, and topiramate had altered markers of vascular risk that might enhance atherosclerosis, whereas levetiracetam exerted minimal effect.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Carotid Arteries; Carotid Intima-Media Thickness; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Epilepsies, Partial; Epilepsy, Generalized; Female; Fructose; Humans; Intracranial Arteriosclerosis; Lamotrigine; Levetiracetam; Male; Piracetam; Topiramate; Triazines; Valproic Acid

This prospective, nationwide, specified drug use-results survey investigated the effects of levetiracetam (LEV) in elderly individuals with partial-onset seizures of advanced-age onset in a practical setting. Participants comprised LEV-naïve patients with onset of focal epilepsy at ≥50 years old and management by at least one antiepileptic drug. Efficacy measures were the physician-rated global improvement scale (GIS), and proportions of patients showing 50% and 100% seizure reduction by comparing seizure frequency during the 4-week pre-treatment period and the last 4 weeks of the 25-week treatment period. Adverse drug reactions (ADRs) and retention rate were also evaluated. Data for safety, GIS evaluation, and seizure frequency analyses were available from 105, 78, and 76, respectively, of 116 enrolled patients, 83 (71.55%) of whom were enrolled by neurosurgeons. Improvement rate (improved or markedly improved) as determined by GIS was 98.72% (77/78). Seventy-four (97.37%) and 64 patients (84.21%) showed 50% and 100% seizure reduction, respectively. Incidence of ADRs was 12.38%, including one serious ADR (mania). LEV retention rate remained high at the end of the 25-week treatment period (96.00%). LEV appears efficacious and well-tolerated in elderly patients with focal epilepsy. Including LEV in the treatment regimen may allow elderly patients to achieve freedom from seizures.

Topics: Aged; Anticonvulsants; Data Collection; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies

It is important to choose an appropriate antiepileptic drug (AED) to manage partial epilepsy. Traditional AEDs, such as carbamazepine (CBZ) and valproate (VPA), have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy.. This is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM), oxcarbazepine (OXC), lamotrigine (LTG), or levetiracetam (LEV), were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated.. A total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64-44.07). CBZ exhibited the highest 12-month remission rate (85.55%), which was significantly higher than those of TPM (69.38%, P = 0.006), LTG (70.79%, P = 0.001), LEV (72.54%, P = 0.005), and VPA (73.33%, P = 0.002). CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%), rashes (7.76%), abnormal hepatic function (6.24%), and drowsiness (6.24%).. This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first seizure, 12-month remission rate, and retention rate.

Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; China; Epilepsies, Partial; Female; Fructose; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Piracetam; Retrospective Studies; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Young Adult

  Levetiracetam [E Keppra(®)] is a second generation antiepileptic drug for different types of epilepsy in adults and children ≥1 month. The objective is to develop a population pharmacokinetic model to describe the pharmacokinetics of levetiracetam in Japanese children and adults as well as North American children, the purpose being to explore potential dosing recommendations in Japanese children. Levetiracetam plasma concentration-time data were obtained from Japanese adult and pediatric clinical studies. The data were analyzed through non-linear mixed effects modelling. The model was used to perform simulations and compare the exposure in Japanese children and adults. It was subsequently extended to North American children through an external validation. A one-compartment model with first-order absorption and first-order elimination adequately described the data. The exposure parameters determined based on the simulations in children were well within the adult range. The external validation against historical data from North American children was successful. The integrated population pharmacokinetic model provided a good description of the data, confirming the similarity of levetiracetam pharmacokinetics in these various populations. In Japanese children, a target dose of 10 to 30 mg/kg twice daily ensures the same exposure as the recommended dose in Japanese adults of 500 to 1,500 mg twice daily.

Topics: Administration, Oral; Adolescent; Adult; Age Factors; Anticonvulsants; Asian People; Black or African American; Child; Child, Preschool; Epilepsies, Partial; Female; Hispanic or Latino; Humans; Japan; Levetiracetam; Male; Middle Aged; Models, Biological; North America; Piracetam; White People; Young Adult

Topics: Acetamides; Anticonvulsants; Electroencephalography; Epilepsies, Partial; Humans; Lacosamide; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Neurologic Examination; Piracetam; Seizures; Toothbrushing

Mu rhythm can be suppressed by movements, the so called event-related desynchronization (ERD). Levetiracetam (LEV) is a newer type of antiepileptic drug. A previous study reported that LEV might enhance mu rhythm and caused mu status in one subject. The main purpose of this study was to investigate the effects of LEV on EEG frequency contents and ERD. Seventeen patients with epileptic foci outside the Rolandic area were recruited. The following studies were performed before and after chronically taking LEV. An electroencephalogram (EEG) with 10 minutes of resting state and 5 minutes covering 10 right thumb movements were recorded. Reaction time was evaluated with a simple visual reaction time test. EEG data were analyzed by S-transformation and relative band powers were calculated. The results showed that the relative powers of theta, alpha and beta band in frontal (F3 and F4) and occipital (O1 and O2) leads and mu band in the centro-parietal (C3, C4, P3 and P4) leads were not changed by chronically taking LEV. No mu status was observed in any subject. However, the mean group ERD was enhanced at C3, Cz and P4 leads. Reaction time was similar before and after taking LEV. In conclusion, chronically taking LEV did not change the frequency contents of EEG and did not cause drowsiness, but enhanced ERD. The results suggest that chronically taking medication, such as LEV, is a plausible method to broaden the applicability of ERD-based brain-computer interfaces.

Topics: Adult; Anticonvulsants; Brain Waves; Electroencephalography; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Piracetam; Reaction Time; Treatment Outcome; Visual Perception; Young Adult

The aim of this observational study was to obtain information regarding efficacy and safety of add-on levetiracetam (LEV; n=32) in Japanese patients with refractory partial seizures in an everyday clinical setting, relative to control AEDs (n=30). This is the first study of LEV add-on therapy conducted in Japan since approval was made. The medical charts of patients were retrospectively reviewed. The efficacy variables were seizure freedom and ≥50% reduction in seizure frequency. A significantly higher response to LEV was demonstrated in patients with all seizure types at baseline, relative to control AEDs. In patients with a duration of epilepsy of at least 10 years, significant effects in response to LEV were demonstrated with regards to efficacy variables, relative to control AEDs, thus providing meaningful results. Only two patients (6.2%) discontinued LEV treatment due to worsening of seizures, but no discontinuation was reported due to adverse events. LEV as add-on therapy to other AEDs is a promising useful treatment option for patients with refractory partial seizures without notable effects on safety, indicating that this treatment regimen might be recommended for such patients.

Topics: Adult; Anticonvulsants; Benzodiazepines; Clobazam; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Complex Partial; Female; Fructose; Humans; Japan; Lamotrigine; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Young Adult

Topics: Anticonvulsants; Carbamazepine; Epilepsies, Partial; Epilepsy, Generalized; Female; Humans; Levetiracetam; Male; Piracetam; Valproic Acid

Levetiracetam has been authorized for use in Israel as an add-on therapy for intractable epilepsy since May 2006. The aim of the present study was to document its effectiveness for this indication in children, adolescents, and young adults. The medical files of 78 patients aged 0.5-39 years (mean, 14.2 years) treated at our center for intractable epilepsy were reviewed. All received levetiracetam as add-on therapy following a failure to respond to at least 3 anti-epileptic drugs. Fifty-two patients (67%) had partial epilepsy and the remainder had primary generalized epilepsy. The epilepsy was symptomatic in 57%, cryptogenic in 27%, and idiopathic in 15%. Average age at first seizure was 4.1 years. In 45% of patients, the number of seizures was reduced by half with levetiracetam treatment; 11.5% of the cohort achieved complete remission. There was a statistically significant correlation between clinical seizure control and improvement in the electroencephalography findings (p = 0.0012). The drug was well tolerated, with a retention rate of 69% after one year. The most common adverse effects were irritability and impulsiveness, in 26.9% of patients. Severe behavioral side effects (psychosis, confusion) were experienced by 6.4%. In conclusion, levetiracetam is an effective and tolerable add-on agent for use in most epileptic children, adolescents, and young adults who fail to respond to at least 3 antiepileptic drugs and should be the treatment of choice in this setting. Despite the relatively high rate of behavioral side effects in this study, the retention rate at one year was high.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Electroencephalography; Epilepsies, Partial; Epilepsy, Generalized; Female; Humans; Infant; Levetiracetam; Male; Pilot Projects; Piracetam; Retrospective Studies; Treatment Outcome; Young Adult

Mutations of the leucine-rich glioma-inactivated 1 (LGI1) gene cause an autosomal dominant partial epilepsy with auditory features also known as autosomal-dominant lateral temporal lobe epilepsy. LGI1 is also the main antigen present in sera and cerebrospinal fluids of patients with limbic encephalitis and seizures, highlighting its importance in a spectrum of epileptic disorders. LGI1 encodes a neuronal secreted protein, whose brain function is still poorly understood. Here, we generated, by ENU (N-ethyl-N-nitrosourea) mutagenesis, Lgi1-mutant rats carrying a missense mutation (L385R). We found that the L385R mutation prevents the secretion of Lgi1 protein by COS7 transfected cells. However, the L385R-Lgi1 protein was found at low levels in the brains and cultured neurons of Lgi1-mutant rats, suggesting that mutant protein may be destabilized in vivo. Studies on the behavioral phenotype and intracranial electroencephalographic signals from Lgi1-mutant rats recalled several features of the human genetic disorder. We show that homozygous Lgi1-mutant rats (Lgi1(L385R/L385R)) generated early-onset spontaneous epileptic seizures from P10 and died prematurely. Heterozygous Lgi1-mutant rats (Lgi1(+/L385R)) were more susceptible to sound-induced, generalized tonic-clonic seizures than control rats. Audiogenic seizures were suppressed by antiepileptic drugs such as carbamazepine, phenytoin and levetiracetam, which are commonly used to treat partial seizures, but not by the prototypic absence seizure drug, ethosuximide. Our findings provide the first rat model with a missense mutation in Lgi1 gene, an original model complementary to knockout mice. This study revealed that LGI1 disease-causing missense mutations might cause a depletion of the protein in neurons, and not only a failure of Lgi1 secretion.

