levetiracetam and Epilepsy

Older adults represent a highly heterogeneous population, with multiple diverse subgroups. Therefore, an individualized approach to treatment is essential to meet the needs of each unique subgroup. Most comparative studies focusing on treatment of epilepsy in older adults have found that levetiracetam has the best chance of long-term seizure freedom. However, there is a lack of studies investigating other newer generation antiseizure medications (ASMs). Although a number of randomized clinical trials have been performed on older adults with epilepsy, the number of participants studied was generally small, and they only investigated short-term efficacy and tolerability. Quality of life as an outcome is often missing but is necessary to understand the effectiveness and possible side effects of treatment. Prognosis needs to move beyond the focus on seizure control to long-term patient-centered outcomes. Dosing studies with newer generation ASMs are needed to understand which treatments are the best in the older adults with different comorbidities. In particular, more high-level evidence is required for older adults with Alzheimer's disease with epilepsy and status epilepticus. Future treatment studies should use greater homogeneity in the inclusion criteria to allow for clearer findings that can be comparable with other studies to build the existing treatment evidence base.

Topics: Aged; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Quality of Life; Seizures

Early life epilepsies are common and often debilitating, but no evidence-based management guidelines exist outside of those for infantile spasms. We conducted a systematic review of the effectiveness and harms of pharmacologic and dietary treatments for epilepsy in children aged 1-36 months without infantile spasms.. We searched EMBASE, MEDLINE, PubMed, and the Cochrane Library for studies published from January 1, 1999, to August 19, 2021. Using prespecified criteria, we identified studies reporting data on children aged 1-36 months receiving pharmacologic or dietary treatments for epilepsy. We did not require that studies report etiology-specific data. We excluded studies of neonates, infantile spasms, and status epilepticus. We included studies administering 1 of 29 pharmacologic treatments and/or 1 of 5 dietary treatments reporting effectiveness outcomes at ≥ 12 weeks. We reviewed the full text to find any subgroup analyses of children aged 1-36 months.. Twenty-three studies met inclusion criteria (6 randomized studies, 2 nonrandomized comparative studies, and 15 prestudies/poststudies). All conclusions were rated low strength of evidence. Levetiracetam leads to seizure freedom in some infants (32% and 66% in studies reporting seizure freedom), but data on 6 other medications were insufficient to permit conclusions about effectiveness (topiramate, lamotrigine, phenytoin, vigabatrin, rufinamide, and stiripentol). Three medications (levetiracetam, topiramate, and lamotrigine) were rarely discontinued because of adverse effects, and severe events were rare. For diets, the ketogenic diet leads to seizure freedom in some infants (rates 12%-37%), and both the ketogenic diet and modified Atkins diet reduce average seizure frequency, but reductions are greater with the ketogenic diet (1 RCT reported a 71% frequency reduction at 6 months for ketogenic diet vs only a 28% reduction for the modified Atkins diet). Dietary harms were not well-reported.. Little high-quality evidence exists on pharmacologic and dietary treatments for early life epilepsies. Future research should isolate how treatments contribute to outcomes, conduct etiology-specific analyses, and report patient-centered outcomes such as hospitalization, neurodevelopment, functional performance, sleep quality, and patient and caregiver quality of life.. This systematic review was registered in PROSPERO (CRD42021220352) on March 5, 2021.

Topics: Anticonvulsants; Child; Diet, Ketogenic; Epilepsy; Humans; Infant; Infant, Newborn; Lamotrigine; Levetiracetam; Quality of Life; Spasms, Infantile; Topiramate

Epilepsy is a chronic disease of the central nervous system characterized by recurrent epileptic seizures. As a result of epileptic seizure or status epilepticus oxidants are excessively formed, which may be one of the causes of neuronal death. Given the role of oxidative stress in epileptogenesis, as well as the participation of this process in other neurological conditions, we decided to review the latest state of knowledge regarding the relationship between selected newer antiepileptic drugs (AEDs), also known as antiseizure drugs, and oxidative stress. The literature review indicates that drugs enhancing GABA-ergic transmission (e.g., vigabatrin, tiagabine, gabapentin, topiramate) or other antiepileptics (e.g., lamotrigine, levetiracetam) reduce neuronal oxidation markers. In particular, levetiracetam may produce ambiguous effects in this regard. However, when a GABA-enhancing drug was applied to the healthy tissue, it tended to increase oxidative stress markers in a dose-dependent manner. Studies on diazepam have shown that it exerts a neuroprotective effect in a "U-shaped" dose-dependent manner after excitotoxic or oxidative stress. Its lower concentrations are insufficient to protect against neuronal damage, while higher concentrations produce neurodegeneration. Therefore, a conclusion follows that newer AEDs, enhancing GABA-ergic neurotransmission, may act similarly to diazepam, causing neurodegeneration and oxidative stress when used in high doses.

Topics: Anticonvulsants; Carbamazepine; Diazepam; Epilepsy; Epilepsy, Generalized; Fructose; Gabapentin; Humans; Levetiracetam; Seizures; Triazines

Epilepsy is the most common symptom in patients with brain tumors. The shared genetic, molecular, and cellular mechanisms between tumorigenesis and epileptogenesis represent 'two sides of the same coin'. These include augmented neuronal excitatory transmission, impaired inhibitory transmission, genetic mutations in the BRAF, IDH, and PIK3CA genes, inflammation, hemodynamic impairments, and astrocyte dysfunction, which are still largely unknown. Low-grade developmental brain tumors are those most commonly associated with epilepsy. Given this strict relationship, drugs able to target both seizures and tumors would be of extreme clinical usefulness. In this regard, anti-seizure medications (ASMs) are optimal candidates as they have well-characterized effects and safety profiles, do not increase the risk of developing cancer, and already offer well-defined seizure control. The most important ASMs showing preclinical and clinical efficacy are brivaracetam, lacosamide, perampanel, and especially valproic acid and levetiracetam. However, the data quality is low or limited to preclinical studies, and results are sometimes conflicting. Future trials with a prospective, randomized, and controlled design accounting for different prognostic factors will help clarify the role of these ASMs and the clinical setting in which they might be used. In conclusion, brain tumor-related epilepsies are clear examples of how close, multidisciplinary collaborations among investigators with different expertise are warranted for pursuing scientific knowledge and, more importantly, for the well-being of patients needing targeted and effective therapies.

Topics: Anticonvulsants; Brain Neoplasms; Epilepsy; Humans; Levetiracetam; Valproic Acid

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

Medical treatment is the primary therapy option for patients with epilepsy. Recently, the International League Against Epilepsy (ILAE) proposed that the current medications used to treat epilepsy should be referred to as 'antiseizure medications' (ASMs) due to the symptomatic effect exerted against seizures. The present article reviews the recent clinical practice guidelines (Clinical Practice Guidelines for Epilepsy 2018, in Japan, and the NICE guideline, published in April 2022) and expert opinions (USA, South Korea, and Spain) based on which the selection of ASMs has been discussed. The classification of seizure types and epilepsies should be examined before selecting the ASMs for each patient with epilepsy. For focal epilepsy, lamotrigine, levetiracetam, and lacosamide would be the first-line ASM, whereas, for generalized epilepsy, valproic acid, lamotrigine, and levetiracetam would be the first-line ASM. However, valproic acid is not to be prescribed to women of childbearing potential.

Topics: Anticonvulsants; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Seizures; Valproic Acid

The late onset myoclonic epilepsy in Down Syndrome (LOMEDS) is a peculiar epilepsy type characterized by cortical myoclonus and generalized tonic-clonic seizures (GTCS), in people suffering from cognitive decline in Down syndrome (DS). In this review, we analyzed available data on the diagnostic and therapeutic management of individuals with LOMEDS.. We performed a systematic search of the literature to identify the diagnostic and therapeutic management of patients with LOMEDS. The following databases were used: PubMed, Google Scholar, EMBASE, CrossRef. The protocol was registered on PROSPERO (registration code: CRD42023390748).. Data from 46 patients were included. DS was diagnosed according to the patient's clinical and genetic characteristics. Diagnosis of Alzheimer's dementia (AD) preceded the onset of epilepsy in all cases. Both myoclonic seizures (MS) and generalized tonic-clonic seizures (GTCS) were reported, the latter preceding the onset of MS in 28 cases. EEG was performed in 45 patients, showing diffuse theta/delta slowing with superimposed generalized spike-and-wave or polyspike-and-wave. A diffuse cortical atrophy was detected in 34 patients on neuroimaging. Twenty-seven patients were treated with antiseizure medication (ASM) monotherapy, with reduced seizure frequency in 17 patients. Levetiracetam and valproic acid were the most used ASMs. Up to 41% of patients were unresponsive to first-line treatment and needed adjunctive therapy for seizure control.. AD-related pathological changes in the brain may play a role in LOMEDS onset, although the mechanism underlying this phenomenon is still unknown. EEG remains the most relevant investigation to be performed. A significant percentage of patients developed a first-line ASM refractory epilepsy. ASMs which modulate the glutamatergic system may represent a good therapeutic option.

Topics: Alzheimer Disease; Anticonvulsants; Down Syndrome; Electroencephalography; Epilepsies, Myoclonic; Epilepsy; Epilepsy, Generalized; Humans; Levetiracetam; Seizures

Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizure

Topics: Anticonvulsants; Consensus; Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenytoin; Seizures

Newborn infants are more prone to seizures than older children and adults. The neuronal injury caused by seizures in neonates often results in long-term neurodevelopmental sequelae. There are several options for anti-seizure medications (ASMs) in neonates. However, the ideal choice of first-, second- and third-line ASM is still unclear. Further, many other aspects of seizure management such as whether ASMs should be initiated for only-electrographic seizures and how long to continue the ASM once seizure control is achieved are elusive.. 1. To assess whether any ASM is more or less effective than an alternative ASM (both ASMs used as first-, second- or third-line treatment) in achieving seizure control and improving neurodevelopmental outcomes in neonates with seizures. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately. 2. To assess maintenance therapy with ASM versus no maintenance therapy after achieving seizure control. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately. 3. To assess treatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates.. We searched MEDLINE, Embase, CENTRAL, Epistemonikos and three databases in May 2022 and June 2023. These searches were not limited other than by study design to trials.. We included randomised controlled trials (RCTs) that included neonates with EEG-confirmed or clinically diagnosed seizures and compared (1) any ASM versus an alternative ASM, (2) maintenance therapy with ASM versus no maintenance therapy, and (3) treatment of clinical or EEG seizures versus treatment of clinical seizures alone.. Two review authors assessed trial eligibility, risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence interval (CI). We used GRADE to assess the certainty of evidence.. We included 18 trials (1342 infants) in this review. Phenobarbital versus levetiracetam as first-line ASM in EEG-confirmed neonatal seizures (one trial) Phenobarbital is probably more effective than levetiracetam in achieving seizure control after first loading dose (RR 2.32, 95% CI 1.63 to 3.30; 106 participants; moderate-certainty evidence), and after maximal loading dose (RR 2.83, 95% CI 1.78 to 4.50; 106 participants; moderate-certainty evidence). However, we are uncertain about the effect of phenobarbital when compared to levetiracetam on mortality before discharge (RR 0.30, 95% CI 0.04 to 2.52; 106 participants; very low-certainty evidence), requirement of mechanical ventilation (RR 1.21, 95% CI 0.76 to 1.91; 106 participants; very low-certainty evidence), sedation/drowsiness (RR 1.74, 95% CI 0.68 to 4.44; 106 participants; very low-certainty evidence) and epilepsy post-discharge (RR 0.92, 95% CI 0.48 to 1.76; 106 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months. Phenobarbital versus phenytoin as first-line ASM in EEG-confirmed neonatal seizures (one trial) We are uncertain about the effect of phenobarbital versus phenytoin on achieving seizure control after maximal loading dose of ASM (RR 0.97, 95% CI 0.54 to 1.72; 59 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months. Maintenance therapy with ASM versus no maintenance therapy in clinically diagnosed neonatal seizures (two trials) We are uncertain about the effect of short-term maintenance therapy with ASM versus no maintenance therapy during the hospital stay (but discontinued before discharge) on the risk of repeat seizures before hospital discharge (RR 0.76, 95% CI 0.56 to 1.01; 373 participants; very low-certainty evidence). Maintenance therapy with ASM compared to no maintenance therapy may have little or no effect on mortality before discharge (RR 0.69, 95% CI 0.39 to 1.22; 373 participants; low-certainty evidence), mortality at 18 to 24 months (RR 0.94, 95% CI 0.34 to 2.61; 111 participants; low-certainty evidence), neurodevelopmental disability at 18 to 24 months (RR 0.89, 95% CI 0.13 to 6.12; 108 participants; low-certainty evidence) and epilepsy post-discharge (RR 3.18, 95% CI 0.69 to 14.72; 126 participants; low-certainty evidence). Treatment of both clinical and electrographic seizures versus treatment of clinical seizure. Phenobarbital as a first-line ASM is probably more effective than levetiracetam in achieving seizure control after the first loading dose and after the maximal loading dose of ASM (moderate-certainty evidence). Phenobarbital + bumetanide may have little or no difference in achieving seizure control when compared to phenobarbital alone (low-certainty evidence). Limited data and very low-certainty evidence preclude us from drawing any reasonable conclusion on the effect of using one ASM versus another on other short- and long-term outcomes. In neonates who achieve seizure control after the first loading dose of phenobarbital, maintenance therapy compared to no maintenance ASM may have little or no effect on all-cause mortality before discharge, mortality by 18 to 24 months, neurodevelopmental disability by 18 to 24 months and epilepsy post-discharge (low-certainty evidence). In neonates with hypoxic-ischaemic encephalopathy, treatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation, all-cause mortality before discharge and epilepsy post-discharge (low-certainty evidence). All findings of this review apply only to term and late preterm neonates. We need well-designed RCTs for each of the three objectives of this review to improve the precision of the results. These RCTs should use EEG to diagnose seizures and should be adequately powered to assess long-term neurodevelopmental outcomes. We need separate RCTs evaluating the choice of ASM in preterm infants.

Topics: Adolescent; Adult; Child; Epilepsy; Humans; Infant; Infant, Newborn; Levetiracetam; Phenobarbital; Phenytoin; Seizures

Antiseizure medications (ASM) have long been examined for their potential to induce thyroid dysfunction. The aim of this systematic review and meta-analysis was to assess the prevalence of thyroid disease in children up to 16 years receiving monotherapy with valproate (VPA), carbamazepine (CBZ) and levetiracetam (LEV).. PubMed/MEDLINE, Cochrane/CENTRAL databases and the gray literature were searched to identify observational studies providing the prevalence of thyroid dysfunction in the target population under VPA, CBZ, or LEV monotherapy schemes. The results were pooled using a random-effects model, and additional subgroup analyses were performed for the three ASM groups.. Fifteen and thirteen studies met inclusion criteria for the qualitative and the quantitative analysis, respectively, with a total of 945 pediatric patients with prevalence data. Only VPA and CBZ were associated with thyroid dysfunction. The overall prevalence of thyroid abnormality was higher in children receiving ASM [odds ratio (OR) 6.82, 95% confidence interval (CI) 3.96-11.75]. In the subgroup analysis, the prevalence of biochemical thyroid abnormality with increased TSH was higher in the VPA (OR 9.54, 95%CI 5.25-17.34) and the CBZ group (OR 4.08, 95%CI 1.84-9.04) compared with controls.. This study confirms the higher prevalence of biochemical thyroid abnormality in children under VPA and CBZ monotherapy, whereas no such evidence is present for LEV. In children with a predisposition for thyroid disease, LEV should be considered over VPA and CBZ, if appropriate for seizure type and epilepsy syndrome. More studies are needed to reach a consensus on monitoring and management of thyroid dysfunction in children receiving ASM therapy.

Topics: Anticonvulsants; Carbamazepine; Child; Epilepsy; Humans; Levetiracetam; Prevalence; Thyroid Diseases; Valproic Acid

To estimate the safety and efficacy of sodium valproate combined with levetiracetam in paediatric patients with epilepsy based on randomized controlled trials (RCTs).. The Cochrane Library, PubMed, Web of Science, Chinese Journal Full-Text Database (CNKI), WANGFANG DATA and Sino Med were searched between January 1946 and May 2021. The included literature was randomized controlled clinical trials focusing on sodium valproate combined with levetiracetam in paediatric patients with epilepsy. Two evaluators separately collected the data based on the retrieval strategy, filtered the literature in accordance with the inclusion and exclusion criteria, and summarized the literature that satisfied the criteria. The statistical programme used for the meta-analysis was Stata V14.0.. Of 577 original titles screened, data were extracted from 7 studies (617 participants). Compared with sodium valproate alone or sodium valproate combined with topiramate, the application of sodium valproate combined with levetiracetam in the treatment of paediatric epilepsy significantly improved the overall therapeutic effect (RR=1.24, 95% CI: 1.16 to 1.33, p=0.927). The observation group significantly reduced the occurrence of adverse drug reactions (ADRs) (RR=0.54, 95% CI: 0.37 to 0.79, p=0.602). Egger's regression test of the overall therapeutic effect showed no potential publication bias (p=0.122).. Based on this meta-analysis, compared with sodium valproate alone or sodium valproate with topiramate, the application of sodium valproate combined with levetiracetam in the treatment of paediatric epilepsy can significantly improve the overall therapeutic effect and simultaneously reduce the occurrence of ADR. Therefore, we recommend sodium valproate combined with levetiracetam for the therapy of paediatric patients with epilepsy.

Topics: Anticonvulsants; Child; Epilepsy; Humans; Levetiracetam; Topiramate; Valproic Acid

Anti-seizure drugs have long been known to affect thyroid hormone levels in epilepsy patients. The current study is a network meta-analysis designed to produce a systematic review and comprehensive evaluation of thyroid hormone changes to inform future research and clinical treatment.. A systematic search of databases, PubMed, EMBASE, Web of Science, and the Cochrane Library, was conducted and all observational studies reporting thyroid hormone levels in epilepsy patients receiving monotherapy and controls were included. Stata MP.14 was used for analysis.. A total of 35 studies, including 4135 participants and 8 anti-seizure drugs, were analyzed. TSH levels were elevated following use of topiramate [mean = 1.86; 95%CI: 0.83 to 2.90], levetiracetam [mean = 1.08; 95%CI: 0.07 to 2.09], and valproic acid [mean = 1.54; 95%CI: 0.58 to 2.50]. FT4 levels may be lowered by oxcarbazepine [mean =  - 6.13; 95%CI: - 8.25 to - 4.02] and T4 was lowered by carbamazepine [mean =  - 1.55; 95%CI: - 2.05 to - 1.05] and phenytoin [mean =  - 1.33; 95%CI: - 1.80 to - 0.85]. No significant changes were reported for FT3, although use of phenobarbital resulted in a non-significant decrease [mean =  - 0.31; 95%CI: - 0.99 to 0.37]. T3 levels were lowered by carbamazepine [mean =  - 0.52; 95%CI: - 0.81 to - 0.24]. Lamotrigine had no significant effect on thyroid hormone levels.. Carbamazepine and phenytoin were the drugs most strongly associated with decreases in T4 and T3 levels while topiramate had the greatest elevating effect on TSH. Oxcarbazepine may lead to decreased serum FT4 and FT3, an effect relevant to central hypothyroidism. Phenobarbital appeared to significantly lower FT3. Use of levetiracetam and valproic acid may result in subclinical hypothyroidism. The anti-seizure drug with the least disruptive effect on thyroid hormone levels was found to be lamotrigine.

Topics: Anticonvulsants; Carbamazepine; Epilepsy; Humans; Lamotrigine; Levetiracetam; Network Meta-Analysis; Oxcarbazepine; Phenobarbital; Phenytoin; Thyroid Hormones; Thyrotropin; Topiramate; Valproic Acid

A concise review of recent findings in brain tumor-related epilepsy (BTRE), with focus on the effect of antitumor treatment on seizure control and the management of antiepileptic drugs (AEDs).. Isocitrate dehydrogenase mutation and its active metabolite d -2-hydroxyglutarate seem important contributing factors to epileptogenesis in BTRE. A beneficial effect of antitumor treatment (i.e. surgery, radiotherapy, and chemotherapy) on seizure control has mainly been demonstrated in low-grade glioma. AED prophylaxis in seizure-naïve BTRE patients is not recommended, but AED treatment should be initiated after a first seizure has occurred. Comparative efficacy randomized controlled trials (RCTs) are currently lacking, but second-generation AED levetiracetam seems the preferred choice in BTRE. Levetiracetam lacks significant drug-drug interactions, has shown favorable efficacy compared to valproic acid in BTRE, generally causes no hematological or neurocognitive functioning adverse effects, but caution should be exercised with regard to psychiatric adverse effects. Potential add-on AEDs in case of uncontrolled seizures include lacosamide, perampanel, and valproic acid. Ultimately, in the end-of-life phase when oral intake of medication is hampered, benzodiazepines via nonoral administration routes are potential alternatives.. Management of seizures in BTRE is complex and with currently available evidence levetiracetam seems the preferred choice. Comparative efficacy RCTs in BTRE are warranted.

Topics: Anticonvulsants; Benzodiazepines; Brain Neoplasms; Epilepsy; Humans; Isocitrate Dehydrogenase; Lacosamide; Levetiracetam; Seizures; Valproic Acid

Levetiracetam (LEV) is one of the most widely used anti-seizure medications (ASMs) in clinical practice. This is due both to a different mechanism of action when compared to other ASMs and its easy handling. Indeed, because of its interesting pharmacokinetic properties, it is often used outside of the labeled indications, notably in the neurocritical setting as prophylaxis of epileptic seizures.. A literature search was conducted and the most relevant studies on the pharmacokinetic properties of LEV were selected by two independent investigators. Current evidence on the use of ASM prophylaxis in the neurocritical setting was also reviewed, highlighting and discussing the strengths and limits of LEV as drug of choice for anti-epileptic prophylaxis in this scenario.. LEV has a 'near-ideal' pharmacokinetic profile, which makes it an attractive drug for ASM prophylaxis in neurocritical care. However, current recommendations restrict ASMs prophylaxis to very selected circumstances and the role of LEV is marginal. Moreover, studies are generally designed to compare LEV versus phenytoin, whereas studies comparing LEV versus placebo are lacking. Further, randomized trials will be needed to better elucidate LEV utility and its neuroprotective role in the neurocritical setting.

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Phenytoin; Piracetam

We carried out a systematic review of published information on transfer of antiseizure medications (ASMs) into breastmilk, ASM serum concentrations in breastfed infants, and the wellbeing of infants breastfed by mothers on ASM treatment. Information was extracted from 85 relevant articles. No data on ASM levels in breastmilk or in breastfed infants was identified for cannabidiol, cenobamate, clobazam, eslicarbazepine-acetate, everolimus, felbamate, fenfluramine, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin. For ASMs, with available information on levels in breastfed infants, very low concentrations (in the order of 10% or less of maternal serum concentrations) were reported for carbamazepine, gabapentin, levetiracetam, oxcarbazepine, phenytoin, valproate, and clonazepam. Slightly higher levels (up to approximately 30% of maternal serum concentrations) have been observed with lamotrigine and topiramate, and in single case reports for brivaracetam, lacosamide, and perampanel. High infant levels (30% up to 100% of maternal serum concentrations) have been reported with ethosuximide, phenobarbital and zonisamide. Adverse infant effects during breastfeeding by mothers on ASMs appear to be rare regardless of the type of ASM, but systematic study is limited. Prospective long-term follow-up studies of developmental outcomes among children who have been breastfed by mothers taking ASMs are sparse and have mainly involved children whose mothers were taking carbamazepine, lamotrigine, levetiracetam, phenytoin or valproate as monotherapy while breastfeeding. Although these studies have not indicated poorer outcome among breastfed children compared with those who were not breastfed, further data on long-term outcomes are needed to draw firm conclusions. It is concluded that breastfeeding should in general be encouraged in women taking ASMs, given the well-established benefits of breastfeeding with regard to both short- and long-term infant health in the general population. Counselling needs to be individualized including information on the current knowledge regarding the woman's specific ASM treatment.

Topics: Breast Feeding; Cannabidiol; Carbamazepine; Child; Clobazam; Clonazepam; Epilepsy; Ethosuximide; Everolimus; Felbamate; Female; Fenfluramine; Gabapentin; Humans; Infant; Lacosamide; Lamotrigine; Levetiracetam; Oxcarbazepine; Phenobarbital; Phenytoin; Prospective Studies; Tiagabine; Topiramate; Valproic Acid; Vigabatrin; Zonisamide

Status epilepticus is defined as the situation resulting from the failure of the mechanisms responsible for terminating an epileptic seizure. In 2015, an operational concept was adopted internationally in which two times are identified: a first time, at which treatment must begin (five minutes for convulsive status, 10-15 minutes for focal and non-convulsive status); and a second time, after which there is considered to be a high risk of subsequent sequelae (30 minutes in the case of the convulsive). It occurs in 3-42/100,000 children per year, who are refractory or super-refractory in 10-40% of cases.. This article will review the different therapeutic options for status, from early treatment at home to the different first-line (benzodiazepines), second-line (phenobarbital, valproic acid, phenytoin, levetiracetam and lacosamide) or third-line treatments, which include both pharmacological (anaesthetics, propofol, ketamine, lidocaine, topiramate, brivaracetam or perampanel) and non-pharmacological (ketogenic diet, immunomodulatory treatments or epilepsy surgery) therapies.. Early identification and treatment of a prolonged crisis are essential to prevent progression to status. Although with fewer sequelae than in adults, status epilepticus in children represents a cause of mortality of up to 3-5%, while 25% of them will develop subsequent epilepsy, as well as a considerable percentage of neurological sequelae.. Estado epiléptico pediátrico.. Introducción. El estado epiléptico se define como la situación resultante del fallo de los mecanismos responsables de finalizar una crisis epiléptica. En 2015, se adoptó internacionalmente un concepto operativo en el que se identifican dos tiempos: un primer momento, en el que hay que comenzar un tratamiento (cinco minutos para los estados convulsivos, 10-15 minutos para los estados focales y no convulsivos); y un segundo tiempo, a partir del cual se considera que hay un riesgo elevado de secuelas posteriores (30 minutos en los convulsivos). Ocurre en 3-42/100.000 niños al año, y son refractarios o superrefractarios en el 10-40% de las ocasiones. Desarrollo. En este artículo se revisarán las diferentes opciones terapéuticas del estado, desde el tratamiento precoz domiciliario hasta los diferentes tratamientos de primera línea (benzodiacepinas), segunda línea (fenobarbital, ácido valproico, fenitoína, levetiracetam y lacosamida) o tercera línea, que incluyen tanto terapias farmacológicas (anestésicos, propofol, cetamina, lidocaína, topiramato, brivaracetam o perampanel) como no farmacológicas (dieta cetógena, tratamientos inmunomoduladores o cirugía de epilepsia). Conclusiones. Son fundamentales la identificación y el tratamiento precoz de una crisis prolongada para evitar la evolución a estado. Aunque con menores secuelas que en los adultos, el estado epiléptico en niños representa una causa de mortalidad hasta del 3-5%, al mismo tiempo que un 25% de ellos desarrollará una epilepsia posterior, así como un porcentaje considerable de secuelas neurológicas.

Topics: Adult; Anesthetics; Anticonvulsants; Benzodiazepines; Child; Epilepsy; Humans; Ketamine; Lacosamide; Levetiracetam; Lidocaine; Phenobarbital; Phenytoin; Propofol; Seizures; Status Epilepticus; Topiramate; Valproic Acid

Neonatal stroke is the second cause of acute symptomatic neonatal seizures after hypoxic-ischemic encephalopathy. The aim of this systematic review is to determine which drug among those available represents the best therapeutic choice for treatment of secondary seizures due to neonatal stroke.. We performed a systematic review searching on PubMed the keywords "Neonatal", "Stroke", "Seizures" and "Treatment". Search was limited only to English language with no time limit. Last literature search was done on May 30, 2022.. We selected 5 articles involving a total of 52 full-term neonates. In 96.1% the first line treatment was phenobarbital and in 3.9% was used phenobarbital associated with midazolam from the seizure onset but in all of these cases it was necessary to introduce further medications for controlling the seizures. As second line treatment was used lidocaine (response rate of 53.3%), midazolam (response rate of 15.38%) bumetanide (response rate of 100%), and fosphenytoin (no response). As third line treatment was used lidocaine (response rate of 87.5%), Midazolam (response rate of 60%), levetiracetam and clonazepam (response rate of 100%).. Our review shows that the use of ASMs that act throughout a gabaergic mechanism are inadequate in controlling seizures secondary to neonatal stroke in full-term newborns. Very effective seems to be lidocaine and levetiracetam with an apparent safer profile in short and long term. Bumetanide shows promising results, but they need to be confirmed by phase 3 studies.

Topics: Anticonvulsants; Bumetanide; Epilepsy; Humans; Infant, Newborn; Infant, Newborn, Diseases; Levetiracetam; Lidocaine; Midazolam; Phenobarbital; Stroke

Neonatal seizures represent the most frequent presenting sign of any neurological abnormality secondary to various etiologies in the neonatal period. Phenobarbitone (PB) has been used as first-line anti-epileptic drug in the treatment of seizures but concerns have been raised regarding its neuro-apoptotic effects over the developing brain. Levetiracetam (LEV) is a newer anti-epileptic drug with neuroprotective property and has been used in adults and pediatric patient but its use in neonates have very limited experience. Recently many neonatal studies have sought the role of LEV in the management of neonatal seizures.. To evaluate the efficacy of Levetiracetam in the management of neonatal seizures.. The literature search was done for this systematic review by searching the Cochrane Central Register of Controlled Trials (CENTRAL), and other various electronic databases including PubMed and various sites for ongoing trials and abstracts of conferences.. Two eligible studies were analyzed that fulfilled the inclusion criteria of the systematic review. Fifteen studies were excluded due to the non-fulfillment of inclusion criteria. The primary outcome of both studies was to see the efficiency of LEV in controlling neonatal seizures when compared to PB. Better seizure control after a single loading dose of LEV was seen. Rates of seizure cessation at 24 h was also better in the LEV arm. Neonatal seizures secondary to hypoxic-ischemic encephalopathy (HIE) and receiving therapeutic hypothermia were better controlled with LEV. The side effect of LEV was significantly less when compared to PB.. Levetiracetam has shown to have promising anti-epileptic properties for the management of neonatal seizure with better efficacy and less or no side effects. There is a need to conduct more randomized controlled trials seeking the role of LEV in the acute management of neonatal seizures and also for assessing its neuroprotective role and neurodevelopmental outcome in these neonates.

Topics: Adult; Anticonvulsants; Child; Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Piracetam; Seizures

Patients with dementia have an increased risk of developing epilepsy, especially in patients with vascular dementia and Alzheimer's disease. In selecting the optimal anti- epileptic drug (AED), the possible side effects such as drowsiness and worsening of cognitive function should be taken into consideration, together with co-morbidities and type of epilepsy.. The current systematic review investigates the efficacy, tolerability, and changes in cognitive function after administration of AED in patients with dementia and epilepsy.. We searched six databases, including MEDLINE and CENTRAL, checked reference lists, contacted experts, and searched Google Scholar to identify studies reporting randomized trials. Studies identified were independently screened, data extracted, and quality appraised by two researchers. A narrative synthesis was used to report findings.. We included one study with 95 patients with Alzheimer's disease randomized to either levetiracetam, lamotrigine, or phenobarbital. No significant differences were found for efficacy, but patients receiving levetiracetam showed an improvement in mini-mental state examination scores and had fewer adverse events.. High-quality evidence in the form of randomized controlled trials to guide clinicians in choosing an AED in patients with dementia and concomitant epilepsy remains scarce. However, levetiracetam has previously been shown to possibly improve cognition in patients with both mild cognitive impairment and Alzheimer's disease, is better tolerated in the elderly population, and has no clinically relevant interaction with either cholinesterase inhibitors or NMDA receptor antagonists.

Topics: Aged; Alzheimer Disease; Anticonvulsants; Epilepsy; Humans; Lamotrigine; Levetiracetam; Randomized Controlled Trials as Topic

It is challenging to balance the fetal risks associated with the use of antiepileptic drugs (AEDs) against maternal and fetal risks of seizure worsening, and therefore it is very important to define and distinguish the possible risks entailed by different AEDs. This paper aims to undertake a comprehensive review regarding the possible risks of four classical (phenytoin, carbamazepine, phenobarbital, and valproate) and two newer (lamotrigine and levetiracetam) AEDs during pregnancy. The review focuses on major and organ-specific malformations, dose-dependent risks, mono vs polytherapy, and clinical pharmacokinetics. A discussion regarding the safety of AED use during breastfeeding is also provided.

Topics: Anticonvulsants; Breast Feeding; Carbamazepine; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Phenobarbital; Phenytoin; Pregnancy; Pregnancy Complications; Valproic Acid

Any type of seizure can be observed in Alzheimer's disease. Antiepileptic drugs seem to prevent the recurrence of epileptic seizures in most people with Alzheimer's disease. There are pharmacological and non-pharmacological treatments for epilepsy in people with Alzheimer's disease, however there are no current systematic reviews to evaluate the efficacy and tolerability of these treatments. This review aims to investigate these different modalities. This is an updated version of the Cochrane Review previously published in 2018.. To assess the efficacy and tolerability of pharmacological or non-pharmacological interventions for the treatment of epilepsy in people with Alzheimer's disease (including sporadic Alzheimer's disease and dominantly inherited Alzheimer's disease).. For the latest update, on 3 August 2020 we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 31 July 2020). CRS Web includes randomized or quasi-randomized controlled trials from PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups, including Cochrane Epilepsy. In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers, reference lists and relevant conference proceedings; we also contacted trial authors and pharmaceutical companies.. We included randomized and quasi-randomized controlled trials investigating treatment for epilepsy in people with Alzheimer's disease, with the primary outcomes of proportion of participants with seizure freedom and proportion of participants experiencing adverse events.. Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to there being limited available data.. We included one randomized controlled trial (RCT) on pharmacological interventions; the trial included 95 participants. No studies were found for non-pharmacological interventions. Concerning the proportion of participants with seizure freedom, no significant differences were found for the comparisons of levetiracetam versus lamotrigine (RR) 1.20, 95% CI 0.53 to 2.71; 67 participants; very low-certainty evidence), levetiracetam versus phenobarbital (RR 1.01, 95% CI 0.47 to 2.19; 66 participants; very low-certainty evidence), or lamotrigine versus phenobarbital (RR 0.84, 95% CI 0.35 to 2.02; 57 participants; very low-certainty evidence). It seemed that levetiracetam could improve cognition and lamotrigine could relieve depression, while phenobarbital and lamotrigine could worsen cognition, and levetiracetam and phenobarbital could worsen mood. The risk of bias relating to allocation, blinding and selective reporting was unclear. We judged the certainty of the evidence for all outcomes to be very low.. This review does not provide sufficient evidence to support levetiracetam, phenobarbital or lamotrigine for the treatment of epilepsy in people with Alzheimer's disease. Regarding efficacy and tolerability, no significant differences were found between levetiracetam, phenobarbital and lamotrigine. Large RCTs with a double-blind, parallel-group design are required to determine the efficacy and tolerability of treatment for epilepsy in people with Alzheimer's disease.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Anticonvulsants; Cognition; Depression; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Phenobarbital; Randomized Controlled Trials as Topic; Secondary Prevention

There is no definite proven or accepted strategy in the management of patients with focal epilepsy uncontrolled by the first anti-seizure medication (ASM). Clinical studies failed to find a significant difference in efficacy or tolerability between alternative monotherapy and/or adjunctive therapy in these patients. A second ASM is often added, the efficacy of the combination is assessed, and the dose of the first drug can be gradually reduced and withdrawn. If seizures recur, the effective combination therapy can be reinstated. In this review, we discussed experimental and clinical data about the efficacy and tolerability of the most frequently used combinations of ASMs. Animal studies suggested that the most favorable combinations are those between ASMs with different or multiple mechanisms of action, whereas combining drugs with similar pharmacodynamic properties is often associated with additive or infra-additive efficacy and additive or synergistic toxicity. Clinical studies have shown that levetiracetam (LEV) can be favorably combined with the sodium channel blockers (SCBs) lacosamide (LCM) and lamotrigine (LTG). Lamotrigine is particularly effective when associated with valproate (VPA) and possibly with LEV and topiramate (TPM). Carbamazepine (CBZ) has negative pharmacokinetic interactions with several ASMs and should not be combined with other SCBs; it could be effectively and safely combined with gabapentin (GBP) and LEV. Valproic acid has enzyme inhibiting properties and can be cautiously used with SCBs; its combination with TPM or zonisamide (ZNS) may be associated with higher toxicity.

Topics: Animals; Anticonvulsants; Epilepsy; Humans; Lamotrigine; Levetiracetam; Seizures

Topics: Adolescent; Adult; Anticonvulsants; Diagnosis, Differential; Electroencephalography; Epilepsy; Ethanol; Female; Humans; Lamotrigine; Levetiracetam; Practice Guidelines as Topic; Seizures; Valproic Acid

Among people with epilepsy, levetiracetam (LEV) can cause neuropsychiatric adverse events (NPAEs) that impact negatively on quality of life. It has been suggested that pyridoxine can ameliorate LEV-related NPAEs. We conducted a systematic review of studies on the use of pyridoxine supplementation to relieve NPAEs associated with LEV therapy.. The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline, EMBASE, Scholar, Cochrane-CENTRAL (2000-2019), and EThOS platform were searched for studies on the use of pyridoxine in patients with LEV-related NPAEs. Proportions of patients reported to benefit from pyridoxine supplementation were tabulated, and a random-effect model meta-analysis was conducted.. Eleven retrospective studies/case reports and one randomized prospective study, mostly including pediatric populations, were identified. Retrospective studies, which were rated as low quality due to failure to control for bias, reported an overall improvement of NPAEs after pyridoxine supplementation in 72.5% (108/149) of patients. The proportion of patients showing improvement in a pooled analysis of the four largest retrospective studies (n = 134) was 72.1% (95% confidence interval (CI) 47.1-88.3), although there was high heterogeneity across studies (I. This systematic review suggests that pyridoxine might be of benefit in relieving LEV-related NPAEs. However, the quality of the evidence is poor, and better-designed prospective studies that include quantitative as well as qualitative data are needed to define the role of pyridoxine in the management of LEV-related NPAEs.

Topics: Anticonvulsants; Diagnostic Tests, Routine; Dietary Supplements; Drug Therapy, Combination; Epilepsy; Humans; Levetiracetam; Mental Disorders; Prospective Studies; Pyridoxine; Quality of Life; Retrospective Studies; Vitamin B Complex

Recently, there have been an increased number of reports on levetiracetam (LEV) induced cutaneous adverse drug reactions (CADRs). We aimed to identify and critically evaluate all the descriptive studies on LEV induced-CADRs and to describe the possible clinical manifestations, management, and treatment outcomes of the condition.. PubMed and grey literature databases were searched from inception to June 2019 without any restriction. We also performed a bibliographic search for additional studies. Only descriptive studies on LEV-induced CADRs were included for our review. Study selection, data abstraction and quality assessment were performed by two contributors independently and disagreements were settled through consensus or through discussion with a third reviewer.. Data from 24 out of 88 studies, which included 25 patients (12 female and 13 male) aged from 40 weeks to 73 years, were reviewed. Patients received between 500 mg/day to 3000 mg/day of LEV. Drug reaction with eosinophilia and systemic symptoms syndrome, Steven-Johnson syndrome, toxic epidermal necrolysis, acute generalised exanthematous pustulosis, generalised hyperpigmentation and leucocytoclastic vasculitis were observed among the included patients. Immediate cessation of LEV, providing supportive care and use of topical antihistamines and anti-inflammatory drugs appeared to be the mainstay of management, and all patients were found to have recovered.. Clinicians should be aware of the possible CADRs induced by LEV to avoid the development of a potentially fatal condition. Immediate withdrawal of the drug and supporting care seem to be effective in the management of the CADRs.. International Prospective Register for Systematic Reviews (PROSPERO) number CRD42019141002.

Topics: Anticonvulsants; Drug Eruptions; Epilepsy; Histamine Antagonists; Humans; Levetiracetam; Withholding Treatment

Prevention of epilepsy is a great unmet need. Acute central nervous system (CNS) insults such as traumatic brain injury (TBI), cerebrovascular accidents (CVA), and CNS infections account for 15%-20% of all epilepsy. Following TBI and CVA, there is a latency of days to years before epilepsy develops. This allows treatment to prevent or modify postinjury epilepsy. No such treatment exists. In animal models of acquired epilepsy, a number of medications in clinical use for diverse indications have been shown to have antiepileptogenic or disease-modifying effects, including medications with excellent side effect profiles. These include atorvastatin, ceftriaxone, losartan, isoflurane, N-acetylcysteine, and the antiseizure medications levetiracetam, brivaracetam, topiramate, gabapentin, pregabalin, vigabatrin, and eslicarbazepine acetate. In addition, there are preclinical antiepileptogenic data for anakinra, rapamycin, fingolimod, and erythropoietin, although these medications have potential for more serious side effects. However, except for vigabatrin, there have been almost no translation studies to prevent or modify epilepsy using these potentially "repurposable" medications. We may be missing an opportunity to develop preventive treatment for epilepsy by not evaluating these medications clinically. One reason for the lack of translation studies is that the preclinical data for most of these medications are disparate in terms of types of injury, models within different injury type, dosing, injury-treatment initiation latencies, treatment duration, and epilepsy outcome evaluation mode and duration. This makes it difficult to compare the relative strength of antiepileptogenic evidence across the molecules, and difficult to determine which drug(s) would be the best to evaluate clinically. Furthermore, most preclinical antiepileptogenic studies lack information needed for translation, such as dose-blood level relationship, brain target engagement, and dose-response, and many use treatment parameters that cannot be applied clinically, for example, treatment initiation before or at the time of injury and dosing higher than tolerated human equivalent dosing. Here, we review animal and human antiepileptogenic evidence for these medications. We highlight the gaps in our knowledge for each molecule that need to be filled in order to consider clinical translation, and we suggest a platform of preclinical antiepileptogenesis evaluation of potentially repurposable molecu

Topics: Acetylcysteine; Animals; Anticonvulsants; Antioxidants; Atorvastatin; Brain Injuries, Traumatic; Ceftriaxone; Dibenzazepines; Drug Repositioning; Epilepsy; Epilepsy, Post-Traumatic; Erythropoietin; Fingolimod Hydrochloride; GABA Agents; Gabapentin; Humans; Immunologic Factors; Inflammation; Interleukin 1 Receptor Antagonist Protein; Isoflurane; Levetiracetam; Losartan; Neuroprotective Agents; Oxidative Stress; Pregabalin; Pyrrolidinones; Sirolimus; Stroke; Topiramate; Translational Research, Biomedical; Vigabatrin

To identify clinical characteristics common among epileptic patients prescribed levetiracetam who report suicidal ideation or who exhibit suicidal behavior. A case is also provided that highlights the need for increased vigilance for neuropsychiatric sequelae in fragile epileptic patients prescribed levetiracetam, especially post dosage adjustment.. PubMed was queried with no time limitation to December 2018 using a combination of controlled terms. Using the Boolean operators "AND" and "OR," the authors searched PubMed for case reports and case series on levetiracetam-related suicidal behavior. The search terms used were [levetiracetam] OR [Keppra] AND in combination with suicidal, suicide, suicidal ideation, suicide attempt, and suicidality.. Relevant English-language human studies on levetiracetam and its effect on suicidal behavior were included. The search terms generated 78 results from the databases. After excluding all duplicates and applying the inclusion and exclusion criteria, a total of 14 clinical studies were retained for review.. Two reviewers independently extracted relevant data and assessed the methodological quality of each study.. The included studies reveal a number of risk factors for suicide ideation, suicide-related behavior, and suicide attempt among individuals taking levetiracetam. These risk factors include a prior psychiatric disorder, a history of traumatic brain injury, a history of substance use disorder, and a structural brain abnormality. Patients with these risk factors constitute a specific subgroup of patients with epilepsy who have an increased vulnerability to suicidal ideation or behavior if prescribed levetiracetam. These patients should, therefore, be monitored closely.. Suicidal behavior in epileptic patients appears to be multifactorial in etiology. Psychiatric disorders are more prevalent in epileptic patients than in the general population and contribute to this risk. In spite of the high risk of suicidal behavior with the use of antiepileptic drugs, studies have shown that the benefits of anticonvulsant therapy often outweigh the risks. Nevertheless, timely consultation with a psychiatrist is invaluable in the care of these patients, particularly those with multiple risk factors, as in the index case. The risk of suicidality should be balanced with the risk of uncontrolled seizures. Specifically, in the case of levetiracetam, it is important to be aware of the subgroup of individuals with prior severe psychiatric illness, a history of traumatic brain injury, or a history of substance use disorder who might be at an increased risk of developing suicide-related behavior and suicidal ideations once levetiracetam is started.

Topics: Aged; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Male; Suicidal Ideation; Suicide, Attempted

We conducted this meta-analysis to evaluate effects of second-generation anti-epileptic drugs (AEDs; levetiracetam, lamotrigine) compared to first-generation AEDs (valproic acid, carbamazepine) on bone metabolism in epilepsy patients. PubMed, Web of Science, Clinical trials.gov, Wanfang, and China national knowledge infrastructure databases were searched. Ten trials were included. Results showed: (1) The overall SMD for changes of serum calcium, phosphorus, ALP, and PTH levels from baseline of LEV versus first-generation AEDs were 1.00 (95% CI=0.23-1.77, Z=2.56, p=0.01), 0.98 (95% CI=- 0.05 to 2.01, Z=1.86, p=0.06), - 1.17 (95% CI=- 2.08 to - 0.25, Z=2.50, p=0.01), 0.07 (95% CI=- 0.14 to 0.27, Z=0.63, p=0.53), respectively. (2) The overall SMD for changes of serum calcium, phosphorus, ALP, and PTH levels from baseline of LTG versus first-generation AEDs were -0.16 (95% CI=- 0.47 to 0.16, Z=0.99, p=0.32), -0.05 (95% CI=- 0.55 to 0.44, Z=0.22, p=0.83), 0.10 (95% CI=- 0.53 to 0.73, Z=0.31, p=0.75), -0.05 (95% CI=- 0.52 to 0.42, Z=0.22, p=0.83), respectively. Overall, our results indicate that compared to first-generation AEDs, LEV has less adverse effects on blood bone metabolism markers in epilepsy patients, while LTG does not. However, due to small number of included studies, our results warrant additional research.

Topics: Anticonvulsants; Bone and Bones; Carbamazepine; Clinical Trials as Topic; Epilepsy; Humans; Lamotrigine; Levetiracetam; Prognosis; Valproic Acid

Perampanel como terapia añadida precoz en el tratamiento de la epilepsia.

Topics: Adolescent; Adult; Anticonvulsants; Drug Synergism; Drug Therapy, Combination; Epilepsy; Gastrointestinal Diseases; Humans; Levetiracetam; Nitriles; Pyridones; Randomized Controlled Trials as Topic; Sleepiness; Treatment Outcome; Young Adult

To estimate the comparative efficacy and safety of antiepileptic drugs (AEDs) in the elderly with new-onset epilepsy.. We searched electronic databases for randomized controlled trials (RCTs) of monotherapy AEDs to treat epilepsy in elderly. The following outcomes were analyzed: seizure freedom and withdrawal from the study for any cause at 6 and 12 months; withdrawal from the study for any adverse event (AE) at 12 months; and occurrence of any AE at 12 months. Effect sizes were estimated by network meta-analyses within a frequentist framework. The hierarchy of competing interventions was established using the surface under the cumulative ranking curve (SUCRA) and mean ranks.. Five RCTs (1425 patients) were included. Included AEDs were carbamazepine immediate- and controlled-release (CBZ-IR, CBZ-CR), gabapentin (GBP), lacosamide (LCM), lamotrigine (LTG), levetiracetam (LEV), phenytoin (PHT), and valproic acid (VPA). At the pairwise and network meta-analyses, there were no differences in any of the comparison according to 6- and 12-month seizure freedom. The treatment with CBZ-IR and CBZ-CR was associated with a higher risk of withdrawal than LTG, LEV, or VPA, and CBZ-IR had the overall highest probability of discontinuation across all AEDs. According to SUCRA, the following had the greatest likelihood ranking best for seizure freedom at 6 and 12 months: LCM, LTG, and LEV. CBZ-CR and CBZ-IR had the highest probabilities of being worst for the 12-month retention. CBZ-IR, CBZ-CR, and GBP had the highest probabilities of withdrawal from the study for AEs, , and VPA had the highest probability of being the best-tolerated option.. Although no significant difference in efficacy was found across treatments, LCM, LTG, and LEV had the highest probability of ranking best for achieving seizure freedom. CBZ-IR and CBZ-CR showed a poor tolerability profile, leading to higher withdrawal rates compared to LEV and VPA.

Topics: Aged; Anticonvulsants; Carbamazepine; Epilepsy; Female; Gabapentin; Humans; Levetiracetam; Male; Network Meta-Analysis; Randomized Controlled Trials as Topic

Seizures are common in patients with brain tumours, even though prophylactic anti-seizure treatment for all patients with brain tumours is not recommended. Newer anti-epileptic drugs have shown benefits that outweigh the side effects of treatment and can also be given in combination with traditional anti-epileptic drugs. The authors have reviewed the literature on the various combinations of anti-epileptics in patients with seizures and brain tumours.

Topics: Anticonvulsants; Brain Neoplasms; Drug Therapy, Combination; Epilepsy; Gabapentin; Glioma; Humans; Lamotrigine; Levetiracetam; Neoplasm Grading; Phenytoin; Survival Rate; Topiramate; Valproic Acid; Zonisamide

Seizures occur commonly in cats and can be classified as idiopathic epilepsy, structural epilepsy, or reactive seizures. Pursuit of a diagnosis may include a complete blood count, serum biochemistry, brain MRI, and cerebrospinal fluid analysis as indicated. Antiepileptic drugs should be considered if a cat is having frequent seizures, or any 1 seizure longer than 5 minutes. Phenobarbital is often the drug of choice; however, levetiracetam may be more useful for certain types of epilepsy in cats. Long-term prognosis depends on the underlying diagnosis and response to therapy.

Topics: Animals; Anticonvulsants; Cat Diseases; Cats; Epilepsy; Levetiracetam; Phenobarbital; Piracetam; Prognosis; Risk Factors; 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

The prevalence of epilepsy is estimated 5-10 per 1000 population and around 70% of patients with epilepsy can be sufficiently controlled by antiepileptic drugs (AEDs). Epileptogenesis is the process responsible for converting normal into an epileptic brain and mechanisms responsible include among others: inflammation, neurodegeneration, neurogenesis, neural reorganization and plasticity. Some AEDs may be antiepileptiogenic (diazepam, eslicarbazepine) but the correlation between neuroprotection and inhibition of epileptogenesis is not evident. Antiepileptogenic activity has been postulated for mTOR ligands, resveratrol and losartan. So far, clinical evidence gives some hope for levetiracetam as an AED inhibiting epileptogenesis in neurosurgical patients. Biomarkers for epileptogenesis are needed for the proper selection of patients for evaluation of potential antiepileptogenic compounds.

Topics: Animals; Anticonvulsants; Biomarkers; Brain; Dibenzazepines; Epilepsy; Humans; Levetiracetam; Piracetam

The case report aims to discuss the clinical symptoms and treatment of encephalopathy caused by a novel syntaxin- binding protein 1 (STXBP1) genetic mutation.. The patient, a girl, was born at 38+4 weeks of gestation. She had frequent spasm attacks accompanied by obvious psychomotor development retardation since the neonatal period. Genetic screening identified a novel STXBP1 genetic mutation.. Early-onset epileptic encephalopathy with STXBP1 mutation.. We adjusted the antiepileptic strategy to oral levetiracetam and topiramate, and intravenous administration of adrenocorticotropic hormone(ACTH) for 2 weeks. Subsequently, prednisone was continued, and gradually reduced and withdrawn over 3 months.. The treatment was effective with complete control of the epileptic seizures and improvements in the electroencephalogram readings. However, the effects on psychomotor ability were slow and limited. A literature review of STXBP1 mutation cases in which ACTH was administered showed that complete seizure control is observed in 60% of cases, 20% are partially affected, and the remaining 20% show no effect.. ACTH and levetiracetam had good therapeutic effects in epilepsy control in this case of de novo STXBP1 mutation. ACTH is an effective drug for early-onset epileptic encephalopathy caused by STXBP1 mutation. However, controlling epilepsy using this therapy does not alter the psychomotor development retardation caused by the STXBP1 mutation.

Topics: Adrenocorticotropic Hormone; Anticonvulsants; Brain Diseases; Electroencephalography; Epilepsy; Female; Hormones; Humans; Infant; Levetiracetam; Munc18 Proteins; Mutation; Piracetam; Prednisone; Psychomotor Performance; Treatment Outcome

Therapeutic Drug Monitoring (TDM) of anti-epileptic drugs (AEDs) is not routinely performed, although this can guide the dosage regimen to achieve greater efficacy and safety. Levetiracetam (LEV) has been introduced as an AED with an almost perfect pharmacokinetic (PK) profile. Nonetheless, recent research challenges this statement and therefore we aimed to explore factors that modify LEV PK. Age and enzyme-inducing drugs (EIDs) appear to be major factors influencing the PK profile of LEV. Therefore, 30-50% lower dosages should be used in the elderly (> 65 years of age) and the dosing regimen should be guided by monitoring SDC (TDM). In contrast, higher LEV dosages are necessary in children aged between 2 months and 12 years (compared to adults) due to a 30-70% increase of LEV clearance (CL). Higher dosages are also required if a patient receives EIDs, again due to a higher CL of LEV (range 24-60%). This could also be true for pregnant women. LEV TDM is currently not common in the clinical setting due to the wide therapeutic range and the low prevalence of side-effects. However, LEV dose should on the one hand be increased in certain physiological situations (pregnancy, neonates) and patients on EIDs (especially carbamazepine). On the other hand, dose reductions are necessary when the LEV CL is impaired (elderly). Nevertheless, current data to support regular LEV TDM are lacking. Prospective research is needed to explore the importance of LEV TDM in elected patient groups; i.e. neonates, elderly, patients on EIDs and pregnant women.

Topics: Anticonvulsants; Drug Monitoring; Epilepsy; Humans; Levetiracetam

Any type of seizure can be observed in Alzheimer's disease (AD). Antiepileptic drugs seem to prevent the recurrence of epileptic seizures in most people with AD. There are pharmacological and non-pharmacological treatments for epilepsy in people with AD. There are no current systematic reviews to evaluate the efficacy and tolerability of these treatments; this review aims to review those different modalities. This is an updated version of the original Cochrane Review published in Issue 11, 2016.. To assess the efficacy and tolerability of pharmacological or non-pharmacological interventions for the treatment of epilepsy in people with AD (including sporadic AD and dominantly inherited AD).. For the latest update, on 10 July 2018 we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group's Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid 1946- ), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted authors and pharmaceutical companies.. We included randomized and quasi-randomized controlled trials investigating treatment for epilepsy in people with AD, with the outcomes of proportion of participants with seizure freedom or proportion of participants experiencing adverse events.. Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to the limited available data.. We included one randomized controlled trial on pharmacological interventions with 95 participants. No studies were found for non-pharmacological interventions. Concerning the proportion of participants with seizure freedom, no significant differences were found for the comparisons of levetiracetam (LEV) versus lamotrigine (LTG) (risk ratio (RR) 1.20, 95% confidence interval (CI) 0.53 to 2.71), LEV versus phenobarbital (PB) (RR 1.01, 95% CI 0.47 to 2.19), or LTG versus PB (RR 0.84, 95% CI 0.35 to 2.02). It seemed that LEV could improve cognition and LTG could relieve depression, while PB and LTG could worsen cognition, and LEV and PB could worsen mood. Unclear risk of bias was found in allocation, blinding and selective reporting. We judged the quality of the evidence to be very low.. This review does not provide sufficient evidence to support LEV, PB or LTG for the treatment of epilepsy in people with AD. Regarding efficacy and tolerability, no significant differences were found between LEV, PB and LTG. Large randomized controlled trials with a double-blind, parallel-group design are required to determine the efficacy and tolerability of treatment for epilepsy in people with AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Anticonvulsants; Cognition; Depression; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Phenobarbital; Secondary Prevention

Antiepileptic drugs (AEDs) are effective against seizures, but their use is often limited by adverse effects, among them psychiatric and behavioral ones including aggressive behavior (AB). Knowledge of the incidence, risk factors, and the underlying mechanisms of AB induced by AEDs may help to facilitate management and reduce the risk of such side effects. The exact incidence of AB as an adverse effect of AEDs is difficult to estimate, but frequencies up to 16% have been reported. Primarily, levetiracetam (LEV), perampanel (PER), and topiramate (TPM), which have diverse mechanisms of action, have been associated with AB. Currently, there is no evidence for a specific pharmacological mechanism solely explaining the increased incidence of AB with LEV, PER, and TPM. Serotonin (5-HT) and GABA, and particularly glutamate (via the AMPA receptor), seem to play key roles. Other mechanisms involve hormones, epigenetics, and "alternative psychosis" and related phenomena. Increased individual susceptibility due to an underlying neurological and/or a mental health disorder may further explain why people with epilepsy are at an increased risk of AB when using AEDs. Remarkably, AB may occur with a delay of weeks or months after start of treatment. Information to patients, relatives, and caregivers, as well as sufficient clinical follow-up, is crucial, and there is a need for further research to understand the complex relationship between AED mechanisms of action and the induction/worsening of AB.

Topics: Aggression; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Nitriles; Pyridones; Topiramate

Levetiracetam is a broad-spectrum antiepileptic drug (AED) with a unique mechanism of action. Older AEDs can cause serious short- and long-term adverse drug reactions and complications, rendering them undesirable to use in pediatric patients. Characteristics that make levetiracetam a near-ideal AED include its broad spectrum of activity, good tolerability profile, and minimal drug-drug interactions. Clinical pharmacokinetic monitoring (CPM) is often recommended in pediatric patients for certain AEDs due to large interindividual pharmacokinetic differences and unpredictable drug disposition. Our objective was to determine whether monitoring levetiracetam concentrations is warranted for pediatric patients with epilepsy, using a previously published 9-step decision-making algorithm. A literature search of the MEDLINE (1946-August 2016), EMBASE (1974-August 2016), CENTRAL, and Google Scholar databases was performed to identify relevant English-language articles and answer the questions posed in the algorithm for levetiracetam CPM in pediatric epilepsies. Additional articles were identified from a manual bibliographic review of the relevant literature. We found that levetiracetam CPM met some criteria of the algorithm: levetiracetam is an appropriate adjunctive or monotherapy for pediatric patients with either focal or generalized seizures; it is readily measurable in plasma, with an appropriate degree of sensitivity, accuracy, and precision; it exhibits interindividual variation in pharmacokinetics; often, its pharmacologic effect cannot be easily measured; and the duration of therapy is expected to be long-term. However, important criteria not met include the following: there is no clear evidence for a concentration-response relationship for efficacy or toxicity; the proposed therapeutic range of 12-46 μg/mL is not well-defined and is generally considered as wide. Thus, clinical decision making is unlikely to be affected as a result of routine levetiracetam CPM. In general, routine CPM of levetiracetam cannot be recommended for pediatric patients with epilepsy. However, CPM may be beneficial in select cases, such as patients in whom noncompliance is suspected, those who have severe overdoses, those switching between product brands, or patients for whom an 'individual therapeutic concentration' is documented. Nonetheless, in the majority of pediatric patients with epilepsy, measurement of levetiracetam concentrations is not expected to yield a therapeutic ben

Topics: Anticonvulsants; Drug Monitoring; Epilepsy; Humans; Levetiracetam; Pediatrics; Piracetam

There is ongoing concern whether switching between different antiepileptic drug (AED) products may compromise patient care. We systematically reviewed changes in healthcare utilization following AED switch.. We searched MEDLINE and EMBASE databases (1980-October 2016) for studies that assessed the effect of AED switching in patients with epilepsy on outpatient visits, emergency room visits, hospitalization and hospital stay duration.. A total of 14 articles met the inclusion criteria. All were retrospective studies. Four provided findings for specific AEDs only (lamotrigine, topiramate, phenytoin and divalproex), 9 presented pooled findings from multiple AEDs, and 1 study provided both specific (lamotrigine, topiramate, oxcarbazepine, and levetiracetam) and pooled findings. Three studies found an association between a switch of topiramate and an increase in healthcare utilization. Another three studies found that a brand-to-generic lamotrigine switch was not associated with an increased risk of emergently treated events (ambulance use, ER visits or hospitalization). The outcomes of the pooled AED switch studies were inconsistent; 5 studies reported an increased healthcare utilization while 5 studies did not.. Studies that have examined the association between an AED switch and a change in healthcare utilization report conflicting findings. Factors that may explain these inconsistent outcomes include inter-study differences in the type of analysis undertaken (pooled vs individual AED data), the covariates used for data adjustment, and the type of switch examined. Future medical claim database studies employing a prospective design are encouraged to address these and other factors in order to enhance inter-study comparability and extrapolation of findings.

Topics: Adult; Anticonvulsants; Drug Substitution; Drugs, Generic; Epilepsy; Female; Fructose; Humans; Levetiracetam; Male; Patient Acceptance of Health Care; Piracetam; Prospective Studies; Retrospective Studies; Topiramate; 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

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

Epilepsy is significantly more frequent in AD patients than in age-matched controls, even though the true extent of the phenomenon is not clear yet. Areas covered: In this review, we describe in detail the available data on the pharmacological treatment of epilepsy in patients with AD. We also briefly describe general principles of AEDs use in elderly, as well as the potential cognitive profile of AEDs and safety of concomitant psychotropic drugs in patients with epilepsy and AD. Expert commentary: As some preclinical data suggest a role of epileptiform discharges in cognitive decline in AD, a prompt diagnosis and treatment of seizures in these patients should be pursued. The few data on the use of AEDs in AD patients suggest that newer AEDs (in particular lamotrigine and levetiracetam) might be good choices. Experimental data even support a potential role of some AEDs in modifying the disease course of AD.

Topics: Alzheimer Disease; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Piracetam; Seizures

New information about antiepileptic drugs has arisen since the publication of the Hong Kong Epilepsy Guideline in 2009. This article set out to fill the knowledge gap between 2007 and 2016 on the use of antiepileptic drugs in Hong Kong.. Between May 2014 and April 2016, four consensus meetings were held in Hong Kong, where a group comprising 15 professionals (neurologists, paediatricians, neurosurgeons, radiologists, and clinical psychologists) from both public and private sectors aimed to review the best available evidence and update all practising physicians on a range of clinical issues including drug-related matters. All participants were council members of The Hong Kong Epilepsy Society.. A literature review of the clinical use of antiepileptic drugs as monotherapy suggested Level A evidence for levetiracetam and Level B evidence for lacosamide. No change in the level of evidence was found for oxcarbazepine (Level A evidence) or pregabalin (undesignated), and no evidence was found for perampanel. A literature review on the clinical use of antiepileptic drugs as adjunctive therapy suggested Level A evidence for both lacosamide and perampanel. No change to the level of evidence was found for levetiracetam (Level A evidence), oxcarbazepine (Level A evidence), or pregabalin (Level A evidence). A literature search on the use of generic antiepileptic drugs suggested Level A evidence for the use of lamotrigine in generic substitution.. Three lead authors of the Subcommittee drafted the manuscript that consisted of two parts-part A: evidence on new antiepileptic drugs, and part B: generic drugs. The recommendations on monotherapy/adjunctive therapy were presented during the meetings. The pros and cons for our health care system of generic substitution were discussed. The recommendations represent the 'general consensus' of the participants in keeping with the evidence found in the literature.. Recommendations for the use of levetiracetam, lacosamide, oxcarbazepine, pregabalin, and perampanel were made. The consensus statements may provide a reference to physicians in their daily practice. Controversy exists over the use of generic products among patients who are currently taking brand medications. In this regard, approvals from prescriber and patient are pivotal. Good communication between doctors and patients is essential, as well as enlisting the assistance of doctors, nurses, and pharmacists, therapeutic blood monitoring if available, and the option of brand antiepileptic drug as a self-financed item. The physical appearance of generic drugs should be considered as it may hamper drug compliance. Support from medical services is recommended. In the longer term, the benefit of flexibility and the options to have a balance between the generic and brand drug market may need to be addressed by institutions and regulatory bodies.

Topics: Acetamides; Anticonvulsants; Carbamazepine; Consensus; Drugs, Generic; Epilepsy; Hong Kong; Humans; Lacosamide; Lamotrigine; Levetiracetam; Oxcarbazepine; Piracetam; Practice Guidelines as Topic; Societies, Medical; Triazines

There are over twenty anti-seizure medications and anti-seizure devices available commercially in the United States. The multitude of treatment options for seizures can present a challenge to clinicians, especially those who are not subspecialists in the epilepsy field. Many clinical questions are not adequately answered in double-blind randomized controlled studies. In the presence of a knowledge gap, many clinicians consult a respected colleague with acknowledged expertise in the field. Our survey was designed to provide expert opinions on the treatment of epilepsy in adults and adolescents.. We surveyed a group of 42 physicians across the United States who are considered experts based on publication record in the field of epilepsy, or a leadership role in a National Association of Epilepsy Centers comprehensive epilepsy program. The survey consisted of 43 multiple-part patient scenario questions and was administered online using Redcap software. The experts provided their opinion on 1126 treatment options based on a modified Rand 9-point scale. The patient scenarios focused on genetically-mediated generalized epilepsy and focal epilepsy. The scenarios first focused on overall treatment strategy and then on specific pharmacotherapies. Other questions focused on treatment of specific patient populations (pregnancy, the elderly, patients with brain tumors, and post organ transplant patients), epilepsy patients with comorbidities (renal and hepatic disease, depression), and how to combine medications after failure of monotherapy. Statistical analysis of data used the expert consensus method.. Valproate was considered a drug of choice in all genetically-mediated generalized epilepsies, except in the population of women of child-bearing age. Ethosuximide was a drug of choice in patient with absence seizures, and levetiracetam was a drug of choice in patients with genetic generalized tonic-clonic seizures and myoclonic seizures. Lamotrigine, levetiracetam and oxcarbazepine were considered drugs of choice for initial treatment of focal seizures. Lamotrigine and levetiracetam were the drugs of choice for women of child-bearing age with either genetic generalized epilepsy or focal epilepsy. Lamotrigine and levetiracetam were the drugs of choice in the elderly population. Lamotrigine was preferred in patients with co-morbid depression. Levetiracetam was the drug of choice in treating patients with hepatic failure, or who have undergone organ transplantation. Compared to the 2005 and 2001 surveys, there was increased preference for the use of levetiracetam and lamotrigine, and decreased preference for the use of phenytoin, gabapentin, phenobarbital and carbamazepine.. The study presented here provides a "snapshot" of the clinical practices of experts in the treatment of epilepsy. The experts were very often in agreement, and reached consensus in 81% of the possible responses. However, expert opinion does not replace the medical literature; instead, it acts to supplement existing information. Using the study results is similar to requesting an expert consultation. Our findings suggest options that the clinician should consider to achieve best practice.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Carbamazepine; Child; Depression; Double-Blind Method; Drug Therapy, Combination; Epilepsy; Expert Testimony; Female; Humans; Lamotrigine; Levetiracetam; Oxcarbazepine; Piracetam; Practice Guidelines as Topic; Pregnancy; Surveys and Questionnaires; Treatment Outcome; Triazines

Topics: Anticonvulsants; Blood Specimen Collection; Chromatography, High Pressure Liquid; Drug Stability; Epilepsy; Humans; Levetiracetam; Limit of Detection; Linear Models; Piracetam; Reproducibility of Results

The foetal outcomes of 2,635 pregnancies recorded in the Australian Pregnancy Register were studied. In at least the initial 4months of 515 pregnancies, there had been no intrauterine exposure to antiepileptic drugs, though the women involved in 264 of these pregnancies took antiepileptic drugs in later pregnancies. Compared with these 515 drug-unexposed pregnancies, foetal malformations risks were increased more than five-fold in association with valproate monotherapy, and more than doubled in association with carbamazepine monotherapy (p<0.05). There were no statistically significant increases in malformation rates associated with other more commonly used antiepileptic drugs, while the malformation risk in relation to levetiracetam exposure was lower than that in the drug-unexposed pregnancies. The published literature has rather consistently shown raised malformation rates associated with carbamazepine monotherapy, though only once was it statistically significant. There now appears to be enough evidence to make it likely that carbamazepine possesses some teratogenic capacity. This makes it unwise to employ the malformation rate associated with carbamazepine monotherapy as a comparator when assessing the foetal hazards from exposure to newer antiepileptic drugs. Levetiracetam may prove a better comparator if adequate untreated control material is unobtainable.

Topics: Abnormalities, Drug-Induced; Adult; Anticonvulsants; Australia; Carbamazepine; Epilepsy; Female; Fetus; Humans; Levetiracetam; Piracetam; Pregnancy; Pregnancy Complications; Registries; Risk; Teratogens; Valproic Acid

Treatment of epilepsy starts with antiepileptic drug (AED) monotherapy. Knowledge of the spectrum of efficacy, clinical pharmacology, and modes of use for individual AEDs is essential for optimal treatment for epilepsy. This article addresses AEDs individually, focusing on key pharmacokinetic characteristics, indications, and modes of use.. Older-generation AEDs are effective but have tolerability and pharmacokinetic disadvantages. Several newer-generation AEDs have undergone comparative trials demonstrating efficacy equal to and tolerability at least equal to or better than older AEDs as first-line therapy. The list includes lamotrigine, oxcarbazepine, levetiracetam, topiramate, and, more recently, zonisamide. Pregabalin was found to be less effective than lamotrigine. Lacosamide, pregabalin, and eslicarbazepine have undergone successful trials of conversion to monotherapy. Other newer-generation AEDs with a variety of mechanisms of action are suitable for adjunctive therapy. Rational AED combinations should avoid AEDs with unfavorable pharmacokinetic interactions or pharmacodynamic interactions related to mechanism of action.. Knowledge of AED pharmacokinetics, efficacy, and tolerability profiles facilitates the choice of appropriate AED therapy for patients with epilepsy.

Topics: Adult; Aged; Anticonvulsants; Carbamazepine; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Oxcarbazepine; Phenytoin; Piracetam; Pregabalin; Seizures; Triazines

The purpose of this study was to assess the efficacy and safety of levetiracetam monotherapy in a pediatric population.. A retrospective review was performed of the charts of 351 consecutive children who were 6 months to 18 years of age and were treated with levetiracetam. Levetiracetam monotherapy was initiated and dosed to efficacy or unacceptable side effects, with a range of 10-112 mg/kg/day. Electroencephalographic examination was performed at pre-treatment and 12th months in the post-treatment period. Following the commencement of levetiracetam treatment, the retention rate at 3, 6 and 12 months was 100%, 75% and 57%, respectively.. The monotherapy retention rate at 3 and 12 months following the commencement of levetiracetam treatment was (231/351, 66%), and (126/200, 63%) respectively. A total of 165 (47%) patients had idiopathic epilepsy and 186 patients (53%) had symptomatic-cryptogenic epilepsy. The >90% seizure reduction rate was 65%, and the 50-90% seizure reduction rate was 14% at the 3rd month of treatment. Similarly, the >90% seizure reduction rate was 63%, and the 50-90% seizure reduction rate was 15% at the 12th month of treatment. EEG improvement (normalization of EEG) was observed in 65 (47%) patients. Overall, 61 (17%) patients showed adverse events. The most reported side effects were irritability (67%), hyperactivity (8%), somnolence (6%), behavioral disorders (5%), restlessness (5%), increased seizure frequency (3%), enuresis (2%), headache (2%) and attempted suicide (2%).. The retrospective study of 231 consecutive pediatric patients to confirm that levetiracetam is effective as initial monotherapy for different types of seizures and/or epilepsy syndromes. However there is still a need for well-designed trials to justify the widespread use of levetiracetam monotherapy in children with specific epilepsy syndromes.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Databases, Factual; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Outcome Assessment, Health Care; Piracetam; Retrospective Studies; Time Factors; Treatment Outcome

To identify adverse events (AEs) associated with Levetiracetam (LEV) in children.. Databases EMBASE (1974-February 2015) and Medline (1946-February 2015) were searched for articles in which paediatric patients (≤18 years) received LEV treatment for epilepsy. All studies with reports on safety were included. Studies involving adults, mixed age population (i.e. children and adults) in which the paediatric subpopulation was not sufficiently described, were excluded. A meta-analysis of the RCTs was carried out and association between the commonly reported AEs or treatment discontinuation and the type of regimen (polytherapy or monotherapy) was determined using Chi2 analysis.. Sixty seven articles involving 3,174 paediatric patients were identified. A total of 1,913 AEs were reported across studies. The most common AEs were behavioural problems and somnolence, which accounted for 10.9% and 8.4% of all AEs in prospective studies. 21 prospective studies involving 1120 children stated the number of children experiencing AEs. 47% of these children experienced AEs. Significantly more children experienced AEs with polytherapy (64%) than monotherapy (22%) (p<0.001). Levetiracetam was discontinued in 4.5% of all children on polytherapy and 0.9% on monotherapy (p<0.001), the majority were due to behavioural problems.. Behavioural problems and somnolence were the most prevalent adverse events to LEV and the most common causes of treatment discontinuation. Children on polytherapy have a greater risk of adverse events than those receiving monotherapy.

Topics: Adolescent; Anticonvulsants; Child; Disorders of Excessive Somnolence; Epilepsy; Humans; Levetiracetam; Mental Disorders; Outcome Assessment, Health Care; Piracetam; Randomized Controlled Trials as Topic

Reproductive-aged women with epilepsy may present a number of specific issues to be managed in daily clinical practice. The impact of epileptic seizures and antiepileptic therapy on pregnancy outcome and the risk of teratogenicity should be minimized, which require careful attention and cooperation between obstetric gynecologyst and neurologist. The aim of the present paper is to review the impact of epilepsy attack on fetus and the pathomechanism and teratogenic effect of antiepileptic drugs.

Topics: Adult; Amines; Anticonvulsants; Benzodiazepines; Carbamazepine; Cyclohexanecarboxylic Acids; Epilepsy; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Levetiracetam; Oxcarbazepine; Parturition; Perinatal Care; Phenobarbital; Phenytoin; Piracetam; Preconception Care; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Teratogens; Triazines; Valproic Acid

Topics: Adult; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Male; Piracetam; Urinary Retention

Any type of seizure can be observed in Alzheimer's disease (AD). Antiepileptic drugs seem to prevent the recurrence of epileptic seizures in most people with AD. There are pharmacological and non-pharmacological treatments for epilepsy in people with AD. There are no current systematic reviews to evaluate the efficacy and tolerability of the treatment. This review aims to review those different modalities.. To assess the efficacy and tolerability of the treatment of epilepsy for people with Alzheimer's disease (AD) (including sporadic AD and dominantly inherited AD).. We searched the Cochrane Epilepsy Group Specialized Register (1 February 2016), the Cochrane Central Register of Controlled Trials (1 February 2016), MEDLINE (Ovid, 1 February 2016) and ClinicalTrials.gov (1 February 2016). In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials' registers, reference lists and relevant conference proceedings, and contacted authors and pharmaceutical companies.. We included randomised and quasi-randomised controlled trials investigating treatment for epilepsy in people with AD, with the outcomes of proportion of seizure freedom or experiencing adverse events.. Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to the limited available data.. We included one randomised controlled trial with 95 participants. Concerning the proportion of participants with seizure freedom, no significant differences were found in levetiracetam (LEV) versus lamotrigine (LTG) (risk ratio (RR) 1.20, 95% confidence interval (CI) 0.53 to 2.71), in levetiracetam versus phenobarbital (PB) (RR 1.01, 95% CI 0.47 to 2.19), or in LTG versus PB (RR 0.84, 95% CI 0.35 to 2.02). It seemed that LEV could improve cognition and LTG could relieve depression; while PB and LTG could worsen cognition, and LEV and PB could worsen mood. We judged the quality of the evidence to be very low.. This review does not provide sufficient evidence to support LEV, PB and LTG for the treatment of epilepsy in people with AD. Regarding the efficacy and tolerability, no significant differences were found between LEV, PB and LTG. In the future, large randomised, double-blind, controlled, parallel-group clinical trials are required to determine the efficacy and tolerability of treatment for epilepsy in people with AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Anticonvulsants; Cognition; Depression; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Phenobarbital; Piracetam; Randomized Controlled Trials as Topic; Triazines

Levetiracetam, a second-generation anti-epileptic drug (AED) with a good efficacy and safety profile, is licensed as monotherapy for adults and children older than 16 years with focal seizures with or without secondary generalization. However, it is increasingly being used off-label in younger children.. We critically reviewed the available evidence and discuss the present status of levetiracetam monotherapy in children 0-16 years old.. We systematically searched the literature using PubMed, Web of Science and Embase up to August 2014 for articles on levetiracetam monotherapy in children. Keywords were levetiracetam, monotherapy and child*. The titles and abstracts of 532 articles were evaluated by AW, of which 480 were excluded. The full texts of the other 52 articles were assessed for relevance.. We covered one review, one opinion statement and 32 studies in this review, including four randomized controlled trials, ten open-label prospective studies, eight retrospective studies, and ten case reports. The formal evidence for levetiracetam monotherapy in children is minimal: it is potentially efficacious or effective as initial monotherapy in children with benign epilepsy with centrotemporal spikes. In all of the published studies, however, efficacy and tolerability of levetiracetam seemed to be good and comparable to other AEDs.. The data of 32 studies on levetiracetam monotherapy in children were insufficient to confirm that levetiracetam is effective as initial monotherapy for different types of seizures and/or epilepsy syndromes. There is still an urgent need for well designed trials to justify the widespread use of levetiracetam monotherapy in children of all ages.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy; Humans; Infant; Infant, Newborn; Levetiracetam; Piracetam; Randomized Controlled Trials as Topic

We conducted a meta-analysis to comprehensively evaluate the current data on the overall efficacy of levetiracetam (LEV), a new generation antiepileptic drug, in patients with brain tumors. The efficacy of LEV in patients diagnosed with brain tumors has been evaluated in several studies, however, with inconsistent results. Bibliographic searches of the EMBASE, MEDLINE, ClinicalTrials.gov and Cochrane Central Register of the Controlled Trials databases were performed to identify articles and conference abstracts that investigated the efficacy of LEV in the treatment of brain tumor patients. Fourteen studies were included in this meta-analysis. Among the 14 included studies, two were randomized controlled trials. The subgroup analysis demonstrated that the complete response rate of LEV was 94% during the postoperative period and 84% during the long-term follow-up period. Our results suggest that LEV is a relatively effective drug for the treatment of brain tumor patients and its efficacy is slightly lower during the long-term follow-up period than during the postoperative period. Further randomized controlled trials are warranted.

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Piracetam; Randomized Controlled Trials as Topic; Supratentorial Neoplasms; Treatment Outcome

Head injury is a common event and can cause a spectrum of motor and cognition disabilities. A frequent complication is seizures. Antiepileptic drugs (AED) such as phenytoin are often used in clinical practice with the hopes of preventing post-traumatic epilepsy. Whether immediate medical intervention following head trauma with either AEDs or neuroprotective drugs can alter the process of epileptogenesis and lead to a more favorable outcome is currently unknown. This review attempted to address the effectiveness of these treatment interventions. This review updates and expands on the earlier Cochrane review.. To compare the efficacy of antiepileptic drugs and neuroprotective agents with placebo, usual care or other pharmacologic agents for the prevention of post-traumatic epilepsy in people diagnosed with any severity of traumatic brain injury.. We searched The Cochrane Epilepsy Group's specialized register, CENTRAL, MEDLINE, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (ICTRP) in January 2015. We searched EMBASE, Biological Abstracts and National Research Register in September 2014 and SCOPUS in December 2013. The Cochrane Epilepsy Group performed handsearches of relevant journals.. We included randomized controlled trials (RCTs) that include AEDs or neuroprotective agents compared with placebo, another pharmacologic agent or a usual care group. The outcomes measured included a seizure occurring within one week of trauma (early seizure), seizure occurring later than one week post-trauma (late seizure), mortality and any adverse events.. Two review authors independently assessed study quality and extracted the data. We calculated risk ratios (RR) and 95% confidence intervals (CI) for each outcome. We used random-effects models in the meta-analyses and performed pre-defined subgroup and sensitivity analyses.. This review included 10 RCTs (reported in 12 articles) consisting of 2326 participants The methodological quality of the studies varied. The type of intervention was separated into three categories; AED versus placebo or standard care, alternative neuroprotective agent versus placebo or standard care and AED versus other AED. Treatment with an AED (phenytoin or carbamazepine) decreased the risk of early seizure compared with placebo or standard care (RR 0.42, 95% CI 0.23 to 0.73; very low quality evidence). There was no evidence of a difference in the risk of late seizure occurrence between AEDs and placebo or standard care (RR 0.91, 95% CI 0.57 to 1.46; very low quality evidence). There was no evidence of a significant difference in all-cause mortality between AEDs and placebo or standard care (RR 1.08 95% CI 0.79 to 1.46,very low quality of evidence). Only one study looked at other potentially neuroprotective agents (magnesium sulfate) compared with placebo. The risk ratios were: late seizure 1.07 (95% CI 0.53 to 2.17) and all-cause mortality 1.20 (95% CI 0.80 to 1.81). The risk ratio for occurrence of early seizure was not estimable.Two studies looked at comparison of two AEDs (levetiracetam, valproate) with phenytoin used as the main comparator in each study. The risk ratio for all-cause mortality was 0.53 (95% CI 0.30 to 0.94). There was no evidence of treatment benefit of phenytoin compared with another AED for early seizures (RR 0.66, 95% 0.20 to 2.12) or late seizures(RR 0.77, 95% CI 0.46 to 1.30).Only two studies reported adverse events. The RR of any adverse event with AED compared with placebo was 1.65 (95% CI 0.73 to 3.66; low quality evidence). There were insufficient data on adverse events in the other treatment comparisons.. This review found low-quality evidence that early treatment with an AED compared with placebo or standard care reduced the risk of early post-traumatic seizures. There was no evidence to support a reduction in the risk of late seizures or mortality. There was insufficient evidence to make any conclusions regarding the effectiveness or safety of other neuroprotective agents compared with placebo or for the comparison of phenytoin, a traditional AED, with another AED.

Topics: Adult; Anticonvulsants; Carbamazepine; Cause of Death; Child; Craniocerebral Trauma; Epilepsy; Humans; Levetiracetam; Magnesium Sulfate; Neuroprotective Agents; Phenytoin; Piracetam; Randomized Controlled Trials as Topic; Valproic Acid

The adverse effects profile of levetiracetam in epilepsy is still being fully described. We recently published a Cochrane Review evaluating the effectiveness of levetiracetam, added on to usual care, in treating drug-resistant focal epilepsy. The five most common adverse effects were reported and analysed with no scope for reporting any less common adverse effects than those. Here, we report and analyse the remaining adverse effects (including the five most common). These were (in decreasing order of frequency) somnolence; headache; asthenia; accidental injury; dizziness; infection; pharyngitis; pain; rhinitis; abdominal pain; flu syndrome; vomiting; diarrhoea; convulsion; nausea; increased cough; anorexia; upper respiratory tract infection; hostility; personality disorder; urinary tract infection; nervousness; depression; aggression; back pain; agitation; emotional liability; psychomotor hyperactivity; pyrexia; rash; ECG abnormalities; decreased appetite; nasal congestion; irritability; abnormal behaviour; epistaxis; insomnia; altered mood; anxiety; bloody urine; diplopia; dissociation; memory impairment; pruritis; increased appetite; acne; and stomach discomfort. Only somnolence and infection were significantly associated with levetiracetam. When adverse effects pertaining to infection were combined, these affected 19.7% and 15.1% of participants on levetiracetam and placebo (relative risk 1.16, CI 0.89-1.50, Chi(2) heterogeneity p = 0.13). Somnolence and infection further retained significance in adults while no single adverse effect was significant in children. This review updates the adverse effects profile data on levetiracetam use by empirically reporting its common and uncommon adverse effects and analysing their relative importance statistically using data from a group of trials that possess low Risk of Bias and high Quality of Evidence GRADE scores.

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Piracetam

Recently, the treatment strategy for pediatric epilepsy has been dramatically changed in Japan, because of the approval of new-generation antiepileptic drugs. Since 2006, a total of 6 new antiepileptic drugs, including gabapentin (GBP; adults/pediatric patients: 2006/2011 [year of approval]), topiramate (TPM; 2007/2013), lamotrigine (LTG; 2008/2008), levetiracetam (LEV; 2010/2013), stiripentol (STP; 2012/2012), and rufinamide (RUF; 2013/2013), have been introduced. Thus far, valproate (VPA) and carbamazepine (CBZ) have been first indicated for "generalized" epilepsy and "focal" epilepsy syndromes/types, respectively, in Japan. However, the approval of these new drugs could allow us to choose more effective and less toxic ones at an early stage of treatment. In this chapter, we describe the latest domestic and foreign guidelines for the treatment of pediatric epilepsy.

Topics: Adolescent; Amines; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Cyclohexanecarboxylic Acids; Dioxolanes; Drug Approval; Drug Substitution; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Infant; Lamotrigine; Levetiracetam; Patient Education as Topic; Piracetam; Practice Guidelines as Topic; Topiramate; Triazines; Triazoles; Valproic Acid

New antiepileptic drugs (AEDs) that have been used in many other countries for more than 10 years have only recently became available for use in Japan. Gabapentin, topiramate, lamotrigine and levetiracetam were licensed for use in Japan between 2006 and 2010. Stiripentol for Dravet syndrome and rufinamide for Lennox-Gastaut syndrome were also approved in 2012 and 2013 as orphan drugs. Clinical trials of other new AEDs such as oxcarbazepine, vigabatrin, lacosamide, and perampanel are in progress. In this review, the general characteristics of the new AEDs are discussed with regards to their effectiveness, tolerability, drug interaction, safety and mechanisms of action. The effectiveness, of the new AEDs compared with established AEDs is also discussed. Clinical applications of the new AEDs, focusing on gabapentin, topiramate, lamotrigine and levetiracetam are also discussed based on our domestic experience as well as overseas reports.

Topics: Amines; Anticonvulsants; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Dioxolanes; Drug Approval; Drug Interactions; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Japan; Lamotrigine; Levetiracetam; Piracetam; Safety; Topiramate; Triazines; Triazoles

Children with epilepsy are more likely to have behavioral problems compared to children without epilepsy. Literature suggests that levetiracetam leads to behavioral side-effects in children with epilepsy. The objective of this study is to provide a better overview of the frequency and variety of behavioral side-effects, which can be initiated by levetiracetam therapy in children with epilepsy.. Electronic databases used in the search were PubMed, Medline, Cochrane and Embase. Studies were eligible for inclusion when they included children from one month to 18 years of age with a diagnosis of epilepsy, used levetiracetam, had other AEDs on a stable regimen for at least two months, reported about behavioral side-effects and had a follow-up of at least two weeks. Quality assessments and data collection were carried out for all eligible studies.. Thirteen studies, including 727 patients using levetiracetam, were included in this systematic review. Three randomized controlled trials showed a total of 62 behavioral side-effects in 203 patients, effects which led to discontinuation of levetiracetam in only two of 102 patients (2.0%). Hostility, nervousness and aggression were reported mostly. Meta-analysis showed a statistically significant relative risk of 2.18 for the total number of behavioral side-effects for levetiracetam versus placebo. Observational studies showed mixed results with both behavioral deteriorations and improvements following levetiracetam.. Based on the findings in this systematic review, children using levetiracetam have a risk of developing several behavioral side-effects such as aggression, hostility and nervousness compared to children who do not use levetiracetam.

Topics: Anticonvulsants; Child; Child Behavior Disorders; Databases, Bibliographic; Epilepsy; Humans; Levetiracetam; Piracetam

Benign Epilepsy with Centro Temporal Spikes (BECTS) is a common epilepsy syndrome with onset in childhood which almost always remits by adolescence. It is characterised by focal seizures associated with motor signs and somatosensory symptoms, at times progressing to become generalised. The characteristic interictal EEG shows normal background activity with centrotemporal spikes which are more prominent in sleep. The prognosis is good though subtle cognitive impairment has been implicated. Antiepileptic drug (AED) treatment is used if seizures are frequent or occurring in the daytime.. To evaluate whether or not treatment with AEDs changes the short- or long-term outcome of children with BECTS or both.. We searched the following databases: the Cochrane Epilepsy Group Specialized Register (30 April 2013), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2013, Issue 4: (April 2013)), MEDLINE (Ovid, 1946 to 30 April 2013), SCOPUS (30 April 2013), ClinicalTrials.gov (30 April 2013) and the WHO International Clinical Trials Registry Platform ICTRP (30 April 2013). We also handsearched the reference lists of articles that were considered for inclusion in the review.. All randomised controlled trials (RCTs) that compared the use of different AEDs, or compared the use of AEDs with no treatment, or placebo in children with BECTS.. Data were independently extracted by all four of the review authors and discrepancies were resolved by discussion. Analysis included assessment of risk of bias, quality of evidence of individual studies, heterogeneity, and statistical analysis of the effects on seizure remission and cognition.. There were six eligible studies but only four had sufficient data at the time of this review. The four RCTs included in this review reported on a total of 262 participants. One study, a placebo-controlled trial with a low risk of bias, found that individuals on sulthiame were significantly more likely to remain in seizure remission during the three and six months from commencement of treatment than those on placebo (3 months: RR 2.26, 95% CI 1.48 to 3.44; 6 months: RR 2.63, 95% CI 1.43 to 4.86, 66 participants, moderate quality evidence). The other three trials, all open-labelled studies, had a high risk of bias and did not show any significant differences in terms of seizure remission between AEDs. One compared levetiracetam with oxcarbazepine (3 months: RR 1.13, 95% CI of 0.93 - 1.36; 12 months: RR of 1.29 with 95% CI of 0.89 - 1.86, 39 participants, low to very low quality evidence), one clobazam with carbamazepine (4-40 weeks: RR of 1.04, 95% CI of 0.67 - 1.62; last 9 months: RR of 1.06 with 95% CI of 0.84, 1.34, 45 participants, low quality evidence), and one carbamazepine with topiramate (28 weeks: RR 1.02 with 95% CI of 0.8 - 1.3, 112 participants, low quality evidence).Other outcome measures assessed included time to first seizure after randomisation which was only obtained in the sulthiame versus placebo study as a hazard ratio of 7.8 (95% CI 2.66 - 22.87). There were no significant differences between the proportion of participants who had adverse events, apart from a higher incidence of rash in the carbamazepine group (14.8%) when compared with topiramate (1.7%), or the proportion who withdrew from treatment due to adverse events, when this was reported. Two trials (carbamazepine versus topiramate, and clobazam versus carbamazepine) evaluated the effects on cognition. The studies were of low to very low quality evidence showing no clear difference in cognition at the end of the study periods between the AEDs compared. A meta-analysis was not performed as the RCTs evaluated different therapies.. There is evidence from one trial reviewed that sulthiame is effective for seizure remission in the short term in children with BECTS although the precision of the effect estimate is uncertain due to its small sample size. There were no significant differences in the proportion of adverse events between treatment groups studied, including those resulting in withdrawal of treatment. There is insufficient evidence about the medium to longer term effects on seizure control, the optimum antiepileptic drug treatment and the effects of AED treatment on cognition. There is a need for more good quality randomised controlled trials to address these questions to aid the management of children with BECTS.

Topics: Anticonvulsants; Benzodiazepines; Carbamazepine; Child; Clobazam; Epilepsy; Fructose; Humans; Induction Chemotherapy; Levetiracetam; Oxcarbazepine; Piracetam; Placebos; Randomized Controlled Trials as Topic; Thiazines; Topiramate; Watchful Waiting

Diagnostic work-up and treatment of patients who have developed epilepsy after the age of 65 can both be difficult. Epilepsy is one of the most common neurological conditions in the elderly, and the incidence of de novo geriatric epilepsy is rising. The aim of this review is to provide guidance on the management of epilepsy in this patient group.. The review is based on a discretionary selection of original articles and reviews found in PubMed using the search term combination 'epilepsy' and 'elderly', and the authors' personal experience.. The seizures, which are most commonly of the focal type, are not infrequently overlooked or misdiagnosed. Cerebrovascular disease is the underlying cause of about half of the cases. When selecting an anticonvulsant, it is important to take age-related physiological changes and comorbidities into consideration. Because elderly patients have a narrower therapeutic window than younger persons and greater susceptibility to cognitive and other side effects, a low starting dose and slower dose titration are particularly important.. The results of studies of young epilepsy patients cannot be extrapolated to apply to elderly patients. More studies directly targeting this patient population are therefore needed. As a general rule, we do not recommend starting on enzyme-inducing drugs such as phenytoin, phenobarbital and carbamazepine, partly because of their high interaction potential.

Topics: Age Factors; Aged; Aging; Anticonvulsants; Dose-Response Relationship, Drug; Epilepsy; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Piracetam; Quality of Life; Seizures; Triazines; Zonisamide

The treatment of neonatal seizures has not changed significantly over the last 50 years despite advances in antiepileptic drug (AED) development for older children and adults. Recently new drugs have emerged some of which address age-specific challenges or mechanisms and will be discussed in this review. The loop diuretic bumetanide blocks the neuronal NKCC1 co-transporter and is thought specifically to supress seizures in the immature brain. Levetiracetam has been used in children and infants with good efficacy, an excellent safety profile, and near-ideal pharmacokinetic characteristics. Randomised controlled trials are now underway to test the efficacy of some newer AEDs for neonatal seizures. Topiramate has been shown to have neuroprotective properties in addition to its antiepileptic action and trials in babies with hypoxic-ischaemic encephalopathy are now planned. There is an urgent need to develop age-specific AEDs for preterm and term babies. These drugs must be evaluated with multicentre, collaborative trials using innovative methods and high ethical standards to overcome age-specific challenges with the ultimate aim of improving the outcome for neonates with seizures.

Topics: Animals; Anticonvulsants; Brain; Bumetanide; Child Development; Epilepsy; Fructose; Humans; Infant, Newborn; Levetiracetam; Neurogenesis; Neurons; Neuroprotective Agents; Piracetam; Seizures; Sodium Potassium Chloride Symporter Inhibitors; Topiramate

Levetiracetam (LEV) is a highly effective antiepileptic agent. A clinically relevant psychiatric complication of LEV treatment, however, is the provocation of irritability and aggression. Recent behavioral research indicates that personality traits may predispose to these side effects. To assess the genetic basis of the adverse psychotropic profile of LEV, a candidate gene-based two-stage association study was conducted.. Polymorphisms were a priori selected according to their relevance for impulsivity and reactive-impulsive aggression. Based on data from both stages, a Bonferroni-corrected joint meta-analysis was computed.. Stage 1 analysis included 290 patients with epilepsy and revealed a higher load of adverse psychotropic side effects of LEV in patients carrying genetic variants associated with decreased dopaminergic activity: rs1611115 (dopamine-β-hydroxylase, DBH), rs4680 (catechol-O-methyltransferase, COMT), and rs1800497 (dopamine receptor D2-associated ANKK1 TAQ-1A). Stage II analysis including 100 patients with epilepsy, and joint meta-analysis confirmed the effect of the rs1800497 polymorphism (Bonferroni corrected significance of the joint meta-analysis, p = 0.0096).. Confirming the suggestion from behavioral observations that patients might be predisposed to develop irritation and aggression under treatment with LEV, the findings provide first evidence of an association of genetic variation in dopaminergic activity and the risk for psychiatric complications of LEV treatment. Replication and further work is required to prove a true causal relationship. Overall, the pharmacogenomic approach to behavioral side effects may provide a future tool to predict adverse psychotropic effects related to antiepileptic drugs.

Topics: Adult; Aggression; Anticonvulsants; Catechol O-Methyltransferase; Dopamine; Dopamine beta-Hydroxylase; Epilepsy; Female; Genetic Predisposition to Disease; Humans; Irritable Mood; Levetiracetam; Male; Piracetam; Polymorphism, Single Nucleotide; Psychiatric Status Rating Scales; Receptors, Dopamine D2; Risk Factors

Acute seizure and status epilepticus constitute one of the major medical emergencies in children. Among children, the incidence ranges from 4-38/100,000 children per year respectively. The incidence in developing countries is somewhat higher because of infections. Although, the definition of status epilepticus is based on duration of seizures, the operational definition is to treat any child who is brought seizing to the emergency room, as status epilepticus. An urgent time bound approach is of paramount importance when managing a child in status epilepticus. Benzodiazepines remain the first line antiepileptic drugs in the emergency room; a long acting drug (Lorazepam) is preferred when available. This is followed by Phenytoin (20 mg/kg) loading. In patients refractory to above drugs, valproate (30 mg/kg) loading is commonly used and if effective, followed by an infusion (5 mg/kg/h) for seizure free period of 6 h. In non-responders, a trial of Levetiracetam (40 mg/kg infused at 5 mg/kg/min) can be used before starting benzodiazepine or thiopental coma (3-4 mg/kg loading dose, followed by 2 mg/kg/min infusion). When pharmacological coma is initiated, the child needs to be shifted to pediatric intensive care unit for proper monitoring and titration of medications.

Topics: Anesthesia, Intravenous; Anticonvulsants; Benzodiazepines; Child; Child, Preschool; Combined Modality Therapy; Cross-Sectional Studies; Developing Countries; Dose-Response Relationship, Drug; Emergency Service, Hospital; Epilepsy; Humans; India; Infant; Infusions, Intravenous; Intensive Care Units, Pediatric; Levetiracetam; Lorazepam; Phenytoin; Piracetam; Seizures; Status Epilepticus; Thiopental; Valproic Acid

Antiepileptic drugs are prescribed to patients of all ages and are commonly prescribed to patients over the age of 65. When prescribing these drugs to patients of this age bracket, treatment should be based not only on the diagnosis and seizure type but also on the propensity of the drugs for adverse effects and their drug-drug interactions.. This article reviews antiepileptic drugs currently used for treating the elderly and highlights the adverse effects and potential drug-drug interactions for these treatments. The article was complied through literature searches of the Cochrane database of systematic reviews, MEDLINE and SCindeks.. In elderly patients who have hepatic diseases, antiepileptic drugs that are not metabolized in the liver, such as levetiracetam, are preferred; in patients with moderate and severe renal failure, carbamazepine and valproic acid are the preferred antiepileptic drugs. Phenytoin, fosphenytoin, carbamazepine, oxcarbazepine and lamotrigine should not be prescribed in elderly patients with cardiac conduction abnormalities or a history of ventricular arrhythmia. While the majority of antiepileptic drugs interact with other drugs, hepatic enzymes and plasma proteins, a few newer antiepileptic drugs are free from such interactions (e.g., gabapentin, levetiracetam and tiagabine), which make them suitable candidates for elderly patients. However, in order to make further recommendations regarding the choice and dosing regimens of antiepileptic drugs in elderly patients, more extensive clinical research in this specific population is necessary.

Topics: Aged; Animals; Anticonvulsants; Carbamazepine; Cardiovascular Diseases; Choice Behavior; Drug Interactions; Epilepsy; Humans; Levetiracetam; Piracetam

Several new antiepileptic drugs (AEDs) have been introduced for clinical use recently. These new AEDs, like the classic AEDs, target multiple cellular sites both pre- and postsynaptically. The use of AEDs as a possible neuroprotective strategy in brain ischemia is receiving increasing attention and the antiepileptic drug levetiracetam, a 2S-(2-oxo-1-pyrrolidiny1) butanamide, belonging to the pyrrolidone family, could have a crucial role in regulation of epileptogenesis and neuroprotection. Recent observations suggest that levetiracetam is both safe and effective against post-stroke seizures. In this review, the potential neuroprotective role in brain ischemia and the therapeutic implications of levetiracetam in post-stroke epilepsy are discussed.

Topics: Animals; Anticonvulsants; Brain Ischemia; Clinical Trials as Topic; Disease Models, Animal; Epilepsy; Humans; Levetiracetam; Neuroprotective Agents; Piracetam; Stroke

Topics: Acute Disease; Allosteric Regulation; Animals; Anticonvulsants; Calcium; Calcium Channel Blockers; Calcium Channels, N-Type; Disease Models, Animal; Epilepsy; Humans; Levetiracetam; Membrane Glycoproteins; Nerve Tissue Proteins; Piracetam; Randomized Controlled Trials as Topic; Seizures

Levetiracetam (Keppra®, E Keppra®) is an established second-generation antiepileptic drug (AED). Worldwide, levetiracetam is most commonly approved as adjunctive treatment of partial onset seizures with or without secondary generalization; other approved indications include monotherapy treatment of partial onset seizures with or without secondary generalization, and adjunctive treatment of myoclonic seizures associated with juvenile myoclonic epilepsy and primary generalized tonic-clonic (GTC) seizures associated with idiopathic generalized epilepsy. Levetiracetam has a novel structure and unique mechanisms of action. Unlike other AEDs, the mechanisms of action of levetiracetam appear to involve neuronal binding to synaptic vesicle protein 2A, inhibiting calcium release from intraneuronal stores, opposing the activity of negative modulators of GABA- and glycin-gated currents and inhibiting excessive synchronized activity between neurons. In addition, levetiracetam inhibits N-type calcium channels. Levetiracetam is associated with rapid and complete absorption, high oral bioavailability, minimal metabolism that consists of hydrolysis of the acetamide group, and primarily renal elimination. It lacks cytochrome P450 isoenzyme-inducing potential and is not associated with clinically significant pharmacokinetic interactions with other drugs, including other AEDs. The efficacy of oral immediate-release levetiracetam in controlling seizures has been established in numerous randomized, double-blind, controlled, multicentre trials in patients with epilepsy. Adjunctive levetiracetam reduced the frequency of seizures in paediatric and adult patients with refractory partial onset seizures to a significantly greater extent than placebo. Monotherapy with levetiracetam was noninferior to that with carbamazepine controlled release in controlling seizures in patients with newly diagnosed partial onset seizures. Levetiracetam also provided seizure control relative to placebo as adjunctive therapy in patients with idiopathic generalized epilepsy with myoclonic seizures or GTC seizures. In addition, patients receiving oral levetiracetam showed improvements in measures of health-related quality of life relative to those receiving placebo. Although treatment-emergent adverse events were commonly reported in the clinical trials of levetiracetam, the overall proportion of patients who experienced at least one treatment-emergent adverse event was broadly similar in the levetirace

Topics: Clinical Trials as Topic; Double-Blind Method; Epilepsy; Humans; Levetiracetam; Multicenter Studies as Topic; Piracetam; Randomized Controlled Trials as Topic

New evidence suggests that levetiracetam may be as effective as traditional agents, with better safety profile.. To synthesize evidence regarding efficacy and tolerability of levetiracetam as first line, adjunctive or prophylactic antiepileptic agent. Study Selection & Data Extraction: Eligible studies were randomized controlled trials (RCTs) of levetiracetam used in adults with epilepsy. MEDLINE, EMBASE, CENTRAL, CINHAL, PAPERSFIRST, PROCEEDINGSFIRST, PROQUEST and conference proceedings identified studies (to September 30, 2010). Two investigators independently selected, appraised studies, collected and analyzed data.. Of ten eligible randomized trials, eight investigated adjunctive levetiracetam for refractory seizures, one as monotherapy for newly diagnosed seizures, one as monotherapy for prophylaxis. Eight RCTs of adjunctive levetiracetam were of moderate quality (GRADE criteria), with two showing lack of allocation concealment. Meta-analyses showed adjunctive levetiracetam was more effective than placebo in achieving at least 50% reduction of seizure frequency, when added to baseline antiepileptic regimen (pooled RR 2.15 [1.65,2.82], I2 = 45%, p value (heterogeneity) = 0.08, p value (overall effect) < 0.01). Likelihood of serious adverse events necessitating withdrawal from study was not significantly different between levetiracetam and control (pooled RR 1.37 [0.88,2.13], I2 = 0%, p value (heterogeneity) = 0.84, p value (overall effect) = 0.17). Subgroup analyses suggested similar effects across different dosages. Sensitivity analysis of studies with adequate concealment showed similar effects.. Levetiracetam is an effective adjunctive agent for refractory epilepsy. More studies are needed to establish whether it is effective as monotherapy for newly diagnosed seizures, and for prophylaxis in traumatic brain injury.

Topics: Adult; Anticonvulsants; Bias; Databases, Bibliographic; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Randomized Controlled Trials as Topic

Although epilepsy surgery is most effective for patients with intractable epilepsy, a majority of them is not eligible for the surgery. Most of patients with refractory epilepsy are eventually treated with polypharmacy in hope of seizure control. Therefore, rational combinations of antiepileptic drugs are needed to control intractable seizures. Drug combinations should be rationally chosen based on the evidence of synergic efficacy and on avoidance of neurotoxicity. Several clinical studies suggest that the combination of valproate with lamotrigine has synergic antiepileptic effect. It has also been reported that the combination of carbamazepine with lamotrigine paradoxically decreases efficacy and increases toxicity. Animal studies using isobolography suggest that the combinations of topiramate with lamotrigine or levetiracetam are also promising on both seizure control and neurotoxicity. Clinical research is needed to examine these combinations.

Topics: Animals; Anticonvulsants; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carbamazepine; Clinical Trials as Topic; Disease Models, Animal; Drug Interactions; Drug Resistance; Drug Therapy, Combination; Epilepsy; Fructose; Humans; Lamotrigine; Levetiracetam; Multidrug Resistance-Associated Proteins; Piracetam; Prognosis; Topiramate; Triazines; Valproic Acid

Levetiracetam (Keppra®, E Keppra®) is an established second-generation antiepileptic drug (AED). Worldwide, levetiracetam is most commonly approved as adjunctive treatment of partial-onset seizures with or without secondary generalization; other approved indications include monotherapy treatment of partial-onset seizures with or without secondary generalization, and adjunctive treatment of myoclonic seizures associated with juvenile myoclonic epilepsy and primary generalized tonic-clonic (GTC) seizures associated with idiopathic generalized epilepsy. Levetiracetam has a novel structure and unique mechanisms of action. Unlike other AEDs, the mechanisms of action of levetiracetam appear to involve neuronal binding to synaptic vesicle protein 2A, inhibiting calcium release from intraneuronal stores, opposing the activity of negative modulators of GABA- and glycin-gated currents and inhibiting excessive synchronized activity between neurons. In addition, levetiracetam inhibits N-type calcium channels. Levetiracetam is associated with rapid and complete absorption, high oral bioavailability, minimal metabolism that consists of hydrolysis of the acetamide group and primarily renal elimination. It lacks cytochrome P450 isoenzyme-inducing potential and is not associated with clinically significant pharmacokinetic interactions with other drugs, including other AEDs. The efficacy of oral immediate-release levetiracetam in controlling seizures has been established in numerous randomized, double-blind, controlled, multicentre trials in patients with epilepsy. Adjunctive levetiracetam reduced the frequency of seizures in paediatric and adult patients with refractory partial-onset seizures to a significantly greater extent than placebo. Monotherapy with levetiracetam was noninferior to that with carbamazepine controlled release in controlling seizures in patients with newly diagnosed partial-onset seizures. Levetiracetam also provided seizure control relative to placebo as adjunctive therapy in patients with idiopathic generalized epilepsy with myoclonic seizures or GTC seizures. In addition, patients receiving oral levetiracetam showed improvements in measures of health-related quality of life relative to those receiving placebo. Although treatment-emergent adverse events were commonly reported in the clinical trials of levetiracetam, the overall proportion of patients who experienced at least one treatment-emergent adverse event was broadly similar in the levetiracet

Topics: Anticonvulsants; Carbamazepine; Chemotherapy, Adjuvant; Epilepsy; Humans; Levetiracetam; Piracetam; Randomized Controlled Trials as Topic; Seizures; Treatment Outcome

Levetiracetam was approved by the US FDA in 1999 after failing the traditional screening tests for antiepileptic drugs. In the 10 years since its introduction, it has become one of the first-line antiepileptic agents and has been evaluated in small uncontrolled studies and case series as an off-label treatment for status epilepticus, for nonepileptic neurological conditions, such as movement disorders, neuropathic pain and headaches, and for some psychiatric conditions. It has not been approved for any indication other than chronic epilepsy. A significant factor in using levetiracetam for seizures and other disorders has been its ease of dosing and tolerability. In this article, we outline how levetiracetam was discovered, the animal and human data showing its antiepileptic activity, its potential use in other neurological conditions and the significant adverse events. We also discuss the direction antiepileptic drug development will take in the future.

Topics: Animals; Anticonvulsants; Clinical Trials as Topic; Epilepsy; Humans; Levetiracetam; Piracetam

Levetiracetam has been widely used for childhood epilepsy, but there is no high quality evidence to support its use. This study performed a systematic review to evaluate the effectiveness and safety of levetiracetam therapy for childhood epilepsy.. The papers related to levetiracetam therapy for childhood epilepsy published up to March, 2009 were retrieved electronically from the PubMed, Embase, the Cochrane Library, Chinese Biomedical Database, Wanfang and Weipu Chinese Journals Full-text Database. The relevant papers on randomized control trials (RCTs) or quasi-RCTs were studied by meta analysis.. Two papers that met the inclusion criteria were included. The first paper involved 198 patients, including 108 cases in the levetiracetam therapy group and 97 cases in the placebo group. Seven cases (6.9%) were seizure free in the levetiracetam therapy group compared with 1 case (1%) in the placebo group (p<0.01) 14 weeks after treatment. Levetiracetam therapy decreased significantly the frequency of seizures compared with the placebo treatment. The second paper involved 39 patients, including 21 cases in the levetiracetam therapy group and 18 cases in the oxcarbazepine therapy group. Nineteen cases (90.5%) were seizure-free in the levetiracetam therapy group compared with 13 cases (72.2%) in the oxcarbazepine therapy group (P=0.410) during a follow-up of 12-24 months. The adverse effects in the levetiracetam therapy group were not significantly different from the placebo and the oxcarbazepine therapy groups.. The current evidence shows that levetiracetam therapy is effective for childhood epilepsy. However, it needs to be proved by the multi-centre, large sample RCTs.

Topics: Anticonvulsants; Child; Epilepsy; Humans; Levetiracetam; Piracetam; Randomized Controlled Trials as Topic

Levetiracetam is an antiepileptic drug that has been shown to be effective in various types of seizures, both partial and generalized. Although it is not yet well established because of the small number of studies, levetiracetam as both add-on therapy and monotherapy can be considered as an alternative to valproic acid in some pediatric patients. We have reviewed the available data on the efficacy, tolerability, and safety of levetiracetam in children with epilepsy. The efficacy of levetiracetam as an adjunctive therapy and as monotherapy for generalized and partial childhood epilepsies and for some types of specific epileptic syndromes of infancy and childhood (such as juvenile myoclonic epilepsy, benign rolandic epilepsy, and Jeavon syndrome) has been demonstrated in some studies. Moreover, levetiracetam may be a valuable option for children with refractory epilepsy. The reported tolerability of levetiracetam and its safety profile are favorable. Among the side effects reported, behavioral changes and even psychotic reactions seem to occur more frequently in younger patients (under 4 years of age). The onset of signs/symptoms usually occurs early, even during the titration phase, and, in many cases, at a low dosage (<20 mg/kg/day). These side effects were always observed to be reversible after discontinuation of levetiracetam. In conclusion, results from clinical trials to date suggest that levetiracetam has a full spectrum of efficacy as well as a favorable safety profile, and this drug can be considered a valuable option in the treatment of epilepsy in pediatric patients.

Topics: Animals; Child; Drug Prescriptions; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Humans; Levetiracetam; Piracetam

Levetiracetam (Keppra) is an antiepileptic drug (AED) characterized by a novel mechanism of action, unique profile of activity in seizure models, and broad-spectrum clinical efficacy. The present report critically reviews several preclinical studies focused on combination therapy with levetiracetam and other anticonvulsants in various seizure and epilepsy models. Administration of levetiracetam together with many different clinically used AEDs or other anticonvulsants generally enhances their protective activity and, among existing AEDs, this was particularly prevalent with valproate. The protective activity of other AEDs was also enhanced by levetiracetam, which seems to be a universal finding that is independent of seizure model or drug combination studied. However, particularly strong enhancement was observed when levetiracetam was combined with agents either enhancing GABAergic or reducing glutamatergic neurotransmission. Importantly, these combinations were not associated with exacerbation of side effects or pharmacokinetic interactions. Based on the available preclinical data, it appears that combination treatment with levetiracetam and other anticonvulsants provides additional therapeutic benefit that may be attributed to its novel and distinct mechanism of action. Moreover, combinations of levetiracetam with clinically used AEDs that enhance GABAergic inhibition may be considered for rational polytherapy, which is often necessary in drug-resistant patients.

Topics: Animals; Anticonvulsants; Brain; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Interactions; Drug Therapy, Combination; Epilepsy; gamma-Aminobutyric Acid; Glutamic Acid; Humans; Levetiracetam; Membrane Glycoproteins; Nerve Tissue Proteins; Piracetam

In this paper we review the current information regarding the use of new antiepileptic drugs (AEDs) used as monotherapy in children. We specifically include the following AEDs: lamotrigine (Lamictal), topiramate (Topamax), zonisamide (Zonegran), levetiracetam (Keppra), and oxcarbazepine (Trileptal). All of these AEDs have a broad spectrum of action in the treatment of partial and generalized seizures, except Oxcarbazepine, which is effective only in partial seizures. It is unclear whether or not monotherapy with the new AEDs offers higher efficacy and/or lower side effects compared to classic AEDs (phenobarbital, phenytoin, carbamazepine, or valproate) thereby significantly improving the quality of life in children with epilepsy. More studies are needed to answer these questions.

Topics: Anticonvulsants; Carbamazepine; Child; Drug Administration Schedule; Epilepsy; Fructose; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Piracetam; Topiramate; Triazines; Zonisamide

To review data evaluating levetiracetam management of epilepsy during pregnancy.. A literature search of PubMed (1966-June 2009) was performed using the terms pregnancy, epilepsy, levetiracetam, and anticonvulsants. Bibliographies of all articles retrieved were reviewed to identify additional relevant articles.. All studies including humans and published in English with data describing levetiracetam management during pregnancy were included.. The pharmacokinetic studies included in this review demonstrate that the clearance of levetiracetam increases during pregnancy, particularly during the third trimester, which subsequently leads to decreased serum levetiracetam concentrations. The increase in clearance is most likely due to an increase in renal blood flow. The teratogenic studies included in this review included a total of 147 patients. Of these patients, 2% experienced a major congenital malformation (MCM) and 4.8% experienced a minor anomaly. All of the patients who had either an MCM or a minor anomaly were receiving antiepileptic drug (AED) polytherapy. It was unknown whether 10.9% of the 147 patients discussed were receiving levetiracetam monotherapy or AED polytherapy. None of the published literature assessed adherence to AED therapy. Folic acid supplementation was addressed in only one of the case series presented.. If levetiracetam is used during pregnancy, women should receive adequate amounts of folic acid (0.4-5 mg/day) and serum concentrations of levetiracetam should be determined before conception if possible and during each trimester, especially during the middle of the third trimester, to assess therapeutic concentrations. The dose may need to be increased during the third trimester to provide concentrations consistent with those before conception. Patients should be informed that there appears to be a small chance of malformations with levetiracetam, but that the data are limited.

Topics: Anticonvulsants; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Monitoring; Epilepsy; Female; Folic Acid; Humans; Levetiracetam; Piracetam; Pregnancy; Pregnancy Complications; Vitamin B Complex

Open-label extension studies, or follow-on randomised controlled trials (FORCTs) are widely believed to be prone to patient selection biases which may inflate effect estimates. This study investigates the reporting and analysis of efficacy outcomes in FORCTs and critically evaluates the associated underlying assumptions. We propose an alternative method of analysis, in line with that recommended in the analysis of RCTs, the intention to treat (ITT) approach, in which it is assumed that all patients who discontinue treatment are non-responders.. A systematic review of FORCTs and randomised controlled trials (RCT) of topiramate, levetiracetam and gabapentin as adjuvant therapy in refractory adult epilepsy was conducted. Sample sizes and numbers of responders, along with reported outcomes were extracted. To evaluate the feasibility of the assumptions underlying the various methods of analysis, the most common causes of discontinuation were evaluated. For each FORCT, we compared the reported outcome to the proposed ITT analysis.. The 10 FORCT reports identified all excluded from the analysis patients who dropped out of the RCT. Adverse events or inefficacy were the main reasons for treatment discontinuation. Analysis based on the ITT method, led to smaller effect estimates than those reported. For example, a FORCT of levetiracetam reported a responder rate of 43%, which reduced to 28% under an ITT analysis, comparable to an ITT analysis outcome of 26% for the parent RCT.. FORCTs can provide important information about long-term efficacy and tolerability of newer therapies. However, current reporting methods are likely to be misleading as outcomes are reported for the subset of patients continuing with treatment at the end of the FORCT. Since the majority of patients who discontinue treatment do so for reasons associated with inefficacy, an analysis based on the ITT approach more closely reflects the outcomes of the patients.

Topics: Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Databases, Factual; Drug Resistance; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Levetiracetam; Patient Dropouts; Piracetam; Randomized Controlled Trials as Topic; Research Design; Topiramate

The "new" antiepileptic drug levetiracetam has the unique mechanisms of antiepileptic activity. Various recent studies revealed its efficacy and safety in different forms of epilepsy both as a monotherapy and an additional therapy. The low frequency of side-effects and minimal interactions with other drugs allow to use levetiracetam in elderly patients and in patients with severe co-morbid diseases including AIDS and hepatitis C receiving the corresponding therapy. Moreover, the efficacy of levetiracepam in other neurological diseases: chronic headaches, i.e., migraine, neuropathic pain, including patients with cancer, movement disorders (myoclonus, dystonia and dyskinesia in Parkinson's disease, essential tremor, have been revealed.

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Piracetam; Treatment Outcome

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Piracetam; Treatment Outcome

Principles of complex mechanisms of action of anticonvulsants including latest reports concerning new antiepileptic drugs (AED) are considered. Different aspects of new anticonvulsant drugs (2nd generation) from preclinical and clinical testing, pharmacokinetics, and mono or combination therapy in children and adults are summarized. In the following condensed synopsis pharmacological and clinical characteristics of gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), pregabalin (PGB) and tiagabine (TGB) as well as topiramate (TPM) and zonisamide (ZNS) are discussed. In addition to the mechanisms of action, pharmacokinetics, interactions, indications and dosages as well as side effects are considered. Important data concerning the effect and tolerability of anticonvulsant drugs can be obtained from controlled studies. In comparison to drugs of the first generation (phenobarbital [PB], primidon [PRD], phenytoin [PHT], carbamazepine [CBZ] and valproic acid [VPA]) the potential for interactions and side effects due to enzyme induction or inhibition is reduced by most of the anticonvulsant drugs of the second generation. New anticonvulsant drugs increase the spectrum of treatment and represent further steps with regard to the optimization of an individual therapy of the epilepsies.

Topics: Amines; Animals; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Piracetam; Pregabalin; Tiagabine; Topiramate; Treatment Outcome; Triazines; Zonisamide

Although epilepsy was believed to have the highest incidence in childhood, recent epidemiologic studies revealed that the incidence increases markedly in elderly. At least 1% of elderly people are estimated to have epilepsy. Cerebrovascular disease is the most common underlying cause although 25% of new onset geriatric epilepsy cases have no obvious etiology. The most common seizure manifestation is atypical complex partial seizures with long-lasting postictal confusion which may lead to underdiagnosis and misdiagnosis. Factors complicating the treatment of geriatric epilepsy include comorbidities, drug interactions due to polytherapy, and aging-related changing of pharmacokinetics. Individualization of dosage and avoidance of unnecessary polypharmacy are essential for safe utilization of anti-epileptic drugs. New generation drugs such as gabapentin and levetiracetam are better tolerated for elderly people.

Topics: Aged; Aged, 80 and over; Aging; Amines; Anticonvulsants; Cerebrovascular Disorders; Comorbidity; Cyclohexanecarboxylic Acids; Diagnosis, Differential; Drug Interactions; Epilepsy; Gabapentin; gamma-Aminobutyric Acid; Humans; Levetiracetam; Pharmacokinetics; Piracetam

The objective of this article was to review and summarize the available reports on the preclinical profile of the novel anticonvulsant drug levetiracetam (LEV). Therefore, a careful search was conducted in the MEDLINE database and combined with guidelines from regulatory agencies, proceedings of professional scientific meetings, and information provided by the manufacturers. This article provides detailed information on the anticonvulsant effects of LEV in various animal models of epilepsy and on its pharmacology in laboratory animals. The mechanism of action of LEV is reviewed, with special regard to its recently discovered binding site, the synaptic vesicle protein 2A. In general, LEV is shown to be a safe, broad-spectrum anticonvulsant drug with highly beneficial pharmacokinetic properties and a distinct mechanism of action. The clinical studies with LEV will be discussed in the second part of this review article to be published subsequently.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Drug Evaluation, Preclinical; Epilepsy; Humans; Levetiracetam; MEDLINE; Piracetam

The objective of this article was to review and summarize the available reports on the profile of the novel anticonvulsant drug levetiracetam (LEV) in a clinical setting. Therefore, a careful search was conducted in the MEDLINE database and combined with guidelines from regulatory agencies, proceedings of professional scientific meetings, and information provided by the manufacturers. This article is devoted to the clinical pharmacology and clinical trials of LEV investigating its efficacy and safety as add-on therapy or monotherapy for various seizure types. Finally, results from postmarketing surveillance of LEV are briefly discussed. In general, LEV is shown to be a safe, broad-spectrum anticonvulsant drug with highly beneficial pharmacokinetic properties, a favorable long-term retention rate, and a high responder rate, indicating that LEV is an efficient therapeutic option for the treatment of several types of epilepsy.

Topics: Animals; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Meta-Analysis as Topic; Piracetam

Levetiracetam is an antiepileptic drug approved for use as an adjunct agent in partial-onset seizures in adults and children aged > or = 4 years. It was also approved as adjunctive therapy in the treatment of adults and adolescents aged > or = 12 years with juvenile myoclonic epilepsy. A parenteral intravenous formulation has recently become available allowing for its use when oral administration is temporarily not feasible. Available literature has demonstrated and supported that levetiracetam has an acceptable safety profile and this review discusses the safety profile of levetiracetam, with attention to special populations. The most common adverse effects are somnolence, asthenia and dizziness, which usually appear early after initiation of levetiracetam therapy and generally resolve without medication withdrawal. The most serious adverse effects are behavioral in nature and are more common in children and in patients with a prior history of behavioral problems.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Blood Cells; Body Weight; Child; Child Behavior; Drug Hypersensitivity; Drug Interactions; Epilepsy; Female; Humans; Injections, Intravenous; Levetiracetam; Piracetam; Pregnancy; Psychoses, Substance-Induced; Safety

To assess the population pharmacokinetics of levetiracetam, a second-generation antiepileptic drug, in adult Japanese and Western populations.. Data were pooled from ten matched clinical trials conducted in Japan and in Europe and the USA, in which levetiracetam was administered orally to healthy subjects and subjects with epilepsy. Overall, 5408 plasma concentrations were available from 524 subjects in six clinical pharmacology studies and two confirmatory and two long-term safety studies of add-on treatment for partial epilepsy. A one-compartment open model with first-order absorption and elimination was fitted to the plasma concentrations using nonlinear mixed-effects modelling with first-order estimation.. Ethnicity had no statistically significant effect on the pharmacokinetics of levetiracetam in the presence of the other covariates. Bodyweight, sex, creatinine clearance and concomitant intake of enzyme inducers or valproic acid had a statistically significant effect on apparent plasma clearance of levetiracetam. Bodyweight, disease and valproic acid had a statistically significant effect on the volume of distribution. Levetiracetam exposure (the area under the plasma concentration-time curve over the 12-hour dosing interval at steady state) was 12% higher in females than in males. Decreasing bodyweight from 70 kg to 40 kg was predicted to increase exposure by 16%, while halving creatinine clearance was predicted to increase exposure by 10%. Enzyme inducers reduced exposure by 8%, while valproic acid resulted in a 23% increase in exposure. The latter effect was assumed to arise from the known association between valproic acid and increased body fat, since levetiracetam is negligibly metabolised by cytochrome P450 enzymes.. Population pharmacokinetic analysis points to the absence of ethnic differences in the pharmacokinetics of levetiracetam between Japanese and Western populations, other than those arising from bodyweight differences. Small, clinically non-relevant differences between individual demographic characteristics suggest that dose adjustment is usually not necessary.

Topics: Administration, Oral; Anticonvulsants; Body Weight; Cytochrome P-450 Enzyme System; Drug Administration Schedule; Drug Interactions; Epilepsy; Ethnicity; Europe; Humans; Japan; Levetiracetam; Metabolic Clearance Rate; Models, Biological; Piracetam; Regression Analysis; United States

Topics: Animals; Anticonvulsants; Benzodiazepines; Carbamazepine; Epilepsy; Felbamate; Humans; Levetiracetam; Phenylcarbamates; Piracetam; Propylene Glycols; Valproic Acid

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

Levetiracetam (LEV) is a broad-spectrum antiepileptic drug that is effective against a variety of seizure types. It is a pyrridoline derivative with a very favourable pharmacokinetic profile: excellent bioavailability, linear kinetics, minimal plasma protein binding and quick achievement of steady state concentrations. It is not metabolized through the P450 hepatic cytochrome system, does not induce its own metabolism and has no clinically relevant drug-drug interactions. It is available as film-coated tablets, liquid formulation for oral ingestion and intravenous concentrated solution. Controlled and open-label studies have shown its efficacy and safety as initial monotherapy and add-on treatment for partial-onset seizures in children and adults, and also as add-on therapy in refractory partial and primary generalized seizures. Its rapid onset of action, lack of drug-drug interactions and availability as an intravenous solution make it an optimal drug to treat epilepsy associated with other medical conditions. Preliminary reports also suggest potential efficacy in refractory status epilepticus, although this is not a registered indication. Levetiracetam is generally well tolerated, and no serious idiosyncratic side effects have been reported so far. Behavioral side effects (hostility up to aggressive behaviour) are not uncommon. Small, uncontrolled studies have suggested potential therapeutic potential in difficult-to-treat dyskinesias in Parkinson's disease, tremors of different etiologies, migraine prophylaxis and mood disorders. This needs to be confirmed in larger, controlled studies.

Topics: Adolescent; Adult; Anticonvulsants; Child; Comorbidity; Controlled Clinical Trials as Topic; Dosage Forms; Drug Interactions; Epilepsy; Humans; Levetiracetam; Piracetam

Topics: Anticonvulsants; Epilepsy; Humans; Infusions, Intravenous; Injections, Intravenous; Levetiracetam; Pharmaceutical Vehicles; Phenytoin; Piracetam; Solubility; Valproic Acid

Epilepsy is a hetergenous syndrome characterized by recurrently and repeatedly occurring seizures. Although able to inhibit the epileptic seizures, the currently available antiepileptic drugs (AEDs) have no effects on epileptogenesis. Such AEDs should be classified as drugs against ictogenesis, which are transient events in ion and/or receptor-gated channels related with triggering to evoke seizures. Epileptogenesis involves long-term and histological/biochemical/physiological alterations formed in brain structures over a long period, ranging from months to years. This review focuses on the effects of AEDs on epileptogenesis and novel candidates of antiepileptogenic drugs using a genetically defined epilepsy model animal, the spontaneous epileptic rat (SER).

Topics: Animals; Anticonvulsants; Disease Models, Animal; Epilepsy; Levetiracetam; Models, Biological; Piracetam; Rats

On the basis of the relevance of adequate epilepsy treatment (antiepileptic drugs, surgery and vagus nerve stimulation) for people with intellectual disabilities, all articles, published from the beginning of 2005 to March 2006 and searched by MEDLINE, on this topic were reviewed.. On pharmacological treatment of epilepsy in people with intellectual disabilities, there were two articles on topiramate and one on levetiracetam. Two studies described the effect of surgical interventions, one of epilepsy surgery in the narrow sense and one of vagus nerve stimulation. Two papers were published on clinical conditions and therapeutic aspects of Angelman syndrome. They highlight the importance of gamma-aminobutyric acidergic mechanism in Angelman syndrome and the antiepileptic drug effects in this syndrome.. A contradiction exists between the relevance of epilepsy treatment in people with intellectual disabilities and the small number of published studies on pharmacological treatment. Some of the reasons are addressed and some alternatives are proposed.

Topics: Anticonvulsants; Brain; Electric Stimulation Therapy; Epilepsy; Fructose; Humans; Intellectual Disability; Levetiracetam; Neurosurgical Procedures; Piracetam; Postoperative Complications; Topiramate; Vagus Nerve

Epilepsy is a neurological disorder consisting of recurrent seizures, resulting from excessive, uncontrolled electrical activity in the brain. Epilepsy treatment is successful in the majority of the cases; however; still one third of the epilepsy patients are refractory to treatment. Besides the ongoing research on the efficacy of antiepileptic treatments in suppressing seizures (anti-seizure effect), we want to seek for therapies that can lead to plastic, neuromodulatory changes in the epileptic network. Neuropharmacological therapy with levetiracetam (LEV) and vagus nerve stimulation (VNS) are two novel treatments for refractory epilepsy. LEV acts rapidly on seizures in both animal models and humans. In addition, preclinical studies suggest that LEV may have antiepileptogenic and neuroprotective effects, with the potential to slow or arrest disease progression. VNS as well can have an immediate effect on seizures in epilepsy models and patients with, in addition, a cumulative effect after prolonged treatment. Studies in man are hampered by the heterogeneity of patient populations and the difficulty to study therapy-related effects in a systematic way. Therefore, investigation was performed utilizing two rodent models mimicking epilepsy in humans. Genetic absence epilepsy rats from Strasbourg (GAERS) have inborn absence epilepsy and Fast rats have a genetically determined sensitivity for electrical amygdala kindling, which is an excellent model of temporal lobe epilepsy. Our findings support the hypothesis that treatment with LEV and VNS can be considered as neuromodulatory: changes are induced in central nervous system function or organization as a result of influencing and initiating neurophysiological signals.

Topics: Animals; Disease Models, Animal; Electric Stimulation Therapy; Epilepsy; Humans; Levetiracetam; Neurotransmitter Agents; Piracetam; Rats; Vagus Nerve

A new generation of antiepileptic drugs (AEDs) has reached the market in recent years with ten new compounds: felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, vigabatrin and zonisamide. The newer AEDs in general have more predictable pharmacokinetics than older AEDs such as phenytoin, carbamazepine and valproic acid (valproate sodium), which have a pronounced inter-individual variability in their pharmacokinetics and a narrow therapeutic range. For these older drugs it has been common practice to adjust the dosage to achieve a serum drug concentration within a predefined 'therapeutic range', representing an interval where most patients are expected to show an optimal response. However, such ranges must be interpreted with caution, since many patients are optimally treated when they have serum concentrations below or above the suggested range. It is often said that there is less need for therapeutic drug monitoring (TDM) with the newer AEDs, although this is partially based on the lack of documented correlation between serum concentration and drug effects. Nevertheless, TDM may be useful despite the shortcomings of existing therapeutic ranges, by utilisation of the concept of 'individual reference concentrations' based on intra-individual comparisons of drug serum concentrations. With this concept, TDM may be indicated regardless of the existence or lack of a well-defined therapeutic range. The ten newer AEDs all have different pharmacological properties, and therefore, the usefulness of TDM for these drugs has to be assessed individually. For vigabatrin, a clear relationship between drug concentration and clinical effect cannot be expected because of its unique mode of action. Therefore, TDM of vigabatrin is mainly to check compliance. The mode of action of the other new AEDs would not preclude the applicability of TDM. For the prodrug oxcarbazepine, TDM is also useful, since the active metabolite licarbazepine is measured. For drugs that are eliminated renally completely unchanged (gabapentin, pregabalin and vigabatrin) or mainly unchanged (levetiracetam and topiramate), the pharmacokinetic variability is less pronounced and more predictable. However, the dose-dependent absorption of gabapentin increases its pharmacokinetic variability. Drug interactions can affect topiramate concentrations markedly, and individual factors such as age, pregnancy and renal function will contribute to the pharmacokinetic

Topics: Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Drug Interactions; Drug Monitoring; Epilepsy; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Phenylcarbamates; Piracetam; Pregabalin; Propylene Glycols; Tiagabine; Topiramate; Triazines; Vigabatrin; Zonisamide

Levetiracetam is a new antiepileptic drug whose efficacy and tolerability are already well known in adults. Few studies are available in children. This review, based on the international literature, aims to identify and make known the possible indications for levetiracetam in childhood. Most studies suggest that levetiracetam is effective against partial and generalized epilepsy. In resistant partial epilepsy, the percentage of responders reaches 64%, with 8 to 23% seizure free. Levetiracetam is used to treat symptomatic and idiopathic epilepsies. The drug has also proven effective against photosensitivity and epileptic and nonepileptic myoclonus. The most frequent side effects involve the behavioral sphere and manifest mostly in patients with a history of behavioral problems. In some patients, levetiracetam increases the number of seizures, but this adverse reaction can be partially avoided with slow titration. Doses for children should be 130 to 140% of those advised for adults. Levetiracetam seems to have a broad spectrum of action and is, on the whole, well tolerated. Its efficacy against generalized epilepsy is particularly promising in childhood.

Topics: Adult; Animals; Anticonvulsants; Child; Epilepsy; Humans; Levetiracetam; Piracetam; Treatment Outcome

The aim of this paper was to summarize of current knowledge about neuronal injuries during epileptogenesis process and possibilities of neuroprotection.. Many of agents from a wide range of classes have been proposed to possess neuroprotective potential, but especially in experimental and preclinical conditions. Among the antiepileptic drugs topiramate (TPM) and levetiracetam (LEV) possess neuroprotective effects in experimental models of brain damage. Promising protection against cell loss display antioxidants and neurotrophins.. Important and difficult problem of neuroprotective therapy in childhood epilepsy require further experimental and clinical investigations.

Topics: Anticonvulsants; Brain Diseases; Child; Epilepsy; Fructose; Humans; Levetiracetam; Neuroprotective Agents; Piracetam; Topiramate

There has been a growing interest in the use of antiepileptic drugs (AEDs) for neuroprotection, and in the possible role of AEDs in disease modification (i.e., antiepileptogenesis). Increased understanding of the mechanisms underlying brain injury has led to advances in the study of neuroprotection. However, defining the clinical paradigm and selecting appropriate outcomes to detect neuroprotective effects present challenges to clinicians studying the neuroprotective properties of drugs. Established AEDs, such as phenytoin, phenobarbital, and carbamazepine, have shown neuroprotective activity in an ischemic/hypoxic model of neuronal injury. Animal model studies also have suggested that newer AEDs, such as levetiracetam, topiramate, and zonisamide, may have neuroprotective or antiepileptogenic properties. However, the prevention of epileptogenesis by an AED has yet to be demonstrated in clinical trials. The future of neuroprotection may involve established and newer AEDs, as well as other compounds, such as immunophilins, caspase inhibitors, endocannabinoids, and antioxidants.

Topics: Animals; Anticonvulsants; Brain; Epilepsy; Fructose; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Neuroprotective Agents; Piracetam; Seizures; Topiramate; Triazines; Zonisamide

Topics: Adolescent; Amines; Animals; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Cyclohexanecarboxylic Acids; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Pediatrics; Piracetam; Tiagabine; Topiramate; Treatment Outcome; Triazines; Vigabatrin; Zonisamide

This review discusses the safety and tolerability of levetiracetam, as presented by the available literature, with attention paid to special populations. In Phase II/III trials, the adverse effects occurring more commonly in the treatment groups versus the placebo group were; somnolence (14.8 versus 8.4%), asthenia (14.7 versus 9.1%), infection (primarily common cold) (13.4 versus 7.5%), and dizziness (8.8 versus 4.1%). Adverse events usually appear within the first month after treatment initiation, are not dose-dependent, are mostly mild-to-moderate, generally resolve without medication withdrawal, and are transient when the medication is stopped. No significant changes in haematology and chemistry profiles or weight occurred. Hypersensitivity reactions were rare and no idiosyncratic event has been reported. Open-label studies have added patient data with other epileptic syndromes and from a wider patient pool, such as children and patients with prior psychiatric history. These studies have supported initial safety findings, but have reported increased behavioural adverse events in children and patients with a history of prior behavioural problems. Levetiracetam is proving to be safe and well-tolerated. So far, it appears to have a favourable safety profile in special populations, such as children, the elderly, and patients with hepatic dysfunction. Preliminary data in pregnancy are promising, but more data are needed on the impact of levetiracetam on the developing fetus and pharmacokinetic alterations caused in pregnancy. Adjustments in dosing are required for decreases in renal clearance.

Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Age Factors; Aged; Animals; Anticonvulsants; Asthenia; Bone Density; Child; Child Behavior Disorders; Clinical Trials as Topic; Disorders of Excessive Somnolence; Dizziness; Drug Evaluation, Preclinical; Epilepsy; Female; Headache; Humans; Infections; Kidney Diseases; Levetiracetam; Liver Diseases; Male; Mental Disorders; Mice; Middle Aged; Patient Acceptance of Health Care; Piracetam; Pregnancy; Pregnancy Complications

Epilepsy is one of the commonest neurological conditions. For historical reasons, this condition is often managed in the UK by non-specialists. Treatment options have increased markedly in the last 15 years, with a resultant increase in the potential for better seizure control and an enhanced quality of life for patients with epilepsy.

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Piracetam; Treatment Outcome

This report reviews behavioral adverse events occurring among adults receiving levetiracetam (LEV) or placebo who participated in short-term, placebo-controlled studies in epilepsy (1023), cognitive disorders (719), or anxiety disorders (1510) and epilepsy patients (1393) observed in long-term trials. Behavioral events (affective, psychotic, and suicidal symptoms) were significantly more common among epilepsy patients than cognition or anxiety patients treated with LEV for similar durations (P=0.022). Affective symptoms occurring at 1% or more often in epilepsy placebo-controlled trials included depression (3.8% LEV-2.1% placebo), nervousness (3.8%-1.8%), hostility (2.3%-0.9%), anxiety (1.8%-1.1%), and emotional lability (1.7%-0.2%). Patients with cognitive and anxiety disorders had lower incidences of these symptoms. The incidence of behavioral events in LEV-treated epilepsy patients was lower than rates reported for some other antiepileptic drugs. These data support the hypothesis that some feature related to epilepsy is the cause of many behavioral events rather than the addition of a specific antiepileptic drug.

Topics: Anticonvulsants; Anxiety Disorders; Cognition Disorders; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Epilepsy; Follow-Up Studies; Humans; Levetiracetam; Mood Disorders; Outcome Assessment, Health Care; Periodicity; Piracetam; Psychotic Disorders; Randomized Controlled Trials as Topic; Suicide, Attempted

Levetiracetam is the latest in a series of nine new antiepileptic drugs (AEDs) to be licensed for clinical use. Its present license is for use as adjunctive therapy for the treatment of patients with partial seizures with or without secondary generalization that are refractory to other established first line AEDs. Pharmacokinetic studies of levetiracetam have been conducted in healthy volunteers, in patients of all ages with epilepsy, and in certain special populations. Results of these studies indicate that levetiracetam has a very favorable pharmacokinetic profile, characterized by excellent oral absorption and bioavailability (> 95%) and a mean elimination half-life in adults, children and the elderly of 7, 6 and 10.5 h, respectively. Levetiracetam is not bound to plasma proteins and is not metabolized in the liver, so it is not expected to be associated with significant pharmacokinetic interactions. Indeed, to the best of the author's knowledge, no clinically relevant pharmacokinetic interactions with levetiracetam have yet been identified. However, pharmacodynamic interactions with carbamazepine and topiramate have been highlighted. As levetiracetam is primarily excreted unchanged in urine, dosage adjustments are necessary for patients with moderate-to-severe renal impairment. Overall, the pharmacokinetic characteristics of levetiracetam can be considered highly desirable.

Topics: Age Factors; Anticonvulsants; Blood Proteins; Clinical Trials as Topic; Drug Interactions; Drug Monitoring; Epilepsy; Humans; Levetiracetam; Piracetam; Protein Binding

The search for antiepileptic drugs (AEDs) using drug screens that test for the ability to suppress paroxysmal events has primarily resulted in the discovery of AEDs that inhibit neuronal excitability. While profoundly reducing expression of epileptic seizures, current pharmacologic treatments have not been able to completely control seizures in all patients, and can impair normal neuronal excitation underlying cognition. A new approach to drug screening, including the process of epileptogenesis, may yield new classes of drugs that not only suppress seizures but also specifically act to protect against the neurobiological changes that contribute to the development of epilepsy. By preventing or reversing the neuronal circuit reorganizations that produce lowered seizure thresholds following brain insults such as head trauma or status epilepticus, these antiepileptogenic drugs could prevent, or reverse, progressive worsening of the epileptic process. It is likely that antiepileptogenic drugs will have mechanisms of action distinct from traditional AEDs, as the molecular mechanisms underlying epileptogenesis and ictogenesis probably differ. One new AED with potential antiepileptogenic properties is levetiracetam, which was discovered using non-conventional drug screens. It markedly suppresses kindling development at doses devoid of adverse effects, with persistent suppression of kindled seizures even after termination of treatment. Further design and implementation of antiepileptogenic drug screens are needed for the discovery of other novel disease-modifying agents.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Epilepsy; Humans; Kindling, Neurologic; Levetiracetam; Neuroprotective Agents; Piracetam

The pharmacokinetic properties of a drug are the primary deter-minant of the extent and duration of drug action, and influence susceptibility to clinically important drug interactions. Most of the older-generation antiepileptic drugs (AEDs) are far from ideal in terms of pharmacokinetics and interaction potential. For example, phenytoin, carbamazepine, and valproic acid exhibit non-linear kinetics; carbamazepine and valproic acid have relatively short half-lives; and most of these drugs cause either enzyme induction (phenytoin, phenobarbital, primidone, carbamazepine) or enzyme inhibition (valproic acid). Compared with older agents, certain new-generation AEDs offer a num-ber of pharmacokinetic advantages, particularly in terms of reduced inter-patient variability in drug clearance and a lower interaction potential. One of the most recently developed of these drugs, levetiracetam, comes especially close to fulfilling the desirable pharmacokinetic characteristics for an AED: (1) it has a high oral bioavailability, which is unaffected by food; (2) it is not significantly bound to plasma proteins; (3) it is eliminated partly in unchanged form by the kidneys and partly by hydrolysis to an inactive metabolite, without involvement of oxidative and conjugative enzymes; (4) it has linear kinetics; and (5) it is not vulnerable to important drug interactions, nor does it cause clinically significant alterations in the kinetics of concomitantly administered drugs. Although its half-life is relatively short (6 to 8 hours), its duration of action is longer than anticipated from its pharmacokinetics in plasma, and a twice-daily dosing regimen is adequate to produce the desired response.

Topics: Acetates; Amines; Animals; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Drug Interactions; Epilepsy; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Half-Life; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Phenylcarbamates; Piracetam; Propylene Glycols; Tiagabine; Topiramate; Triazines; Vigabatrin; 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

Although short-term clinical trials provide important data regard-ing efficacy and tolerability, long-term studies are needed to address important aspects of clinical practice, such as long-term efficacy and safety. Long-term studies and post-marketing data show that the efficacy of levetiracetam is sustained over the long term and that this antiepileptic drug continues to be well tolerated, with low withdrawal rates and high retention rates. Patients continue to achieve significant reductions in seizure frequency and may achieve seizure freedom. Levetiracetam may allow patients to decrease the number of concomi-tant antiepileptic medications or withdraw to monotherapy. Add-on therapy with levetiracetam should be considered when additional control of seizures is needed.

Topics: Anticonvulsants; Drug Evaluation; Drug Therapy, Combination; Epilepsy; Humans; Levetiracetam; Longitudinal Studies; Piracetam; Product Surveillance, Postmarketing; Quality of Life; Seizures

Levetiracetam is a novel antiepileptic drug (AED) with proven efficacy against partial seizures, but there is limited information about its effectiveness against generalized seizures. In animal models, levetiracetam protects against seizures in audiogenic susceptible rodents, and it is effective in the Genetic Absence Epilepsy Rat from Strasbourg, a model of absence seizures. In these models, levetiracetam has a therapeutic index that is higher than those of other AEDs. A number of small open-label studies suggest that levetiracetam reduces seizure frequency in patients with generalized seizures, including primarily generalized seizures and myoclonic seizures. Case reports provide additional information regarding the potential efficacy of levetiracetam in postanoxic, post-encephalitic and progressive myoclonus. Although random-ized controlled studies of patients with generalized seizures have not yet been conducted, on the basis of available information, levetiracetam may be prom-ising in the treatment of generalized seizures.

Topics: Animals; Anticonvulsants; Clinical Trials as Topic; Electroencephalography; Epilepsy; Follow-Up Studies; Humans; Levetiracetam; Piracetam; Product Surveillance, Postmarketing; Prospective Studies; Seizures

Treatment of seizures in pediatric patients is complicated by the fact that the etiology of the disorder and the pharmacokinetics, efficacy, and safety of antiepileptic drugs (AEDs) may differ from that in adults. With few controlled clinical trials of AEDs in children, the selection of agents to treat pediatric patients must be made on the basis of information from small uncontrolled studies or the extrapolation of clinical trial results in adults. Data from a large number of children with a wide range of seizure disorders who were treated in small-scale prospective studies, or whose records were retrospectively evaluated, indicate that levetiracetam reduces the frequency of seizures in pediatric patients. Available data also indicate that levetiracetam is well tolerated in pediatric patients, with a safety profile similar to that in adults, a low potential for behavioral disturbances, and no reported idiosyncratic adverse reactions. As with other AEDs, children metabolize and clear levetiracetam more rapidly than adults, and somewhat higher doses (based on body weight) are needed to achieve desired plasma concentrations. Several ongoing studies will provide further information on the pharmacokinetics, efficacy, and safety of levetiracetam in this patient population.

Topics: Anticonvulsants; Child; Drug Administration Schedule; Epilepsy; Humans; Levetiracetam; Piracetam; Prospective Studies; Seizures

The standard of care for prescribing antiepileptic drugs (AEDs) has come to favor the use of monotherapy when possible; i.e., when compa-rable efficacy can be achieved with fewer risks of adverse events and drug interactions. Most patients with epilepsy are started on one of the classic AEDs and, if it proves ineffective, another drug is tried, usually as monotherapy. While most of the newer AEDs that have come into clinical use in recent years are initially used as add-on therapy, their success at improving seizure control in combination treatments has led to their cautious use as monotherapy even before they have been approved for this indication. As a first study to determine the potential efficacy of levetiracetam in monotherapy, a withdrawal trial model was used. Patients who achieved adequate seizure control with levetiracetam as add-on therapy in a double-blind, placebo-controlled study entered a monotherapy phase of the trial in which the baseline AED was gradually withdrawn. Also, long-term data of 505 patients who received levetiracetam for refractory partial seizures were reviewed and found to include 49 patients still treated with levetiracetam monotherapy at the end of the study for a duration between 3 months and 5.5 years. Data from patients in the two trials lend supportive evidence that levetiracetam monotherapy is safe and effective for partial seizures.

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Piracetam; Seizures; Time Factors

A good balance between safety and tolerability is necessary for an antiepileptic drug (AED) to be successful in the management of patients with epilepsy. Levetiracetam is one of the new generation of AEDs licensed as an add-on therapy for the treatment of patients with partial-onset seizures. Leveti-racetam's mechanisms of action are not fully understood. Controlled clinical trials, open-label studies, and postmarketing surveillance indicate that leveti-racetam has a favorable safety profile characterized by little effect on vital signs or clinical laboratory values, reported adverse events that are mild to moderate, and no known drug-drug interactions. The tolerability of levetiracetam may extend to both pediatric and elderly patients based on analyses of small numbers of patients. Tolerability is maintained over the long term. Levetirac-etam does not appear to have a different safety profile in learning-disabled patients. Levetiracetam appears to have a good balance between tolerability and efficacy in the treatment of a wide variety of patients with partial epilepsy.

Topics: Age Factors; Anticonvulsants; Drug Interactions; Epilepsy; Humans; Levetiracetam; Persons with Mental Disabilities; Piracetam; Renal Insufficiency; Seizures

Physicians treating patients with epilepsy have a host of thera-peutic options. Drug choice is dictated first by the seizure(s) and/or epilepsy syndrome. Age is also a factor. Special considerations apply to women, particu-larly during their childbearing years, and to patients who are learning-disabled. Drug selection is further influenced by such characteristics as spectrum of activity, rapid response, low potential for drug-drug interactions, and ease of use. In addition to clinical trial data, postmarketing assessments of the new antiepileptic drugs provide useful clinical information on efficacy and safety. Levetiracetam has specific characteristics that make it an optimal choice for many patient populations.

Topics: Adult; Age Factors; Aged; Anticonvulsants; Drug Resistance; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Persons with Mental Disabilities; Piracetam; Prospective Studies; Seizures

Levetiracetam (LEV) is the most recently licensed antiepileptic drug (AED) for adjunctive therapy of partial seizures. Its mechanism of action is uncertain but it exhibits a unique profile of anticonvulsant activity in models of chronic epilepsy. Three randomised, double-blind, placebo-controlled trials enrolling 904 patients with refractory partial epilepsy have demonstrated the efficacy of LEV as adjunctive therapy, with a responder rate (> or = 50% reduction in seizure frequency) of 28-41%. Long-term efficacy studies suggest retention rates of 60% after one year, with 13% of patients seizure-free for six months of the study and 8% seizure-free for one year. Adverse effects of LEV, including somnolence, lethargy and dizziness, were generally mild and the frequency of incidents was not significantly different between the active treatment and placebo groups in clinical trials. LEV has no clinically significant pharmacokinetic interactions (PKI) with other AEDs, or with commonly prescribed medications. Preliminary data suggest that LEV has efficacy in primary generalised epilepsy and further randomised trials are under way. The combination of potent antiepileptic properties with a relatively mild adverse effect profile makes LEV an attractive adjunctive therapy for partial seizures.

Topics: Animals; Anticonvulsants; Chronic Disease; Drug Evaluation; Drug Interactions; Epilepsy; Humans; Levetiracetam; Long-Term Care; Piracetam; Randomized Controlled Trials as Topic; Recurrence; Treatment Outcome

A large number of new antiepileptic drugs (AEDs) have become available over the last 10 years. Results from placebo-controlled clinical trials and community-based practice have demonstrated that levetiracetam has a broad spectrum of activity in suppressing seizures as add-on treatment and monotherapy and that it is safe and well-tolerated. Levetiracetam also has a favourable pharmacokinetic profile characterised by rapid and nearly complete absorption, very low potential for drug interactions and a prolonged pharmacodynamic effect that permits twice-daily dosing. Although, the mechanism of action of levetiracetam is not completely understood, preclinical studies suggest that it may have antiepileptogenic and neuroprotective effects, with the potential to slow or arrest disease progression.

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Piracetam; Quality of Life

Increases in body weight gain are important, and clinically significant adverse effects of several antiepileptic drugs (AED) including valproate and gabapentin. Weight gain may contribute to medication non-compliance, discontinuation, and importantly, may have secondary medical implications as well. Levetiracetam (LEV) is indicated for adjunctive treatment of partial seizures. The objective of the present evaluation was to examine the effects of LEV treatment on body weight in adult patients.. We analyzed data derived from four prospective, placebo-controlled randomized, clinical trials conducted in both in the US and Europe. Patients included in the present analysis were both men and women, greater than 16 years old, and who had LEV exposure for at least 1 month. Body weight was measured at baseline and at the final LEV study visit. Data are analyzed for all patients, by gender, body mass index (BMI), duration of LEV exposure and by concomitant AED treatment. Wilcoxan Signed Rank, or Rank Sum test used where appropriate, with significance assigned at P<0.05. Data are presented as mean values+/-1 S.D.. Nine-hundred and seventy patients (age=37.5 years, 54% men/46% women) were evaluated. There were no significant differences in baseline demographics between LEV (n=631) or placebo (n=339) treated patient groups. Mean LEV dose and duration of treatment were 2053 mg/day (maximum dose of 4000 mg/day) and 125 days (maximum=181 days), respectively. Concomitant AED therapy included CBZ, PHT, VPA, PB, GBP, LTG, and VGB. For LEV-treated patients, no significant changes in body weight were noted. Mean body weight at baseline versus final study visit for LEV was 74.3+/-16.6 kg and 74.3+/-16.6 kg, respectively. For placebo-treated patients, baseline versus end of treatment weight was 72.4+/-15.4 kg and 72.7+/-15.9 kg, respectively, representing a slight, yet clinically trivial increase. Clinically significant weight change as defined as >7% change from baseline weight, occurred in 9% of LEV-treated patients (4.5% had increase in weight/4.5% decrease) versus 9.4% (5.9% had increase/3.5% decrease) in placebo-treated patients. Weight changes were not significantly different between groups. Neither baseline BMI, gender, or background AEDs, appeared to predispose to significant weight change for LEV-treated patients.. We conclude that treatment with LEV at clinically relevant dosages is not associated with significant weight change. LEV would, therefore, appear to be a weight neutral AED.

Topics: Adult; Anticonvulsants; Body Weight; Epilepsy; Europe; Female; Humans; Levetiracetam; Male; Piracetam; United States

To describe the data contained in the most important studies published on the pharmacokinetic and pharmacodynamic properties of levetiracetam, and also the main clinical trials carried out using this new antiepileptic drug.. Derived from piracetam, but with very different properties, levetiracetam is ineffective in the usual models of seizures induced in experimental animals, although it acts in models of prolonged activation, audiogenous seizures and absences and has a novel mode of action. It has pharmacokinetic properties which are nearer to that of the ideal anti epileptic drug. In clinical trials done in adults with partial epilepsies use of 1,000 to 4,000 mg of levetiracetam was significantly more effective than a placebo, and the drug was very well tolerated.. Levetiracetam is the newest antiepileptic drug to appear on the market. Its pharmacodynamic and pharmacokinetic characteristics are excellent. It has currently been approved for use in the polytherapy of patients with partial seizures aged over 16 years. Several studies indicate that its therapeutic spectrum is probably wider, particularly in generalized seizures such as the myoclonias, absences and seizures induced by light stimulation. Thus the indications for levetiracetam may become clear over the next few years.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Epilepsy; Humans; Ion Channels; Levetiracetam; Molecular Structure; Piracetam; Treatment Outcome

Although antiepileptic drugs (AEDs) are commonly used to control and prevent seizures, their long-term use carries a considerable risk of morbidity. The decision to start AEDs is made once the risks of further seizures outweigh the risks of treatment. Despite a large body of literature on the subject, this common clinical issue perplexes many practitioners because of its neurologic, psychological, and, at times, legal implications. Adding to the confusion is the recent approval of several new AEDs. This article summarizes the current evidence to support individual clinical decisions regarding initiation of AEDs in adults and considers the use of AEDs as seizure prophylaxis. Recently approved AEDs are discussed to help the practitioner understand when to initiate and how to choose the appropriate AED for the patient with seizures.

Topics: Acetates; Adult; Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Epilepsy; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Phenylcarbamates; Piracetam; Propylene Glycols; Recurrence; Risk Factors; Tiagabine; Topiramate; Treatment Outcome; Triazines; Zonisamide

The introduction of these new antiepileptic drugs, from felbamate to levetiracetam, raised hope of control of epilepsy with fewer adverse effects and improved quality of life. Unfortunately, many patients continue to experience refractory epilepsy despite the use of these new agents, and dose-related adverse effects and idiosyncratic reactions continue to be problematic. A recent report describes six new compounds in preclinical development, and five in clinical trials [131]. As the number of available, effective, but imperfect antiepileptic drugs increases, many challenges remain. These include: choosing the drug appropriate for the epileptic syndrome, assessing accurately the range of a drug's adverse effects in an individual patient, and considering carefully the drug's interactions in combination drug therapy. In considering drug combinations, differing mechanisms of drug action and favorable pharmacodynamic interactions (an area requiring additional studies) are of importance. Clinicians caring for children who have epilepsy anticipate further advances in the pharmacogenetics and molecular pathophysiology of epilepsy, leading to individually tailored, effective, and safe therapy.

Topics: Acetates; Amines; Anticonvulsants; Carbamazepine; Child; Cyclohexanecarboxylic Acids; Dioxolanes; Epilepsy; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Phenylcarbamates; Phenytoin; Piracetam; Propylene Glycols; Thiazines; Tiagabine; Topiramate; Triazines; Vigabatrin; Zonisamide

To provide a review of recent developments in the pharmacotherapy of epilepsy.. A MEDLINE search was performed to identify pertinent literature (1966-June 2001). Selected articles emphasized those published from 1997 to 2001. Bibliographies of identified articles were also evaluated.. All identifiable sources written in English.. Epilepsy is a common neurologic disorder, and antiepileptic drugs (AEDs) are the mainstays of therapy. The focus of this article is on the 3 latest AEDs--levetiracetam, oxcarbazepine, and zonisamide. We discuss human data published as both original studies and reviews from the last 4 years, except where noted. We apply a general template for all 3 drugs and provide information on clinical trials, adverse effects, pharmacokinetics, drug interactions, and clinical use.. Levetiracetam, oxcarbazepine, and zonisamide are reasonable options for many patients whose seizures are not yet controlled or who suffer from intolerable adverse effects. All 3 agents are approved for adjunctive use in patients with partial seizures. Oxcarbazepine also has approval for monotherapy in partial seizures. All 3 drugs are well tolerated by most patients and have characteristics that potentially make them easier to use with medications other than the older AEDs. Further clinical experience is needed before specific recommendations can be given for their place among older and newer AEDs.

Topics: Anticonvulsants; Carbamazepine; Clinical Trials as Topic; Drug Interactions; Epilepsy; Humans; Isoxazoles; Levetiracetam; Oxcarbazepine; Piracetam; Zonisamide

To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of levetiracetam in the treatment of epilepsy.. A MEDLINE search restricted to English-language publications was conducted (January 1993-October 2000). Unpublished data provided by the manufacturer and information found in proceedings of professional meetings were also included. DATA EXTRACTION/STUDY SELECTION: Information regarding basic pharmacology was collected from studies in animals. Pharmacokinetic data were collected from human trials. Only randomized, placebo-controlled clinical trials were included to describe the efficacy and safety of levetiracetam.. Levetiracetam is a new antiepileptic drug (AED) that appears to work by a unique mechanism. Animal studies have shown that levetiracetam may prevent epileptogenesis. Levetiracetam is rapidly and completely absorbed, minimally bound to plasma proteins, eliminated through the kidneys, and has a half-life of 6-8 hours. Doses must be adjusted for varying degrees of renal function. In clinical trials, levetiracetam significantly decreased seizure frequency compared with placebo when added to existing AED regimens. One clinical trial indicated that levetiracetam may be effective as monotherapy. Few major adverse effects were reported in the clinical trials; however, several patients reported psychological and psychotic reactions.. Levetiracetam is a safe and effective new AED. Its apparent unique mechanism of action makes levetiracetam an important addition to therapy with older medications. Caution should be exercised when administering levetiracetam to individuals who may be prone to psychotic or psychiatric reactions.

Topics: Animals; Anticonvulsants; Epilepsy; Humans; Levetiracetam; MEDLINE; Piracetam; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Anticonvulsants; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsy; Humans; Levetiracetam; Piracetam; Randomized Controlled Trials as Topic; Treatment Outcome

During the last decade, nine new antiepileptic drugs were approved for use by the US Food and Drug Administration. The characteristics of three of these new antiepileptic drugs-levetiracetam, oxcarbazepine, and zonisamide--are reviewed here. Their individual characteristics, including mechanism of action, efficacy, safety, and pharmacokinetics, are compared, and their effectiveness in treating specific seizure types is noted. As with all antiepileptic drugs, the efficacy, side-effect, and pharmacokinetic profiles must be matched to each individual's clinical profile to attain the maximum benefit. All three are unique and will be useful in expanding the aggregate of therapies available to clinicians treating diverse epilepsy syndromes and seizure types. This review focuses on results in adults; pediatric experience is reported in other articles in this supplement.

Topics: Anticonvulsants; Carbamazepine; Clinical Trials as Topic; Epilepsy; Humans; Isoxazoles; Levetiracetam; Oxcarbazepine; Piracetam; Treatment Outcome; Zonisamide

New epilepsy treatment options are becoming available to physicians and may help provide safe and effective seizure management in patients for whom traditional drug therapies have been unsuccessful. Presented here is a brief discussion on the screening models used to test drugs for efficacy against various seizure types and the mechanisms of action and pharmacology of antiepilepsy drugs. This is followed by a more detailed review of the clinical pharmacology of the latest three antiepilepsy drugs introduced to the United States: levetiracetam, oxcarbazepine, and zonisamide. All three appear to have advantages over some traditional antiepilepsy drugs and with more clinical experience may replace them in certain seizure types or epilepsy syndromes.

Topics: Anticonvulsants; Carbamazepine; Child; Clinical Trials as Topic; Epilepsy; Humans; Isoxazoles; Levetiracetam; Oxcarbazepine; Piracetam; Treatment Outcome; Zonisamide

Topics: Anticonvulsants; Data Interpretation, Statistical; Epilepsy; Humans; Levetiracetam; Piracetam; Randomized Controlled Trials as Topic; Sample Size

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of levetiracetam are reviewed. Levetiracetam is an adjunctive treatment for partial-onset epileptic seizures. This drug inhibits seizure activity via a mechanism that does not involve excitatory or inhibitory neuronal pathways. Oral bioavailability is about 100%, and food does not alter absorption. Levetiracetam is minimally plasma protein bound (10%). Peak time to absorption after oral administration is one hour, and steady state is achieved in two days with twice-daily administration. Three clinical studies have demonstrated levetiracetam's ability to reduce seizure frequency in patients with partial-onset epilepsy. The most commonly reported adverse effects in clinical trials were somnolence, dizziness, infection, and asthenia. The potential for interactions with medications that are hepatically metabolized is minimal. The starting dosage is 500 mg twice a day; the maximum dosage is 3000 mg/day within four weeks. Levetiracetam is effective as an adjunctive treatment of partial-onset epilepsy with or without secondary generalization.

Topics: Anticonvulsants; Area Under Curve; Biological Availability; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Epilepsy; Half-Life; Humans; Intestinal Absorption; Levetiracetam; Piracetam; Randomized Controlled Trials as Topic; Tissue Distribution

Topics: Anticonvulsants; Drug Approval; Drug Interactions; Epilepsy; Female; Humans; Levetiracetam; Liver; Male; Piracetam; United States

Levetiracetam is a new antiepileptic drug (AED) devoid of anticonvulsant activity in the two classic screening models for AEDs, the maximal electroshock and pentylenetetrazol seizure tests in both mice and rats. This contrasts a potent seizure suppression in genetic and kindled mice and rats and against chemoconvulsants inducing partial seizures in rats. The highly selective action in "epileptic" animals distinguishes levetiracetam from classic and other new AEDs that have nearly equipotent effects in normal and "epileptic" animals. Levetiracetam induces minor behavioral alterations in normal and in kindled mice and rats. This results in an unusually high safety margin in animal models reflecting both partial and primary generalized epilepsy. Furthermore, experiments in the kindling model suggest that levetiracetam may possess antiepileptogenic properties due to a potent ability to prevent the development of kindling in mice and rats at doses devoid of adverse effects. Electrophysiologic recordings from different experimental models suggest that levetiracetam exerts a selective action against abnormal patterns of neuronal activity, which probably explains its selective protection in epileptic animals and its unique tolerability. This effect appears to derive from one or more novel mechanisms of action that do not involve a conventional interaction with traditional drug targets implicated in the modulation of inhibitory and excitatory neurotransmission. Instead, ligand-binding assays have disclosed a brain-specific binding site for levetiracetam. These studies reveal a unique preclinical profile of levetiracetam, distinct from that of all known AEDs, suggesting that levetiracetam could represent the first agent in a new class of AEDs.

Topics: Amygdala; Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Electric Stimulation; Epilepsy; Kindling, Neurologic; Levetiracetam; Mice; Piracetam; Rats; Seizures

Each antiepileptic drug has a characteristic pharmacokinetic profile, and the unique properties of each must be considered when selecting the optimal agent for a particular patient. Detailed pharmacologic data are obtained during the preapproval evaluation of a drug, particularly in early phase studies in healthy volunteers. Each drug is then evaluated in the target population in later phase trials and in certain populations, such as children and individuals with various types of organ failure. Key considerations are bioavailability, protein binding, metabolism and elimination, and drug interactions. Important pharmacokinetic considerations in the selection and use of these drugs are presented in this review, with examples from currently available drugs.

Topics: Adult; Age Factors; Aged; Anticonvulsants; Biological Availability; Child; Drug Interactions; Drug Prescriptions; Drug Therapy, Combination; Epilepsy; Female; Half-Life; Humans; Levetiracetam; Male; Piracetam; Pregnancy; Protein Binding; Sex Factors

Major considerations in the acceptance and impact of new antiepileptic drugs include their pharmacokinetics and their potential for interaction with other drugs. The pharmacokinetics of levetiracetam, a newly approved add-on antiepileptic agent for partial-onset seizures in adults, has been evaluated in 27 phase I and II studies. Consistent findings in these studies include rapid and complete oral absorption, linear dose kinetics, a minimal degree of protein binding, and predominantly renal excretion. Because of the lack of hepatic metabolism and low protein binding, the risk of interaction with other drugs is considered low.

Topics: Administration, Oral; Adult; Age Factors; Aged; Anticonvulsants; Biological Availability; Child; Clinical Trials as Topic; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Epilepsy; Half-Life; Humans; Levetiracetam; Piracetam

A number of commonly used antiepileptic drugs (AEDs) produce severe adverse effects if they are introduced at their usual daily maintenance doses. Gradual slow titration of the dose often avoids these adverse effects almost entirely. Conversely, some AEDs can be started at their effective maintenance dose and perhaps even with a loading dose. Although the mechanisms of these distinctions among antiepileptic compounds are poorly understood, the phenomenon clearly has important implications for the optimal use of the drugs, especially when rapid seizure control is desired. Examples of drugs that require gradual introduction are lamotrigine, carbamazepine, topiramate, tiagabine, and zonisamide. Phenytoin, oxcarbazepine, gabapentin, valproate, and levetiracetam are examples of drugs that can be started at an effective dose.