Topics: Amino Acid Sequence; Animals; Anticonvulsants; Brain; Carbamazepine; Cells, Cultured; Chlorocebus aethiops; COS Cells; Disease Models, Animal; Electroencephalography; Epilepsies, Partial; Epilepsy; Epilepsy, Reflex; Ethosuximide; Heterozygote; Homozygote; Humans; Intercellular Signaling Peptides and Proteins; Levetiracetam; Molecular Sequence Data; Mutation, Missense; Neurons; Phenytoin; Piracetam; Proteins; Rats, Mutant Strains

This study investigated the effect of the novel antiepileptic drug levetiracetam (LEV) on sleep in eleven patients with partial epilepsy. At baseline and one week after therapy with LEV (1000 mg/day), patients underwent polysomnography (PSG) and the Multiple Sleep Latency Test (MSLT). Patients also rated their own degree of sleep disturbance and daytime sleepiness with the Athens Insomnia Scale (AIS) and the Epworth Sleepiness Scale (ESS). A group of 10 age- and gender-matched control participants were also included in the study. Patients had decreased total sleep time and increased daytime sleepiness compared to baseline, as evaluated by AIS subscales. Furthermore, LEV therapy significantly decreased the rapid eye movement sleep time and percentage as measured by PSG. Patients reported a significant increase in ESS score but did not exhibit changes in MSLT performance after LEV treatment. The study demonstrated that short-course LEV treatment can affect subjective sleep time and objective sleep architecture. Furthermore, LEV treatment affected subjective daytime sleepiness but did not influence objective mean daytime sleep latencies in patients with partial epilepsy.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Disorders of Excessive Somnolence; Electroencephalography; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Polysomnography; Severity of Illness Index; Sleep Initiation and Maintenance Disorders; Surveys and Questionnaires; Young Adult

Topics: Anticonvulsants; Bacteriuria; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Electroencephalography; Epilepsies, Partial; Facial Paralysis; Hemiplegia; Humans; Hydrocephalus; Levetiracetam; Male; Meningitis, Listeria; Middle Aged; Piracetam; Postoperative Complications; Status Epilepticus; Stroke; Ventriculoperitoneal Shunt

Topics: Aged; Anticonvulsants; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Stroke; Treatment Outcome

In this retrospective study, we evaluated the safety and efficacy of levetiracetam (LEV) as an antiepileptic drug by using data in our hospital database from October 2010, when LEV became available in Japan, through August 2011. Data from patients aged 16 years or more (n=132) with localization-related epilepsy (n=112) and generalized epilepsy (n=19) were reviewed. Among patients with localization-related epilepsy, 53.6% showed a greater than 50% reduction in seizure frequency compared with the pretreatment baseline, and 28.6% of them became seizure free during the treatment period. Adverse events were reported in 27.3% of patients and caused discontinuation of LEV in 10.6%. The most frequent adverse events were somnolence (14.4%), irritability or aggressiveness (6.1%), and depression (4.5%). However, most of the adverse events were of mild to moderate severity. More than 80% of patients continued LEV treatment. The frequency of adverse events and discontinuation rate after LEV treatment were not associated with the starting dose (1,000 mg/day or less). LEV was well tolerated and efficacious as an adjunctive therapy for localization-related epilepsy.

Topics: Adolescent; Adult; Anticonvulsants; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Japan; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Treatment Outcome; Young Adult

Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy, Tonic-Clonic; Humans; Levetiracetam; Male; Piracetam; Psychoses, Substance-Induced; Young Adult

The syndrome of malignant migrating partial seizures in infancy is a devastating, age-specific, epileptic encephalopathy, which still presents an aetiological, pathophysiological and therapeutic problem. In this study, we present two patients who were diagnosed with the disease, based on electroclinical symptoms. The patients were treated with a combination of sodium bromide, stiripentol and levetiracetam. The first patient unequivocally responded, following a course of ineffective conventional drugs, and the second, who was diagnosed and treated immediately, showed a more significant therapeutic response. Antiepileptic drugs, previously reported to be beneficial in case reports, when given concomitantly, may substantially reduce the number and severity of seizures, without influence on psychomotor development. [Published with video sequences].

Topics: Anticonvulsants; Bromides; Dioxolanes; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Female; Humans; Infant; Infant, Newborn; Levetiracetam; Piracetam; Sodium Compounds; Treatment Outcome

Some patients with epilepsy require treatment with >1 adjunctive antiepileptic drug (AED) to achieve adequate seizure remission. The purpose of this analysis was to evaluate the efficacy and safety of adding adjunctive pregabalin to an AED regimen that included levetiracetam in patients with refractory partial-onset epilepsy.. Data from the pregabalin and placebo arms of two placebo-controlled, double-blind, randomized studies of pregabalin in patients who received adjunctive treatment with levetiracetam in addition to ≥1 other AEDs were pooled for this post hoc analysis. Patients (aged ≥18 years) had ≥4 partial-onset seizures and no 28-day period free of seizures during baseline. Efficacy outcomes included Response Ratio (RRatio), change from baseline in seizure frequency, proportion of patients with ≥50% reduction in seizure frequency, and 28-day seizure-freedom rate. Safety was evaluated using adverse events (AEs).. In total, 138 patients were included in the analysis (placebo, n = 47; pregabalin, n = 91). Pregabalin was significantly better than placebo for difference in least squares mean of the RRatio (-16.4; 95% confidence interval [CI]: -28.5, -4.5; p = 0.0085), median of the difference in percentage change from baseline in seizure frequency (-22.3; 95% CI: -40.1, -7.2; p = 0.0095), and proportion of 50% responders (36.3 vs. 17.0; odds ratio, 3.2; 95% CI: 1.3, 8.3; p = 0.018), but not 28-day seizure-freedom rate (7 [7.7%] vs. 2 [4.3%]; p = 0.353). The most common AEs when adding pregabalin were dizziness/vertigo, fatigue, somnolence, blurred vision, and increased weight that were not proportional to the number of concomitant AEDs.. In this population of patients with refractory partial-onset seizures, adding pregabalin to an AED regimen with levetiracetam produced further seizure reductions. The safety profile of pregabalin in patients receiving levetiracetam and ≥1 other AEDs did not appear to be compromised by the number of concomitant AEDs.

Topics: Adult; Anticonvulsants; Double-Blind Method; Drug Resistance; Drug Therapy, Combination; Epilepsies, Partial; Female; gamma-Aminobutyric Acid; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Placebos; Pregabalin; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Failure; Treatment Outcome

Topics: Anticonvulsants; Child, Preschool; Epilepsies, Partial; Female; Humans; Levetiracetam; Ocular Motility Disorders; Piracetam; Valproic Acid

We studied 1036 children with epileptic seizures, aged from 1 to 18 years, during 2004-2008. One hundred and six patients were diagnosed with idiopathic focal epilepsy (IFE). The following forms of IFE were singled out: benign seizures of infancy (familial and non-familial) - Watanabe--Vigevano syndrome - 5,7%, occipital epilepsy of childhood with early manifestation (Panayiotopoulos syndrome) -26,4%, occipital epilepsy of childhood with late manifestation (Gastaut syndrome) - 12,3%, benign epilepsy of childhood with central-temporal spikes (rolandic epilepsy) - 51%, benign focal epilepsy with affective symptoms - 4,7%. The efficacy of the first monotherapy was significantly worse in rolandic epilepsy compared to the other IFE forms. Prescription of valproate or the combination of valproate, ethosuximidum and levetiracetam, in case of resistant course, as a starting therapy was found optimal.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Resistance; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Epilepsy, Rolandic; Ethosuximide; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Valproic Acid