Topics: Anticonvulsants; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Epilepsy; Humans; Levetiracetam; Piracetam; Treatment Outcome

Levetiracetam is a novel antiepileptic drug (AED) with favorable pharmacologic characteristics and demonstrated activity in improving seizure control. Three multicenter double-blind, placebo-controlled studies were conducted in 904 patients with refractory partial-onset seizures. Patients were required to have a minimum of two or four seizures per week (depending on the study) and were maintained on a stable regimen of one or two AEDs at baseline that was continued during the study period. Patients ranged in age from 14 to 70 years, with a mean age of approximately 37 years. After an 8- to 12-week baseline period, patients were randomized and had doses titrated upward every 2 weeks over a period of 4 weeks to a target dose of 1,000, 2,000, or 3,000 mg/day of levetiracetam or placebo. Treatment was continued for a 12- to 14-week evaluation phase followed by an optional open-label treatment phase. The treatment period consisted of the dose titration period combined with the evaluation period. The median percentage reduction in seizure frequency (over placebo) was calculated for each of the levetiracetam treatment groups over the entire treatment period. For all levetiracetam dose groups, in all studies, reduction in seizure frequency over placebo was statistically significant (p < or = 0.001). Median percentage reductions were 26.1% and 17.1% in the 1,000-mg/day groups (study 1 and study 2, respectively), 21.4% in the 2,000-mg/day group (study 2), and 30.1% and 23.0% in the 3,000-mg/day groups (study 1 and study 3, respectively). The percentage of patients achieving a > or = 50% reduction from baseline in seizure frequency compared with the treatment period was 37.1% and 20.8% in the 1,000-mg/day groups (study 1 and study 2, respectively), 35.2% in the 2,000-mg/day group (study 2), and 39.6% and 39.4% in the 3,000-mg/day groups (study 1 and study 3, respectively). These responder rates were significantly higher than those for placebo (p < 0.001 for all comparisons). Levetiracetam was generally well tolerated in all studies. Results from these three pivotal studies demonstrate that levetiracetam, as adjunctive therapy, is a safe and effective treatment for refractory partial-onset seizures in adults.

Topics: Adolescent; Adult; Age Factors; Aged; Anticonvulsants; Drug Administration Schedule; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Multicenter Studies as Topic; Piracetam; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome

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

A subset of the 27 safety and pharmacokinetic studies of levetiracetam has been conducted in selected special populations: children, the elderly, and people with renal or hepatic impairment. The results of these studies indicate that higher doses need to be used for children (on a per-weight basis), and individuals with renal dysfunction require dosage modifications related to creatinine clearance. Individuals with hepatic impairment do not require modifications from standard doses. Little information is available on the effect of levetiracetam on the developing fetus, so cautious use during pregnancy is recommended until more information is available. Additional studies will refine the recommendations for use of levetiracetam in these special populations.

Topics: Adult; Age Factors; Aged; Anticonvulsants; Child; Comorbidity; Contraceptives, Oral; Drug Approval; Drug Interactions; Epilepsy; Female; Humans; Kidney Failure, Chronic; Levetiracetam; Liver Diseases; Male; Middle Aged; Piracetam; Sex Factors

This report provides detailed review of safety information on levetiracetam (LEV) (Keppra), a new antiepileptic drug.. The integrated summary of safety report submitted for regulatory review was examined to collate information about abnormal laboratory tests values and adverse event reports collected during the overall LEV development program. Analyses included 3347 patients exposed to LEV in clinical trials for epilepsy, cognition, and anxiety disorders.. Safety data from all studies depict a similar pattern of adverse effects, predominantly somnolence, asthenia, and dizziness that occurred most frequently during the first month of LEV treatment. Changes in laboratory test values from placebo-controlled trials that were statistically significant remained in the normal range (red blood cells, hematocrit, hemoglobin, white blood cells, and neutrophils). Reports of the coding term 'infection' (common cold, upper respiratory infection) were not preceded by low neutrophil counts that might suggest impaired immunological status. Selection of adverse event coding terms probably contributed to the high rate of adverse effects termed 'infection.' Higher incidences of adverse effects, particularly behavioral effects, were found among epilepsy patients than in elderly patients with cognitive disorders or patients with anxiety disorders given lower doses.. This review of patients evaluated during the clinical development program suggests that LEV was well tolerated and safe for patients with seizure, cognitive and anxiety disorders. Overall incidence of adverse effects in the LEV groups was little higher than reports from the placebo groups. Of course, this data was derived from clinical trials that are of relatively short duration, and provide data on only several thousand patients. Therefore, long-term side effects, and/or rare side effects cannot be ruled out on the basis of this analysis.

Topics: Anticonvulsants; Clinical Trials as Topic; Epilepsy; Levetiracetam; Piracetam

Levetiracetam is a novel orally active antiepileptic drug with a unique preclinical profile. It has a high therapeutic index and potential antiepileptogenic effects. Results of clinical trials indicate activity in partial-onset and generalized seizures. The pharmacokinetic profile of levetiracetam closely approximates the ideal characteristics expected of an antiepileptic drug, with good bioavailability, rapid achievement of steady-state concentrations, linear and time-invariant kinetics, minimal protein binding, and minimal metabolism. The major metabolic pathway of levetiracetam is not dependent on the hepatic cytochrome P450 system, and levetiracetam does not inhibit or induce hepatic enzymes to produce clinically relevant interactions. Sixty-six percent of an administered levetiracetam dose is eliminated unchanged in urine; 24% is metabolized to an inactive metabolite that is detectable in blood and is also excreted in urine. Total body clearance of levetiracetam is decreased in patients with renal impairment, and doses should be modified according to creatinine clearance values. Levetiracetam is not appreciably protein-bound, nor does it affect the protein binding of other drugs. Thus, because of its minimal protein binding and lack of hepatic metabolism, the risk of drug interactions is very low. Levetiracetam has a wide margin of safety and patient-friendly pharmacokinetics that distinguish it from other currently available antiepileptic drugs. This profile may facilitate the clinical management of patients with epilepsy by providing a safer and less-complicated therapeutic strategy.

Topics: Absorption; Adolescent; Adult; Aged; Anticonvulsants; Child; Cytochrome P-450 Enzyme System; Drug Interactions; Epilepsy; Humans; Kidney Diseases; Levetiracetam; Liver Diseases; Middle Aged; Piracetam; Therapeutic Equivalency

Piracetam (PIR) and levetiracetam (LEV), an S-enantiomer, are pyrrolidone derivatives that share similar chemical structures but have distinct pharmacological profiles and consequently different clinical uses. Although the mode of action of neither drug has been fully elucidated, they do not interact with inhibitory or excitatory neurotransmission or alter membrane excitability. A brain-specific stereoselective binding site has been identified for which LEV and other S-enantiomers, but not PIR, have high affinity. In preclinical studies, PIR significantly improves learning and memory; in contrast, LEV has less effect but is much more active in preventing seizures. Both drugs have a high therapeutic index and are well tolerated. PIR, a nootropic drug, is used in the therapy of age-related cognitive disturbances and poststroke aphasia. Clinical experience has also shown that at high doses it is effective against cortical myoclonus. LEV is an antiepileptic drug. Clinical trials have confirmed its efficacy in partial seizures and preliminary findings suggest that it is also effective in generalized seizures and myoclonus.

Topics: Animals; Anticonvulsants; Brain; Cognition Disorders; Dogs; Epilepsy; Humans; Learning; Levetiracetam; Memory; Mice; Nootropic Agents; Piracetam; Rats

A brief review of epilepsy as a disease, anti-epileptic drugs (AEDs) and methods of evaluation of AEDs are presented as a background for the assessment of levetiracetam which has been approved by the FDA as add-on therapy for the treatment of partial seizures with or without secondary generalisation in adults. The exact mechanism of action of levetiracetam is not known but its action differs from that of other anti-epileptic drugs. A specific binding site for levetiracetam has been identified and is possibly related to anticonvulsant activity. Levetiracetam offers an effective and broad spectrum treatment of epileptic seizures, partial as well as generalised epilepsy. Levetiracetam has been shown to be effective in genetic and kindled animal models of epilepsy and against chemoconvulsant-induced partial epileptic seizures. Levetiracetam has a near perfect pharmacokinetic profile, with rapid absorption following oral administration, excellent bioavailability, quick attainment of steady-state concentrations, linear kinetics and minimal plasma protein binding. Levetiracetam does not interact with commonly used drugs and other AEDs. In recent Phase III clinical trials, the responder rate was 39.4 - 42.1% on 3000 mg dose, compared with placebo rates of 10.9 - 16.7%. Levetiracetam has a favourable safety profile and the most frequently reported adverse events were somnolence, asthenia and dizziness. Overall, levetiracetam is considered to have several advantages over current AEDs.

Topics: Animals; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Piracetam

Epilepsy is one of the most common neurological disorders. Even though existing antiepileptic drugs can render 80% of newly diagnosed patients seizure free, a significant number of patients have chronic intractable epilepsy causing disability with considerable socioeconomic implications. There is, therefore, a need for more potent and effective antiepileptic drugs and drugs with fewer adverse effects, particularly CNS effects. Drugs for the treatment of partial seizures are particularly needed. With major advances in our understanding of the basic neuropathology, neuropharmacology and neurophysiology of epilepsy, numerous candidate novel antiepileptic drugs have been developed in recent years. This review comparatively evaluates the pharmacokinetics, efficacy and adverse effects of 12 new antiepileptic drugs namely vigabatrin, lamotrigine, gabapentin, oxcarbazepine, felbamate, tiagabine, eterobarb, zonisamide, remacemide, stiripentol, topiramate and levetiracetam (ucb-L059). Of the 12 drugs, vigabatrin, lamotrigine and gabapentin have recently been marketed in the UK. Five of these new drugs have known mechanisms of action (vigabatrin, lamotrigine, tiagabine, oxcarbazepine and eterobarb), which may provide for a more rational approach to the treatment of epilepsy. Oxcarbazepine, remacemide and eterobarb are prodrugs. Vigabatrin, gabapentin and topiramate are more promising on the basis of their pharmacokinetic characteristics in that they are excreted mainly unchanged in urine and not susceptible to significant pharmacokinetic interactions. In contrast, lamotrigine, felbamate and stiripentol exhibit significant drug interactions. Essentially, all the drugs are effective in partial or secondarily generalised seizures and are effective to varying degrees in other seizure types. Particularly welcome is the possible effectiveness of zonisamide in myoclonus and felbamate in Lennox-Gastaut syndrome. In relation to adverse effects, CNS effects are observed with all drugs, however, gabapentin, remacemide and levetiracetam appear to exhibit least. There is also the possibility of rational duotherapy, using drugs with known mechanisms of action, as an additional therapeutic approach. The efficacy of these 12 antiepileptic drug occurs despite the fact that candidate antiepileptic drugs are evaluated under highly unfavourable conditions, namely as add-on therapy in patients refractory to drug management and with high seizure frequency. Thus, whilst candidate drugs wh

Topics: Acetamides; Acetates; Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Dioxolanes; Epilepsy; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Phenobarbital; Phenylcarbamates; Piracetam; Propylene Glycols; Risk Factors; Tiagabine; Topiramate; Triazines; Vigabatrin; Zonisamide

Via measures of efficacy, tolerability, and safety, this open-label, single-center study assessed the overall effectiveness of Brivaracetam (BRV) for the treatment of epilepsy in the context of 'real-world' clinical practice.. Unselected consecutive patients were recruited and stratified into 3 cohorts with either fully prospective, fully retrospective or mixed data collection, dependent on whether their BRV prescriptions were historical, current, or pending. Prospective data were obtained at baseline, 3 and 6 months, and at 6-month intervals thereafter, from patient interviews and seizure diaries, and retrospective data from medical records. Efficacy variables were derived from seizure-related changes, and tolerability and safety variables from reported treatment-emergent adverse events (TEAEs), BRV withdrawal, and changes to questionnaire scores. Additionally, we investigated treatment outcomes for those with previous levetiracetam (LEV) use, a history of psychiatric comorbidity, a learning disability, and of older age.. One hundred and nine patients (58.7% female, mean age 42 years, range: 18 to 72) were included, 59 with prospective follow-up for a minimum of 6 (47 patients, excluding those who withdrew) and a maximum of 24 months (2 patients). Of the full cohort, 87.2% had drug-resistant epilepsy. Retention: At the study end, the median treatment duration was 384 days (range: 6 to 1514 days), and BRV retention was 68.8%. Kaplan-Meier survival functions predicted retention rates of 74.0% and 70.0% at 6 and 12 months respectively.. At the last follow-up, there was a ≥ 50% responder rate of 30.8%, with 12.1% seizure-free. Seizure frequency categories improved in 31.4% of patients, remained the same in 44.2%, and worsened in 24.4%. Monthly tonic-clonic seizure frequency had significantly decreased, and of those reporting these seizures, 58.3% showed reductions and 25.0% showed complete tonic-clonic seizure freedom.. 91.7% of patients reported at least 1 TEAE, with fatigue (30.3%), irritability (29.4%), and depression/low mood (28.4%) as the most common. Only 58.4% of all TEAEs were persistent. Brivaracetam discontinuation due to side effects occurred in 27.5% of the cohort. Depression and anxiety scores remained stable over time, and quality-of-life scores improved. Subgroups: Measures of BRV efficacy and tolerability did not differ according to previous LEV exposure. Tolerability profiles of those with learning disabilities, histories of psychiatric comorbidities, and older age did not greatly differ from the rest of the cohort. Of note, specific history of depression predicted the reporting of suicidal ideation.. The BRIVEST study provides real-world evidence of the effectiveness of BRV, suggesting that neither drug-resistant epilepsy nor previous LEV failure should preclude its use. Furthermore, BRV appears to be well-tolerated, even among those from vulnerable patient populations.

Topics: Adult; Anticonvulsants; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Prospective Studies; Pyrrolidinones; Retrospective Studies; Seizures; Treatment Outcome

Topics: Anticonvulsants; Developing Countries; Epilepsy; Humans; Infant, Newborn; Infant, Newborn, Diseases; Levetiracetam; Phenobarbital; Pilot Projects; Seizures

Levetiracetam is a commonly used anti-seizure medication, with the development of neuropsychiatric symptoms being the most common side effect. Preliminary literature describes the improvement of these symptoms with pyridoxine, mostly within the pediatric population. However, randomized control trial data investigating this relationship is sparse.. The objective of this study was to critically assess evidence regarding the role of pyridoxine in the treatment of neuropsychiatric symptoms from levetiracetam.. The objective was addressed through the development of a structured, critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, medical librarians, clinical epidemiologists, and content experts in the field of epilepsy.. A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared pyridoxine versus placebo for the treatment of neuropsychiatric symptoms from levetiracetam in a pediatric population and included 105 patients (46/105 received pyridoxine, 59/105 received placebo). It found that both groups had a significant reduction in behavioral symptoms at the 2-,4-and 6-week time points ( P <0.05). However, the authors noted that the pyridoxine group had almost double the relative reduction when compared with the placebo group at all time points: 1.9 at 2 weeks, 2.0 at 4 weeks, and 1.8 at 6 weeks ( P =0.001).. This study suggests that pyridoxine for the treatment of levetiracetam-induced behavioral side effects may result in modest improvement, although many limitations prevent conclusive results. There remains a need for a double-blinded, randomized control trial in both the adult and pediatric populations.

Topics: Adult; Child; Epilepsy; Humans; Levetiracetam; Pyridoxine

Neonatal seizures are one of the most challenging problems for experts across the globe. Although there is no consensus on the "ideal" treatment of neonatal seizures, phenobarbitone has been the drug of choice for decades. Unfortunately, although extensively studied in adults and children, levetiracetam lacks rigorous evaluation in the neonatal population, despite its frequent use as an off-label drug. The objective of this open-label, randomized, active-control, single-center, pragmatic trial was to compare the effectiveness of levetiracetam with phenobarbitone for term asphyxiated infants as a first-line drug.. The participants included in this study were inborn term asphyxiated infants with seizures in the first 48 hours of life. Infants satisfying the inclusion criteria were randomized to receive levetiracetam (20 mg/kg) or phenobarbitone (20 mg/kg). Clinical seizure control was noted. Infants who failed to respond to the primary drug were given the other group drug.. Of 103 eligible infants, 82 were randomly assigned (44 levetiracetam group, 38 phenobarbitone group). Clinical seizure control with the primary drug and maintenance of the same for 24 hours was observed in 29 infants (65.9%) in the levetiracetam group and 13 infants (34.2%) in the phenobarbitone group (P < .05, relative risk 0.52, 95% confidence interval 0.32-0.84). Of the infants in the phenobarbitone group who did not respond to the primary drug, 57.8% were controlled after adding levetiracetam.. Levetiracetam can be used with effectiveness as a first- and second-line drug in asphyxiated term infants. A more extensive study on pharmacokinetics and optimal regimen is required.

Topics: Adult; Anticonvulsants; Child; Epilepsy; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Levetiracetam; Off-Label Use; Phenobarbital; Seizures

The incidence of early seizures (occurring within 7 days of stroke onset) after intracerebral haemorrhage reaches 30% when subclinical seizures are diagnosed by continuous EEG. Early seizures might be associated with haematoma expansion and worse neurological outcomes. Current guidelines do not recommend prophylactic antiseizure treatment in this setting. We aimed to assess whether prophylactic levetiracetam would reduce the risk of acute seizures in patients with intracerebral haemorrhage.. The double-blind, randomised, placebo-controlled, phase 3 PEACH trial was conducted at three stroke units in France. Patients (aged 18 years or older) who presented with a non-traumatic intracerebral haemorrhage within 24 h after onset were randomly assigned (1:1) to levetiracetam (intravenous 500 mg every 12 h) or matching placebo. Randomisation was done with a web-based system and stratified by centre and National Institutes of Health Stroke Scale (NIHSS) score at baseline. Treatment was continued for 6 weeks. Continuous EEG was started within 24 h after inclusion and recorded over 48 h. The primary endpoint was the occurrence of at least one clinical seizure within 72 h of inclusion or at least one electrographic seizure recorded on continuous EEG, analysed in the modified intention-to-treat population, which comprised all patients who were randomly assigned to treatment and who had a continuous EEG performed. This trial was registered at ClinicalTrials.gov, NCT02631759, and is now closed. Recruitment was prematurely stopped after 48% of the recruitment target was reached due to a low recruitment rate and cessation of funding.. Between June 1, 2017, and April 14, 2020, 50 patients with mild-to-moderate severity intracerebral haemorrhage were included: 24 were assigned to levetiracetam and 26 to placebo. During the first 72 h, a clinical or electrographic seizure was observed in three (16%) of 19 patients in the levetiracetam group versus ten (43%) of 23 patients in the placebo group (odds ratio 0·16, 95% CI 0·03-0·94, p=0·043). All seizures in the first 72 h were electrographic seizures only. No difference in depression or anxiety reporting was observed between the groups at 1 month or 3 months. Depression was recorded in three (13%) patients who received levetiracetam versus four (15%) patients who received placebo, and anxiety was reported for two (8%) patients versus one (4%) patient. The most common treatment-emergent adverse events in the levetiracetam group versus the placebo group were headache (nine [39%] vs six [24%]), pain (three [13%] vs ten [40%]), and falls (seven [30%] vs four [16%]). The most frequent serious adverse events were neurological deterioration due to the intracerebral haemorrhage (one [4%] vs four [16%]) and severe pneumonia (two [9%] vs two [8%]). No treatment-related death was reported in either group.. Levetiracetam might be effective in preventing acute seizures in intracerebral haemorrhage. Larger studies are needed to determine whether seizure prophylaxis improves functional outcome in patients with intracerebral haemorrhage.. French Ministry of Health.

Topics: Cerebral Hemorrhage; Epilepsy; Humans; Levetiracetam; Seizures; Stroke; Treatment Outcome; United States

Levetiracetam is a broad-spectrum antiseizure medication with known behavioral side effects. The possible beneficial effect of pyridoxine on improvement of these psychiatric problems has been suggested in few previous studies. This clinical trial aimed to investigate the effect of pyridoxine on behavioral side effects of levetiracetam in adult patients with epilepsy.. This study was a randomized double-blind placebo-controlled clinical trial on 53 adult patients with epilepsy with behavioral side effects after treatment by levetiracetam. Patients who met the study criteria were randomized to receive 40 mg/day pyridoxine or placebo. Their psychiatric state was surveyed by SCL-90-R questionnaire before and three weeks after initiation of treatment.. There were no statistically significant differences in the behavioral adverse effects between the pyridoxine-treated group and the placebo group.. Although this study showed no statistically significant beneficial effects of pyridoxine on the behavioral adverse effects of levetiracetam, placebo-controlled trials with a larger size and higher doses are needed to determine whether it is effective or not.

Topics: Adult; Anticonvulsants; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Humans; Levetiracetam; Piracetam; Pyridoxine; Treatment Outcome

Anti-seizure medications are used to manage epilepsy and require long-term adherence to maintain therapeutic drug levels. We assessed adherence to levetiracetam and the use of a digital intervention to improve adherence in patients with epilepsy.. 30 participants with epilepsy were randomized 1:1 either to a digital email adherence intervention or control group. All patients were provided levetiracetam equipped with electronic monitoring caps to assess patient adherence to medication. Patients were followed for 6 months, with return visits at 1 month, 3 months, and 6 months.. Subjects randomized to the control arm (n = 15) took 66% of the prescribed doses compared to the intervention group, who took 65% of prescribed doses (n = 15). Nine participants did not complete the study. Of the twenty-one participants that completed the study, the overall rate of adherence was 72% of prescribed doses taken. Two subjects in the control group and three subjects in the intervention group were adherent every month of the study-taking at least 80% of prescribed doses. Those randomized to the control group took the correct number of doses 44% of days in the study, and those in the intervention group took the correct number of doses 37% of days.. Poor adherence to levetiracetam is common. An internet-based email survey intervention did not improve adherence to levetiracetam in epilepsy patients. Further advances in adherence are needed to help patients receive the maximum benefit of their medical treatments.

Topics: Electronics; Epilepsy; Humans; Levetiracetam; Medication Adherence; Patient Compliance; Surveys and Questionnaires

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

The choice of antiepileptic drug (AED) in newly diagnosed neurocysticercosis (NCC) patients with epilepsy continues to be arbitrary. We compared efficacy and side effect profile of levetiracetam (LEV) and carbamazepine (CBZ) for the treatment of seizures in newly diagnosed patients with NCC.. This was an open-labeled randomized comparative monotherapy study including newly diagnosed drug naïve patients of NCC (n = 99) presenting with seizures who were randomized in 1:1 ratio using computed generated numbers. All patients were followed up for at least six months after start of treatment. The primary outcome measure was seizure control over six months following start of AEDs.. Fifteen (15.2%) patients [CBZ- 4(8.2%); LEV- 11(22%)] developed recurrence of seizures. A trend (p = 0.09) was found toward better control of seizures in CBZ compared to LEV. Two (4%) patients in LEV group and 17 (34.6%) patients in CBZ group developed drug-related minor side effects (p < 0.0001). Three patients in CBZ group needed discontinuation of therapy due to skin rash. Eleven patients who relapsed while on LEV did not have any recurrence of seizures after switching over to CBZ. Out of 3 patients who relapsed while receiving CBZ and were changed to LEV, two developed seizures during follow-up.. CBZ and LEV could be used as alternatives in newly diagnosed patients of NCC at the behest of minor side effects in the CBZ group.

Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; Child; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Neurocysticercosis; Young Adult

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

Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment. Over the past 20 years, a number of new drugs have been approved for National Health Service (NHS) use on the basis of information from short-term trials that demonstrate efficacy. These trials do not provide information about the longer term outcomes, which inform treatment policy. This trial will assess the long-term clinical and cost-effectiveness of the newer treatment levetiracetam and zonisamide.. This is a phase IV, multicentre, open-label, randomised, controlled clinical trial comparing new and standard treatments for patients with newly diagnosed epilepsy. Arm A of the trial randomised 990 patients with focal epilepsy to standard AED lamotrigine or new AED levetiracetam or zonisamide. Arm B randomised 520 patients with generalised epilepsy to standard AED sodium valproate or new AED levetiracetam. Patients are recruited from UK NHS outpatient epilepsy, general neurology and paediatric clinics. Included patients are aged 5 years or older with two or more spontaneous seizures requiring AED monotherapy, who are not previously treated with AEDs. Patients are followed up for a minimum of 2 years. The primary outcome is time to 12-month remission from seizures. Secondary outcomes include time to treatment failure (including due to inadequate seizure control or unacceptable adverse reactions); time to first seizure; time to 24-month remission; adverse reactions and quality of life. All primary analyses will be on an intention to treat basis. Separate analyses will be undertaken for each arm. Health economic analysis will be conducted from the perspective of the NHS to assess the cost-effectiveness of each AED.. This trial has been approved by the North West-Liverpool East REC (Ref. 12/NW/0361). The trial team will disseminate the results through scientific meetings, peer-reviewed publications and patient and public involvement.. EudraCT 2012-001884-64; ISRCTN30294119.

Topics: Anticonvulsants; Carbamazepine; Child; Child, Preschool; Clinical Trials as Topic; Cost-Benefit Analysis; Epilepsy; Humans; Levetiracetam; Multicenter Studies as Topic; Pragmatic Clinical Trials as Topic; Quality of Life; Randomized Controlled Trials as Topic; State Medicine; Zonisamide

To evaluate pregnancy outcomes among women participating in the antiepileptic drug (AED) Levetiracetam Registry (LEV-Registry), and to review the impact of using two other registries' outcome definitions on the number of major congenital malformations (MCMs).. This US-based prospective study (ClinicalTrials.gov NCT00345475) was overseen by an independent Expert Panel. Women exposed to levetiracetam at any time during pregnancy enrolled, directly, or via their healthcare provider. The primary outcome was prevalence of MCMs, defined according to a modified version of the Metropolitan Atlanta Congenital Defects Program criteria.. Of 491 women enrolled, 465 (94.7%) had a documented outcome. Most (92.3%) received levetiracetam for epilepsy; 323 (69.4%) as monotherapy and 142 (30.5%) as polytherapy. With three twin pregnancies, there were 468 outcomes-444 livebirths, 3 stillbirths, 19 miscarriages, and 2 terminations. Based on the MCM definition used by LEV-Registry, 46 infants among 444 livebirths had MCMs resulting in 10.4% (95% CI 7.7, 13.6) for overall prevalence, 9.4% (95% CI 6.4, 13.2) with monotherapy, and 12.6% (95% CI 7.5, 19.4) with polytherapy. When MCM reports were reviewed independently by staff at EURAP (International Registry of AEDs) and North American AED Pregnancy Registry according to their respective criteria, only 22 and 7 infants of the 46, respectively, were classified as having MCMs.. The LEV-Registry Expert Panel did not find evidence suggestive of teratogenic association with prenatal exposure to levetiracetam. The substantial differences in which physical findings were considered MCMs highlight the major impact of pregnancy registry methodology on MCM prevalence estimates.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Adult; Anticonvulsants; Congenital Abnormalities; Epilepsy; Female; Humans; Levetiracetam; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prevalence; Prospective Studies; Registries; Stillbirth; United States

The objective of this study was to explore whether chronic electrocorticographic (ECoG) data recorded by a responsive neurostimulation system could be used to assess clinical responses to antiepileptic drugs (AEDs).. Antiepileptic drugs initiated and maintained for ≥3 months by patients participating in clinical trials of the RNS. The most commonly added medications were clobazam (n = 41), lacosamide (n = 96), levetiracetam (n = 31), and pregabalin (n = 25). Across all four medications, there were sufficient clinical data for 193 AED Starts to be included in the analyses, and 59 AED Starts were considered clinically beneficial. The proportion of AED Starts that qualified as clinically beneficial was higher for clobazam (53.7%) and levetiracetam (51.6%) than for lacosamide (18.8%) and pregabalin (12%). Across all AED Starts for which RNS ECoG detection settings were held constant, the clinically beneficial AED Starts were associated with a significantly greater reduction in the detection of epileptiform activity (p < 0.001) at 1 (n = 33) and 3 months (n = 30) compared with AED Starts that were not beneficial at 1 (n = 71) and 3 months (n = 60). Furthermore, there was a significant reduction in interictal spike rate and spectral power (1-125 Hz) associated with a clinically beneficial response to an AED Start at 1 (n = 32) and 3 months (n = 35) (p < 0.001). These reductions were not observed at either 1 (n = 59) or 3 months (n = 60) for AED Starts that were not clinically beneficial.. Significant quantitative changes in ECoG data recorded by the RNS System were observed in patients who experienced an additional clinical response to a new AED. While there was variability across patients in the changes observed, the results suggest that quantitative ECoG data may provide useful information when assessing whether a patient may have a favorable clinical response to an AED.

Topics: Adolescent; Adult; Anticonvulsants; Clobazam; Electrocorticography; Epilepsy; Female; Humans; Lacosamide; Levetiracetam; Male; Middle Aged; Pregabalin; Prospective Studies; Retrospective Studies; Treatment Outcome; Young Adult

Pregnant women with epilepsy on antiepileptic drugs (AEDs) may experience a reduction in serum AED levels. This has the potential to worsen seizure control.. To determine if, in pregnant women with epilepsy on AEDs, additional therapeutic drug monitoring reduces seizure deterioration compared with clinical features monitoring after a reduction in serum AED levels.. A double-blind, randomised trial nested within a cohort study was conducted and a qualitative study of acceptability of the two strategies was undertaken. Stratified block randomisation with a 1 : 1 allocation method was carried out.. Fifty obstetric and epilepsy clinics in secondary and tertiary care units in the UK.. Pregnant women with epilepsy on one or more of the following AEDs: lamotrigine, carbamazepine, phenytoin or levetiracetam. Women with a ≥ 25% decrease in serum AED level from baseline were randomised to therapeutic drug monitoring or clinical features monitoring strategies.. In the therapeutic drug monitoring group, clinicians had access to clinical findings and monthly serum AED levels to guide AED dosage adjustment for seizure control. In the clinical features monitoring group, AED dosage adjustment was based only on clinical features.. Primary outcome - seizure deterioration, defined as time to first seizure and to all seizures after randomisation per woman until 6 weeks post partum. Secondary outcomes - pregnancy complications in mother and offspring, maternal quality of life, seizure rates in cohorts with stable serum AED level, AED dose exposure and adverse events related to AEDs.. Analysis of time to first and to all seizures after randomisation was performed using a Cox proportional hazards model, and multivariate failure time analysis by the Andersen-Gill model. The effects were reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Secondary outcomes were reported as mean differences (MDs) or odds ratios.. A total of 130 women were randomised to the therapeutic drug monitoring group and 133 to the clinical features monitoring group; 294 women did not have a reduction in serum AED level. A total of 127 women in the therapeutic drug monitoring group and 130 women in the clinical features monitoring group (98% of complete data) were included in the primary analysis. There were no significant differences in the time to first seizure (HR 0.82, 95% CI 0.55 to 1.2) or timing of all seizures after randomisation (HR 1.3, 95% CI 0.7 to 2.5) between both trial groups. In comparison with the group with stable serum AED levels, there were no significant increases in seizures in the clinical features monitoring (odds ratio 0.93, 95% CI 0.56 to 1.5) or therapeutic drug monitoring group (odds ratio 0.93, 95% CI 0.56 to 1.5) associated with a reduction in serum AED levels. Maternal and neonatal outcomes were similar in both groups, except for higher cord blood levels of lamotrigine (MD 0.55 mg/l, 95% CI 0.11 to 1 mg/l) or levetiracetam (MD 7.8 mg/l, 95% CI 0.86 to 14.8 mg/l) in the therapeutic drug monitoring group than in the clinical features monitoring group. There were no differences between the groups on daily AED exposure or quality of life. An increase in exposure to lamotrigine, levetiracetam and carbamazepine significantly increased the cord blood levels of the AEDs, but not maternal or fetal complications. Women with epilepsy perceived the need for weighing up their increased vulnerability to seizures during pregnancy against the side effects of AEDs.. Fewer women than the original target were recruited.. There is no evidence to suggest that regular monitoring of serum AED levels in pregnancy improves seizure control or affects maternal or fetal outcomes.. Further evaluation of the risks of seizure deterioration for various threshold levels of reduction in AEDs and the long-term neurodevelopment of infants born to mothers in both randomised groups is needed. An individualised prediction model will help to identify those women who need close monitoring in pregnancy.. Current Controlled Trials ISRCTN01253916.. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in

Topics: Anticonvulsants; Carbamazepine; Double-Blind Method; Drug Monitoring; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Phenytoin; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Quality of Life; Seizures; United Kingdom

This study aimed to evaluate the safety and tolerability of intravenous (IV) levetiracetam (LEV) as a monotherapy in children aged 1 month-16 years and to explore the pharmacokinetics (PK) of IV LEV and the time to seizure after IV then oral administration of LEV in pediatric children with epilepsy. Children diagnosed with acute unprovoked seizures requiring in-hospital IV LEV administration were included. After administration, the clinical seizure outcomes, side effects, and the Korean-Child Behavior Checklist were monitored and the PK and repeated time to seizure were analyzed via modeling using NONMEM software. Overall, 37 children with epilepsy were enrolled and underwent a PK analysis (median age, 4.6 years; median weight, 18.0 kg). Nine children (24.3%) had seizure recurrence during the follow-up period (median, 3.8 months) and 5 children (13.5%) experienced LEV-associated adverse events such as irritability (n = 2; 5.4%) and somnolence (n = 3; 8.1%). The plasma LEV concentrations after IV LEV were best described by a one-compartment linear PK model. Only body weight was associated with both the clearance and volume of distribution of LEV. The Weibull distribution model described the time to seizure recurrence well; no statistically significant predictor for the time to seizure was identified. Therefore, IV LEV was a well-tolerated and effective alternative in children with acute unprovoked seizures, and models for the PK and time to repeated seizure recurrence after LEV were successfully developed. In particular, the current use of a weight-based IV LEV dosing regimen in pediatric children is practical.

Topics: Administration, Oral; Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Injections, Intravenous; Levetiracetam; Male

To examine serologic markers of vascular risk under treatment with commonly used antiepileptic drugs (AEDs) in the elderly in a randomized setting, and to determine whether the reduced exposure to hydroxymethylglutaryl-CoA reductase inhibitors ("statins") caused by carbamazepine reduces the effectiveness of the drugs as lipid-lowering agents.. Standard lipid fractions, lipoprotein(a), and C-reactive protein (CRP) were examined in a subset of those participating in the STEP-ONE trial, in which elderly patients with new epilepsy were randomized to treatment with carbamazepine, lamotrigine, or levetiracetam. Separate comparisons were made by individual AED, among those treated with statins, and, for CRP, among those treated with anti-inflammatory drugs.. One hundred ninety-four patients had the aforementioned serologic measurements. In patients not taking statins, those treated with carbamazepine had higher total cholesterol than those treated with levetiracetam (+16.6 mg/dL, P = 0.053), with values from patients on lamotrigine intermediate, whereas cholesterol fractions were subject to drug-gender interactions which did not show a consistent pattern. Lipoprotein(a) was significantly lower in lamotrigine patients than in the carbamazepine and levetiracetam groups. After accounting for the effects of steroids, CRP was higher in carbamazepine patients than in other patients. Patients taking a statin had lower lipid levels than those not taking a statin regardless of AED, but the differences between statin-treated and non-statin-treated patients were much larger (50%-100% or more) in the lamotrigine and levetiracetam groups than in the carbamazepine group (P = 0.035 for interaction effect of statin use and AED on total cholesterol).. Here, we demonstrate that carbamazepine significantly interferes with the ability of statins to lower total cholesterol, thus making it a poor choice for hyperlipidemic patients or those with cardiovascular disease. Native AED effects on lipids were inconsistent and subject to drug-gender interaction, in contrast with other studies; further investigation is necessary to determine if these latter findings are genuine or spurious.

Topics: Aged; Aged, 80 and over; Anticonvulsants; C-Reactive Protein; Carbamazepine; Cholesterol, LDL; Double-Blind Method; Drug Interactions; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Lipid Metabolism; Lipoproteins; Male; Triglycerides

The therapeutic equivalence of generic and brand antiepileptic drugs, based on studies performed on healthy volunteers, has been questioned. We compare, in a routine clinical setting, brand versus generic levetiracetam (LEV) bioequivalence in patients with epilepsy and also the clinical efficacy and tolerability of the substitution.. A prospective, open-label, non-randomized, steady-state, multiple-dose, bioequivalence study was conducted in 12 patients with epilepsy (5 females), with a mean age of 38.4±16.2 years. Patients treated with the brand LEV (Keppra; UCB Pharma) were closely followed for a four-week period and subsequently switched to a generic LEV (Pharmaten) and followed for another four-week period. Blood samples were collected at the end of each 4-week period, during a dose interval for each formulation, for LEV concentration measurements by liquid chromatography mass spectrometry. Steady-state area under the curve (AUC) and peak plasma concentration (Cmax) data were subjected to conventional average bioequivalence analysis. Secondary clinical outcomes, including seizure frequency and adverse events, were recorded.. Patients had epilepsy for a mean period of 14.1±10.6years and the mean daily LEV dose was 2583.3±763.7mg. The mean AUC±SD and Cmax±SD was 288.4±86.3(mg/L)h and 37.8±10.4mg/L respectively for brand LEV and 319.2±104.7(mg/L)h and 41.6±12.3mg/L respectively for the generic LEV. Statistic analysis showed no statistical significant difference in bioequivalence. Also, no change in seizures frequency and/or adverse events was recorded.. In our clinical setting, generic LEV was determined to be bioequivalent to brand LEV. Furthermore, seizures frequency or/and adverse events were not affected upon switching from brand to generic LEV.

Topics: Adult; Anticonvulsants; Drug Substitution; Drugs, Generic; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Prospective Studies; Therapeutic Equivalency; Treatment Outcome

Treatment of canine epilepsy is problematic. Few antiepileptic drugs have proven efficacy in dogs and undesirable adverse effects and pharmacoresistance are not uncommon. Consequently, the need for investigation of alternative treatment options is ongoing. The objective of this study was to investigate the efficacy and tolerability of levetiracetam as mono-therapy in dogs with idiopathic epilepsy. The study used a prospective single-blinded parallel group design. Twelve client-owned dogs were included and were randomised to treatment with levetiracetam (30 mg/kg/day or 60 mg/kg/day divided into three daily dosages) or phenobarbital (4 mg/kg/day divided twice daily). Control visits were at days 30, 60 and then every 3 months for up to 1 year. Two or more seizures within 3 months led to an increase in drug dosage (levetiracetam: 10 mg/kg/day, phenobarbital: 1 mg/kg/day). Five of six levetiracetam treated dogs and one of six phenobarbital treated dogs withdrew from the study within 2-5 months due to insufficient seizure control. In the levetiracetam treated dogs there was no significant difference in the monthly number of seizures before and after treatment, whereas in the phenobarbital treated dogs there were significantly (P = 0.013) fewer seizures after treatment. Five phenobarbital treated dogs were classified as true responders (≥50% reduction in seizures/month) whereas none of the levetiracetam treated dogs fulfilled this criterion. Adverse effects were reported in both groups but were more frequent in the phenobarbital group. In this study levetiracetam was well tolerated but was not effective at the given doses as mono-therapy in dogs with idiopathic epilepsy.

Topics: Animals; Anticonvulsants; Dog Diseases; Dogs; Epilepsy; Female; Levetiracetam; Male; Phenobarbital; Piracetam; Prospective Studies; Seizures; Single-Blind Method

Long-term anti-epileptic drug (AED) therapy is associated with increased fracture risk. This study tested whether substituting the newer AED levetiracetam has less adverse effects on bone than older AEDs. An open-label randomized comparative trial. Participants had "failed" initial monotherapy for partial epilepsy and were randomized to substitution monotherapy with levetiracetam or an older AED (carbamazepine or valproate sodium). Bone health assessments, performed at 3 and 15 months, included areal bone mineral density (aBMD) and content at lumbar spine (LS), total hip (TH), forearm (FA), and femoral neck (FN), radial and tibial peripheral quantitative computed tomography and serum bone turnover markers. Main outcomes were changes by treatment group in aBMD at LS, TH, and FA, radial and tibial trabecular BMD and cortical thickness. 70/84 patients completed assessments (40 in levetiracetam- and 30 in older AED group). Within-group analyses showed decreases in both groups in LS (-9.0 %; p < 0.001 in levetiracetam vs. -9.8 %; p < 0.001 in older AED group), FA (-1.46 %; p < 0.001 vs. -0.96 %; p < 0.001, respectively) and radial trabecular BMD (-1.46 %; p = 0.048 and -2.31 %; p = 0.013, respectively). C-terminal telopeptides of type I collagen (βCTX; bone resorption marker) decreased in both groups (-16.1 %; p = 0.021 vs. -15.2 %; p = 0.028, respectively) whereas procollagen Ι N-terminal peptide (PΙNP; bone formation marker) decreased in older AED group (-27.3 %; p = 0.008). The treatment groups did not differ in any of these measures. In conclusion, use of both levetiracetam and older AEDs was associated with bone loss over 1 year at clinically relevant fracture sites and a reduction in bone turnover.

Topics: Absorptiometry, Photon; Adult; Aged; Anticonvulsants; Bone and Bones; Bone Density; Bone Remodeling; Carbamazepine; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Tomography, X-Ray Computed; Valproic Acid

Few clinical trials have evaluated the efficacy and tolerability of antiepileptic drugs (AEDs) as initial monotherapy for elderly patients.. This post-hoc subgroup analysis of data from an unblinded, randomized, 52-week superiority study (KOMET) compared the effectiveness of levetiracetam (LEV) with extended-release sodium valproate (VPA-ER) and controlled-release carbamazepine (CBZ-CR) as monotherapy in patients aged ≥ 60 years with newly diagnosed epilepsy. The physician chose VPA or CBZ as preferred standard treatment; patients were randomized to standard AEDs or LEV. The primary endpoint was time to treatment withdrawal. Results are exploratory, since KOMET was not powered for a subgroup analysis by age.. Patients (n = 308) were randomized to LEV (n = 48) or VPA-ER (n = 53) in the VPE-ER stratum or to LEV (n = 104) or CBZ-CR (n = 103) in the CBZ-CR stratum. Mean age was 69.6 years, range 60.2-89.9 years (intention-to-treat population n = 307). Time to treatment withdrawal hazard ratio [HR] (95 % confidence interval [CI]) for LEV vs. standard AEDs was 0.44 (0.28-0.67); LEV vs.. 0.46 (0.16-1.33); LEV vs.. 0.45 (0.28-0.72). Twelve-month withdrawal rates were: LEV vs. standard AEDs, 20.4 vs. 38.7 %; LEV vs. VPA-ER, 10.4 vs. 23.1 %; LEV vs. CBZ-CR, 25.0 vs. 46.6 %. Time to first seizure was similar between LEV and standard AEDs (HR: 0.92, 95 % CI: 0.63-1.35), LEV and VPA-ER (0.77, 0.38-1.56), and LEV and CBZ-CR (1.02, 0.64-1.63). Adverse events were reported by 76.2, 67.3, and 82.5 % of patients for LEV, VPA-ER, and CBZ-CR, respectively. Discontinuation rates due to AEs were 11.3, 10.2, and 35.0 % for LEV, VPA-ER, and CBZ-CR, respectively.. Time to treatment withdrawal was longer with LEV compared with standard AEDs. This finding was driven primarly by the result in the CBZ-CR stratum, which in turn was likely due to the more favorable tolerability profile of LEV. Results of this post-hoc analysis suggest that LEV may be a suitable option for initial monotherapy for patients aged ≥ 60 years with newly diagnosed epilepsy.. ClinicalTrials.gov: NCT00175903 ; September 9, 2005.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Carbamazepine; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Seizures; Valproic Acid

The number of patients who suffer from symptomatic partial epilepsy is significant, and those who undergo neurosurgery often experience refractory seizures. Levetiracetam (LEV) is a new-generation anti epileptic drug (AED). Previous studies have shown that LEV has favorable efficacy and a good safety profile with few drug interactions, as it has a unique pharmacological mechanism and acts on synaptic vesicle protein. This study aimed at estimate the efficacy and safety of 1,000 to 2,000 mg/day of LEV as an add-on therapy for refractory symptomatic seizures treated in the department of neurosurgery of our hospital. Twelve patients with >1 seizure attack per year who were administrated one to three AED(s) and had never used LEV were enrolled in this study. The follow-up period was at least 6 months. Seizure-free ratio, health-related quality of life (QOL), and tolerability were assessed. Fifty-eight percent (7/12) of patients were seizure-free, and their "overall QOL", "energy/fatigue" and "health status" distress-item scores in the QOLIE-31-P had improved. All patients were able to continue oral treatment with LEV without major side effects. Thus, the efficacy and safety of oral add-on LEV therapy were high for these patients. (Received January 19, 2016; Accepted September 2, 2016; Published December 1, 2016).

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Quality of Life; Treatment Outcome

We evaluated nonpsychotic behavioral adverse events (BAEs) in patients receiving levetiracetam (LEV) who switched to brivaracetam (BRV). Patients ≥16 years of age, receiving 2-3 antiepileptic drugs (AEDs), including LEV 1-3g/day, and experiencing BAEs within 16 weeks of LEV treatment initiation, enrolled in an open-label Phase 3b study (NCT01653262) comprising a ≤1-week screening period, an immediate switch from LEV to BRV 200mg/day (without titration), and a 12-week treatment period. The percentages of patients with investigator-assessed clinically meaningful reduction in BAEs, shift in maximum BAE intensity, and change in health-related quality of life (HRQoL) (Patient-Weighted Quality of Life in Epilepsy Inventory-Form 31 [QOLIE-31-P]) were assessed. Of 29 patients enrolled, 26 (89.7%) completed the study. At the end of the treatment period, 27/29 (93.1%) patients switched to BRV had clinically meaningful reductions in BAEs. Physicians reported a reduction in the maximum intensity of primary BAEs in 27/29 (93.1%) patients. Mean change from baseline to Week 12 in QOLIE-31-P total score was 12.1, indicating improved HRQoL. During the treatment period, 23/29 (79.3%) patients reported treatment-emergent adverse events (TEAEs). One patient reported a serious TEAE (suicidal ideation and suicide attempt). Two patients discontinued BRV because of TEAEs. Findings from this small study suggest that patients experiencing BAEs associated with LEV may benefit from switching to BRV.

Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Male; Mental Disorders; Middle Aged; Piracetam; Prospective Studies; Pyrrolidinones; Quality of Life; Suicidal Ideation; Suicide, Attempted; Treatment Outcome; Young Adult

In patients with brain tumors, the choice of antiepileptic medication is guided by tolerability and pharmacokinetic interactions. This study investigated the effectiveness of levetiracetam (LEV) and pregabalin (PGB), 2 non-enzyme-inducing agents, in this setting.. In this pragmatic, randomized, unblinded phase II trial (NCT00629889), patients with primary brain tumors and epilepsy were titrated to a monotherapy of LEV or PGB. Efficacy and tolerability were assessed using structured questionnaires. The primary composite endpoint was the need to discontinue the study drug, add-on of a further antiepileptic treatment, or occurrence of at least 2 seizures with impaired consciousness during 1 year follow-up.. Over 40 months, 25 patients were randomized to LEV, and 27 to PGB. Most were middle-aged men, with a high-grade tumor and at least one generalized convulsion. Mean daily doses were 1125 mg (LEV) and 294 mg (PGB). Retention rates were 59% in the LEV group, and 41% in the PGB group. The composite endpoint was reached in 9 LEV and 12 PGB patients-need to discontinue: side effects, 6 LEV, 3 PGB; lack of efficacy, 1 and 2; impaired oral administration, 0 and 2; add-on of another agent: 1 LEV, 4 PGB; and seizures impairing consciousness: 1 in each. Seven LEV and 5 PGB subjects died of tumor progression.. This study shows that LEV and PGB represent valuable monotherapy options in this setting, with very good antiepileptic efficacy and an acceptable tolerability profile, and provides important data for the design of a phase III trial.

Topics: Anticonvulsants; Brain Neoplasms; Epilepsy; Female; Follow-Up Studies; gamma-Aminobutyric Acid; Humans; Levetiracetam; Male; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Piracetam; Pregabalin; Prognosis; Survival Rate

We sought to determine the effect of changing phenytoin therapy on bone mineral density (BMD) and 25-hydroxyvitamin D in patients with epilepsy. Of the 90 patients, 54 patients had switched to levetiracetam, 19 patients had stopped, and 17 patients continued taking phenytoin. We proposed a 2-year period to examine 25-hydroxyvitamin D, parathyroid hormone, and BMD. The patients who switched or stopped phenytoin showed a significant increase in BMD of the lumbar spine and left femur, and in 25-hydroxyvitamin D. In contrast, those who continued phenytoin had a significant decrease in BMD at both sites and in 25-hydroxyvitamin D. Patients who were taken off phenytoin and those switching to levetiracetam did not show a significant difference in BMD, 25-hydroxyvitamin D, parathyroid, or calcium at follow-up. Compared with those who continued phenytoin, the BMD was significantly higher in patients switching to levetiracetam and those who stopped using phenytoin. Switching medications may be necessary in some cases to avoid low BMD.

Topics: Adult; Anticonvulsants; Bone Density; Epilepsy; Female; Femur; Humans; Levetiracetam; Lumbar Vertebrae; Male; Parathyroid Hormone; Phenytoin; Piracetam; Vitamin D; Young Adult

To show non-inferiority of levetiracetam to sulthiame with respect to efficacy, tolerability and safety in benign epilepsy with centrotemporal spikes in a prospective, double-blinded randomized controlled trial.. A sample size of 60 subjects (treatment group) was calculated to show reliable statistical results for non-inferiority. A total of 44 patients could be randomly allocated to either (LEV or STM) treatment group. Explorative data analysis was performed to investigate differences in the number of treatment failure events (occurrence of a seizure during the observation period of 6 months) and total dropouts. In addition, information of the occurrence of adverse events was collected.. 43 patients were analyzed. One patient had to be excluded due to protocol violation. Treatment failure events occurred in four patients (19.0%) in the LEV treatment group and in two patients (9.1%) in the STM treatment group, respectively, (p = 0.412). The number of dropouts due to adverse reactions was five in the LEV treatment group and one in STM treatment group (23.8% vs. 4.5%, respectively, p = 0.095). Severe adverse events occurred in patients treated with LEV (n = 2, 9.5%). The total number of dropouts due to either seizure recurrence or adverse events was significantly higher in the LEV group (n = 9, 42.9%) compared to the STM group (n = 3, 13.6%, p = 0.03).. The study results concerning non-inferiority were not conclusive, as the calculated sample size was not reached to support sufficient statistical power due to limited recruitment in a 26 months period. The rates of seizure free patients were [relatively] high in both groups. However, the results indicate that termination of drug treatment due to seizure recurrence or adverse events occurred more frequently in the LEV group compared to STM. Behavioral disturbances were the most common adverse event causing study termination.

Topics: Anticonvulsants; Child; Double-Blind Method; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Prospective Studies; Secondary Prevention; Thiazines; Treatment Failure; Treatment Outcome

We examined 76 children and adolescents (45 boys (59.2%), 31 girls (40.8%), aged from 6 to 17 years (mean age 14.31 ± 0.3), with the diagnosis of refractory epilepsy using a clinical/psychopathological method and psychometric scales. Marked non-psychotic mental disorders of varying severity were observed in all patients. The patients were treated with levetiracetam in a dose of 60 mg/kg/day during one year. The reduction in the frequency of epileptic seizures was achieved in 77.6% of patients. The significant (p<0.01) improvement in cognitive functions and speech were found in 81.6% cases. The treatment reduced stress and improved mood in 63.1% of patients.

Topics: Adolescent; Affective Symptoms; Child; Cognition; Cognition Disorders; Dose-Response Relationship, Drug; Emotions; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Nootropic Agents; Piracetam; Treatment Outcome

To estimate the effect of levetiracetam (LEV) on cognitive function and mood status in newly diagnosed epilepsy patients.. Fifty-five drug-naïve epilepsy patients (M:F ratio = 31:24; mean age = 30.9 years) were included. All patients underwent two neuropsychological (NP) tests, one before receiving LEV and then another 12.9 ± 5.0 months after starting LEV monotherapy. We evaluated general cognitive function, verbal/visual attention and memory, linguistic and visuospatial functions, frontal lobe function, and mood status. Repeated-measures regression and generalized estimating equation models were applied to assess the effects of all the confounding variables such as seizure control, average LEV dose, duration of epilepsy, inter-test interval, and subtype of epilepsy syndrome.. LEV monotherapy over 1 year revealed significant improvements in the following domains of NP tests with the correction of possible confounding variables: verbal and visual attention, psychomotor speed, mental flexibility, executive function, verbal fluency and word generation. No NP domains showed any significant decrease.. Our study suggested that LEV monotherapy had no harmful effect on cognitive function in drug-naïve patients with epilepsy.

Topics: Adolescent; Adult; Anticonvulsants; Child; Cognition; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Piracetam; Young Adult

The aim of the study was to investigate immunoglobulin levels in patients with epilepsy using the antiepileptic drugs (AED) levetiracetam (LEV), carbamazepine (CBZ), or lamotrigine (LTG).. A total of 211 patients and 80 controls (age: 18-45 years) of both genders were included. The patients had been treated with either LEV (n = 47), CBZ (n = 90), or LTG (n = 74) monotherapy for at least 6 months. Total concentrations of immunoglobulin G (IgG), IgG subclasses (IgG1, IgG2, IgG3, and IgG4), immunoglobulin A (IgA), and immunoglobulin M (IgM) were measured. Smoking, drinking habits, and physical activity were recorded, and body mass index (BMI) was calculated.. A significantly lower total IgG and IgG1 was found in both men and women treated with LTG and in men on CBZ. IgG2 and IgG4 were also lower in LTG-treated women, and IgA and IgM were lower in LTG-treated men. Patients treated with LEV did not differ from the control group.. Low levels of immunoglobulins were found in patients with epilepsy treated with LTG or CBZ. As our group of patients consisted of otherwise healthy young adults, one should be especially aware of a possible effect of AEDs on immunoglobulin levels when treating selected patient groups, for example immunocompromised patients. Immunoglobulin concentrations should be measured in patients treated with LTG or CBZ who experience recurrent infections, and a change in medication should be considered.

Topics: Adolescent; Adult; Anticonvulsants; Body Mass Index; Carbamazepine; Double-Blind Method; Epilepsy; Female; Humans; Immunoglobulins; Lamotrigine; Levetiracetam; Male; Middle Aged; Piracetam; Statistics, Nonparametric; Triazines; Young Adult

Of the newer antiepileptic drugs, lamotrigine (LTG) and levetiracetam (LEV) are popular first choice drugs for epilepsy. The authors compared these drugs with regard to their efficacy and tolerability in the initial monotherapy for epilepsy.. A randomised, open-label, controlled, parallel group, multicenter trial was conducted to test the superiority of the LEV arm over the LTG arm. The primary endpoint was the rate of seizure-free patients in the first 6 weeks (two-sided Fisher's exact test, α=0.05, intent-to-treat set). Furthermore, efficacy, tolerability and quality of life were evaluated. The authors included 409 patients aged ≥12 years with newly diagnosed focal or generalised epilepsy defined by either two or more unprovoked seizures or one first seizure with high risk for recurrence. Patients were titrated to 2000 mg/day of LEV or 200 mg/day of LTG reached on day 22 or 71, respectively. Two dose adjustments by 500/50 mg were allowed.. The proportions of seizure-free patients were 67.5% (LEV) versus 64.0% (LTG) 6 weeks after randomisation (p=0.47), and 45.2% (LEV) versus 47.8% (LTG) during the whole treatment period of 26 weeks. The HR (LEV vs. LTG) for seizure-free time was 0.86 (95% CI, 0.61 to 1.22). Adverse events occurred in 74.5% (LEV) versus 70.6% (LTG) of the patients (p=0.38). Adverse events associated with study discontinuation occurred in 17/204 (LEV) versus 8/201 (LTG) patients (p=0.07).. There were no significant differences with regard to efficacy and tolerability of LEV and LTG in newly diagnosed focal and generalised epilepsy despite more rapid titration in the LEV arm.. ClinicalTrials.gov identifier NCT00242606.

Topics: Adolescent; Adult; Anticonvulsants; Child; Early Diagnosis; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Piracetam; Quality of Life; Triazines

Levetiracetam (LEV) has antiepileptogenic effects in animals and is a candidate for prevention of epilepsy after traumatic brain injury. Pharmacokinetics of LEV in TBI patients was unknown. We report pharmacokinetics of TBI subjects≥6years with high PTE risk treated with LEV 55mg/kg/day orally, nasogastrically or intravenously for 30days starting ≤8h after injury in a phase II safety and pharmacokinetic study. Forty-one subjects (26 adults and 15 children) were randomized to PK studies on treatment days 3 and 30. Thirty-six out of forty-one randomized subjects underwent PK study on treatment day 3, and 24/41 subjects underwent PK study on day 30. On day 3, mean T(max) was 2.2h, C(max) was 60.2μg/ml and AUC was 403.7μg/h/ml. T(max) was longer in the elderly than in children and non-elderly adults (5.96h vs. 1.5h and 1.8h; p=0.0001). AUC was non-significantly lower in children compared with adults and the elderly (317.4μg/h/ml vs. 461.4μg/h/ml and 450.2μg/h/ml; p=0.08). C(max) trended higher in i.v.- versus tablet- or n.g.-treated subjects (78.4μg/ml vs. 59μg/ml and 48.2μg/ml; p=0.07). AUC of n.g. and i.v. administrations was 79% and 88% of AUC of oral administration. There were no significant PK differences between days 3 and 30. Treatment of TBI patients with high PTE risk with 55mg/kg/day LEV, a dose with antiepileptogenic effect in animals, results in plasma LEV levels comparable to those in animal studies.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Analysis of Variance; Anticonvulsants; Area Under Curve; Brain Injuries; Child; Creatinine; Epilepsy; Female; Follow-Up Studies; Glasgow Coma Scale; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Protein Kinases; Saliva; Young Adult

To evaluate the safety and tolerability of treatment with levetiracetam and determine the trough levels of levetiracetam in patients with traumatic brain injury (TBI) who are at high risk for posttraumatic epilepsy (PTE).. Open-label, nonrandomized phase 2 study with 2 arms comparing levetiracetam treatment vs observation.. Two level 1 trauma centers.. A total of 422 participants 6 years or older with TBI who have a 20% risk for PTE were screened. Of these participants, 205 (48.6%) were eligible. A total of 126 participants were enrolled: 86 adults and 40 children. A total of 66 participants were in the treatment group (46 adults and 20 children), and a total of 60 participants were in the observation group (40 adults and 20 children). Participants presenting within 8 hours after TBI received treatment, and those presenting more than 8 to 24 hours after TBI did not.. Treatment with levetiracetam (55 mg/kg/d) for 30 days starting within 8 hours after injury.. Number of adverse events, mood score, number of infections, trough level of levetiracetam, and PTE.. Of the 66 participants treated with levetiracetam, 2 (3%) stopped treatment owing to toxicity (somnolence). The most common adverse events were fatigue, headache, and somnolence. Mood scores and number of infections did not differ between the treatment and observation groups. Mean trough levels of levetiracetam on days 2 to 30 ranged from 19.6 to 26.7 μg/mL. At 2 years, 13 of 86 adults (15.1%) and 1 of 40 children (2.5%) developed PTE. At 2 years, 5 of 46 treated adults (10.9%) and 8 of 40 untreated adults (20.0%) developed PTE (relative risk, 0.47; P=.18).. Treatment with 55 mg/kg/d of levetiracetam (a dose with an antiepileptogenic effect on animals) for patients with TBI at risk for PTE is safe and well tolerated, with plasma levels similar to those in animal studies. The findings support further evaluation of levetiracetam treatment for the prevention of PTE.. clinicaltrials.gov Identifier: NCT01463033.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Brain Injuries; Child; Chromatography, High Pressure Liquid; Epilepsy; Feasibility Studies; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Patient Compliance; Phenytoin; Piracetam; Survival Analysis; Tandem Mass Spectrometry; Time Factors; Young Adult

We performed a case series analysis to evaluate the effects of levetiracetam (LEV) monotherapy on seizures, adverse events, cognitive functioning and quality of life (QoL) in patients with brain tumor-related epilepsy (BTRE). We also explored the possible effects of systemic therapies on the efficacy of LEV. Twenty-nine patients were followed (13 female, 16 male; age 24-75 years) with 12 months of follow-up. Patients were evaluated by QoL and neuropsychological tests. At final follow-up, mean LEV dosage was 1991.4 mg/day. Among patients who reached the final follow-up of 12 months (n = 15), 1 patient had ≥50% reduction of seizure frequency (SF), and 14/15 were seizure free. The difference in presence/absence of seizures between baseline and final follow-up was significant (p < 0.001). Responder rate was 100%. We observed five side-effects: four mild (reversible) and one severe. Logistic regression revealed that chemotherapy and radiotherapy did not affect the efficacy of LEV in seizure outcome (p = 0.999). The following statistically significant observations emerged by tests' evaluation: less worry about seizures, effects of antiepileptic, and ability to maintain social functions. Our data suggest that seizure occurrence can be an important warning sign that the clinician should heed throughout the duration of the illness. Patients with BTRE represent a unique patient population that presents difficulties regarding management of two very different pathologies: epilepsy on the one hand, and brain tumor on the other. Our data indicate that LEV, in patients with BTRE, is safe and efficacious, with positive impact on QoL.

Topics: Adult; Aged; Anticonvulsants; Brain Neoplasms; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Piracetam; Quality of Life; Statistics, Nonparametric; Treatment Outcome; Young Adult

Although LVT is currently extensively prescribed in childhood epilepsy, its effect on the panel of refractory epilepsy syndromes has not been entirely evaluated prospectively. In order to study the efficacy and safety of LVT as adjunctive therapy according to syndromes, we included 102 patients with refractory seizures (6 months to 15 years) in a prospective open-labeled trial. The responder rate was respectively 36% and 32% at 3 and 6 months with 6% and 7% patients becoming seizure free. Among the responders at 6 months (n=33), seizure frequency decreased by 66% and 79% at 3 and 6 months LVT compared to baseline. The highest benefit was for CSWS patients with 2/3 responders, 50% seizure free and no aggravation. LVT provided respectively 39% and 42% responders in focal and absence epilepsies. Infantile spasms and Dravet syndrome experienced the lowest efficacy. No patient with myoclonic-astatic epilepsy or Lennox-Gastaut syndrome was aggravated. LVT dose over 40 mg/kg/d was associated with a lower response rate. Tolerability was excellent. In spite of a small sample, we assume that CSWS is a good candidate for a randomized-controlled trial with LVT.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Sleep

Epileptic seizures in stroke patients are a common complication and adversely affect neurological outcome. We tried to perform a trial aimed at preventing the development of late poststroke seizures using levetiracetam. Levetiracetam is assumed to have anti-epileptogenic properties and might be suitable to prevent late epileptic seizures in stroke patients.. Stroke patients with a cortical syndrome and a modified Rankin score ≥ 3 or NIHSS ≥ 6 were treated with either levetiracetam 1500 mg daily divided in two doses or placebo during 12 weeks following stroke. Treatment was started within 7 days following stroke onset.. Only 16 patients were included in this trial. Problems during the execution of this prophylactic trial concerned the assessment of the occurrence of epileptic seizures, a very slow inclusion rate, the use of anticonvulsive co-medication, continuation of the trial medication after discharge, and the evaluation of possible side effects of the trial medication.. Due to too few participants, no conclusions could be drawn regarding the ability of levetiracetam to prevent poststroke seizures. The problems encountered during execution of this trial seem to be inherent to performing a trial aimed at preventing the development of epileptic seizures in stroke patients.. A prophylactic trial in stroke patients aimed at preventing poststroke seizures and epilepsy seems not feasible.

Topics: Aged; Anticonvulsants; Double-Blind Method; Epilepsy; Female; Humans; Levetiracetam; Male; Multicenter Studies as Topic; Patient Selection; Piracetam; Randomized Controlled Trials as Topic; Stroke

To assess whether levetiracetam elimination is influenced by enzyme inducing antiepileptic drugs (EIAEDs), serum levetiracetam levels were determined at frequent intervals after a single oral 1000mg dose in 15 subjects co-medicated with EIAEDs and 15 matched controls. The EIAED group showed a higher levetiracetam oral clearance (p=0.01) and a shorter half-life (p=0.02) than controls. Although the magnitude of interaction is relatively modest, it could have clinical significance for some patients.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Area Under Curve; Case-Control Studies; Enzyme Induction; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Time Factors; Young Adult

There is relatively little known about the effects of new antiepileptic drugs (AEDs) on sleep. This study was done to evaluate the effect of levetiracetam (LEV) on subjective sleep quality and sleep architecture in patients with epilepsy, and the results were compared with the effects of carbamazepine-CR (CBZ-CR).. This is a longitudinal randomized controlled trial using two different treatments, LEV (1000 mg/day) or CBZ-CR (400mg/day). Thirty-one subjects (16 LEV and 15 CBZ-CR) had partial epilepsy and were tested with an overnight polysomnography (PSG) with full 10-20 electrodes. Sleep questionnaires and National Hospital Seizure severity Scale (NHS3) were evaluated. PSG and the questionnaires were repeated after 4-6 weeks of treatment.. In the LEV group, when treatment PSG findings were compared with baseline, there was a significant increase in sleep efficiency (p=0.039) but no changes in subjective sleep parameters. In the CBZ-CR group, there was a significant increase in the percentage of slow wave sleep (p=0.038) while other sleep parameters were not significantly changed after treatment. There were no significant differences in effects on sleep between the LEV and CBZ-CR groups.. LEV may increase sleep efficiency without major effects on sleep structure with an overall effect on sleep parameters comparable to CBZ-CR.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Carbamazepine; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Polysomnography; Sleep; Young Adult

The objective of the study described here was to evaluate the efficacy, tolerability, and cognitive effects of levetiracetam (LEV) in patients with seizures and Alzheimer's disease (AD). This was a prospective, randomized, three-arm parallel-group, case-control study of 95 patients taking LEV (n=38), phenobarbital (PB) (n=28), and lamotrigine (LTG) (n=29). A 4-week dose adjustment was followed by a 12-month evaluation period. The three groups were compared to a control group (n=68) to evaluate cognitive effects of the antiepileptic drugs. We examined drug effects cross-sectionally at baseline, 6 months, and 12 months. There were no significant differences in efficacy among the three AEDs. LEV caused fewer adverse events than the other AEDs. PB produced persistent negative cognitive side effects. LEV was associated with improved cognitive performance, specifically attention level and oral fluency items. LTG had a better effect on mood. LEV had a benign neuropsychological side effect profile, making it a cognitively safe drug to use for controlling established seizures in elderly patients with Alzheimer's disease.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Analysis of Variance; Anticonvulsants; Case-Control Studies; Cognition Disorders; Cross-Sectional Studies; Double-Blind Method; Electroencephalography; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Mental Status Schedule; Middle Aged; Neuropsychological Tests; Phenobarbital; Piracetam; Time Factors; Treatment Outcome; Triazines

This open-label, non-interventional, controlled surveillance study evaluated the cognitive outcome of patients administered levetiracetam (LEV) or carbamazepine (CBZ) monotherapy as primary treatment or as substitution for previous treatment. Executive functions, verbal memory, and subjective ratings were assessed before and 6 months after initiation of LEV or CBZ monotherapy. Analyses included 498 patients: 370 received LEV (63% pretreated), and 128 CBZ (34% pretreated). Mostly because of the substitution condition, the seizure freedom rate was slightly higher with LEV as opposed to CBZ (78% vs 69%). Almost all cognitive measures improved with LEV but not with CBZ, and repeated-measures MANOVA did not indicate seizure control or pretreatment as decisive with respect to cognitive change. With LEV, executive functions improved in 15% and deteriorated in 5% of patients; the opposite pattern was seen under CBZ (improvement with LEV OR=2.3, deterioration with CBZ OR=3.4). The findings suggest a mild but definitely superior cognitive outcome with LEV as opposed to CBZ monotherapy.

Topics: Adult; Analysis of Variance; Anticonvulsants; Carbamazepine; Chi-Square Distribution; Epilepsy; Executive Function; Female; Humans; Levetiracetam; Male; Memory; Middle Aged; Piracetam; Quality of Life; Treatment Outcome

This study was carried out to determine the effects of valproate (VPA), carbamazepine, and levetiracetam (LEV) on antioxidant and oxidant enzyme activities and the clinical importance of these effects.. We enrolled 32 patients receiving VPA, 17 receiving carbamazepine, 8 receiving LEV, 11 on multidrug therapy, and 30 sex- and age-matched healthy volunteers. We measured the serum activities of paraoxonase and arylesterase and the levels of 8-hydroxyguanine (8-OHG) and oxidized low-density lipoprotein in all the subjects. We also determined the clinical features of the patients.. The serum paraoxonase and arylesterase activities were significantly lower (P = 0.003 and P = 0.0001, respectively), and the oxidized low-density lipoprotein and 8-OHG levels were higher (P = 0.029 and P = 0.0001, respectively) in the patients than in the controls. The serum antioxidant activity was low, and the oxidant activity was high in the monotherapy patients (P < 0.05). Comparing the monotherapy with the polytherapy, only the combination of VPA-LEV was associated with a high 8-OHG level (P = 0.04). The serum 8-OHG level was higher in the patients taking antiepileptic drugs (AEDs) for the first 2 months than in the controls (P = 0.0001) and positively correlated with the duration of epilepsy (r = 0.387, P < 0.01).. Oxidative stress is seen in each of the AEDs after the first 2 months. There was no dominance of the monotherapy over the polytherapy, except for the VPA-LEV combination. None of the patients' characteristic features were related to oxidative damage, except for the duration of the epilepsy and the AED therapy.

Topics: Adolescent; Adult; Anticonvulsants; Antioxidants; Aryldialkylphosphatase; Biomarkers; Carbamazepine; Carboxylic Ester Hydrolases; Drug Therapy, Combination; Epilepsy; Female; Guanine; Humans; Levetiracetam; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Piracetam; Valproic Acid; Young Adult

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

To investigate the efficacy and safety of levetiracetam in adults with intellectual disabilities who have uncontrolled partial or generalised epilepsy.. An open label prospective study compared seizure frequency, adverse effects, participant challenging behaviour, carers' concerns about epilepsy and perceived participant quality of life between a baseline observation prior to the use of levetiracetam and follow-up observations at 3, 6, 9 and 12 months afterwards. Challenging behaviour, carers' concerns about epilepsy and perceived quality of life were assessed using standardized measures.. Recruitment was low (n=42). Six participants did not enter the trial. Two participants withdrew at initiation of treatment, one with seizures worsening and one with a rash, and a further one later on with a rash; all were felt to be drug related. Three other participants withdrew for independent reasons. Twelve months follow-up was achieved for 26 participants (62%) and at least 6 months follow-up for 30 participants (71%). Median seizure frequency reduced from baseline levels of 4.2 per week to average post-intervention levels of 2.2 for the 30 participants (z=-2.53, p<.05). No overall change in challenging behaviour was found, although increases in behaviour problems were reported for a minority. Patient concerns about seizures and medical treatment declined and perceived quality of life relating to seizure severity improved whilst that related to behaviour deteriorated. Increased adverse effects were reported immediately after initiation of levetiracetam but declined towards baseline levels by study completion.. Conclusions must remain tentative due to methodological weaknesses. Further investigation of the possible changes found here within a controlled study is merited.

Topics: Adult; Aged; Anticonvulsants; Drug Therapy, Combination; Epilepsy; Female; Follow-Up Studies; Humans; Intellectual Disability; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Quality of Life; Time Factors; Treatment Outcome; Young Adult

To determine long-term retention, percentage of patients withdrawing because of adverse events, percentage of patients achieving seizure freedom, safety profile of the new anti-epileptic drugs lamotrigine, levetiracetam and topiramate.. All patients treated with lamotrigine, levetiracetam or topiramate in the Epilepsy Centre were identified. Each drug was analyzed from introduction of the drug in the Netherlands up to a final assessment point 2 years later.. Data from 1066 patients were included: 336 for lamotrigine, 301 for levetiracetam, 429 for topiramate. Two-year retention rates were 69.2% (lamotrigine), 45.8% (levetiracetam), 38.3% (topiramate); (LTG vs. LEV at p<0.001; LTG vs. TPM at p<0.001; LEV vs. TPM at p=0.005). Seizure freedom rates were lowest for lamotrigine and highest for levetiracetam. Adverse events played a role in drug discontinuation in 154/429 patients (35.9%) on topiramate, 52/336 patients (15.5%) on lamotrigine (p<0.001), 68/301 patients (22.5%) on levetiracetam (p<0.001). Mood and general CNS-effects are common in patients on lamotrigine and levetiracetam, and neurocognitive side effects are most prevalent in patients on topiramate. A positive effect on cognition is frequently noted in patients on lamotrigine.. A drug that is only modestly efficacious but has a favourable safety profile may look better than a drug that is more efficacious but produces clinically meaningful adverse events. Therefore, a drug's retention rate is mainly determined by its side effect profile. As a consequence, retention rate was highest for lamotrigine and lowest for topiramate. Intermediate retention rates were seen with levetiracetam use.

Topics: Anticonvulsants; Drug Utilization; Epilepsy; Fructose; Humans; Lamotrigine; Levetiracetam; Longitudinal Studies; Patient Compliance; Piracetam; Time Factors; Topiramate; Treatment Outcome; Triazines

The purpose of this prospective, open-label pilot study was to determine whether treatment with levetiracetam improves neuropsychological functioning in children and adolescents who have evidence of subclinical spike production associated with attention and learning difficulties. Six participants (mean age 9.8 years) were treated with levetiracetam up to 40 mg/kg per day and evaluated using neuropsychological (Wide Range Assessment of Memory and Learning, Second Edition), academic (Wechsler Individual Achievement Test, Second Edition, Abbreviated), and electroencephalographic assessments at baseline and after 10 weeks of treatment. Statistically significant improvements on indexes of the Wide Range Assessment of Memory and Learning, Second Edition were observed in 4 participants after 10 weeks. No statistically significant differences were observed for the Wechsler Individual Achievement Test, Second Edition, Abbreviated. Concomitant spike suppression was observed. Levetiracetam was generally well tolerated. A subset of patients exists with attention and learning problems that have associated aberrant cortical electrical activity without clinical seizures and associated neuropsychological deficits that may improve after treatment with levetiracetam.

Topics: Adolescent; Anticonvulsants; Attention; Attention Deficit and Disruptive Behavior Disorders; Brain; Child; Electroencephalography; Epilepsy; Female; Humans; Learning Disabilities; Levetiracetam; Male; Memory; Neuropsychological Tests; Pilot Projects; Piracetam; Prospective Studies; Treatment Outcome

Intravenous antiepileptic drugs are required in patients needing urgent treatment or unable to take oral medication. The safety of intravenous levetiracetam has been established in prospective studies of adult epilepsy and healthy participants. The authors performed a prospective, single-center study to evaluate the safety of a rapid loading dose of intravenous levetiracetam. Patients were divided into 3 equal dosing groups (N = 15 each): 20, 40, and 60 mg/kg (corresponding to maximum doses of 1, 2, and 3 g). Electrocardiogram and safety assessment were performed during the infusion. Ages were 4 to 32 years. Postinfusion serum levetiracetam concentrations were 14 to 189 microg/mL. There were no significant changes in blood pressure, no local infusion site reactions, and no electrocardiogram abnormalities. The authors concluded that high serum levels of parenteral levetiracetam can be achieved rapidly and safely, in a small infusion volume. This finding has important implications for the treatment of status epilepticus.

Topics: Adolescent; Adult; Anticonvulsants; Blood Pressure; Child; Child, Preschool; Electrocardiography; Epilepsy; Female; Heart; Humans; Injections, Intravenous; Levetiracetam; Male; Piracetam; Seizures; Time Factors; Young Adult

The EEG background activity reflects the functional state of the brain. The established sensitivity of EEG to drug intoxication and in particular to antiepileptic drugs (AEDs) made that EEG has become useful as an objective measure for monitoring chronic AED therapy and in investigation of cognitive functions. Therapy with classical AEDs has become associated with slowing of EEG background rhythm and the EEG changes correlated to changes on cognitive measures. So far, it has not been tested whether the relatively new AED, levetiracetam (LEV) has a detrimental effect on the EEG background frequencies, too.. During the time of 6 months 28 patients underwent EEG-recording and neuropsychological testing at the three timepoints: before initiating LEV therapy, after 2 months and again after 4 months after achieving plateau dosing of LEV. EEG background frequency was analysed by using the fast Fourier Transform (FFT).. The titration and the following treatment with LEV add-on showed no negative effect on any of the measures analysed. In particular it did not lead to the lower peak frequency within the alpha band, it neither decreased the percentage of alpha band nor increase the percentage of theta and delta band. In addition there could be noticed an increase of the percentage of beta band.. Our findings demonstrate, that a LEV add-on therapy is not associated with a slowing of the EEG background frequency. This is in accordance with neuropsychological reports of our own lab and others showing that LEV add-on therapy has no negative effects on cognitive functions, either.

Topics: Anticonvulsants; Electroencephalography; Epilepsy; Female; Fourier Analysis; Humans; Levetiracetam; Male; Neuropsychological Tests; Occipital Lobe; Piracetam; Statistics, Nonparametric; Time Factors

The goals of this study are to evaluate the efficacy and tolerability of levetiracetam (LEV) as add-on therapy in children with refractory epilepsies and to determine the value of LEV blood level monitoring in this population.. Sixty-nine children (39 males and 30 females) treated with LEV between 2006 and 2007 were selected. Their medical files were reviewed for LEV efficacy and tolerability. In a subgroup of children currently taking LEV, plasma concentrations were determined by high performance liquid chromatography by ultraviolet detection (HPLC-UV) method and correlated with the given dose per kilo as well as clinical response.. Fifty-one patients (74%) had a more than 50% reduction in seizure frequency with 16 patients (23%) becoming seizure free on LEV. Eighteen (26%) patients had a less than 50% reduction in seizure frequency. Adverse events due to LEV ranged from mild to moderate in only 18 patients (26%). The most frequently observed were drowsiness, behavioral difficulties, increase in seizure frequency and headaches. The majority (60.5%) of the responders received doses between 10 and 50mg/kg/day and had a plasma concentration (PC) between 5 and 40microg/ml. However, we found no clear correlation between PC and efficacy.. Levetiracetam given twice a day in children with refractory epilepsy reduces seizure frequency in all types of epilepsy. In children, LEV is a broad spectrum anticonvulsant with a favourable safety profile.

Topics: Adolescent; Anticonvulsants; Chi-Square Distribution; Child; Child, Preschool; Chromatography, High Pressure Liquid; Epilepsy; Female; Humans; Infant; Infant, Newborn; Levetiracetam; Male; Piracetam; Retrospective Studies; Secondary Prevention; Treatment Outcome

Animal studies have shown endocrine changes after levetiracetam treatment. The present study investigated reproductive and sexual function in patients with epilepsy (aged 18-45) treated with levetiracetam (LEV: 30 men/26 women), carbamazepine (CBZ: 63 men/30 women), or lamotrigine (LTG: 37 men/40 women) monotherapy and in healthy controls (36 men/44 women). In women, no endocrine changes were observed during LEV treatment, whereas steroid hormone-binding globulin levels were greater and progesterone levels lower in women using CBZ. Dehydroepiandrosterone sulfate levels were higher and androstenedione levels lower in LTG-treated women. Arizona Sexual Experience Scale scores, which were significantly lower in females using LTG or LEV, suggesting they have better sexual function than CBZ users and controls. In men, no drug-specific hormonal pattern was observed after LEV treatment. Male patients in all treatment groups had lower androstenedione and free testosterone. Those using CBZ had lower free androgen indices and dehydroepiandrosterone sulfate levels, and higher steroid hormone-binding globulin, follicle-stimulating hormone, and luteinizing hormone levels. Arizona Sexual Experience Scale scores for men were similar in all groups. In conclusion, LEV treatment apparently has no drug-specific sexual or endocrine side effects in men or women in this age group.

Topics: Adolescent; Adult; Age Factors; Anticonvulsants; Carbamazepine; Cross-Sectional Studies; Epilepsy; Female; Gonadal Steroid Hormones; Gonadotropins; Humans; Immunoassay; Lamotrigine; Levetiracetam; Male; Middle Aged; Piracetam; Sex Factors; Surveys and Questionnaires; Testosterone; Triazines; Young Adult

The aim of this prospective, multicenter, open-label study was to investigate the efficacy of levetiracetam (LEV) and determine its effects on cognitive and neuropsychological function. Sixty-nine patients were evaluated for effects of LEV on seizure control, cognitive (Mini-Mental State Examination [MMSE]) and neuropsychological (Symptom Checklist-90 Revised [SCL-90-R]) functions, and quality of life (Quality of Life in Epilepsy--10 [QOLIE-10]) assessments at 3 and 12 months of follow-up. Thirty-nine percent of patients achieved seizure freedom, and 68% had a > or =50% seizure frequency reduction after 1 year of LEV (1235.5+/-392.7 mg/day). There were also significant improvements in mean MMSE score and in the recall and language items of MMSE. There were modest improvements in interpersonal sensitivity and paranoid ideation scales of the SCL-90-R, and improvements in cognition and medication effect items of the QOLIE-10. The results demonstrate that LEV not only effectively reduces seizure frequency, but also possibly contributes to improvements in neuropsychological functions such as recall, language, interpersonal sensitivity, and paranoid ideation.

Topics: Adult; Analysis of Variance; Anticonvulsants; Cognition Disorders; Epilepsy; Female; Humans; Levetiracetam; Male; Mental Status Schedule; Middle Aged; Neuropsychological Tests; Perception; Piracetam; Prospective Studies; Quality of Life; Retrospective Studies; Taiwan; Time Factors

Treatment-emergent side effects are frequent events, particularly during the uptitration of antiepileptic drugs. So far, monitoring of such adverse events in outpatients has often been limited to intervals of weeks or months. We here report the application of a new device for temporally fine-grained assessment of objective well-being and cognitive performance using personal digital assistants (PDAs).. Twenty adult patients with epilepsy participated in this pilot study. Ten received add-on treatment with levetiracetam. Ten patients with constant medication served as a control group. Differences between groups with respect to self-rated cognitive condition, psychophysical condition, aggressiveness, and cognitive test performance in a concentration test assessed three times daily (morning, early afternoon, and evening), over the course of 6 days, were analyzed.. Levetiracetam-treated patients manifested an early augmentation of self-rated aggressiveness, which increased in intensity over the course of days. Aggressiveness reached a maximum in the early afternoon across days. There were no major changes in cognitive performance, except for an increase in morning performance in the control group.. This study demonstrates the feasibility of a new method of ambulatory assessment of behavioral and cognitive data during titration of antiepileptic drugs. Significant changes in aggressiveness under add-on treatment with levetiracetam were found to be dependent on the time of assessment during the day. These results suggest that PDA-based ambulatory monitoring of patients with epilepsy may be a promising tool for early detection of drug-related side effects and, thus, may constitute a significant improvement in patient care.

Topics: Adult; Aggression; Ambulatory Care; Anticonvulsants; Attention; Attitude to Computers; Cognition; Computers, Handheld; Drug Therapy, Combination; Epilepsy; Feasibility Studies; Female; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Patient Compliance; Pilot Projects; Piracetam

Stroke is the most common cause of seizures in the elderly. Antiepileptic drugs are used to treat most patients with late poststroke seizures. The aim of this study was to evaluate the efficacy and tolerability of levetiracetam (LEV) in patients aged 60 or older with late-onset poststroke seizures. This prospective study evaluated patients 60 years of age or older, who had at least two late-onset poststroke seizures and were given LEV monotherapy. Demographic data and seizure and stroke characteristics were recorded. Outpatient visits were made after 2, 4, 6, 9, and 12 months and every 3 months thereafter, and the effectiveness and tolerability of LEV were investigated. Thirty-four patients with a mean age of 69.76+/-6.41 were included in this study. Average seizure frequency before treatment was 3.61+/-3.02/month. Mean follow-up time was 17.68+/-3.24 months. At daily doses of 1000-2000 mg, 82.4% of the patients were seizure free, and 7 patients (20.6%) had side effects. LEV was discontinued in one patient because of severe somnolence. Two patients were switched to another antiepileptic drug because of uncontrolled seizures despite an increase in dose up to 3000 mg/day. LEV monotherapy can be effective and well tolerated in elderly patients with late-onset poststroke seizures.

Topics: Aged; Anticonvulsants; Drug Evaluation; Epilepsy; Female; Follow-Up Studies; Geriatrics; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Stroke; Time Factors

The goals of this study were to observe behavioral changes in patients receiving levetiracetam (LEV), a newer antiepileptic drug (AED), and to answer the question of whether LEV exerts a specific effect on impulse control and aggression.. We asked 288 consecutive patients with epilepsy on LEV (90% polytherapy, mean dose=2689 mg) and 135 relatives whether LEV caused a positive or negative behavioral change. Forty-three patients on other AEDs served as a control group. Ratings were related to patient characteristics, efficacy, dose, drug load, bidirectional ratings of change in behavioral domains, and questionnaires on personality (Fragebogens zur Persönlichkeit bei zerebralen Erkrankungen) and impulsivity (Barratt Impulsiveness Scale-11).. LEV was rated as very effective by 40% of the patients. In contrast to only 9% of the controls, a considerable number of patients reported a behavioral change while taking LEV (12% very negative, 25% negative, 16% positive, 6% very positive). Negative ratings were due to loss of self-control, restlessness, sleep problems, and, most importantly, aggression. Positive ratings were due to increased energy, vigilance, and activation. Increases in psychomotor speed, concentration, and remote memory indicated subjectively experienced positive effects on cognition. The proxy reports indicated reliable self-reports. Reported change was not related to type of epilepsy, co-therapy, dose, drug load, or psychiatric history. Negative effects were, however, associated with poorer seizure control, mental retardation, indicators of an organic psychosyndrome, and nonplanning impulsiveness.. The results indicate that LEV exerts a dose-independent stimulating effect that can be positive or negative. Aggression is a prominent feature. Lack of efficacy, mental retardation, and presumably also pre-intake disposition (organic psychosyndrome, impulsivity) may be helpful in predicting whether additional activation under LEV will be positive or negative.

Topics: Adolescent; Adult; Affect; Analysis of Variance; Anticonvulsants; Behavioral Symptoms; Child; Cognition; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Personality; Piracetam; Young Adult

Behavioral side effects related to the use of levetiracetam (LEV) in epilepsy are increasingly being recognized. Patients followed in our center have reported improvement of these side effects after starting pyridoxine (vitamin B(6)) supplements. Using mailed questionnaires, retrospective chart reviews, and phone call follow-ups, we analyzed 42 pediatric patients who had been treated with LEV and pyridoxine. Twenty-two patients started pyridoxine after being on LEV, and significant behavioral improvement was observed in nine (41%), no effect in eight (36%), deterioration in four (18%), and an uncertain effect in one. The effects of pyridoxine supplementation were observed during the first week. The remaining patients (20) were already on pyridoxine before LEV was started, started pyridoxine and LEV at the same time, or took pyridoxine intermittently. Pyridoxine is an easily available, inexpensive, and safe therapeutic option. Given these preliminary results, we plan to conduct a placebo-controlled cross-over study to better characterize these observations.

Topics: Adolescent; Anticonvulsants; Behavioral Symptoms; Child; Child, Preschool; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Pyridoxine; Retrospective Studies; Vitamin B Complex; Young Adult

Objective and subjective cognitive measures were evaluated in 401 patients before and 3 and 6 months after introducing levetiracetam (LEV). Initially, cognitive impairment was indicated in 37-44% of the patients, and subjective impairments in 32-67%. With LEV, 87% of untreated patients changed to monotherapy, and 94% changed from mono- to polytherapy. The rate of retention of LEV was 97%; adverse events were reported by 7%. Under LEV, 36% achieved early seizure control, 25% achieved late seizure control, 33% continued to have seizures, and 7% had a relapse. Very good tolerance was reported by 68%, and cognitive improvement by 58%. Objective improvement was significant in 23-29% of the patients; 5-6% deteriorated. Better baseline scores, later-onset epilepsies, fewer initial antiepileptic drugs, and seizure control were predictive of a better cognitive outcome. Considering the uncontrolled study design and the increase in total drug load, LEV appeared safe and efficacious, and a general subjective and objective cognitive improvement could be noted. However, a controlled study design would be required to attribute these improvements to a specific drug action.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Cognition Disorders; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Piracetam; Prospective Studies; Regression Analysis; Young Adult

Levetiracetam (LEV) monotherapy was investigated in 35 patients (pts) (16M/19F, 71.9+/-7.3 years of age) with late-onset post-stroke seizures (i.e. seizures occurring at least 2 weeks after an ischemic stroke) in a prospective open-label study. Overall, 27 pts (77.1%) achieved a condition of seizure freedom (defined as 1 year without seizures): 19 (54.3%) at a daily LEV dose of 1000mg, 7 (20.0%) at 1500mg, 1 (2.8%) at 2000mg. Four pts (11.4%) discontinued the drug because of intolerable side effects (drowsiness associated to gait disturbance in 1 pt, and aggressive behaviour in the remaining 3 pts); 3 pts were unresponsive at a dose of 3000mg, and 1 pt was lost at follow-up. These observations suggest that LEV exhibits safety and efficacy profiles which make it an optimal candidate as a first-choice drug against post-stroke seizures.

Topics: Aged; Aged, 80 and over; Aggression; Anticonvulsants; Brain Ischemia; Cardiovascular Agents; Drug Interactions; Epilepsy; Female; Fibrinolytic Agents; Gait Ataxia; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Sleep Stages

This aim of the study was to ascertain the importance of clinical parameters on the response to treatment in refractory epilepsy patients on levetiracetam (LEV).. We retrospectively evaluated medical records of 132 patients aged 17-78 years with refractory epilepsy (defined as a failure of at least two antiepileptic drugs due to the lack of efficacy) exposed to LEV. We analyzed the response (seizure freedom or continuing LEV) using logistic regression.. Of 132 patients exposed to LEV, 103 cases continued the drug. Of the discontinuations (29/132), 75% were for lack of efficacy and 25% for tolerability problems. Twenty-three percent of the previously refractory patients achieved seizure freedom for at least 1 year with LEV in combination therapy. The dose of LEV in 80% of seizure-free patients was 1000 mg/day or less. The duration of epilepsy, age and sex were not associated with response to LEV. Seizure freedom was associated with epileptic syndrome or etiology. If no specific syndrome was recognized, there was a significantly greater chance for response compared with temporal lobe epilepsy (OR 20.76; 95% CI 2.12-203.61).. Our study was based on the careful clinical evaluation of the patients with extensive use of video EEG (50%) and MRI scans (95%). These clinical predictors were evasive in previous studies. This study showed that they are worth pursuing but significantly larger groups of patients need to be investigated to reach significant findings.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Drug Evaluation; Epilepsy; Female; Humans; Levetiracetam; Logistic Models; Male; Middle Aged; Piracetam; Predictive Value of Tests; Retrospective Studies; Treatment Outcome

Intravenous levetiracetam recently became available for use in patients aged >16 years. There are few data about its safety and efficacy in children. We retrospectively analyzed data from children treated with intravenous levetiracetam. Ten patients (6 female, 4 male), aged 3 weeks to 19 years, were treated with intravenous levetiracetam at a mean dose of 50.5 mg/kg/day for a mean duration of 4.9 days. Four patients received intravenous levetiracetam for acute repetitive seizures/status epilepticus, and three as replacement for oral levetiracetam because administration of oral levetiracetam was temporarily infeasible. One patient each received intravenous levetiracetam for seizure prophylaxis during brain biopsy, as maintenance treatment after acute seizures, and as substitute for sodium valproate. Three of four patients with acute repetitive seizures/status epilepticus became seizure-free; the fourth patient had a partial reduction in seizure frequency. All three patients who received intravenous levetiracetam as substitute for oral levetiracetam tolerated the switch well. The other three patients were seizure-free on intravenous levetiracetam. No serious adverse effects were observed, and all patients completed treatment with intravenous levetiracetam for the intended period. Intravenous levetiracetam may be effective in various clinical situations requiring intravenous administration of an antiepileptic drug.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Infant, Newborn; Injections, Intraventricular; Levetiracetam; Male; Piracetam

Levetiracetam (LEV) is a broad-spectrum antiepileptic drug with no known interactions and a favorable profile of adverse events. These properties make it a good candidate for use in critically ill patients. An intravenous formulation of LEV was recently approved. The present study retrospectively assesses the safety and efficacy of LEV in the first 50 critically ill patients treated with intravenous LEV. Indications for use were seizure prophylaxis, acute symptomatic seizures, and all forms of status epilepticus. There were no major adverse effects, although less prominent changes may have been masked by the already severely compromised condition of these patients. Two patients (4%) had transiently lowered platelet counts (55,000 and 82,000, respectively). Efficacy, defined as cessation of seizure activity or prevention of its recurrence, was observed in 41 of 50 patients (82%). Antiepileptic treatment of critically ill patients with LEV seems to be effective and safe according to the data for this small cohort, but this observation warrants further prospective investigation in a larger number of patients.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Blood Platelets; Critical Illness; Dose-Response Relationship, Drug; Drug Evaluation; Epilepsy; Female; Humans; Injections, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Retrospective Studies

Despite the high incidence of epilepsy in very young children, the availability of approved antiepileptic drugs for this population is limited. This study assessed the efficacy and tolerability of levetiracetam in children younger than 2 years of age with various types of epilepsy. A single-center, retrospective chart review of 28 patients ranging in age from 2 weeks to 22 months treated with levetiracetam over a 2.5-year period was conducted. The mean dosage of levetiracetam was 39 mg/kg per day, and the mean duration of treatment was 6.3 months. The majority of patients (54%) were also taking 1 or 2 other antiepileptic drugs. A reduction in seizure frequency was found in 54%, with 14% achieving seizure freedom. Eight patients showed no response to levetiracetam treatment. Efficacy was highest among patients with generalized epilepsy. Adverse effects occurred in 2 patients and were behavioral in nature. Levetiracetam treatment was safe and effective in this group of very young patients with various types of epilepsy.

Topics: Anticonvulsants; Drug Evaluation; Epilepsy; Female; Humans; Infant; Infant, Newborn; Levetiracetam; Male; Piracetam; Retrospective Studies

Nonsedating antiepileptic drugs (AEDs) that can be initiated rapidly are desirable in a variety of clinical situations. Levetiracetam (LEV) is a newer AED, with a recently approved parenteral formulation, that can be initiated at doses effective in controlling seizures. We investigated whether oral loading of levetiracetam is well tolerated and facilitates stabilization and discharge of patients in epilepsy monitoring units (EMU).. Adult patients in the EMU at two centers were identified who received 1,500 mg of LEV in a single dose. This was an observational study of these patients where LEV was thought to be an appropriate component of the therapeutic regimen. Patients were either LEV naive or had been off all LEV for at least 3 days. LEV maintenance was begun 12 hours later at doses of 500 to 1,000 mg twice a day.. A total of 37 adult patients (20 female) were identified. There were no spontaneous complaints of side effects. Upon questioning, 33 patients (89%) denied side effects. The remaining 4 patients (11%) reported transient irritability, imbalance, tiredness, or lightheadedness. Eleven patients (mean weight = 85.0 Kg) had mean LEV serum concentration of 31.5 microg/mL after 1 hour, 23 (mean weight 85.7 Kg) had mean concentration of 30.77 microg/mL after 2 hours, five (mean weight 84.3 Kg) had mean concentration of 12.1 microg/mL after 12 hours, and two (mean weight 94 Kg) had mean concentration of 7.4 microg/mL after 14 hours. No seizures occurred within 24 hours of loading. All patients were able to be discharged 3 to 30 hours after loading.. In the population surveyed, oral loading with levetiracetam was well-tolerated and rapidly yielded serum concentrations thought to decrease seizure frequency. This regimen facilitated discharge from the epilepsy monitoring units.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticonvulsants; Drug Evaluation; Drug Tolerance; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Time Factors

We report the results of a prospective study of the efficacy and tolerability of levetiracetam, a new antiepileptic drug with a unique mechanism of action, in comparison with controlled-release carbamazepine as first treatment in newly diagnosed epilepsy.. Adults with > or =2 partial or generalized tonic-clonic seizures in the previous year were randomly assigned to levetiracetam (500 mg twice daily, n = 288) or controlled-release carbamazepine (200 mg twice daily, n = 291) in a multicenter, double-blind, noninferiority, parallel-group trial. If a seizure occurred within 26 weeks of stabilization, dosage was increased incrementally to a maximum of levetiracetam 1,500 mg twice daily or carbamazepine 600 mg twice daily. Patients achieving the primary endpoint (6-month seizure freedom) continued on treatment for a further 6-month maintenance period.. At per-protocol analysis, 73.0% (56.6%) of patients randomized to levetiracetam and 72.8% (58.5%) receiving controlled-release carbamazepine were seizure free at the last evaluated dose (adjusted absolute difference 0.2%, 95% CI -7.8% to 8.2%) for > or =6 months (1 year). Of all patients achieving 6-month (1-year) remission, 80.1% (86.0%) in the levetiracetam group and 85.4% (89.3%) in the carbamazepine group did so at the lowest dose level. Withdrawal rates for adverse events were 14.4% with levetiracetam and 19.2% with carbamazepine.. Levetiracetam and controlled-release carbamazepine produced equivalent seizure freedom rates in newly diagnosed epilepsy at optimal dosing in a setting mimicking clinical practice. This trial has confirmed in a randomized, double-blind setting previously uncontrolled observations that most people with epilepsy will respond to their first-ever antiepileptic drug at low dosage.

Topics: Adult; Anticonvulsants; Carbamazepine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Treatment Outcome

To assess the efficacy and tolerability of Levetiracetam (LEV) in children and adolescents with refractory epilepsy with a special interest in the long-term retention rate.. One hundred and twenty-nine patients (83 male, 46 female; mean age 10.6 years/range: 6 months-39 years 9 months) were included in a prospective, open-label, add-on trial of LEV for up to 3 years. All patients had severe forms of epilepsy starting before the age of 10 often accompanied by mental retardation. Primary outcome measures were changes in seizure frequency after 6 months on the medication with LEV, with initial responders (>50% seizure reduction). Further objective was the retention rate of LEV therapy after 3 years defined as percentage of patients still taking LEV.. Thirty-five patients (27.1%) were initial responders of which 5 became seizure free. The average maximum LEV dosage was 39.8 mg/kg/day (range: 6-70 mg/kg/day) with no difference responders vs. no responders. The retention rate for responders after 3 years was 22.5%. The rate of side effects was 39.8% in all patients, with the most frequent side effects being fatigue (12.5%), aggressiveness (7.8%) and gastrointestinal disorders (13.3%).. Our study in patients with refractory epilepsy suggests that our initial responders were very likely to be still taking LEV after 3 years. We therefore consider treatment with LEV in this special group of patients with refractory epilepsy a promising therapeutic option, because of its favourable tolerance profile, the option of fast titration and the absence of drug interactions.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Drug Evaluation; Epilepsy; Female; Humans; Infant; Levetiracetam; Longitudinal Studies; Male; Piracetam; Prospective Studies; Severity of Illness Index

Levetiracetam (LEV) is a new generation anti-epileptic drug, which has been approved as add-on therapy for partial epilepsy. The mechanism of LEV is not yet completely understood.. To evaluate the efficacy and tolerability of LEV in adult patients with refractory epilepsy.. We report the results of 49 patients with refractory epilepsy, with partial and generalized seizures, who received LEV as an add-on treatment, in two tertiary medical centers. There were 27 males, mean age 35.4+13 years. The average duration of epilepsy was 21 + 11 years, the average seizure rate was 31 + 30 per month. The patients were treated with a mean of 2.6 AED when LEV was introduced. The patients were treated for 12.6 + 9.7 months with an average dose of 1964 + 743.7 mg LEV per day.. Five (10%) patients became seizure free, 12 (25%) responded with seizure reduction of more than 50% following the introduction of LEV, 8 (16%) responded with seizure reduction of less than 50%, no response to LEV was reported in 20 (41%) and seizure aggravation occurred in 4 (8%). No serious persistent adverse events were reported. The main side effect was drowsiness in 10% of patients.. The results of this study, as well as previous studies, suggest that LEV is a well-tolerated new antiepileptic drug, and as an add-on therapy it may effectively improve seizure control in patients with intractable epilepsy.

Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Seizures; Treatment Outcome

Although antiepileptic drug (AED) monitoring in saliva may have some clinical applicability, it has not yet come into routine use. The correlation between levetiracetam (LEV) saliva and serum concentrations also remains unclear. To confirm LEV saliva assay as a useful, noninvasive alternative to serum measurement, we investigated the possible correlation between saliva and serum LEV concentrations. Samples of saliva and blood were collected from 30 patients with epilepsy receiving chronic therapy with LEV as monotherapy or add-on therapy, and LEV concentrations were assayed in saliva and serum. Linear regression analyses showed a close correlation between saliva and serum LEV concentrations (r2 = 0.90; P < 0.001). LEV blood and saliva concentrations were linearly related to daily drug doses (r2 = 0.78 and 0.70; P < 0.01). When data were analyzed for subgroups (patients receiving LEV in monotherapy, as add-on therapy with enzyme-inducer AEDs, and as add-on therapy with noninducer or moderate-inducer AEDs), no significant difference was found between saliva and serum LEV concentrations among groups. These preliminary results indicate that LEV, like other AEDs, can be measured in saliva as an alternative to blood-based assays. Saliva LEV collection and assay is a valid noninvasive, more convenient alternative to serum measurement.

Topics: Adult; Aged; Anticonvulsants; Drug Monitoring; Epilepsy; Female; Humans; Levetiracetam; Linear Models; Male; Middle Aged; Piracetam; Saliva

To determine whether levetiracetam (LEV) affects plasma concentrations of carbamazepine, valproic acid, topiramate, and lamotrigine in children with epilepsy.. The potential for interaction of LEV with other antiepileptic drugs (AEDs) was assessed using plasma drug levels obtained in a randomized placebo-controlled phase III trial of adjunctive LEV in children receiving one or two concomitant AEDs. Multiple plasma AED levels at baseline and during adjunctive treatment with LEV or placebo were compared by repeated measures analysis of covariance and mean concentration ratios (treatment/baseline) were estimated with their 90% confidence intervals (CI).. The study population included 187 children receiving any concomitant AED alone or in combination. The geometric mean concentrations at baseline and during LEV treatment were carbamazepine 8.4 microg/ml versus 8.1 microg/ml (coefficient of variation, CV = 30%; n = 35); valproic acid 83.8 versus 82.5 microg/ml (CV = 38%; n = 23); topiramate 7.3 versus 7.2 microg/ml (CV = 82%; n = 28); lamotrigine 8.2 versus 7.7 microg/ml (CV = 62%; n = 22). For each AED, the mean concentration ratios (LEV/baseline) and their 90% CIs showed that AED concentrations were unaffected by concomitant LEV administration. No differences were observed between LEV and placebo.. LEV does not affect plasma concentrations of carbamazepine, valproic acid, topiramate, or lamotrigine in children with epilepsy.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Drug Interactions; Drug Therapy, Combination; Epilepsy; Female; Fructose; Humans; Lamotrigine; Levetiracetam; Male; Outcome Assessment, Health Care; Piracetam; Placebos; Topiramate; Triazines; Valproic Acid

Individuals with epilepsy commonly report daytime sleepiness, attributed to sleep disruption (frequent arousals, awakenings, and stage shifts) induced by ictal and interictal activity or antiepileptic drugs (AEDs) or both. To study the effect of levetiracetam (LEV) on sleep, at full doses but without the interference of epilepsy, we investigated the sleep architecture and daytime vigilance in healthy adults after 3 weeks of treatment.. The study was of a double-blind crossover design with random allocation of multiple doses of two different treatments (randomly first LEV

Topics: Adult; Anticonvulsants; Arousal; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Placebos; Polysomnography; Sleep; Sleep Wake Disorders; Treatment Outcome

To prospectively assess the safety and efficacy of levetiracetam in patients with uncontrolled focal epilepsy, in a common practice-based setting.. In this phase IV, open-label, 16-week community-based study, adult patients with focal seizures initially received levetiracetam 1,000 mg/day. Throughout the study, the dose was adjusted in increments of 1,000 mg (maximum 3,000 mg/day) to achieve seizure control and maintain tolerability. The outcome parameters were the percentage reduction in partial and total seizure frequency per week from historical baseline, global evaluation scale (GES), and adverse events (AE).. Seven hundred and thirty-one patients were included in this analysis and 84.4% completed the study. The median percent reduction in all seizures was 47.8%, and 49.3% for all partial seizures. The 50% responder rate was 49%, and the seizure-free rate was 17.2% for all partial seizures. Approximately 60% of patients showed moderate to marked improvement on the GES. The majority of AE were of mild to moderate severity; the most commonly reported being asthenia, somnolence, headache, and dizziness.. Levetiracetam is both efficacious and safe as an add-on therapy in patients with refractory epilepsy treated by clinicians in their daily practice.

Topics: Adult; Anticonvulsants; Disorders of Excessive Somnolence; Dizziness; Dose-Response Relationship, Drug; Drug Resistance; Epilepsy; Female; Headache; Humans; International Cooperation; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Sensation Disorders; Treatment Outcome

Epilepsy is a common clinical problem in patients with brain tumours, strongly affecting patients' quality of life. Tumour-related seizures are often difficult to control, and the clinical picture is complicated by frequent interactions between antiepileptic drugs (AEDs) and antineoplastic agents. We studied the safety and efficacy of levetiracetam (LEV), a new AED with a different pharmacological profile from traditional anticonvulsants, in 19 patients (6 females; age range 28-70 years, mean 48 years) with supratentorial gliomas and epilepsy. Seizure types were simple partial in four patients, complex partial in 4, complex partial with secondary generalization in 7, and generalized tonic-clonic in 4. LEV was added to the existing AED treatment on account of persisting seizures, and titrated at dosages of 1,000-3,000 mg/day. Patients were seen at the Outpatient's Centre every 1-3 months, and followed-up for 7-50 months (mean 25 months, median 20 months). At the end of the observation period, nine patients were seizure free (seizure free period ranging from 7 to 33 months, mean 16, median 12) and five patients reported an improvement in seizure-frequency from daily to weekly (n=1) or from weekly to monthly (n=3). Seizure frequency was unmodified in four patients and increased (from monthly to weekly) in one. No LEV-related adverse effects were observed. LEV plasma concentrations monitored in 12 subjects ranged from 11.9 to 82.1 microg/ml. Our preliminary open data indicate that add-on treatment with LEV in patients with brain tumours is safe and appears to be effective in reducing seizure frequency. Controlled studies on larger populations are warranted to confirm these open observations.

Topics: Adult; Aged; Anticonvulsants; Brain Neoplasms; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam

The primary objective of this placebo-controlled study was to evaluate the safety and tolerability of levetiracetam (LEV) administered intravenously (IV) at higher doses and/or at a faster infusion rate than proposed. The secondary objective was to assess LEV pharmacokinetics.. Single ascending doses of LEV administered by IV infusion (2,000, 3,000, 4,000 mg over 15 min; 1,500, 2,000, 2,500 mg over 5 min) were evaluated in 48 healthy subjects in a randomized, single-blind, placebo-controlled study.. All randomized subjects completed the study. Adverse events reported after IV administration of LEV (

Topics: Administration, Oral; Adult; Anticonvulsants; Area Under Curve; Blood Pressure; Disorders of Excessive Somnolence; Dizziness; Dose-Response Relationship, Drug; Epilepsy; Fatigue; Female; Half-Life; Headache; Heart Rate; Humans; Infusions, Intravenous; Levetiracetam; Male; Piracetam; Placebos; Single-Blind Method; Time Factors

To evaluate the efficacy and safety of long-term add-on treatment with levetiracetam 1,000-4,000 mg/day.. In this multicenter, open-label follow-up study, 505 patients, from 10 European countries, who had benefited from previous add-on treatment with levetiracetam in a clinical trial or compassionate-use program were enrolled; 274 (54.3%) stayed to the end. Most then continued levetiracetam by prescription or in a named patient program, where it was not yet commercially available. Mean treatment duration was 1,045 days (range: 24 days to >7 years). Median daily dosage was 3,000 mg/day (range: 250-6,000 mg/day), with 250 (49.5%) patients receiving levetiracetam for >3 years.. Median total and partial seizure frequency per week over the evaluation period were 0.8 and 0.7; seizure frequency per week was generally stable over time and remained low. There was a probability of 6.6% of remaining seizure-free for the first 3 years, and of 18.9% of having a seizure-free period of at least 3 years at any time. Most adverse events were mild or moderate and unrelated to study drug. Levetiracetam was well tolerated, and provided stable seizure control during long-term treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Treatment Outcome

The aim of this study was to assess the relationship between levetiracetam dose and both efficacy and safety in adult patients with refractory partial epilepsy. Dose-response relationships for levetiracetam efficacy were evaluated using pooled data from three trials including adults with refractory partial epilepsy. Two were randomized, double-blind, placebo-controlled, parallel-group trials in which doses of 1000-3000 mg/day of levetiracetam were administered as adjunctive therapy. The third consisted of the two parts of a crossover randomized, double-blind study in which levetiracetam (1000 or 2000 mg/day) or placebo was added to ongoing therapy. Data from each part of the crossover trial were included as if it was an independent parallel-group study. A fourth randomized double-blind trial was added for the safety evaluation. It included data from adults receiving placebo or 2000 mg/day of levetiracetam as adjunctive therapy for refractory partial seizures. The combined analysis showed an increasing effect with increasing dose. The responder rates (> or = 50% reduction in seizures) for placebo and levetiracetam 1000, 2000, and 3000 mg/day were 13.1%, 28.5%, 34.3%, and 41.3%, respectively. The respective values for seizure freedom were 0.8%, 4.7%, 6.3%, and 8.6%. There was no evidence of a dose-response relationship with regard to adverse events, including those (asthenia, dizziness, somnolence) most commonly associated with this antiepileptic drug. Patients who do not become seizure-free at the lowest recommended levetiracetam dose (1000 mg/day) should be titrated to 2000 or 3000 mg/day to provide the greatest opportunity for efficacy with little or no increased risk for adverse events.

Topics: Anticonvulsants; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Evaluation; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Humans; Levetiracetam; Outcome Assessment, Health Care; Piracetam

Topics: Adolescent; Adult; Anticonvulsants; Child; Drug Administration Schedule; Drug Tolerance; Epilepsy; Humans; Levetiracetam; Periodicity; Piracetam

Mood-modulating profiles of antiepileptic drugs (AEDs) have been classified by Ketter, Post, and Theodore [Neurology 1999; 53 (5, Suppl. 2) S53-76] into two classes: the first class is assumed to have deactivating effects related to GABA potentiation, and the second class is assumed to have activating effects that are associated with glutamate attenuation. We tested this hypothesis by reviewing the multiple mechanisms of action of topiramate (TPM) and levetiracetam (LEV) together with clinical behavioral side effects of patients who had been treated with TPM and LEV in a tertiary referral center for epilepsy. We found LEV to manifest activating and deactivating side effects equally and TPM to act as a deactivating AED, with tiredness/sleepiness side effects being predominant. TPM, in comparison to LEV, was found to be associated with a high incidence of side effects. Testing the hypothesis of Ketter et al. (1999) the deactivating effects of TPM may be coupled to a predominance of potentiation of GABA, but the oversimplified basis of the model needs to be acknowledged.

Topics: Adult; Anticonvulsants; Chi-Square Distribution; Demography; Drug Therapy, Combination; Epilepsy; Female; Follow-Up Studies; Fructose; gamma-Aminobutyric Acid; Glutamic Acid; Humans; Levetiracetam; Male; Middle Aged; Models, Biological; Mood Disorders; Odds Ratio; Piracetam; Time Factors; Topiramate

The aim of this multicentric, prospective and uncontrolled study was to evaluate the efficacy and safety of levetiracetam in 110 children with refractory epilepsy, of whom 21 were less than 4 years old. After a median follow-up period of 7 months, levetiracetam administration was effective (responders with >50% decrease in seizure frequency) in 39% of children, of whom 10 (9%) became seizure-free. The efficacy was higher in patients with localization-related epilepsy (58% of responders) than in those with generalized epilepsy (37% of responders). Levetiracetam was well tolerated. The main side effects of somnolence and irritability occurred in 14% of patients. In one patient acute choreoathetosis occurred after few doses of levetiracetam. Overall, the adverse effects were not severe. Children younger than 4 years were particularly tolerant. In conclusion, the present study confirms that levetiracetam is effective and well tolerated as an add-on treatment in children with refractory epilepsy. Our preliminary data also indicate that levetiracetam may be a valid therapeutic option for epilepsy in infants and young children.

Topics: Anticonvulsants; Dose-Response Relationship, Drug; Drug Evaluation; Drug Therapy, Combination; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Humans; Infant; Levetiracetam; Male; Neurologic Examination; Piracetam; Prospective Studies; Retrospective Studies; Treatment Outcome

To further evaluate the safety, efficacy and optimal dose of levetiracetam (LEV) in daily clinical practice among patients with uncontrolled partial epilepsy with or without secondary generalization.. In this phase IV, open-label, 16-week community-based study, 178 at least 16-year-old patients with refractory focal epilepsy were treated with 1000, 2000 or 3000 mg levetiracetam as adjunctive therapy. All patients started with 500 mg LEV b.i.d. (1000 mg/day); the dose was adjusted in 2-week intervals up to 1500 b.i.d. (3000 mg/day) depending on seizure control and tolerability. The main objectives were the adverse events, the percentage reduction in partial and total seizure frequency per week from baseline and the retention rate, defined as the percentage of patients taking LEV at the end of the 16-week treatment period.. Of the 178 patients who took at least one dose of LEV 151 completed the study. Thus, the retention rate (number of patients taking LEV at the end of the 16-week treatment period) was 84.8%. Most frequently reported adverse events were asthenia, dizziness, headache, nausea, somnolence and hostility; the majority of these events were of mild to moderate intensity. The seizure-free rate of the ITT population with focal seizures was 16.7%, for all seizures 16.6%; the median reduction of focal seizure frequency was 47.6%, and 46.5% for all seizures. The 50% responder rate was 46.6% for focal seizures and 45.1% for all seizures.. Add-on treatment with LEV in patients with refractory partial epilepsy was safe and effective in this study.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Austria; Demography; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation; Epilepsy; Female; Germany; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Switzerland; Time Factors; Treatment Outcome

To evaluate the efficacy and tolerability of Levetiracetam (LEV) in a large pediatric cohort with drug-resistant epilepsy from a prospective multicenter observational study.. We report the results of a multicenter observational survey of a cohort of 285 pediatric patients (mean: 9.9 years, range: 0; 6-17; 11) with refractory generalized and focal epilepsy who received Levetiracetam as an add-on open label treatment trial. The average duration of epilepsy was 6.0 years and the patients were treated with a mean of 7.0 antiepileptic drugs (AED) before LEV was introduced.. No serious persistent adverse events were reported. Reversible colitis and an apnoea syndrome in a child with phosphorylase-A-kinase-deficiency were noted. Mild to moderate side effects were reported in 128 patients (44.9%), consisting most frequently of somnolence (23.9%), general behavioral changes (15.4%), aggression (10.5%) and sleep disturbances (3.2%). In 209 patients, efficacy was analyzed over a treatment period of at least 12 weeks compared to a baseline of 2 weeks. Thirteen patients (6.2%) became seizure free, 39 (18.7%) responded with a seizure reduction of more than 50% following introduction of LEV. No response to LEV was reported in 65.1% (n=136). A decrease of initial treatment effect was seen in 37 patients (17.8%) while in 6.7% the seizure frequency doubled to the baseline (n=14). In seven patients (3.3%), the effect of LEV on seizure frequency could not be evaluated. A positive psychotropic effect was observed in 18 patients (8.6%). Mental retardation was associated with poor response and associated with more side effects and earlier discontinuation of LEV therapy.. LEV is a well-tolerated new AED that may effectively improve seizure control as an add-on drug in resistant epilepsy in childhood with good tolerability. However, neurologically handicapped children appear at increased risk for reversible neurocognitive side effects and have a poorer treatment response.

Topics: Anticonvulsants; Child; Child, Preschool; Demography; Drug Evaluation; Drug Therapy, Combination; Epilepsy; Female; Germany; Humans; Infant; Infant, Newborn; Levetiracetam; Male; Piracetam; Prospective Studies; Retrospective Studies; Single-Blind Method; Treatment Outcome

To assess the add-on efficacy of levetiracetam on the EEG, behavior, and cognition of children with continuous spikes and waves during slow sleep (CSWS).. Charts of children with behavioral and/or cognitive deterioration associated with CSWS who received levetiracetam at 50 mg/kg/day as add-on treatment were retrospectively reviewed. Awake and sleep EEG recordings and detailed neuropsychological and behavioral assessments were available at baseline and 2 months after levetiracetam initiation. In children showing clinical and/or electrophysiological improvement after 2 months, levetiracetam was continued with a new evaluation at 1 year.. Twelve patients were included (9 cryptogenic and 3 symptomatic cases). Seven patients (58.3%) showed improvement of EEG record. Among these seven patients, neuropsychological evaluation was improved in three, and in the other four patients, not testable because of severe cognitive impairment, behavior was improved. Two patients improved in neuropsychological evaluation despite the lack of EEG improvement. Eight patients (66.6%) continued levetiracetam treatment after 2 months. After 1 year, four patients were still on levetiracetam, two because sustained effect on EEG and behavior and the two others because improvement in neuropsychological testing despite unchanged EEG. Levetiracetam was discontinued in the other four patients because of neuropsychological or behavioral deterioration associated with CSWS pattern, between 9 and 11 months after treatment initiation.. This retrospective study suggests that levetiracetam has a positive effect on the EEG, the behavior, and the cognition of patients with epilepsy and CSWS. Additional studies are warranted in order to assess the place of this drug in these epileptic conditions.

Topics: Adolescent; Anticonvulsants; Cerebral Cortex; Child; Child Behavior Disorders; Child, Preschool; Cognition Disorders; Comorbidity; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Neuropsychological Tests; Piracetam; Retrospective Studies; Sleep Stages; Syndrome; Treatment Outcome

The authors assessed the effect of concomitant antiepileptic therapy on steady-state plasma concentrations of the new anti-epileptic drug (AED) levetiracetam in a cohort of 100 adult patients with epilepsy. On the basis of concomitant AEDs, patients were divided into two groups, otherwise comparable for age, gender, weight-adjusted daily dose of levetiracetam, and dosing frequency: group A (n = 65), receiving levetiracetam plus AED inducers of cytochrome P450 (CYP) metabolism, such as carbamazepine, phenobarbital, and phenytoin; group B (n = 35), receiving levetiracetam plus AEDs without inducing properties of CYP metabolism, namely valproic acid and lamotrigine. Plasma levetiracetam concentrations were measured by HPLC with spectrophotometric detection. Median morning trough levetiracetam plasma concentrations were significantly lower in patients of group A than in patients of group B (10.4 microg/mL versus 14.7 microg/mL, P < 0.001). Median weight-normalized levetiracetam apparent oral clearance (CL/F) was 1.3-fold in patients receiving AED inducers compared with patients on AED noninducers (1.93 versus 1.45 mL x min(-1) x kg, P < 0.001). No gender-related difference was observed in CL/F values. Levetiracetam plasma concentrations were linearly related to daily drug doses, regardless of concomitant AED therapy, over a dose range from 500 to 5000 mg/d, although at a given daily dose an appreciable interpatient variability was observed in matched plasma drug concentrations. Concomitant AED inducers can contribute to variability in levetiracetam disposition in patients with epilepsy. The observed differences were moderate and possibly of minor clinical significance.

Topics: Adult; Anticonvulsants; Chromatography, High Pressure Liquid; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Prospective Studies

In this postlicensing surveillance study in a large unselected population, data were collected prospectively on all patients prescribed levetiracetam (LEV) at a regional epilepsy clinic over a 2-year period. Two hundred forty-five (69.2%) patients remained on LEV, with 8.8% achieving remission and some improvement in seizure control in 49.3%. Sedation was the most common adverse effect (10.7%), but mood disturbance was more likely to lead to discontinuation (4.8%). Cumulative probability of remaining on LEV at 12 months was 0.74 (95% CI 0.69 to 0.79). Factors predictive of a poorer retention were a greater number of previous antiepileptic drugs and a faster initial titration regimen.

Topics: Anticonvulsants; Consciousness Disorders; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Life Tables; Male; Mood Disorders; Patient Dropouts; Piracetam; Product Surveillance, Postmarketing; Prospective Studies; Remission Induction; Treatment Outcome

Levetiracetam (LEV) is a novel antiepileptic drug (AED) with efficacy against a wide range of seizures types. The aim of this observational study was to assess its effectiveness in patients with mental retardation and refractory epilepsy. Sixty-four patients were started on adjunctive LEV after a 3-month baseline. LEV was initially dosed at 250 mg daily and increased by 250 mg every 2 weeks thereafter according to clinical response. Caregivers rated the patient's sleep, appetite, alertness, and behavior as poor (1), reasonable (2), or good (3) at each clinic visit. Patients were reviewed until one of four endpoints was reached: seizure freedom for at least 6 months, > or = 50% reduction in seizure frequency (responder) over a 6-month period, <50% reduction in seizure frequency (marginal effect) over a 6-month period, or LEV withdrawal due to lack of efficacy, adverse effects, or both. Twenty-four (38%) patients became seizure-free, 10 of whom were controlled on LEV 250 mg twice daily. An additional 18 (28%) patients were classified as responders, and 8 (12%) reported only marginal benefit from adjunctive LEV. Fourteen (22%) patients discontinued LEV (6 worsening seizures, 1 lack of efficacy, 7 adverse effects). Caregivers rated combined sleep, appetite, alertness, and behavior scores as "improved" at the end of follow-up (P<0.001). LEV improved seizure control in the majority of patients with mental retardation and may also have enhanced their quality of life.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Behavior; Child; Drug Administration Schedule; Drug Evaluation; Epilepsy; Female; Follow-Up Studies; Humans; Intellectual Disability; Levetiracetam; Male; Middle Aged; Neurologic Examination; Piracetam; Sleep; Treatment Outcome

The aim of this prospective, uncontrolled clinical study was to evaluate the tolerability and the efficacy of levetiracetam as add-on treatment in 78 adults and 44 children with intractable epilepsy. The patients' seizure frequency in the 8 weeks baseline period was compared to their seizure frequency after a mean follow-up of 8 months of treatment.A greater than 50% reduction in seizure frequency was achieved in 31 adults (40%) and 9 children (20%), of whom 7 adults (9%) and 3 children (7%) became seizure free. Most often levetiracetam was well tolerated, somnolence being the most frequently reported side effect (18% in adults and 7% in children). However, in 14 adults (18%) and 19 children (43%) levetiracetam was associated with an increase (>25%) in seizure frequency. Such a paradoxical effect, including the development of status epilepticus in three adults and four children, appeared most often in mentally retarded patients during the first 2 months of treatment, and on relatively high doses. Two children developed status epilepticus after 5 and 7 months, respectively. In conclusion, levetiracetam is usually well tolerated as add-on treatment in patients with difficult-to-treat partial onset seizures. By using a lower initial dose and a slower dose escalation than recommended by the manufacturer, a paradoxical effect may perhaps be avoided. In children, doses >20 mgkg(-1) per day should be introduced with caution.

Topics: Adolescent; Adult; Anticonvulsants; Drug Resistance; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome

To evaluate the long-term clinical usefulness of levetiracetam (LEV, Keppra((R))(1)) as add-on therapy in patients with refractory epilepsy.. Data for all 1422 patients with refractory epilepsy treated with LEV during the development program were analyzed for changes in seizure frequency per week, seizure freedom, and adverse events.. Median percent reduction from baseline in seizure frequency per week over the whole treatment period was 39.6%, and no decrease over time was observed within each cohort exposed to LEV for durations ranging from 6 to 54 months. The median treatment period was 399 days (range 1-8 years). The proportion of responders during the first 3 months of LEV treatment was 39.2%. This proportion remained stable at 6 months (36.1%). Overall, 38.6 and 20.1% of patients had reductions in seizure frequency of at least 50 and 75%. Sixty-five (4.6%) patients were seizure-free over their entire treatment period, compared with 167 (11.7%) and 126 (8.9%) during their last 6 and 12 months of follow-up. Ninety-seven (19.8%) of 491 patients who received only one other antiepileptic drug (AED) in addition to LEV were seizure-free during their last 6 months. The proportion of patients who reduced their number of concomitant AEDs was 14.4% (205 patients), while 5.5% (79 patients) were treated with LEV only at the end of follow-up. Accidental injury (28.0%), infection (26.6%), headache (25.8%), somnolence (23%), asthenia (22.6%), and dizziness (18.9%) were among the most common adverse events.. LEV offers sustained efficacy in patients with refractory partial seizures, and its long-term tolerability is similar to that seen in the short-term placebo-controlled trials.

Topics: Adolescent; Adult; Anticonvulsants; Behavior; Cognition Disorders; Double-Blind Method; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Seizures

Levetiracetam (LEV) is a new antiepileptic drug shown to be effective for the treatment of partial seizures in pivotal clinical trials. We investigated the long-term efficacy and tolerability of LEV as add-on therapy, regardless of seizure type, especially in persons who would not be eligible for clinical trials due to factors such as mental retardation and concomitant psychiatric disorders.. Ninety-eight patients participated and were followed for 1 year. Demographic data, seizure frequency, and side effects were recorded at baseline and during the 1-year follow-up. The first 35 patients were given LEV at a starting dose of 500 mg b.i.d. with weekly increments of 1000 mg (fast titration). The other patients were given LEV with a starting dose of 250 mg b.i.d. with weekly increments of 250 mg (slow titration).. Fourteen patients were completely seizure free after titration to effective dose and 57 were responders with >50% seizure reduction for the first year. In the group with generalized seizures, 1 out of 19 became seizure free, but 8 patients had >50% decrease. Average dose at 1 year was 1900 mg (+/-900). Seventeen of 38 discontinuations were due to adverse effects and 21 were due to lack of efficacy. With fast titration, 15 out of 35 (43%) experienced tiredness during the first 12 weeks, and with slower titration 20 of 63 (32%) experienced tiredness. The difference was not statistically significant. Four out of the five patients who discontinued due to behavioral adverse events (mainly irritability) previously had behavioral problems and/or mental retardation. One patient discontinued due to psychosis.. Levetiracetam appears to be well tolerated in patients with severe epilepsy and shows efficacy in a long-term follow-up. Behavioral adverse events were noted in a small number of patients and occurred mainly in patients who had a history of behavioral disturbance or were mentally retarded. These data from an open population are consistent with the findings of clinical trials.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Drug Tolerance; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Survival Analysis; Treatment Outcome

Levetiracetam is a new anti-convulsant with impressive pivotal trial credentials. We examined its effectiveness in refractory clinic patients with epilepsy with a year's follow up. Six months after initiation 32% of the patients were seizure free, and 26% at one year. By the end of the 12 months follow up 77% of patients were still taking the drug, having gained benefit from it: 23% had dropped out due to intolerable side effects, seizure increase or lack of efficacy. There is evidence that the drug is broad spectrum and as effective in primary generalised epilepsy as in partial onset epilepsy. Our audit of its use and effectiveness has led us to position it as our first choice add-on drug if the initial monotherapy drug fails.

Topics: Anticonvulsants; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Epilepsy; Follow-Up Studies; Humans; Levetiracetam; Piracetam; Treatment Outcome

The novel antiepileptic drug (AED) levetiracetam (LEV, Keppra) is indicated as adjunctive therapy for partial epilepsy. The primary aim of this study was to measure the safety and tolerability of LEV individualised dosing in a heterogeneous refractory epilepsy population.. LEV was evaluated in a 10- to 16-week open-label, multicentre study in adult patients with epilepsy refractory to previous treatment with at least two AEDs. Individualised LEV doses up to 3000 mg x day(-1) were determined in an initial up-titration phase, and optimal doses were administered as adjunctive treatment during an 8- to 10-week evaluation period. Concomitant AEDs and their doses could not be changed during the study. Safety and tolerability were monitored by expression of adverse events as well as by retention rate. The effect of LEV on concomitant AED concentration was also studied. Efficacy was assessed using global clinical evaluation (GCE) scores, seizure frequency, and >or=50% responder rate.. LEV therapy was initiated in 219 patients; 183 had localisation-related epilepsy and 37 had generalised epilepsy. In one patient, epileptic syndrome was defined as both localisation-related and generalised. About 81.7% (179/219) continued and completed treatment throughout the study, and 79% (172/219) chose to continue LEV in a follow-up study. The most common adverse events were asthenia, dizziness, and somnolence. Most adverse events occurred during up-titration. LEV treatment did not alter the concentration of concomitant AEDs. LEV improved GCE scores in 79.5% (152/191) of patients. LEV reduced the median total seizure frequency of all patients from a median of 2.25 seizures per week at baseline (n=219) to 1.10 seizures per week during the evaluation period (n=191 patients with at least one seizure count during evaluation). The >or=50% responder rate was 48.2% for all seizure types, 49.4% for partial-onset, and 51.4% for generalised-onset seizures. Throughout the evaluation period (i.e. from the start of the evaluation period until completion or early discontinuation), 26/191 (13.6%) had a 100% reduction in total seizure frequency, while in a follow-up study, 10.5% (18/172) were seizure-free for at least 6 months and 6.4% (11/172) were seizure-free for at least 1 year.. LEV was well tolerated, as evidenced by limited adverse event reporting and the high retention rate, and appeared effective in both generalised and partial epilepsy.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Neurologic Examination; Piracetam; Single-Blind Method; Treatment Outcome

Health-related quality of life (HRQOL) of patients taking levetiracetam (LEV) was evaluated in long-term follow-up. Short-term assessments compared LEV and placebo add-on therapy in an 18-week clinical trial, with long-term follow-up for a mean of 4.1 years. The QOLIE-31 was expanded to assess distress associated with each domain, change, and priority of importance of each domain. Significant improvements were observed at short-term in patients starting with LEV (N=66), whereas patients initially randomized to placebo (N=35) were unchanged. Improvement observed in LEV starters remained stable long-term. Placebo starters reached the same level of improvement in HRQOL at long-term. Correlations between the QOLIE-31-P distress items and domain items indicated that distress was significantly lower when HRQOL was better (P<0.0001, all domains). At long-term, highest-priority QOLIE-31-P domains were Social Functioning, Cognitive Function, and Overall QOL. Thus, gains in HRQOL were maintained during long-term LEV treatment, whether LEV was initiated early or late. Patient distress and importance of domains are useful data in determining how treatments impact on HRQOL.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Cognition Disorders; Drug Administration Schedule; Epilepsy; Female; Follow-Up Studies; Health Status; Humans; Levetiracetam; Male; Mental Disorders; Middle Aged; Neuropsychological Tests; Piracetam; Quality of Life; Social Behavior; Surveys and Questionnaires

Increases in body weight gain are important, and clinically significant adverse effects of several antiepileptic drugs (AED) including valproate and gabapentin. Weight gain may contribute to medication non-compliance, discontinuation, and importantly, may have secondary medical implications as well. Levetiracetam (LEV) is indicated for adjunctive treatment of partial seizures. The objective of the present evaluation was to examine the effects of LEV treatment on body weight in adult patients.. We analyzed data derived from four prospective, placebo-controlled randomized, clinical trials conducted in both in the US and Europe. Patients included in the present analysis were both men and women, greater than 16 years old, and who had LEV exposure for at least 1 month. Body weight was measured at baseline and at the final LEV study visit. Data are analyzed for all patients, by gender, body mass index (BMI), duration of LEV exposure and by concomitant AED treatment. Wilcoxan Signed Rank, or Rank Sum test used where appropriate, with significance assigned at P<0.05. Data are presented as mean values+/-1 S.D.. Nine-hundred and seventy patients (age=37.5 years, 54% men/46% women) were evaluated. There were no significant differences in baseline demographics between LEV (n=631) or placebo (n=339) treated patient groups. Mean LEV dose and duration of treatment were 2053 mg/day (maximum dose of 4000 mg/day) and 125 days (maximum=181 days), respectively. Concomitant AED therapy included CBZ, PHT, VPA, PB, GBP, LTG, and VGB. For LEV-treated patients, no significant changes in body weight were noted. Mean body weight at baseline versus final study visit for LEV was 74.3+/-16.6 kg and 74.3+/-16.6 kg, respectively. For placebo-treated patients, baseline versus end of treatment weight was 72.4+/-15.4 kg and 72.7+/-15.9 kg, respectively, representing a slight, yet clinically trivial increase. Clinically significant weight change as defined as >7% change from baseline weight, occurred in 9% of LEV-treated patients (4.5% had increase in weight/4.5% decrease) versus 9.4% (5.9% had increase/3.5% decrease) in placebo-treated patients. Weight changes were not significantly different between groups. Neither baseline BMI, gender, or background AEDs, appeared to predispose to significant weight change for LEV-treated patients.. We conclude that treatment with LEV at clinically relevant dosages is not associated with significant weight change. LEV would, therefore, appear to be a weight neutral AED.

Topics: Adult; Anticonvulsants; Body Weight; Epilepsy; Europe; Female; Humans; Levetiracetam; Male; Piracetam; United States

Levetiracetam (Keppra) was evaluated in a subset of patients aged >/=65 years (n=78) enrolled in a large (n=1030) open-label, phase IV trial (the KEEPER trial). A 4-week dose adjustment was followed by a 12-week evaluation period. An overall median reduction in partial seizures of 80.1% (n=65) was observed. Overall, 76.9% of patients were >/=50% responders, 56.9% were >/=75% responders, and 40.0% were 100% responders. Levetiracetam was well tolerated, with 42.3% of patients reporting one or more adverse events. A total of 15 patients (19.2%) experienced an adverse event that led to discontinuation. Somnolence (n=13,16.7%) and dizziness (n=7,9.0%) were the most commonly reported adverse events. Despite the limitations of the open-label study design, these data provide information regarding the use of levetiracetam as add-on therapy for the treatment of partial-onset seizures in patients >/=65 years of age, including those requiring concomitant medications.

Topics: Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Drug Tolerance; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Piracetam; Seizures; Time Factors; Treatment Outcome

Levetiracetam, one of the newer-generation antiepilepsy drugs, is not currently approved for use in children. Given its favorable efficacy, pharmacokinetic, and, particularly, safety profile in adults, we felt that it may be a useful antiepilepsy drug for children with refractory epilepsy. We treated 39 patients (mean age 8.6 years) with open-label levetiracetam for up to 9 months. Seizure frequency, drug dosages, adverse events, and neurologic examinations were documented at baseline and routine follow-up visits. Levetiracetam, as add-on therapy, was effective in reducing seizure frequency in a variety of seizure types but was most effective for partial-onset seizures. Fourteen patients were discontinued for lack of efficacy or adverse events. Ten patients reported improvements in cognition or behavior. Levetiracetam was generally effective and well tolerated in this open-label study. Its apparent positive effects on cognition in some patients are encouraging. Large, well-controlled studies are needed to fully define levetiracetam's potential in children with refractory epilepsy.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Cognition; Drug Administration Schedule; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Treatment Outcome

The pharmacokinetics of the novel antiepileptic drug (AED) levetiracetam and its major metabolite, ucb L057, were studied in children with partial seizures in a multicenter, open-label, single-dose study.. Twenty-four children (15 boys, nine girls), 6 to 12 years old, received a single dose of levetiracetam (20 mg/kg) as an adjunct to their stable regimen of a single concomitant AED, followed by a 24-h pharmacokinetic evaluation.. In children, the half-lives of levetiracetam and its metabolite ucb L057 were 6.0 +/- 1.1 and 8.1 +/-2.7 hours, respectively. The Cmax and area under the curve (AUC) of levetiracetam equated for a 1-mg/kg dose were lower in children (Cmax, norm=1.33 plus minus 0.35 microg/ml; AUCnorm=12.4 +/- 3.5 microg/h/ml) than in adults (Cmax, norm=1.38 +/- 0.05 microg/ml; AUCnorm=11.48 +/- 0.63 microg/h/ml), whereas the renal clearance was higher. The apparent body clearance (1.43 +/- 0.36 ml/min/kg) was approximately 30-40% higher in children than in adults. Levetiracetam was generally well tolerated.. On the basis of these data, a daily maintenance dose equivalent to 130-140% of the usual daily adult maintenance dosage (1,000-3,000 mg/day) in two divided doses, on a weight-normalized level (mg/kg/day) is initially recommended. Clinical efficacy trials in children are ongoing with dosages of 20 to 60 mg/kg/day.

Topics: Adult; Age Factors; Anticonvulsants; Child; Creatine; Epilepsy; Female; Humans; Levetiracetam; Male; Metabolic Clearance Rate; Middle Aged; Piracetam

The aim of this study was to determine the tolerability and efficacy of two oral regimens of levetiracetam, 1000 mg and 2000 mg twice daily, as add-on treatment without titration in patients with refractory epilepsy. After a 1- to 4-week baseline, 119 patients were randomized to receive levetiracetam 2000 mg daily, 4000 mg daily, or placebo for a 24-week double-blind period, then levetiracetam 4000 mg daily in a 24-week open-label phase. Somnolence was the most common reason for discontinuation, and along with asthenia, occurred more frequently with levetiracetam than placebo. Responder rates were higher with levetiracetam 2000 mg and 4000 mg daily (48.1% [P < 0.05] and 28.6% [NS], respectively) than placebo (16.1%). In the open-label phase, the overall responder rate was 43.0%. Switching from placebo to levetiracetam increased the overall responder rate from 16.7% to 44.0%. No such increase was observed with patients initiated on levetiracetam 2000 mg daily. Levetiracetam initiated at doses of 2000 mg or 4000 mg daily without titration is well-tolerated and effective as add-on therapy in patients with partial and/or generalized seizures. The higher dose may be related to an increased incidence of somnolence and is not necessarily more effective than the lower dose.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Drug Tolerance; Epilepsy; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Treatment Outcome

The aim of this study was to determine the efficacy and tolerability of 1000-4000 mg/day of levetiracetam (LEV, Keppra) as add-on treatment for refractory epilepsy. This was a dose-escalation study of 29 patients with refractory epilepsy. Patients received placebo for 4 weeks (baseline) followed by levetiracetam 1000 and 2000 mg per day each for 2 weeks, and then 3000 and 4000 mg per day each for 4 weeks. Primary efficacy was assessed by seizure frequency (number/week). Tolerability was assessed by adverse events, laboratory parameters, clinical evaluations, and electrocardiogram. All the study periods were completed by 27 of the 29 patients. A substantially lower median seizure frequency was observed at all levetiracetam dosing periods (1000 mg per day, 1.0 seizures per week; 2000 mg per day, 1.5 seizures per week; 3000 mg per day, 1.0 seizures per week; 4000 mg per day, 0.75 seizures per week) compared with the placebo treatment (2.06 seizures per week). In addition, 22-33% of these patients were seizure free during treatment with levetiracetam compared with only 14% with placebo. Levetiracetam was well tolerated. The most common adverse events were somnolence and asthenia; frequency and severity increased with increasing doses of levetiracetam. Levetiracetam in doses from 1000 to 4000 mg per day is effective. Somnolence and asthenia were more frequent with the highest dose, suggesting that 4000 mg per day may be the upper limit in some patients, although individual susceptibility to somnolence was variable.

Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Pilot Projects; Piracetam; Single-Blind Method; Statistics, Nonparametric

The experimental antiepileptic drug, levetiracetam (UCB L059), a piracetam analogue has been investigated in photosensitive patients in the "photosensitivity model", an early phase II study. A total of 12 patients (10 females, 2 males) with a mean age of 21.5 years (range 13-38) were investigated during a 3 day period in 3 centres (France, The Netherlands, Germany), using the same standardised method. The subjects were either treated with a single oral dose of 250 mg, 500 mg, 750 mg or 1,000 mg. In addition, 4 patients took 250 mg b.i.d. for 3-5 days, after which they were re-examined. In 9 of 12 photosensitive patients (75%) a clear suppression (3 patients) or abolishment (6 patients) of IPS evoked photoparoxysmal EEG responses was found. This effect appeared to be dose-dependent, the higher the dose the greater the effect; complete abolishment was only seen at dosages of 750 mg and 1,000 mg, occurring at peak plasma levels and lasting between 6 and 30 h. There was no indication of pharmacokinetic interaction with concomitant antiepileptic drugs such as valproic acid, ethosuximide or phenobarbitone. No serious side-effects were seen and some patients reported enhancement of their mood. Two patients with myoclonic jerks noticed a clear reduction of their myoclonus, although this was not one of the objectives of the study. In conclusion, levetiracetam showed a clear antiepileptic effect in the photosensitivity model.

Topics: Administration, Oral; Adolescent; Adult; Anticonvulsants; Electroencephalography; Epilepsy; Europe; Evaluation Studies as Topic; Female; Humans; Levetiracetam; Male; Models, Neurological; Nootropic Agents; Photic Stimulation; Piracetam; Treatment Outcome

1. A new pyrrolidine derivative (levetiracetam), resembling piracetam, was given as antiepileptic concomitant drug to patients with chronic epilepsy. 2. In a single-blind add-on rising-dose study the cognitive side-effects were investigated twice after one week of administration. 3. The results did not show any significant changes in cognitive performances.

Topics: Administration, Oral; Adult; Anticonvulsants; Cognition; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Memory; Middle Aged; Neuropsychological Tests; Piracetam; Psychiatric Status Rating Scales; Reaction Time

Antiepileptic drugs (AEDs) are a chemically diverse group of medications that are used to control seizures and different clinical forms of epilepsy. AEDs can be used as single agents but are commonly administered in combination, as a multi-drug regimen. AEDs have narrow therapeutic windows. Therapeutic ranges may not be properly defined, and symptoms of toxic serum concentrations may include increased frequency of seizures, as seen when AED concentrations are subtherapeutic. Pentobarbital, a barbiturate, is a potent anti-seizure medication, but it is also used in the treatment of head injury. Therapeutic drug monitoring (TDM) is required for optimal treatment of epilepsy. The method presented here is designed to measure serum concentrations of six commonly administered antiepileptic drugs (levetiracetam (Keppra), lamotrigine, lacosamide, 10-hydroxycarbazepine (oxcarbazepine metabolite), topiramate, zonisamide) and that of pentobarbital by LC-MS/MS. Liquid-liquid sample extraction is followed by reversed-phase chromatography using biphenyl HPLC column and gradient elution. Two MRM transitions are monitored for each drug, and their heavy isotope labeled internal standards. Six-point calibration curve is generated with each batch of analysis for quantitation of AEDs. The method's AMR covers the clinically relevant concentration range for each AED. The method has <10% CV throughout the AMR, is free of matrix effect commonly found in clinical samples, and is free from cross reactivity by other AEDs.

Topics: Anticonvulsants; Chromatography, Liquid; Drug Monitoring; Epilepsy; Humans; Levetiracetam; Pentobarbital; Tandem Mass Spectrometry

The management of epilepsy during pregnancy requires optimal seizure control, avoiding the potential teratogenic effects of antiepileptic drugs.. This study aims to describe the clinical characteristics and perinatal outcomes of pregnant patients with epilepsy; to analyse the factors associated with seizures during pregnancy; to describe the most commonly used antiseizure drugs in these patients; and to analyse changes in treatment regimens in 2 periods, 2000-2010 and 2011-2018.. We conducted a prospective observational study of patients with epilepsy who reported their pregnancy between 2000 and 2018. Patients were evaluated in the first and second trimesters of pregnancy, after delivery, and at one year. Data were collected on demographic variables, epilepsy, and perinatal and obstetric variables.. A total of 101 pregnancies were included. Patients' mean age was 32.6 years; 55.4% had focal epilepsy, 38.6% had generalised epilepsy, and 5.9% had undetermined epilepsy. We recorded 90 live births, 9 miscarriages, and 5 cases of congenital malformations, 4 of which were born to women who received valproate monotherapy. Forty patients (39.6%) presented seizures, with 16 (40%) presenting generalised tonic-clonic seizures. The variables associated with seizures during pregnancy were poor seizure control in the year prior to pregnancy (66.7% vs 15.1%; P < .001), treatment with 2 or more antiseizure drugs (30% vs 14.8%; P < .001), and untreated epilepsy (25% vs 0%; P < .001). Antiseizure medications most widely used in monotherapy were lamotrigine (n = 19; 27.1%), valproate (n = 17; 24.2%), and levetiracetam (n = 12; 17.1%). In the most recent period (2011-2018), we observed a greater proportion of patients receiving monotherapy (81.5%, vs 55.3%), as well as a decrease in the use of carbamazepine (2.3%, vs 23.1%) and valproate (20.5%, vs 30.8%); and a marked increase in the use of levetiracetam (27.3%, vs 0%).. The factors associated with the presence of seizures during pregnancy were previous poor seizure control, treatment with 2 or more antiseizure drugs, and lack of treatment during pregnancy. The most commonly used drugs were lamotrigine, valproate, and levetiracetam, with an increase in levetiracetam use and a decrease in valproate use being observed in the later period (2011-2018).

Topics: Adult; Anticonvulsants; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Pregnancy; Seizures; Valproic Acid

In this study, the dose schedule efficacy, safety and late adverse effects of stereotactic radiosurgery (SRS) were evaluated for patients with symptomatic cavernomas who were not eligible for surgery and treated with SRS. Between January 2013 and December 2018, 53 patients with cavernomas were treated using SRS with the CyberKnife® system. Patients' diseases were deeply located or were in subcortical functional brain regions. In addition to bleeding, 23 (43.4%) patients had epilepsy, 12 (22.6%) had neurologic symptoms and 16 patients (30.2%) had severe headaches. The median volume was 741 (range, 421-1351) mm3, and the median dose was 15 (range, 14-16) Gy in one fraction. After treatment, six (50%) of 12 patients with neurologic deficits still had deficits. Rebleeding after treatment developed in only two (3.8%) patients. The drug was completely stopped in 14 (60.9%) out of 23 patients who received epilepsy treatment, and the dose of levetiracetam decreased from 2000 mg to 1000 mg in four (17.3%) of nine patients. Radiologically, complete response (CR) was observed in 13 (24.5%) patients, and partial responses (PR) were observed in 32 (60.2%) patients. Clinical response of CR was observed in 30 (56.6%) patients, PR was observed in 16 (30.2%), stable disease (SD) was observed in three (5.7%) and four (7.5%) patients progressed. In conclusion, SRS applied in the appropriate dose schedule may be an effective and reliable method in terms of symptom control and prevention of rebleeding, especially in patients with inoperable cavernomas.

Topics: Brain; Epilepsy; Follow-Up Studies; Hemangioma, Cavernous, Central Nervous System; Humans; Levetiracetam; Radiosurgery; Retrospective Studies; Treatment Outcome

Topics: Epilepsy; Humans; Infant, Newborn; Infant, Newborn, Diseases; Levetiracetam; Seizures

Pharmacologic treatment of epilepsy in pregnant women is balancing between risks for the mother and fetus. Levetiracetam (LEV) is considered to be safe during pregnancy because of its low teratogenic potential and lack of drug-drug interaction with other antiseizure medications (ASMs). Recent studies have shown decline of ASM concentrations during pregnancy because of physiologically based pharmacokinetic changes. In this study, we established this decrease in LEV concentration during pregnancy. In addition, we aimed at investigating the effect of the low LEV levels during pregnancy and developing a target value for the level during pregnancy.. Pregnant patients using levetiracetam were studied in this retrospective cohort study. Blood samples were monthly collected through venous puncture or the dried blood spot method. ASM serum concentrations were determined at least 6 months before conception and for each month of pregnancy. Seizure frequency and ASM dosages during pregnancy were obtained from patient records. Patients were divided into 2 groups: a seizure-free group and a non-seizure-free group, which contained pregnancies in which the mother had experienced an epileptic seizure more than 12 months and less than 12 months before pregnancy, respectively.. We found decreased concentration/dose ratios in 29 pregnancies throughout all months of pregnancy. In the non-seizure-free group, it was found that low LEV concentrations were associated with seizure increase frequency (. All in all, we recommend therapeutic drug monitoring for all pregnant patients on LEV as the concentrations of LEV significantly decrease throughout most months of pregnancy. However, this decrease in LEV concentration was only significantly correlated with seizure deterioration in patients who had a seizure in the year preceding the pregnancy. Therefore, we suggest more careful monitoring of non-seizure-free patients as they are at higher risk for experiencing an increase of seizure frequency. For this group, we advise physicians to keep LEV concentration above 65% of the preconceptional concentration. For seizure-free patients, we recommend an LEV threshold value of approximately 46% of the preconceptional concentration.

Topics: Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Piracetam; Pregnancy; Pregnant Women; Retrospective Studies; Seizures; Treatment Outcome

The pharmacokinetics of levetiracetam (LEV) significantly changed during pregnancy. It is a great challenge to predict the adjusted doses of LEV to reach the preconception target concentrations. This study aimed to establish a population pharmacokinetic model of LEV in women with epilepsy (WWE) during pregnancy to analyse the factors of pharmacokinetic variability and to develop a model-based individualized dosing regimen.. A total of 166 concentration-time points from 37 WWE during pregnancy treated with LEV were collected to analyse LEV pharmacokinetics with nonlinear mixed-effects modelling. The dosing regimen was optimized by Monte Carlo simulations based on the final model.. The LEV pharmacokinetics in pregnant WWE were best described by a 1-compartment model of first-order absorption and elimination. The population typical value of apparent clearance (CL/F) in the final model was estimated to be 3.82 L/h (95% confidence interval 3.283-4.357 L/h) with a relative standard error of 7.2%. Both total body weight (TBW) and trimester of pregnancy were significantly associated with LEV-CL/F during pregnancy; LEV-CL/F increased by 42.72% when TBW increased from 55 to 65 kg from the first trimester to the second trimester. Monte Carlo simulations showed that dosing regimens for LEV should be individualized based on the patient's TBW and trimester of pregnancy to maximize the likelihood of achieving the therapeutic range.. This first population pharmacokinetic study of LEV in WWE during pregnancy supports the use of a weight-based and pregnancy-based dosing regimen and can lay a foundation for further optimizing the individualized dosing regimens.

Topics: Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Monte Carlo Method; Pregnancy; Pregnancy Trimester, First

Estimation of serum concentrations of antiseizure medications (ASMs) based on dried capillary blood is an alternative method for therapeutic drug monitoring of epilepsy. The aim of this study was to validate the conversion factors for lacosamide (LCM), lamotrigine (LTG), and levetiracetam (LEV), which were determined in an independent patient sample in a previous study, and identify the most accurate conversion method (simple ratio and regression).. Venous and capillary blood samples were collected from adult inpatients with epilepsy treated with LCM (n = 25), LTG (n = 27), and/or LEV (n = 29) before the morning dose (T1) and approximately 2 hours after (T2). Capillary blood was collected using volumetric absorptive microsampling, and the ASM concentrations were measured using a validated liquid chromatography-mass spectrometry method for dried blood samples. Serum concentrations were estimated using conversion factors and compared with those measured using routine laboratory methods.. For all 3 ASMs, the simple ratio approach performed better than the regression approach. Intraclass correlation coefficients revealed a high agreement between the estimated and measured serum concentrations (LCM T1: 0.93, T2: 0.90; LTG T1: 0.91, T2: 0.91; and LEV T1: 0.97, T2: 0.94). The criteria of the European Medicines Agency for cross-validation were fulfilled for LCM (T1: 72%; T2: 75%) and LEV (T1: 86%; T2: 75%), whereas for LTG, this was only true for capillary blood concentrations ≤11 µ g/mL [42.9 µ mol/L; T1: 72% (vs. 63% for total range), T2: 67% (vs. 62%)].. Estimating serum concentrations using capillary blood concentrations is feasible and accurate for LCM and LEV over a wide concentration range, as found in clinical practice. The applicability of this mehod for LTG is limited by its greater variability at higher concentrations; however, acceptable results were achieved for the large proportion of patients with low and medium LTG concentrations.

Topics: Adult; Anticonvulsants; Drug Monitoring; Epilepsy; Humans; Lacosamide; Lamotrigine; Levetiracetam

This study aimed to directly compare the effectiveness of first-line monotherapy levetiracetam (LEV) versus enzyme-inducing antiseizure medications (EIASMs) in glioma patients.. In this nationwide retrospective observational cohort study, Grade 2-4 glioma patients were included, with a maximum duration of follow-up of 36 months. Primary outcome was antiseizure medication (ASM) treatment failure for any reason, and secondary outcomes were treatment failure due to uncontrolled seizures and due to adverse effects. For estimation of the association between ASM treatment and ASM treatment failure, multivariate cause-specific cox proportional hazard models were estimated, adjusting for potential confounders.. In the original cohort, a total of 808 brain tumor patients with epilepsy were included, of whom 109 glioma patients were prescribed first-line LEV and 183 glioma patients first-line EIASMs. The EIASM group had a significantly higher risk of treatment failure for any reason compared to LEV (adjusted hazard ratio [aHR] = 1.82, 95% confidence interval [CI] = 1.20-2.75, p = .005). Treatment failure due to uncontrolled seizures did not differ significantly between EIASMs and LEV (aHR = 1.32, 95% CI = .78-2.25, p = .300), but treatment failure due to adverse effects differed significantly (aHR = 4.87, 95% CI = 1.89-12.55, p = .001).. In this study, it was demonstrated that LEV had a significantly better effectiveness (i.e., less ASM treatment failure for any reason or due to adverse effects) compared to EIASMs, supporting the current neuro-oncology guideline recommendations to avoid EIASMs in glioma patients.

Topics: Anticonvulsants; Epilepsy; Glioma; Humans; Levetiracetam; Retrospective Studies; Seizures

Although phenobarbital (PB) is commonly used as a first-line antiseizure medication (ASM) for neonatal seizures, in 2015 we chose to replace it with levetiracetam (LEV), a third-generation ASM. Here, we compared the safety and efficacy of LEV and PB as first-line ASM, considering the years before and after modifying our treatment protocol.. We conducted a retrospective cohort study of 108 neonates with electroencephalography (EEG)-confirmed seizures treated with first-line LEV or PB in 2012 to 2020.. First-line ASM was LEV in 33 (31%) and PB in 75 (69%) neonates. The etiology included acute symptomatic seizures in 69% of cases (30% hypoxic-ischemic encephalopathy, 32% structural vascular, 6% infectious, otherwise metabolic) and neonatal epilepsy in 22% (5% structural due to brain malformation, 17% genetic). Forty-two of 108 (39%) neonates reached seizure freedom following first-line therapy. Treatment response did not vary by first-line ASM among all neonates, those with acute symptomatic seizures, or those with neonatal-onset epilepsy. Treatment response was lowest for neonates with a higher seizure frequency, particularly for those with status epilepticus versus rare seizures (P < 0.001), irrespective of gestational age, etiology, or EEG findings. Adverse events were noted in 22 neonates treated with PB and in only one treated with LEV (P < 0.001).. Our study suggests a potential noninferiority and a more acceptable safety profile for LEV, which may thus be a reasonable option as first-line ASM for neonatal seizures in place of PB. Treatment should be initiated as early as possible since higher seizure frequencies predispose to less favorable responses.

Topics: Anticonvulsants; Epilepsy; Humans; Infant, Newborn; Infant, Newborn, Diseases; Levetiracetam; Phenobarbital; Retrospective Studies; Seizures

This study was undertaken to examine the comparative safety of antiseizure medication (ASM) monotherapy in pregnancy with respect to risk of major congenital malformations (MCMs), overall and by MCM subtype.. We conducted a population-based cohort study using national health register data from Denmark, Finland, Iceland, Norway, and Sweden (1996-2020). We compared pregnancies with first trimester exposure to lamotrigine monotherapy to ASM-unexposed, carbamazepine, valproate, oxcarbazepine, levetiracetam, and topiramate to lamotrigine monotherapy, and stratified monotherapy groups by dose. The outcome was nongenetic MCM and specific subtypes. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) with log-binomial regression and propensity score weights.. There was a higher crude risk of any MCM in pregnancies exposed to lamotrigine monotherapy (n = 8,339) compared to ASM-unexposed pregnancies (n = 4,866,362), but not after confounder adjustment (aRR = 0.97, 95% CI = 0.87-1.08). Compared to lamotrigine, there was an increased risk of malformations associated with valproate (n = 2,031, aRR = 2.05, 95% CI = 1.70-2.46) and topiramate (n = 509, aRR = 1.81, 95% CI = 1.26-2.60), which increased in a dose-dependent manner. We found no differences in malformation risk for carbamazepine (n = 2,674, aRR = 0.91, 95% CI = 0.72-1.15), oxcarbazepine (n = 1,313, aRR = 1.09, 95% CI = 0.83-1.44), or levetiracetam (n = 1,040, aRR = 0.78, 95% CI = 0.53-1.13). Valproate was associated with several malformation subtypes, including nervous system, cardiac, oral clefts, clubfoot, and hypospadias, whereas lamotrigine and carbamazepine were not.. Topiramate is associated with an increased risk of MCM similar to that associated with valproate, but lower doses may mitigate the risks for both drugs. Conversely, we found no increased risks for lamotrigine, carbamazepine, oxcarbazepine, or levetiracetam, which is reassuring. ANN NEUROL 2023;93:551-562.

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Benzodiazepines; Carbamazepine; Cohort Studies; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Oxcarbazepine; Pregnancy; Topiramate; Valproic Acid

The purpose of this study was to compare the electrocardiographic parameters before and at the sixth month of treatment of patients diagnosed with epilepsy and who were started on levetiracetam therapy.. The files of 30 patients diagnosed with epilepsy and on levetiracetam therapy were examined in this study. Clinical findings, electroencephalography (EEG), cranial magnetic resonance imaging (MRI) and electrocardiography (ECG) data before and at the sixth month of treatment were recorded.. The patients' mean age was 10.93 ± 3.74 (4-17) years; 16 (53.33%) patients were boys. In total, 13 (43.3%) were found to experience focal seizures, and 17 (56.7%) generalized epilepsy-type seizures. Comparison of the ECG parameters (PR interval, QTc, QT interval, and QRS duration) revealed a shortening in the PR interval and QTc values at the sixth month of treatment, although the changes were not statistically significant. No significant differences in terms of gender and epilepsy types were observed between the ECG parameters before treatment and at the sixth month (p > 0.05).. In this study, levetiracetam was found to have no effect on ECG parameters.

Topics: Adolescent; Child; Electrocardiography; Epilepsy; Female; Humans; Levetiracetam; Male; Seizures

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

There are no clinical guidelines dedicated to the treatment of epilepsy in older adults. We investigated physician opinion and practice regarding the treatment of people with epilepsy aged 65 years or older. We also sought to study how our opinion and practice varied between geriatricians, general neurologists, and epilepsy neurologists (i.e., epileptologists).. We initially piloted our survey to measure test-retest reliability. Once finalized, we disseminated the survey via two rounds of facsimiles, and then conventional mail, to eligible individuals listed in a national directory of Canadian physicians. We used descriptive statistics such as stacked bar charts and tables to illustrate our findings.. One hundred forty-four physicians (104 general neurologists, 25 geriatricians, and 15 epileptologists) answered our survey in its entirety (overall response rate of 13.2%). Levetiracetam and lamotrigine were the preferred antiseizure medications (ASMs) to treat older adults with epilepsy. Two thirds of epileptologists and almost half of general neurologists would consider prescribing lacosamide in >50% of people aged >65 years; only one geriatrician was of the same opinion. More than 40% of general neurologists and geriatricians erroneously believed that none of the ASMs mentioned in our survey was previously studied in randomized controlled trials specific to the treatment of epilepsy in older adults. Epileptologists were more likely as compared to general neurologists and geriatricians to recommend epilepsy surgery (e.g., 66.6% vs. 22.9%-37.5% among older adults).. Therapeutic decisions for older adults with epilepsy are heterogeneous between physician groups and sometimes misalign with available clinical evidence. Our surveyed physicians differed in their approach to ASM choice as well as perception of surgery in older adults with epilepsy. These findings likely reflect the lack of clinical guidelines dedicated to this population and the deficient implementation of best practices.

Topics: Aged; Anticonvulsants; Canada; Epilepsy; Humans; Levetiracetam; Reproducibility of Results

To determine trends in the use of antiseizure medications (ASMs) among women of childbearing age (WOCA) and girls aged 12-14 years with epilepsy between 2015 and 2019 in Poland.. The study used data from the Pex database, which captures information on prescriptions dispensed from 85% of community pharmacies in Poland. The prescriptions issued by neurologists who provide epilepsy care in Poland were studied. Six of the most commonly prescribed ASMs were analyzed: carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, topiramate, and valproate.. The use of valproate and carbamazepine decreased in all age groups. Among the newer ASMs, the use of lamotrigine, levetiracetam, and topiramate increased and oxcarbazepine decreased significantly in WOCA. The only subgroup with statistically significant changes in all ASMs prescriptions were women aged 19-34 years. For girls aged 12-14 years, significant changes were found only for valproate and carbamazepine. In the last year of observation (2019) valproate and lamotrigine accounted for two-thirds of ASMs units prescribed to WOCA. Valproate accounted for half of the prescribed drug units in girls aged 12-14 years. The lowest rates of VPA prescriptions were found in women aged 19-34 years.. There is a change in prescribing habits in WOCA with epilepsy in Poland with trends toward using less teratogenic ASMs. However, many WOCAs are treated with valproate and topiramate despite their known teratogenicity risk. Valproate is still the most commonly prescribed ASM in WOCA and girls aged 12-14 years. Educational interventions for healthcare professionals are needed to improve prescribing practices in WOCA with epilepsy in Poland.

Topics: Anticonvulsants; Benzodiazepines; Carbamazepine; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Oxcarbazepine; Poland; Topiramate; Valproic Acid

Missense variants in the synaptic vesicle glycoprotein SV2A gene have been previously found in a few individuals with epilepsy. Adverse reaction to levetiracetam in individuals with various variants of this gene has recently been described. Here, we report on a family with several members affected by epilepsy. In affected members of this family, we identified a variant in the SV2A gene (NM_014849.5: c.1978 G>A, p.(Gly660Arg). This family case further supports the role of the SV2A gene in autosomal dominant epilepsy. It provides new information on the course of epilepsy in people with variants in the SV2A gene who have never been treated with SV2A agonists and specific neurodevelopmental features of this syndrome.

Topics: Arthrogryposis; Epilepsy; Genetic Variation; Humans; Levetiracetam; Membrane Glycoproteins; Nerve Tissue Proteins

To identify pediatric patients who require therapeutic drug monitoring (TDM) of levetiracetam (LEV).. We retrospectively investigated 2413 routine therapeutic drug monitoring data on serum LEV concentration from 1398 pediatric patients (age, 0-15 years). Samples were grouped by age (infants, < 1 year; preschool children, 1-5 years; primary school children, 6-11 years; and adolescents, 12-15 years), and the LEV concentration-to-dose (CD) ratio was calculated.. The mean CD ratio was highest in adolescents (analysis of variance, p < 0.001); 22.5 % and 15.7 % higher in adolescents than in preschool children and school children, respectively (Scheffé test, p < 0.001); and higher in infants than in preschool children. Preschool children had the lowest ratio and tended to show an increase in the ratio from age 2 to 5 years. Use of enzyme-inducing antiseizure medication reduced the CD ratio by 6.1 % in infants, 12.2 % in preschool children, 5.9 % in primary school children, and 9.4 % in adolescents. The mean CD ratio was 2.7 %, 26.9 %, and 39.3 % higher in preschool children, primary school children, and adolescents with defined chronic kidney disease (CKD) than in the respective age group of patients without CKD. The therapeutic concentration range for a long-term LEV therapy was 11 to 32 μg/mL.. LEV pharmacokinetics are significantly different between infant and preschool children, so TDM of LEV is clinically useful in these patients. In pediatric patients at higher risk for CKD, glomerular filtration rate and LEV levels should be carefully monitored.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Monitoring; Epilepsy; Humans; Infant; Infant, Newborn; Levetiracetam; Piracetam; Retrospective Studies

This study aimed to examine differential prescribing due to channeling and propensity score non-overlap over time in new versus established treatments for common neurological conditions. We conducted cross-sectional analyses on a national sample of US commercially insured adults using 2005-2019 data. We compared new users of recently approved versus established medications for management of diabetic peripheral neuropathy (pregabalin versus gabapentin), Parkinson disease psychosis (pimavanserin versus quetiapine), and epilepsy (brivaracetam versus levetiracetam). Within these drug pairs, we compared demographic, clinical, and healthcare utilization characteristics of recipients of each drug. In addition, we fit yearly propensity score models for each condition and assessed propensity score non-overlap over time. For all three drug pairs, users of the more recently approved medications more frequently had prior treatment (pregabalin = 73.9%, gabapentin = 38.7%; pimavanserin = 41.1%, quetiapine = 14.0%; brivaracetam = 93.4%, levetiracetam = 32.1%). Propensity score non-overlap and its resulting sample loss after trimming were the greatest in the first year that the more recently approved medication was available (diabetic peripheral neuropathy, 12.4% non-overlap; Parkinson disease psychosis, 6.1%; epilepsy, 43.2%) and subsequently improved. Newer neuropsychiatric therapies appear to be channeled to individuals with refractory disease or intolerance to other treatments, leading to potential confounding and biased comparative effectiveness and safety study findings when compared to established treatments. Propensity score non-overlap should be reported in comparative studies that include newer medications. When studies comparing newer and established treatments are critically needed as soon as new treatments enter the market, investigators should recognize the potential for channeling bias and implement methodological approaches like those demonstrated in this study to understand and improve this issue in such studies.