Several recent studies have shown that levetiracetam (LEV) can be beneficial in the treatment of children with typical rolandic epilepsy (RE). Reports about the effectiveness of LEV in the treatment of children with the less benign variants in the spectrum of "benign" idiopathic focal epilepsies are still rare. Little is known about the effect of LEV on interictal epileptiform discharges in these syndromes. We report on LEV therapy in 32 children (mean age: 10.6 years, range: 4-14) with RE or variants like atypical benign idiopathic partial epilepsy of childhood (ABIPEC), Landau-Kleffner syndrome (LKS), and continuous spikes and waves during sleep (CSWS) and in children with benign idiopathic focal epileptiform discharges of childhood (BIFEDC). Cognitive and behavioral problems, not seizures, may be related to the pathological EEG. Patients with a reduction in seizure frequency >50% and/or reduction in BIFEDC >90% 3 months after having started LEV therapy were defined as responders. The average dose of LEV was 39 mg/kg body wt per day; LEV was given in monotherapy to 31.3% of the patients. Overall, 20 of 32 patients (62.5%) did benefit: 12 of 24 patients had a >50% reduction in seizure frequency; 2 of 24 patients (8.3%) were completely seizure free; 18 of 32 patients (56.3%) had a >90% reduction in BIFEDC (including CSWS); 6 of 32 (18.8%) had an EEG completely free of epileptiform discharges; and 17 of 32 (53.1%) showed improvement in cognition and/or language functions and/or behavior. Surprisingly, LEV tended to be more helpful in atypical rolandic epilepsies and other variants.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Cognition Disorders; Electroencephalography; Epilepsies, Partial; Female; Humans; Landau-Kleffner Syndrome; Language Disorders; Language Tests; Levetiracetam; Male; Neuropsychological Tests; Piracetam; Severity of Illness Index

Levetiracetam is an antiepileptic drug (AED) with a favourable tolerability profile with little or no effect on liver function. We describe an epileptic patient who developed a significant increase in gamma glutamyltransferase (gammaGT) while on levetiracetam monotherapy.

Topics: Anticonvulsants; Drug Monitoring; Epilepsies, Partial; Female; gamma-Glutamyltransferase; Humans; Levetiracetam; Liver; Middle Aged; Piracetam; Treatment Outcome

The objective of this study was to determine if levetiracetam (LEV) modulates brain γ-aminobutyric acid (GABA) in patients with epilepsy.. Occipital GABA was assessed by protein magnetic resonance spectroscopy (¹H-MRS) in 16 patients with focal epilepsy at baseline and following the initiation of oral administration of LEV as monotherapy. Responder profiles were calculated as percentage of baseline seizure frequency. Alterations of GABA/Cr (creatine) of baseline measurements compared to GABA/Cr under LEV therapy were analyzed by Student's t-test for paired samples.. After administration of LEV, partial seizure reduction (> 50%) was noticed in 5 of 16 patients (31%; 7 of 16 (44%) patients turned out to be free of seizures. Patients with 50-100% seizure reduction under LEV titration were referred to as LEV responders. Of the 32 GABA spectra, only 22 (approximately 70%) yielded a result that met the criteria for spectral quality; therefore, GABA/Cr data from only seven patients were paired. A significant increase of GABA/Cr during titration with LEV was noted in patients responding to LEV (n = 5; p = 0.007). No differences in baseline GABA/Cr levels were detected between patients with and without previous antiepileptic treatment (p = 0.74).. The increasing GABA/Cr levels under drug titration only in LEV-responding epilepsy patients suggest a more complex and indirect influence of LEV on the GABAergic system.

Topics: Adult; Anticonvulsants; Creatine; Electroencephalography; Electrons; Epilepsies, Partial; Female; gamma-Aminobutyric Acid; Humans; Levetiracetam; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Occipital Lobe; Piracetam; Protons; Radionuclide Imaging; Young Adult

We present a patient with cryptogenic focal epilepsy and another with Dravet syndrome, who experienced seizure aggravation and negative myoclonus, associated with continuous spikes and waves during slow sleep, induced by levetiracetam. For both patients levetiracetam was discontinued, and there was significant improvement of this particular electroclinical picture.

Topics: Anticonvulsants; Child; Drug Therapy, Combination; Electroencephalography; Epilepsies, Myoclonic; Epilepsies, Partial; Epilepsy, Tonic-Clonic; Evoked Potentials; Female; Humans; Levetiracetam; Male; Piracetam; Seizures; Sleep; Syndrome

A 34-year-old woman developed a sustained right homonymous hemianopia and episodic visual hallucinations 8 days after liver transplant surgery. Neuro-ophthalmologic examination and perimetry confirmed a right homonymous hemianopia with macular sparing. The patient's vital signs and laboratory values, including a comprehensive metabolic panel and drug levels, were unremarkable. Brain MRI with and without contrast was also unremarkable. A video electroencephalogram revealed frequent, recurrent, left occipitoparietotemporal simple partial seizures associated with episodes of eyelid fluttering, right gaze preference, visual hallucinations, and a dense right hemianopia that persisted interictally. After treatment of the seizures with levetiracetam, perimetry showed resolution of the right homonymous hemianopia. This case demonstrates many classic features of occipital and parietal seizures. It also suggests that, unlike previously reported cases of enduring visual field deficits after cessation of seizures, early diagnosis and management of visual seizures may prevent permanent visual field deficits.

Topics: Adult; Anticonvulsants; Brain; Electroencephalography; Epilepsies, Partial; Female; Hemianopsia; Humans; Illusions; Levetiracetam; Liver Diseases; Liver Transplantation; Magnetic Resonance Imaging; Piracetam; Visual Field Tests

Rare cases of levetiracetam-induced thrombocytopenia have been reported in the literature. We report a case of glioblastoma multiforme and partial epilepsy treated with levetiracetam with subsequent development of thrombocytopenia. After ruling out all other possible causes of a decreased platelet count, we conclude that levetiracetam was the cause of this adverse event.

Topics: Anticonvulsants; Brain Neoplasms; Epilepsies, Partial; Female; Frontal Lobe; Glioblastoma; Humans; Levetiracetam; Middle Aged; Piracetam; Platelet Count; Thrombocytopenia; Treatment Outcome

In a recent double-blind, placebo-controlled study, adjunctive levetiracetam (LEV) was reported to be effective and well tolerated during 5-day treatment in patients aged 1 month to <4 years with partial-onset seizures. A study was planned to fulfill the regulatory requirement to evaluate the long-term safety of LEV as adjunctive therapy for partial-onset seizures in pediatric patients.. This study evaluated the long-term effectiveness and tolerability of adjunctive LEV in infants and young children with partial-onset seizures.. This was a prospective, open-label, outpatient, multicenter study (N01148; ClinicalTrials.gov identifier NCT00152516) conducted as an extension of a previously published study (N01009; NCT00175890). Patients were enrolled from 3 sources, as follows: (1) patients who had completed study N01009; (2) patients who had failed screening for entry into study N01009 but fulfilled the eligibility criteria for entry into this study; and (3) patients who were directly enrolled. The study consisted of a 2- to 4-week retrospective baseline period (and a 3- to 10-day prospective baseline period for directly enrolled patients), a 2- to 8-week uptitration/conversion period, and a maintenance period. Eligible patients were required to have epilepsy with partial-onset seizures, treated with a stable regimen of 1 or 2 antiepileptic drugs. Patients received adjunctive LEV, 20 to 80 mg/kg/d, for up to 48 weeks (total study duration). The primary variable for effectiveness was the percentage reduction from baseline in the weekly frequency of partial-onset seizures, as recorded in patients' diaries. Data for effectiveness were also analyzed by age strata (1 month to <1 year, 1 to <2 years, and 2 to <4 years). Neuropsychological assessment was conducted with the Bayley Scales of Infant Development, Second Edition (BSID-II). All analyses were performed on observed data, and the last-observation-carried-forward approach was not used. The intent-to-treat (ITT) population was defined as all patients who took at least one dose of LEV during the study. Treatment-emergent adverse events (TEAEs) were assessed by observation, spontaneous reporting, standard questions, review of diary cards, and neuropsychologists' clinical reports. Additional measures included physical and neurologic examinations, vital signs, ECGs, routine blood chemistry, and routine hematology assessments.. The study included 152 patients in the ITT population. In total, 51.3% (78/152) of the patients were male, and mean (SD) age was 23.5 (12.4) months. The mean LEV maintenance dose was 56.1 (16.2) mg/kg/d, and the median (Q1-Q3) treatment duration was 287.8 (209.0-295.5) days. Ninety-seven patients (63.8%) completed the study. The BSID-II subpopulation included 51 patients. During maintenance, the overall median (Q1-Q3) percentage reduction from baseline in the weekly frequency of partial-onset seizures was 56.0% (-10.9% to 92.8%), which was sustained over time and appeared comparable across the age strata (1 month to <1 year, n = 25, 50.9%; 1 to <2 years, n = 48, 58.0%; and 2 to <4 years, n = 59, 55.0%). The overall responder rate (ie, ≥50% reduction from baseline in weekly partial-onset seizures) was 53.8% (71/132), was maintained over time, and was consistent across the age strata (1 month to <1 year, 52.0%; 1 to <2 years, 56.3%; and 2 to <4 years, 52.5%). Mean BSID-II raw scores for psychomotor development and behavioral functioning remained static, whereas mental development appeared to improve over time, although this was not tested statistically. At least one TEAE was reported in 143 patients (94.1%). The most frequently reported TEAEs were pyrexia (60/152; 39.5%), upper respiratory tract infection (42/152; 27.6%), and vomiting (28/152; 18.4%). The most common TEAEs affecting the central nervous system were convulsion (25/152; 16.4%), irritability (19/152; 12.5%), and somnolence (16/152; 10.5%). Most TEAEs (77.0%) were mild or moderate in intensity.. Adjunctive LEV treatment for up to 48 weeks was associated with effective and sustained seizure control and had an acceptable tolerability profile in this small, selected population of infants and young children aged 1 month to <4 years with partial-onset seizures.

Topics: Anticonvulsants; Child, Preschool; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Infant; Levetiracetam; Male; Piracetam; Prospective Studies; Retrospective Studies; Time Factors; Treatment Outcome

Depression in children and adolescents with epilepsy is common. Depression worsen quality of life in epilepsy patients. Neurobiological, social, and iatrogenic factors may play a role in depressive disorder development. We report a patient with partial epilepsy secondary to neonatal stroke, who developed depressive disorder as a result of levetiracetam (LEV) treatment. Our report illustrates the possible implication of iatrogenic factors in depression among epilepsy patients. However, recent data suggest that LEV may be effective in case of affective disorders. We discuss the factors linking epilepsy with depression. Because of its high incidence and its multiple physiopathologic factors, psychiatric comorbidity should be always assessed in pediatric epileptic patients.

Topics: Anticonvulsants; Child, Preschool; Depression; Epilepsies, Partial; Humans; Levetiracetam; Male; Piracetam

Since 1994, 10 new antiepileptics drugs have been developed and many others will be available in a near future. Effectiveness of theses new antiepileptic drugs is similar to the old ones but they have a better side-effect profile. This article updates their clinical use, taking into account the recent studies. These new antiepileptics drugs improve quality of life of the patients, but their use is not entirely safe, including the possible aggravation of certain forms of epilepsy. A better physiopathological knowledge of the epilepsy will help in the future to choose the most adequate drug(s) for each patient.

Topics: Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Epilepsies, Partial; Epilepsy; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Oxcarbazepine; Piracetam; Pregabalin; Triazines; Zonisamide

Panayiotopoulos syndrome (PS) represents the second commonest benign partial epilepsy of childhood. This study evaluated the effects of levetiracetam (LEV) in three children with this syndrome. All three children (aged 8, 12 and 10 years) had episodic autonomic symptoms for 4, 6 and 2 years, respectively. Symptoms duration varied between a few minutes and 5-7 days, reflecting an autonomic status epilepticus. Children previously controlled on valproate (VPA) but with recurring seizures, were given LEV (1000-2000 mg/day) initially as add-on therapy, and after as monotherapy. All three children received LEV monotherapy and remained seizure-free after 3, 3 and 2 years of treatment, respectively. One child, after 2 years seizure free, stopped LEV treatment. Now, he is asymptomatic for 2 years. LEV has shown efficacy on autonomic seizure control in three patients with PS where VPA was ineffective.

Topics: Anticonvulsants; Child; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Female; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Piracetam; Status Epilepticus; Syndrome; Valproic Acid

Since its introduction in 2006, 43 patients with various forms of status epilepticus (SE) have been treated with the intravenous formulation of levetiracetam (LEV) in our clinic. After ineffective treatment with benzodiazepines, intravenous LEV was administered as a short infusion (nonconvulsive and subtle SE) at a dose of 1000 or 2000 mg. In cases of convulsive SE, a fractionated injection of 1000 or 2000 mg was used. When the results for both are combined, SE could be terminated in 19 of 43 patients. Intravenous LEV was more effective in simple focal SE (3/5), complex focal SE (11/18) and myoclonic status (2/2) than in nonconvulsive (2/8) and subtle (1/2) SE. In no case was (secondarily) generalized convulsive status epilepticus (0/8) terminated. Intravenous LEV was also well-tolerated when injected in fractionated form. No severe adverse reactions were observed. As a result of this investigation, intravenous LEV in moderate doses may represent an efficacious and well-tolerated alternative for the treatment of focal (simple and complex focal) and myoclonic SE. Further investigations are needed to confirm this assumption as the patient numbers are quite low.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Cerebrovascular Disorders; Epilepsies, Myoclonic; Epilepsies, Partial; Female; Germany; Humans; Injections, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Status Epilepticus

We report on a case of epilepsia partialis continua with rapid response to intravenous bolus administration of levetiracetam. A 60-year-old woman presented with continuous jerking of the right foot and hallux persisting for more than two days. She had a 9-year history of epilepsy due to a left temporoparietal oligodendroglioma with occasional focal seizures clinically presenting as speech arrest, which was treated with levetiracetam and oxcarbazepine administered orally. After hospital admission, the twitching of the foot and toe was refractory to add-on treatment with lorazepam and diazepam but stopped within 15 min after intravenous bolus administration of 2000 mg levetiracetam. This observation suggests that intravenous bolus administration of levetiracetam may be an effective therapeutic option in epilepsia partialis continua.

Topics: Anticonvulsants; Brain Neoplasms; Epilepsies, Partial; Female; Humans; Injections, Intravenous; Levetiracetam; Middle Aged; Oligodendroglioma; Piracetam; Speech Disorders

Compared with traditional antiepileptic drugs, levetiracetam has a unique mechanism of action and unique properties, including predominant renal excretion and lack of drug-drug interactions. In the elderly, depression associated with levetiracetam has not been reported.. A 73-year-old black man (height, 172.7 cm; weight, 92.7 kg; body mass index [BMI], 31 kg/m(2)) with stage 4 kidney disease was taking levetiracetam 500 mg BID for partial complex seizures. After 5 months of taking medication, new-onset depression, evidenced by depressed mood, weight loss, fatigue, and appearing withdrawn, was noted in this patient. Levetiracetam was discontinued by order of the patient's primary care physician. At a follow-up appointment 4 weeks later, the depressive symptoms had nearly resolved. The patient's Naranjo Adverse Drug Reaction Probability Scale score was 6, indicating levetiracetam to be a probable cause of depression in this patient. In a second case, a 92-year-old white woman (height, 154.9 cm; weight, 54.5 kg; BMI, 22.7 kg/m(2)) with existing chronic kidney disease and new-onset partial seizure, likely due to a meningioma, was initiated on levetiracetam 500 mg once daily. Depressive symptoms (eg, anhedonia, hypersomnolence, decreased appetite) were noted within 5 weeks. Cessation led to improvement in mood and cognition within 8 days. Based on this patient's Naranjo Adverse Drug Reaction Probability Scale score of 6, levetiracetam was a probable cause of depression in this patient.. Levetiracetam was a probable cause of depression in these 2 elderly patients. Cautious use and additional monitoring may be necessary when prescribing levetiracetam to elderly patients, especially when prescribing to those with a history of renal impairment.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Chronic Disease; Depression; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Kidney Diseases; Levetiracetam; Male; Piracetam

To assess pharmacokinetics, efficacy, and tolerability of oral levetiracetam administered as an adjunct to phenobarbital treatment in cats with poorly controlled suspected idiopathic epilepsy. DESIGN-Open-label, noncomparative clinical trial.. 12 cats suspected to have idiopathic epilepsy that was poorly controlled with phenobarbital or that had unacceptable adverse effects when treated with phenobarbital.. Cats were treated with levetiracetam (20 mg/kg [9.1 mg/lb], PO, q 8 h). After a minimum of 1 week of treatment, serum levetiracetam concentrations were measured before and 2, 4, and 6 hours after drug administration, and maximum and minimum serum concentrations and elimination half-life were calculated. Seizure frequencies before and after initiation of levetiracetam treatment were compared, and adverse effects were recorded.. Median maximum serum levetiracetam concentration was 25.5 microg/mL, median minimum serum levetiracetam concentration was 8.3 microg/mL, and median elimination half-life was 2.9 hours. Median seizure frequency prior to treatment with levetiracetam (2.1 seizures/mo) was significantly higher than median seizure frequency after initiation of levetiracetam treatment (0.42 seizures/mo), and 7 of 10 cats were classified as having responded to levetiracetam treatment (ie, reduction in seizure frequency of >or=50%). Two cats had transient lethargy and inappetence.. Results suggested that levetiracetam is well tolerated in cats and may be useful as an adjunct to phenobarbital treatment in cats with idiopathic epilepsy.