Topics: Adult; Cross-Sectional Studies; Diabetic Neuropathies; Epilepsy; Gabapentin; Humans; Levetiracetam; Parkinson Disease; Pregabalin; Quetiapine Fumarate

To investigate caregivers' assessments of outcome in dogs with idiopathic epilepsy (IE) administered levetiracetam (LEV), zonisamide (ZNS), or phenobarbital (PB) monotherapy.. 100 dogs with IE administered LEV (n = 34), ZNS (31), or PB (35) monotherapy between January 1, 2003, and February 6, 2019, and survey responses from their caregivers.. Information on duration of therapy, adverse effects (AEs), and outcome was obtained from medical record review and caregiver questionnaire.. A significant improvement in mean quality of life score was reported during monotherapy (7.7; SD, 2.14) compared to before treatment (6.25; SD, 2.63; P < .0001), with no difference identified between monotherapy groups. Compared to ZNS monotherapy, dogs prescribed PB monotherapy had a significantly younger median age at seizure onset (2.6 vs 4.3 years; P = .024). A significant relationship was identified between the occurrence of reported AEs and monotherapy group, with a higher prevalence in the PB group (77% [27/35]) and a lower prevalence in the ZNS group (39% [12/31]; P = .0066). Treatment failure rates for PB, LEV, and ZNS monotherapy were 51%, 35%, and 45%, respectively, with failure attributed most commonly to inadequate seizure control. No significant difference was identified between groups with respect to rate of or time to failure.. Most caregivers reported a favorable outcome with administration of LEV, ZNS, or PB monotherapy to dogs with IE. Phenobarbital is associated with the highest prevalence of AEs but no difference in quality of life score. Prospective controlled studies are needed to further compare the efficacy and safety of these monotherapies in dogs with IE.

Topics: Animals; Anticonvulsants; Caregivers; Dog Diseases; Dogs; Epilepsy; Humans; Levetiracetam; Phenobarbital; Prospective Studies; Quality of Life; Seizures; Zonisamide

Levetiracetam (Lev) is an antiepileptic drug that has been increasingly used in the epilepsy pediatric population in recent years, but its pharmacokinetic behavior in pediatric population needs to be characterized clearly. Clinical trials for the pediatric drug remain difficult to conduct due to ethical and practical factors. The purpose of this study was to use the physiologically based pharmacokinetic (PBPK) model to predict changes in plasma exposure of Lev in pediatric patients and to provide recommendations for dose adjustment. A PBPK model of Lev in adults was developed using PK-Sim® software and extrapolated to the entire age range of the pediatric population. The model was evaluated using clinical pharmacokinetic data. The results showed the good fit between predictions and observations of the adult and pediatric models. The recommended doses for neonates, infants and children are 0.78, 1.67 and 1.22 times that of adults, respectively. Moreover, at the same dose, plasma exposure in adolescents was similar to that of adults. The PBPK models of Lev for adults and pediatrics were successfully developed and validated to provide a reference for the rational administration of drugs in the pediatric population.

Topics: Adolescent; Adult; Anticonvulsants; Child; Computer Simulation; Epilepsy; Humans; Infant; Infant, Newborn; Levetiracetam; Models, Biological; Pharmaceutical Preparations

Patients with epilepsy often show treatment-related psychiatric symptoms. Among the novel antiseizure medications (ASM), Perampanel (PER), Levetiracetam (LEV), and Topiramate (TPM) have been reported to have a relatively high frequency of psychiatric adverse events. However, these psychiatric symptoms are not identical; PER and LEV show adverse events of irritability and aggression, while TPM shows typical symptoms of depression and schizophrenia. It is important to understand the characteristics of these psychiatric adverse events to design appropriate treatment regimens for epileptic patients. (Received August 1, 2022; Accepted December 24, 2022; Published April 1, 2023).

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Mental Disorders; Topiramate

Prenatal antiseizure medication (ASM) exposure has been associated with adverse early neurodevelopment, but associations with a wider range of psychiatric end points have not been studied.. To examine the association between prenatal exposure to ASM with a spectrum of psychiatric disorders in childhood and adolescence in children of mothers with epilepsy.. This prospective, population-based register study assessed 4 546 605 singleton children born alive in Denmark, Finland, Iceland, Norway, and Sweden from January 1, 1996, to December 31, 2017. Of the 4 546 605 children, 54 953 with chromosomal disorders or uncertain birth characteristics were excluded, and 38 661 children of mothers with epilepsy were identified. Data analysis was performed from August 2021 to January 2023.. Prenatal exposure to ASM was defined as maternal prescription fills from 30 days before the first day of the last menstrual period until birth.. The main outcome measure was diagnosis of psychiatric disorders (a combined end point and 13 individual disorders). Estimated adjusted hazard ratios (aHRs) using Cox proportional hazards regression and cumulative incidences with 95% CIs are reported.. Among the 38 661 children of mothers with epilepsy (16 458 [42.6%] exposed to ASM; 19 582 [51.3%] male; mean [SD] age at the end of study, 7.5 [4.6] years), prenatal valproate exposure was associated with an increased risk of the combined psychiatric end point (aHR, 1.80 [95% CI, 1.60-2.03]; cumulative risk at 18 years in ASM-exposed children, 42.1% [95% CI, 38.2%-45.8%]; cumulative risk at 18 years in unexposed children, 31.3% [95% CI, 28.9%-33.6%]), which was driven mainly by disorders within the neurodevelopmental spectrum. Prenatal exposure to lamotrigine, carbamazepine, and oxcarbazepine was not associated with an increased risk of psychiatric disorders, whereas associations were found for prenatal exposure to topiramate with attention-deficit/hyperactivity disorder (aHR, 2.38; 95% CI, 1.40-4.06) and exposure to levetiracetam with anxiety (aHR, 2.17; 95% CI, 1.26-3.72) and attention-deficit/hyperactivity disorder (aHR, 1.78; 95% CI, 1.03-3.07).. Findings from this explorative study strengthen the evidence for the warning against the use of valproate in pregnancy and raise concern of risks of specific psychiatric disorders associated with topiramate and levetiracetam. This study provides reassuring evidence that lamotrigine, carbamazepine, and oxcarbazepine are not associated with long-term behavioral or developmental disorders but cannot rule out risks with higher doses.

Topics: Adolescent; Anticonvulsants; Attention Deficit Disorder with Hyperactivity; Carbamazepine; Child; Child, Preschool; Epilepsy; Female; Humans; Incidence; Lamotrigine; Levetiracetam; Male; Oxcarbazepine; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies; Topiramate; Valproic Acid

Wolf-Hirschhorn syndrome (WHS) is caused by deletion of the terminal region of chromosome 4 short arm and is frequently associated with intractable epilepsy. This article evaluates the clinical features of epileptic seizures in WHS and the therapeutic efficacy of oral antiseizure medications (ASMs). Patients with WHS who were treated for epilepsy at the Saitama Children's Medical Center under 5 years of age were included. WHS was diagnosed based on genetic tests and clinical symptoms. Medical records regarding the age of onset of epilepsy, seizure type, treatment of status epilepticus (SE), and effectiveness of ASMs were retrospectively reviewed. Oral ASMs were considered effective when seizures were reduced by at least 50% compared with the premedication level. Eleven patients were included in the study. The median age at the onset of epilepsy was 9 months (range: 5-32 months). Unknown-onset bilateral tonic-clonic seizure was the most common type of seizure, occurring in 10 patients. Focal clonic seizures occurred in four patients. Ten patients exhibited recurrent episodes of SE, and its frequency during infancy was monthly in eight patients and yearly in two. SE occurrence peaked at 1 year of age and decreased after 3 years of age. The most effective ASM was levetiracetam. Although WHS-associated epilepsy is intractable with frequent SE occurrence during infancy, improvement in seizure control is expected with age. Levetiracetam may be a novel ASM for WHS.

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Retrospective Studies; Seizures; Status Epilepticus; Wolf-Hirschhorn Syndrome

Knowledge on antiseizure medication (ASM) use and retention for children with epilepsy is limited, partly because of extensive off-label use of newer drugs with limited registration. We used prescription data to study prescription patterns on a population-wide scale and compared the proportion of patients remaining on monotherapy of ASMs with and without formal indication for different age groups.. A total of 14,681 individuals aged <18 years were included, using cross-referenced Swedish registers from 2007 to 2020. Kaplan-Meier retention rates were calculated for all ASMs. The most common pathways of the first three medications per patient were analyzed.. In children older than one month and up to age one year, monotherapy retention rates were the highest for oxcarbazepine, valproic acid, and carbamazepine. Among children aged one to five years, oxcarbazepine and levetiracetam were among ASMs that do not have a monotherapy indication in Sweden but still had high retention rates. In the age group five to 12 years, lamotrigine and oxcarbazepine had the highest retention rate. In males aged 12 to 18 years, valproic acid was the most common choice followed by lamotrigine, whereas lamotrigine was the first choice of ASM for females, exceeding the second and third most common options levetiracetam and oxcarbazepine by a factor of two and three, respectively.. Off-label medication is common in children with epilepsy but does not seem to be associated with lower retention. The restrictions regarding valproic acid for females of childbearing age seem to have been well implemented in Swedish neuropediatric care.

Topics: Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Lamotrigine; Levetiracetam; Male; Oxcarbazepine; Sweden; Triazines; Valproic Acid

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

Levetiracetam (LEV) is widely used in the clinical monotherapy or multi-drug combination treatment of seizures due to its good tolerability and efficacy. Due to a lack of large-scale clinical studies, the relationship between levetiracetam concentrations, disease activity and adverse is unclear, limiting the usefulness of therapeutic drug monitoring (TDM) based LEV plasma levels. This study was intended to investigate factors influencing the pharmacokinetics of and the appropriate reference range of LEV concentration using available LEV TDM data.. A rapid, accurate and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) method was established to determine LEV plasma concentrations. In this study, the levetiracetam plasma concentration monitoring data from 352 samples (taken from 248 patients) were used to explore the relationship between levetiracetam dose, age, combined administration with other antiseizure medications in patients with epilepsy.. Age and combined administration emerged as important affecting factors for the correlation of LEV concentration and dose. The correlation between concentration and dose was better in monotherapy. Combined administration may affect LEV concentration, especially when LEV is combined with oxcarbazepine, which might decrease the LEV concentration.. These findings emphasize the need to monitor LEV routinely LEV, especially among children and older adults when other antiseizure comedications are prescribed in the treatment regimen. LEV TDM is a well-established tool for the management of patients with epilepsy.

Topics: Anticonvulsants; Drug Monitoring; East Asian People; Epilepsy; Humans; Levetiracetam; Reference Values

Antiseizure medication (ASM) as monotherapy or in combination is the treatment of choice for most patients with epilepsy. Therefore, knowledge about the typical adverse events (AEs) for ASMs and other coadministered drugs (CDs) is essential for practitioners and patients. Due to frequent polypharmacy, it is often difficult to clinically assess the AE profiles of ASMs and differentiate the influence of CDs.. This retrospective analysis aimed to determine typical AE profiles for ASMs and assess the impact of CDs on AEs in clinical practice.. The Liverpool AE Profile (LAEP) and its domains were used to identify the AE profiles of ASMs based on data from a large German multicenter study (Epi2020). Following established classifications, drugs were grouped according to their mode of action (ASMs) or clinical indication (CDs). Bivariate correlation, multivariate ordinal regression (MORA), and artificial neural network (ANNA) analyses were performed. Bivariate correlation with Fisher's z-transformation was used to compare the correlation strength of LAEP with the Hospital Anxiety and Depression Scale (HADS) and Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) to avoid LAEP bias in the context of antidepressant therapy.. Data from 486 patients were analyzed. The AE profiles of ASM categories and single ASMs matched those reported in the literature. Synaptic vesicle glycoprotein 2A (SV2A) and voltage-gated sodium channel (VGSC) modulators had favorable AE profiles, while brivaracetam was superior to levetiracetam regarding psychobehavioral AEs. MORA revealed that, in addition to seizure frequency, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) modulators and antidepressants were the only independent predictors of high LAEP values. After Fisher's z-transformation, correlations were significantly lower between LAEP and antidepressants than between LAEP and HADS or NDDI-E. Therefore, a bias in the results toward over interpreting the impact of antidepressants on LAEP was presumed. In the ANNA, perampanel, zonisamide, topiramate, and valproic acid were important nodes in the network, while VGSC and SV2A modulators had low relevance for predicting relevant AEs. Similarly, cardiovascular agents, analgesics, and antipsychotics were important CDs in the ANNA model.. ASMs have characteristic AE profiles that are highly reproducible and must be considered in therapeutic decision-making. Therapy using perampanel as an AMPA modulator should be considered cautiously due to its relatively high AE profile. Drugs acting via VGSCs and SV2A receptors are significantly better tolerated than other ASM categories or substances (e.g., topiramate, zonisamide, and valproate). Switching to brivaracetam is advisable in patients with psychobehavioral AEs who take levetiracetam. Because CDs frequently pharmacokinetically interact with ASMs, the cumulative AE profile must be considered.. DRKS00022024, U1111-1252-5331.

Topics: Adult; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Retrospective Studies; Topiramate; Valproic Acid; Zonisamide

Antiseizure medications (ASMs) are frequently used for other indications, such as migraine, pain syndromes, and psychiatric disorders. Possible teratogenic effects are therefore of wide concern and the risks imposed by the medications must be weighed against the risk with the disorder treated. It is our objective to update family practitioners on the implications of starting ASM for women with epilepsy during childbearing age. We hypothesized that clinicians would prescribe ASM based on avoiding teratogenesis and treating associated comorbidities simultaneously.. The study cohort was derived from women veterans with epilepsy (WVWE) prescribed ASM who received Veterans Health Administration care for at least 3 years in Veterans Health Administration between fiscal years (FY)01 and FY19. Regimens were classified as monotherapy or polytherapy. Multivariant logistic regression examined the association between demographics, military characteristics, physical/psychiatric comorbidities, neurological care, and use of each ASM.. Among 2,283 WVWE, in ages between 17 and 45, the majority (61%) received monotherapy in FY19. Commonly prescribed ASM included 29% gabapentin, 27% topiramate, 20% lamotrigine, 16% levetiracetam, and 8% valproate (VPA). Comorbid diagnosis of headache predicted use of topiramate and VPA, bipolar disease predicted use of LMT and VPA, pain predicted gabapentin, and schizophrenia was associated with VPAs use. Women receiving levetiracetam and lamotrigine were significantly more likely to receive neurology care previously.. The presence of medical comorbidities influences the selection of ASM. VPAs use in WVWE during childbearing age continues, despite the high teratogenic risk, especially in women with bipolar disorder and headaches. Multidisciplinary care integrating family practice doctors, mental health, and neurology can prevent the enduring problem of teratogenesis in women taking ASM.

Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Female; Gabapentin; Humans; Lamotrigine; Levetiracetam; Middle Aged; Pain; Pharmaceutical Preparations; Teratogenesis; Topiramate; Valproic Acid; Veterans; Young Adult

A prospective longitudinal study was conducted to assess the Apo B100/A1 ratio as a marker of cardiovascular risk in children with epilepsy aged 5-14 years on long-term anti-seizure medication monotherapy with either sodium valproate, oxcarbazepine, or levetiracetam. Apo B100/A1 ratio showed an increase after six months of monotherapy with oxcarbazepine (P=0.05).

Topics: Anticonvulsants; Carbamazepine; Child; Epilepsy; Humans; Levetiracetam; Longitudinal Studies; Oxcarbazepine; Prospective Studies; Valproic Acid

Despite widespread monotherapy use of lamotrigine or levetiracetam during pregnancy, prospectively collected, blinded child development data are still limited. The NaME (Neurodevelopment of Babies Born to Mothers With Epilepsy) Study prospectively recruited a new cohort of women with epilepsy and their offspring for longitudinal follow-up.. Pregnant women of <21 weeks gestation (n = 401) were recruited from 21 hospitals in the UK. Data collection occurred during pregnancy (recruitment, trimester 3) and at 12 and 24 months of age. The primary outcome was blinded assessment of infant cognitive, language, and motor development on the Bayley Scales of Infant and Toddler Development (3rd edition) at 24 months of age with supplementary parent reporting on the Vinelands Adaptive Behavior Scales (2nd edition).. There were 394 live births, with 277 children (70%) completing the Bayley assessment at 24 months. There was no evidence of an association of prenatal exposure to monotherapy lamotrigine (-.74, SE = 2.9, 95% confidence interval [CI] = -6.5 to 5.0, p = .80) or levetiracetam (-1.57, SE = 3.1, 95% CI = -4.6 to 7.7, p = .62) with poorer infant cognition, following adjustment for other maternal and child factors in comparison to nonexposed children. Similar results were observed for language and motor scores. There was no evidence of an association between increasing doses of either lamotrigine or levetiracetam. Nor was there evidence that higher dose folic acid supplementation (≥5 mg/day) or convulsive seizure exposure was associated with child development scores. Continued infant exposure to antiseizure medications through breast milk was not associated with poorer outcomes, but the number of women breastfeeding beyond 3 months was low.. These data are reassuring for infant development following in utero exposure to monotherapy lamotrigine or levetiracetam, but child development is dynamic, and future follow-up is required to rule out later emerging effects.

Topics: Anticonvulsants; Child Development; Epilepsy; Female; Humans; Infant; Lamotrigine; Levetiracetam; Mothers; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies

The AntiEpileptic Drug Monitoring in PREgnancy (EMPiRE) model is the only available tool for predicting seizures in pregnant women with epilepsy (WWE) using anti-seizure medications (ASMs); however, its predictive performance requires validation. This study aimed to evaluate the predictive ability of this model in pregnant Chinese WWE and its potential usefulness in clinical practice.. Data of the EMPiRE model were derived from the EMPiRE study, a prospective multicenter cohort study that recruited women on ASM monotherapy (lamotrigine, carbamazepine, phenytoin or levetiracetam) or polytherapy (lamotrigine with either carbamazepine, phenytoin or levetiracetam). Based on the applicable population of the EMPiRE model, we evaluated 280 patients registered in the Wenzhou Epilepsy Follow-up Registry Database from January 1, 2010, to December 31, 2020. A total of 158 eligible patients were included in the validation cohort. We collected data on the baseline characteristics of patients, eight predictors of the EMPiRE model and outcome events. The outcome was the occurrence of tonic-clonic or non-tonic-clonic seizures at any time in pregnancy up to 6 weeks postpartum. We used the equation of the EMPiRE model to obtain the predicted probabilities of seizures. The predictive ability of the EMPiRE model was quantified by the C-statistic (scale 0-1, values > 0.5 show discrimination), GiViTI calibration test and decision curve analysis (DCA).. Of 158 eligible patients, 96 patients (60.8%, 96/158) experienced one or more seizures at any time between pregnancy and 6 weeks postpartum. The EMPiRE model showed good discrimination with a C-statistic of 0.76 (95% confidence interval [CI] 0.70-0.84). The GiViTI calibration belt showed that the predicted probabilities, which ranged from 16 to 96% (95% CI), were lower than the actual probabilities. DCA indicated that the highest net proportional benefit was obtained for predicted probability thresholds of 15-18% and 54-96%.. The EMPiRE model could discriminate well between WWE with and without seizures during pregnancy and 6 weeks postpartum, but the risk of seizures may be underestimated. The limitations of the model for specific medication regimens may limit its real-world application. If the model is further improved, it will be incredibly valuable.

Topics: Anticonvulsants; Carbamazepine; Cohort Studies; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Phenytoin; Pregnancy; Pregnant Women; Prospective Studies

Patients with epilepsy are significantly burdened by the disease due to long-term health risks, the severe side effect profiles of anti-epileptic drugs, and the strong possibility of pharmacoresistant refractory seizures. New animal models of epilepsy with unique characteristics promise to further research to address these ongoing problems. Here, we characterize a newly developed line of prairie voles (Microtus ochrogaster, UTol:HIC or "Toledo" line) that presents with a hereditary, adult-onset, handling-induced convulsion phenotype. Toledo voles were bred for four generations and tested to determine whether the observed phenotype was consistent with epileptic seizures. Toledo voles maintained a stable 22 % incidence of convulsions across generations, with an average age of onset of 12-16 weeks. Convulsions in Toledo voles were reliably evoked by rodent seizure screens and were phenotypically consistent with murine seizures. At the colony level, Toledo voles had a 7-fold increase in risk for sudden unexpected death from unknown causes, which parallels sudden unexpected death in epilepsy (SUDEP) in human patients. Finally, convulsions in Toledo voles were reduced or prevented by treatment with the anti-epileptic drug levetiracetam. Taken in combination, these results suggest that convulsions in Toledo voles may be epileptic seizures. The Toledo prairie vole strain may serve as a new rodent model of epilepsy in an undomesticated, outbred species.

Topics: Animals; Arvicolinae; Epilepsy; Grassland; Humans; Infant; Levetiracetam; Mice; Seizures

Cognitive rigidity (CR) refers to inadequate executive adaptation in the face of changing circumstances. Increased CR is associated with a number of psychiatric disorders, for example, obsessive-compulsive disorder, and improving cognitive functioning by targeting CR in these conditions, may be fruitful. Levetiracetam (LEV), clinically used to treat epilepsy, may have pro-cognitive effects by restoring balance to neuronal signalling. To explore this possibility, we applied apomorphine (APO) exposure in an attempt to induce rigid cue-directed responses following a cue (visual pattern)-reward (social conspecifics) contingency learning phase and to assess the effects of LEV on such behaviours. Briefly, zebrafish were divided into four different 39-day-long exposure groups ( n  = 9-10) as follows: control (CTRL), APO (100 µg/L), LEV (750 µg/L) and APO + LEV (100 µg/L + 750 µg/L). The main findings of this experiment were that 1) all four exposure groups performed similarly with respect to reward- and cue-directed learning over the first two study phases, 2) compared to the CTRL group, all drug interventions, but notably the APO + LEV combination, lowered the degree of reward-directed behaviour during a dissociated presentation of the cue and reward, and 3) temporal and spatial factors influenced the manner in which zebrafish responded to the presentation of the reward. Future studies are needed to explore the relevance of these findings for our understanding of the potential cognitive effects of LEV.

Topics: Animals; Anticonvulsants; Apomorphine; Epilepsy; Levetiracetam; Piracetam; Zebrafish

Approximately one quarter of people with an intellectual disability (PwID) have epilepsy of whom nearly three-quarters are pharmaco-resistant. There are higher reported neuropsychiatric side-effects to anti-seizure medication (ASM) in this group. Levetiracetam (LEV) is a first-line ASM with a stronger association with neuropsychiatric symptoms for PwID than other ASMs. Brivaracetam (BRV) is a newer ASM. Recent studies suggest a beneficial effect of swapping people who experience neuropsychiatric events with LEV to BRV. However, there is limited evidence of this for PwID. This evaluation analyses real world outcomes of LEV to BRV swap for PwID compared to those without ID.. We performed a multicentre, retrospective review of clinical records. Demographic, clinical characteristics and reported adverse events of patients switched from LEV to BRV (2016-2020) were recorded at 3 months pre and 6- and 12-month post-BRV initiation. Outcomes were compared between PwID and those without and summarised using cross-tabulations and logistic regression models. A Bonferroni correction was applied.. Of 77 participants, 46 had ID and 52% had a past psychiatric illness. 71% participants switched overnight from LEV to BRV. Seizure reduction of > 50% was seen in 40% patients. Psychiatric illness history was predictive of having neuropsychiatric side-effects with LEV but not BRV (p = 0.001). There was no significant difference for any primary outcomes between PwID versus without ID.. Switching from LEV to BRV appears as well tolerated and efficacious in PwID as those without ID with over 90% still on BRV after 12 months.

Topics: Anticonvulsants; Case-Control Studies; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Humans; Intellectual Disability; Levetiracetam; Substance Abuse, Intravenous; Treatment Outcome

In women with epilepsy, antiepileptic drugs with low teratogenic risk should be used at the lowest dose necessary to control seizures. The medication adjustment and folic acid supplementation are started before pregnancy. Valproic acid should be avoided unless indispensable. Levetiracetam and lamotrigine are often used as less teratogenic agents. Moreover, appropriate information on possible changes in seizure frequency with pregnancy and childbirth preparation and breastfeeding should be provided. Generally, women taking antiepileptic drugs for epilepsy treatment may undergo natural delivery and breastfeeding. We should collaborate with obstetricians and other professionals to help ensure a safe environment for pregnancy and childbirth.

Topics: Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Pregnancy; Seizures; Valproic Acid

Epilepsy is a major symptom in patients with glioma. Levetiracetam (LEV) is recognized as a first-line treatment for glioma-related epilepsy. Increasing the LEV dose is allowed into patients with seizure occurrence against its initial dose. However, the therapeutic efficacy of increasing the LEV dose in response to seizure occurrence remains unclear.. We retrospectively analyzed 236 glioma patients who were treated with antiseizure medications (ASMs) internally at our institute between September 2010 and December 2017. Of these, the analysis focused on 156 patients treated with LEV who had a clear history of administration.. Seizure occurrences were observed in 21 of 75 patients (26.7%) who received LEV as first-line therapy and in 33 of 81 patients (40.7%) who received LEV as non-first-line treatment. The seizure control rate for seizure occurrence with LEV as first-line treatment was significantly higher in patients treated with addition of other ASMs (72.7%) than in those treated with increasing dose of LEV (20.0%) (p = 0.016). The seizure control rate for seizure occurrence with LEV as non-first-line treatment did not differ significantly between patients with addition of other ASMs (58.3%) and those treated with increasing dose of LEV (47.6%) (p = 0.554).. Adding other ASMs was more effective than increasing the LEV dose for seizure control in patients treated with LEV as first-line treatment, but they demonstrated comparable efficacy in patients treated with LEV as non-first-line treatment.

Topics: Epilepsy; Glioma; Humans; Levetiracetam; Patients; Retrospective Studies

People with epilepsy (PWE) have a high prevalence of developing depression and anxiety. The objective is to determine the feasibility of brief screening tools to screen for depression and anxiety in epilepsy, and the predictive factors.. This is a cross-sectional study in the neurology clinic in a tertiary teaching hospital in Kuala Lumpur. The screening tools used were the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and the General Anxiety Disorder Form (GAD-7).. Five hundred and eighty-five patients were recruited in this study, and 50.8% of them were male, predominantly Chinese (46.7%), with a mean age of seizure onset of 21.8 ± 16.1 years. The majority had focal seizures (75.0%), and 41.9% had seizure remission. There were 15.5% who scored ≥15 in the NDDI-E, and 17.0% had moderate or severe anxiety (scored ≥10 in the GAD-7). In a regression model to predict the NDDI-E score, the age of seizure onset recorded a higher beta value (β = -0.265, p =< 0.001), followed by the duration of epilepsy (β = -0.213, p =< 0.001), use of levetiracetam (LEV) (β = 0.147, p = 0.002), clonazepam (CLZ) (β = 0.127, p = 0.011), and lamotrigine (LTG) (β = 0.125, p = 0.011), number of current antiseizure medications (β = -0.124, p = 0.049), seizure remission for ≥1 year (β = -0.108, p = 0.011), and female (β = 0.082, p = 0.049). For the GAD-7 score, the predictors included current age (β = -0.152, p = 0.001), the use of LEV (β = 0.122, p = 0.011), Indian ethnicity (β = 0.114, p = 0.006), and the use of carbamazepine (β = -0.090, p = 0.043).. Implementation of simple psychological screening using self-administered questionnaires was feasible in a busy tertiary epilepsy clinic.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Cross-Sectional Studies; Depression; Epilepsy; Feasibility Studies; Female; Humans; Levetiracetam; Male; Seizures; Young Adult

After the recent limitations to prescribing valproate, many studies have highlighted the challenging management of female patients of reproductive age with idiopathic generalized epilepsy (IGE). However, no study, to the authors' knowledge, has addressed the comparative effectiveness of alternative antiseizure medications (ASMs) in these patients.. To compare the effectiveness and safety of levetiracetam and lamotrigine as initial monotherapy in female patients of childbearing age with IGE.. This was a multicenter, retrospective, comparative effectiveness cohort study analyzing data from patients followed up from 1994 to 2022. Patients were recruited from 22 primary, secondary, and tertiary adult and child epilepsy centers from 4 countries. Eligible patients were female individuals of childbearing age, diagnosed with IGE according to International League Against Epilepsy (2022) criteria and who initiated levetiracetam or lamotrigine as initial monotherapy. Patients were excluded due to insufficient follow-up after ASM prescription.. Levetiracetam or lamotrigine as initial monotherapy.. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards regression was performed to compare treatment failure (TF) among patients who received levetiracetam or lamotrigine as initial monotherapy.. A total of 543 patients were included in the study, with a median (IQR) age at ASM prescription of 17 (15-21) years and a median (IQR) follow-up of 60 (24-108) months. Of the study population, 312 patients (57.5%) were prescribed levetiracetam, and 231 (42.5%) were prescribed lamotrigine. An IPTW-adjusted Cox model showed that levetiracetam was associated with a reduced risk of treatment failure after adjustment for all baseline variables (IPTW-adjusted hazard ratio [HR], 0.77; 95% CI, 0.59-0.99; P = .04). However, after stratification according to different IGE syndromes, the higher effectiveness of levetiracetam was confirmed only in patients with juvenile myoclonic epilepsy (JME; IPTW-adjusted HR, 0.47; 95% CI, 0.32-0.68; P < .001), whereas no significant differences were found in other syndromes. Patients treated with levetiracetam experienced adverse effects more frequently compared with those treated with lamotrigine (88 of 312 [28.2%] vs 42 of 231 [18.1%]), whereas the 2 ASMs had similar retention rates during follow-up (IPTW-adjusted HR, 0.91; 95% CI, 0.65-1.23; P = .60).. Results of this comparative effectiveness research study suggest the use of levetiracetam as initial alternative monotherapy in female patients with JME. Further studies are needed to identify the most effective ASM alternative in other IGE syndromes.

Topics: Adult; Anticonvulsants; Child; Cohort Studies; Epilepsy; Female; Humans; Immunoglobulin E; Lamotrigine; Levetiracetam; Male; Retrospective Studies

To describe the evolution in use and cost of antiseizure medications (ASM) in the United States of America (USA).. Retrospective descriptive study using the IBM MarketScan Commercial Database (data of privately-insured patients) for the years 2006 to 2021. We identified patients with epilepsy who were on ASM. We adjusted cost for inflation with the Gross Domestic Product Implicit Price Deflator.. We evaluated 347,158 patients (46.9 % males; median (p. The median cost of ASMs per person-year approximately doubled from 2006 to 2021. The increase in use of generic ASMs probably helped buffer the growing costs of ASMs. However, generic ASMs already represent 83 % of prescription days in 2021, with limited room to further contain costs by just increasing the proportion of generics.

Topics: Adult; Anticonvulsants; Child; Drugs, Generic; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Phenytoin; Retrospective Studies

To evaluate using optical coherence tomography angiography the macular and optic nerve head blood flow in pediatric patients with epilepsy treated with levetiracetam for at least 12 months.. This study included 33 pediatric patients with epilepsy and 30 sex- and age-matched healthy volunteer children were included in the study. Optical coherence tomography angiography was used to evaluate the optic nerve head and macular perfusion changes. The mean ocular perfusion pressures were also calculated. Patients who were using multiple antiepileptic drugs or had a prior history of using different drugs were excluded.. The choriocapillaris flow area was significantly lower in the Study Group than in the Control Group (p=0.006). However, the foveal avascular zone and vessel densities of the macula in the superficial capillary plexus, deep capillary plexus, and optic nerve head of the study group were not significantly different from those of the control group (p>0.05). Moreover, no significant difference in means of mean ocular perfusion pressure was found between the two groups (p=0.211). No obvious correlation was found between treatment duration and optical coherence tomography angiography parameters or mean ocular perfusion pressure.. Choroidal perfusion was reduced in children taking levetiracetam compared with that in the control group, whereas retinal perfusion was not affected in this optical coherence tomography angiography study.

Topics: Child; Epilepsy; Fluorescein Angiography; Humans; Levetiracetam; Perfusion; Retinal Vessels; Tomography, Optical Coherence

Self-limited infantile epilepsy (SeLIE) is a benign epilepsy. Previous studies have shown that monotherapy with most antiseizure medications can effectively relieve seizures in patients with SeLIE, but the efficacy of levetiracetam has not been investigated.. This study aimed to investigate the efficacy of levetiracetam in the treatment of SeLIE patients with PRRT2 mutations.. The clinical data of 39 SeLIE patients (21 males and 18 females, aged 4.79 ± 1.60 months) with pathogenic variants in PRRT2 or 16p11.2 microdeletion were retrospectively analyzed. Based on the use of initial antiseizure medication (ASM), the patients were classified into two groups: Levetiracetam group (LEG) and Other ASMs group (OAG). The difference of efficacy between the two groups was compared.. Among the 39 SeLIE patients, 16 were LEG (10 males and 6 females, aged 5.25 ± 2.07 months), with whom two obtained a seizure-free status (12.50%) and 14 ineffective or even deteriorated (87.50%). Among the 14 ineffective or deteriorated cases, 13 were seizure-controlled after replacing levetiracetam with other ASMs including topiramate, oxcarbazepine, lamotrigine, and valproate, and the remaining one finally achieved remission at age 3. Of the 39 patients, 23 were OAG (11 males and 12 females; aged 4.48 ± 1.12 months), of whom 22 achieved seizure remission, except for one patient who was ineffective with topiramate initially and relieved by oxcarbazepine instead. Although there were no significant differences in gender and age of onset between the two groups, the effective rate was significantly different (12.50% in LEG vs. 95.65% in OAG) (P < 0.01).. The findings showed that patients with SeLIE caused by the PRRT2 mutations did not benefit from the use of levetiracetam, but could benefit from other ASMs.

Topics: Anticonvulsants; Child, Preschool; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Membrane Proteins; Nerve Tissue Proteins; Oxcarbazepine; Retrospective Studies; Seizures; Topiramate

Alterations in zinc and copper homeostasis may contribute to seizure susceptibility, development, termination, and response to antiepileptic medications. The current study examined the profile of zinc, copper, and their ratio in childhood epilepsy and its pharmacological variants (pharmacoresistant and pharmacoresponsive).. The study included 100 epileptic children (50 pharmacoresistant and 50 pharmacoresponsive) and 50 healthy, age- and gender-matched controls. History, clinical examination, and assays of serum zinc and copper were performed. Zinc/copper ratio was calculated.. Serum zinc and the zinc/copper ratio were significantly lower in epileptic children than in controls (p < 0.001). Significantly lower zinc and zinc/copper ratio and higher copper levels were found in children treated with levetiracetam/sodium valproate/oxcarbazepine than those treated with levetiracetam alone or combined with sodium valproate (p < 0.05 for all). Epileptic children, particularly pharmacoresistant, exhibited significant negative correlations between the serum levels of zinc and copper (r = -0.279, p = 0.005, and r = -0.363 and p = 0.010, respectively). At cutoff value of zinc/copper ratio < 1.118 in diagnosing children with epilepsy, it gives a sensitivity of 64% and a specificity of 85% with the AUC = 0.8092. At cutoff value of zinc/copper ratio ≤ 0.7826 in distinguishing pharmacoresistant epilepsy, it produced 52% sensitivity, 64% specificity with AUC = 0.576 Conclusions: Low zinc and high copper levels were associated with childhood epilepsy especially those with pharmacoresistant type and treated with Oxcarbazepine. Zinc/copper ratio might be a potential biomarker in diagnosing childhood epilepsy and to some extent in predicting pharmacoresistant type.

Topics: Anticonvulsants; Biomarkers; Child; Copper; Epilepsy; Humans; Levetiracetam; Oxcarbazepine; Valproic Acid; Zinc

Data of large pregnancy registries have improved the recommendations for women with epilepsy before pregnancy. Monotherapy containing antiepileptic drugs with a low malformation rate (lamotrigine or levetiracetam) is recommended as well as preconceptional folic acid supplementation, while valproic acid should be avoided. The practicability of these recommendations remains controversial.. Retrospective case series of 160 women with epilepsy over a period of 5 years who were advised in our outpatient department before and during pregnancy.. Only 18.9% of women presented with valproic acid. Even without valproic acid, complications or emergency admissions rarely occurred under specialist supervision. In our case series, lamotrigine proved to be less effective and less controllable than other drugs during pregnancy. Levetiracetam also has a low malformation rate, but showed a better effect on seizure outcome during pregnancy than lamotrigine. Only 12% of women who wanted to have children took folic acid.. This case series comes from a tertiary center; the referred women were mainly accompanied by neurologists with special expertise in epileptology. In this group valproate could be avoided in most cases. Lamotrigine is probably less effective due to the drop in blood levels during pregnancy. Levetiracetam seems to be a good alternative, working well against focal and generalized seizures. Folic acid may be taken later than recommended.. HINTERGRUND: Die Auswertung großer Schwangerschaftsregister hat die Empfehlungen für Frauen mit Epilepsie und Kinderwunsch in den letzten Jahren verbessert. So werden eine Monotherapie mit einem fehlbildungsarmen Medikament (Lamotrigin oder Levetiracetam) unter Vermeidung von Valproinsäure sowie eine präkonzeptionelle Folsäureprophylaxe empfohlen. Die Praktikabilität dieser Empfehlungen ist umstritten.. Retrospektive Fallserie von 160 Frauen mit Epilepsie über einen Zeitraum von 5 Jahren, die vor und bei Schwangerschaften in unserer Ambulanz beraten wurden.. Nur 18,9 % der Frauen stellten sich noch mit Valproinsäure vor. Auch ohne Valproinsäure kam es unter fachärztlicher Kontrolle selten zu Komplikationen oder Notfalleinweisungen. Lamotrigin erwies sich in unserer Fallserie in der Schwangerschaft als weniger gut wirksam und schlechter steuerbar als andere Medikamente. Levetiracetam ist ebenfalls wenig teratogen, kontrollierte Anfälle in der Schwangerschaft aber besser als Lamotrigin. Nur 12 % der Frauen mit Kinderwunsch nahmen Folsäure ein.. Diese Fallserie stammt aus einem tertiären Zentrum; die zugewiesenen Frauen wurden überwiegend von epileptologisch kompetenten Fachärzten für Neurologie betreut. In dieser Gruppe konnte auf Valproat in den meisten Fällen verzichtet werden. Lamotrigin ist vermutlich wegen des Spiegelabfalls in der Schwangerschaft weniger effektiv. Eine gute Alternative scheint Levetiracetam zu sein, das gut gegen fokale und generalisierte Anfälle wirkt. Folsäure wird möglicherweise später eingenommen als empfohlen.

Topics: Anticonvulsants; Counseling; Epilepsy; Female; Folic Acid; Humans; Lamotrigine; Levetiracetam; Outpatients; Pregnancy; Pregnancy Complications; Retrospective Studies; Seizures; Valproic Acid

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam

Valproic acid (VPA) and levetiracetam (LEV) are used in epilepsy treatment. However, their use to treat short-bowel syndrome has not been reported. We herein report a 68-year-old man who was hospitalized for symptomatic epilepsy following cerebral infarction. He had a history of superior mesenteric arterial occlusion, and only 30 cm of his jejunum was intact. VPA and LEV were administered, and good blood levels were achieved at clinical doses. This suggests that the gastrointestinal tract absorption of LEV and VPA is good even in patients with short-bowel syndrome and a 30-cm jejunum.

Topics: Aged; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Male; Piracetam; Valproic Acid

This study aimed to comprehensively examine the genetic and phenotypic aspects of GABRB3-related epilepsy and to explore the potential prospects of personalized medicine.. Genetic testing was conducted in all epilepsy patients without acquired factors for epilepsy. Through the collaboration of multicenter in China, we analyzed the genotype-phenotype correlation and antiepileptic therapy of 26 patients with GABRB3-related epilepsy.. Thirteen GABRB3 variants were novel, and 25 were de novo. The seizure onset age ranged from 1 to 21 months (median age 3.75 months). Seizure types predominated including focal seizures (92.3%), generalized tonic-clonic seizures (23.1%), and epileptic spasms (15.4%). Clinical features included cluster seizures (80.8%), fever sensitivity (53.8%), and developmental delay (96.2%). Neuroimaging was abnormal in 10 patients, including dysplasia of the cerebral cortex, dysplasia of the frontal and temporal cortex, delayed myelination, and corpus callosum dysplasia. Eleven patients were diagnosed with developmental and epileptic encephalopathy (DEE), four with West syndrome, three with epilepsy of infancy with migrating focal seizures (EIMFS), one with epilepsy with myoclonic-atonic seizures (EMAS), one with Dravet syndrome, and one with febrile seizures plus (FS+). Seizures were controlled in 57.7% of patients by valproate, levetiracetam, or perampanel in the majority.. The clinical features of GABRB3-related epilepsy included seizure onset in early infancy, cluster seizures and fever sensitivity. Most patients manifest severe epilepsy phenotypes. Valproate, levetiracetam and perampanel seem to have positive effects on seizure control for patients with GABRB3 variants.

Topics: Electroencephalography; Epilepsies, Myoclonic; Epilepsy; Fever; Humans; Infant; Levetiracetam; Receptors, GABA-A; Seizures, Febrile; Valproic Acid

Oxcarbazepine (OXZ) and levetiracetam (LEV) are two new generation anti-epileptic drugs, often co-administered in children with enzyme-inducing antiepileptic drugs (EIAEDs). The anti-epileptic effect of OXZ and LEV are linked to the exposure of OXZ's active metabolite 10-monohydroxy derivative (MHD) and (the parent) LEV, respectively. However, little is known about the confounding effect of age and EIAEDs on the pharmacokinetics (PKs) of MHD and LEV. To address this knowledge gap, physiologically-based pharmacokinetic (PBPK) modeling was performed in the PK-Sim software using literature data from children greater than or equal to 2 years of age. Age-related changes in clearance (CL) of MHD and LEV were characterized, both in the presence (group 1) and absence (group 2) of concomitant EIAEDs. The drug-drug interaction effect of EIAEDs was estimated as the difference in CL estimates between groups 1 and 2. PBPK modeling suggests that bodyweight normalized CL (ml/min/kg) is higher in younger children than their older counterparts (i.e., due to an influence of age). Concomitant EIAEDs further increase MHD's CL to a fixed extent of 25% at any age, but EIAEDs' effect on LEV's CL increases with age from 20% (at 2 years) to 30% (at adolescence). Simulations with the maximum recommended doses (MRDs) revealed that children between 2 and 4 years and greater than 4 years, who are not on EIAEDs, are at risk of exceeding the reference exposure range for OXZ and LEV, respectively. This analysis demonstrates the use of PBPK modeling in understanding the confounding effect of age and comedications on PKs in children and adolescents.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Interactions; Epilepsy; Humans; Levetiracetam; Oxcarbazepine

Epileptic seizures are increasingly recognized as part of the clinical phenotype of patients with Alzheimer's disease (AD). However, the evidence base on which to make treatment decisions for such patients is slim, there being no clear recommendation based on systematic review of the few existing studies of anti-seizure drugs in AD patients. Here the authors examine the potential implications for the treatment of seizures in AD of the results of the recently published SANAD II pragmatic study, which examined the effectiveness of levetiracetam, zonisamide, or lamotrigine in newly diagnosed focal epilepsy, and of valproate and levetiracetam in generalized and unclassifiable epilepsy.

Topics: Alzheimer Disease; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Seizures

Aggression is the most commonly encountered antiepileptic-drug (AED)-induced psychiatric adverse effects. Levetiracetam (LEV) is well known to be associated with increased rates of aggression, while perampanel (PER) is also recognized as a potentially aggression-promoting agent, though opinions vary. However, few studies have addressed questions regarding whether the nature of irritability-aggression differs between those drugs. The present study used a standardized rating scale to examine aggression among patient with epilepsy who received LEV or PER using specific measures to confirm the effects of the drugs.. We enrolled 144 consecutive outpatients receiving treatment for epilepsy with LEV (n = 103) or PER (n = 41), and determined their effects regarding aggression using the Buss-Perry Aggression Questionnaire (BAQ). For analysis, total BAQ scores for the LEV and PER subjects were compared to determine whether the aggression-promoting effects of the agents differed, and which BAQ subdomains (physical aggression, verbal aggression, anger, hostility) were related to production of aggression in patients taking either LEV or PER. As a subsidiary analysis, clinical variables inclusive of administered AED type that showed a significant impact on BAQ scores were determined.. The LEV group had a significantly higher hostility score (19.4 ± 5.8) as compared to the PER group (17.2 ± 6.3) in subscale analysis (p < 0.05). In multiple regression analysis, LEV had a significant association with higher hostility score (P = 0.006).. Our results indicate that while easily visible outward-directed aggression tends to be dominant in patients given PER, aggression provoked by LEV may be felt more subjectively or in an inward-directed manner, which can lead to more diverse expression and misrecognition.

Topics: Aggression; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Nitriles; Pyridones

During pregnancy in women with epilepsy, lower blood concentrations of antiseizure medications can have adverse clinical consequences.. To characterize pregnancy-associated concentration changes for several antiseizure medications among women with epilepsy.. Enrollment in this prospective, observational cohort study, Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD), occurred from December 19, 2012, to February 11, 2016, at 20 US sites. Enrolled cohorts included pregnant women with epilepsy and nonpregnant control participants with epilepsy. Inclusion criteria were women aged 14 to 45 years, an intelligence quotient greater than 70 points, and, for the cohort of pregnant women, a fetal gestational age younger than 20 weeks. A total of 1087 women were assessed for eligibility; 397 were excluded and 230 declined. Data were analyzed from May 1, 2014, to June 30, 2021.. Medication plasma concentrations in women taking monotherapy or in combination with noninteracting medications. The cohort of pregnant women was monitored through 9 months post partum, with similar time points for control participants.. Dose-normalized concentrations were calculated as total or unbound plasma medication concentrations divided by total daily dose. Phlebotomy was performed during 4 pregnancy study visits and 3 postpartum visits for the pregnant women and 7 visits over 18 months for control participants. The primary hypothesis was to test pregnancy changes of dose-normalized concentrations from nonpregnant postpartum samples compared with those of control participants.. Of the 351 pregnant women and 109 control participants enrolled in MONEAD, 326 pregnant women (median [range] age, 29 [19-43] years) and 104 control participants (median [range] age, 29 [16-43] years) met eligibility criteria for this analysis. Compared with postpartum values, dose-normalized concentrations during pregnancy were decreased by up to 56.1% for lamotrigine (15.60 μg/L/mg to 6.85 μg/L/mg; P < .001), 36.8% for levetiracetam (11.33 μg/L/mg to 7.16 μg/L/mg; P < .001), 17.3% for carbamazepine (11.56 μg/L/mg to 7.97 μg/L/mg; P = .03), 32.6% for oxcarbazepine (11.55 μg/L/mg to 7.79 μg/L/mg; P < .001), 30.6% for unbound oxcarbazepine (6.15 μg/L/mg to 4.27 μg/L/mg; P < .001), 39.9% for lacosamide (26.14 μg/L/mg to 15.71 μg/L/mg; P < .001), and 29.8% for zonisamide (40.12 μg/L/mg to 28.15 μg/L/mg; P < .001). No significant changes occurred for unbound carbamazepine, carbamazepine-10,11-epoxide, and topiramate, although a decrease was observed for topiramate (29.83 μg/L/mg to 13.77 μg/L/mg; P = .18). Additionally, compared with dose-normalized concentrations from control participants, pregnancy dose-normalized median (SE) concentrations decreased significantly by week of gestational age: carbamazepine, -0.14 (0.06) μg/L/mg (P = .02); carbamazepine unbound, -0.04 (0.01) μg/L/mg (P = .01); lacosamide, -0.23 (0.07) μg/L/mg (P < .001); lamotrigine, -0.20 (0.02) μg/L/mg (P < .001); levetiracetam, -0.06 (0.03) μg/L/mg (P = .01); oxcarbazepine, -0.14 (0.04) μg/L/mg (P < .001); oxcarbazepine unbound, -0.11 (0.03) μg/L/mg (P < .001); and zonisamide, -0.53 (0.14) μg/L/mg (P < .001) except for topiramate (-0.35 [0.20] μg/L/mg per week) and carbamazepine-10,11-epoxide (0.02 [0.01] μg/L/mg).. Study results suggest that therapeutic drug monitoring should begin early in pregnancy and that increasing doses of these anticonvulsants may be needed throughout the course of pregnancy.

Topics: Adult; Anticonvulsants; Carbamazepine; Epilepsy; Female; Humans; Lacosamide; Lamotrigine; Levetiracetam; Oxcarbazepine; Pregnancy; Prospective Studies; Topiramate; Zonisamide

To investigate possible factors that influenced whether pregnancy in women with epilepsy resulted in the desirable outcome of a live-born non-malformed infant and a mother whose pregnancy had been seizure free.. The desirable outcome, as defined, occurred in 46.3% of unselected pregnancies in the database of the Australian Register of Antiepileptic Drugs in Pregnancy (APR). The only factor investigated that had a statistically significant (P < 0.05) effect, increasing the chance of such a desirable outcome, was freedom from seizures in the pre-pregnancy year. However, anti-seizure medication (ASM) doses, particularly valproate doses, had been reduced prior to 15.6% of the pregnancies, and this may have concealed factors that otherwise may have adversely affected the desirable outcome rate. Analysis of data for monotherapy with the more commonly used ASMs appears to suggest that employing levetiracetam at the outset of antiseizure therapy may offer a better chance of a desirable outcome to future pregnancies than monotherapy with other ASMs, but this finding is not confirmed statistically.. In pregnancies where valproate use has already been minimized, seizure control throughout the pre-pregnancy year was associated with the best chance of a desirable outcome, as defined above. In most Australian women starting therapy for epilepsy initiating treatment with levetiracetam monotherapy may offer the best chance of such a desirable outcome to a future pregnancy, yet to be confirmed.

Topics: Anticonvulsants; Australia; Epilepsy; Female; Humans; Levetiracetam; Pregnancy; Pregnancy Complications; Valproic Acid

The use of antiseizure medications (ASMs) in the pediatric population is poorly studied. The purpose of this study was to investigate changes in the use of ASMs in children and adolescents compared to adults, and to elucidate safety considerations of certain drugs.. In this population-based pharmacoepidemiological study we used the Norwegian Prescription Database (NorPD), 2009-2018. The use of ASMs is presented as 1-year prevalence per 1000: number of ASM users in a year * 1000 / number of inhabitants that year. Variables included predetermined 5-year age groups, gender, ASMs, diagnosis-specific reimbursement codes, user, and population numbers. Selected ASMs used for specific indications or subgroups included ethosuximide, sulthiame, rufinamide, stiripentol, and clobazam. Gender differences in the use of valproate was examined due to safety considerations in girls/women.. The total number of ASM users (all indications) for the age groups 0-19 and 20-59 years was 5807 and 47,481 respectively in 2009, and 5906 and 61,447 respectively in 2018. The 1-year prevalence for children/adolescents (0-19 years) using ASMs in epilepsy remained stable from 2008 to 2018, 4.3-4.2/1000 inhabitants, as compared to 8.2-7.6/1000 in adults (20-59 years). Valproate, lamotrigine, and levetiracetam were the three most used ASMs in epilepsy in children/adolescents, similar to adults. The selected ASMs were mainly used in children/ adolescents, accounting for 0.74/1000 in 2018 versus 0.17/1000 in adults. A significant increase was seen for sulthiame (8-fold), ethosuximide (4-fold), clobazam (3-fold), and stiripentol (2-fold). The use of ASMs in non-epilepsy indications was limited and stable (17% in 2018); mainly lamotrigine in psychiatry in adolescents (15-19 years). This finding was in contrast to extensive non-epilepsy use in adults (71% in 2018).. Changes in the use of ASMs in children/adolescents differ as compared to adults, most notably extensive and increasing use of selected ASMs and limited non-epilepsy. This is an important part of pharmacovigilance and patient safety evaluations.

Topics: Adolescent; Adult; Anticonvulsants; Child; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Valproic Acid

To systematically collect, critically evaluate, and synthesize current evidence with respect to the efficacy, safety, and tolerability of levetiracetam as mono- or adjunctive therapy for children and adolescents with all types of epilepsy.. The presentation of methods and results in this systematic review was performed according to the evaluation guidelines for health care interventions provided in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol. Literature retrieval will use the Cochrane Library, Web of Science, PubMed, Embase, Allied and Complementary Medicine Database, China Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and Ongoing Clinical Trials Database.The risk of bias of included studies is estimated by taking into consideration the characteristics including random sequence generation, allocation concealment, blinding of patients, blinding of outcome assessment, completeness of outcome data, selective reporting and other bias by Cochrane Collaboration's tool. Data synthesis and analyses are performed using RevMan 5.4 software.. The results of this systematic review and meta-analysis will be published in a peer-reviewed journal.. Levetiracetam seems to be effective and safe for the treatment of pediatric epilepsy.

Topics: Adolescent; Child; Epilepsy; Humans; Levetiracetam; Meta-Analysis as Topic; Systematic Reviews as Topic

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

Epilepsy is one of the most common neurologic unit diseases that have different prevalence in different parts of the world. Antiepileptic drugs (AEDs) are associated with major fertility risks for women of childbearing age. Due to the fact that studies on family planning methods in married women with epilepsy (WWE) have not been conducted in Iran, the aim of this study was to evaluate the family planning methods in married WWE in Birjand, Iran.. An analytical-descriptive study was performed on 126 married WWE hospitalized in the neurology ward or referred to Vali-e-Asr specialized and sub-specialized clinic in Birjand. Demographic information of patients as well as data on the type of used AED, and various methods of family planning were collected in a questionnaire. Data analysis was performed using Chi-square and Fisher tests. All of the above analyses were considered at a significance level of less than 5% by SPSS v.19 software.. The mean age of the patients was 33.41 ± 9.15 years. The mean age of experiencing the first seizure and the onset of menstruation were 24.82 and 13.79 years, respectively. Fifty (35.5%), 38 (27%), 15 (10.6%), 14 (9.9%), and 14 (9.9%) patients used sodium valproate, carbamazepine, phenytoin, levetiracetam, and lamotrigine, respectively. The results showed that 72 sexually active patients (70.6%) used family planning methods, of which 43 patients (59.7%) used withdrawal method, 20 patients (27.8%) used condoms, and 6 patients (8.3%) used oral contraceptive pills (OCP). Eight patients (9.6%) had a history of unintended pregnancy and 3 patients (3.6%) had a history of abortion.. It is recommended to apply effective family planning methods in married WWE to prevent unintended pregnancies and the subsequent adverse effects in the fetus, considering the fact that a significant percentage of WWE did not use effective family planning methods and 8 cases of unintended pregnancies were reported. Because of high consumption of valproate in women of childbearing age in our study and concerning issue about its fetal malformation, it is recommended to reduce the administration of valproate in this population. Moreover, regarding the low consumption of folic acid, especially for women of childbearing age and pregnant WWE who are taking AED, the necessary recommendations should be made by our physicians.

Topics: Adult; Anticonvulsants; Epilepsy; Family Planning Services; Female; Humans; Lamotrigine; Levetiracetam; Pregnancy; Pregnancy Complications; Young Adult

Efforts to characterize variability in epilepsy treatment pathways are limited by the large number of possible antiseizure medication (ASM) regimens and sequences, heterogeneity of patients, and challenges of measuring confounding variables and outcomes across institutions. The Observational Health Data Science and Informatics (OHDSI) collaborative is an international data network representing over 1 billion patient records using common data standards. However, few studies have applied OHDSI's Common Data Model (CDM) to the population with epilepsy and none have validated relevant concepts. The goals of this study were to demonstrate the feasibility of characterizing adult patients with epilepsy and ASM treatment pathways using the CDM in an electronic health record (EHR)-derived database.. We validated a phenotype algorithm for epilepsy in adults using the CDM in an EHR-derived database (2001-2020) against source records and a prospectively maintained database of patients with confirmed epilepsy. We obtained the frequency of all antecedent conditions and procedures for patients meeting the epilepsy phenotype criteria and characterized ASM exposure sequences over time and by age and sex.. The phenotype algorithm identified epilepsy with 73.0-85.0% positive predictive value and 86.3% sensitivity. Many patients had neurologic conditions and diagnoses antecedent to meeting epilepsy criteria. Levetiracetam incrementally replaced phenytoin as the most common first-line agent, but significant heterogeneity remained, particularly in second-line and subsequent agents. Drug sequences included up to 8 unique ingredients and a total of 1,235 unique pathways were observed.. Despite the availability of additional ASMs in the last 2 decades and accumulated guidelines and evidence, ASM use varies significantly in practice, particularly for second-line and subsequent agents. Multi-center OHDSI studies have the potential to better characterize the full extent of variability and support observational comparative effectiveness research, but additional work is needed to validate covariates and outcomes.

Topics: Databases, Factual; Electronic Health Records; Epilepsy; Feasibility Studies; Humans; Levetiracetam

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

Topics: Aged; Anticonvulsants; Epilepsy; Gabapentin; Humans; Lacosamide; Lamotrigine; Levetiracetam; Medicare; Retrospective Studies; United States; Valproic Acid

High neonatal seizure burden is associated with worsened neurodevelopmental outcomes. We compared the efficacy of initial treatment with levetiracetam vs phenobarbital for maintaining low seizure burden in a retrospective cohort of 25 neonates monitored with video electroencephalography (EEG). Video EEG tracing were reviewed and paired with medication bolus times to determine seizure burden after treatment. Initial cumulative dose of phenobarbital was 20 mg/kg in all but 1 case; initial cumulative dose of levetiracetam ranged from 50 to 100 mg/kg. Eleven of 17 (65%) patients sustained seizure burden <10% following initial treatment with levetiracetam, compared with 5 of 8 (63%) with phenobarbital. Thirteen (76%) patients treated with levetiracetam had sustained seizure burden <20% compared with 6 (75%) treated with phenobarbital. The phenobarbital group showed a larger absolute reduction in average seizure burden in the hour before and after treatment (-24.3  vs -14.2 minutes/h). Six of 17 (35%) patients treated with levetiracetam remained seizure free after initial treatment, compared with 2 of 8 (25%) patients treated with phenobarbital. Initial treatment with levetiracetam was associated with shorter average time to seizure freedom (15 vs 21 hours). None of these results were statistically significant. Cumulative doses of levetiracetam 100 mg/kg were well tolerated and associated with substantial decrease in seizure burden in several cases. Levetiracetam remains a promising first-line treatment for neonatal seizures; additional randomized controlled trials evaluating the effects of high-dose levetiracetam on seizure burden and long-term outcomes are warranted.

Topics: Anticonvulsants; Epilepsy; Humans; Infant, Newborn; Infant, Newborn, Diseases; Levetiracetam; Phenobarbital; Retrospective Studies; Seizures

The prescription patterns of antiseizure medication (ASM) are subject to new scientific evidence and sociodemographic and practical aspects. This study analyzed trends in ASM prescription patterns among all adults with epilepsy, with special consideration for women of childbearing potential (WOCBP) and older adult (≥65 years old) patients.. Data from four questionnaire-based cohort studies, conducted in 2008, 2013, 2016, and 2020, were analyzed for ASM prescription frequencies and common mono- and dual therapy regimens. Statistical comparisons were performed with the Chi-square test and one-way analysis of variance.. Overall, the individual prescription patterns among 1,642 adult patients with epilepsy were analyzed. A significant increase in the prescription frequency of third-generation ASMs, from 59.3% to 84.2% (p = 0.004), was accompanied by a decrease in the frequency of first- and second-generation ASMs (5.4% to 2.1% and 34.9% to 12.6%, respectively). This trend was accompanied by a significant decrease in the use of enzyme-inducing ASMs, from 23.9% to 4.6% (p = 0.004). Among frequently prescribed ASMs, prescriptions of carbamazepine (18.6% to 3.1%, p = 0.004) and valproate (15.4% to 8.7%, p = 0.004) decreased, whereas prescriptions of levetiracetam (18.0% up to 32.4%, p = 0.004) increased significantly. The prescription frequency of lamotrigine remained largely constant at approximately 20% (p = 0.859). Among WOCBP, the prescription frequencies of carbamazepine (11.4% to 2.0%, p = 0.004) and valproate (16.1% to 6.1%, p = 0.004) decreased significantly. Levetiracetam monotherapy prescriptions increased significantly (6.6% to 30.4%, p = 0.004) for WOCBP, whereas lamotrigine prescriptions remained consistent (37.7% to 44.9%, p = 0.911). Among older adult patients, a significant decrease in carbamazepine prescriptions (30.1% to 7.8%, p = 0.025) was the only relevant change in ASM regimens between 2008 and 2020. In patients with genetic generalized epilepsies, levetiracetam was frequently used as an off-label monotherapy (25.0% to 35.3%).. These results show a clear trend toward the use of newer and less interacting third-generation ASMs, with lamotrigine, levetiracetam, and lacosamide representing the current ASMs of choice, displacing valproate and carbamazepine over the last decade. In WOCBP, prescription patterns shifted to minimize teratogenic effects, whereas, among older adults, the decrease in carbamazepine use may reflect the avoidance of hyponatremia risks and attempts to reduce the interaction potential with other drugs and ASMs. Levetiracetam is frequently used off-label as a monotherapy in patients with genetic generalized epilepsy.

Topics: Aged; Anticonvulsants; Benzodiazepines; Carbamazepine; Drug Prescriptions; Epilepsy; Epilepsy, Generalized; Female; Humans; Lamotrigine; Levetiracetam; Valproic Acid

To study the efficacy and safety of domestic generic levetiracetam in replacement of brand-name levetiracetam in the treatment of children with epilepsy.. A retrospective analysis was performed on the medical data of 154 children with epilepsy who received domestic generic levetiracetam in the inpatient or outpatient service of Guangdong Provincial People's Hospital from May 2019 to December 2020. Domestic generic levetiracetam and brand-name levetiracetam were compared in terms of efficacy and safety.. For these 154 children, the epilepsy control rate was 77.3% (119/154) at baseline. At 6 months after switching to domestic generic levetiracetam, the epilepsy control rate reached 83.8% (129/154), which showed a significant increase (. Switching from brand-name to generic levetiracetam is safe and effective and holds promise for clinical application, but more prospective randomized controlled trials are required in future.

Topics: Child; Epilepsy; Humans; Levetiracetam; Prospective Studies; Retrospective Studies; Seizures

Epilepsy is a chronic neurological disorder that is characterized by episodes of seizure.. In this study, patients with status epilepticus in the Intensive Care Unit of the Department of Neurology of Qujing First People's Hospital were collected and treated with levetiracetam injection, continuous bedside EEG monitoring (cEEG) technology, and quantitative EEG (qEEG) technique. The inhibitory effects of different doses of levetiracetam injection and sodium valproate on abnormal discharge, the improvement of clinical symptoms, the incidence of adverse reactions, and prognosis were monitored, analyzed, and compared.. Compared with the experimental group of sodium valproate, 1000 mg/d levetiracetam group and 1500 mg/d levetiracetam group had a high probability of successful symptom control and a short control time. The patients had a low recurrence rate and a long recurrence time, and the probability of abnormal discharge in EEG was low.. The recording results showed that levetiracetam could significantly inhibit the abnormal discharge of patients. Compared with sodium valproate, high-dose levetiracetam is a drug with a rapid effect, good effect, and long action time.

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Phenytoin; Valproic Acid

The temporal trends in prescribing anti-seizure medicines (ASMs) for pregnant women with epilepsy are unclear. In this study, we investigated the trends in ASM prescriptions in pregnant Japanese women with epilepsy.. Administrative data (as of December 2021), pertaining to Japanese pregnant outpatient women with epilepsy, aged 16-49 years, who visited hospitals between January 1, 2016 and December 31, 2020 were included in the study. Annual prescription trends in ASMs during this period were calculated based on the proportions. The Cochran-Armitage trend test was used to evaluate the proportion of prescriptions for each ASM.. The numbers of pregnant women with epilepsy were 404, 421, 368, 378, 386 for the years 2016, 2017, 2018, 2019, and 2020, respectively. As of 2020, levetiracetam had the highest proportion of prescriptions, followed by lamotrigine and valproic acid. From 2016 to 2020, the proportions of levetiracetam and lamotrigine prescribed for pregnant women with epilepsy have increased significantly from 19.1% to 30.8% and from 12.1% to 18.4%, respectively. In contrast, there was no temporal change in the proportion of valproic acid prescribed, which was 12.4% in 2016 and 10.1% in 2020.. Our findings suggest that the trends in the prescription of ASMs in Japanese pregnant women outpatients with epilepsy have shifted toward ASMs with a lower teratogenic risk.

Topics: Anticonvulsants; Epilepsy; Female; Humans; Japan; Lamotrigine; Levetiracetam; Outpatients; Pregnancy; Pregnant Women; Prescriptions; Valproic Acid

This method can be used to monitor drug concentrations and decision-making in epileptic patients.

Topics: Anticonvulsants; Carbamazepine; Chromatography, High Pressure Liquid; Chromatography, Liquid; Drug Monitoring; Epilepsy; Humans; Lamotrigine; Levetiracetam; Reproducibility of Results; Tandem Mass Spectrometry

The purpose of our study was the evaluation of the effect of 2,000 mg levetiracetam monotherapy over a 3-month period on nocturnal sleep in patients with epilepsy.. Levetiracetam (LEV) is a novel antiepileptic drug with a unique anticonvulsive mechanism of action. It has been commonly reported to cause sleep disruption and daytime sleepiness in epilepsy patients. Its advantages (its broad antiepileptic spectrum, optimal pharmacokinetics, good safety and tolerability) have led to its frequent use in clinical practice, although little is yet known about LEV's effect on nocturnal sleep architecture.. The effect of LEV on nocturnal sleep was assessed through a full-night lab polysomnography (PSG), followed by a four-nap multiple sleep latency test. Both procedures were performed at baseline and after three months of LEV treatment. The dynamics of seven main PSG variables was evaluated prior to, and three months after, LEV therapy.. Twenty five patients with newly diagnosed or untreated epilepsy completed the study. We found no statistically significant difference at baseline and after LEV therapy in the following sleep parameters: total sleep time, sleep onset, wake after sleep onset, N1 stage and rapid eye movement (REM) sleep (minutes and percentages), and latency of all sleep stages including REM sleep. However, we found a statistically significant increase in the number of awakenings and arousals, an increase in N2 and a decrease in N3 stages (minutes and percentages) after therapy. We also observed an increase in N1 stage and a trend toward a reduction in REM sleep (in both minutes and percentages), but they did not reach statistical significance.. Levetiracetam 2,000 mg/day does not affect sleep continuity and may be considered a sleep-friendly antiepileptic drug.

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Piracetam; Sleep

Brivaracetam (BRV) is one of our latest antiseizure medications (ASMs). It is an analogue of levetiracetam with limited real-life experience. The purpose of this study was to evaluate clinical experience with BRV with focus on efficacy, tolerability and pharmacokinetic variability among adult patients with difficult-to-treat epilepsy.. We retrospectively collected clinical and laboratory data from patients aged > 18 years who initiated treatment with BRV during 2016-2019 and were followed for > one year or cessation of BRV.. The study cohort consisted of 120 adults with drug-resistant epilepsy. Serum concentrations of BRV were available in 72 patients. After one-year follow-up, the retention rate of BRV was 52%. Fifty-seven patients (48%) were responders (>50 reduction of seizure frequency), of whom six became seizure free. Adverse effects were reported in 78 patients (65%); 37 (31%) experienced psychiatric problems like increased irritability, anxiety and depressive symptoms. The mean daily BRV dose was 159 mg (SD 80 mg) and the mean serum concentration 5.4 μmol/L (SD 4.1 μmol/L). In 24 patients, BRV replaced levetiracetam. Pharmacokinetic variability between patients was considerable; 14-fold variation in concentration/dose (C/D)-ratios. Concomitant use of enzyme-inducing ASMs decreased the C/D-ratio by 48%. There were no significant differences in serum concentrations between responders vs. non-responders, or those who experienced adverse effects or not.. After > 1 year of treatment with BRV, we found a responder rate of 48% in adult patients with difficult-to-treat epilepsy. The drug was largely well tolerated, but one third experienced psychiatric adverse effects. The combination of clinical and pharmacokinetic data provides insight into factors contributing to efficacy and tolerability of new ASMs.

Topics: Adult; Anticonvulsants; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Humans; Levetiracetam; Pyrrolidinones; Retrospective Studies; Treatment Outcome

Levetiracetam (LEV) is an anti-seizure drug (ASD). A consensus has not been reached regarding its effects on bone health. This cross sectional study was planned to assess short, medium and long-term effects on bone density and blood parameters that are associated with bone metabolism.. The sample consisted of 47 patients with epilepsy, who had been on LEV monotherapy for more than six months. All participants were over 18 years of age and had no other risk factors for osteoporosis. None of them used any other anti-seizure drug before. Bone mineral density (BMD) was evaluated with dual energy X-ray absorptiometry (DEXA) and biochemical markers associated with bone health were measured. Patients were divided into three groups depending on how long they had been on LEV for (Group A: <1 year; Group B: 1-5 years, Group C: >5 years) and compared with each other in terms of BMD scores and blood parameters.. The mean age of patients was 32. 6 ± 13.3 and 20 patients were female (42.5%). The mean onset age of epilepsy was 28.1 ± 13.4 years. Average LEV period of consumption was 2.7 ± 2.7 years and mean daily dose was 1041.7 ± 393.9 milligrams. Lumbar BMD scores of the group with LEV usage < 1 year were significantly lower than those of the group with LEV usage of 1-5 years (p < 0.05). Lumbar vertebra scores were found to be lower in group of LEV usage duration of < 1 year when compared with LEV usage duration > 5 years but the difference was not statistically significant.. We argue that LEV might have a negative effect on bone densitometry at the lumbar level in short-time usage for less than one year. Furthermore, no deleterious impact on bone metabolism was observed in long-term treatment. LEV seems as a rational drug for treatment of epilepsy patients, particularly for those with osteoporosis, since the comparative results of one year and longer than 5-years usage data did not show any statistically significant difference.

Topics: Adolescent; Adult; Anticonvulsants; Bone Density; Cross-Sectional Studies; Epilepsy; Female; Humans; Levetiracetam; Male; Osteoporosis; Piracetam; Treatment Outcome; Young Adult

The ARHGEF9 gene variants have phenotypic heterogeneity, the number of reported clinical cases are limited and the genotype-phenotype relationship is still unpredictable.. Clinical data of the patients and their family members were gathered in a retrospective study. The exome sequencing that was performed on peripheral blood samples was applied for genetic analysis. We used the ARHGEF9 gene as a key word to search the PubMed database for cases of ARHGEF9 gene variants that have previously been reported and summarized the reported ARHGEF9 gene variant sites, their corresponding clinical phenotypes, and effective treatment.. We described five patients with developmental and epileptic encephalopathy caused by ARHGEF9 gene variants. Among them, the antiepileptic treatment of valproic acid and levetiracetam was effective in two cases individually. The exome sequencing results showed five children with point mutations in the ARHGEF9 gene: p.R365H, p.M388V, p.D213E, and p.R63H. So far, a total of 40 children with ARHGEF9 gene variants have been reported. Their main clinical phenotypes include developmental delay, epilepsy, epileptic encephalopathy, and autism spectrum disorders. The variants reported in the literature, including 22 de novo variants, nine maternal variants, and one unknown variant. There were 20 variants associated with epileptic phenotypes, of which six variants are effective for valproic acid treatment.. The genotypes and phenotypes of ARHGEF9 gene variants represent a wide spectrum, and the clinical phenotype of epilepsy is often refractory and the prognosis is poor. The p.R365H, p.M388V, p.D213E, and p.R63H variants have not been reported in the current literature, and our study has expanded the genotype spectrum of ARHGEF9 gene. Our findings indicate that levetiracetam and valproic acid can effectively control seizures in children with epileptic phenotype caused by ARGHEF9 gene variations. These findings will help clinicians improve the level of diagnosis and treatment of the genetic disease.

Topics: Epilepsy; Epilepsy, Generalized; Humans; Levetiracetam; Phenotype; Retrospective Studies; Rho Guanine Nucleotide Exchange Factors; Valproic Acid

Women with epilepsy frequently need antiseizure medication (ASM) to prevent seizures in pregnancy. Risk of neurodevelopmental disorders after prenatal exposure to AMSs is uncertain.. To determine whether children exposed prenatally to ASMs in monotherapy and duotherapy have increased risk of neurodevelopmental disorders.. The Nordic register-based study of antiepileptic drugs in pregnancy (SCAN-AED) is a population-based cohort study using health register and social register data from Denmark, Finland, Iceland, Norway, and Sweden (1996-2017; analysis performed February 2022). From 4 702 774 alive-born children with available mother-child identities and maternal prescription data, this study included 4 494 926 participants. Children from a multiple pregnancy or with chromosomal disorders or uncertain pregnancy length were excluded (n = 207 848).. Prenatal exposure to ASM determined from maternal prescription fills between last menstrual period and birth.. We estimated cumulative incidence at age 8 years in exposed and unexposed children. Cox regression adjusted for potential confounders yielded adjusted hazard ratios (aHRs) with 95% CIs for autism spectrum disorder (ASD), intellectual disability (ID), or any neurodevelopmental disorder (ASD and/or ID).. A total of 4 494 926 children were included; 2 306 993 (51.3%) were male, and the median (IQR) age at end of follow-up was 8 (4.0-12.1) years. Among 21 634 unexposed children of mothers with epilepsy, 1.5% had a diagnosis of ASD and 0.8% (numerators were not available because of personal data regulations in Denmark) of ID by age 8 years. In same-aged children of mothers with epilepsy exposed to topiramate and valproate monotherapy, 4.3% and 2.7%, respectively, had ASD, and 3.1% and 2.4% had ID. The aHRs for ASD and ID after topiramate exposure were 2.8 (95% CI, 1.4-5.7) and 3.5 (95% CI, 1.4-8.6), respectively, and after valproate exposure were 2.4 (95% CI, 1.7-3.3) and 2.5 (95% CI, 1.7-3.7). The aHRs were elevated with higher ASM doses compared with children from the general population. The duotherapies levetiracetam with carbamazepine and lamotrigine with topiramate were associated with increased risks of neurodevelopmental disorders in children of women with epilepsy: levetiracetam with carbamazepine: 8-year cumulative incidence, 5.7%; aHR, 3.5; 95% CI, 1.5-8.2; lamotrigine with topiramate: 8-year cumulative incidence, 7.5%; aHR, 2.4; 95% CI, 1.1-4.9. No increased risk was associated with levetiracetam with lamotrigine (8-year cumulative incidence, 1.6%; aHR, 0.9; 95% CI, 0.3-2.5). No consistently increased risks were observed for neurodevelopmental disorders after prenatal exposure to monotherapy with lamotrigine, levetiracetam, carbamazepin, oxcarbazepine, gapapentin, pregabalin, clonazepam, or phenobarbital.. In this cohort study, prenatal exposure to topiramate, valproate, and several duotherapies were associated with increased risks of neurodevelopmental disorders.

Topics: Anticonvulsants; Autism Spectrum Disorder; Autistic Disorder; Carbamazepine; Child; Cohort Studies; Epilepsy; Female; Humans; Intellectual Disability; Lamotrigine; Levetiracetam; Male; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Topiramate; Valproic Acid

Epilepsy is a neurological disease that requires long-term antiepileptic drugs (AEDs). The old generation of AEDs may affect serum homocysteine and asymmetric dimethylarginine (ADMA) and disturb lipid levels. The aim of the study was to evaluate serum ADMA, homocysteine, lipid profile, and carotid intima-media thickness (CIMT) in epileptic children.. This study was implemented on 159 epileptic children who were subdivided into 3 subgroups, with 53 receiving sodium valproate, 53 receiving levetiracetam, and 53 receiving polytherapy, for over 6 months and 53 healthy children.. Low-density lipoprotein, triglycerides, and cholesterol levels were increased in epileptic children (p < 0.001), which were higher in those receiving multidrug followed by a valproate receiver. While high-density lipoprotein was lower in those receiving multidrug more than those receiving valproate. ADMA and homocysteine levels increased in epileptic patients than in controls (p < 0.001). Higher ADMA was also observed in the multidrug receiver (5.78 ± 0.62), followed by the levetiracetam group (5.56 ± 0.61). Homocysteine levels were significantly higher in multidrug and valproate-treated children than those treated with levetiracetam. CIMT was significantly higher in multidrug and valproate-treated patients (p < 0.001).. Long-term use of AEDs, especially old-generation polytherapy, can elevate lipid profiles, homocysteine, ADMA levels, and carotid intima-media thickness compared to the minimal effect of new AEDs.. The long-term use of antiepileptic drugs, especially old-generation polytherapy, can increase lipid profiles, homocysteine levels, ADMA, and carotid intima thickness compared to the minimal effect of new antiepileptic generation. A routine follow-up of these markers and a lifestyle modification are recommended to avoid cerebrovascular events as much as possible.

Topics: Anticonvulsants; Arginine; Carotid Intima-Media Thickness; Child; Epilepsy; Homocysteine; Humans; Levetiracetam; Valproic Acid

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsies. Pharmacological treatment with anti-seizure drugs (ASDs) remains the mainstay in epilepsy management. Levetiracetam (LEV) is a second-generation ASD with a novel SV2A protein target and is indicated for treating focal epilepsies. While there is considerable literature in acute models, its effect in chronic epilepsy is less clear. Particularly, its effects on neuronal excitability, synaptic plasticity, adult hippocampal neurogenesis, and histological changes in chronic epilepsy have not been evaluated thus far, which formed the basis of the present study. Six weeks post-lithium-pilocarpine-induced status epilepticus (SE), epileptic rats were injected with levetiracetam (54 mg/kg b.w. i.p.) once daily for two weeks. Following LEV treatment, Schaffer collateral - CA1 (CA3-CA1) synaptic plasticity and structural changes in hippocampal subregions CA3 and CA1 were evaluated. The number of doublecortin (DCX

Topics: Animals; Dentate Gyrus; Epilepsy; Epilepsy, Temporal Lobe; Hippocampus; Levetiracetam; Mossy Fibers, Hippocampal; Neuronal Plasticity; Rats

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

Levetiracetam (LEV) is an anti-seizure medication (ASM) known to have significant behavioral side effects in children with epilepsy. These side effects may be improved by supplemental vitamin B6 (pyridoxine) use. Our research aimed to study risk factors for LEV side effects and the role of vitamin B6 in altering this risk.. We retrospectively analyzed the demographic and clinical profile of all pediatric patients on LEV treatment between July 2019 and December 2020. T-tests, Chi-square and Fisher exact tests were used to assess predictors of LEV discontinuation. A p-value of <0.05 was considered statistically significant.. 150/240 (62%) children were on additional medications besides LEV for epilepsy management. Thirty-five percent children reported side effects, especially behavioral and mood concerns. Of the patients who reported side effects on LEV, 71% were taking vitamin B6 (n = 59). The rate of LEV discontinuation was significantly lower for children on vitamin B6 than children not taking B6, regardless of monotherapy or polypharmacy (49% v 88% respectively, p = 0.001). Over half of the patients who were able to remain on LEV reported improved behavior with B6 supplementation as compared to those who were unable to continue LEV (17/30, 57% versus 0/26, 0%; p < 0.001).. Levetiracetam side effects significantly impact the tolerability of this ASM in children with epilepsy. Our results suggest that vitamin B6 supplementation can significantly reduce the odds of discontinuing LEV due to its behavioral side effects.

Topics: Anticonvulsants; Child; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Humans; Levetiracetam; Piracetam; Pyridoxine; Retrospective Studies; Vitamin B 6

Levetiracetam (LEV) suppresses the upregulation of proinflammatory molecules that occurs during epileptogenesis after status epilepticus (SE). Based on previous studies, LEV likely helps prevent the onset of epilepsy after insults to the brain, unlike other conventional anti-epileptic drugs. Recently, we discovered that the increase in

Topics: Animals; Anticonvulsants; Disease Models, Animal; Epilepsy; Inflammation; Levetiracetam; Mice; Pilocarpine; Piracetam; Status Epilepticus

Angelman's syndrome (AS) is accompanied by specific changes in the EEG and genetically determined epilepsy. To analyze the neurological status, changes on EEG, MRI, the course of epilepsy in patients with Angelman syndrome (observed at the Svt. uca`s Institute of Child Neurology and Epilepsy).. 47 patients with a genetically verified diagnosis of AS (aged 2 to 20 years, mean age 8.5 years; 26 boys and 21 girls) were included. The diagnosis was established by DNA methylation in 32 patients and sequencing in 15 patients (12 cases of deletion and 3 cases of nucleotide substitution were identified).. Of the 47 patients, 45 have epilepsy. The seizures start up to 5 years of age, inclusive. For treatment, patients received various antiepileptic drugs. Long-term follow-up of epilepsy was followed in 40 of 47 patients, and 36 of 40 achieved drug remission. After several years without seizures, 24 out of 30 had a relapse, which was quickly stopped in 23 out of 30 patients. The severity of the disease is influenced by the nature of the mutation and the length of the deletion, as well as persistent epileptic seizures. The most effective AEDs in patients in our study are: in monotherapy, valproic acid, levetiraceiam, ethosuximide; in duotherapy, valproic acid in combination with levetiracetam or ethosuximide, less often levetiracetam with ethosuximide.. Early genetic diagnosis of AS facilitates the selection of AET.. Изучение неврологического статуса, клинико-ЭЭГ-картины, нейровизуализации и течения эпилепсии у детей с генетически подтвержденным синдромом Ангельмана.. Проанализированы данные 47 пациентов (26 мальчиков и 21 девочка в возрасте от 2 до 20 лет, средний возраст 8,5 года) с генетически верифицированным диагнозом «синдром Ангельмана». Диагноз установлен методом метилирования ДНК у 32 пациентов и секвенирования у 15 (при этом выявлено 12 случаев делеции и 3 — нуклеотидной замены).. У 45 из 47 пациентов отмечается эпилепсия. Приступы дебютировали до 5 лет включительно. Для лечения пациенты получали различные антиэпилептические препараты. Длительный катамнез по эпилепсии удалось проследить у 40 из 47 пациентов, у 36 из 40 — достигнута медикаментозная ремиссия. Через несколько лет ремиссии у 24 из 36 пациентов произошел рецидив, который удалось быстро купировать у 23 пациентов. На степень тяжести заболевания влияют характер мутации и протяженность делеции, а также персистирующие эпилептические приступы. Максимально эффективными антиэпилептическими препаратами у пациентов в исследовании оказались вальпроевая кислота, леветирацетам, этосуксимид в монотерапии; вальпроевая кислота в сочетании с леветирацетамом или этосуксимидом, реже леветирацетам с этосуксимидом в дуотерапии.. Ранняя генетическая диагностика синдрома Ангельмана облегчает подбор противоэпилептической терапии.