Topics: Animals; Anticonvulsants; Cat Diseases; Cats; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Female; Half-Life; Levetiracetam; Male; Phenobarbital; Piracetam; Treatment Outcome

Objectives - The use of telencephalin as a possible marker for altered cortical function as demonstrated by functional MRI was investigated in a pilot study with 16 patients with localization-related epilepsy and secondarily generalized seizures. Materials and methods - Functional MRI of verbal working memory performance (Sternberg paradigm) and self-regulatory control processes (Stroop paradigm) was used to examine cortical activation in 16 patients with localization-related epilepsy and secondarily generalized seizures. Additionally, blood serum concentrations of soluble telencephalin (marker for neuronal damage) were determined. Results - In three patients (one temporal and two frontal focus), telencephalin was detected. All three patients had lower functional MRI activation in the frontotemporal region (P = 0.04), but not in other regions (P > 0.35) compared with patients without detectable telencephalin. Additionally, an association of levetiracetam and frontotemporal activation was observed. Conclusions - These preliminary data in a heterogeneous group suggest an association between decreased frontotemporal activation on fMRI and both detectable telencephalin serum levels and levetiracetam use. Future longitudinal studies with larger patient groups are required to confirm these observations. It is hypothesized that altered local function of the frontotemporal cortex in localization-related epilepsy might be better predicted by the biochemical marker telencephalin than epilepsy characteristics such as seizure focus.

Topics: Adult; Anticonvulsants; Biomarkers; Brain; Cell Adhesion Molecules; Epilepsies, Partial; Female; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Tissue Proteins; Neuropsychological Tests; Pilot Projects; Piracetam

Non-convulsive status epilepticus (NCSE) is characterized by continuous or recurrent, generalized or focal epileptiform activity on the electroencephalogram and diverse clinical symptoms with alterations of mental state and vigilance. NCSE is not rare but certainly under diagnosed. There is some debate about how aggressive NCSE should be treated, as high dose anticonvulsants maybe partially responsible for the morbidity and mortality of patients with NCSE. We hypothesized that levetiracetam (LEV) as a well tolerated, highly effective new anticonvulsant, may be a safe treatment option. We retrospectively analyzed all (8) patients with NCSE who received levetiracetam from our database, compared with 11 patients with NCSE treated with conventional intravenous status medication as controls. These eight patients showed a marked clinical improvement with final cessation of ictal EEG-activity and clinical symptoms of NCSE after initiation of LEV within 3 days (mean 1.5 days). The response to conventional treatment was similarly effective but there were severe side effects whereas no relevant side effects in the LEV-treated group were noticed. A long-term follow up (6-36 months from discharge) revealed six patients with a persisting reduction in seizure frequency on medication with LEV. One patient changed the anticonvulsive medication because of inefficacy and one died from other causes than epilepsy 2 months after discharge from hospital. We found no significant differences in hospitalisation time, time in intensive care unit and outcome between the LEV group and the control group. This retrospectively acquired data suggests that LEV may be a well tolerated, effective treatment option in NCSE. This highlights the need for a prospective controlled study to further elucidate the utility of LEV in the treatment of NCSE, particularly as an intravenous formulation is now available.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Electroencephalography; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Levetiracetam; Middle Aged; Piracetam; Retrospective Studies; Status Epilepticus

Topics: Anticonvulsants; Anxiety; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Middle Aged; Piracetam; Psychomotor Agitation; Sleep Initiation and Maintenance Disorders; Valproic Acid

To review our experience of the efficacy and tolerability of levetiracetam (LEV) in children younger than 4 years.. We used retrospective chart review to identify 122 children with seizures who were younger than 4 years and followed for >or=6 months. Efficacy was evaluated on the basis of the occurrence and durability of seizure remission. Tolerability was based on parent- and patient-reported side effects.. Seventy (57%) subjects achieved seizure remission, and 52 (43%) did not. In univariate analysis, those achieving seizure remission were more likely to have partial epilepsy, require lower maintenance doses of LEV, and have fewer than two seizures per month at initiation of the medication. Only seizure frequency at initiation of LEV remained significant in multivariate analysis. The median duration of seizure freedom (8.9 month) was not influenced by age, epilepsy type, gender, or pretreatment seizure frequency. The dose of LEV was the only significant predictor of the duration of seizure remission, with longer duration of seizure remission seen in those taking <30 mg/kg/day compared with those taking > 30 mg/kg/day (median, 12.8 months vs. 3 months; p<0.0001). Side effects of LEV occurred in 34% of subjects but required discontinuation in only 16%, most commonly because of behavioral disturbances.. LEV is an effective medication in children younger than 4 years and at doses lower than previously reported. It also well tolerated, suggesting that it represents an important option for the treatment of epilepsy in this age group.

Topics: Age Factors; Anticonvulsants; Child Behavior; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy; Female; Follow-Up Studies; Humans; Infant; Irritable Mood; Levetiracetam; Male; Patient Dropouts; Piracetam; Proportional Hazards Models; Retrospective Studies; Sleep Wake Disorders; Survival Analysis; Treatment Outcome

A retrospective study to evaluate the efficacy of levetiracetam in the treatment of adult pharmacoresistant epilepsy.. Retrospective work up of our treatment-experiences with 55 pharmacoresistant patients treated with levetiracetam (11 of them on monotherapy) for 6-39 months. Three treatment groups were analysed: idiopathic generalised epilepsy (9 patients); partial epilepsy (30 patients); malignant or malignated epileptic syndromes (16 patients).. Seven idiopathic generalised patients (77%) and 5 partial epilepsy patients (16%) became seizure free. One idiopathic generalised epileptic patient, 10 partial epilepsy patients (33%) significantly improved. Six patients (37%) from the group of malignant or malignated epileptic syndromes also significantly improved. Five of the improved idiopathic generalised epilepsy patients and 6 of the improved partial epilepsy patients received levetiracetam monotherapy. Altogether seven patients (12% of the whole population) relapsed after a 4-15 months improved period. Fifteen patients (27%) suffered side effects (mainly somnolence, headache, dizziness and irritability) improving after dose reduction of levetiracetam (generally below 2000 mg pro day).. Levetiracetam is an effective, well tolerable, broad-spectrum drug as adjunctive treatment or monotherapy in adult patients unsuccessfully treated with other antiepileptic drugs.

Topics: Adult; Aged; Anticonvulsants; Drug Resistance; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Recurrence; Retrospective Studies; Syndrome; Treatment Outcome

Although levetiracetam has shown efficacy in children with epilepsy, when used as adjunctive therapy, limited data are available regarding its use as monotherapy. The objective of this study is to evaluate the efficacy and tolerability of levetiracetam monotherapy in a cohort of pediatric patients with epilepsy. A retrospective analysis of pediatric epilepsy patients receiving levetiracetam at a single institution was performed over a 3-year period. Eighty-one patients were identified, 18 of whom received levetiracetam as monotherapy (mean age, 9.6 years). Epilepsy types were partial in 14 and generalized in 4. Conversion to levetiracetam monotherapy occurred in 16 patients due to lack of efficacy or adverse events, and 2 patients were initially started on monotherapy. Dose range of levetiracetam was 14-60 mg/kg, and duration of therapy ranged from 2-24 months. Eleven patients became seizure free on levetiracetam, one had at least 50% reduction in seizures, and six others had no change in seizure frequency. Adverse events included worsening of behavior, irritability, and possible cognitive changes, seen in 4 patients. Levetiracetam was discontinued in seven patients overall. Levetiracetam monotherapy appeared to be effective and well tolerated in this group of children with epilepsy and warrants further investigation in a well-controlled, prospective study.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsies, Partial; Epilepsy, Generalized; Female; Humans; Levetiracetam; Male; Piracetam; Retrospective Studies; Treatment Outcome

We report the case of a five-year-old girl, presenting with difficult-to-treat, symptomatic focal epilepsy, who developed status gelasticus following the introduction of levetiracetam as add-on treatment to oxcarbazepine and diazepam. Gelastic seizures were documented by video-EEG and were responsive to i.v. administration of diazepam. A possible causative role of levetiracetam is suggested. Specific susceptibility to some AEDs is also discussed, as this patient, at the age of four years, had presented an episode of non-convulsive status epilepticus, following introduction of tiagabine, in association with vigabatrin and nitrazepam.[Published with video sequences].

Topics: Anticonvulsants; Brain; Child, Preschool; Electroencephalography; Epilepsies, Partial; Female; Humans; Laughter; Levetiracetam; Magnetic Resonance Imaging; Piracetam; Seizures; Stereotyped Behavior

Levetiracetam (Keppra) is a novel antiepileptic drug approved as adjunctive treatment for adults with partial onset seizures. Although the drug is generally well tolerated, behavioral side effects have been reported in variable frequency. Most behavioral problems are mild in nature (agitation, hostility, anxiety, emotional lability, apathy, depression) and quickly resolve with discontinuation of medication. However, serious psychiatric adverse events may also occur with rare cases of psychosis and suicidal behavior. We report here the case of a 43-year-old woman who developed symptoms compatible with catatonia after being exposed to levetiracetam for the treatment of epilepsy. To our knowledge, it is the first reported case of catatonia induced by levetiracetam. We review the difficulties that may be encountered in the differential diagnosis of medical catatonia.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Catatonia; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Paranoid Disorders; Piracetam; Risperidone

This report describes the first neonatal case of "malignant migrating partial seizures in infancy" with a positive therapeutic response to levetiracetam. This patient is the youngest reported infant with this rare syndrome, and the report provides the first documentation on levetiracetam treatment in a neonatal patient. Treatment with levetiracetam improved both ictal and interictal status. This observation also highlights the need to consider and include malignant migrating partial seizures in the differential diagnosis of early neonatal seizure disorders, even during the first hours of life.