Topics: Angelman Syndrome; Anticonvulsants; Child; Electroencephalography; Epilepsy; Ethosuximide; Female; Humans; Levetiracetam; Male; Seizures; Valproic Acid

The prevalence of epilepsy is slightly higher in women than in men and sensitivity to seizure stimuli differs between sexes. Some evidence suggests sex differences in response to antiseizure medications exist mainly due to inconsistent pharmacokinetic differences; however, there is a lack of real-world evidence examining differences in response to antiseizure medications between men and women.. This was a retrospective population-based cohort study in five large US healthcare databases. The population included adult patients with epilepsy, newly exposed to levetiracetam, and naive to antiseizure medication. The first exposure to levetiracetam was the index date. The requirement that all patients received the same medication was done to avoid potential confounding due to differences in index treatment. The outcome was the development of treatment resistant epilepsy (TRE), defined as having at least three distinct antiseizure medications in 1 year. The proportion of patients who developed TRE within 1 year following the index date was calculated. To compare the risk of developing TRE between sexes, relative risks (RR) and 95% confidence intervals (CI) were calculated, and estimates were pooled using meta-analytic techniques stratified by gender and age.. A total of 147 334 subjects were included in the databases, 50.8% were women, and 4.27% developed TRE. The comorbid profile differed greatly between men and women; however, the types of epilepsy syndromes observed during baseline were similar between the two groups. Across all databases, women were more likely to develop TRE than men (pooled RR 1.27, 95% CI 1.17-1.38). Results remained similar when stratified by age.. This study assessed sex differences in response to antiseizure medications using the development of TRE as a proxy for effectiveness. Women newly exposed to levetiracetam were 27% more likely to develop TRE than men, independent of age.

Topics: Adult; Anticonvulsants; Cohort Studies; Epilepsy; Female; Humans; Levetiracetam; Male; Retrospective Studies

Levetiracetam, a widely used anticonvulsant drug in children and adolescents, has been associated with irritability, psychosocial symptoms, and low quality of life, which are also influenced by other epilepsy variables.. The objective of this study was to investigate the level of treatment-related irritability in adolescents receiving levetiracetam, and to evaluate the relationship between irritability levels and psychosocial symptoms, and quality of life.. A cross-sectional, case-control study was conducted. Consecutive adolescent patients with epilepsy aged 11-17 years with partial or generalized seizures, treated with either levetiracetam or valproic acid for at least 6 months, and healthy controls were recruited. The Affective Reactivity Index parent report and self-report, Strengths and Difficulties Questionnaire, and Pediatric Quality of Life Inventory-Psychosocial subscale were utilized to assess irritability, psychosocial symptoms, and functioning.. A total of 120 participants were analyzed; 33 patients in the LEV group, 45 patients in the VPA group, and 42 healthy controls. Both self and parent report irritability levels of the LEV group were found to be significantly higher than those of healthy controls. The irritability levels of the LEV and VPA groups were not statistically different, but still the LEV group had higher irritability levels on both scales. In the LEV group, irritability was positively correlated with behavioral, emotional, and attention/hyperactivity problems, and also negatively correlated with psychosocial quality of life.. Adolescents with epilepsy using LEV have a high level of irritability and this is associated with some psychosocial symptoms and poor quality of life.

Topics: Adolescent; Anticonvulsants; Case-Control Studies; Child; Cross-Sectional Studies; Epilepsy; Humans; Levetiracetam; Piracetam; Quality of Life; Valproic Acid

Pharmacokinetics (PK) of a drug drive its exposure, efficacy, and tolerability. A thorough preclinical PK assessment of antiseizure medications (ASMs) is therefore essential to evaluate the clinical potential. We tested protection against evoked seizures of prototype ASMs in conjunction with analysis of plasma and brain PK as a proof-of-principle study to enhance our understanding of drug efficacy and duration of action using rodent seizure models.. In vivo seizure protection assays were performed in adult male CF-1 mice and Sprague Dawley rats. Clobazam (CLB), N-desmethyl CLB (NCLB), carbamazepine (CBZ), CBZ-10,11-epoxide (CBZE), sodium valproate (VPA), and levetiracetam (LEV) concentrations were quantified in plasma and brain using liquid chromatography-tandem mass spectrometry. Mean concentrations of each analyte were calculated and used to determine PK parameters via noncompartmental analysis in Phoenix WinNonLin.. NCLB concentrations were approximately 10-fold greater than CLB in mice. The antiseizure profile of CLB was partially sustained by NCLB in mice. CLB concentrations were lower in rats than in mice. CBZE plasma exposures were approximately 70% of CBZ in both mice and rats, likely contributing to the antiseizure effect of CBZ. VPA showed a relatively short half-life in both mice and rats, which correlated with a sharp decline in efficacy. LEV had a prolonged brain and plasma half-life, associated with a prolonged duration of action in mice.. The study demonstrates the utility of PK analyses for understanding the seizure protection time course in mice and rats. The data indicate that distinct PK profiles of ASMs between mice and rats likely drive differences in drug efficacy between rodent models.

Topics: Animals; Anticonvulsants; Benzodiazepines; Carbamazepine; Clobazam; Epilepsy; Levetiracetam; Male; Mice; Rats; Rats, Sprague-Dawley; Seizures

To determine which antiepileptic drugs pregnant women receive by trimester.. This retrospective cohort study using the IBM Watson Health MarketScan Research Databases evaluated which antiepileptic drugs pregnant women with epilepsy received by trimester. Women with aged 15-54 years with a history of seizure disorder who underwent a delivery hospitalization between 2008 and 2017 were included in the analysis. Descriptive statistics were performed.. Of 34,144 women with a seizure disorder diagnosis and a delivery hospitalization, 10,289 (30.1%) received an anti-epileptic medication during pregnancy of which more than half received lamotrigine or levetiracetam. Other antiepileptic medications used by >5% of the population during any one trimester in the study period included carbamazepine, clonazepam, and topiramate. In evaluating medication use in the 1st trimester versus the 2nd trimester, clonazepam use decreased 32.0% (95% CI 60.0%, 77.0%) from 5.6% to 3.8% of patients receiving antiepileptics from the 1st to the 2nd trimester, gabapentin deceased 22.1% (95% CI 0.68%, 0.90%) from 4.1% to 3.2%, and topiramate decreased 30.0% (95% CI 62.8%, 77.9%) from 7.2% to 5.1%. In comparison, levetiracetam increased from 22.5% to 33.3% between the 1st and 3rd trimester and lamotrigine 22.2% to 27.5% between the 1st and 3rd trimester, 48.3% and 24.0% increases respectively.. Antiepileptic drugs with less favorable fetal risk profiles such as topiramate decreased by trimester while medications with more favorable fetal risk profiles such as lamotrigine and levetiracetam increased. These findings broadly support that there are opportunities to improve pre-conceptional counseling of women with epilepsy.

Topics: Anticonvulsants; Clonazepam; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Pregnancy; Retrospective Studies; Topiramate

The management of pregnant women with epilepsy (WWE) treated with antiepileptic drugs (AEDs) polytherapy poses a great challenge. The purpose of this study was to evaluate the major congenital malformations (MCMs) associated with AED polytherapy, to assess the impacts of polytherapy regimens on seizure control and breastfeeding, and to determine the potential predictors for pregnancy outcomes.. This study was based on prospectively acquired data from a registry enrolling WWE in early pregnancy from Feb 2010 to July 2019, in which 123 pregnancies in 110 WWE were exposed to 27 different AED combinations.. There were 123 pregnancies in 110 WWE analyzed in our study. The live birth rate was 86.2 % and the risk of MCMs was 10.4 %. Multivariate analysis indicated that prenatal exposure to phenobarbital (odds ratio [OR], 17.424; 95 %CI, 1.510-201.067; P = 0.022) and topiramate (OR, 9.469; 95 %CI, 1.149-62.402; P = 0.036) was associated with increased risk of MCMs. Valproate (OR, 4.441; 95 %CI, 1.165-16.934; P = 0.029), phenobarbital (OR, 13.636; 95 %CI, 2.146-86.660; P = 0.006) and topiramate (OR, 7.527; 95 %CI, 1.764-32.118; P = 0.006) were significantly correlated with adverse pregnancy outcomes. Among 67 pregnancies in four combinations over 10 patients, 15 (22.4 %) remained seizure free through pregnancy, seizure frequency increased in 17 (25.4 %), decreased in 24 (35.8 %) women, in 26 (38.8 %) remained unchanged. Only 23.6 % of mothers undertook exclusive breastfeeding. Planned pregnancy was the only independent factor significantly associated with decreased risk of adverse pregnancy outcomes (OR, 0.139; 95 % CI, 0.051-0.382; P < 0.001). Notably, no adverse pregnancy outcome was recorded in pregnancies exposed to the combination of lamotrigine plus levetiracetam.. Prenatal exposure to the combinations containing valproate, phenobarbital, or topiramate was associated with increased risk of adverse pregnant outcomes. AED-related teratogenicity may be reduced by planned pregnancy in WWE exposed to polytherapy. Our findings also suggest the combination of lamotrigine and levetiracetam seems to be most desirable to balance seizure control and fetal safety.

Topics: Anticonvulsants; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Phenobarbital; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Registries; Topiramate; Valproic Acid

To study the prevalence and directionality of comorbid epilepsy and psychosis in Norway.. The Norwegian Prescription Database (NorPD) provided individual-based information on all antiseizure medications (ASMs) and antipsychotic drugs (APDs) dispensed during 2004-2017. Subjects were ≥18 years of age at the end of the study period. Diagnosis-specific reimbursement codes from the 10th revision of the International Classification of Diseases/2nd edition of the International Classification of Primary Care (ICD-10/ICPC-2) combined with ATC codes were used as indicators of diagnosis. Subjects had collected ASMs for epilepsy or APDs for psychosis at least four times, at least once issued with an ICD-10 code from the specialist healthcare service. Directionality was analyzed in subjects receiving both treatments. To reduce prevalent comorbidity bias, we employed a four-year comorbidity-free period (2004-2007). The use of specific ASMs and APDs was analyzed.. A total of 31,289 subjects had collected an ASM for epilepsy at least four times, 28,889 an APD for psychosis. Both the prevalence of treatment for epilepsy and of treatment for psychosis was 0.8%. Further, 891 subjects had been treated for both conditions; 2.8% with epilepsy had been treated for psychosis, and 3.1% with psychosis had been treated for epilepsy. Among 558 subjects included in the analyses of directionality, 56% had collected the first APD before an ASM, whereas 41% had collected an ASM first. During the last year prior to comorbidity onset, levetiracetam, topiramate, or zonisamide had been used for epilepsy by approximately 40%, whereas olanzapine and quetiapine were most used in patients with psychosis, and clozapine in 13%.. The proportion of patients with prior antipsychotic treatment at onset of epilepsy is higher than previously acknowledged, as demonstrated in this nation-wide study. Apart from a shared neurobiological susceptibility, the bidirectionality of epilepsy and psychosis may be influenced by various environmental factors, including the interaction of pharmacodynamic effects. APDs may facilitate seizures; ASMs may induce psychiatric symptoms. In patients with combined treatment, these potential drug effects should receive ample attention, along with the psychosocial consequences of the disorders. A prudent multi-professional approach is required.

Topics: Anticonvulsants; Antipsychotic Agents; Epilepsy; Humans; Levetiracetam; Psychotic Disorders; Zonisamide

The use of many antiseizure medications (ASMs) is limited due to pharmacoresistance and dose-limiting side effects, suggesting an unmet need for novel therapeutic approaches. The neuropeptide galanin reduces seizures in several preclinical seizure and epilepsy models, but its clinical utility is limited due to rapid metabolism and poor blood-brain barrier penetration. The lead galanin analog 810-2 is systemically bioavailable and reduces seizures when administered alone. Further development of this analog, with the potential for use as an add-on therapy in patients with epilepsy, requires a better understanding of the use of this analog in combination with approved ASMs. We sought to evaluate 810-2 in combination with commonly used ASMs in rodent models of seizures.. The mouse 6-Hz seizure assay was used to test efficacy of 810-2 in combination with levetiracetam (LEV), valproic acid (VPA), or lacosamide (LCM) using a 1:1 dose ratio in isobolographic studies. Further characterization was performed for the combination of 810-2 and LEV in the mouse corneal kindling and rat 6-Hz assays.. Whereas the combination of 810-2 with VPA and LCM yielded additive interactions, the combination of 810-2 with LEV demonstrated a synergistic interaction in the mouse 6-Hz assay. Supra-additive effects were also observed in the mouse corneal kindling and rat 6-Hz assays for this combination.. The combination of 810-2 with LEV suggests the potential for this galanin analog to be further developed as an add-on therapy for patients with epilepsy, particularly when coadministered with LEV.

Topics: Animals; Epilepsy; Levetiracetam; Mice; Rats; Rodentia; Seizures

Triple X syndrome, is an often undiagnosed chromosomal abnormality with an incidence of 1/1000 females. Main associated disorders are urogenital malformations, premature ovarian failure or primary amenorrhea, gastrointestinal problems, psychiatric disorders and epilepsy. To date, triple X is not related to a specific epileptic syndrome. Therefore, the purpose of this clinical series is to analyze seizure semiology, electroencephalogram features and the long-term outcome of 13 patients with epilepsy and triple X syndrome.. We retrospectively evaluated the long-term seizure outcome in patients with triple X syndrome who had been referred to 11 Epilepsy Centers in Italy. A close electroclinical follow-up was made for at least 2 years and outcomes were reported.. Our case series confirms that epilepsy is not an occasional finding but part of the phenotypic spectrum of this syndrome. The seizure semiology shows an higher prevalence of focal seizures in 62% of patients. EEG findings of focal epileptic activity were reported in 85% of patients. Anti-seizure medications were successful in all our patients whom in most cases were responsive to monotherapy.. According to our case series most successful drugs were VPA and LEV. Long term prognosis of epilepsy in our case series was good. Our experience suggests that all triple X patients achieve good seizure control and in 69% of cases normalization of the EEG.

Topics: Anticonvulsants; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Retrospective Studies; Valproic Acid

Levetiracetam was presented as a drug with linear pharmacokinetics. There is currently evidence on its extensive pharmacokinetic variability in real clinical practice.. To describe levetiracetam pharmacokinetic variability in patients with epilepsy in real clinical practice. To evaluate the effect on levetiracetam levels of gender, age, renal function, and polytherapy. To describe how clinicians prescribe based on age and co-medication.. Retrospective analysis of epilepsy patients treated with levetiracetam for whom plasma levels were available.. 151 patients. Median levetiracetam level of 17.75 mg/L, median dose of 2000 mg/day. There was a significant correlation between daily dose and serum levels (p < 0.01). There was a 18.1% increase in levetiracetam concentration/dose ratio in patients over 65 years of age (p < 0.05) that also correlated with decreased glomerular filtration (p < 0.01). Clinicians corrected doses so patients over 65 years had similar levels than younger patients. There was a 30.1% decrease of concentration/dose ratio in patients on polytherapy with potent enzyme inducer antiseizure medication (p < 0.05), and a 46.3% decrease for carbamazepine (p < 0.01). Clinicians did not correct doses, so patients treated with levetiracetam and carbamazepine had 27.5% lower levels than patients taking other polytherapy.. The pharmacokinetic variability of levetiracetam is wider than originally thought. Age and co-medication with strong enzyme-inducing drugs, especially carbamazepine, significantly influence levetiracetam levels. Clinicians at our center did not consider this interaction and prescribed similar doses of levetiracetam when it was used in combination with these drugs or with others, so they probably were not aware of this interaction.

Topics: Anticonvulsants; Carbamazepine; Epilepsy; Humans; Levetiracetam; Piracetam; Retrospective Studies

Topics: Anticonvulsants; Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Piracetam; Seizures

Lamotrigine toxicity can cause coma, seizures, and intraventricular conduction disturbances, and treatment options include good supportive care. We report two cases of lamotrigine poisoning in which multiple-dose activated charcoal may have shortened the elimination half-life of lamotrigine.. A 21-year-old woman ingested 15.6 g lamotrigine, 14 g levetiracetam, and 15 mg clonazepam. She became comatose and developed generalized tonic seizure. One hour post-ingestion, 50 g activated charcoal was administered. Starting 11 h post-ingestion, 25 g activated charcoal was administered every 4 h for 4 doses. The peak concentration of serum lamotrigine was 49.5 µg/mL, and the elimination half-life after commencement of multiple-dose activated charcoal was 6.5 h.. A 46-year-old woman ingested 0.3 g lamotrigine and 0.1 g topiramate twice, 2 h apart. She became drowsy, complained of blurred vision, vertigo, nausea, and vomited. An initial dose of 50 g activated charcoal was administered at 4.5 h post-second ingestion, and subsequent doses of 25 g (total of 3 doses) were administered every 4 h, commencing at 8.5 h post-second ingestion. The peak concentration of serum lamotrigine was 19.9 µg/mL, and the elimination half-life after commencement of multiple-dose activated charcoal was 9.3 h.. The mean elimination half-life of lamotrigine in healthy volunteers and epileptic patients receiving lamotrigine monotherapy is 22.8-37.4 h. In our two cases, multiple-dose activated charcoal may have shortened the elimination half-life of lamotrigine, possibly by inhibiting enterohepatic circulation. Multiple-dose activated charcoal should be considered an option for treating lamotrigine poisoning.

Topics: Adult; Anticonvulsants; Charcoal; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Middle Aged; Poisoning; Young Adult

To compare the hazard for all-cause mortality and mortality due to heart failure (HF) between valproate (VPA) and levetiracetam (LEV)/lamotrigine (LTG) users in patients aged ≥ 65 with comorbidities of epilepsy and HF.. This was a cohort study using Danish registers during the period from January 1996 to July 2018. The study population included new users of LTG, LEV or VPA. A Cox regression model was used to compute crude and adjusted hazard ratios for the outcome, using an intention-to-treat approach. Average treatment effects (eg, 1-year absolute risks), risk differences and the ratio of risks were computed using the G-formula based on a Cox regression model for the outcomes at the end of the follow-up period.. We included 1345 subjects in the study population. VPA users (n = 696), when compared to LTG/LEV users (n = 649), had an increased hazard of mortality due to HF (hazard ratio [HR] 2.39; 95% CI 1.02-5.60) and to all-cause mortality (HR 1.37; 95% CI 1.01-1.85) in both crude and adjusted analyses. The 1-year absolute risks for all-cause mortality were 29% (95% CI 25%-33%) and 22% (95% CI 18%-26%) for VPA and LTG/LEV users. For mortality due to HF, 1-year absolute risks were 5% (95% CI 3%-7%) and 2% (95% CI 1%-4%) for VPA and LTG/LEV users. The average risk ratio, with LTG/LEV as the reference group, was 1.31 (95% CI 1.02-1.71) for all-cause mortality and 2.35 (95% CI 1.11-5.76) for HF mortality.. In older people with HF and epilepsy, treatment with VPA was associated with a higher risk of all-cause and HF mortality compared to treatment with LTG and LEV.

Topics: Aged; Anticonvulsants; Cohort Studies; Denmark; Epilepsy; Heart Failure; Humans; Lamotrigine; Levetiracetam; Prognosis; Valproic Acid

Topics: Accidental Falls; Aged; Anticonvulsants; Clinical Pharmacy Information Systems; Deprescriptions; Drug Prescriptions; Drug-Related Side Effects and Adverse Reactions; Electronic Health Records; Electronic Prescribing; Epilepsy; Female; Humans; Levetiracetam; Medical Record Linkage; Medication Therapy Management; Phenytoin; Practice Patterns, Physicians'

This study was undertaken to evaluate the long-term efficacy, retention, and tolerability of add-on brivaracetam (BRV) in clinical practice.. A multicenter, retrospective cohort study recruited all patients who initiated BRV between February and November 2016, with observation until February 2021.. Long-term data for 262 patients (mean age = 40 years, range = 5-81 years, 129 men) were analyzed, including 227 (87%) diagnosed with focal epilepsy, 19 (7%) with genetic generalized epilepsy, and 16 (6%) with other or unclassified epilepsy syndromes. Only 26 (10%) patients had never received levetiracetam (LEV), whereas 133 (50.8%) were switched from LEV. The length of BRV exposure ranged from 1 day to 5 years, with a median retention time of 1.6 years, resulting in a total BRV exposure time of 6829 months (569 years). The retention rate was 61.1% at 12 months, with a reported efficacy of 33.1% (79/239; 50% responder rate, 23 patients lost-to-follow-up), including 10.9% reported as seizure-free. The retention rate for the entire study period was 50.8%, and at last follow-up, 133 patients were receiving BRV at a mean dose of 222 ± 104 mg (median = 200, range = 25-400), including 52 (39.1%) who exceeded the recommended upper dose of 200 mg. Fewer concomitant antiseizure medications and switching from LEV to BRV correlated with better short-term responses, but no investigated parameters correlated with positive long-term outcomes. BRV was discontinued in 63 (24%) patients due to insufficient efficacy, in 29 (11%) for psychobehavioral adverse events, in 25 (10%) for other adverse events, and in 24 (9%) for other reasons.. BRV showed a clinically useful 50% responder rate of 33% at 12 months and overall retention of >50%, despite 90% of included patients having previous LEV exposure. BRV was well tolerated; however, psychobehavioral adverse events occurred in one out of 10 patients. Although we identified short-term response and retention predictors, we could not identify significant predictors for long-term outcomes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Child; Child, Preschool; Drug Therapy, Combination; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Pyrrolidinones; Retrospective Studies; Treatment Outcome; Young Adult

Contemporary research indicates the role of neuroinflammation/inflammatory markers in epilepsy. In addition, comorbidities such as anxiety and poor health-related quality of life are vital concerns in clinical care of pediatric patients with epilepsy. This open-label, prospective, observational study evaluated the effect of valproate and add-on levetiracetam on serum levels of C-C motif ligand 2 (CCL2) and Interleukin-1 beta (IL-1β) in pediatric patients with epilepsy. We also studied effect of valproate and add-on levetiracetam on anxiety and health-related quality of life (HRQoL) in specified age subgroups.. Children aged 1 to 12 years, diagnosed with epilepsy (generalized or focal seizures), treated with valproate (n = 40) and valproate with add-on levetiracetam (n = 40) were included. All patients were followed up for 16 weeks and assessed for changes in serum CCL2 and IL-1β levels. Spence Children Anxiety Scale short version (SCAS-S) and QOLCE-16 scales were used to measure anxiety and HRQoL, respectively, in specific age groups.. The serum CCL2 level decreased significantly (p < .001) from 327.95 ± 59.07 pg/ml to 207.02 ± 41.50 pg/ml in the valproate group and from 420.65 ± 83.72 pg/ml to 250.06 ± 46.05 pg/ml in the add-on levetiracetam group. Serum IL-1β level did not change significantly in both groups. Spence Children Anxiety Scale short version scores were decreased and QOLCE-16 scores were increased significantly (p < .001) in both valproate and add-on levetiracetam groups.. The results of our study suggest that valproate and levetiracetam led to decrease serum CCL2 levels without any change in serum IL-1β levels in children with epilepsy. Anti-inflammatory property of valproate and levetiracetam might underlie their antiepileptic effect and CCL2 could be a potential marker of drug efficacy in epilepsy. Also, valproate and levetiracetam reduced anxiety and improved quality of life in children with epilepsy in the age groups evaluated.

Topics: Anticonvulsants; Biomarkers; Child; Epilepsy; Humans; Levetiracetam; Neuroinflammatory Diseases; Piracetam; Prospective Studies; Quality of Life; Valproic Acid

Patients with brain tumor-related epilepsy (BTRE) are at a higher risk of significant morbidity, lower quality of life, and increased risk of mortality. We surveyed providers regarding anti-seizure medication (ASM) management in pediatric BTRE to determine if practices are standard or markedly variable.. An anonymous voluntary online survey was sent to members of the Child Neurology Society. Providers were asked specific questions regarding initiation and wean of ASMs and if this was dependent on multiple factors. Demographic information was collected.. Fifty-one providers responded to the survey. Ninety-four percent of providers would start an ASM after a second seizure. Eighty-four percent chose levetiracetam as the preferred ASM. Management was variable when based on tumor location, extent of surgical resection, pathology, and tumor prognosis. Statistically significant differences in responses regarding management were identified when comparing neurologists and epileptologists, providers with formal neuro-oncology or epilepsy training, providers at large institutions, and years of experience. For patients who underwent a gross total resection of the tumor, neuro-oncology and epilepsy-trained providers were more likely to wean off ASMs (p < 0.049). Providers without formal training in neuro-oncology or epilepsy were more likely to get an EEG prior to making a decision about weaning off ASMs (p < 0.016).. These results suggest that ASM management in BTRE varies greatly according to sub-specialty and experience. Further studies and potential development of guidelines are needed to identify the most appropriate management of ASMs for BTRE.

Topics: Anticonvulsants; Brain Neoplasms; Child; Epilepsy; Humans; Levetiracetam; Quality of Life

To evaluate the current trends and factors associated with the first anti-seizure medications (ASMs) prescribed for epilepsy in Taiwan.. Data for patients with epilepsy were collected from the National Health Insurance Research Database, a population-based claims database. We selected patients with newly diagnosed epilepsy from 2013 to 2016. Multivariate logistic regression was used to examine the factors associated with the selection of newer ASMs for the first prescription.. A total of 73,891 patients with newly diagnosed epilepsy were eligible for the study, and the annual incidence was approximately 0.79 per 1,000 people. The five ASMs most prescribed for monotherapy were valproic acid, phenytoin, levetiracetam, gabapentin, and oxcarbazepine, accounting for nearly 90% of all ASMs. Valproic acid was the most-prescribed ASM (more than 30%), and levetiracetam has replaced phenytoin as the second choice since 2015. Factors associated with the selection of newer ASMs for the first prescription were patients' year of diagnosis, gender, socioeconomic level, and previous or existing comorbidities and the profiles of the care providers (accreditation level, service volume, geographic location, and degree of urbanization of the surrounding area).. The data indicated that the trends in ASMs first prescribed for patients in Taiwan accorded with most of the international epilepsy treatment guidelines. However, there were some differences between our results and those in developed countries. In addition, we observed a large urban-rural disparity in the administration of ASMs.

Topics: Anticonvulsants; Epilepsy; Humans; Lamotrigine; Levetiracetam; Taiwan

Patients with epilepsy have a higher mortality rate than the general population. Up-to-date estimates of epilepsy incidence, prevalence, and medication use are critical to assist policymaking.. Using the National Taiwan Insurance Research Database, the standardized incidence and prevalence of epilepsy were estimated in each calendar year from 2007 to 2015. We used the incident cases of epilepsy to analyze the change in prescribing patterns from 2007 to 2015. Joinpoint regression was used to estimate secular trends.. From 2007 to 2015, the age- and sex-standardized incidence decreased from 0.72 (95% confidence interval [CI] 0.70-0.73) to 0.54 (95% CI 0.53-0.55) per 1,000 person-years, giving an annual percentage change (APC) of -2.73 (p < 0.05). Among patients younger than 20 years, the incidence did not change significantly. The age- and sex-standardized prevalence decreased from 6.94 (95% CI 6.90-6.98) to 6.86 (95% CI, 6.82-6.89) per 1,000 people, giving an APC of -0.31 (p < 0.05). However, the prevalence increased in the 35- to 49- and 50- to 64-year age-groups. The most common first-line anticonvulsant was phenytoin in 2007 and valproate in 2015. The use of levetiracetam, clobazam, and valproate increased during the study period, with APCs of 25.48% (95% CI 19.97-31.24), 6.41 (3.09-9.85), and 2.83 (1.51-4.16), respectively. The use of carbamazepine, phenytoin, and topiramate decreased; the APCs were -23.86% (95% CI -25.25 to -22.44), -6.61 (-8.40 to -4.79), and -4.29% (-7.87 to -0.57), respectively.. The overall prevalence and incidence of epilepsy decreased slightly from 2007 to 2015. The prescribed first-line anticonvulsant also changed over time.

Topics: Epilepsy; Humans; Incidence; Levetiracetam; Prevalence; Taiwan

Epilepsy, a neuronal disorder has affected 1% of the world's population. Almost 35-40% of these patients get resistant to available anti-epileptic drugs (AEDs). Recent studies have shown the role of inflammation in the pathophysiology of epilepsy and a combination of anti-inflammatory and antiepileptic drugs could prove beneficial against epileptic seizures. Therefore, we aimed to examine the effect of levetiracetam (LEV) and diclofenac sodium (DFS) combination on pilocarpine (PLC) induced epileptic seizures in mice. Mice were divided into control and treatment groups. LEV alone and in combination with DFS was given for 3 days. On 3rd day after administering the required drugs, pilocarpine challenge was given intraperitoneally. Then, behavioral changes were observed for 90 minutes, including latency to first seizure, continuous seizures, duration of continuous seizures, and survival rate. Results showed significant improvement in the latencies to first (P<0.001) and continuous seizures (P<0.05), duration of the continuous seizure (p=0.001), and survival rate (P<0.01) in the combination treatment group as compared to the control or individual drug treatment groups. DFS enhances the efficacy of LEV, however, further mechanistic studies will be required to conclude if DFS can be given in combination with LEV for epilepsy treatment.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Behavior, Animal; Convulsants; Diclofenac; Drug Synergism; Epilepsy; Levetiracetam; Male; Mice; Pilocarpine; Seizures; Survival Analysis

Sleep is a reversible behavioural state of perceptual disengagement from and unresponsiveness to the environment, which is required for neural plasticity and memory consolidation. Sleep disorders are common in patients with epilepsy. The main causes of sleep disturbances are coexisting sleep disorders, impact of seizures and epileptic activity, and the effects of antiepileptic drugs. Sleep and epilepsy have reciprocal effects - on one hand electrical brain activity during sleep is a strong modulator of epileptic activity and on the other epileptic activity during sleep may disrupt sleep architecture. The most common side effects of anticonvulsants include alterations in sleep architecture and variation in the degree of daytime sleepiness. Their effects on sleep and daytime sleepiness are variable and it is often difficult to distinguish whether the improved seizure control and epileptic activity is a direct result of anticonvulsants or associated with improved sleep quality. Levetiracetam is a new generation anticonvulsant used to treat both focal and generalized epilepsy. Its satisfactory safety and tolerability explain its wide usage in the clinical practice and necessitates more profound knowledge on its effects on sleep quality. There have been few reports about its effects on sleep architecture and daytime sleepiness. A short summary of the studies concerning this topic is presented. Main disadvantages of the studies are: the small sample size, comparison of the results obtained in healthy volunteers with patients with epilepsy, short observation duration, variations of dosage, different evaluation modalities and concomitant AED therapy. Future prospective studies on subjective and objective effects of Levetiracetam on sleep architecture and daytime sleepiness are needed to better understand its impact on sleep in order to improve epilepsy patients' quality of life, seizure control and sleep disturbances.

Topics: Anticonvulsants; Disorders of Excessive Somnolence; Epilepsy; Humans; Levetiracetam; Prospective Studies; Quality of Life; Seizures; Sleep; Sleep Wake Disorders

The study is aimed at comparing effects of older drugs like carbamazepine (CBZ) and newer agent like levetiracetam (LEV) on polycystic ovarian syndrome (PCOS) in women with epilepsy (WWE).. An interviewer-based questionnaire was used to obtain relevant clinical information from 50 WWE on CBZ and LEV monotherapy, respectively, and 50 age-matched controls. The diagnosis of epilepsy was clinical with electroencephalographic features taken into consideration and the seizures classified using the 2017 International League Against Epilepsy classification. The diagnosis of PCOS was based on the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine.. The frequency of PCOS and its subcomponent were higher among WWE compare to controls. PCOS was present in 22 (44%) of LEV group compare to 8 (16%) CBZ group. The frequency of its subcomponent was higher among those on LEV except for comparable effect with regard to oligomenorrhea. The levels of the sex steroid hormone were comparable in both groups of WWE except luteal phase luteinizing hormone, which was lower among the LEV group (P .001). The follicular phase estradiol level was lower (P .021), and follicle-stimulating hormone level was about 2-fold higher (P .03) among WWE compare to controls. The mean value testosterone was significantly lower among controls compared to WWE.. The increased frequency of PCOS and its subcomponent and the unsatisfactory effect of LEV compared to CBZ on reproductive endocrine function underscore the need for routine reproductive endocrine evaluation to improve overall quality of life.

Topics: Adult; Anticonvulsants; Carbamazepine; Epilepsy; Female; Humans; Levetiracetam; Nigeria; Polycystic Ovary Syndrome

Symptoms of COVID-19, as reported during the SARS-CoV-2 pandemic in 2019-2020, are primarily respiratory and gastrointestinal, with sparse reports on neurological manifestations. We describe the case of a 17-year old female with Cornelia de Lange syndrome and well controlled epilepsy, who sustained significant cortical injury during a COVID-19 associated multi-inflammatory syndrome.

Topics: Acute Kidney Injury; Adolescent; Airway Extubation; Anticonvulsants; Blood Coagulation Disorders; Bone Marrow Failure Disorders; Brain Diseases; Brain Edema; C-Reactive Protein; COVID-19; De Lange Syndrome; Disease Progression; Electroencephalography; Epilepsy; Female; Ferritins; Humans; Influenza B virus; Influenza, Human; Levetiracetam; Magnetic Resonance Imaging; Midazolam; Necrosis; Phenobarbital; Pseudomonas Infections; Respiration, Artificial; Rhabdomyolysis; SARS-CoV-2; Seizures; Sepsis; Systemic Inflammatory Response Syndrome; Tachycardia, Ventricular

This study examined the antiepileptogenic potential of the antiseizure drug (ASD) levetiracetam (LEV) using the in vitro traumatized-slice and in vivo controlled cortical impact (CCI) models of traumatic brain injury (TBI) in rats when administered early after the injury. For the in vitro model, acute coronal slices (400-450 μm) of rat neocortex (P21-32) were injured via a surgical cut that separated the superficial layers from the deeper regions. Persistent stimulus-evoked epileptiform activity developed within 1-2 h after trauma. In randomly selected slices, LEV (500 μM) was bath-applied for 1 h starting immediately or delayed by 30-80 min after injury. Treated and untreated slices were examined for epileptiform activity via intracellular and extracellular recordings. For the in vivo model, rats (P24-32) were subjected to a non-penetrating, focal, CCI injury targeting the neocortex (5.0 mm diameter; 2.0 mm depth). Immediately after injury, rats were given either a single dose of LEV (60-150 mg/kg, i.p.) or the saline vehicle. At 2-3 weeks after the injury, ex vivo cortical slices were examined for epileptiform activity. The results from the traumatized-slice experiments showed that in vitro treatment with LEV within 60 min of injury significantly reduced (> 50%) the proportion of slices that exhibited stimulus-evoked epileptiform activity. LEV treatment also increased the stimulus intensity required to trigger epileptiform bursts in injured slices by 2-4 fold. Consistent with these findings, LEV treatment of CCI-injured rats (n = 15) significantly reduced the proportion of animals that exhibited spontaneous and stimulus-evoked epileptiform bursts in ex vivo cortical slices compared to saline-treated controls (n = 15 rats), and also significantly increased the stimulus intensity required to evoke epileptiform bursts. These results suggest that early administration of LEV has the potential to prevent or reduce posttraumatic epileptogenesis and that there may be a narrow therapeutic window for successful prophylactic intervention.

Topics: Animals; Brain Injuries, Traumatic; Cerebral Cortex; Electrophysiological Phenomena; Epilepsy; Female; Levetiracetam; Male; Neocortex; Nootropic Agents; Rats; Rats, Sprague-Dawley; Time-to-Treatment

Epileptogenesis, the gradual process that leads to epilepsy after brain injury or genetic mutations, is a complex network phenomenon, involving a variety of morphological, biochemical and functional brain alterations. Although risk factors for developing epilepsy are known, there is currently no treatment available to prevent epilepsy. We recently proposed a multitargeted, network-based approach to prevent epileptogenesis by rationally combining clinically available drugs and provided first proof-of-concept that this strategy is effective. Here we evaluated eight novel rationally chosen combinations of 14 drugs with mechanisms that target different epileptogenic processes. The combinations consisted of 2-4 different drugs per combination and were administered systemically over 5 days during the latent epileptogenic period in the intrahippocampal kainate mouse model of acquired temporal lobe epilepsy, starting 6 h after kainate. Doses and dosing intervals were based on previous pharmacokinetic and tolerability studies in mice. The incidence and frequency of spontaneous electrographic and electroclinical seizures were recorded by continuous (24/7) video linked EEG monitoring done for seven days at 4 and 12 weeks post-kainate, i.e., long after termination of drug treatment. Compared to vehicle controls, the most effective drug combination consisted of low doses of levetiracetam, atorvastatin and ceftriaxone, which markedly reduced the incidence of electrographic seizures (by 60%; p<0.05) and electroclinical seizures (by 100%; p<0.05) recorded at 12 weeks after kainate. This effect was lost when higher doses of the three drugs were administered, indicating a synergistic drug-drug interaction at the low doses. The potential mechanisms underlying this interaction are discussed. We have discovered a promising novel multitargeted combination treatment for modifying the development of acquired epilepsy.

Topics: Animals; Anticonvulsants; Atorvastatin; Ceftriaxone; Drug Delivery Systems; Drug Evaluation, Preclinical; Drug Therapy, Combination; Electroencephalography; Epilepsy; Kainic Acid; Levetiracetam; Male; Mice; Treatment Outcome

Topics: Anticonvulsants; Brain Neoplasms; Cerebral Cortex; Constriction, Pathologic; Electrodes, Implanted; Electroencephalography; Epilepsy; Glioma; Humans; Laryngeal Diseases; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Seizures

We analyzed the resting state functional magnetic resonance images to investigate the alterations of neural networks in patients with glioma-related epilepsy (GRE).. Fifty-six patients with right temporal lower-grade glioma were divided into GRE (n = 28) and non-GRE groups. Twenty-eight healthy subjects were recruited after matching age, sex, and education level. Sensorimotor, visual, language, and left executive control networks were applied to generate functional connectivity matrices, and their topological properties were investigated.. No significant alterations in functional connectivity were found. The least significant discovery test revealed differences only in the language network. The shortest path length, clustering coefficient, local efficiency, and vulnerability were greater in the non-GRE group than in the other groups. The nodal efficiencies of two nodes (mirror areas to Broca and Wernicke) were weaker in the non-GRE group than in the other groups. The node of degree centrality (Broca), nodal local efficiency (Wernicke), and nodal clustering coefficient (temporal polar) were greater in the non-GRE group than in the healthy group.. Different tumor locations alter different neural networks. Temporal lobe gliomas in the right hemisphere altered the language network. Glioma itself and GRE altered the network in opposing ways in patients with right temporal glioma.

Topics: Adult; Anticonvulsants; Brain Neoplasms; Epilepsy; Female; Glioma; Humans; Language; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Net; Temporal Lobe

Levetiracetam (LEV) is a second-generation antiepileptic drug with high efficacy and tolerability in children and adults with epilepsy. We aimed to retrospectively assess the long-term efficacy, tolerability, and safety of LEV monotherapy in children with epilepsy.. All patients who received LEV monotherapy at the Ankara University Children Hospital between January 2010 and June 2020 were evaluated. This retrospective pediatric cohort study determined the efficacy and safety of LEV monotherapy in 281 outpatients with epilepsy.. There were 281 patients, 50.5% female, aged 5 months to 18 years with a mean age of 9 years. Of these, 48% of patients had idiopathic epilepsy, 40.6% had symptomatic epilepsy, and 11,4% had cryptogenic/genetic epilepsy. Primary generalized seizures occurred in 61.6% of patients, focal seizures in 19.6%, both generalized and focal seizures in 15,3%, focal to bilateral tonic-clonic seizures in 2.5%, and undefined type of seizure in 1.1%. A total of 22.8% patients had an accompanying extra neurological disease, mostly cardiological and hematological. The range of final daily dose was 10-71 mg/kg/day, with mean 29.5 mg/kg/day. Duration of therapy ranged from 7 days to 96 months, with median 12 months (IQR: 6-22). For the all cohort, a 6th month retention rate was 81%, a 12th month retention rate was 71.4%, and a 24th month retention rate was 61.8%. Eighty five percent of the patients had a seizure reduction of at least 50% and 55.9% of patients remained seizure-free for median 12 months treatment duration with LEV monotherapy. Improvement of electroencephalography (EEG) findings was found in 42% of patients on control EEGs. A total of 67 adverse events were documented in 45 (16%) patients. The most common adverse events were behavioral problems such as aggression (n:18) and irritability (n:17). The discontinuation rate due to adverse events was 2.5%, and due to inefficacy was 5.3%.. The present study suggests that the high retention rates, high percentage of seizure reduction, the low discontinuation rate due to adverse events and inefficacy, and the relatively benign and transient profile of adverse events make LEV preferable as monotherapy in the pediatric population.

Topics: Adult; Anticonvulsants; Child; Cohort Studies; Epilepsy; Female; Humans; Levetiracetam; Male; Neurology; Piracetam; Retrospective Studies; Treatment Outcome

People with epilepsy (PWE) have an increased suicide prevalence. This study aimed to identify the risk factors for suicidal tendency among PWE in West China. A nested case-control study was designed in a cohort of patients with epilepsy (n = 2087). In total, 28 variates were calculated. In the univariate analysis, unemployment, low income, seizure frequency, seizure-free time, infectious or structural etiology, levetiracetam or phenobarbital use, anxiety, depression, and stigma were associated with suicidal tendency. A multivariate analysis indicated that unemployment (odds ratio [OR] 5.74, 95% confidence interval [CI] 2.13-15.48), levetiracetam use (OR 2.80, 95%CI 1.11-7.05), depression (C-NDDI-E score ≥ 13; OR 3.21, 95%CI 1.26-8.21), and stigma (SSCI score ≥ 16; OR 6.67, 95%CI 1.80-24.69) were independently associated with suicidal tendency. Conditional inference tree analysis indicated that SSCI and C-NDDI-E scores could effectively identify patients with suicidal tendency. Thus, this study suggests that unemployment, levetiracetam use, depression, and stigma are independent risk factors for suicidal tendency in PWE in China.

Topics: Adolescent; Adult; Case-Control Studies; China; Depression; Epilepsy; Female; Follow-Up Studies; Humans; Income; Levetiracetam; Male; Prevalence; Risk Factors; Severity of Illness Index; Social Stigma; Suicidal Ideation; Unemployment; Young Adult

The present study evaluated whether patients with epilepsy who received both levetiracetam (LEV) and perampanel (PER) therapy showed side effects of irritability. The study also examined the relationship between patient characteristics and irritability when it occurred as a side effect.. We retrospectively examined medical records of 98 patients with epilepsy who were treated with both LEV and PER at the Department of Psychiatry in the Epilepsy Center of Nishiniigata Chuo National Hospital in Japan. We performed multiple regression analyses with the presence/absence of irritability due to LEV or PER as the dependent variables and clinical characteristics of the patients as independent variables.. LEV and PER caused irritability in 7 and 17 of 98 patients, respectively. LEV- and PER-related irritability did not occur in the same patients. A logistic multiple regression analysis revealed that EEG findings of temporal focal epileptic discharge were significantly associated with increased incidence of irritability due to LEV. LEV-related irritability decreased significantly with higher dosages of LEV. Another logistic multiple regression analysis revealed that a psychiatric comorbidity of irritability and EEG findings of nontemporal focal epileptic discharge were significantly associated with increased incidence of irritability due to PER.. LEV and PER cause irritability in different patient groups. Additionally, irritability as a side effect was present only at low dosages of LEV, but PER tended to cause irritability even at high dosages.

Topics: Anticonvulsants; Epilepsy; Humans; Japan; Levetiracetam; Nitriles; Piracetam; Pyridones; Retrospective Studies

This study aims to identify the determinants of cognitive dysfunction and compare the effect of CPZ and LTC on cognition in WWE.. An observational study involving 87 consenting adult WWE aged between 16 and 40 years on LTC or CZP monotherapy. At enrollment, an interviewer-based questionnaire was used to obtain demographic and clinical information from participants. The diagnosis of epilepsy was mainly clinical and supported by electroencephalographic (EEG) features and classified based on recommendation by the 2017 International League Against Epilepsy (ILAE). Zung Self-Reporting Depression Scale (ZSRDS) was used to assess the mood of participants. The Community Screening Interview for Dementia (CSID) was used to assess various cognition domains. The National Hospital Seizure Severity Scale (NHS-3) was used to assess disease severity.. There were statistical differences between the CZP and LTC groups in all domains of cognition assessed except for orientation. The total CSID scores of the LTC group were 59.2 (4.9) as opposed to CZP group, 57.2 (5.0); p: .005. Those with focal onset seizures had lower median total CSID score (58; IQR: 54-62) when compared to those with generalized onset seizures (62; IQR: 58-62), p: .012. There was a significant correlation between ZSRD score and NHS-3 score; rho: 0.30, p: .007. Bivariate analysis shows statistically significant correlation between total CSID score and ZSRDS (rho: -0.65), BMI (rho: 0.22), and NHSS-3 score (rho: -0.36), respectively. However, the effect of AED on CSID scores was lost after multivariate quantile regression with only ZSRDS retaining significance.. Depression, seizure severity, type and structural etiology were associated with cognitive impairment among WWE. However, on regression model, only depression was statistically significant. The presence of more risks for cognitive impairment in the CZP group limits possible conclusion of LTC superiority.

Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; Cognitive Dysfunction; Epilepsy; Female; Humans; Levetiracetam; Nigeria; Young Adult

Topics: Anticonvulsants; Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Seizures

Studies of the effect of valproate (VPA) on the background EEG have shown varying results. Therefore, we compared the effect of VPA and levetiracetam (LEV) on the EEG alpha peak frequency (APF).. We retrospectively examined the APF in resting-state EEG of patients undergoing inpatient video-EEG monitoring (VEM) during withdrawal of VPA or LEV. We assessed APF trends by computing linear fits across individual patients' APF as a function of consecutive days, and correlated the APF and daily antiseizure medication (ASM) doses on a single-patient and group level.. The APF in the VPA-group significantly increased over days with falling VPA doses (p = 0.005, n = 13), but did not change significantly in the LEV-group (p = 0.47, n = 18). APF correlated negatively with daily ASM doses in the VPA-group (average of r = -0.74 ± 0.12 across patients, p = 0.0039), but not in the LEV-group (average of r = -0.17 ± 0.18 across patients, p = 0.4072).. Our results suggest that VPA treatment slows the APF. This APF reduction correlates with the daily dose of VPA and is not present in LEV treatment.. Our study identifies a VPA-related slowing of the APF even in patients without electroencephalographic or overt clinical signs of encephalopathy.

Topics: Adolescent; Adult; Aged; Alpha Rhythm; Anticonvulsants; Brain; Child; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Retrospective Studies; Valproic Acid; Young Adult

Epilepsy is the third most frequent neurological disorder in aged patients after stroke and dementia. The incidence of epilepsy increases with age with the highest rates in patients ≥ 65 years old. Due to demographic changes the number of aged patients with epilepsy is expected to increase further in the coming years. The leading cause of new onset epilepsy in aged patients is cerebrovascular disease followed by dementia. The recognition of seizures in aged patients is often delayed. Status epilepticus occurs more frequently in aged patients and is associated with a high mortality and morbidity. Antiepileptic drug (AED) treatment of aged patients is complicated by comorbidities and polypharmacy and AEDs with a low interaction profile and high tolerability should be selected. Levetiracetam and lamotrigine are the AEDs of choice due to low interactions and good tolerability.. Epilepsien stellen nach Demenzen und Schlaganfall die dritthäufigste neurologische Krankheitsgruppe bei älteren Menschen dar. Die Inzidenz der Epilepsien steigt im Alter, sodass aufgrund demografischer Entwicklungen in den kommenden Jahren mit einer weiteren Zunahme älterer Patienten mit Epilepsie zu rechnen ist. Die häufigsten Ursachen der Altersepilepsie stellen zerebrovaskuläre Erkrankungen und Demenzen dar. Anfälle bei älteren Menschen werden oft spät erkannt. Das Auftreten eines Status epilepticus ist bei älteren Patienten häufiger und mit erhöhter Morbidität und Letalität vergesellschaftet. Die medikamentöse Behandlung älterer Patienten wird durch Komorbiditäten und Polypharmazie erschwert, wobei Antiepileptika mit geringem Interaktionsprofil und guter Verträglichkeit zur Behandlung der Altersepilepsie gewählt werden sollten. Levetiracetam und Lamotrigin sind aufgrund geringer Interaktionen und guter Verträglichkeit Antiepileptika erster Wahl beim älteren Patienten.

Topics: Aged; Anticonvulsants; Carbamazepine; Epilepsy; Humans; Lamotrigine; Levetiracetam

Visuospatial abilities are fundamental for good school achievements and good daily functioning. Previous studies showed an impairment of visuospatial skills in pediatric patients with epilepsy; pharmacological treatment, although indispensable for the seizure control, could further affect cognitive functions. The aim of our study was to evaluate the visuospatial skills in children and adolescents with different forms of epilepsy well-controlled by antiseizure monotherapy, both at baseline and after one year follow-up, through a standardized neuropsychological assessment.. We recruited 207 children and adolescents (mean age = 10.35 ± 2.39 years) with epilepsy, well controlled by monotherapy with levetiracetam, valproic acid, ethosuximide, oxcarbazepine or carbamazepine and 45 age/sex-matched controls. All the participants performed the Rey-Osterrieth Complex Figure, a standardized test for visuospatial perception and visuospatial memory assessment, at baseline and after 12 month of drug therapy. Age, sex, executive functions, non-verbal intelligence, age at onset of epilepsy, epilepsy duration, epilepsy type, lobe and side of seizure onset were considered in our analysis. EEG, seizure frequency, and drug dose were also recorded.. At baseline, the epilepsy group performed significantly worse than controls in the Immediate Recall test but not the Direct Copy test, without differences between epilepsy subgroups. Immediate Recall scores were related to age of seizure onset and epilepsy duration and executive functions. The re-assessment after 1 year showed that the Immediate Recall mean scores were not significantly changed in the levetiracetam and oxcarbazepine group, while they significantly worsened in the valproic acid, ethosuximide and carbamazepine groups. The Immediate Recall scores were correlated to age, age at onset of epilepsy, epilepsy duration, and executive functions.. Children with epilepsy may exhibit visuospatial memory impairment compared to their peer, that may be correlated to some features of the epilepsy itself and to the impairment of executive functions. Different antiseizure medications can affect visuospatial memory differently, so it is important monitoring this aspect in pediatric patients.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Epilepsy; Ethosuximide; Executive Function; Female; Humans; Levetiracetam; Longitudinal Studies; Male; Neuropsychological Tests; Retrospective Studies; Spatial Memory; Valproic Acid

There are no reliable prospective studies on the effectiveness of LEV in Bulgarian adult patients with drug-resistant epilepsy.. The study aimed at conducting an open, prospective study on various aspects of levetiracetam (LEV) effectiveness in Bulgarian patients with drug-resistant epilepsy.. The study was performed with patients with epilepsy recruited from those attending the Department of Neurology at the University Hospital in Plovdiv, Bulgaria. The patients completed diaries about seizure frequency, severity, and adverse events. There were regular documented visits at 3 or 6 months during the first year of treatment with LEV and at 6 months afterwards, with dynamic assessment of seizure frequency, severity, adverse events, and EEG recordings.. LEV was applied as an add-on therapy in 135 patients (86 males, mean age 35 years). There was a relatively mild and persisting dynamic improvement of seizure severity, a satisfactory seizure frequency reduction in 49.6% of participants, a persisting mean seizure frequency reduction (48-58%) from 6 to 36 months of treatment and a high responder rate (53-60%) during the same period. New seizure types (focal with impaired awareness with /without evolution to bilateral tonic-clonic seizures) occurred in 4 patients. There were adverse events (dizziness, memory impairment, aggressiveness, numbness, non-epileptic seizures, depression, anxiety, speech disturbances, visual hallucinations, sleepiness, pelvic muscles weakness, confusion, sleep disturbances, loss of appetite, unstable gait, hair loss, acne, generalized rash) in 13.33% of patients.. LEV treatment is associated with: low and persisting improvement of seizure severity, a good and persisting improvement of seizure frequency, a possible worsening of seizure control, a possible appearance of new seizure types, a good safety and tolerability.

Topics: Adult; Anticonvulsants; Bulgaria; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Pharmaceutical Preparations; Prospective Studies; Seizures; Treatment Outcome

Valproate (VPA) use was restricted due to its teratogenic risks in women with epilepsy (WWE). We aimed to assess the outcome and predictors of treatment decisions of withdrawal/switch or continuation of VPA in WWE.. We included 214 consecutive WWE with a follow-up time of 9.57 ± 7.04 years, who have used (n = 142) or are still using VPA (n = 72) during their reproductive ages. The demographic, clinical, and electroencephalography (EEG) properties of WWE who could withdraw (successful withdrawal; n = 142) and could not withdraw VPA (unsuccessful withdrawal; n = 36) were compared statistically.. The main reasons for still using VPA were high risk of seizure recurrence (63.9%), cognitive impairment (27.8%), and no pregnancy prospect (8.3%). In the successful withdrawal group, 67 (47.1%) patients maintained remission after VPA withdrawal and 26 of them (38.8%) had relapse during the follow-up. The rate of side effects related to the new drugs (levetiracetam and lamotrigine) was 52/142 (36.6%). The unsuccessful withdrawal rate was 13.9% in focal epilepsy whereas it was 86.1% in generalized epilepsy (p = 0.002). Co-occurrence of three types of seizures and anti-seizure medication (ASM)-resistance was related to unsuccessful withdrawal in genetic generalized epilepsy (GGE) (p = 0.02 for both).. Although women with focal epilepsies are more ASM-resistant and more likely to have continuing seizures, they do not usually deteriorate after VPA discontinuation, therefore posing them to teratogenic risk is often unnecessary. In GGE, certain predictors such as previous ASM-resistance and the presence of three seizure types must be taken into account, before a withdrawal attempt of VPA treatment.

Topics: Anticonvulsants; Epilepsy; Epilepsy, Generalized; Female; Humans; Levetiracetam; Valproic Acid

Levetiracetam is approved as an add-on therapy to treat refractory partial seizures in pediatric patients over four years old. The efficacy and safety in pediatric patients with epilepsy in Uygur, China, is unknown. Therefore, the objective of this study was to investigate the safety, efficacy, and tolerability of levetiracetam in pediatric patients with epilepsy in Uygur, China.. This retrospective study compared the efficacy and safety of levetiracetam monotherapy and in combination with other antiseizure medications (ASMs) in 1055 pediatric patients with epilepsy treated with levetiracetam. The seizure frequencies at 1, 2, and 3 years after starting levetiracetam therapy were recorded and compared with the baseline yearly frequency. Safety variables included the incidence and type of adverse reactions.. A total of 680 (64%) pediatric patients responded to levetiracetam therapy with a more than 50% reduction in the frequency of seizures. Seizure-free rates increased over time, 13%, 15%, and 18% at 1, 2, and 3 years, respectively. The number of baseline ASMs and the order of levetiracetam introduction were highly significant, impacting the likelihood of seizure remission during a 3-year follow-up period (p < 0.001). During levetiracetam treatment, 233 pediatric patients (22%) experienced at least one adverse reaction.. These significant findings indicate that levetiracetam is likely to become a widely prescribed ASM for epilepsy in pediatric clinical practice because of its long-term safety, efficacy, and tolerability.

Topics: Anticonvulsants; Child; Child, Preschool; China; Epilepsy; Humans; Levetiracetam; Piracetam; Retrospective Studies; Treatment Outcome

Evidence-based recommendations for choice of antiepileptic drug (AED) in post-stroke epilepsy (PSE) are lacking. The aim of this study was to describe the use and persistence of AEDs when initiating treatment in men and women with PSE. An observational study based on individual-level patient data from a regional healthcare register in Stockholm, Sweden, was conducted. Adults (≥18 years) with a stroke diagnosis 2012-2016, a dispensed prescription of any AED within two years after the stroke, and with an epilepsy-related diagnosis were identified. Multinomial logistic regression and logistic regression were used to identify factors associated with choice of AED and discontinuation within 90 days, respectively. Of 9652 men and 9844 women with a stroke diagnosis, 287 men and 273 women had PSE and were dispensed AED. More than 60% of both men and women with PSE were treated with levetiracetam. Carbamazepine was the second most common drug followed by lamotrigine and valproic acid. There were significant differences in AED choice depending on for instance sex, age and renal impairment. Levetiracetam had the highest persistence in both men and women. Choice of AED, oral anticoagulant use and percutaneous endoscopic gastrostomy (PEG) showed an association with the persistence to therapy. We conclude that in both men and women with PSE, levetiracetam was the most used AED for initiation of treatment and also had the highest persistence.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Carbamazepine; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Medication Adherence; Middle Aged; Phenytoin; Stroke; Sweden; Valproic Acid

Operational delays have the potential to lead to suboptimal time to seizure control during status epilepticus. Levetiracetam (LEV) is an urgent control antiepileptic medication that offers relative lack of adverse effects and ease of monitoring. There are limited data published demonstrating safety and tolerability of undiluted rapid intravenous (IV) push of LEV in doses of 1000 mg or less. The purpose of this study was to evaluate the safety of IV push administration of LEV doses up to 4500 mg.. This is a retrospective, observational, cohort analysis of adult patients who received at least one dose of undiluted IV push LEV from October 15, 2019 to August 31, 2020 at a large academic medical center in Phoenix, Arizona. Outcomes of interest include safety and tolerability of rapid administration of undiluted LEV.. There were 953 unique patients included during the study period. LEV was a new medication for witnessed or suspected seizure in 51.9% of patients, and 40.7% of patients had a documented history of epilepsy or seizure disorder. There were 8561 undiluted IV push LEV doses administered, 3674 (42.9%) of which were greater than 1000 mg. LEV was administered most often through a peripheral IV (79.1%). There were 12 patients with documented adverse drug events during the study period, with four potentially directly related to IV push LEV administration. These events were limited to local injection site reactions and included redness, burning, and loss of a peripheral IV line.. Rapid IV administration of undiluted LEV is both safe and tolerable in doses of up to 4500 mg, allowing for rapid drug administration, which is paramount during neurologic emergencies.

Topics: Adult; Anticonvulsants; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Humans; Levetiracetam; Piracetam; Seizures; Status Epilepticus; Treatment Outcome

The first antiseizure medication (ASM) is ineffective or intolerable in 50% of epilepsy cases. Selection between more than 25 available ASMs is guided by epilepsy factors, but also age and comorbidities. Randomized evidence for particular patient subgroups is seldom available. We asked whether register data could be used for retention rate calculations based on demographics, comorbidities, and ASM history, and quantified the potential improvement in retention rates of the first ASM in several large epilepsy cohorts. We also describe retention rates in patients with epilepsy after traumatic brain injury and dementia, patient groups with little available evidence.. We used medical, demographic, and drug prescription data from epilepsy cohorts from comprehensive Swedish registers, containing 6380 observations. By analyzing 381 840 prescriptions, we studied retention rates of first- and second-line ASMs for patients with epilepsy in multiple sclerosis (MS), brain infection, dementia, traumatic brain injury, or stroke. The rank of retention rates of ASMs was validated by comparison to published randomized control trials. We identified the optimal stratification for each brain disease, and quantified the potential improvement if all patients had received the optimal ASM.. Using optimal stratification for each brain disease, the potential improvement in retention rate (percentage points) was MS, 20%; brain infection, 21%; dementia, 14%; trauma, 21%; and stroke, 14%. In epilepsy after trauma, levetiracetam had the highest retention rate at 80% (95% confidence interval [CI] = 65-89), exceeding that of the most commonly prescribed ASM, carbamazepine (p = .04). In epilepsy after dementia, lamotrigine (77%, 95% CI = 68-84) and levetiracetam (74%, 95% CI = 68-79) had higher retention rates than carbamazepine (p = .006 and p = .01, respectively).. We conclude that personalized ASM selection could improve retention rates and that national registers have potential as big data sources for personalized medicine in epilepsy.

Topics: Anticonvulsants; Brain Injuries, Traumatic; Carbamazepine; Dementia; Epilepsy; Humans; Levetiracetam; Registries; Stroke

The objective of this study was to determine whether two commonly prescribed antiseizure medications (ASMs), levetiracetam (LEV) and oxcarbazepine (OXC), were associated with an increased risk of fragility fracture in children with epilepsy when initiating therapy during a crucial period of bone development, namely, pre- and midpuberty.. Claims data from January 1, 2009 to December 31, 2018 were extracted from the Optum Clinformatics Data Mart. Children aged 4-13 years at baseline with at least 5 years of continuous health plan enrollment were included to allow for a 1-year baseline (e.g., pre-ASM exposure) and 4 years of follow-up. Children with epilepsy who were ASM naïve were grouped based on whether ASM treatment initiation included LEV or OXC. The comparison group included children without epilepsy and without ASM exposure. Crude incidence rate (IR; n per 1000 person-years) and IR ratio (IRR; with 95% confidence interval [CI]) were estimated for nontrauma fracture (NTFx), a claims-based proxy for fragility fracture, for up to 4 years of follow-up. Cox proportional hazards regression estimated the hazard ratio (HR; with 95% CI) after adjusting for demographic variables, motor impairment, and baseline fracture.. The crude IR (95% CI) of NTFx was 21.5 (21.2-21.8) for non-ASM-users without epilepsy (n = 271 346), 19.8 (12.3-27.2) for LEV (n = 358), and 34.4 (21.1-47.7) for OXC (n = 203). Compared to non-ASM-users, the crude IRR of NTFx was similar for LEV (IRR = .92, 95% CI = .63-1.34) and elevated for OXC (IRR = 1.60, 95% CI = 1.09-2.35); the crude IRR of NTFx was elevated for OXC compared to LEV (IRR = 1.74, 95% CI = 1.02-2.99). The findings were consistent after adjusting for covariates, except when comparing OXC to LEV (HR = 1.71, 95% CI = .99-2.93), which was marginally statistically insignificant (p = .053).. Initiating OXC, but not LEV, therapy among 4-13-year-olds with epilepsy is associated with an elevated risk of fragility fracture. Studies are needed to determine whether these children could benefit from adjunct bone fragility therapies.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy; Fractures, Bone; Humans; Incidence; Levetiracetam; Oxcarbazepine

There have been recommendations to improve therapy discovery for epilepsy by incorporating chronic epilepsy models into the preclinical process, but unpredictable seizures and difficulties in maintaining drug levels over prolonged periods have been obstacles to using these animals. We report new protocols in which drugs are administered through a new chronic gastric tube to rats with higher seizure frequencies to minimize these obstacles.. Adult rats with spontaneous limbic seizures following an episode of limbic status epilepticus induced by electrical hippocampal stimulation were monitored with long-term video- electroencephalography (EEG). Animals with a predetermined baseline seizure frequency received an intragastric tube for drug administration. Carbamazepine, levetiracetam, phenobarbital, and phenytoin were tested with either an acute protocol (an increasing single dose every other day for a maximum of three doses) or with a chronic protocol (multiple administrations of one dose for a week). Drug levels were obtained to correlate the effect with the level.. With the acute protocol, all four drugs induced a clear dose-related response. Similar dose-related responses were seen following the week-long dosing protocol for carbamazepine, phenobarbital, and phenytoin, and these responses were associated with drug levels that were in the human therapeutic range. The response to chronic levetiracetam was much less robust. The gastric tube route of administration was well tolerated over a number of months.. Using rats with stable, higher seizure frequencies made it possible to identify the potential of a drug to suppress seizures in a realistic model of epilepsy with drug levels that are similar to those of human therapeutic levels. The acute protocol provided a full dose response in 1 week. The chronic administration protocol further differentiated drugs that may be effective long term. The gastric tube facilitates a less stressful, humane, and consistent administration of multiple doses.

Topics: Animals; Anticonvulsants; Carbamazepine; Disease Models, Animal; Epilepsy; Levetiracetam; Pharmaceutical Preparations; Phenobarbital; Phenytoin; Rats; Seizures

In our recent studies, we identified compound N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) as a broad-spectrum hybrid anticonvulsant which showed potent protection across the most important animal acute seizure models such as the maximal electroshock (MES) test, the subcutaneous pentylenetetrazole (s.c. PTZ) test, and the 6-Hz (32 mA) test in mice. Therefore, AS-1 may be recognized as a candidate for new anticonvulsant effective in different types of human epilepsy with a favorable safety margin profile determined in the rotarod test in mice. In the aim of further pharmacological evaluation of AS-1, in the current study, we examined its activity in the 6-Hz (44 mA) test, which is known as the model of drug-resistant epilepsy. Furthermore, we determined also the antiseizure activity in the kindling model of epilepsy induced by repeated injection of pentylenetetrazole (PTZ) in mice. As a result, AS-1 revealed relatively potent protection in the 6-Hz (44 mA) test, as well as delayed the progression of kindling induced by repeated injection of PTZ in mice at doses of 15 mg/kg, 30 mg/kg, and 60 mg/kg. Importantly, the isobolographic analysis showed that a combination of AS-1 and valproic acid (VPA) at the fixed ratio of 1:1 displayed a supra-additive (synergistic) interaction against PTZ-induced seizures in mice. Thus, AS-1 may be potentially used in an add-on therapy with VPA. Moreover, incubation of zebrafish larvae with AS-1 substantially decreased the number, cumulative but not the mean duration of epileptiform-like events in electroencephalographic assay. Finally, the in vitro ADME-Tox studies revealed that AS-1 is characterized by a very good permeability in the parallel artificial membrane permeability assay test, excellent metabolic stability on human liver microsomes (HLMs), no significant influence on CYP3A4/CYP2D6 activity, and moderate inhibition of CYP2C9 in a concentration of 10 μM, as well as no hepatotoxic properties in HepG2 cells (concentration of 10 μM).

Topics: Animals; Anticonvulsants; Behavior, Animal; Dose-Response Relationship, Drug; Epilepsy; Ethosuximide; Lacosamide; Levetiracetam; Male; Mice; Pentylenetetrazole; Pyrrolidines; Seizures; Valproic Acid; Zebrafish

Searching for the new and effective anticonvulsants in our previous study we developed a new hybrid compound C-11 derived from 2-(2,5-dioxopyrrolidin-1-yl) propanamide. C11 revealed high efficacy in acute animal seizure models such as the maximal electroshock model (MES), the pentylenetetrazole model (PTZ) and the 6 Hz (6 Hz, 32 mA) seizure model, as well as in the kindling model of epilepsy induced by repeated injection of PTZ in mice. In the aim of further in vivo C11 characterization, in the current studies we evaluated its influence on cognitive functions, neurodegeneration and neurogenesis process in mice after chronical treatment. All experiments were performed on 6 weeks old male C57/BL mice. The following drugs were used: C11, levetiracetam (LEV), ethosuximide (ETS) and lacosamide (LCM). We analyzed proliferation, migration and differentiation of newborn cells as well as neurodegenerative changes in a mouse brain after long-term treatment with aforementioned AEDs. Additionally, we evaluated changes in learning and memory functions in response to chronic C11, LEV, LCM and ETS treatment. C11 as well as LEV and ETS did not disturb the proliferation of newborn cells compared to the control mice, whereas LCM treatment significantly decreased it. Chronic AEDs therapy did not induce significant neurodegenerative changes. Behavioral studies with using Morris Water Maze test did not indicate any disturbances in the spatial learning and memory after C11 as well as LEV and ETS treatment in comparison to the control group except LCM mice where significant dysfunctions in time, distance and direct swim to the platform were observed. Interestingly, results obtained from in vivo MRI spectroscopy showed a statistically significant increase of one of the neurometabolites- N-acetyloaspartate (NAA) for LCM and LEV mice. A new hybrid compound C11 in contrast to LCM has no negative impact on the process of neurogenesis and neurodegeneration in the mouse hippocampus. Furthermore, chronic treatment with C11 turned out to have no negative impact on cognitive functions of treated mice, which, is certainly of great importance for further more advanced preclinical and especially clinical trials.

Topics: Animals; Anticonvulsants; Brain; Cognition; Epilepsy; Ethosuximide; Hippocampus; Lacosamide; Levetiracetam; Male; Mice; Mice, Inbred C57BL; Neurogenesis; Pentylenetetrazole; Spatial Memory

Cognitive abilities and executive functions in children and adolescents are important indicators of quality of life as well as academic and social achievements. Cognitive and executive functioning are often impaired in patients with epilepsy and can be exacerbated by seizures and antiseizure drugs. The aim of our observational retrospective study was to assess executive functioning in patients with pediatric epilepsy, currently taking a single antiseizure medication.. Records of 172 children and adolescents aged between 6 and 18 years (mean age = 12 ± 3.4 years) with newly diagnosed epilepsy who had not yet commenced an antiepileptic treatment were included in the study. Longitudinal changes in executive functioning were assessed using the EpiTrack Junior test at baseline, before the introduction of antiepileptic monotherapy, and at 3-month, 6-month, and 9-month follow-up visits. All patients commenced a single antiepileptic treatment (levetiracetam n = 54; valproic acid n = 52; ethosuximide n = 20; oxcarbazepine n = 22; carbamazepine n = 24). Age, sex, seizure types, and seizure baseline frequency were also recorded.. Relative to baseline, Epitrack Junior mean scores deteriorated at the 9-month follow-up visit for patients taking valproic acid, ethosuximide, and carbamazepine, but this was only statistically significant for patients taking carbamazepine. In contrast, mean scores improved for subjects taking levetiracetam and oxcarbazepine at the 9-month follow-up visit relative to baseline, but this was only statistically significant for patients taking levetiracetam.. Levetiracetam was the only antiseizure medication that led to slight improvements in executive functioning; whereas carbamazepine led to deteriorations in cognitive functioning. Further research using double-blinded, placebo-controlled trials are needed to confirm these results.

Topics: Adolescent; Age Factors; Anticonvulsants; Carbamazepine; Child; Epilepsy; Executive Function; Female; Humans; Levetiracetam; Male; Oxcarbazepine; Quality of Life; Retrospective Studies

Ocimum sanctum L. commonly known as tulsi (synonym of Ocimum tenuiflorum L.) is widely used in Ayurveda medicine and is having multitude neuromodulatory effect including the anticonvulsant effect in acute seizure models as per previous studies. In India, it is used for the treatment of epilepsy as traditional medicine. However, its role in chronic seizure model and interaction with newer antiepileptic drugs has not been investigated, which will enhance its translational value.. Current study investigated the effect of Ocimum on chronic seizure model and its interaction with levetiracetam (LEV), a newer antiepileptic drug.. The adjuvant role of Ocimum sanctum hydroalcoholic extracts (OSHE) 1000 mg/kg along with LEV 300 mg/kg was studied in adult male Wistar rats with mean weight of 227.84 ± 21.68 g using pentylenetetrazole (30 mg/kg, i.p.) kindling (K) (with maximum 24 injections on alternate days and challenge on 7th-day). Along with seizure score, neurobehavioral, brain tissue oxidative stress and histopathology status were assessed. Pharmacokinetic interaction was assessed between LEV and OSHE after 14 days of drug treatment.. Ocimum per se and combination with levetiracetam treatment exerted better seizure control, memory retention, oxidative stress reduction, and neuronal structure preservation than kindling control group. There was a very minimal drug interaction between Ocimum and LEV. So, Ocimum as an adjuvant to LEV may be shelpful in enhancing the antiepileptic effect and also in minimizing the adverse effects.

Topics: Animals; Anticonvulsants; Avoidance Learning; Disease Models, Animal; Drug Therapy, Combination; Epilepsy; Herb-Drug Interactions; Kindling, Neurologic; Levetiracetam; Male; Maze Learning; Ocimum sanctum; Oxidative Stress; Pentylenetetrazole; Plant Extracts; Rats; Rats, Wistar; Seizures

The aim of the study was to investigate the risk of subclinical atherosclerosis independent from obesity and high blood lipid levels in pediatric patients with idiopathic epilepsy receiving valproic acid or levetiracetam monotherapy by evaluating carotid intima-media thickness (CIMT) and Epicardial adipose tissue thickness (EATT).. A total of 75 patients (38 males, 37 females; mean age 127.2 ± 37.9 months) with epilepsy receiving either valproic acid or levetiracetam monotherapy for more than 12 months (Epilepsy Group) and 75 sex, age, body mass index (BMI) matched healthy children (40 males, 35 females; mean age 133.8 ± 38.7 months) (Control Group) were included in the study. The mean duration of therapy was 27.6 ± 10.5 months. Serum lipid levels (total cholesterol, triglycerides, low density lipoprotein, high density lipoprotein) and CIMT-EATT of the patients and controls were assessed. Also, epilepsy group were divided according to antiepileptic drugs (valproic acid group and levetiracetam group).. The CIMT was determined as 0.6 ± 0.08 mm in epilepsy group and 0.49 ± 0.15 mm in control group (p < 0.001). The EATT was measured as 5.96 ± 0.8 mm in epilepsy group and 3.7 ± 0.5 mm in control group (p < 0.001). Of epileptic patients, 45 were using valproic acid monotherapy and 30 were on levetiracetam monotherapy. There was no significant difference in terms of CIMT between valproic acid and levetiracetam groups (0.61 ± 0.09 mm vs. 0.57 ± 0.07 mm; p = 0.07). EATT measurements were significantly higher in valproic acid group compared to levetiracetam group (6.14 ± 0.8 mm vs. 5.7 ± 0.7 mm; p = 0.02). CIMT and EATT values were not associated with the dosage and duration of each antiepileptic drug.. Non-obese children with epilepsy receiving valproic acid or levetiracetam monotherapy might have an increased risk for developing subclinical atherosclerosis despite normal lipid levels. The effect of valproic acid was more evident especially on EATT.

Topics: Adipose Tissue; Anticonvulsants; Atherosclerosis; Body Mass Index; Carotid Arteries; Carotid Intima-Media Thickness; Child; Epilepsy; Female; Humans; Levetiracetam; Male; Pericardium; Risk Factors; Valproic Acid

Antiepileptic drug (AED) therapy is symptomatic. New AED:s have not decreased the proportion of epilepsy patients resistant to pharmacological treatment. Lamotrigine, levetiracetam and carbamazepine are first-line options for focal seizures. Lamotrigine, levetiracetam and valproic acid are first-line options for generalized seizures. However, valproic acid is contraindicated during pregnancy unless there is no other effective treatment available, as well as for fertile girls/women unless the conditions of a specific pregnancy prevention programme are met.

Topics: Anticonvulsants; Carbamazepine; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Pregnancy; Pregnancy Complications

Topics: Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Seizures

Topics: Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Seizures

ATP1A3 related disease is a clinically heterogeneous condition currently classified as alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss. Recently, it has become apparent that a remarkably large subgroup is suffering from often difficult-to-treat epilepsy. The aim of the present study was to assess the prevalence and efficacy of commonly used anti-epileptic-drugs (AEDs) in patients with ATP1A3 related seizures. Therefore, we performed a retrospective study of patients in combination with a systematic literature-based review. Inclusion criteria were: verified ATP1A3 mutation, seizures and information about AED treatment. The literature review yielded records for 188 epileptic ATP1A3 patients. For 14/188 cases, information about anti-epileptic treatment was available. Combined with seven unpublished records of ATP1A3 patients, a sample size of 21 patients was reached. Most used AED were levetiracetam (n = 9), phenobarbital (n = 8), valproic acid (n = 7), and topiramate (n = 5). Seizure reduction was reported for 57% of patients (n = 12). No individual AEDs used (either alone or combined) had a success rate over 50%. There was no significant difference in the response rate between various AEDs. Ketogenic diet was effective in 2/4 patients. 43% of patients (n = 9) did not show any seizure relief. Even though Epilepsy is a significant clinical issue in ATP1A3 patients, only a minority of publications provide any information about patients' anti-epileptic treatment. The findings of treatment effectiveness in only 57% (or lower) of patients, and the non-existence of a clear first-line AED in ATP1A3 related epilepsy stresses the need for further research.

Topics: Adult; Anticonvulsants; Cerebellar Ataxia; Child; Dystonic Disorders; Epilepsy; Female; Hearing Loss, Sensorineural; Hemiplegia; Humans; Levetiracetam; Male; Mutation; Optic Atrophy; Reflex, Abnormal; Retrospective Studies; Seizures; Sodium-Potassium-Exchanging ATPase; Topiramate; Valproic Acid

Liver transplant is currently the most effective option for patients with end-stage liver disease. Seizures are the most common neurologic complication after liver transplant. Posterior reversible encephalopathy syndrome is a neurologic syndrome characterized by lethargy, seizures, visual disturbances, and radiologic findings of edema in the posterior regions of the cerebral hemispheres. Levetiracetam is prescribed for a broad spectrum of seizure types but does not have a specific indication for epilepsy in children after solid-organ transplant. Our aim was to investigate the efficacy and tolerability of levetiracetam in pediatric transplant recipients with posterior reversible encephalopathy syndrome and epilepsy.. We reviewed records of patients treated for epilepsy due to posterior reversible encephalopathy syndrome after liver transplant seen at our pediatric neurology clinic between January 2010 and March 2019. Patients were assessed clinically and by neurologic examination, electroencephalography, and cerebral magnetic resonance imaging.. Among 134 children who had undergone liver transplant between 2010 and 2019, 10 patients (6 males, 4 females; age range,7-19 y) who were diag-nosed with posterior reversible encephalopathy syndrome and epilepsy were included in the study. All patients received levetiracetam at 20 mg/kg/day. After a mean follow-up of 28.9 months (range, 24-40 mo), 9 patients (90%) attained complete seizure freedom. One patient who had an underlying neurodegenerative disease (hemophagocytic syndrome) other than posterior reversible encephalopathy syndrome continued to have seizures under levetiracetam treatment. One patient had a mild adverse reaction (irritability) due to levetiracetam but did not require drug discontinuation.. In this study, 90% of patients with posterior reversible encephalopathy syndrome became seizure free with levetiracetam treatment. Our findings suggest that levetiracetam has a favorable efficacy for epilepsy due to posterior reversible encephalopathy syndrome in pediatric liver transplant recipients with tolerable adverse effects.

Topics: Adolescent; Anticonvulsants; Child; Epilepsy; Female; Humans; Immunosuppressive Agents; Levetiracetam; Liver Transplantation; Male; Posterior Leukoencephalopathy Syndrome; Retrospective Studies; Risk Factors; Treatment Outcome; Young Adult

To retrospectively evaluate the pharmacological profiles of antiepileptic drugs (AEDs) in epilepsy patients during haemodialysis using therapeutic drug monitoring data. The serum concentration of AEDs was collected before and after haemodialysis, and the clearance rate and concentration-to-dose ratio were calculated as pharmacological parameters. Thirty-six patients were enrolled in the study (25 males, 11 females; age: 65.3 ± 14.8 years). In 24 of the 36 patients, epilepsy was associated with cerebrovascular disorders, and diabetes was the most common reason for haemodialysis in 16 patients. With regards to seizure type, focal aware seizures were less frequent than focal impaired awareness seizures and focal-to-bilateral tonic-clonic seizures. Interictal EEG showed intermittent rhythmic slow waves and intermittent slow waves more often than spikes or sharp waves. Levetiracetam was the most commonly used AED and led to the highest percentage of responders (80%; 16/20 patients). However, the clearance rate of levetiracetam during dialysis was highest among the antiepileptic drugs used, requiring supplementary doses after haemodialysis in all 20 patients. Valproic acid was not effective for focal epilepsy for patients on haemodialysis, and non-responders to phenytoin had low serum concentration of phenytoin both before and after haemodialysis. The pre-haemodialysis concentration of levetiracetam tended to be higher than the reference range, suggesting a potential risk of overdosing before haemodialysis. The pre- and post-haemodialysis concentrations of valproic acid tended to be lower than the reference range, suggesting a potential risk of underdosing. The concentration-to-dose ratios for levetiracetam, valproic acid, phenytoin, and carbamazepine were significantly lower after than before haemodialysis. The majority of patients with epilepsy on haemodialysis had cerebrovascular diseases, and therapeutic drug monitoring for levetiracetam, valproic acid, and phenytoin, before and after haemodialysis, is needed to ensure proper dosing.

Topics: Aged; Anticonvulsants; Cerebrovascular Disorders; Comorbidity; Drug Monitoring; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Seizures

Annual completion of a Valproate Risk Acknowledgement Form (RAF) is mandated in the United Kingdom due to neurodevelopmental risks of in utero valproate exposure. The number of women of childbearing potential taking valproate, the uptake of the RAF within this population and their clinical outcomes is not known or monitored. This study surveyed responses of clinicians administering the RAF to women of childbearing potential taking valproate medications.. Study design-national online survey distributed to clinical specialists throughout the United Kingdom via their national organizations. Participants-clinicians qualified to counsel and administer the valproate RAF (as defined by the Medicines and Healthcare products Regulatory Agency). Main outcome measures-quantitative and qualitative responses regarding identification, uptake, effects and reactions to the RAF. Trial registration-registered at the Clinical Governance and Audit Committee at Royal Free London NHS Foundation Trust Hospital.. 215 respondents covering more than 4775 patient encounters were captured. Most patients continued on valproate, 90% with epilepsy as the indication. Respondents reported that seizure control deteriorated when switched to levetiracetam (33%) and lamotrigine (43%), compared to 7% when continuing valproate (P < .001).. 33%-43% of clinicians reported seizure control deterioration in women changed to alternatives to valproate. Informed consent requires women considering a change are given this information. Systematic capture of data automated through online RAFs and linked to patient outcomes is needed. There remains little data on valproate given for indications other than epilepsy.

Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Physicians; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Risk Assessment; Surveys and Questionnaires; United Kingdom; Valproic Acid

Certain antiepileptic drugs (AEDs) may be more suitable for elderly patients with epilepsy (EWE) relative to others. However, little is known regarding which antiepileptic drugs (AEDs) are being used to treat EWE in the United States and how it has changed over time.. We performed a serial cross-sectional study evaluating noninstitutionalized US adults aged 65 years or older with a diagnosis of epilepsy using data from the Medical Expenditure Panel Survey (MEPS) from 2004 through 2015. Trends in AEDs used among EWE were examined. Using each AED as a dependent variable, we determined the p-value for the trend by performing a linear regression with the time interval as the explanatory variable.. There was a weighted total of 399,801 EWE. Between the years 2004-2006 and 2013-2015 use of phenytoin, carbamazepine and phenobarbital decreased from 60.7% to 31.1% (p ≤ 0.001), 13.7 % to 5.22 % (p = 0.03) and 12.5 % to 5.91 % (p = 0.04), respectively. Use of levetiracetam concomitantly increased from 6.70 % to 43.1 % (p ≤ 0.001). Patients with more medical comorbidities as measured by the Charlson Comorbidity Index had higher odds of levetiracetam use (OR = 2.52, 95 % CI = 1.19-5.34) and lower odds of phenytoin use (OR = 0.46, 95 % CI = 0.24-0.88).. There have been significant changes in AED prescriptions to EWE between 2004-2015. However, potentially harmful AEDs (e.g. phenytoin, carbamazepine, phenobarbital, primidone and valproate) were still being prescribed to 42.9 % of all patients between 2013-2015. Increased work to educate providers regarding the use of more appropriate AEDs in this population is needed.

Topics: Aged; Aged, 80 and over; Aging; Anticonvulsants; Carbamazepine; Cross-Sectional Studies; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Seizures; Zonisamide

Newer antiepileptic drugs (AEDs) are preferred over conventional AEDs with the perception of better safety profile and efficacy though there is a lack of confirmatory evidence. The present study assessed the adverse drug reactions' (ADRs) profile of AEDs prescribed in persons with epilepsy (PWE) as per the System Organ Class (SOC) and compared them on the basis of demographics and treatment pattern.. This prospective, cross-sectional, and observational study was conducted in PWE attending Neurology Outpatient-Department from February 2016 to April 2019 who were presented with any ADR. World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale was used for the causality assessment of suspected ADRs.. Among the 1011 PWE on AEDs, male:female ratio was 622:389, adult:pediatric ratio 736:275, and conventional:newer AEDs ratio 624:387. Among monotherapy PWE (47.1%), commonly used AEDs were levetiracetam (34.4%), valproic acid (22.9%), carbamazepine (18.3%), phenytoin (11.9%), and other AEDs (12.5%). A total of 1990 ADRs (1.96 ADRs per PWE) were reported as per SOC; among them, newer vs. conventional AEDs did not reveal any significant difference; however, monotherapy vs. polytherapy showed differences in nervous system disorders (p = 0.01) and skin and subcutaneous tissue disorders (p = 0.005). Causality assessment revealed 0.3% certain, 27.3% probable, 61.3% possible, and 11.1% unlikely association of ADRs with AEDs. Depending on the ADRs, there was either withdrawal of AED (0.9%), reduction in dose (48.4%), or continuation in the same dose as before (50.7%).. The ADR analysis showed that newer AEDs were associated with a similar trend of ADRs as that of conventional AEDs. Thus, the choice among newer and conventional AEDs should preferably focus on the experience of better efficacy in addition to safety data.

Topics: Adolescent; Adult; Anticonvulsants; Benzodiazepines; Child; Cross-Sectional Studies; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Prospective Studies; Valproic Acid; Young Adult

The objective was to develop and externally validate a population pharmacokinetic model of levetiracetam in adult and elderly patients with epilepsy, and to perform dosing simulations to propose individualized dosing regimens more likely to achieve therapeutic concentrations. This prospective study included 367 plasma samples from 107 patients receiving oral levetiracetam. Samples were analyzed by HPLC-UV. Pharmacokinetic data, as well as patient demographic, clinical characteristics, other drug therapy, and the use of innovator or generic products of levetiracetam, were collected. Population modeling was performed with NONMEM and included internal and external validations of the final model. Simulations were used to propose optimized dosing regimens. The pharmacokinetics of levetiracetam was described by a one-compartment model with first-order absorption and linear elimination. Body surface area had a significant effect on the apparent volume of distribution, as did creatinine clearance (CrCL) over the drug clearance (p < 0.01). The final model performed adequately during external validation testing. The final model showed a better predictive performance. Dosing simulations support 1000 mg 12-hourly dosing of levetiracetam for patients with CrCL ~60-75 mL/min with higher dose needed for higher values (1500 mg 12-hourly for CrCL ~93-111 mL/min). Dosing regimens should be personalized to the patient's CrCL to maximize the likelihood of therapeutic concentrations.

Topics: Adult; Aged; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Models, Biological; Piracetam; Prospective Studies

Drug resistance is a major concern in the treatment of individuals with epilepsy. No genetic markers for resistance to individual antiseizure medication (ASM) have yet been identified. We aimed to identify the role of rare genetic variants in drug resistance for three common ASMs: levetiracetam (LEV), lamotrigine (LTG), and valproic acid (VPA).. A cohort of 1622 individuals of European descent with epilepsy was deeply phenotyped and underwent whole exome sequencing (WES), comprising 575 taking LEV, 826 LTG, and 782 VPA. We performed gene- and gene set-based collapsing analyses comparing responders and nonresponders to the three drugs to determine the burden of different categories of rare genetic variants.. We observed a marginally significant enrichment of rare missense, truncating, and splice region variants in individuals who were resistant to VPA compared to VPA responders for genes involved in VPA pharmacokinetics. We also found a borderline significant enrichment of truncating and splice region variants in the synaptic vesicle glycoprotein (SV2) gene family in nonresponders compared to responders to LEV. We did not see any significant enrichment using a gene-based approach.. In our pharmacogenetic study, we identified a slightly increased burden of damaging variants in gene groups related to drug kinetics or targeting in individuals presenting with drug resistance to VPA or LEV. Such variants could thus determine a genetic contribution to drug resistance.

Topics: Anticonvulsants; Case-Control Studies; Drug Resistance; Epilepsy; Female; Genotype; Humans; Lamotrigine; Levetiracetam; Male; Pharmacogenomic Variants; Valproic Acid

Antiseizure drugs (ASDs) are known to cause a wide range of adverse drug reactions (ADRs). Recently, electronic health care data using the common data model (CDM) have been introduced and commonly adopted in pharmacovigilance research. We aimed to analyze ASD-related ADRs using CDM and to assess the feasibility of CDM analysis in monitoring ADR in a single tertiary hospital.. We selected five ASDs: oxcarbazepine (OXC), lamotrigine (LTG), levetiracetam (LEV), valproic acid (VPA), and topiramate (TPM). Patients diagnosed with epilepsy and exposed to monotherapy with one of the ASDs before age 18 years were included. We measured four ADR outcomes: (1) hematologic abnormality, (2) hyponatremia, (3) elevation of liver enzymes, and (4) subclinical hypothyroidism. We performed a subgroup analysis to exclude the effects of concomitant medications.. From the database, 1344 patients were included for the study. Of the 1344 patients, 436 were receiving OXC, 293 were receiving LTG, 275 were receiving LEV, 180 were receiving VPA, and 160 were receiving TPM. Thrombocytopenia developed in 14.1% of patients taking VPA. Hyponatremia occurred in 10.5% of patients taking OXC. Variable ranges of liver enzyme elevation were detected in 19.3% of patients taking VPA. Subclinical hypothyroidism occurred in approximately 21.5% to 28% of patients with ASD monotherapy, which did not significantly differ according to the type of ASD. In a subgroup analysis, we observed similar ADR tendencies, but with less thrombocytopenia in the TPM group.. The incidence and trends of ADRs that were evaluated by CDM were similar to the previous literature. CDM can be a useful tool for analyzing ASD-related ADRs in a multicenter study. The strengths and limitations of CDM should be carefully addressed.

Topics: Anticonvulsants; Common Data Elements; Drug-Related Side Effects and Adverse Reactions; Electronic Health Records; Epilepsy; Humans; Lamotrigine; Levetiracetam; Oxcarbazepine; Topiramate; Valproic Acid

Metabolic bone disease and fractures are a great problem for patients with epilepsy. The use of antiepileptic drugs (AEDs) is known to play an essential role in the progression of bone loss by various pathophysiological mechanisms. The aim of this study was to evaluate the effects of AEDs on bone microstructure as an additional cause of an increased fracture risk in patients with epilepsy.. Five groups of each of 12 female rats were orally dosed daily for 8 weeks with either carbamazepine (CBZ) (60 mg/kg), eslicarbazepine (ESL) (80 mg/kg), valproic acid (VPA) (300 mg/kg), levetiracetam (LEV) (50 mg/kg) or saline (control (CTL)). Following killing, dissected femurs were analyzed using X-ray micro-computed tomography (µCT), dual-energy X-ray absorptiometry (DXA) and biomechanical testing. In addition, serum bone turnover markers (BTM) were monitored throughout the experiment.. Compared to CTL treatment, VPA decreased bone volume fraction by 19%, decreased apparent density by 14% and increased structural model index by 41%. No changes were observed in bone biomechanics nor mineral density evaluated by DXA or in levels of BTM.. Our findings suggest that VPA affects the microarchitectural properties of the bone. The AEDs CBZ, ESL and LEV appear to have less adverse effects on bone biology and may be a better choice when treating patients with respect to bone health.

Topics: Animals; Anticonvulsants; Bone and Bones; Carbamazepine; Dibenzazepines; Disease Models, Animal; Epilepsy; Female; Levetiracetam; Rats; Rats, Sprague-Dawley; Valproic Acid; X-Ray Microtomography

Topics: Aged; Anti-Inflammatory Agents; Anticonvulsants; Cerebral Palsy; Cytochrome P-450 CYP3A Inducers; Drug Substitution; Epilepsy; Humans; Levetiracetam; Male; Pemphigoid, Bullous; Phenytoin; Prednisolone

Ring chromosome 20 syndrome is a rare chromosomal disorder characterized by refractory seizure, mental retardation, and behavioral problems. Although there are reports of the effective treatment of patients with antiepileptic drugs (AEDs), no study has reported the effects of lacosamide(LCM) in children with this syndrome. We report a 7-year-old boy with this syndrome whose refractory and behavioral abnormalities have been remarkably improved by treatment with LCM.. The patient was a 7-year-old boy with no medical or family history of epilepsy. He developed epilepsy with cessation of movement and derivation of the eyes followed by hyperkinetic seizures that made him squeak strangely and cling to his parents. The seizures lasted for less than a minute and were frequent (they occurred more than 30 times a day), particularly at night. Behavioral abnormalities such as hyperactivity also presented. Brain magnetic resonance imaging revealed no structural abnormalities, but an interictal electroencephalogram (EEG) indicated spikes and waves in the frontal lobe dominantly, and ictal single-photon emission computed tomography (SPECT) revealed a blood flow increase in the bilateral orbital frontal area in comparison to interictal SPECT. After chromosome examination, we diagnosed the patient with ring chromosome 20 syndrome (4/30 mosaic). Carbamazepine was ineffective, and seizures were exacerbated with levetiracetam (LEV). LCM was added to the treatment regimen with valproic acid (VPA) and lamotrigine (LTG); consequently, the seizures disappeared, and EEG results also improved. The patient's behavioral disorders, such as hyperactivity, were improved, and he was able to return to elementary school.. Although VPA and LTG are generally effective for the treatment of ring chromosome 20 syndrome, they do not completely suppress seizures. LCM can be considered an effective option for seizure control in patients with this syndrome.

Topics: Anticonvulsants; Carbamazepine; Child; Electroencephalography; Epilepsy; Humans; Lacosamide; Lamotrigine; Levetiracetam; Male; Ring Chromosomes; Seizures; Treatment Outcome; Valproic Acid

Although levetiracetam presents an easy dosing and tolerability, therapeutic drug monitoring may be recommended in certain situations. Measurement of levetiracetam in serum plasma is commonly done by high performance liquid chromatography (HPLC). After ARK Diagnostics marketed an enzyme immunoassay (IA) for levetiracetam in serum or plasma, automated determinations are possible. In this study, the performance of this immunoassay and the impact of automation on the follow-up in patients treated with levetiracetam is evaluated. We also detected those subpopulations of patients who may benefit the most from this therapeutic drug monitoring.. Samples from 50 outpatients diagnosed with epilepsy and treated with levetiracetam were collected. This new IA was performed on the Architect c4000 analyser and compared with the HPLC. Then, a retrospective observational study that included serum samples of levetiracetam for 24 months, was conducted to evaluate the impact of automattion and the influence of some variables (age, sex, renal function, and co-administration of valproic acid and glucuronidation-inducing drugs) in levetiracetam apparent oral clearance (CLp/F) by a multivariate linear regression.. The Ark method performed on the Architect is fully acceptable and can be used routinely to measure levetiracetam plasmatic concentration levels. It has demonstrated the need for closer monitoring in patients with renal failure or co-administration of glucuronidation-inducing drugs.

Topics: Anticonvulsants; Chromatography, High Pressure Liquid; Drug Monitoring; Epilepsy; Female; Humans; Immunoassay; Levetiracetam; Male; Retrospective Studies

Topics: Adolescent; Anticonvulsants; Benzodiazepines; Child; Child, Preschool; Emergency Treatment; Epilepsy; Evidence-Based Medicine; Humans; Infant; Infant, Newborn; Levetiracetam; Parents; Patient Care Planning; Phenytoin; Practice Guidelines as Topic; Status Epilepticus; Time Factors; Treatment Failure

To evaluate P-wave dispersion before and after antiepileptic drug (AED) treatment as well as to investigate the risk of ventricular repolarization using the Tpeak-Tend (Tp-e) interval and Tp-e/QT ratio in patients with epileptic disorder.. A total of 63 patients receiving AED therapy and 35 healthy adults were included. ECG recordings were obtained before and 3 months after anti-epileptic treatment among patients with epilepsy. For both groups, Tp-e and Tp-e/QT ratio were measured using a 12-lead ECG device.. Tp-e interval, Tpe/QT and Tp-e/QTc ratios were found to be higher in the patient group than in the control group (p<0.05, for all), while QTmax ratio was significantly lower in the patient group. After 3 months of AED therapy, significant increases in QT max, QTc max, QTcd, Tp-e, Tp-e/QT, and Tp-e/QTc were found among the patients (p<0.05). When the arrhythmic effects of the drugs before and after treatment were compared, especially in the valproic acid group, there were significant increases in Tp-e interval, Tp-e/QT and Tp-e/QTc values after three months of treatment (p<0.05). Carbamazepine and levetiracetam groups were not statistically significant in terms of pre- and post-treatment values.. It was concluded that an arrhythmogenic environment may be associated with the disease, and patients who received AED monotherapy may need to be followed up more closely for arrhythmia.. A P-hullám-diszperzió értékelése antiepileptikus kezelés (AETh) előtt és után, valamint a ventricularis repolarizáció kockázatának vizsgálata a Tpeak-Tend (Tp-e) intervallum és a Tp-e/QT arány használatával epilepsziás betegek körében.. Hatvanhárom, AETh-ban részesülő beteget és 35 egészséges kontrollszemélyt vontunk be a vizsgálatba. Az epilepsziás betegek körében az EKG-vizsgálatot az AETh előtt és utána három hónappal végeztük. A Tp-e intervallumot és a Tp-e/QT arányt mindkét csoport esetében 12 elvezetéses EKG-berendezéssel mértük.. A Tp-e intervallum hosszabbnak, a Tp-e/QT és a Tp-e/QTc arányok magasabbnak bizonyultak a betegcsoportban, mint a kontrollok között (p < 0,05, mind­egyik esetében), ugyanakkor a QTmax-arány szignifikánsan alacsonyabb volt a betegcsoportban. Három hónap AETh után a betegek körében szignifikáns mértékben növekedett a QTmax, a QTcmax, a QTcd, a Tp-e, a Tp-e/QT és a Tp-e/QTc (p < 0,05). Miután értékelték az AETh arrhythmiás hatását, három hónapos kezelés után különösen a valproinsavval kezeltek esetében észlelték a Tp-e intervallum, a Tp-e/QT és a Tp-e/QTc arányok szignifikáns növekedését (p < 0,05). A carbamazepinnel és a levetiracetammal kezeltek esetében nem különböztek szignifikáns mértékben a terápia előtti és utáni értékek.. Az epilepszia arrhythmogen környezettel társulhat, és az AETh-ban részesülő betegeket szorosan monitorozni érdemes az arrhythmia kiszűrése érdekében.

Topics: Adult; Anticonvulsants; Arrhythmias, Cardiac; Carbamazepine; Case-Control Studies; Electrocardiography; Epilepsy; Heart Conduction System; Heart Ventricles; Humans; Levetiracetam; Valproic Acid

Introduction To examine efficacy and tolerability of Levetiracetam monotherapy as a first line agent in a national cohort of children with epilepsy, naïve to anti-epileptic medication. Methods A retrospective analysis of children with epilepsy who attended 4 Irish tertiary Paediatric Neurology Clinics (2009-2015) started on Levetiracetam as a first line monotherapy. Results 182 children were identified aged one month to 16 years (mean 6.2 years (SD=5.1) Retention at 6 and 12 months was 88% (n=161) and 83% (n=145) respectively. 75% (n=104) achieved seizure freedom or > 50% improvement in seizure control at 12 months. 30% (n=55) experienced ≥1 adverse effect with aggression (12%; n=21) the most frequent. Treatment was discontinued in 16% (n=29) because of intolerance. Underlying conditions and epilepsy type were not found to influence efficacy or tolerability. Conclusion Levetiracetam monotherapy was observed as effective and safe for children with epilepsy although side effects limit tolerance in a sizeable minority.

Topics: Adolescent; Child; Child, Preschool; Drug Tolerance; Epilepsy; Female; Humans; Infant; Ireland; Levetiracetam; Male; Retrospective Studies; Safety; Treatment Outcome

Topics: Brain; Epilepsy; Female; Humans; Infant, Newborn; Levetiracetam; Magnetic Resonance Imaging; Mutation; Phenobarbital; Phenotype; Sodium Channel Blockers; Vesicular Transport Proteins

Asparagine synthetase deficiency (ASNSD) refers to a congenital metabolic abnormality caused by mutation in the asparagine synthetase (ASNS) gene encoded by chromosome 7q21. Herein, we report the first case of ASNSD in China, in which novel ASNS mutations were identified.. A 6-month-old boy presented with a 4-month history of microcephaly and psychomotor developmental retardation and a 2-month history of epilepsy. Four months after birth, magnetic resonance imaging demonstrated a giant cyst in the right lateral ventricle, and a ventriculoperitoneal shunt was placed. Video electroencephalography showed a hypsarrhythmia pattern with a string of tonic-clonic and myoclonic seizures. On admission, physical examination showed microcephaly. Neurologic examination showed a decreased tension in the trunk muscles and an increased tension in the extremity muscles; tendon hyperreflexia was noted, and bilateral pathologic reflexes were positive.. A diagnosed of congenital microcephaly was made. Whole-exome sequencing revealed a heterozygous deletion mutation c.666_667delCT (p.L2221Lfs*5) in exon 6 of the ASNS gene and a heterozygous missense mutation c.1424C>T (p.T457I) in exon 13 of the ASNS gene.. After admission, intravenous adrenocorticotropic hormone and oral topiramate was administrated for 4 weeks, while the seizures persisted. Then, levetiracetam and clonazepam were added.. After the follow-up period of 18 months, video electroencephalography showed that complex episodes disappeared with changes in multiple focal spike and sharp waves; 1 focal attack arising from the left occipital region and 2 focal attacks arising from the right middle temporal and the right occipital region were recorded.. This is the first case of ASNSD in China. We identified 2 novel mutations (c.666_667delCT and c.1424C>T) in the ASNS gene, which expands the ASNS gene mutation profile and will be beneficial for genetic diagnosis.

Topics: Anticonvulsants; Aspartate-Ammonia Ligase; China; Clonazepam; Electroencephalography; Epilepsy; Humans; Infant; Levetiracetam; Male; Microcephaly; Mutation, Missense

Topics: Amnesia; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Male; Memory Disorders; Middle Aged

This study aims to compare the neurocognitive outcome in term infants who were treated using phenobarbital (PB) and levetiracetam (LEV) monotherapy for neonatal clinical seizures.. Term infants who were treated using PB or LEV monotherapy as the first-line anti-epileptic treatment for neonatal clinical seizures and followed-up in a pediatric neurology outpatient clinic were enrolled in this study. Neurodevelopmental outcome assessments were carried out using the Bayley Scales of Infant Development, third edition (BSID-III), including cognitive, receptive language, expressive language, fine motor and gross motor subscales.. The study group consisted of 62 infants who received monotherapy with PB monotherapy (n = 22) and LEV (n = 40). The mean duration of monotherapy treatment was 8 ± 6 months. There was no statistically significant difference between PB and LEV monotherapy groups concerning each outcome parameter on the BSID-III. There was also no statistically significant difference between PB and LEV monotherapy subgroups excluding the infants with neurodevelopmental impairment with a BSID-III scale score<7 or a composite score<85.. Our findings suggest that both LEV and PB therapy can be equally safe as monotherapy for neonatal clinical seizures for the neurodevelopmental outcome assessment with BSID-III.

Topics: Anticonvulsants; Child; Epilepsy; Humans; Infant; Infant, Newborn; Levetiracetam; Phenobarbital; Seizures

To examine central macular, RNFL (retinal nerve fibre layer), GCC (ganglion cell complex) thicknesses; and VEPs (visual evoked potential) in epileptic patients using levetiracetam for at least one year.. Sixteen focal epileptic patients receiving levetiracetam monotherapy and 16 healthy subjects were included in the study. Central macular, RNFL and GCC thicknesses according to spectral domain OCT (optical coherence tomography); and VEPs parameters were compared between patients and healthy subjects.. The mean age of patient and control groups were 40 ± 16 and 38 ± 12 years respectively (. Central macular and GCC thicknesses; and VEP parameters in patients receiving levetiracetam treatment may differ from healthy subjects.

Topics: Adult; Anticonvulsants; Epilepsy; Evoked Potentials, Visual; Female; Humans; Levetiracetam; Male; Middle Aged; Nerve Fibers; Retinal Ganglion Cells; Tomography, Optical Coherence

The use of therapeutic drug monitoring (TDM) for antiseizure medications (ASMs) may contribute to treatment optimization in individual patients. This study included patients with Dravet syndrome as they often require close monitoring because of polypharmacy with various ASMs. The aim was to use long-term TDM to investigate pharmacokinetic variability of ASMs in these patients.. Retrospective data from patients with Dravet syndrome were collected from the TDM database at the Section for Clinical Pharmacology, National Center for Epilepsy in Norway (2008-2018). Concentration/(dose/kg)ratios (C/D ratios) were calculated for the ASMs and the concentration (C/C ratio) for N-desmethylclobazam. In patients with at least 3 measurements, the CV for C/D ratios for intrapatient and interpatient variability was calculated.. Fifty-three patients (30 male patients/23 female patients) between 2 and 50 years of age (mean, 16 years) were included. Pharmacokinetic variability of the total number of measurements of valproate (n = 417), clobazam and N-desmethylclobazam (n = 328), and levetiracetam (n = 238) was determined. Interpatient variability was more pronounced than intrapatient variability (coefficient of variations: valproate, 65% vs. 24%; levetiracetam, 71% vs. 27%; and clobazam/N-desmethylclobazam, 47%/77% vs. 35%/55%) (P < 0.01). Comedication with stiripentol (n = 16) increased the C/D ratio of valproate by 63% and of clobazam by 133% and the C/C ratio of N-desmethylclobazam/clobazam by 104% (P < 0.05). Younger age also contributed to pharmacokinetic variability.. Long-term TDM revealed extensive variability in serum concentrations over time; the variability was lowest for levetiracetam, moderate for valproate, and highest for clobazam. Pharmacokinetic variability and interactions can thus be identified and adjusted to facilitate decision making to achieve the optimal treatment outcome.

Topics: Adolescent; Adult; Anticonvulsants; Benzodiazepines; Child; Child, Preschool; Clobazam; Dioxolanes; Drug Monitoring; Epilepsies, Myoclonic; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Norway; Retrospective Studies; Valproic Acid; Young Adult

The purpose of this study was to determine the efficacy of perampanel (PER) on secondary bilateral synchrony (SBS) and behavioral problems in adolescents with epilepsy who showed insufficient response to levetiracetam (LEV).. The primary criterion for patient selection was the presence of SBS. The criteria such as age between 12 and 18 years, seizures refractory to antiseizure medications including LEV, at least four seizures a month, neuropsychological impairments, and at least 12 months of follow-up also had to be fulfilled. Patients were given PER at an initial dose of 2 mg/day, followed by increments of +2 mg/day every 2 weeks. Concomitant medications remained unchanged during evaluation period. Responders for electroencephalogram (EEG) and seizures were identified as showing a ≥50 % reduction from the baseline SBS on EEG and seizure frequency, respectively. Neuropsychological impairments as per the Japanese manuals for the Aberrant Behavior Checklist (ABC-J) were evaluated before and after PER administration.. Eight of 14 patients were considered responders for seizures. Among these 8 responders, 6 patients were considered responders for EEG and behavioral problems. Mean ABC-J scores in both EEG non-responders and responders were decreased significantly at 12 months (p < 0.05 and p < 0.05, respectively). ABC-J scores were significantly lower in EEG responders than in EEG non-responders at 12 months (p < 0.01). Moreover, among patients with decreased ABC-J scores, the degree of decrease was larger in EEG responders than in EEG non-responders (p < 0.01).. PER may be useful in reducing SBS on EEG, seizure frequency, and behavioral problems.

Topics: Adolescent; Anticonvulsants; Epilepsy; Humans; Infant; Levetiracetam; Nitriles; Piracetam; Problem Behavior; Pyridones; Treatment Outcome

Topics: 3-Hydroxybutyric Acid; Action Potentials; Alzheimer Disease; Animals; Anticonvulsants; Atropine; Disease Models, Animal; Donepezil; Drug Administration Schedule; Electroencephalography; Epilepsy; Ethosuximide; GABA Antagonists; Humans; Injections, Intraperitoneal; Lactic Acid; Levetiracetam; Male; Mice; Mice, Transgenic; Nootropic Agents; Organophosphorus Compounds; Parasympatholytics; Plaque, Amyloid; Pyruvic Acid; Video Recording

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are immune-mediated diseases characterized by an extensive loss of the epidermal skin layer, often resulting in death. SJS and TEN are often triggered by certain drugs, including antiepileptic drugs (AEDs). Epilepsy is very difficult to treat and often involves the combination of two or more AEDs. In this study, we quantified not only the risk of SJS or TEN associated with single-AED therapy but also the risk related to concomitant AED treatment using reporting-derived signals.. An analysis of the Japanese Adverse Drug Event Report (JADER) database was performed from the first quarter of 2004 to the fourth quarter of 2018. The single-AED signals were evaluated using the proportional reporting ratio (PRR), and the combination therapy signals were evaluated using Ω shrinkage measure and combination risk ratio (CRR).. SJS signals were associated with 11 AEDs, and TEN signals were related to 12 AEDs. Moreover, the following AED combinations were associated with SJS signals: carbamazepine-lorazepam (Ω. This study identified two AED combinations that increased the SJS signals and seven combinations that increased the TEN signals. Although AED monotherapies require attention for SJS and TEN, some AED combinations require extra caution.

Topics: Anticonvulsants; Carbamazepine; Clobazam; Clonazepam; Databases, Factual; Drug Therapy, Combination; Epilepsy; Gabapentin; Humans; Japan; Lacosamide; Lamotrigine; Levetiracetam; Lorazepam; Pharmacovigilance; Phenytoin; Stevens-Johnson Syndrome; Valproic Acid

The study aimed to determine the frequency of metabolic syndrome (MetS) and obstructive sleep apnea syndrome (OSAS) in patients with epilepsy receiving monotherapy and the relationship between these syndromes and antiepileptic drugs (AEDs).. Two hundred and ninety-seven patients with epilepsy between the ages of 18-65 years receiving monotherapy for at least one year and 50 healthy participants were enrolled. Body mass indices and waist circumferences were measured. Serum fasting glucose levels, high-density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol (TC), triglyceride, and serum AED concentrations were noted. The frequency of MetS in patients with epilepsy was calculated. The snoring, tiredness, observed apnea, high blood pressure, body mass index, age, neck circumference, and male gender (STOP-Bang) questionnaire was used to determine the risk of OSAS. The relationship between these two syndromes and seizure type, disease duration, AED dosage, and treatment duration was analyzed.. Metabolic syndrome was more frequent in patients with epilepsy compared with healthy participants (32.6% vs. 12.0%), and it was diagnosed in 37.8% of patients receiving valproic acid (VPA), 36.1% of patients receiving carbamazepine (CBZ), 34.9% of patients receiving oxcarbazepine (OXC), and 30.5% of patients on levetiracetam (LEV). There was a positive correlation between VPA treatment duration and MetS existence (p < 0.05). However, MetS frequency did not change because of seizure type, disease duration, or AED dosages in patients with epilepsy receiving monotherapy. The risk for OSAS was higher in patients with epilepsy compared with healthy participants (24.6% vs. 12%), and it was calculated high in 27.7% of patients receiving CBZ, 32.2% of patients receiving LEV, and 30.2% of patients receiving OXC. The OSAS risk was higher in patients who have focal seizures than generalized seizures (p = 0.044). There was no relationship between OSAS risk and duration of epilepsy, duration of treatment, drug doses, and serum drug levels (p > 0.05).. Higher frequency of MetS and OSAS risk should be kept in mind on clinical follow-up of patients with epilepsy receiving monotherapy.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Carbamazepine; Cross-Sectional Studies; Epilepsy; Female; Humans; Levetiracetam; Male; Metabolic Syndrome; Middle Aged; Oxcarbazepine; Sleep Apnea, Obstructive; Valproic Acid; Young Adult

Interindividual variations in the efficacy of antiseizure medications make epilepsy treatment challenging. This is due to genetic factors such as gene polymorphisms in Adenosine-triphosphate (ATP)-binding cassette sub-family B member 1 (ABCB1). In this article, the impact of polymorphisms in the P-glycoprotein-encoding gene, ABCB1 (C1236T, G2677T/A, and C3435T), on levetiracetam disposition was evaluated in Uygur Chinese children with epilepsy.. MDR1 C3435T polymorphism was analyzed by polymerase chain reaction-fluorescence staining in situ hybridization. The χ test and Fisher exact test were used to analyze the allelic and genotypic distribution of ABCB1, C1236T, G2677T, and C3435T between the drug-resistant and drug-responsive groups. Differences in steady-state and dose-corrected levetiracetam serum concentrations between the different genotypes were analyzed using 1-way analysis of variance and Mann-Whitney test.. Total 245 Uygur children with epilepsy were analyzed [drug-resistant, n = 117 (males:females = 53:64) and drug-responsive, n = 128 (males:females = 76:52)]. The frequency of ABCB1 C1236T, G2677T/A, and ABCB1 C3435T genotypes, alleles, haplotypes, or diplotypes did not differ significantly between the 2 groups (P > 0.05). Significantly higher levetiracetam concentrations and serum concentration/body mass dose were seen in ABCB1 2677-GT, TT, GA, and AT genotypes and 3435-TT carriers compared with GG and CC carriers (P = 0.021 and P = 0.002 versus P = 0.001 and P = 0.000, respectively).. ABCB1 G2677T/A and C3435T may affect levetiracetam disposition and therapeutic efficacy in Uygur children with epilepsy. Genetic analysis could be a valuable tool for predicting the response to antiseizure medications before the start of treatment and could contribute to personalized medicine for Uygur children with epilepsy.

Topics: Anticonvulsants; ATP Binding Cassette Transporter, Subfamily B; Child; Child, Preschool; China; Epilepsy; Female; Gene Frequency; Genotype; Haplotypes; Humans; Levetiracetam; Male; Polymorphism, Single Nucleotide

The aim of this study was to describe the prevalence of the use and prescribing patterns of anti-seizure medications (ASMs) over a six-year period, and to provide real-world evidence on medicine utilization of pediatric patients with epilepsy in China.. ASM prescriptions for pediatric patients written from 2013 to 2018 were extracted from the database of the Hospital Prescription Analysis Cooperative Project. Trends of ASM use were analyzed by total prescriptions, cost, age, sex, ASM class and specific ASM. Prescribing patterns of ASMs were also analyzed.. A total of 44,675 ASM prescriptions were extracted for analysis in this study. Throughout the study period, a slight increase of ASM prescriptions was observed from 6170 in 2013 to 8211 in 2018. Children aged between 6 and 18 years, accounted for 78 % of total prescriptions every year. ASM use in boys was about 1.5 times higher than that in girls. Newer ASMs were prescribed more than older ASMs during this period. Sodium valproate was the most frequently prescribed ASM in 2013, and its use decreased in girls in 2016. Levetiracetam increased from 19.10 % in 2013 to 28.09 % in 2018 and became the most common ASM at the end of this study. Meanwhile, the use of oxcarbazepine increased from 19.31 % to 22.04 %, whereas the use of lamotrigine had declined from 18.43 % to 10.72 %. Monotherapy (66.24 %) was more frequently used than combined therapy, which included dual combination (25.80 %) and triple or more combinations (7.96 %).. There is an increased ASM prescription trend in childhood usage. Levetiracetam has replaced sodium valproate as the most frequently prescribed ASM in pediatric patients. Newer ASMs with fewer side effects and drug interactions are increasingly utilized, which is consistent with evolving recommendations by the medical community.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; China; Epilepsy; Female; Humans; Infant; Lamotrigine; Levetiracetam; Male; Oxcarbazepine; Piracetam; Seizures; Valproic Acid

Topics: Epilepsy; Female; Humans; Levetiracetam; Middle Aged; Psychoses, Substance-Induced; Schizophrenia

Topics: Aged, 80 and over; Anticonvulsants; Epilepsy; Female; Humans; Joint Dislocations; Levetiracetam; Recurrence; Temporomandibular Joint Disorders

There is a limited amount of data regarding levetiracetam (LEV), an antiepileptic drug.. This study was conducted to assess the effect of LEV on antioxidant status and liver enzymes.. In this case-control study, 33 epileptic patients under treatment with LEV for at least 6 months were compared with 35 healthy subjects. We measured serum total antioxidant capacity (TAC), salivary superoxide dismutase (SOD), alanine aminoteransferase (ALT), and aspartate aminoteransferase (AST) levels in both groups. Dietary intakes were collected using a Food Frequency Questionnaire (FFQ).. The level of TAC in the healthy subjects was significantly higher than it was in the patients (P=0.02), but the mean of ALT (P=0.02) and AST (P=0.03) was significantly higher in the patients in comparison with the controls. Mean salivary SOD showed no difference between the two groups. In the patients, the duration of drug use was inversely correlated with serum TAC (p=0.04) and had a direct correlation with ALT (p=0.01) and AST (p=0.03.).. The results of our study indicated that LEV increased liver enzymes Also, treatment with this drug did not improve oxidative stress, but this could be due to the different in the dietary antioxidant intake. Routine screening of the liver and antioxidant enzymes in patients with chronic use of LEV is recommended.

Topics: Adult; Amylases; Anticonvulsants; Antioxidants; Epilepsy; Female; Humans; Levetiracetam; Liver; Male; Middle Aged; Oxidative Stress; Superoxide Dismutase

Levetiracetam (LEV) has an improved pharmacological profile and is one of the most commonly used antiepileptic drugs (AEDs). However, associations between this pharmacological profile and behavioral side effects have been extensively reported in pediatric populations. We assessed behavioral changes after initiation of LEV, prescribed by the treating neurologist, in Chilean patients with epilepsy aged 4-15 years. A behavioral questionnaire was applied at baseline and at two, four, and twelve weeks of treatment. Thirty patients were enrolled: 16 males, 14 females, average age 8 years (range: 4-14). By week four, 23.3% of patients showed significant behavioral alterations that persisted throughout the observation period. No significant alterations emerged after four weeks in the remaining patients. Family history of psychiatric disease and prior behavioral difficulties were predisposing factors for adverse behavioral effects. Although previous studies associated adverse behavioral effects with LEV in pediatric patients with epilepsy, we believe that this is the first study to use a prospective methodology and standardized tools to quantify the symptomatology. Adverse behavioral effects may significantly affect quality of life for patients and families, diminishing the tolerability of treatment. To ensure successful therapy and improve medical decision-making, it is essential to consider predisposing factors for drug-related adverse effects and to regularly assess for behavioral alterations during treatment.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Prospective Studies; Quality of Life

Although levetiracetam (LEV) is globally established as a leading antiseizure medication (ASM) it is still a controversial matter whether dose increases correspond with an increased efficacy if LEV in the recommended dose range did not show satisfying efficacy. In our clinical perception we questioned the value of dose increases in such non-responders.. In this retrospective monocenter study we analyzed the data of adult people with epilepsies (PWE) with focal-onset seizures who had been treated at the department of adults of the Kork Epilepsy Center between 2009 and 2019, who had been on a stable daily LEV dose and in whom LEV was further increased due to further seizures in spite of baseline LEV in a recommended daily dose range. For reasons of data homogeneity, we included only PWE with at least two definite seizures during the hospital stay under the baseline LEV dose who were treated and observed as in-patients after the increase of LEV for a period at least three-fold longer than the baseline interval before. Additional data acquisition comprised clinical data including adverse events, serum concentrations of LEV and other ASMs, and additional laboratory findings. The primary outcome variable was the change of seizure frequency prior to and after the increase of LEV.. Out of 518 PWE who had been on LEV during their hospital stay, a total of 61 PWE fulfilled the inclusion criteria. After a gradual dose increment, 91,8 % of PWE showed a reduced seizure frequency, 73,8 % had a reduction of seizures of 50 % or more, and 21,3 % were seizure-free during the observation period. A significant seizure reduction could be shown with a seizure count of 2,5/week prior to the increment and 0,7/week after dose increment (p < 0,00001). Seven PWE reported minor adverse events and ten PWE showed slight laboratory changes (within normal levels).. Contrary to our long-term clinical impression, LEV dose increments were reasonable and improved the seizure situation in PWE, usually without additional safety hazards.

Topics: Adult; Anticonvulsants; Drug Therapy, Combination; Epilepsy; Humans; Levetiracetam; Male; Middle Aged; Seizures; Treatment Outcome; Young Adult

The aim of this study was to evaluate the effects of valproate (VPA), lamotrigine (LTG), and levetiracetam (LEV) on bone turnover and bone mineral density (BMD) in newly diagnosed adult patients with epilepsy.. Eligible adult patients who were newly diagnosed with epilepsy were treated with VPA, LTG, and LEV. The chemical indicators of bone metabolism and BMD were measured before treatment and 2 years after treatment with different antiseizure medication (ASM) monotherapies. Then, the differences in these parameters before and after treatment were analyzed.. One hundred twenty-four patients completed the 2 years follow-up; 43 received monotherapy with VPA, 32 received LTG, and 49 received LEV. Serum parathyroid hormone (PTH), bone alkaline phosphatase (B-ALP), and β-cross-linked C-telopeptide of type I collagen (β-CTX) levels were elevated in adult patients after 2 years of VPA administration; the serum procollagen I intact N-terminal peptide (PINP) level was noticeably higher in patients after LEV treatment than before treatment. Meanwhile, the BMD of the lumbar spine and femoral neck did not change in patients treated with VPA, LTG, and LEV.. Valproate altered bone turnover in adult patients with epilepsy, while LTG and LEV did not exert harmful effects on bone health in adult patients.

Topics: Adult; Anticonvulsants; Bone Density; Epilepsy; Humans; Lamotrigine; Levetiracetam; Triazines; Valproic Acid

Atorvastatin and aspirin have been used in treating different forms of epilepsy. However, their effect on post-stroke epilepsy (PSE) still needs to be validated by large-scale clinical studies. In addition, their impact on the use of the antiepileptic drug levetiracetam for post-stroke epilepsy remains to be explored. Thus, the aim of this study was to further evaluate the effect of atorvastatin and aspirin on PSE and their effect on the usage of the antiepileptic drug levetiracetam in PSE patients.. Patients, aged 65 to 85 years, with newly diagnosed post-ischemic stroke epilepsy from August 30, 2014 to August 30, 2018 were included in the study, with the exclusion of those with coexisting conditions.. Initially, 1321 patients were included, and 780 remained in the study at the 1-year follow-up. During the study, atorvastatin treatment with or without aspirin reduced the number of clinical epileptic episodes in PSE patients. It also reduced the dosage of levetiracetam and achieved better control of epilepsy compared to levetiracetam mono-treatment. Aspirin co-treatment with levetiracetam did not result in a significant improvement. However, the combination of aspirin with atorvastatin significantly reduced the number of seizures compared to atorvastatin treatment alone.. Atorvastatin and aspirin co-treatment with levetiracetam can reduce epilepsy in PSE patients and reduce the dosage of levetiracetam required for effective control of PSE.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Aspirin; Atorvastatin; Cerebral Infarction; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Severity of Illness Index; Stroke

To assess the possibility that the occurrence of seizures or the use of antiepileptic drug (AED) therapy might have influenced the rate of occurrence of volunteered histories of patient-recognized depression during pregnancy in women with epilepsy.. Analysis of data from 2039 pregnancies in the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy (APR) followed during pregnancy and to the end of the year after its end.. Patient-recognized depression occurrence rates during pregnancy were a little lower rather than higher in seizure-affected than in seizure-free pregnancies (5.67% vs 6.41%), though higher in AED-treated than AED-untreated pregnancies (6.24% vs 5.26%; RR = 1.185, 95% CI 0.612, 2.295). Logistic regression analysis showed that carbamazepine dosage had a statistically significant relationship with a decreasing rate of patient-recognized depression occurring during pregnancy and topiramate dosage with an increasing rate.. Carbamazepine and topiramate both have established potentials for causing teratogenesis, and it is possible that replacement of carbamazepine with a less teratogenic AED, for example levetiracetam, might result in any subsequent depression that occurs in pregnancy being inappropriately attributed to the newly introduced agent.

Topics: Adult; Anticonvulsants; Australia; Carbamazepine; Depression; Epilepsy; Female; Humans; Levetiracetam; Pregnancy; Pregnancy Complications; Seizures; Topiramate

The aim of the study was to assess whether, male patients with epilepsy, switching from valproic acid (VPA) to levetiracetam (LEV) or lamotrigine (LMG) critically improves sperm counts and parameters, increasing chance of patients' female partners to spontaneously conceive.. This is an observational prospective study recruiting all consecutive infertile male patients with epilepsy followed up at the outpatient Epilepsy Clinic of University Hospital of Ioannina, Northwest Greece. Infertile couples were referred to the Laboratory of Assisted Reproduction and Treatment of the University Hospital of Ioannina to conduct semen analysis. The first sample was collected while the patients were receiving VPA, and the second semen sample was collected after the patients were switched to LEV or LMG.. Seventeen infertile male patients were recruited in the study. Nine patients were switched to LEV, and eight patients were switched to LMG. The mean sperm count increased after VPA withdraw P = .06. Motility was improved with an increase of total motility and non-progressive motility (P = .02 and P = .03, accordingly), whether sperm defects were decreased, mainly head defects (P = .03). Differences between patients switched to LEV or LMG were minimal and showed no significant findings. Spontaneous pregnancies were reported in three of the patients' partners, without any other clinical intervention offered to the couple.. Switching from valproic acid to levetiracetam or lamotrigine improved sperm counts and other sperm parameters in subfertile male patients and increased the chance of spontaneously conceiving in subfertile couples.

Topics: Adult; Anticonvulsants; Drug Substitution; Epilepsy; Female; Greece; Humans; Infertility, Male; Lamotrigine; Levetiracetam; Male; Pregnancy; Pregnancy Rate; Prospective Studies; Sperm Count; Sperm Motility; Spermatozoa; Valproic Acid

The study aims to quantify the types of antiepileptic drugs (AED) prescribed in neurology consultations.. This descriptive, observational study included a sample of 559 patients older than 14 years, diagnosed with epilepsy, and receiving pharmacological treatment. Data were collected at outpatient consultations by 47 Spanish neurologists in May 2016. Epilepsy was defined based on the International League Against Epilepsy classification. According to the year of marketing, AEDs were categorised as classic (before 1990) or new (after 1990). We performed a descriptive analysis of qualitative and quantitative variables.. Female patients accounted for 54.6% of the sample. Mean age was 42.7 years; mean age of onset was 22.4. Regarding epilepsy type, 75.7% of patients experienced partial seizures, 51.5% were symptomatic,32.4% had refractory epilepsy, 35.6% had been seizure-free for the previous year, and 59.2% had associated comorbidities.A total of 1103 AED prescriptions were made; 64.6% of prescriptions were for new AEDs; 85.4% of patients received new AEDs. Patients received a mean of 2 AEDs (range, 1-5). A total of 59.6% of patients received polytherapy.The most frequently prescribed AEDs were levetiracetam (42.6%), valproic acid (25.4%), lamotrigine (19.5%), carbamazepine (17.9%), and lacosamide (17.5%). No AED was employed exclusively as monotherapy. The most frequently prescribed AEDs for generalised and partial seizures were valproic acid (48.2%) and levetiracetam (43.2%), respectively. Valproic acid was less frequently prescribed to female patients. Patients with refractory epilepsy or with associated comorbidities were more frequently prescribed a combination of new and classic AEDs (48.7% and 45.6%, respectively) than only one type of AED.. The majority of patients received new AEDs. The combination of classic and new AEDs was more frequently prescribed to patients with refractory epilepsy or with associated comorbidities.

Topics: Adult; Anticonvulsants; Drug Therapy, Combination; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Neurology; Referral and Consultation; Seizures; Spain; Valproic Acid

The association of depression and epilepsy is thought to be bidirectional. The present study aimed to evaluate the prevalence of depression in patients on antiepileptic drugs (AEDs) and factors affecting it.. In this preliminary cross sectional study, patients at epilepsy clinic of a tertiary care centre were studied for occurrence of depression, using Hospital Anxiety and Depression Scale (HADS-D) and Patient Health Questionnaire (PHQ-2) scales. Correlation analysis was carried out to determine the factors associated with presence of depression in these patients.. A total of 12 AEDs (maximum 5 per patient including older and newer) were prescribed to 933 patients in different treatment regimens over a period of 3 years. The median age of the patients was 22 years (10-77) and among them 63.5% were men. Mild and clinically relevant depression occurred in 279 (29.9%) and 223 (23.9%) patients, respectively. Mean HADS-D and PHQ-2 score was significantly higher with polytherapy as compared to monotherapy (p < 0.001). Patients on levetiracetam exhibited significantly higher HADS-D score in comparison to phenytoin (p < 0.001), carbamazepine (p < 0.001) and sodium valproate (p < 0.05). However, there was no significant difference in PHQ score among patients on monotherapy of different AEDs. Multivariate regression analysis suggested correlation between depression and seizure frequency, total number of AEDs and their load (p < 0.001).. Depressive symptoms were found to be present in more than half of the patients with epilepsy which require detailed work up for depression. Levetiracetam was found to be associated with a higher incidence of subclinical depression which needs further investigation.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Cross-Sectional Studies; Depression; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Patient Health Questionnaire; Prevalence; Risk Factors; Tertiary Care Centers; Young Adult

Levetiracetam is an antiepileptic drug with good tolerability that is used for focal and generalized epilepsy as well as acute treatment of status epilepticus; it is also a first-line antiepileptic drug for patients with concomitant medical conditions. The effect of blood levetiracetam concentration on its efficacy and safety in Japanese patients with epilepsy is unknown.. This retrospective cohort study compared the efficacy and safety of levetiracetam alone and in combination with other antiepileptic drugs in 255 outpatients with epilepsy treated with levetiracetam. Electronic medical records were accessed to analyse clinical parameters including blood concentrations of levetiracetam and concomitant antiepileptic drugs, clinical laboratory values and adverse reactions.. Combination of levetiracetam with antiepileptic drugs, even those that alter cytochrome P450 activity, did not affect blood levetiracetam concentrations. Similarly, levetiracetam use did not significantly affect blood concentrations of concomitantly used antiepileptic drugs. Although blood levetiracetam concentration was significantly increased in older patients and those with renal dysfunction, the rates of adverse reactions were not increased.. Levetiracetam may be used effectively and safely without dose adjustment using blood concentration monitoring even when administered in combination with other antiepileptics for Japanese patients with epilepsy.

Topics: Adult; Anticonvulsants; Asian People; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Retrospective Studies

Topics: Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Piracetam; Seizures

Topics: Epilepsy; Humans; Levetiracetam; Phenobarbital

The objective of this study was to describe antiepileptic drug (AED) treatment patterns in patients with epilepsy, with and without psychiatric comorbidities.. This was a retrospective claims-based cohort study using Truven Health MarketScan databases (Commercial and supplemental Medicare, calendar years 2012-2017; Medicaid, 2012-2016). Persons met epilepsy diagnostic criteria, had an index date (first epilepsy diagnosis) with a preceding 2-year baseline (<1 year for persons of 1 to <2 years of age; none for persons <1 year), and continuous medical and pharmacy enrolment without epilepsy/seizure diagnosis or AED prescription during baseline. Based on presence/absence of psychiatric diagnosis codes in the baseline period, persons were classified into two cohorts: with or without psychiatric comorbidities. Outcomes included percentage of treated persons (AED prescription), type, duration, and outcome of first-line AED treatment.. There were 18,062 persons in each cohort with and without psychiatric comorbidities, matched by age, sex, and insurance type, who met selection (or inclusion) criteria. More patients with psychiatric comorbidities were prescribed an AED after diagnosis (57.6% vs. 52.8%), and had at least two AEDs prescribed during follow-up (16.7% vs. 11.4%) than patients without psychiatric comorbidities. Most patients with and without psychiatric comorbidities prescribed AED monotherapy as first-line treatment (73.0% vs. 78.7%). Levetiracetam was the most common AED prescribed less frequently in patients with than without psychiatric comorbidities (40.8% vs. 56.7%). More patients with psychiatric comorbidities changed first-line AED treatment than patients without psychiatric comorbidities.. The presence of psychiatric comorbidities may impact treatment decisions in newly diagnosed persons with epilepsy to optimize patient outcomes.

Topics: Adolescent; Adult; Anticonvulsants; Child, Preschool; Cohort Studies; Comorbidity; Epilepsy; Female; Humans; Levetiracetam; Longitudinal Studies; Male; Medicaid; Medicare; Mental Disorders; Middle Aged; Retrospective Studies; United States

While levetiracetam (LEV) usage is a known risk factor for psychosis in epilepsy, the modulating effect of certain patient and treatment characteristics on the risk of psychosis has yet to be fully elucidated.. In our tertiary epilepsy center, 84 patients with psychotic symptoms during LEV usage and 100 controls without psychotic symptoms during LEV usage were selected. Patient records were reviewed including demographics, medical history, antiepileptic drug use, and cognitive abilities. Univariate comparisons were performed, and variables with p < 0.1 were selected for binary logistic regression analysis.. The total incidence of psychosis during LEV therapy in our population was 3.7%. The timing of psychotic symptoms was classified as postictal in 20 (19.8%), interictal in 14 (15.4%), postepilepsy surgery in 1 (1.1%), and unknown in 18 cases (19.8%). In 31 cases (34.1%), psychotic symptoms were classified as an antiepileptic drug-induced psychotic disorder (AIPD) as a result of LEV. In 7 cases (7.7%), AIPD occurred as a result of a different antiepileptic drug. A significant association was found between the experience of psychotic symptoms and status epilepticus (p = 0.002), a history of psychotic symptoms (p < 0.000), a history of psychiatric illness other than psychosis (p = 0.010), and concomitant phenytoin (PHT) usage (p = 0.044). Cotherapy with lamotrigine (LTG) was protective (p = 0.042). A separate analysis of controls and exclusively the 31 cases with LEV-induced AIPD yielded comparable results; a significant association was confirmed with status epilepticus (p = 0.021) and history of psychotic symptoms (p = 0.018), as well as with female gender (p = 0.047) and intellectual disability (p = 0.043).. Our retrospective study found that psychotic symptoms during LEV therapy were significantly associated with status epilepticus, a history of psychotic symptoms, a history of psychiatric illness other than psychosis, and concomitant PHT usage, whereas concomitant LTG usage was protective. Psychotic symptoms specifically as an adverse drug reaction to LEV were significantly associated with female gender, intellectual disability, status epilepticus, and a history of psychotic symptoms.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Case-Control Studies; Epilepsy; Female; Humans; Incidence; Levetiracetam; Logistic Models; Male; Middle Aged; Psychoses, Substance-Induced; Retrospective Studies; Risk Factors; Young Adult

Topics: Anticoagulants; Atrial Fibrillation; Epilepsy; Humans; Levetiracetam; Warfarin

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease (PD). The LRRK2 physiological and pathological function is still debated. However, different experimental evidence based on LRRK2 cellular localization and LRRK2 protein interactors suggests that LRRK2 may be part and regulate a protein network modulating vesicle dynamics/trafficking. Interestingly, the synaptic vesicle protein SV2A is part of this protein complex. Importantly, SV2A is the binding site of the levetiracetam (LEV), a compound largely used in human therapy for epilepsy treatment. The binding of LEV to SV2A reduces the neuronal firing by the modulation of vesicle trafficking although by an unclear molecular mechanism. In this short communication, we have analysed the interaction between the LRRK2 and SV2A pathways by LEV treatment. Interestingly, LEV significantly counteracts the effect of LRRK2 G2019S pathological mutant expression in three different cellular experimental models. Our data strongly suggest that LEV treatment may have a neuroprotective effect on LRRK2 pathological mutant toxicity and that LEV repositioning could be a viable compound for PD treatment.

Topics: Animals; Anticonvulsants; Cell Line, Tumor; Cells, Cultured; Epilepsy; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Levetiracetam; Membrane Glycoproteins; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Mutation; Nerve Tissue Proteins; Neurites; Neurons; Parkinson Disease; PC12 Cells; Protein Binding; Rats; Signal Transduction; Synaptic Vesicles

The objective was to describe the frequency, mode of presentation and characteristics of epilepsy in children with congenital hemiparesis (CH). It is a etrospective, descriptive and multicenter study, based on the collection of data from the clinical records of patients from 0 to 19 years with CH secondary to perinatal infarction in different centers of the community of Catalonia. A total of 310 children were included (55% males and 45% females), from a total of 13 centers in Catalonia. Average age of onset of the crises was 2 ± 1 year. Epilepsy was present in 29.5% (n = 76), among which the most frequent vascular subtype was arterial presumed perinatal ischemic stroke (51.3%), followed by neonatal arterial ischemic stroke (18.4%), periventricular venous infarction (15.8%), neonatal hemorrhagic stroke (10.5%) and neonatal cerebral sinovenous thrombosis (3.9%). Semiology of the most frequent seizures was motor focal in 82%, followed by focal motor with secondary bilateralization in 23%, focal discognitive in 13.5%, generalized by 2% and spasms in 6.5%. The 67.3% were controlled with monotherapy and the drugs used were valproate, levetiracetam or carbamazepine. The antecedent of electrical status during sleep was identified in 3 patients, all associated with extensive lesions that included the thalamus. Of the total number of children with epilepsy, 35% began with neonatal seizu res in the first 3 days of life. The 30% of children with perinatal stroke and CH present a risk of epilepsy during childhood. Children with ischemic strock have the highest risk, so they will require a follow-up aimed at detecting prematurely the epilepsy and start a treatment.. El objetivo fue describir la frecuencia, modo de presentación y características de la epilepsia en niños con hemiparesia congénita (HC). Estudio retrospectivo, descriptivo y multicéntrico, basado en la recolección de datos de las historias clínicas de pacientes de 0 a 19 años con HC secundaria a infarto perinatal en diferentes centros de la comunidad de Cataluña. Se incluyeron 310 niños (55% varones y 45% mujeres) de un total de 13 centros de Cataluña. Edad media del debut de las crisis fue de 2 ± 1 año. Presentaron epilepsia el 29.5% (n = 76), el subtipo vascular más frecuente fue el infarto presumiblemente perinatal (51.3%), seguido del accidente isquémico arterial neonatal (18.4%), infarto hemorrágico venoso periventricular (15.8%), infarto hemorrágico neonatal (10.5%) y trombosis venosa neonatal (3.9%). La semiología de las crisis más frecuente fue la focal motora en un 82%, seguida de las focales motoras con bilateralización secundaria en el 23%, focales discognitivas en 13.5%, generalizadas 2% y espasmos 6.5%. El 67.3% se controló con monoterapia y los fármacos empleados fueron el valproato, levetiracetam o carbamacepina. Se identificó el antecedente de estatus eléctrico durante el sueño en 3 pacientes, todos asociados a lesiones extensas que incluían al tálamo. Del total con epilepsia, el 35% debutaron con convulsiones neonatales en los primeros 3 días de vida. El 30% con accidente cerebrovascular perinatal y HC presentan riesgo de padecer epilepsia durante la infancia. Aquellos con infartos isquémicos tienen el riesgo más alto, por lo que requerirán un seguimiento dirigido a detectar precozmente la epilepsia e iniciar tratamiento.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Infant, Newborn; Levetiracetam; Male; Paresis; Retrospective Studies; Risk Factors; Seizures; Spain; Stroke; Valproic Acid; Young Adult

Several antiepileptic drugs (AEDs) are administrated during pregnancy according to recent therapeutic protocols. Ten percent of pregnant women with epilepsy give birth to offspring with malformations and teratogenic defects. Since the mechanism of action of AEDs is not yet completely understood, therefore, it could be hypothesized that they may cause cyto- or genotoxicity in embryonic fetus cells. To investigate this hypothesis, the genotoxicity and cell survival of AEDs treated human embryonic stem cells (hESCs) were investigated by single-cell gel electrophoresis (Comet assay) and MTS assay, respectively. HESCs (Royan H6 cell line) were treated in-vitro with high therapeutic doses of Carbamazepine, Gabapentin, Lamotrigine, Levetiracetam or Topiramate as monotherapy or combination therapy of each drug with Folic acid. After hESCs pluripotency confirmation, the effect of AEDs on cellular DNA damage of hESCs was investigated. levetiracetam and topiramate were found to damage the DNA significantly compared to untreated cells. The amount of DNA damage produced by carbamazepine and lamotrigine was similar while for gabapentin, the amount of DNA migration was very low and produced less DNA damage than the others. A considerable reduction in DNA damages occurred in genotoxicity in the presence of Folic acid in comparison to AEDs monotherapies. According to our results, all mentioned AEDs caused DNA damage, while Levetiracetam and topiramate caused more extensive DNA damages than the others. Noticeably, the addition of Folic acid to the treated cells decreased the DNA damages considerably.

Topics: Anticonvulsants; Carbamazepine; DNA Damage; Epilepsy; Female; Human Embryonic Stem Cells; Humans; Lamotrigine; Levetiracetam; Phenytoin; Pregnancy

Topics: Child; Epilepsy; Humans; Levetiracetam; Phenytoin; Seizures; Status Epilepticus

Topics: Aggression; Akathisia, Drug-Induced; Anticonvulsants; Autism Spectrum Disorder; Child; Epilepsy; Humans; Levetiracetam; Male; Mental Disorders; Self-Injurious Behavior; Treatment Outcome

Topics: Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Seizures

Topics: Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Seizures

Incidence and prevalence of epilepsy increase with advancing age. Although the majority of late-onset epilepsies are of lesional origin, a considerable proportion of patients present with unknown etiology. The aim of this study was to evaluate the semiological, electroencephalographic (EEG), and cerebrospinal fluid (CSF) characteristics as well as the 12-month seizure outcome in a cohort of patients with nonlesional late-onset epilepsy (≥55 years).. A total of 54 patients with newly diagnosed nonlesional late-onset epilepsy (NLLOE) were retrospectively evaluated for seizure type using the most recent International League Against Epilepsy (ILAE) classification of seizure types, EEG characteristics, and CSF profile and followed-up for at least 12 months after epilepsy onset. Results were compared with a gender-matched control group of 58 patients with nonlesional early-onset epilepsy (NLEOE).. The predominant seizure types in NLLOE were focal to bilateral tonic-clonic seizures (30%) as well as focal onset impaired awareness motor seizures (IAMS) (22%) and focal onset impaired awareness nonmotor seizures (IANMS) (22%). The predominant seizure types in NLEOE were focal to bilateral tonic-clonic seizures (43%) as well as focal onset aware nonmotor seizures (ANMS) (31%) and IAMS (31%). Focal onset impaired awareness nonmotor seizures were found to be more characteristic in patients with NLLOE (p = 0.019; α < 0.05; NLLOE: 22.2% vs. NLEOE: 8.6%). Electroencephalography revealed no significant differences between groups. Of interest, three patients with NLLOE (8%) presented with oligoclonal bands (OCB) in CSF albeit absence of antineuronal antibodies. Seizure-free rate was 70%. Adverse effects from medication leading to antiepileptic drug (AED) change were reported in 12 patients (22%), valproate was the best tolerated AED in patients with NLLOE [adverse effects in 9%, compared with 12% (gabapentin) and 26% (levetiracetam)].. Using the most recent classification system, different patterns of semiological characteristics were identified: NLLOE more frequently present with IANMS, whereas patients with NLEOE rather have ANMS. Oligoclonal bands were only detected in patients with NLLOE, indicating that careful exclusion of autoimmune encephalitis in this patient group is warranted. Our findings may help to more accurately identify and characterize patients with NLLOE to improve targeted diagnostics and adequate treatment in this challenging group of patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Electroencephalography; Epilepsy; Female; Gabapentin; Humans; Late Onset Disorders; Levetiracetam; Male; Middle Aged; Retrospective Studies; Seizures; Treatment Outcome; Valproic Acid; Young Adult

Topics: Anticonvulsants; Behavior; Child, Preschool; Cognitive Dysfunction; Epilepsy; Humans; Levetiracetam; Male; Neuropsychiatry; Phenytoin; Seizures; Vasculitis

Although previous studies have investigated the influence of antiepileptic drugs (AEDs) on lipid profiles and thyroid hormone levels, there is little evidence regarding the effects of levetiracetam (LEV). Therefore, we conducted a prospective longitudinal study to evaluate the effects of LEV and carbamazepine (CBZ) treatment on lipid profile and thyroid hormone levels in patients newly diagnosed with epilepsy. Inclusion criteria were as follows: (a) age between 4 and 15 years, (b) diagnosis of epilepsy with at least two focal seizures within a year, and (c) newly treated with LEV or CBZ monotherapy. Serum lipid profile and thyroid hormone levels were measured before and after 1 and 6 months of AED initiation. Among the 21 included patients (LEV: 13 patients, CBZ: 8 patients), all but one patient in the LEV group continued AED monotherapy during the study period. Although triglyceride (TG) levels tended to be increased in the CBZ group (baseline: 58.3 ± 22.0 mg/dl, 1 month: 63.8 ± 21.6 mg/dl, 6 months: 92.3 ± 63.6 mg/dl, p = 0.22, analyses of variance (ANOVA)), there were no significant changes in total cholesterol (TC), TG levels, high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C) in either group. Serum free thyroxine (fT4) levels were significantly decreased in the CBZ group (baseline: 1.15 ± 0.06 ng/dl, 1 month: 1.00 ± 0.16 ng/dl, 6 months: 0.98 ± 0.14 ng/dl, p = 0.03, ANOVA). In contrast, there were no significant changes in fT4 or thyroid-stimulating hormone (TSH) levels in the LEV group. The results of the present study suggest that LEV monotherapy does not affect lipid profile or thyroid function while CBZ monotherapy may cause thyroid dysfunction.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Cholesterol, HDL; Cholesterol, LDL; Epilepsy; Female; Humans; Levetiracetam; Male; Prospective Studies; Thyroid Diseases; Thyrotropin; Thyroxine; Triglycerides

Pregnant women with epilepsy (PWWE) require continuous anti-epileptic drug (AED) treatment to avoid risk to themselves and fetal risks secondary to maternal seizures, resulting in prolonged AED exposure to the developing embryo and fetus. The objectives of this study were to determine whether high-resolution metabolomics is able to link the metabolite profile of PWWE receiving lamotrigine or levetiracetam for seizure control to associated pharmacodynamic (PD) biological responses. Untargeted metabolomic analysis of plasma obtained from 82 PWWE was completed using high-resolution mass spectrometry. Biological alterations due to lamotrigine or levetiracetam monotherapy were determined by a metabolome-wide association study that compared patients taking either drug to those who did not require AED treatment. Metabolic changes associated with AED use were then evaluated by testing for drug-dose associated metabolic variations and pathway enrichment. AED therapy resulted in drug-associated metabolic profiles recognizable within maternal plasma. Both the parent compounds and major metabolites were detected, and each AED was correlated with other metabolic features and pathways. Changes in metabolites and metabolic pathways important to maternal health and linked to fetal neurodevelopment were detected for both drugs, including changes in one‑carbon metabolism, neurotransmitter biosynthesis and steroid metabolism. In addition, decreased levels of 5-methyltetrahydrofolate and tetrahydrofolate were detected in women taking lamotrigine, which is consistent with recent findings showing increased risk of autism spectrum disorder traits in PWWE using AED. These results represent a first step in development of pharmacometabolomic framework with potential to detect adverse AED-related metabolic changes during pregnancy.

Topics: Adult; Anticonvulsants; Carbon; Epilepsy; Female; Fetus; Folic Acid; Humans; Lamotrigine; Levetiracetam; Metabolic Networks and Pathways; Metabolome; Metabolomics; Neurotransmitter Agents; Pregnancy; Pregnancy Complications; Prospective Studies; Steroids; Treatment Outcome

To describe the retention rates of first antiepileptic drugs (AEDs) in patients with poststroke epilepsy on a nationwide scale.. The Swedish Stroke Register, which has 94% coverage and high-resolution data on stroke, comorbidities, and disability, was cross-referenced to the National Patient Register, Drug Register, and Cause-of-Death Register. Patients with onset of AED-treated epilepsy after stroke in 2005-2010 were included. An algorithm based on prescription renewal intervals was used to analyze treatment data until the end of 2014.. A total of 4991 patients were included. First AEDs analyzed were carbamazepine (n = 2373), valproic acid (n = 943), levetiracetam (n = 555), lamotrigine (n = 519), phenytoin (n = 176), and oxcarbazepine (n = 89). The five-year retention rate was highest for lamotrigine (75%, 95%CI:70.4-79.4), followed by levetiracetam (69%, 95%CI:62.9-74.3), oxcarbazepine (68%, 95%CI:55.2-79.8), valproic acid (62%, 95%CI:57.8-66.4), carbamazepine (60%, 95%CI:57.6-62.4), and phenytoin (55%, 95%CI:45.2-64.0). There were minor differences in baseline characteristics with low levels of disability being slightly more common in patients treated with lamotrigine and levetiracetam. Atrial fibrillation and hypertension were more common in patients treated with levetiracetam, and atrial fibrillation was less common in patients treated with carbamazepine. In a Cox model adjusted for baseline characteristics, the risk of discontinuation was lower for lamotrigine (HR 0.53, 95%CI:0.43-0.67) and levetiracetam (HR 0.75, 95%CI:0.60-0.94) when compared to carbamazepine.. Lamotrigine and levetiracetam have higher retention rates than carbamazepine in poststroke epilepsy. This is in agreement with existing small RCTs in this patient group.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Carbamazepine; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Proportional Hazards Models; Registries; Stroke; Sweden

There is limited literature on cognitive, behaviour and sleep-related adverse effects of levetiracetam and oxcarbazepine among adult epilepsy patients, except for what is available from the initial efficacy trials. This study was initiated with the aim to evaluate the incidence and prevalence of various cognitive, behaviour and sleep-related adverse effects of levetiracetam versus oxcarbazepine among people with epilepsy.. The study was conducted in two parts: part A was a cross-sectional study, and part B was a longitudinal study. Trail making test A & B, digit symbol substitution test, Stroop colour and word test, controlled oral word association test and PGI memory scale, Neuropsychiatric Inventory, sleep log and ESS-I were used for assessment of cognitive, behaviour and sleep-related adverse effects.. In the cross-sectional as well as prospective study, no significant difference was observed in the cognitive performance of patients in levetiracetam and oxcarbazepine group in any of the cognitive assessment. Among 120 patients enrolled in the cross-sectional study, significantly higher number of patients in the levetiracetam group compared to the oxcarbazepine group,had agitation/aggression (20% vs10%, p =  0.047) and irritability (26.7% vs 3.3%, p = 0.007).Among 132 patients enrolled in the prospective study, significantly higher increase in the domain score of agitation/aggression (14.5% vs 1.6%, p = 0.028) and irritability (17.7% vs 1.6%, p =  0.018) was observed in the levetiracetam group compared to oxcarbazepine group. A significantly higher proportion of patients in the oxcarbazepine group had hypersomnolence (11.3% vs 1.6%, p =  0.026), as compared to the levetiracetam group.. On cross-sectional as well as on longitudinal assessment, nearly one-fifth of patients on levetiracetam have behaviour related adverse effects, with dose modification required for half among these. Nearly 11% of patients on oxcarbazepine reported sleep-related adverse effects (higher total sleep duration per 24 h).

Topics: Adult; Anticonvulsants; Cognition Disorders; Cross-Sectional Studies; Epilepsy; Female; Humans; Levetiracetam; Longitudinal Studies; Male; Mental Disorders; Neuropsychological Tests; Oxcarbazepine; Psychiatric Status Rating Scales; Sleep Wake Disorders; Young Adult

This active, open observational study aimed to investigate adverse drug reactions (ADRs) associated with six commonly used antiepileptic drugs (AEDs) in southern Chinese outpatients with epilepsy from 2003 to 2015.. The Wenzhou Epilepsy Follow-Up Registry Database (WEFURD) was established by a single epilepsy center in China in January 2003 to record AED efficacy and the associated ADRs by registered outpatients diagnosed with epilepsy. We reviewed the data of outpatients who had only taken one or more of six commonly used AEDs, namely, carbamazepine (CBZ), valproate (VPA), lamotrigine (LTG), oxcarbazepine (OXC), topiramate (TPM) and levetiracetam (LEV), and were registered in the WEFURD between 2003 and 2015. We evaluated the ADRs caused by the single or combined use of the above six specific AEDs based on the WHO-UMC scale. The data of the ADRs were categorized by age, sex, number of AEDs related to ADRs, medications, seriousness of ADRs, causality levels of the WHO-UMC scale and system organ class (SOC). The unit of analysis was one ADR.. A total of 3069 epilepsy outpatients (1807 outpatients with 5049 eligible ADRs and 1262 outpatients without ADRs) were included. The overall ADR rate was 58.88% (1807/3069). An average of 2.79 ADRs (5049/1807) occurred per patient with an ADR; 53.8% of the 5049 ADRs were recorded in females, and 50.4% were caused by monotherapy. Of the ADRs, 10.6% (537/5049) were severe adverse reactions (SARs), including 34 serious adverse effects (SAEs). The SAR rates caused by one, two and three or more AEDs were 9.9, 10.0 and 19.6%, respectively (p <  0.001). Eighteen SOC categories were identified, and the top three were psychiatric disorders (1633/5049, 32.3%), neurological disorders (1222/5049, 24.2%) and gastrointestinal disorders (564/5049, 11.2%). Of the 537 SARs, skin and appendage disorders accounted for 24.4% (131/537). Among the 34 SAEs, serious allergies, fetal malformations, renal calculus and pancreatitis accounted for the majority.. Our findings suggest that clinicians should pay attention to psychiatric ADRs and be alert for SARs, especially when three or more AEDs are used together. Moreover, active surveillance might provide another method of pharmacovigilance in China.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Child; Child, Preschool; China; Epilepsy; Female; Humans; Infant; Lamotrigine; Levetiracetam; Male; Middle Aged; Outpatients; Oxcarbazepine; Topiramate; Valproic Acid; Young Adult

Irritability has been described as a frequent adverse event in patients affected by epilepsy and treated with perampanel (PER), levetiracetam (LEV), and less frequently with valproic acid (VPA). Since the questionnaire for irritability (I-EPI) is a validated instrument to measure this psychiatric manifestation in patients affected by epilepsy, in this study we aimed at investigating the effect of PER as first add-on therapy on I-EPI. Moreover, we compared the effectiveness and I-EPI scores obtained at 12-month follow-up visits in patients treated by PER, LEV, or VPA in order to measure irritability as a consequence of these treatments.. We collected data from 17 patients treated by PER, 16 patients treated by LEV, and 16 patients under VPA treatment followed for 12 months.. We did not document significant changes of I-EPI questionnaire between baseline and follow-up in the PER group. As concerning the comparison of I-EPI among PER, LEV, and VPA groups, we documented lower global scores in PER than both LEV (P < 0.05) and VPA (P < 0.05) groups. Moreover, patients under PER treatment showed lower scores than LEV and VPA (P < 0.05) in I-EPI items measuring the gentle personality, anxiety of having epileptic seizures in front of others, and irritability in thinking that they can have an epileptic seizure.. This retrospective study described a stable and possibly lower degree of irritability in patients starting PER than LEV and VPA treatments, although we documented the comparable effectiveness of PER, LEV, and VPA as first add-on treatments in patients affected by uncontrolled epileptic seizures. However, the small sample of patients included in this study and the absence of I-EPI scores obtained at baseline visits in LEV and VPA groups require further investigations to confirm this preliminary evidence.

Topics: Adult; Anticonvulsants; Anxiety; Drug Therapy, Combination; Epilepsy; Female; Humans; Irritable Mood; Levetiracetam; Male; Nitriles; Personality; Preliminary Data; Pyridones; Retrospective Studies; Treatment Outcome; Valproic Acid

The aim was to study the impact of therapeutic drug monitoring (TDM) on paediatric patients on lamotrigine therapy and the evaluation of possible drug interactions, especially in triple antiepileptic drug combinations. During the period of 2001-2015, 1308 pre-dose samples were taken from 430 patients <15 years of age as part of routine TDM. Drug interactions were evaluated using calculation of lamotrigine clearance. Valproic acid decreased lamotrigine clearance by 54% in bitherapy, and by 21% in triple therapy with carbamazepine. Carbamazepine increased lamotrigine clearance by 191% in bitherapy. Levetiracetam and topiramate had no effect. The upper limit of lamotrigine therapeutic range (TR) was exceeded in 2% of cases in monotherapy, and in 6%-7% of cases in bi- or triple therapy. About 61% of plasma levels were found within the TR during 2001-2005, compared to 75% and 74% during 2006-2010 and 2011-2015, respectively. Adverse drug reactions (ADRs) were reported in 22 cases. Higher number of supratherapeutic levels in combination therapy led to a 3-fold increase in incidence of ADRs. Seizures occurred more often daily and monthly during 2001-2005 and in patients with three or four antiepileptic drugs in combination. Carbamazepine only partially compensated for the inhibitory effect of valproic acid. Lamotrigine clearance in monotherapy in children is similar to adults, but in polytherapy was found higher susceptibility to induction. A significantly higher number of supratherapeutic lamotrigine levels were found in combinations with valproate. Despite poor correlation with TR, both seizure frequency and ADRs declined after the implementation of TDM.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Czech Republic; Dose-Response Relationship, Drug; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Humans; Incidence; Lamotrigine; Levetiracetam; Male; Metabolic Clearance Rate; Severity of Illness Index; Topiramate; Valproic Acid

Levetiracetam is a commonly used antiepileptic drug, yet psychiatric adverse effects are common and may lead to treatment discontinuation.. To derive prediction models to estimate the risk of psychiatric adverse effects from levetiracetam use.. Retrospective open cohort study. All patients meeting the case definition for epilepsy after the Acceptable Mortality Reporting date in The Health Improvement Network (THIN) database based in the United Kingdom (inclusive January 1, 2000, to May 31, 2012) who received a first-ever prescription for levetiracetam were included. Of 11 194 182 patients registered in THIN, this study identified 7400 presumed incident cases (66.1 cases per 100 000 persons) over a maximum of 12 years' follow-up. The index date was when patients received their first prescription code for levetiracetam, and follow-up lasted 2 years or until an event, loss to follow-up, or censoring. The analyses were performed on April 22, 2018.. A presumed first-ever prescription for levetiracetam.. The outcome of interest was a Read code for any psychiatric sign, symptom, or disorder as reached through consensus by 2 authors. This study used regression techniques to derive 2 prediction models, one for the overall population and one for those without a history of a psychiatric sign, symptom, or disorder during the study period.. Among 1173 patients with epilepsy receiving levetiracetam, the overall median age was 39 (interquartile range, 25-56) years, and 590 (50.3%) were female. A total of 14.1% (165 of 1173) experienced a psychiatric symptom or disorder within 2 years of index prescription. The odds of reporting a psychiatric symptom were significantly elevated for women (odds ratio [OR], 1.41; 95% CI, 0.99-2.01; P = .05) and those with a preexposure history of higher social deprivation (OR, 1.15; 95% CI, 1.01-1.31; P = .03), depression (OR, 2.20; 95% CI, 1.49-3.24; P < .001), anxiety (OR, 1.74; 95% CI, 1.11-2.72; P = .02), or recreational drug use (OR, 2.02; 95% CI, 1.20-3.37; P = .008). The model performed well after stratified k = 5-fold cross-validation (area under the curve [AUC], 0.68; 95% CI, 0.58-0.79). There was a gradient in risk, with probabilities increasing from 8% for 0 risk factors to 11% to 17% for 1, 17% to 31% for 2, 30% to 42% for 3, and 49% when all risk factors were present. For those free of a preexposure psychiatric code, a second model performed comparably well after k = 5-fold cross-validation (AUC, 0.72; 95% CI, 0.54-0.90). Specificity was maximized using threshold cutoffs of 0.10 (full model) and 0.14 (second model); a score below these thresholds indicates safety of prescription.. This study derived 2 simple models that predict the risk of a psychiatric adverse effect from levetiracetam. These algorithms can be used to guide prescription in clinical practice.

Topics: Adult; Anticonvulsants; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Mental Disorders; Middle Aged; Models, Statistical; Prognosis; Retrospective Studies; Risk Assessment; Young Adult

To investigate the potential toxic effects of levetiracetam monotherapy on ocular tissues in cases of pediatric epilepsy using optical coherence tomography (OCT).. Thirty epileptic children (group 1) receiving levetiracetam monotherapy at a dosage of 20-40 mg/kg/day for at least 1 year with a first diagnosis of epilepsy and 30 age- and gender-matched healthy children (group 2) were included in the study. In addition to a detailed eye examination, peripapillary retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, foveal thickness (FT), and central corneal thickness (CCT) were measured in all children by means of spectral domain OCT. The data obtained from the two groups were then subjected to statistical analysis.. The mean age of both groups was 12 ± 3.64 years [1-12]. The mean duration of levetiracetam in group 1 was 24.07 ± 12.82 months. Mean RNFL values in groups 1 and 2 were 106.1 ± 10.42 and 104.98 ± 10.04 μm, mean GCC values were 94.72 ± 6.26 and 94.4 ± 6 μm, mean FT values were 240.73 ± 17.94 and 240.77 ± 15.97 μm, and mean CCT values were 555.1 ± 44.88 and 540.97 ± 32.65 μm, respectively. No significant difference was determined between the two groups in terms of any parameter. Best corrected visual acuity values of the subjects in both groups were 10/10, and no color vision or visual field deficit was determined.. Levetiracetam monotherapy causes no significant function or morphological change in ocular tissues in pediatric epilepsies.

Topics: Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Optic Disk; Retina; Single-Blind Method; Tomography, Optical Coherence

Topics: Adolescent; Child; Child, Preschool; Cross-Sectional Studies; Epilepsy; Evoked Potentials; Humans; Levetiracetam; Phenytoin; Valproic Acid

The relationship between anti-epileptic usage and oxidative damage has not yet been clearly understood. In our study, we investigated oxidative stress parameters, carnitine levels, liver function tests (LFT) and their relationship in epileptic children treated with valproic acid or levetiracetam.. LFTs, serum free carnitine and oxidative damage markers and their relations with each other were determined in patients who are on valproic acid or levetiracetam treatment at least for 6 months. 25 patients on therapeutic doses of valproic acid, 26 patients on therapeutic doses of levetiracetam and 26 healthy volunteers as controls were included. LFTs, ammonia, carnitine, lipid peroxidation biomarker malondialdehyde (MDA) and a sensitive marker of DNA damage, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were measured. Results of patients are compared to healthy controls. The data is evaluated with IBM SPSS Statistics 22.0.. Ammonia and MDA levels were elevated in patients using levetiracetam; 8-OHdG levels were elevated in both patient groups. Carnitine levels were significantly low in patients under valproic acid therapy, however they were not found to be correlated with MDA, 8-OHdG or LFTs. MDA showed positive correlation with ammonia and 8-OHdG in the levetiracetam group.. We did not observe hepatotoxicity in patients under therapeutic doses of valproic acid. However, epileptic children under therapeutic doses of levetiracetam showed significantly elevated levels of MDA and 8-OHdG, which is supportive for oxidative damage under levetiracetam therapy. This result was observed for the first time in childhood epilepsies and further studies are needed to understand its mechanism.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Anticonvulsants; Carnitine; Child; Deoxyguanosine; Epilepsy; Female; Humans; Levetiracetam; Lipid Peroxidation; Liver; Liver Function Tests; Male; Malondialdehyde; Retrospective Studies; Thiobarbituric Acid Reactive Substances; Valproic Acid

Topics: Anticonvulsants; Child, Preschool; Comparative Effectiveness Research; Epilepsy; Humans; Infant; Levetiracetam; Observational Studies as Topic; Phenobarbital

Cleidocranial dysplasia is a rare autosomal dominant disorder resulting in skeletal and dental abnormalities due to the disturbance in ossification of the bones. The prevalence of CCD is one in a million of live births, and epileptic seizures are rarer in this disease.. Herein, we present a case of a 10-year-old girl, who not only suffered with cleidocranial dysplasia, but experienced frequent seizures. We initiated an anti-epileptic treatment for this patient with dose adjustments to her weight of levetiracetam (10 mg/kg, bid) for 3 months. The epileptic seizures were controlled, but the intelligence level and control of epilepsy need to be followed up for a longer duration.. In clinical practice, if a patient has unusual facies, typical clavicle defect, skull bone enlargement, and unclosed anterior fontanelle, we should consider the possibility of cleidocranial dysplasia, genetic detection are helpful to make a confirmed diagnosis. In such cases, early diagnosis and treatment is important to correct deformities and improve the quality of life of patients.

Topics: Anticonvulsants; Child; Clavicle; Cleidocranial Dysplasia; Delayed Diagnosis; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Radiography; Skull

Topics: Adolescent; Anticonvulsants; Child; Epilepsy; Estradiol; Female; Humans; Levetiracetam; Menstrual Cycle; Pilot Projects; Progesterone; Valproic Acid

Topics: Adolescent; Albendazole; Anthelmintics; Anticonvulsants; Brain; Brain Diseases; Emigrants and Immigrants; Epilepsy; Hispanic or Latino; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Mutism; Neurocysticercosis

More than a third of patients with epilepsy cannot achieve freedom from seizures despite taking multiple medications. This article compares brivaracetam to levetiracetam, and provides guidelines for the safe and effective use of brivaracetam.

Topics: Anticonvulsants; Drug Costs; Epilepsy; Humans; Insurance Coverage; Levetiracetam; Practice Guidelines as Topic; Pyrrolidinones

Oxcarbazepine (OXC) is almost completely metabolized to its10-monohydroxy derivative (MHD), which is responsible for the pharmacological effects of the drug. Several studies have described the population pharmacokinetics (PPK) of MHD in pediatric patients, but little is known about its pharmacokinetics in adult patients. In addition, no study to date has proposed a model to investigate the influence of genetic polymorphisms on MHD pharmacokinetics. The aim of this study was to establish a PPK model of MHD to investigate the effects of genetic polymorphisms in UGT2B7, UGT1A9, ABCB1, and ABCB2 in adult Chinese patients with epilepsy and to develop a new dosage guideline for OXC.. Data were prospectively collected from 187 adult patients with epilepsy who were taking OXC. MHD trough concentrations were detected by enzyme-multiplied immunoassay. Patients were genotyped for 4 single nucleotide polymorphisms (UGT2B7 802T>C, UGT1A9 I399C>T, ABCB1 3435C>T, and ABCB2 1249G>A). Other covariates included sex, age, body weight (BW), hepato-renal function, and concomitant medications. Data were analyzed using the nonlinear mixed effects modelling software.. The apparent clearance (CL) of MHD was significantly influenced by glomerular filtration rate and BW, and was unrelated to other covariates such as genetic polymorphisms and coadministration with levetiracetam, lamotrigine, and topiramate. Moreover, a new dosage guideline was proposed based on the final model to individualize OXC regimens for adult patients with varying BW and renal function.. Glomerular filtration rate was first found as an important covariate influencing MHD CL. A PPK model was established to estimate the individual MHD CL for adult patients taking OXC and may be applied for individualizing doses in the target population.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Asian People; Body Weight; Drug Monitoring; Epilepsy; Female; Genotype; Glomerular Filtration Rate; Humans; Kinetics; Lamotrigine; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Polymorphism, Single Nucleotide; Topiramate; Young Adult

Levetiracetam was initially developed as a nootropic drug, although since 2002 it has been used as anticonvulsant for the treatment of partial and generalized epilepsy syndromes. The purpose of the research was to investigate anti-paroxysmal activity of levetiracetam (LEV) on the model of cobalt-induced chronic epilepsy caused by the application of cobalt to the sensorimotor area of the rat cortex to evaluate LEV impact on the different stages of epileptogenesis. LEV effects were studied at the initial stage of the epileptogenesis (2nd day after the cobalt application) and at the stage of generalized paroxysmal activity (6th day after the cobalt application). The research showed that levetiracetam administration (dosages 50 mg/kg and 200 mg/kg) at the early stage of the epileptogenesis had no statistically significant effect on the development of paroxysmal activity in both primary and secondary epileptic areas: in the ipsi- and contralateral cortex, hypothalamus and hippocampus. LEV administration on 6th day (dosage 50 mg/kg) did not have statistical effect on the epileptogenesis, while at a dosage of 200 mg/kg on 6th day LEV significantly suppressed paroxysmal activity in the studied structures of rats with cobalt epilepsy. The strongest anti-paroxysmal effect was detected in hippocampus and was expressed as the normalization of bioelectrical activity and the appearance of a regular theta rhythm. Thus, LEV effects are mostly directed to the hippocampal area of epileptiform activity and, to a lesser extent, to the cortical area.