Topics: Anticonvulsants; Electroencephalography; Epilepsies, Partial; Humans; Infant, Newborn; Levetiracetam; Male; Piracetam

Levetiracetam (LEV) is approved for use as add-on therapy in adult patients with partial epilepsy. It is apparent from clinical trials that up to 8% of previously drug-resistant patients may be rendered seizure-free by adding-on levetiracetam. As yet there is no way of predicting these unexpectedly responsive patients. We set out to identify our previously refractory patients who had demonstrated unexpected responsiveness to add-on therapy with levetiracetam, and compared these to patients who had not responded to the drug. We then attempted to characterise any clinical features that differentiated these groups of patients.. We included all patients with a history of present or previous exposure to levetiracetam who had been unresponsive to at least two other prior anti-epileptic drugs (AEDs) and recorded their demographic and clinical data. We divided response into (a) 'seizure-free' (seizure-free for a minimum of 6 months after commencing LEV); (b) 'partial > 50%' (greater than 50% reduction in seizures for a minimum of 6 months after commencing LEV); (c) 'honeymoon' (seizure-free for less than 6 months after commencing LEV and then returned towards baseline frequency); and (d) 'no-response'. For the purpose of analysis we considered the 'seizure-free' and 'partial > 50%' groups as 'responders', and the 'no response' group as 'non responders'.. 344 patients were included in the analysis. Fifty-six patients (16.3%) were rendered seizure-free on levetiracetam. Idiopathic generalised epilepsy and post-traumatic partial epilepsy were more common in the responder than the non-responder group (p = 0.005 and 0.05 respectively). Lamotrigine was used significantly more often in combination with levetiracetam in responders than non-responders (p = 0.003). The mean daily dose of levetiracetam was lower in responders than non-responders.. A higher than expected number of previously drug resistant patients was rendered seizure-free by add-on therapy with levetiracetam. Those who respond best appear to do so at relatively low doses and our data suggest the possibility of a beneficial pharmacodynamic interaction between levetiracetam and lamotrigine. We were unable to identify any clinical factors that clearly predicted which patients would become seizure-free and we hypothesise that response may be determined by genetic or molecular factors. All drug-resistant patients, including those being assessed for surgery, should be considered for a trial of levetiracetam, regardless of their epilepsy classification.

Topics: Anticonvulsants; Drug Resistance; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Generalized; Female; Humans; Levetiracetam; Male; Piracetam; Remission Induction

Cognitive and behavioral impairments are common in patients with epilepsy. Multiple factors may contribute to these difficulties; among them is antiepileptic drug (AED) treatment. We examined the short-term impact of two new add-on AEDs, pregabalin (PGB) and levetiracetam (LEV), on cognition and psychiatric states in 20 adult patients with medically refractory partial epilepsy, before and shortly after add-on titration. According to an open, prospective comparative trial, add-on PGB was titrated to 300 mg and add-on LEV to 1000 mg in 10 patients each. Patients were assessed before (T1) and 2 weeks after (T2) addition of the AED. During the trial, seizure frequency did not change significantly in either group. With PGB, patients manifested partly significant impairments in episodic memory of verbal and visual information. Psychiatric states were unchanged. With LEV treatment, we saw improvements in visual short-term memory performance and psychiatric states (i.e., interpersonal sensibility, depression, and anxiety). The comparison between PGB and LEV revealed a trend toward higher anxiety scores and higher variability in hostility scores with PGB that was significantly different from the trend with LEV. No significant differences were apparent in all other neuropsychological and psychiatric parameters investigated. This short-term study suggests that add-on LEV has a favorable neuropsychological and psychiatric impact. The negative neuropsychological effects of PGB may reflect temporary effects under titration. Still, the results did not confirm the promising effects on psychiatric comorbidity that have been emphasized by other reports.

Topics: Adult; Anticonvulsants; Anxiety; Depression; Epilepsies, Partial; Female; gamma-Aminobutyric Acid; Humans; Levetiracetam; Male; Memory; Middle Aged; Neuropsychological Tests; Piracetam; Pregabalin

The objective of the study was to analyze the short-term efficacy and safety of levetiracetam (LEV) to treat repetitive seizures in hospitalized patients.. During admission to a tertiary hospital, we retrospectively identified patients with repetitive seizures who were treated for the first time with LEV during a hospital stay. LEV was considered effective if seizure cessation or >75% seizure reduction occurred in the 24 h after starting LEV (compared with the previous 48 h), requiring no further antiepileptic drug (AED) treatment.. Thirty patients (12 men, 18 women) were included. Mean age was 59.7 years. Most frequent seizure type was focal motor in 12 (40%) of 30 patients. Most frequent etiology was stroke: nine (30%) of 30 patients. Relevant medical conditions included atrial fibrillation (three) and hepatic disease (three). Concomitant medications included oral anticoagulants (seven), corticosteroids (two), and chemotherapy (two). Four patients received LEV as the only AED. Six patients with focal SE and 20 (66.6%) patients with clusters of seizures but not in SE received LEV as add-on treatment after lack of response to first-line AEDs. Mean LEV dose during first day was 1,119 mg. Mean daily maintenance dose was 1,724 mg. LEV was effective in 24 (80%) patients, all four patients who received it as the only AED, four of six patients with focal SE, and 16 of 20 patients with clusters of seizures. Three (10%) elderly patients with seizures secondary to stroke and chronic obstructive pulmonary disease (COPD) reported moderate/severe somnolence and dizziness, leading to treatment discontinuation in one. On discharge, 20 (66.7%) patients continued on LEV, nine (30%) as the only AED.. LEV is effective and safe to treat repetitive seizures in hospitalized patients, including patients in focal SE.

Topics: Adult; Aged; Anticonvulsants; Comorbidity; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Hospitalization; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Secondary Prevention; Seizures; Status Epilepticus; Treatment Outcome

This prospective open-label study used flexible dosing schedules of levetiracetam (LEV) in patients with refractory epilepsy attending a single centre to explore its effectiveness in everyday clinical practice. One hundred and fifty-six patients with uncontrolled localisation-related or idiopathic-generalised epilepsy were prescribed adjunctive LEV following a 3-month baseline. The primary end points were seizure freedom for at least 6 months, > or = 50% reduction (responder) or <50% reduction for 6 months, or discontinuation of LEV due to lack of efficacy, adverse effects or both. Overall, 40 (26%) patients became seizure free on adjunctive LEV, including 8 (40%) with idiopathic-generalised epilepsy. Twenty-five (63%) of the seizure-free patients took 1000 mg LEV per day or less. A further 33 (21%) patients were classified as responders. LEV was withdrawn in 46 (29%) patients (27 adverse effects, 8 lack of efficacy, 11 both). Intolerable sedation, reported by 20 (13%) patients, was the commonest complaint leading to treatment failure. Behavioural side effects led to LEV withdrawal in 7 (5%) patients. LEV is an effective adjunctive treatment for refractory idiopathic and localisation-related epilepsies. Many patients who responded optimally to LEV did so at 1000 mg per day or less.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Drug Resistance; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Epilepsy, Generalized; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Treatment Outcome

We examined the efficacy, optimum dosage and adverse effects of levetiracetam in two prospective trials in children with epilepsy. In the add-on trial, 67 children between 6 months and 16 years were included. In the mono-therapy trial, 10 children between 4 years and 16 years were included. Levetiracetam was titrated up to an optimal dosage for every individual patient, depending on efficacy and tolerability, and reflecting clinical practice. The range of dosages used was between 12 and 62 mg/kg/day, with a median of 33 mg/kg/day. Overall, 20 weeks after the start of levetiracetam, there was a median seizure reduction of 60% (add-on trial 50%; mono-therapy trial 81%). Levetiracetam was equally effective for partial and generalized seizures. Side effects were less common in the mono-therapy trial. Tiredness (7.8%) and aggressiveness (5%) were the most common side effects, and were dose-related, but were no reason to discontinue levetiracetam. In 25% of the children, a positive effect was seen on behaviour and/or alertness. This could not be related directly to seizure control. Overall, these two clinical trials confirm that levetiracetam is a broad spectrum anti-epileptic drug with a favourable safety profile. The positive effect on behaviour needs further quantitative study.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Electroencephalography; Epilepsies, Myoclonic; Epilepsies, Partial; Epilepsy, Absence; Epilepsy, Generalized; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Prospective Studies; Syndrome; Treatment Outcome

We identified 46 patients with a history of partial seizures, with and without secondarily generalization, who received levetiracetam (LEV) (Keppra) monotherapy. Patients began LEV either as first line therapy (n=11) or were converted to LEV monotherapy (n=35) after failing prior antiepileptic medications (AEDs). Patients were followed up to 12 months after LEV started. The majority of these patients were able to continue on LEV and a small number of patients discontinued LEV secondary to lack of efficacy. One third of the non-seizure free group at 6 months of follow-up had worse seizure control at 12 months and two thirds had the same or better seizure control. Our 1-year follow-up data of LEV as monotherapy suggests that LEV can be effective and well tolerated in adults with either new or difficult to control epilepsy. A prospective, large, long-term double-blind study is needed to confirm this finding.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Electroencephalography; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Video Recording

We report a patient with focal epilepsy in whom increased sleep needs (hypersomnia) developed in the absence of subjective excessive daytime sleepiness (EDS) during an add-on treatment with levetiracetam (LEV).

Topics: Adult; Anticonvulsants; Disorders of Excessive Somnolence; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Piracetam

In a retrospective study of 59 children (ages 9 months to 23 years; mean age 11 years) with intractable epilepsy, seizure frequency was determined before and after 12 months of levetiracetam therapy. Charts were reviewed for seizure type (focal, generalized, or mixed), cognitive function (no special education versus special education), concomitant anticonvulsant medications (range 0-5), and the number of previous anticonvulsant drugs (range 1-12). Good to excellent seizure control (50-100% reduction) was attained in 6 (40%) patients with focal seizures, 16 (55%) patients with generalized seizures, and 8 (61%) patients with mixed seizures; these efficacy rates were not significantly different. The efficacy of levetiracetam was independent of cognitive status. Adverse effects were not associated with higher mean doses. This could be attributable to different rates of metabolism or represent idiosyncratic responses to the medication. Our finding that those children taking the combination of levetiracetam and zonisamide had a significantly worse outcome than those on levetiracetam and a different drug warrants further study, both clinically and from the standpoint of the mechanisms of action of levetiracetam and zonisamide and/or their pharmacodynamic interactions.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Cognition; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Generalized; Female; Follow-Up Studies; Humans; Infant; Isoxazoles; Levetiracetam; Male; Piracetam; Retrospective Studies; Treatment Outcome; Zonisamide

In a retrospective study of 35 children (ages 8 months to 22 years; mean age 9 years) with intractable epilepsy, seizure frequency was determined before and after 12 months of zonisamide therapy. Charts were reviewed for seizure type (focal, generalized, or mixed), cognitive function (no special education versus special education), concomitant anticonvulsant medications, and the number of previous anticonvulsant drugs. Good to excellent seizure control (50-100% reduction) was attained in seven (54%) patients with generalized seizures, two (40%) patients with focal seizures, five (35%) patients with mixed seizures, and one (33%) patient with infantile spasms. In this group of children, the efficacy of zonisamide was comparable for focal, generalized, and mixed seizures. The efficacy of zonisamide was independent of cognitive status. Adverse effects were not associated with a higher mean dose. This could be attributable to different rates of metabolism or represent idiosyncratic responses to the medication. Our finding that those children taking the combination of zonisamide and levetiracetam had a significantly worse outcome than those on levetiracetam and a different drug warrants further study, both clinically and from the standpoint of mechanisms of action of zonisamide and levetiracetam and/or their pharmacodynamic interactions.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Cognition; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Generalized; Female; Follow-Up Studies; Humans; Infant; Isoxazoles; Levetiracetam; Male; Piracetam; Retrospective Studies; Treatment Outcome; Zonisamide

Levetiracetam was released in 2000 as an antiepileptic drug for add-on treatment of focal epilepsies. Its efficacy and tolerability were investigated in this retrospective study.. The effects of add-on treatment with levetiracetam on seizure frequency and side effects were analyzed retrospectively in 80 consecutive patients with focal epilepsy.. With a mean follow-up of 12.3 months, 18.8% of patients treated with levetiracetam became seizure-free, and additional 15.0% and 3.8% had reductions in seizure frequency of 75% and 50%, respectively. Increasing the dosage to more than 3,500 mg/day did not improve efficacy but could induce a paradoxical increase in seizure frequency and psychic side effects. Levetiracetam was efficacious against all seizure types independently of focus localization. There was no evidence for the development of tolerance with longer periods of treatment. The most common adverse effects were somnolence and aggressiveness; tolerability did not decrease with rapid titration.. Levetiracetam is a potent and generally well tolerable new antiepileptic drug which is also efficacious in patients with difficult-to-treat focal epilepsies.

Topics: Adult; Anticonvulsants; Combined Modality Therapy; Disease-Free Survival; Disorders of Excessive Somnolence; Dose-Response Relationship, Drug; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Piracetam; Retrospective Studies; Severity of Illness Index; Treatment Outcome

We report a patient with focal epilepsy and latent hereditary coproporphyria who had exacerbation of clinical symptoms of porphyria under treatment with valproate and primidone and was then treated with levetiracetam without exacerbation of clinically latent porphyria.

Topics: Acute Disease; Adult; Anticonvulsants; Comorbidity; Epilepsies, Partial; Female; Humans; Levetiracetam; Piracetam; Porphyrias, Hepatic; Primidone; Valproic Acid

Optimal antiepileptic drug treatment in patients with learning disability (LD) represents a particular challenge. These patients are often unable to report toxicity, and side effects may manifest as behavioral problems. The aim of this open study was to compare efficacy and tolerability of levetiracetam (LEV) in patients with LD and those without LD. One hundred eighty-four consecutive adult patients who received LEV were followed for an average of 8.1 months. Fifty-six patients (30%) had LD. Thirty-nine percent of patients with refractory epilepsy (37% with and 40% without LD) had > 50% seizure reduction. Significantly more behavioral side effects (23% vs 10%) and a tendency toward less reported somatic central nervous side effects were found in the LD group. We conclude that LEV is equally effective and well tolerated in both patients with LD and patients without LD. However, behavioral problems are more frequent in patients with LD, whereas the tendency toward seizure increase is not enhanced.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Dose-Response Relationship, Drug; Drug Resistance; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Generalized; Female; Humans; Intellectual Disability; Levetiracetam; Male; Mental Disorders; Middle Aged; Myoclonic Epilepsy, Juvenile; Piracetam; Retrospective Studies

We conducted a retrospective study to evaluate the efficacy of levetiracetam as adjunctive therapy in patients with localization-related epilepsy, and specifically in the subset of patients for whom epilepsy surgery failed.. Eighty-two patients with uncontrolled partial-onset seizures treated with levetiracetam were identified; epilepsy surgery had failed for 21 (25.6%; group I), and 61 (74.4%) had no prior surgery (group II). Group I and group II patients were comparable in age (mean, 40.7 vs. 41.5 years) and age at seizure onset (mean, 14.4 vs. 18.2 years). Patients who had >/=50% reduction in seizure frequency were considered responders; the remaining patients were considered nonresponders.. In patients (group I) for whom surgery had failed, responder rate was 76.1% (16 of 21), including 10 (47.6%) patients who became seizure free. In nonsurgical patients (group II), responder rate was 34.3% (21 of 61), including nine (14.7%) patients who became seizure free. In group I, 11 (91.6%) of 12 temporal resection patients were responders, of whom eight were seizure free; of the remaining nine operated (extratemporal) patients, five (55.5%) were responders, and two were seizure free. In three responders, all in group I, a severe, delayed psychotic syndrome developed 4 to 9 months after levetiracetam introduction, leading to its discontinuation.. These findings suggest that adjunctive levetiracetam therapy should be considered early after failed epilepsy surgery, especially after temporal resection, and may have implications for its use before surgical intervention. Patients should be under close psychiatric observation in this clinical setting.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Postoperative Complications; Retrospective Studies; Treatment Failure; Treatment Outcome

Topics: Child, Preschool; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Humans; Levetiracetam; Male; Nootropic Agents; Piracetam; Sleep

In this open-label add-on study of levetiracetam in refractory childhood epilepsy syndromes, we studied the effect of a rapid introduction of levetiracetam on the total seizure frequency in 21 children, known to have partial and generalized seizures. Starting dosage was 10 mg/kg/day, increased every 4th day by 10 mg/kg up to a maximum of 60 mg/kg/day, depending on efficacy and tolerability. In this highly refractory population, 47% showed a seizure frequency reduction of more than 50%. Levetiracetam was effective both in partial and generalized seizures, with a significant effect on myoclonic seizures. Only mild side-effects were observed in four of 21 children, at a dosage of more than 40 mg/kg/day.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Administration Schedule; Epilepsies, Partial; Epilepsy, Generalized; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Syndrome

A twelve year-old-girl with idiopathic partial epilepsy with secondary generalization, developed acute psychosis 10 days after the administration of levetiracetam. The patient was already on sodium valproate, and levetiracetam was given as add on therapy. A final dosage of 60 mg/kg was used. Complete seizure control was achieved but the patient developed hallucinations, agitation and self-harming behaviour, as well as poor social contact. The psychotic behavior resolved completely soon after the discontinuation of levetiracetam.

Topics: Anticonvulsants; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Piracetam; Psychoses, Substance-Induced; Valproic Acid

Topics: Acetates; Amines; Anticonvulsants; Carbamazepine; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Epilepsies, Partial; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Piracetam; Tiagabine; Topiramate; Triazines; Vigabatrin; Zonisamide

Many agents are available for treating epilepsy; however, population studies have failed to show overall differences in efficacy for a given seizure type. Clinical experience suggests that certain individuals will respond to a given agent while others with the same seizure type will not.. To examine a population of patients who received one of the newer antiepileptic drugs, levetiracetam, and to identify those who had either a dramatic improvement or a significant worsening of seizures.. Retrospective medical record review of patients with refractory epilepsy.. Patients who responded well to levetiracetam therapy were older at the onset of epileptic seizure than those who did not (mean [SD] age, 51 [5] vs 27 [3] years; P<.05). This was also true of the subset of patients who had localization-related epilepsy. Patients with temporal lobe onset were likely to do well whereas patients with frontal lobe onset were not.. These results suggest that certain subpopulations may be particularly likely to respond to levetiracetam therapy. These need to be confirmed in a larger prospective trial; however, looking for specific characteristics of patients who respond to certain drugs may lead to useful guidelines for drug choices in treating epilepsy.

Topics: Adult; Age of Onset; Anticonvulsants; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Piracetam; Postoperative Period; Preoperative Care; Retrospective Studies; Verbal Learning

To assess clinical trials for evidence that antiepileptic drugs (AED) aggravate partial seizures. To determine if the methodology used to examine drug efficacy can also be used to examine seizure aggravation.. It is widely accepted that AED aggravate epilepsy in some patients. However, there is little published objective or quantitative evidence. Most reports concern generalized epilepsies.. Pharmaceutical companies responsible for the development of five of the new AED were asked to provide data concerning seizure increases during randomized placebo-controlled, add-on clinical trials in patients with uncontrolled partial seizures. Seizure frequency in individual patients taking drug or placebo was compared with the baseline pretreatment seizure frequency. The counterpart of the 50% reduction used in efficacy analyses is a 100% increase, because both represent a twofold change. A dose-response relationship was also explored.. More than 40% of subjects in clinical trials of tiagabine (TGB), topiramate (TPM), and levetiracetam (LEV) experienced an increase in seizures while taking a placebo. Seizure increases were no more likely to occur when taking any of the three drugs than taking placebo. A doubling or more of seizure frequency was less likely to occur with TPM or LEV than with placebo but more likely with TGB. However, for TGB, this did not reach significance. There was some evidence for a dose-response effect with TGB but a negative effect with TPM (aggravation less likely with increasing dose). Data on gabapentin and lamotrigine were not provided.. Many patients with partial seizures experience an increase in seizures when a new AED is added to their therapy. However, it occurs no more frequently when taking drug than placebo. It probably represents the spontaneous fluctuation of seizure frequency. When a patient who has started a new AED deteriorates, this is not necessarily a drug effect.

Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy, Generalized; Fructose; Humans; Levetiracetam; Nipecotic Acids; Piracetam; Randomized Controlled Trials as Topic; Retrospective Studies; Tiagabine; Topiramate

Topics: Adult; Animals; Anticonvulsants; Drug Approval; Epilepsies, Partial; Epilepsy; Humans; Levetiracetam; Piracetam; United States

Levetiracetam is a new antiepileptic drug with a chemical structure similar to piracetam, but different pharmacological properties. The pharmacokinetic profile of levetiracetam closely approximates the ideal characteristics expected of an antiepileptic drug: good bioavailability, linear kinetics, rapid achievement of steady-state concentrations, minimal protein binding and minimal metabolism. It has been approved as add-on therapy for the treatment of partial-onset seizures in adults. Its efficacy has been proved through four pivotal double-blind, aleatorized, placebo-controlled trials. Levetiracetam is well-tolerated and the incidence of adverse events is similar to placebo. There is no evidence of any specific interactions between levetiracetam and digoxin, warfarin, probenecid or other antiepileptic drugs. Preclinical studies have shown potential efficacy against generalized seizures. Antidystonic and antimyoclonic effects have been also suggested. There are few data of its efficacy on monotherapy and pediatric population.

Topics: Adult; Animals; Anticonvulsants; Drug Interactions; Epilepsies, Partial; Humans; Learning; Levetiracetam; Memory; Molecular Structure; Piracetam

Epileptogenesis induced by electrical kindling of rats appears to be superior to the acute maximal electroshock seizure (MES) test in normal animals in predicting the efficacy and adverse effect potential of drugs in patients with partial epilepsy. Unfortunately, inclusion of such kindling models in primary screening is hampered by the laborious and expensive procedure of stimulation and recording with implanted brain electrodes. Furthermore the size of the rats excludes their use in initial testing where compound availability is often limited for the 'first batch synthesis'. The present study demonstrates that chronic electrical stimulation with corneal electrodes in mice can rapidly yield large numbers of kindled animals with a seizure phenomenology reflecting partial seizures in man. A pharmacological characterisation showed that corneally kindled mice can be used repeatedly for several drug experiments with reproducible results. The seizure protection and adverse effect potential obtained with proven antiepileptic drugs were similar to the effects observed in amygdala kindled rats and their corresponding clinical profile in partial epilepsy. Protection was obtained with vigabatrin and levetiracetam in this new model despite their lack of anticonvulsant activity in the acute MES test. Furthermore, in agreement with clinical findings with NMDA antagonists, MK-801 revealed more severe adverse effects in corneally kindled mice than in normal animals. These results suggest that corneal kindling of mice represents a sensitive and valid screening model for the identification of new therapies for partial epilepsy in man.

Topics: Amygdala; Animals; Anticonvulsants; Carbamazepine; Cornea; Disease Models, Animal; Dizocilpine Maleate; Drug Evaluation, Preclinical; Electric Stimulation; Electroshock; Epilepsies, Partial; gamma-Aminobutyric Acid; Kindling, Neurologic; Levetiracetam; Male; Mice; Piracetam; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Retina; Seizures; Sensitivity and Specificity; Time Factors; Valproic Acid; Vigabatrin

The anticonvulsant effects of levetiracetam were assessed in two genetic rat models. In the audiogenic-seizure prone rat, levetiracetam, 5.4 to 96 mg/kg i.p. dose-dependently inhibited both wild running and tonic-clonic convulsions. In the GAERS model of petit mal epilepsy, levetiracetam markedly suppressed spontaneous spike-and-wave discharge (SWD) but left the underlying EEG trace normal. The effects were already marked at 5.4 mg/kg and did not increase significantly up to 170 mg/kg although more animals were completely protected. Levetiracetam produced no observable effects on behaviour apart from slight reversible sedation at 170 mg/kg. In contrast, piracetam, a structural analogue of levetiracetam, significantly and consistently suppressed SWD in GAERS rats only at the high dose of 1000 mg/kg with some slight effects at lower doses. The effect of piracetam appeared to be due to increased sleeping rather than to a direct antiepileptic effect. The results with levetiracetam argue for a clinical application in both petit mal, absence epilepsy and in treating generalised tonic-clonic and partial seizures.

Topics: Acoustic Stimulation; Animals; Anticonvulsants; Behavior, Animal; Electroencephalography; Epilepsies, Partial; Epilepsy; Epilepsy, Absence; Epilepsy, Tonic-Clonic; Female; Levetiracetam; Male; Piracetam; Rats; Rats, Inbred Strains; Rats, Wistar

The novel anticonvulsant drug ucb L059 ((S)-alpha-ethyl-2-oxo-1-pyrrolidineacetamide) was evaluated in several rodent models of partial and generalized seizures. Ucb L059 (27-108 mg/kg i.p.) increased the thresholds for tonic electroconvulsions and myoclonic and clonic seizures induced by timed i.v. infusion of pentylenetetrazol (PTZ), but was ineffective in the traditional maximal electroshock seizure and s.c. PTZ seizure tests in mice and rats in doses up to 500 mg/kg. The anticonvulsant potency of ucb L059 in seizure threshold tests was similar to that of standard drugs, such as valproate. In amygdala-kindled rats, ucb L059 exerted potent anticonvulsant activity against both focal and secondarily generalized seizures at doses of 13-108 mg/kg. The adverse effects of ucb L059 were quantitated in the open field and in standard tests for motor impairment, such as the rotarod and chimney tests. Ucb L059 exerted only minimal effects on behaviour, e.g. slight hyperactivity, and did not impair muscle activity in the rotarod test in doses up to 1700 mg/kg i.p. The data indicate that ucb L059 is an interesting new anticonvulsant agent with a broad spectrum of activity and high therapeutic index.

Topics: Amygdala; Animals; Anticonvulsants; Behavior, Animal; Dose-Response Relationship, Drug; Electrodes; Electroshock; Epilepsies, Partial; Epilepsy, Generalized; Female; Kindling, Neurologic; Levetiracetam; Male; Mice; Myoclonus; Pentylenetetrazole; Piracetam; Postural Balance; Psychomotor Performance; Rats; Rats, Wistar; Stereotaxic Techniques