Topics: Animals; Anticonvulsants; Chronic Disease; Cobalt; Dose-Response Relationship, Drug; Electroencephalography; Electrophysiological Phenomena; Epilepsy; Levetiracetam; Male; Rats; Rats, Wistar

No guidelines exist concerning the maintenance antiepileptic drug to use after neonatal seizures. Practices vary from one hospital to another. The aim of this study was to investigate etiologies and to report on the use of maintenance antiepileptic therapy in our population of full-term neonates presenting neonatal seizures.. From January 2004 to October 2014, we retrospectively collected data from all full-term neonates with neonatal seizures admitted to the Children's Hospital of Toulouse, France.. Two hundred and forty-three neonates were included (59% males, 48% electroencephalographic confirmation). The frequencies of etiologies of neonatal seizures were: hypoxic-ischemic encephalopathy (HIE) (n = 91; 37%), ischemic infarction (n = 36; 15%), intracranial hemorrhage (n = 29; 12%), intracranial infection (n = 19; 8%), metabolic or electrolyte disorders (n = 9; 3%), inborn errors of metabolism (n = 5; 2%), congenital malformations of the central nervous system (n = 11; 5%), epileptic syndromes (n = 27; 12%) and unknown (n = 16; 7%). A maintenance therapy was prescribed in 180 (72%) newborns: valproic acid (n = 123), carbamazepine (n = 28), levetiracetam (n = 17), vigabatrin (n = 2), and phenobarbital (n = 4). In our cohort, the choice of antiepileptic drug depended mainly on etiology. The average duration of treatment was six months.. In our cohort, valproic acid was the most frequently prescribed maintenance antiepileptic therapy. However, the arrival on the market of new antiepileptic drugs and a better understanding of the physiopathology of genetic encephalopathies is changing our practice.. Retrospectively registered. Patient data were reported to the "Commission Nationale Informatique et Libertés" under the number 2106953 .

Topics: Anticonvulsants; Carbamazepine; Clonazepam; Cohort Studies; Databases, Factual; Dose-Response Relationship, Drug; Drug Administration Schedule; Electroencephalography; Epilepsy; Female; France; Hospitals, Pediatric; Hospitals, University; Humans; Infant, Newborn; Levetiracetam; Magnetic Resonance Imaging; Male; Phenobarbital; Piracetam; Prognosis; Retrospective Studies; Risk Assessment; Severity of Illness Index; Survival Rate; Term Birth; Time Factors; Treatment Outcome; Valproic Acid

The main objective of this study was to assess the efficacy, safety, and retention rates of levetiracetam monotherapy in children with epilepsy. A retrospective review of pediatric patients receiving levetiracetam monotherapy at 2 large tertiary epilepsy centers over an 11-year period was conducted. One hundred two patients using levetiracetam monotherapy with a mean age of 13.1 years were identified. For the entire cohort, a 6-month retention rate was 61.1% and a 12-month retention rate 53.1%. With regard to seizure freedom, 46.8% of those patients that remained on monotherapy for at least 6 months became seizure free. Twelve-month seizure freedom was reached by 41.2%. About one-third (32.4%) of patients reported adverse effects, with irritability, moodiness, and depression being the most common. Despite a number of patients that reported adverse events, levetiracetam monotherapy was found to be potentially effective in this cohort of children with epilepsy and warrants further, prospective studies.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Patient Compliance; Retrospective Studies; Treatment Outcome

Improved quality of life (QoL) is one of the most important objectives in the treatment of epilepsy. Recent prospective, clinical studies proved no significant differences between brand antiepileptic drugs (AEDs) and their generic equivalents in terms of seizure control, pharmacokinetics, or safety. In this study, we focused on possible changes in QoL and adverse events in connection with generic substitution of levetiracetam (LEV).. This was a prospective, naturalistic, two-cohort, twin-center study. After a baseline period of 10 weeks, outpatients with epilepsy on stable treatment with Keppra® either continued on this brand (reference group, n = 16) or switched to generic LEV (1A Pharma®) (study group, n = 16) for an eight-week study period. The Quality of Life in Epilepsy Inventory-31 (QOLIE-31) and an adverse events' questionnaire were administered at inclusion, after baseline, and at the end of the study period. The study protocol included a close clinical follow-up with repeated LEV serum concentration measurements and nurse-led outpatient visits.. Clinically relevant improvements in overall QOLIE-31 scores according to minimally important change (MIC) estimates were seen in both groups. QOLIE-31 subscales in both groups showed significantly less worry about seizures at the end of the study compared to scores at inclusion (study group: p = 0.01; reference group: p = 0.02). No significant deterioration in QoL or adverse events were observed following generic substitution. No switchbacks occurred.. We found reduced seizure worries over time among people with epilepsy allocated to either generic switch or continued treatment with brand LEV. We hypothesize that the nurse-led structured follow-up had an impact on seizure worries and switchback rates because of reduced nocebo effects. Further studies on generic AED substitution, focusing on psychological outcome measures, are warranted to test this supposition.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Drug Substitution; Drugs, Generic; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Prospective Studies; Quality of Life; Seizures; Surveys and Questionnaires; Young Adult

Topics: Adolescent; Anticonvulsants; Blood Coagulation Disorders; Child; Child, Preschool; Drug Monitoring; Epilepsy; Female; Humans; Hypokalemia; Hyponatremia; Infant; International Normalized Ratio; Levetiracetam; Magnesium; Male; Partial Thromboplastin Time; Potassium; Prospective Studies; Prothrombin Time; Serum Albumin; Serum Globulins; Sodium; Water-Electrolyte Imbalance

To examine the behavioral functioning of children prenatally exposed to carbamazepine (CBZ), lamotrigine (LTG), levetiracetam (LEV), or valproate (VPA) monotherapy.. In collaboration with the European Registry of Antiepileptic Drugs and Pregnancy (EURAP), the Dutch EURAP & Development study was designed, a prospective observational study. Between January 2015 and March 2018, the Child Behavior Checklist and the Social Emotional Questionnaire were used to examine the nature and severity of behavioral problems. VPA-exposed children were compared to children exposed to CBZ, LTG, or LEV, taking potential confounders into account. A direct comparison was also made between LTG and LEV, as these are first-choice treatments for many women with epilepsy of childbearing potential.. Of the 405 invited, 181 children were included; 26 were exposed to VPA, 37 to CBZ, 88 to LTG, and 30 to LEV. For most children, both parents completed the behavioral questionnaires. Across all four antiepileptic drug (AED) exposure groups, high percentages of children with clinically relevant behavior problems were found, with behavioral problems occurring in 32% of VPA-exposed children, 14% of CBZ, 16% of LTG, and 14% of LEV. After controlling for potential confounders, VPA-exposed children had significantly more social problems than those exposed to LTG (-2.8, 95% confidence interval [CI] = -5.2 to -0.4; P = 0.022) or LEV (-3.2, CI: -6.1 to -0.3; P = 0.028), and significantly more attention problems than LEV-exposed children (-3.7, CI: -6.7 to -0.8; P = 0.013). LTG-exposed children had significantly more attention deficit (-9.2, CI: -17.3 to 1.1; P = 0.026), but significantly less anxious behavior when compared to LEV-exposed children (9.0, CI: 0.3-17.6; P = 0.042).. Compared to population norms, a high proportion of children of mothers with epilepsy exposed prenatally to monotherapy with four common AEDs had clinical behavioral problems reported by parents. Different patterns were seen, with some but not all subscales raised for all AED exposure groups. It is important that prenatally AED-exposed children are regularly screened for behavioral problems so that appropriate help can be provided.

Topics: Adult; Anticonvulsants; Carbamazepine; Child; Child Behavior Disorders; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Mothers; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies; Registries; Social Behavior Disorders; Valproic Acid

The efficacy of levetiracetam (LEV) in controlling seizures in patients with brain tumor-related epilepsy (BTRE) depends on tumoral expression of synaptic vesicle protein 2A (SV2A). Although LEV is generally well tolerated, neuropsychiatric adverse events (NPAEs) might occur, limiting compliance and seizure control. We aimed to assess the influence of tumoral SV2A expression on the occurrence of LEV-related NPAEs in patients with glioma.. Specimens from patients enrolled in the multicenter COMPO study, with glioma and BTRE treated with LEV, undergoing neurosurgery were retrieved. Immunohistochemistry-based expression of SV2A in tumoral and peritumoral tissue was scored in a four-point scale from absent (score = 0) to strong (score = 3). Low immunoreactivity (IR) corresponded to scores < 2. Staining ratios (tumoral SV2A IR/peritumoral SV2A IR) were grouped into low (≤ 0.5) and high (> 0.5). NPAEs were assessed longitudinally with the Neuropsychiatry Inventory 12 test (NPI-12).. Overall, 18 patients were eligible for analysis. All received LEV monotherapy, with 67% developing NPAEs. Patients with NPAEs had significantly lower median SV2A intensity score compared to patients without NPAEs (score 1 vs 0, p = 0.025). Low staining ratio (≤ 0.5) associated with higher NPAE occurrence compared to SR > 0.5 (85.7% vs 0%, p < 0.01). A SR ≤ 0.5 predicted a consistent increase in risk of NPAEs (OR 45.0; 95% CI 1.8-1128; p = 0.02).. Our results suggest that SV2A expression in tumoral and peritumoral tissue correlates with the occurrence of LEV-related NPAEs. Thus, considering that SV2A expression also influences LEV effectiveness, SV2A staining might help in tailoring treatment to patients.

Topics: Adult; Aged; Anticonvulsants; Biomarkers; Brain Neoplasms; Epilepsy; Female; Gene Expression; Humans; Levetiracetam; Male; Membrane Glycoproteins; Mental Disorders; Middle Aged; Nerve Tissue Proteins; Predictive Value of Tests; Prospective Studies

We report two cases of adults presenting with transient loss of consciousness (TLoC) followed by a rapid recovery. Careful history taking revealed a stereotyped prodrome of déjà vu, raising the possibility of these events being focal seizures rather than syncope. The patients were commenced on antiepileptic drugs (AEDs) at the same time as having cardiac monitoring organised. This confirmed asystole during the seizure symptoms, resulting in TLoC. It was assumed that the cardiac arrhythmia explained the entire picture, a permanent pacemaker (PPM) was inserted, and the AEDs were withdrawn in one patient and not commenced in the other. However, they both subsequently presented with worsening seizures, including generalised tonic-clonic seizures, despite a functioning pacemaker. The seizures improved on restarting AEDs. The cases illustrate the diagnostic and management difficulties of patients presenting with ictal asystole, a condition that requires input from various medical specialities. There is no strong evidence base for the management of ictal asystole, but we favour a combined approach of AEDs and PPM insertion.

Topics: Anticonvulsants; Bradycardia; Carbamazepine; Deja Vu; Epilepsy; Female; Heart Arrest; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Pacemaker, Artificial; Unconsciousness

Previous surveys of Australian primary care physicians' attitudes regarding epilepsy and persons with epilepsy (PWE), conducted 20-30 years ago, identified the need for further education in epilepsy care for frontline clinicians. This follow-up study of general practitioners (GPs) in Sydney was conducted to determine the degree of changes in knowledge, attitudes, and management of PWE, with the purpose of evaluating if there had been significant improvement during this period.. A questionnaire, evaluating various aspects of epilepsy care, including investigations, preferred healthcare provider (HCP), and attitudes toward epilepsy was developed, largely based on the previous work, piloted, and completed by a representative sample of Sydney GPs.. A total of 52 completed responses were received. Thirty-six out of 47 GPs (77%) chose neurologists as the most important HCP followed by the GP (9/47; 18.7%). Almost half of the GPs (25/51; 49%) mentioned that they never initiated antiepileptic medication (AEM) therapy by themselves yet half of these GPs would alter the neurologist's regimen, without necessitating referral back to that neurologist. Another 27% (14/51 GPs) rarely commenced AEM therapy. Six out of 50 GPs did not mention an electroencephalogram (EEG) as a routine investigation, and 21/50 did not mention magnetic resonance imaging (MRI) as routine for PWE. The five most commonly used AEMs, identified by at least 10% of respondents, were sodium valproate (42), carbamazepine (37), levetiracetam (31), lamotrigine (16), and phenytoin (15). Emotional, behavioral, and psychosocial issues were perceived to be more common among PWE; however, they could contribute equally well to society as people without epilepsy.. The results of the study indicate a perceptual shift regarding GP's attitudes to epilepsy; however, there remain deficiencies in knowledge, particularly with regard to investigations and management. The study highlights the need for more formal training of GPs in caring for PWE.

Topics: Adult; Anticonvulsants; Attitude of Health Personnel; Australia; Carbamazepine; Clinical Competence; Electroencephalography; Epilepsy; Female; Follow-Up Studies; General Practitioners; Humans; Lamotrigine; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Neurology; Phenytoin; Referral and Consultation; Surveys and Questionnaires; Valproic Acid

Epilepsy causes serious suffering in children and is associated with high morbidity and increased mortality. It impairs children's quality of life and places a heavy burden on healthcare resources. Levetiracetam has been used to prevent and treat paediatric epilepsy for years. To date, a number of systematic reviews have been performed to assess the efficacy and safety of levetiracetam in a variety of clinical settings. Conflicting outcomes have been reported for the same clinical issues. Our objective is to provide a comprehensive overview of the literature for clinicians and policymakers via an umbrella review that assesses the efficacy and safety of levetiracetam in children with epilepsy.. We will follow the Joanna Briggs Institute's guidelines for umbrella reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The following seven databases will be searched from 1990 to February 2019: PubMed, Embase, Cochrane Database of Systematic Reviews, JBISRIR, EPPI, Epistemonikos and PROSPERO. We will provide evidence from existing systematic reviews and meta-analyses of randomised controlled trials regarding the use of levetiracetam in children with epilepsy. The intervention of interest is levetiracetam monotherapy and add-on therapies for prevention or treatment purposes. Studies will be individually selected and assessed by two reviewers. The primary outcomes of interest are epilepsy control, the efficacy of prophylaxis for provoked seizures and the mortality rate of children with epilepsy who received levetiracetam treatment. The secondary outcomes are adverse events and withdrawal rates due to adverse effects. The methodological quality of all reviews will be individually assessed by two reviewers using the 'A Measurement Tool to Assess Systematic Reviews' instrument. The Grading of Recommendations Assessment, Development and Evaluation assessment will be applied to evaluate the quality of evidence for each outcome of interest. A narrative description of an analysis of the systematic reviews will be tabulated to address objective and specific questions. Information from each review will be detailed in a table including the population, number of studies, total number of participants, year range of the trials, study designs of the primary trials, countries and settings of the trials, heterogeneity of results and assessment tools. Recommendations regarding each outcome of levetiracetam will be categorised based on a protocol.. This umbrella review will inform clinical and policy decisions regarding the efficacy and safety of levetiracetam for preventing and treating paediatric epilepsy. The results will be disseminated through a peer-reviewed publication and conference presentations. Ethical approval is not required for this study.

Topics: Child; Epilepsy; Humans; Levetiracetam; Meta-Analysis as Topic; Quality of Life; Randomized Controlled Trials as Topic; Research Design; Systematic Reviews as Topic; Treatment Outcome

Epilepsy is a common worldwide neurological disorder. For people with epilepsy (PWE), adherence and attitudes towards medication is a crucial step to improve efficacy of prescribed treatment and to prevent seizures.. The first aim of this study was to evaluate attitudes towards antiepileptic medications in Lebanese population. Secondary aims were to assess factors affecting attitudes and associated with epilepsy control.. A cross-sectional study was conducted in outpatient neurology clinics located in Beirut-Lebanon. Data were collected using a structured questionnaire. Self-report of medication taking behaviors were assessed using the abbreviated (4 items) Morisky Medication Adherence Scale (MMAS-4). Epilepsy was considered as controlled if the patient had no seizures in the last 6 months.. Among 250 PWE recruited in this study, male-to-female ratio was 0.87 (116/134), and 50.8% were married. Mean duration of epilepsy was 13.7 ± 12.8 years. Valproate was the most common antiepileptic drug (AED) used followed by levetiracetam and carbamazepine. About 60.8% of the population presented partial epilepsy. Uncontrolled epilepsy was present in more than half of participants (55.2%), with only 32.4% had positive attitudes to their medication. Positive attitudes towards antiepileptic increased in people who found that their treatment was efficacious (odds ratio (OR) = 4.9; 95% confidence interval (CI): 1.2-20.0; p = 0.03), who had controlled epilepsy (OR = 3.4; 95%CI 1.6-7.1; p = 0.001), and who were diagnosed as PWE between the age of 12-20 years (OR = 3.1; 95%CI 1.1-8.4; p = 0.03). Oppositely, these attitudes decreased in participants who felt their treatment as an economic burden (OR = 0.2; 95%CI 0.1-0.4; p ≪ 0.001), and in people with depression (OR = 0.4; 95%CI 0.2-0.9; p = 0.04). Controlled epilepsy was higher in people who contacted a neurologist if seizure occurred, in people with positive attitudes, and after a long duration of disease, but it decreased if patient did not follow neurologist's instructions in fasting period.. Lebanese PWE were less likely to have positive attitudes towards medication, which may lead to poor epilepsy control. Depression and economic burden were the major factors that decreased these attitudes. Identifying factors affecting attitudes to medication and leading to controlled epilepsy may help clinicians to elaborate educational programs to optimize medication adherence.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Attitude to Health; Carbamazepine; Cross-Sectional Studies; Epilepsy; Female; Humans; Lebanon; Levetiracetam; Male; Medication Adherence; Middle Aged; Self Report; Time Factors; Valproic Acid; Young Adult

Long-term treatment with some older antiepileptic drugs may lead to dyslipidemia or thyroid disturbances. The effect of levetiracetam (LEV), a newer broad spectrum antiepileptic agent, on cardiovascular risk factors is not yet sufficiently investigated. The purpose of this study was to investigate prospectively the effect of LEV monotherapy on serum lipid profile and thyroid hormones levels in children with epilepsy. The study population consisted of 39 children (21 females, 18 males, mean age 6.8 ± 4,1 years, range 2-15 years) that were treated for new-onset epilepsy with LEV monotherapy. Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), lipoprotein (a) [Lp(a)], thyroxine (T4), free thyroxine (FT4) and thyrotropin (TSH), were evaluated before and at 6 and 12 (n = 28) months of LEV monotherapy. TGs were significantly decreased at 6 and 12 months of LEV treatment (p = 0.026 and p = 0.001, respectively). TGs/HDL-C ratio was significantly decreased at 6 and 12 months of LEV treatment (p = 0.024 and p = 0.003, respectively), while LDL-C/HDL-C ratio was significantly decreased at 12 months of LEV treatment (p = 0.025). There were no significant alterations in the other parameters during the study. In conclusion, long-term LEV monotherapy does not cause adverse alterations on thyroid hormones and serum lipids in children with epilepsy. More studies are needed to clarify whether LEV monotherapy have a favourable effect on serum lipids and whether LEV may be considered as a safer alternative drug for the prevention of antiepileptic drug-induced cardiovascular complications in adult life.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Humans; Levetiracetam; Lipids; Male; Prospective Studies; Thyroid Hormones; Treatment Outcome

We studied the use of antiepileptic drugs (AEDs) in women of fertile age and pregnant women in a 16-year-period in Denmark.. We included all women of fertile age (age 18-44 years) and pregnant women from 2001 to 2016 identified from Danish registers.. The median proportion of women of fertile age who took AEDs increased from 10.7‰ (95% confidence interval (CI): 10.5-10.9‰) in 2001 to 27.1‰ (95% CI: 26.8-27.4‰) in 2016. Lamotrigine, levetiracetam, gabapentin and pregabalin have been increasingly used over time and have been the main AEDs used in recent years. The use of valproate in women of fertile age decreased slightly from 2.1‰ (95% CI: 2.0-2.2‰) to 1.9‰ (95% CI: 1.8-2.0‰), which was explained by a decrease in the use after 2014 among women aged 18-24 years. The increased use of AEDs was likely owed to use for other indications than epilepsy. The overall use of AEDs in pregnant women increased from 3.8‰ (95% CI: 3.3-4.3‰) in 2001 to 6.9‰ (95% CI: 6.2-7.6‰) in 2016, and the use of valproate decreased from 0.6‰ (95% CI: 0.4-0.8‰) in 2001 to 0.2‰ (95% CI: 0.1-0.4‰) in 2016.. The overall use of AEDs in women of fertile age and pregnant women has increased in the past 16 years, especially due to an increased use of lamotrigine. However, valproate use in pregnant women and in younger women of fertile age has become less frequent.. This study received funding from the Lundbeck Foundation, the Danish Epilepsy Association, the Central Denmark Region and the Novo Nordisk Foundation (NNF16OC0019126).. none.

Topics: Adolescent; Adult; Anticonvulsants; Denmark; Epilepsy; Female; Gabapentin; Humans; Lamotrigine; Levetiracetam; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Valproic Acid; Young Adult

This study aimed to explore the clinical effect of levetiracetam in the treatment of children with epilepsy.. 136 children with epilepsy were selected from January 2017 to December 2017. According to the random number table method, they were divided into the experimental group and the conventional group, with 68 cases in each group. The conventional group was treated with valproate, while the experimental group was treated with levetiracetam. The effective rate, the cognitive function and the frequency of clonic seizures in the two groups were compared.. There was no significant difference in the total effective rate between the two groups (P>0.05). There was no significant difference in attention, executive ability, abstract and orientation scores between the two groups before treatment (P>0.05). After treatment, the focus of attention (106.54±6.56), executive ability (105.76±6.77), abstract and directional score (106.65±6.57) were significantly higher than that of the conventional group. The difference in the two groups was statistically significant (P<0.05). After 3 months of treatment, the frequency of myoclonic seizures (9.22±0.95) and the frequency of tonic-clonic seizures (11.68±1.36) were found to be significantly lower than those of the conventional group, and the difference between the two groups was statistically significant (P<0.05).. Levetiracetam is effective in the treatment of children with epilepsy. It can effectively improve the cognitive function of the patients, reduce the frequency of myoclonic seizures and tonic-clonic seizures, and has a high promotion value.

Topics: Age Factors; Anticonvulsants; Child; Child, Preschool; Cognition; Epilepsy; Female; Humans; Infant; Levetiracetam; Magnetic Resonance Imaging; Male; Seizures; Tomography, X-Ray Computed; Treatment Outcome

Adenoid cystic carcinoma (ACC) is a rare cancer, and there are no standard-of-care treatments for patients with metastatic ACC. We herein report a patient with lung metastasis of ACC who achieved a favorable response to levetiracetam. A 52-year-old Japanese man was admitted to our hospital because of multiple lung metastases of ACC. We performed first-line chemotherapy with cisplatin plus gemcitabine, and subsequently oral S-1 as second-line chemotherapy, which resulted in disease progression. The patient developed symptomatic epilepsy and received levetiracetam (250 mg twice daily). At five months after the initiation of levetiracetam, chest computed tomography showed regression of the metastatic lung lesions.

Topics: Anticonvulsants; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenoid Cystic; Cisplatin; Deoxycytidine; Epilepsy; Gemcitabine; Humans; Levetiracetam; Lung Neoplasms; Male; Middle Aged; Piracetam; Tomography, X-Ray Computed

Epilepsy is a common symptom in patients with glioblastoma (GB). 213 patients with GB from RedLANO follow-up registry were included. All patients underwent surgery, if feasible, followed by chemoradiation based on temozolomide (Stupp platform). Information was recorded regarding demographics, seizure timing, anti-epileptic drugs (AEDs), dosage, time to next seizure, total seizures in 6 months, and main side effects of AEDs. The relationship between epilepsy treatment and overall survival (OS) was evaluated. Mean age was 53 years old and 56.8% were male. Seventy-eight patients (37%) were treated with levetiracetam (LEV), 27% were given another AED and 36% did not require any AED. Choice of AED was not associated with age (p = 0.67), performance status (p = 0.24) or anatomic tumor site (p = 0.34). Seizures and AED requirement were greater in those having primary GB (p = 0.04). After starting an AED, the mean time until next crisis was 9.9 days (SD ± 6.3), which was shorter in those receiving LEV (p = 0.03); mean number of seizures during the first 3 and 6 months were 2.9 and 4, respectively. Most patients treated with LEV (n = 46) required less than two medication adjustments compared to those treated with other AEDs (p = 0.02). Likewise, less patients exposed to LEV required a coadjuvant drug (p = 0.04). Additionally, patients receiving LEV had significantly less adverse effects compared to patients treated with another AED. OS was significantly higher in the group treated with LEV compared to other AEDs (25.5 vs. 17.9 months; p = 0.047). Patients treated with LEV had better seizure control and longer OS compared to other AEDs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Epilepsy; Female; Glioblastoma; Hispanic or Latino; Humans; Kaplan-Meier Estimate; Levetiracetam; Male; Middle Aged; Prospective Studies; Young Adult

The aim of this study is to evaluate if valproate (VPA) and levetiracetam (LEV) as monotherapy are associated with vitamin D deficiency among children with epilepsy.. A cross-sectional clinical (seizure types, aetiology of epilepsy, dosage, drug levels, and duration of AED treatment) and blood testing (calcium, phosphorus, 25-OHD and PTH) study was accomplished in 90 epileptic children (AED group: 59 receiving VPA, and 31 receiving LEV) and a control group (244 healthy subjects). 25-OHD levels were categorized as low (<20ng/ml), borderline (20-29ng/ml), or normal (>30ng/ml) RESULTS: The average dosage of VPA and LEV was 20.7±4.7mg/kg/d and 24.1±7.9mg/kg/d, respectively. The mean duration of VPA therapy was 2.5±1.4years, and with LEV was 2.3±1.6years. Mean calcium and 25-OHD levels were significantly higher (p <0.05) in the control group. There was a negative correlation (p <0.01) between 25-OHD and VPA levels (r=-0.442). Vitamin D deficiency (%) was significantly higher (p <0.05) in VPA (24.1%) and LEV (35.5%) groups than in control group (14%). The multiple logistic regression analysis showed that VPA monotherapy (OR: 1.9, CI 95%: 1.1-3.8) and LEV monotherapy (OR: 3.3, CI 95%: 1.5-7.5) were associated with an increased risk of vitamin D deficiency.. The prevalence of vitamin D deficiency is common in children with epilepsy taking VPA or LEV. Hence vitamin D status of children treated with VPA and LEV should be regularly monitored and vitamin D supplements should be considered on an individual basis.

Topics: Adolescent; Child; Cross-Sectional Studies; Epilepsy; Female; Humans; Levetiracetam; Male; Prevalence; Valproic Acid; Vitamin D Deficiency

Levetiracetam (LEV), and its newer selective analog brivaracetam (BRV), are two seizure medications that share an innovative mechanism of action targeting the Synaptic Vesicle Protein 2A (SV2A), altering neurotransmitter release and decreasing seizure frequency. Behavioral changes are the most significant adverse effects reported by patients taking LEV. We hypothesize that BRV, the more potent SV2A analog, could exert less behavioral side effects, as it requires lower doses than LEV. Using Kainic Acid (KA)-treated and control rats, we measured adverse behavioral effect profiles of LEV, BRV, or Saline, on social and nonsocial behaviors. Our data indicate that both tested drugs had no effect on locomotion, anxiety levels, fear learning, depression-like behavior, and memory retention in rats. However, when considering social interactions, we first confirmed the epilepsy-induced strong increase in aggressive behaviors and specific hippocampal neuronal loss. We furthermore observed, in Sham rats, that LEV-treated animals were 2 times faster to attack at first encounter, had 5 times more aggressive behaviors, and had significantly less social behaviors than control rats. In all circumstances, BRV rats behaved like Saline rats, suggesting that BRV treatment in rats leads to significantly less aggressive behaviors than LEV treatment at the doses used, while there are limited differential effects between these two drugs on other types of behaviors. Since increased aggressiveness has been reported in patients well controlled on LEV, this study indicates based on our findings, that BRV could represent an effective alternative to LEV to limit aggressiveness problems due to this antiepileptic drug (AED) therapy.

Topics: Animals; Anticonvulsants; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Hippocampus; Humans; Kainic Acid; Levetiracetam; Male; Pyrrolidinones; Rats; Seizures; Synaptic Transmission

Perampanel (PER) is a third generation antiepileptic drug (AED), recently approved as add-on therapy in both focal and generalized seizures. Levetiracetam (LEV) is a second generation AED, widely used in patients with epilepsy because of its favorable safety and efficacy profiles. Perampanel and LEV treatments have been associated with the occurrence of similar adverse events (AEs) (sleepiness, irritability, depression, anxiety, aggressiveness). The aim of the present retrospective single center study was to verify the efficacy and tolerability of PER and LEV used as first add-on therapy in patients with epilepsy affected by secondarily generalized seizures. We collected data from 15 patients treated with PER and 26 patients treated with LEV and followed at our site with follow-up visits at 3, 6, and 12months. This retrospective study documented the comparable efficacy of PER and LEV as first add-on treatments in patients affected by uncontrolled secondarily generalized seizures. However, more patients withdrawn LEV because of AEs compared with PER at the 3- and 12-month follow-up visits. The better tolerability of PER observed in this study could be related to the low therapeutic dose of PER prescribed when it is used as first adjunctive treatment for better controlling secondarily generalized seizures.

Topics: Adult; Aggression; Anticonvulsants; Anxiety; Depression; Dizziness; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Humans; Irritable Mood; Levetiracetam; Male; Middle Aged; Nitriles; Pyridones; Retrospective Studies; Seizures; Treatment Outcome; Wakefulness

Psychiatric and behavioral side effects (PBSEs) are a major cause of antiepileptic drug (AED) withdrawal. Levetiracetam (LEV) is a recognized first-line AED with good seizure outcomes but recognized with PBSEs. Eslicarbazepine (ESL) is considered to function similarly to an active metabolite of the commonly used carbamazepine (CBZ). Carbamazepine is used as psychotropic medication to assist in various psychiatric illnesses such as mood disorders, aggression, and anxiety.. The aim was to evaluate the psychiatric profile of ESL in people who had LEV withdrawn due to PBSEs in routine clinical practice to see if ESL can be used as a possible alternative to LEV.. A retrospective observational review was conducted in two UK epilepsy centers looking at all cases exposed to ESL since its licensing in 2010. The ESL group was all patients with treatment-resistant epilepsy who developed intolerable PBSEs to LEV, subsequently trialed on ESL. The ESL group was matched to a group who tolerated LEV without intolerable PBSEs. Psychiatric disorders were identified from case notes. The Hamilton Depression Scale (HAM-D) was used to outcome change in mood. Clinical diagnoses of a mental disorder were compared between groups using the Fisher's exact test. Group differences in HAM-D scores were assessed using the independent samples t-test (alpha=0.05).. The total number of people with active epilepsy in the two centers was 2142 of whom 46 had been exposed to ESL. Twenty-six had previous exposure to LEV and had intolerable PBSEs who were matched to a person tolerating LEV. There was no statistical differences in the two groups for mental disorders including mood as measured by HAM-D (Chi-square test: p=0.28).. The ESL was well tolerated and did not produce significant PBSEs in those who had PBSEs with LEV leading to withdrawal of the drug. Though numbers were small, the findings suggest that ESL could be a treatment option in those who develop PBSEs with LEV and possibly other AEDs.

Topics: Adult; Anticonvulsants; Dibenzazepines; Drug Substitution; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Humans; Levetiracetam; Male; Mental Disorders; Middle Aged; Psychiatric Status Rating Scales; Retrospective Studies; Seizures; Substance Withdrawal Syndrome; Treatment Outcome; Voltage-Gated Sodium Channel Blockers

This study aims to describe the incidence of adverse drug reactions (ADRs) in children receiving antiepileptic drugs (AEDs) and compare ADRs to the individual drugs when given as monotherapy.. Paediatric patients (≤18 years old) were enrolled for this prospective observational study over a 6-month period, between September 2015 and March 2016. Adverse reactions to antiepileptic drugs (AEDs) were elicited at the time of enrolment and after 3 months using the Paediatric Epilepsy Side Effects Questionnaire.. A total of 1139 suspected ADRs were reported in 124 participants. Eighteen different AEDs were prescribed. Sixty-six children (53%) were receiving AED monotherapy at the time of recruitment; 34/66 (52%) of whom received new generation AEDs. Levetiracetam was the most frequently prescribed AED (62/124, 50%). When only children receiving AED monotherapy were considered, fatigue, drowsiness, weight gain, dizziness were less likely with levetiracetam (p < .01). Slow thinking and decreased concentration were less likely with levetiracetam or carbamazepine than valproic acid (p < .05). Five patients (four on polytherapy) discontinued AED treatment due to ADRs and 2 had a dose reduction.. Levetiracetam and carbamazepine were better tolerated than sodium valproate.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Chi-Square Distribution; Child; Child, Preschool; Cohort Studies; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Surveys and Questionnaires; Valproic Acid

More than half of infants with new-onset epilepsy have electroencephalographic and clinical features that do not conform to known electroclinical syndromes (ie, nonsyndromic epilepsy). Levetiracetam and phenobarbital are the most commonly prescribed medications for epilepsy in infants, but their comparative effectiveness is unknown.. To compare the effectiveness of levetiracetam vs phenobarbital for nonsyndromic infantile epilepsy.. The Early Life Epilepsy Study-a prospective, multicenter, observational cohort study conducted from March 1, 2012, to April 30, 2015, in 17 US medical centers-enrolled infants with nonsyndromic epilepsy and a first afebrile seizure between 1 month and 1 year of age.. Use of levetiracetam or phenobarbital as initial monotherapy within 1 year of the first seizure.. The binary outcome was freedom from monotherapy failure at 6 months, defined as no second prescribed antiepileptic medication and freedom from seizures beginning within 3 months of initiation of treatment. Outcomes were adjusted for demographics, epilepsy characteristics, and neurologic history, as well as for observable selection bias using propensity score weighting and for within-center correlation using generalized estimating equations.. Of the 155 infants in the study (81 girls and 74 boys; median age, 4.7 months [interquartile range, 3.0-7.1 months]), those treated with levetiracetam (n = 117) were older at the time of the first seizure than those treated with phenobarbital (n = 38) (median age, 5.2 months [interquartile range, 3.5-8.2 months] vs 3.0 months [interquartile range, 2.0-4.4 months]; P < .001). There were no other significant bivariate differences. Infants treated with levetiracetam were free from monotherapy failure more often than those treated with phenobarbital (47 [40.2%] vs 6 [15.8%]; P = .01). The superiority of levetiracetam over phenobarbital persisted after adjusting for covariates, observable selection bias, and within-center correlation (odds ratio, 4.2; 95% CI, 1.1-16; number needed to treat, 3.5 [95% CI, 1.7-60]).. Levetiracetam may have superior effectiveness compared with phenobarbital for initial monotherapy of nonsyndromic epilepsy in infants. If 100 infants who received phenobarbital were instead treated with levetiracetam, 44 would be free from monotherapy failure instead of 16 by the estimates in this study. Randomized clinical trials are necessary to confirm these findings.

Topics: Anticonvulsants; Cohort Studies; Drug Prescriptions; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Phenobarbital; United States

Levetiracetam is a broad-spectrum anti-epileptic drug that is effective against both focal and generalized epilepsies. In this study, we aimed to evaluate the efficacy, tolerability and safety of levetiracetam monotherapy in the management of different seizure types in children with epilepsy under the age of two.. This retrospective study was conducted on children with a diagnosis of epilepsy from January 2014 to January 2017. To be included in the study, patients were required to be less than two years of age at the time levetiracetam was initiated as initial monotherapy and to be followed clinically for at least 6 months.. Of the 92 patients, 61 (66%) patients were seizure free. Fifty-eight percent of the patients (31 of 53) with focal epilepsy were seizure free and 77% (30 of 39) generalized epilepsy were seizure free. We found that levetiracetam monotherapy was effective in both focal and generalized epilepsy. Levetiracetam monotherapy was significantly more effective in patients with unknown etiologies (p = 0.004). Seizure freedom rate under levetiracetam monotherapy was significantly higher in patients with normal psychomotor development (p = 0.000). Seizure freedom rate under levetiracetam monotherapy was significantly higher in patients with unknown etiologies and normal psychomotor development. Normal psychomotor development was the strongest predictor of seizure control under levetiracetam monotherapy (OR = 6; 95% CI = 2.3-16.0; p < 0.001). Five children (1%) reported irritability. No hematological or biochemical, or behavioral adverse side effects except irritability were reported in any children. No patient discontinued levetiracetam therapy because of treatment-related side effects.. Our study showed levetiracetam to be an effective, well tolerated and safe agent for the treatment of a variety of seizure types and etiologies seen in infants.

Topics: Anticonvulsants; Child, Preschool; Electroencephalography; Epilepsy; Female; Humans; Infant; Infant, Newborn; Levetiracetam; Male; Piracetam; Retrospective Studies; Treatment Outcome

Long-term anti-epileptic drug (AED) therapy compromises bone health. Although vitamin D deficiency is proposed to be involved, it alone is not held responsible. This accounts for investigating other mechanisms in bone accrual. Recent studies have shown modulation of inhibitors of wnt pathway, sclerostin and dickkopf-1 (DKK-1), in glucocorticoids-induced osteoporosis. We investigated whether AED monotherapy modulates wnt inhibitors in Indian women with epilepsy. Women of age > 20-40 years with the diagnosis of epilepsy and receiving AEDs (carbamazepine, valproate and levetiracetam) for at least a year were enrolled. The results were compared with age-matched healthy controls with no evidence of metabolic bone disease. Women undergoing treatment with AEDs (mean duration: 50.59 ± 37.929 months) exhibited higher serum sclerostin and receptor activator of nuclear factor κ B ligand (RANKL) and lower vitamin D (25-hydroxy vitamin D) and DKK-1 levels when compared to age-matched healthy controls. Sclerostin showed a positive correlation with RANKL, while DKK-1 presented no such relationship. However, no association was evident after adjusting for age, duration of treatment and total daily dose. Although a correlation between wnt inhibitors and RANKL could not be obtained, AEDs displayed changes in serum levels of wnt inhibitors in persons with epilepsy and hence these drugs may compromise bone health through a disturbance in wnt signalling mechanisms.

Topics: Adaptor Proteins, Signal Transducing; Adult; Anticonvulsants; Bone Morphogenetic Proteins; Carbamazepine; Case-Control Studies; Cross-Sectional Studies; Epilepsy; Female; Genetic Markers; Humans; India; Intercellular Signaling Peptides and Proteins; Levetiracetam; Piracetam; RANK Ligand; Valproic Acid; Vitamin D; Wnt Signaling Pathway; Young Adult

De novo heterozygous mutations in STXBP1/Munc18-1 cause early infantile epileptic encephalopathies (EIEE4, OMIM #612164) characterized by infantile epilepsy, developmental delay, intellectual disability, and can include autistic features. We characterized the cellular deficits for an allelic series of seven STXBP1 mutations and developed four mouse models that recapitulate the abnormal EEG activity and cognitive aspects of human STXBP1-encephalopathy. Disease-causing STXBP1 variants supported synaptic transmission to a variable extent on a null background, but had no effect when overexpressed on a heterozygous background. All disease variants had severely decreased protein levels. Together, these cellular studies suggest that impaired protein stability and STXBP1 haploinsufficiency explain STXBP1-encephalopathy and that, therefore, Stxbp1+/- mice provide a valid mouse model. Simultaneous video and EEG recordings revealed that Stxbp1+/- mice with different genomic backgrounds recapitulate the seizure/spasm phenotype observed in humans, characterized by myoclonic jerks and spike-wave discharges that were suppressed by the antiepileptic drug levetiracetam. Mice heterozygous for Stxbp1 in GABAergic neurons only, showed impaired viability, 50% died within 2-3 weeks, and the rest showed stronger epileptic activity. c-Fos staining implicated neocortical areas, but not other brain regions, as the seizure foci. Stxbp1+/- mice showed impaired cognitive performance, hyperactivity and anxiety-like behaviour, without altered social behaviour. Taken together, these data demonstrate the construct, face and predictive validity of Stxbp1+/- mice and point to protein instability, haploinsufficiency and imbalanced excitation in neocortex, as the underlying mechanism of STXBP1-encephalopathy. The mouse models reported here are valid models for development of therapeutic interventions targeting STXBP1-encephalopathy.

Topics: Animals; Anticonvulsants; Brain Diseases; Cells, Cultured; Cerebral Cortex; Embryo, Mammalian; Epilepsy; Exploratory Behavior; Gene Expression Regulation; Haploinsufficiency; HEK293 Cells; Humans; Intellectual Disability; Levetiracetam; Mice; Mice, Inbred C57BL; Mice, Transgenic; Munc18 Proteins; Nerve Tissue Proteins; Synapsins; Synaptic Transmission

Seizures may occur after stroke. Though the majority of clinicians are aware of this, a consensus-based treatment and management strategy for post-stroke seizures is not available because there have only been a few large-scale studies that have explored this. This study has surveyed the actual state of medical treatment for post-stroke seizure and epilepsy in Japan. We conducted a nationwide questionnaire survey of the top 500 institutions regarding the number of cerebral infarction cases between February 2015 and May 2015. The questionnaire contained 14 items regarding the number of patients, type of tests and treatments conducted, and patient response to the treatments. Surveys from 189 institutions were obtained. A history of previous stroke was reported in 41% of hospitalized patients with epilepsy. The sensitivity of diffusion-weighted MRI and electroencephalography was not sufficient to detect the abnormalities seen in epilepsy. Carbamazepine was the most chosen antiepileptic drug for secondary prophylaxis, followed by valproate acid, and levetiracetam.

Topics: Anticonvulsants; Carbamazepine; Epilepsy; Female; Humans; Japan; Levetiracetam; Male; Piracetam; Seizures; Stroke; Surveys and Questionnaires; Valproic Acid

Withdrawal of antiepileptic drugs (AEDs) is a standard procedure during presurgical epilepsy assessment. Rapid and, at times, even pre-hospital withdrawal of medication is performed in some centres to enhance the yield of recorded seizures during video-EEG monitoring. AED withdrawal, however, affects the propensity and speed of propagation of epileptic activity, may evoke more severe seizures, and may cause pitfalls in EEG interpretation. We report a case which had been recommended to undergo intracranial EEG recordings in order to clarify apparently discordant MRI findings and ictal EEG patterns when monitoring was performed following complete AED withdrawal. Re-evaluation to assess scalp EEG patterns at several drug levels during slow AED tapering showed a loss of localizing information with AED withdrawal due to contralateral and bitemporal spread of frontal epileptic activity. Our report demonstrates that in individual cases, rapid AED withdrawal during presurgical video-EEG monitoring can impair the validity of EEG recordings and lead to unnecessary risks and investigations during workup.

Topics: Acetamides; Anticonvulsants; Brain; Electroencephalography; Epilepsy; Humans; Lacosamide; Levetiracetam; Male; Piracetam; Preoperative Period; Seizures; Young Adult

Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the eight most commonly used antiepileptic drugs in monotherapy.. We did a longitudinal, prospective cohort study based on the EURAP international registry. We included data from pregnancies in women who were exposed to antiepileptic drug monotherapy at conception, prospectively identified from 42 countries contributing to EURAP. Follow-up data were obtained after each trimester, at birth, and 1 year after birth. The primary objective was to compare the risk of major congenital malformations assessed at 1 year after birth in offspring exposed prenatally to one of eight commonly used antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate) and, whenever a dose dependency was identified, to compare the risks at different dose ranges. Logistic regression was used to make direct comparisons between treatments after adjustment for potential confounders and prognostic factors.. Between June 20, 1999, and May 20, 2016, 7555 prospective pregnancies met the eligibility criteria. Of those eligible, 7355 pregnancies were exposed to one of the eight antiepileptic drugs for which the prevalence of major congenital malformations was 142 (10·3%) of 1381 pregnancies for valproate, 19 (6·5%) of 294 for phenobarbital, eight (6·4%) of 125 for phenytoin, 107 (5·5%) of 1957 for carbamazepine, six (3·9%) of 152 for topiramate, ten (3·0%) of 333 for oxcarbazepine, 74 (2·9%) of 2514 for lamotrigine, and 17 (2·8%) of 599 for levetiracetam. The prevalence of major congenital malformations increased with the dose at time of conception for carbamazepine (p=0·0140), lamotrigine (p=0·0145), phenobarbital (p=0·0390), and valproate (p<0·0001). After adjustment, multivariable analysis showed that the prevalence of major congenital malformations was significantly higher for all doses of carbamazepine and valproate as well as for phenobarbital at doses of more than 80 mg/day than for lamotrigine at doses of 325 mg/day or less. Valproate at doses of 650 mg/day or less was also associated with increased risk of major congenital malformations compared with levetiracetam at doses of 250-4000 mg/day (odds ratio [OR] 2·43, 95% CI 1·30-4·55; p=0·0069). Carbamazepine at doses of more than 700 mg/day was associated with increased risk of major congenital malformations compared with levetiracetam at doses of 250-4000 mg/day (OR 2·41, 95% CI 1·33-4·38; p=0·0055) and oxcarbazepine at doses of 75-4500 mg/day (2·37, 1·17-4·80; p=0·0169).. Different antiepileptic drugs and dosages have different teratogenic risks. Risks of major congenital malformation associated with lamotrigine, levetiracetam, and oxcarbazepine were within the range reported in the literature for offspring unexposed to antiepileptic drugs. These findings facilitate rational selection of these drugs, taking into account comparative risks associated with treatment alternatives. Data for topiramate and phenytoin should be interpreted cautiously because of the small number of exposures in this study.. Bial, Eisai, GlaxoSmithKline, Janssen-Cilag, Novartis, Pfizer, Sanofi-Aventis, UCB, the Netherlands Epilepsy Foundation, and Stockholm County Council.

Topics: Abnormalities, Drug-Induced; Adult; Anticonvulsants; Carbamazepine; Dose-Response Relationship, Drug; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Logistic Models; Male; Oxcarbazepine; Phenobarbital; Phenytoin; Pregnancy; Pregnancy Complications; Topiramate; Valproic Acid; Young Adult

Topics: Adolescent; Anticonvulsants; Biomarkers; Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Levetiracetam; Magnesium; Male; Potassium; Prospective Studies; Sodium; Treatment Outcome

This study compared the frontal lobe functioning and anger rumination between patients with epilepsy and healthy individuals. The second objective was to examine the efficacy of levetiracetam therapy on frontal lobe dysfunctions and anger rumination in patients with epilepsy. Participants (50 patients with epilepsy and 50 healthy individuals) completed the Frontal Assessment Battery (FAB) and Anger Rumination Scale (ARS). The patients had two testing sessions: pre- and post-levetiracetam therapies. The results showed that patients with epilepsy had frontal lobe dysfunctions in contrast with healthy individuals. Patients with epilepsy had higher anger rumination than healthy individuals. Compared with baseline performance, frontal lobe dysfunctions and anger rumination were significantly reduced after three months of levetiracetam therapy in patients with epilepsy. It is concluded that levetiracetam therapy may be beneficial in improving frontal lobe functioning and anger rumination thought pattern in patients with epilepsy. However, further studies are required to confirm this evidence.

Topics: Adult; Aggression; Anger; Anticonvulsants; Epilepsy; Female; Frontal Lobe; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Rumination, Cognitive; Young Adult

In previous study, we have found intermittent oral levetiracetam (LEV) can effectively prevent recurrence of febrile seizure (FS). This study aimed to analyze the effects of the preventive on the patients with frequent FS accompanied with epileptiform discharge.. Patients with frequent FS were assigned to undergo Electroencephalogram (EEG). At the onset of fever, the patients who presented epileptiform discharge were orally administered with LEV with a dose of 15-30 mg/kg per day twice daily for 1 week, thereafter, the dosage was gradually reduced until totally discontinued in the second week. The seizure frequency associated with febrile events and FS recurrence rate during a 48-week follow-up were analyzed.. among the 19 patients presented epileptiform discharge on EEG, 31.58% (6 of 19) had complex FS, 68.42% (13 of 19) had simple FS. Up to 57.89% (11 of 19) had a family history of seizure disorder and 36.84% (7 of 19) had a family history of FS in first-degree relatives. 42.11% (8 of 19) happened the first FS episode at the age < 18 months. 36.84% (7/19) presented generalized spikes, 63.16% (12/19) showed focal spikes. During the 48-week follow-up period, the patients experienced 26 febrile episodes, none of them presented seizure recurrence.. Intermittent oral LEV can prevent the seizure recurrence of FS accompanied with epileptiform discharge in 48-week. However, further randomized controlled trials should be conducted.. ChiCTR-IPR-15007241 ; Registered 1 January 2014 - Retrospectively registered.

Topics: Administration, Oral; Ambulatory Care; Anticonvulsants; Child, Preschool; Cohort Studies; Comorbidity; Dose-Response Relationship, Drug; Drug Administration Schedule; Electroencephalography; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Pilot Projects; Piracetam; Prognosis; Recurrence; Retrospective Studies; Seizures, Febrile; Severity of Illness Index; Treatment Outcome

Charles Bonnet Syndrome (CBS) is a disorder with visual deficit and complex recurrent visual hallucination in conscious patients, described for the first time by Charles Bonnet. It has been found in association with variable pathologic conditions of the eyes, central visual pathways and occipital lobe. Occipital lobe lesion is an important cause of visual field deficit associated with elementary simple hallucinations, whereas complex hallucinations are related to occipitotemporal and occipitoparietal visual association neocortex damage.

Topics: Aged; Anticonvulsants; Charles Bonnet Syndrome; Diagnosis, Differential; Electroencephalography; Epilepsy; Female; Hallucinations; Humans; Levetiracetam; Magnetic Resonance Imaging; Occipital Lobe; Risk Assessment; Severity of Illness Index; Treatment Outcome; Vision Disorders

Levetiracetam is one of the most widely used antiepileptic drugs, but the evidence related to the safety of substitution from brand name to generic levetiracetam is scarce. The present study evaluated the risk of increased frequency of seizures after replacement of a brand-name levetiracetam with a generic product.. We enrolled patients with epilepsy who were treated with branded levetiracetam for at least 6 months of sustained use. Patients were advised to switch to the generic levetiracetam. We analyzed data from 6 months before, to 6 months after, generic substitution. Increased seizure frequency was defined as a≥ 50% increase in seizure frequency after conversion date compared with seizure frequency before the conversion date. We analyzed changes in seizure frequency and performed subgroup analysis according to changes in seizure frequency.. We analyzed 148 epilepsy patients. Among the 148 patients, 109 (73.6%) were seizure-free before substitution and 105 patients remained seizure-free after switching. After generic substitution, an increased seizure frequency was noted in seven patients (4.7%), and a decreased seizure frequency was noted in 10 (6.8%). Patients with decreased seizure frequency were significantly younger (p = 0.035) than those with an unchanged seizure frequency.. This study suggests that the risk of increased seizure frequency after generic substitution was minimal. The generic substitution of levetiracetam was generally safe, although larger prospective studies are warranted to corroborate our findings.

Topics: Adult; Anticonvulsants; Drug Substitution; Drugs, Generic; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures; Treatment Outcome; Young Adult

Aphasia is a language disorder characterised by loss of ability to produce or comprehend written or spoken language. In majority of the cases, it is due to stroke. Aphasia may also present as an ictal or postictal state of temporal or frontal lobe seizures. Nevertheless, its isolated occurrence in individuals without a clear-cut history of seizures raises diagnostic difficulties with important therapeutic implications.A case of epileptic aphasia is reported in which the diagnosis was confirmed by electroencephalogram with a dramatic therapeutic response to an antiepileptic drug.

Topics: Aged; Anticonvulsants; Aphasia; Cerebral Cortex; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Magnetic Resonance Angiography; Piracetam

Studies evaluating the effect of Levetiracetam (LEV) on haematological parameters in patients with epilepsy are very limited. Short-term effects on haematological parameters in children with epilepsy, at 2 and 6 months of LEV treatment, have been previously reported in the literature. Purpose of the current study was to further investigate the long-term changes on haematological parameters in children with epilepsy during LEV monotherapy. White blood cell, neutrophils, lymphocytes, monocytes, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and platelets were measured in 20 children (11 females, mean age 6,5 ± 4,4 years, range 2-15 years) with epilepsy, before and after 12 months of LEV monotherapy. Lymphocyte count was significantly decreased at 12 months (p = 0.003) of LEV treatment. Three children (15%) at 12 months of treatment had lymphocyte count below 10th percentile for age. Neutrophils counts were significantly increased and platelets counts were significantly decreased at 12 months of treatment (p = 0.046 and p = 0.006, respectively). In addition, haematocrit and mean corpuscular volume were significantly increased at 12 months of treatment (p = 0.036 and p = 0.031, respectively). There were no significant alterations in the other parameters evaluated during the study. No association was found between all parameters and LEV dosage (mg/kg) at 12 months of treatment. Large, prospective studies are needed to investigate the clinical significance of the above haematological changes and whether these parameters should be monitored periodically in children taking LEV.

Topics: Adolescent; Analysis of Variance; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Hematocrit; Humans; Levetiracetam; Longitudinal Studies; Lymphocytes; Male; Neutrophils; Treatment Outcome

Levetiracetam (LEV) is effective for focal and generalized epilepsy and is used worldwide because of its relatively few drug interactions and favorable tolerability. However, some psychiatric adverse events (PAEs) have been reported, resulting in drug withdrawal. The pathophysiology of LEV-induced PAE has not yet been elucidated. In this study, we investigated the relationship between PAEs and human leukocyte antigen (HLA) genes. Eleven epilepsy patients, who developed PAEs after the administration of LEV and spontaneously improved after drug withdrawal, were enrolled retrospectively. Genomic DNA from the peripheral blood was extracted, and four-digit allele genotyping of HLA genes was performed. The genotype frequencies of HLA genes were compared to those of 80 patients in which LEV was well tolerated, as well as to 485 individuals from the general Korean population. The frequency of the HLA-A*1101 allele was significantly higher in the LEV-induced PAEs group compared to both the LEV-tolerant group (p = 0.021, OR 4.80, 95% CI 1.30-17.74) and the general Korean population (p = 0.015, OR 4.62, 95% CI 1.38-15.45). This study is the first attempt at investigating the relationship between the HLA system and LEV-induced PAE. The results of this study suggest that the HLA-A*1101 allele could be a risk factor for the development of PAEs.

Topics: Adult; Aged; Alleles; Epilepsy; Female; Genotype; HLA-A Antigens; Humans; Levetiracetam; Male; Middle Aged; Republic of Korea; Retrospective Studies

To predict the probability of a seizure-free (SF) state in patients with epilepsy (PWEs) after treatment with levetiracetam and to identify the clinical and electroencephalographic (EEG) factors that affect outcomes.. Retrospective analysis of PWEs treated with levetiracetam for 3 years identified 22 patients who were SF and 24 who were not. Before starting levetiracetam, 11 clinical factors and four EEG features (sample entropy of α, β, θ, δ) were identified. Overall, 80% of each the two groups were chosen to establish a support vector machine (SVM) model with 5-fold cross-validation, hold-out validation and jack-knife validation. The other 20% were used to predict the efficacy of levetiracetam. The mean impact value (MIV) algorithm was used to rank the relativity between factors and outcomes.. Compared with SF patients, not SF patients displayed a specific decrease in EEG sample entropy in α band from the F4 channel, β band from Fp2 and F8 channels, θ band from C3 channel (P < 0.05). The SVM model based on the clinical and EEG features yielded 72.2% accuracy of 5-fold cross-validation, 75.0% accuracy of jack-knife validation, 67.7% accuracy of hold-out validation in the training set and had a high prediction accuracy of 90% in test set (sensitivity was 100%, area under the receiver operating characteristic curve was 0.96). The feature of β band from Fp2 weighs heavily in the prediction model according to the mean impact value algorithm.. The efficacy of levetiracetam on newly diagnosed PWEs could be predicted using an SVM model, which could guide antiepileptic drug selection.

Topics: Adolescent; Adult; Algorithms; Anticonvulsants; Child; Electroencephalography; Epilepsy; Humans; Levetiracetam; Precision Medicine; Retrospective Studies; Seizures; Sensitivity and Specificity; Support Vector Machine; Young Adult

The purpose of this study was to determine the effect of lamotrigine (LTG) and levetiracetam (LEV) as mono- and polytherapy on biochemical markers of bone turnover and bone mineral density in Egyptian adult patients with epilepsy.. Forty-eight patients were divided into four groups: two received monotherapy of either LTG or LEV, and the other two groups received polytherapy comprising (valproate [VPA] + LTG or VPA + LEV). Thirty matched healthy participants were included in the study. Participants completed a nutritional and physical activity questionnaire. Biochemical markers of bone and mineral metabolism and bone mineral density of the lumbar spine were measured at baseline and at six months.. In the LEV monotherapy group, the bone formation markers showed a significant decrease in serum alkaline phosphatase and serum osteocalcin levels while the bone resorption marker showed a significant increase in urinary deoxypyridinoline levels. After six months of treatment, bone mineral density showed a significant decrease in all treated groups, while among monotherapy groups, this significant decrease was more prevalent in the LEV monotherapy group compared with the LTG monotherapy group. Furthermore, there was significant negative correlation between urinary deoxypyridinoline levels and bone mineral density in the LEV monotherapy group.. Using new generation antiepileptics, LEV monotherapies and polytherapy showed harmful effects on bone but LTG did not.

Topics: Adolescent; Adult; Amino Acids; Anticonvulsants; Biomarkers; Bone Density; Bone Remodeling; Case-Control Studies; Drug Therapy, Combination; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Osteocalcin; Piracetam; Triazines; Valproic Acid; Young Adult

To ascertain the risk of spontaneous fetal loss (SPFL) in women with epilepsy (WWE) on antiepileptic drugs (AED), and explore the association between specific AED usage and risk of SPFL.. We identified all SPFL (including stillbirths) among pregnancies registered at Kerala Registry for Epilepsy and Pregnancy between 1998 and 2015. Rates of SPFL were compared between the AED exposed and unexposed groups.. There were 139 SPFL out of 1987 eligible pregnancies. The AED exposed had excess SPFL (7.4%, 134 out of 1809, Odds Ratio [OR] 2.77, 95% Confidence Interval [CI] 1.17-6.39) than AED unexposed (2.8%, 5 out of 178). The adjusted OR (95% CI) for SPFL for monotherapies with levetiracetam, phenobarbitone and clobazam were comparable to unexposed, while it was significantly higher for topiramate (OR 38.86, CI 5.02-301.19), lamotrigine (OR 13.33, CI 1.41-125.78), oxcarbazepine (OR 7.53, CI 1.54-36.89), valproate (OR 6.92, CI 1.70-28.18), phenytoin (OR 5.82, CI 1.43-23.73) and carbamazepine (OR 3.53, CI 1.15-10.90). With reference to levetiracetam, only topiramate had significantly higher SPFL (OR 11.14, CI 1.56-79.55).. SPFL risk is increased in pregnancies with AED exposure, being least with levetiracetam and highest with topiramate.

Topics: Abortion, Spontaneous; Adult; Anticonvulsants; Epilepsy; Female; Humans; India; Levetiracetam; Prospective Studies; Registries; Risk Factors; Topiramate

The mTOR signaling pathway has emerged as a possible therapeutic target for epilepsy. Clinical trials have shown that mTOR inhibitors such as everolimus reduce seizures in tuberous sclerosis complex patients with intractable epilepsy. Furthermore, accumulating preclinical data suggest that mTOR inhibitors may have anti-seizure or anti-epileptogenic actions in other types of epilepsy. However, the chronic use of rapalogs such as everolimus is limited by poor tolerability, particularly by immunosuppression, poor brain penetration and induction of feedback loops which might contribute to their limited therapeutic efficacy. Here we describe two novel, brain-permeable and well tolerated small molecule 1,3,5-triazine derivatives, the catalytic mTORC1/C2 inhibitor PQR620 and the dual pan-PI3K/mTOR inhibitor PQR530. These derivatives were compared with the mTORC1 inhibitors rapamycin and everolimus as well as the anti-seizure drugs phenobarbital and levetiracetam. The anti-seizure potential of these compounds was determined by evaluating the electroconvulsive seizure threshold in normal and epileptic mice. Rapamycin and everolimus only poorly penetrated into the brain (brain:plasma ratio 0.0057 for rapamycin and 0.016 for everolimus). In contrast, the novel compounds rapidly entered the brain, reaching brain:plasma ratios of ∼1.6. Furthermore, they significantly decreased phosphorylation of S6 ribosomal protein in the hippocampus of normal and epileptic mice, demonstrating effective mTOR inhibition. PQR620 and PQR530 significantly increased seizure threshold at tolerable doses. The effect of PQR620 was more marked in epileptic vs. nonepileptic mice, matching the efficacy of levetiracetam. Overall, the novel compounds described here have the potential to overcome the disadvantages of rapalogs for treatment of epilepsy and mTORopathies directly connected to mutations in the mTOR signaling cascade.

Topics: Animals; Anticonvulsants; Azabicyclo Compounds; Blood-Brain Barrier; Catalysis; Electroshock; Enzyme Inhibitors; Epilepsy; Everolimus; Female; Hippocampus; Levetiracetam; Mechanistic Target of Rapamycin Complex 1; Mechanistic Target of Rapamycin Complex 2; Mice; Morpholines; Phenobarbital; Phosphoinositide-3 Kinase Inhibitors; Phosphorylation; Pyridines; Ribosomal Proteins; Seizures; Sirolimus; Triazines

To determine the potential for improvement of tolerability and efficacy by the use of Brivaracetam (BRV) in patients previously treated with Levetiracetam (LEV).. We retrospectively analyzed data from patients treated with BRV at the Freiburg Epilepsy Center.. 102 patients with a minimum follow up of 6 months were included. The mean duration of treatment was 301.6 (± 156.8) days. 60 patients underwent an overnight switch from LEV to BRV, 42 patients have had LEV at some time in the past. Out of 46 patients with a quantifiable seizure baseline and follow-up of 6 months 10 patients (21.7%) had an increase in seizure frequency, 15 (32.6%) were 50%-responders, and 10 patients (21.7%) became newly seizure-free. Patients with an overnight switch from LEV to BRV who had a reduction in seizure frequency had the highest dose ratio of the final BRV dose to LEV (1:10.1) and the biggest difference between the starting and final dose of BRV, suggesting that previously seizure control was limited by the tolerated LEV dosage. The retention rate after 6 months was 80.4%. 28 out of 49 (57.1%) patients directly switched from LEV to BRV because of psychiatric side effects reported an improved tolerability. 10 out of 42 (23.8%) patients not directly switched but with a history of LEV use had predominantly psychiatric side effects during BRV treatment.. Overall, intolerability or ineffectiveness of prior treatment with LEV seems not to preclude a good response to BRV. BRV was substantially better tolerated than LEV.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug Tolerance; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Pyrrolidinones; Retrospective Studies; Treatment Outcome; Young Adult

Extended-release levetiracetam (LEV-XR) has gained acceptance as an antiepileptic drug in dogs. No studies have evaluated its disposition in dogs with epilepsy.. To evaluate the pharmacokinetics of LEV-XR in epileptic dogs when administered alone or with phenobarbital or zonisamide.. Eighteen client-owned dogs on steady-state maintenance treatment with LEV-XR (Group L, n = 6), LEV-XR and phenobarbital (Group LP, n = 6), or LEV-XR and zonisamide (Group LZ, n = 6).. Pharmacokinetic study. Blood samples were collected at 0, 2, 4, 8, and 12 hours after LEV-XR was administered with food. Plasma LEV concentrations were determined by high-pressure liquid chromatography. A population pharmacokinetic approach and nonlinear mixed effects modeling were used to analyze the data.. Considerable variation exists in the pharmacokinetics of LEV-XR in dogs with epilepsy being treated with a common dose regimen. Concurrent administration of phenobarbital contributed significantly to the variation. Other factors evaluated, including co-administration of zonisamide, were not shown to contribute to the variability. Drug monitoring may be beneficial to determine the most appropriate dose of LEV-XR in individual dogs.

Topics: Animals; Anticonvulsants; Delayed-Action Preparations; Dog Diseases; Dogs; Drug Interactions; Epilepsy; Levetiracetam; Phenobarbital; Zonisamide

Assessment of the relevance between serum drug concentration to its therapeutic response is a valid monitoring strategy for the clinical efficacy of antiepileptic drugs (AEDs). Levetiracetam (LEV) is a broad spectrum AED with a possible anti-inflammatory effect. We aimed to determine the relationship between LEV concentrations and its therapeutic response, and the effect of LEV on IL1-beta concentrations in patients with epilepsy.. Patients on monotherapy (n = 7) or polytherapy (n = 15) with LEV for their seizures management were included. Blood samples of each patient were collected: just before LEV intake, 1 h, 2 h, 4 h and 8 h following the last dose. Serum LEV concentrations were measured by liquid chromatography mass spectrometry and IL1-beta concentrations by chemiluminescent immunometric assay. Concentration to dose (C/D) ratio values was used for analyses. LEV concentrations were compared between responders (≤1 seizure/month) and non-responders (>1 seizure/month) and patients with or without adverse reactions. IL1-beta concentrations before and at 2 h following LEV ingestion were compared in order to detect the effect of the increase in serum LEV concentration on IL1-beta.. Although there was no change in LEV (C/D) ratio or LEV maximum concentration (Cmax)/D ratio of the responders and non-responders, the C/D ratio following 1 h of LEV intake (2.17 ± 0.59 kg.day/L) and Cmax/D ratio (2.25 ± 0.56 kg.day/L) in the patients with adverse effects was significantly higher than for the patients without adverse effects (1.09 ± 0.12 kg.day/L and 1.49 ± 0.14 kg.day/L respectively). A statistically significant decrease was found in the IL1-beta concentration to LEV (C/D) ratio with the increase in LEV concentration in patients on LEV monotherapy.. The possible relationship between LEV Cmax and its therapeutic response or IL1-beta concentrations may be an importance indication of LEV antiepileptic efficacy. Consequently, monitoring LEV Cmax values may enhance LEV adherence because patients would be less likely to develop adverse effects.

Topics: Adult; Anticonvulsants; Biomarkers; Epilepsy; Female; Humans; Interleukin-1beta; Levetiracetam; Male; Middle Aged; Seizures; Treatment Outcome; Young Adult

Topics: Child; Epilepsy; Humans; Levetiracetam; Piracetam; Valproic Acid; Vitamin D; Vitamin D Deficiency

Few studies have been published on new-onset geriatric epilepsy especially in older Chinese people. This study was to have a comprehensive understanding of new-onset geriatric epilepsy and find a more reasonable diagnosis and management of epilepsy in older people.. One hundred and three patients with onset age 60 years and older were admitted between January 2008 and December 2016. Electronic medical records were reviewed to collect information.. There were 103 older patients with new-onset epilepsy. The mean age of the patients was 68.5 ± 6.4 years (range: 60-89 years), and there were 67 (65%) men and 36 (35%) women. The mean onset age was 67.9 ± 6.2 years (range: 60-89 years). The most common identifiable etiology of symptomatic seizures was autoimmune epilepsy in 43 (41.7%) patients. The second most common etiology was stroke in 15 (14.6%) patients. Seven (6.8%) older patients with acute seizures present with status epilepticus and 26 (25.2%) patients experienced clustered seizures (more than three events in 24 h) at seizure onset. Focal seizures (96.1%) were more common than generalized seizures (3.9%). Fifty-three (51.5%) patients had an abnormal brain magnetic resonance imaging (MRI) scan. Among them, video-electroencephalogram findings in 31 (30.1%) patients correlated with MRI abnormalities. Levetiracetam was the most used drugs before admission, in hospital, and during follow-up.. Autoimmune encephalitis is becoming an increasing risk factor of subsequent epilepsy in older people. Older patients with new epilepsy are more likely to respond to antiepileptic drugs, and drug-resistant epilepsy is uncommon.

Topics: Aged; Aged, 80 and over; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Prognosis

Objectives To study the clinical profile and outcome in patients with epilepsy who developed psychogenic non-epileptic seizures (PNES) associated with levetiracetam (LEV) use.   Methods In this prospective observational study, conducted over 1 year, 13 patients with epilepsy and PNES, documented by video electroencephalogram (VEEG) while on LEV, were included. Those with past history of psychiatric illnesses were excluded. VEEG, high-resolution magnetic resonance imaging, neuropsychological and psychiatric evaluation were performed. Patients in Group I (07) were treated with psychotherapy, psychiatric medications and immediate withdrawal of LEV while, those in Group II (06) received psychotherapy, anxiolytics and LEV for initial 2 months after which it was stopped. Follow-up period was six months. There was subsidence of PNES on discontinuation of LEV in these patients.   Results Mean (±SD) age of patients was 25 ± 12.28 years; there were 11 (84.62%) females. All were on antiepileptic agents which included LEV >1000 mg/day, except one. Mean dose of LEV was 1269.23 ± 483.71 mg/day. Three patient's scores were suggestive of depression or anxiety; one had both depression and anxiety. Eight patients had mood disorders; three had a history of emotional abuse or neglect. PNES subsided within 1-3 months and did not recur after withdrawal of LEV in any patient.   Conclusion LEV can induce PNES in susceptible populations. Awareness of this association is crucial for timely withdrawal of triggering factor and appropriate management. This will reduce inadvertent additional prescription of antiepileptic agents.

Topics: Adolescent; Adult; Anti-Anxiety Agents; Anticonvulsants; Anxiety; Child; Depression; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Prospective Studies; Psychotherapy; Risk Factors; Seizures; Young Adult

The prescription pattern of antiepileptic drugs (AEDs) during pregnancy is changing but to what extent this is occurring in Spain remains unknown. The efficacy of newer drugs for controlling seizures is a key issue and may have changed over the years as doctors gained familiarity with these drugs during pregnancy. To assess these 2 topics, we report the results from the Spanish EURAP register gathered over a 12-year period.. After signing informed consent forms, patients were included in the register and evaluated at onset of pregnancy, at the end of the second and third trimesters, after delivery, and one year after delivery. For the purposes of this study, we analysed AEDs, type of epilepsy, seizure frequency per trimester and throughout pregnancy, percentage of seizure-free pregnancies, and frequency of congenital malformations. We then compared data from 2 periods (June 2001-October 2007) and (January 2008-May 2015) RESULTS: We compared 304 monotherapies from the older period to 127 from the more recent one. There was a clear increase in the use of levetiracetam (LEV) with declining use of carbamazepine (CBZ), phenytoin, and phenobarbital; a slight decline in use of valproate (VPA), and a slight increase in the use of lamotrigine (LTG) and oxcarbazepine (OXC). Epilepsy types treated with CBZ and VPA remained unchanged, whereas fewer cases of generalised epilepsy were treated with LTG in the new period. This trend was not associated with significant changes in seizure frequency, but rather linked to better control over de novo seizures in the third trimester. LEV was similar to CBZ and VPA with regard to levels of seizure control, and more effective than LTG. Generalised epilepsy accounted for 64% of the cases treated with LEV.. The prescription pattern of AEDs during pregnancy has changed in Spain, with diminishing use of CBZ, phenytoin, and phenobarbital. Changes also reflect the type of epilepsy, since there is less use of LTG for generalised epilepsy. LEV provides similar seizure control to that of the older AEDs, and it is more effective and better than LTG.

Topics: Adult; Anticonvulsants; Carbamazepine; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Longitudinal Studies; Oxcarbazepine; Piracetam; Pregnancy; Seizures; Spain; Triazines

To explore possible correlations among brain lesion location, development of psychiatric symptoms and the use of antiepileptic drugs (AEDs) in a population of patients with brain tumor and epilepsy. The medical records of 283 patients with various types of brain tumor (161 M/122 F, mean age 64.9 years) were analysed retrospectively. Patients with grade III and IV glioma, previous history of epileptic seizures and/or psychiatric disorders were excluded. Psychiatric symptoms occurring after initiation of AED therapy were considered as treatment emergent psychiatric adverse events (TE-PAEs) if they fulfilled the following conditions: (1) onset within 4 weeks after the beginning of AED therapy; (2) disappearance on drug discontinuation; (3) absence of any other identified possible concurrent cause. The possible influence of the following variables were analysed: (a) AED drug and dose; (b) location and neuroradiologic features of the tumor, (c) location and type of EEG epileptic abnormalities, (d) tumor excision already or not yet performed; (e) initiation or not of radiotherapy. TE-PAEs occurred in 27 of the 175 AED-treated patients (15.4%). Multivariate analysis showed a significant association of TE-PAEs occurrence with location of the tumor in the frontal lobe (Odds ratio: 5.56; 95% confidence interval 1.95-15.82; p value: 0.005) and treatment with levetiracetam (Odds ratio: 3.61; 95% confidence interval 1.48-8.2; p value: 0.001). Drug-unrelated acute psychiatric symptoms were observed in 4 of the 108 AED-untreated patients (3.7%) and in 7 of the 175 AED-treated patients (4%). The results of the present study suggest that an AED alternative to levetiracetam should be chosen to treat epileptic seizures in patients with a brain tumor located in the frontal lobe to minimize the possible onset of TE-PAEs.

Topics: Aged; Anticonvulsants; Brain Neoplasms; Cohort Studies; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Male; Mental Disorders; Middle Aged; Piracetam; Psychiatric Status Rating Scales; ROC Curve

Topics: Amnesia; Anticonvulsants; Electroencephalography; Epilepsy; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Seizures; Treatment Outcome

To assess the efficiency of brivaracetam under real-world conditions in a tertiary referral epilepsy center.. We consecutively collected patients treated at our center with brivaracetam (BRV). After a minimum observation period of six months we retrospectively analyzed the efficiency of BRV.. Data of 101 patients (mean age 42 years, range 18-81 years, 54 females,) were analyzed. The median number of antiepileptic drugs (AEDs) used prior to BRV was 10 (range 2-18). The initial dose of BRV was at least 50mg per day, the mean maintenance dose at cut-off was 168.6mg (median 200mg, range 50-400mg). Efficacy data were assessed for the last three months or at the time of the last observation carried forward if BRV had been discontinued prematurely. Responder rate was 27.8% (n=28) with 7% seizure-free patients. Adverse events (AEs) occurred in 37 patients (37%). Most frequent AEs were dizziness (16%) and somnolence (11%). Psychiatric adverse events comprised irritability, aggression, depression and psychosis in single cases. Retention rate after six months was 51.5%. Main reason for discontinuation was a lack of efficacy. In 43 cases LEV and BRV were switched. The switch was performed abruptly without complications. In 26 cases (60%) BRV was discontinued and re-switched to LEV within weeks, mainly due to a lack of better efficacy. After the switch from LEV to BRV we even saw an aggravation both of seizure frequency and severity in 5 cases. Retention rate in patients who had not been on LEV was 57%.. In our hands BRV appeared to be well tolerated and easy to handle. The retention rate was influenced by patients who were switched from LEV and re-switched because BRV was not more efficient. Switching from and re-switching to LEV was easy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Drug Substitution; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Pyrrolidinones; Treatment Failure; Treatment Outcome; Young Adult

Levetiracetam (LEV) is an antiepileptic drug commonly used in the treatment of epilepsy because of its excellent safety profile in all age groups. It is remarkable that there are no studies evaluating the toxic effects of this drug on the male reproductive system, as it is commonly used in male patients of reproductive age. From this point of view, our aim was to evaluate the possible toxic effects of LEV on the male reproductive system. Therefore, LEV was administered to male rats orally at 50, 150, and 300 mg/kg for 70 consecutive days. At the end of this period, alterations to body and organ weights were calculated, and sperm concentration, motility, and morphology were investigated by a computer-assisted sperm analysis system. Sperm DNA damage was determined by comet assay and histopathological examination of the testes was carried out. Serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were measured by ELISAs to determine the effects of hormonal status, while glutathione, superoxide dismutase, catalase, and malondialdehyde levels in the testes were measured by colorimetric assay kits to determine the role of oxidative status in potential toxicity. According to the results, sperm quality was decreased by LEV treatment in a dose-dependent manner. LEV induced significant DNA damage in the 150 and 300 mg/kg LEV-administered groups. Histopathology of the testes showed that LEV resulted in testicular injury in the 300 mg/kg LEV-administered group. Serum testosterone, FSH, and LH levels were significantly decreased in the 300 mg/kg LEV-administered group. Glutathione, superoxide dismutase, and catalase levels were significantly decreased in all experimental groups while malondialdehyde levels were significantly increased in 150 and 300 mg/kg LEV-administered groups. According to these results, it was determined that LEV administration decreased sperm quality and it was alleged that hormonal alteration and oxidative stress are potential contributors to reproductive toxicity.

Topics: Animals; Anticonvulsants; DNA Damage; Epilepsy; Follicle Stimulating Hormone; Levetiracetam; Luteinizing Hormone; Male; Oxidative Stress; Piracetam; Rats; Rats, Wistar; Reproduction; Sperm Count; Sperm Motility; Spermatozoa; Testis; Testosterone

Previous findings revealed high correlations between serum/plasma and saliva levetiracetam concentrations, indicating saliva as an alternative matrix for monitoring levetiracetam therapy. Levetiracetam concentration in the hair, which could reflect long-term drug exposure and patients' compliance, has not been systematically tested, as yet. The aim of this study was to determine the correlation between plasma, saliva, and hair levetiracetam concentrations in 47 patients with epilepsy.. Plasma, saliva, and hair levetiracetam concentrations were measured by liquid chromatography-tandem mass spectrometry with positive ionization.. Levetiracetam saliva and plasma concentrations were highly correlated (r = 0.93). Plasma concentrations were not influenced by sex, age, and other concomitant antiepileptic drugs. Levetiracetam hair concentrations correlated with plasma concentrations (r = 0.36) but not daily dose (mg/kg). Drug hair concentrations were not influenced by hair color or treatment (dyed).. The results tend to indicate that saliva may be a reliable alternative to plasma for monitoring levetiracetam concentrations. Levetiracetam can also be detected in human hair.

Topics: Adolescent; Adult; Anticonvulsants; Chromatography, Liquid; Drug Monitoring; Epilepsy; Female; Hair; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Plasma; Saliva; Tandem Mass Spectrometry; Young Adult

Psychiatric comorbidities are common in people with epilepsy. A retrospective study of characteristics associated with withdrawal due to psychiatric side effects was undertaken in patients with treated epilepsy participating in prospective audits with new antiepileptic drugs (AEDs). A total of 1058 treated patients with uncontrolled seizures (942 focal-onset seizures, 116 generalized genetic epilepsies [GGEs]) participated in eight prospective, observational audits from 1996 to 2014. These patients were prescribed adjunctive topiramate (n=170), levetiracetam (n=220), pregabalin (n=135), zonisamide (n=203), lacosamide (n=160), eslicarbazepine acetate (n=52), retigabine (n=64), or perampanel (n=54). Doses were titrated according to efficacy and tolerability to optimize zeizure outcomes and reduce side effects. Psychiatric comorbidities were recorded prior to and after the addition of each AED. At baseline, patients with focal-onset seizures (189 of 942; 20.1%) were statistically more likely to have psychiatric diagnoses compared to patients with GGEs (14 of 116, 12.1%; p=0.039). Following adjunctive AED treatment, neuropsychiatric adverse effects led to AED withdrawal in 1.9-16.7% of patients. Patients with a pre-treatment psychiatric history (22 of 209; 10.5%) were statistically more likely to discontinue their new AED due to psychiatric issues compared to patients with no previous psychiatric diagnosis (50 of 849; 5.9%; p=0.017). Patients receiving sodium channel blocking AEDs (4 of 212, 1.9%) were statistically less likely to develop intolerable psychiatric problems, compared to those on AEDs possessing other mechanisms of action (68 of 846, 8.0%; p=0.012). Depression was the commonest problem, leading to discontinuation of AEDs in 2.8% (n=30) patients. Aggression was statistically more common in men (11 of 527, 2.1%) compared to women (1 of 531, 0.2%; p=0.004). Patients with learning disability (12 of 122, 9.8%; p=0.0015) were statistically less likely to have psychiatric issues prior to adjunctive AED treatment compared to other patients (208 of 936, 22.2%), but there were no statistically significant differences once the new AEDs were added (8 of 122 patients with learning disability, 6.6%; 64 of 936 other patients, 6.8%). Awareness of these issues may assist clinicians in avoiding, identifying and treating psychiatric comorbidities in people with epilepsy.

Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Dibenzazepines; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Fructose; Humans; Lacosamide; Levetiracetam; Male; Medical Audit; Mental Disorders; Middle Aged; Nitriles; Piracetam; Pregabalin; Prospective Studies; Pyridones; Retrospective Studies; Seizures; Sodium Channel Blockers; Topiramate; Young Adult

Levetiracetam is used in the treatment of some forms of epilepsy. In renal impairment and patients on chronic haemodialysis, dose adjustment is required. We report a case.. This case report describes a woman on levetiracetam treatment who presented with generalized tonic-clonic seizures during a haemodialysis session. We report on treatment adjustment and on the impact of dialysis on levetiracetam levels.. Haemodialysis reduces serum levetiracetam concentration and can lead to subtherapeutic levels. Close monitoring is necessary when dialysis is used on patients receiving anticonvulsant drugs that are extensively eliminated by the procedure.

Topics: Adult; Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Piracetam; Renal Dialysis; Seizures

To examine the prevalence and clinical correlates of fatigue as an adverse event (AE) of antiepileptic drug (AED) treatment in patients with epilepsy.. Data from 443 adult outpatients with epilepsy assessed with the Adverse Event Profile (AEP) and the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) were analysed.. Fatigue is reported by 36.6% of patients as always a problem during AED treatment. Fatigue is more likely to be reported by females (64.8% vs. 35.2%; Chi-Square=16.762; df=3; p=0.001) and during treatment with levetiracetam (42.3% vs. 33.2%; Chi-Square=11.462; df=3; p=0.009). The associations with the female gender and levetiracetam treatment were not mediated by depression, as identified with the NDDIE, and could not be simply explained by the large number of subjects on levetiracetam treatment, as analogous figures resulted from the analysis of a monotherapy subsample (41.7% vs. 30.3%; Chi-Square=11.547; df=3; p=0.009).. One third of patients with epilepsy reports fatigue as a significant problem during AED treatment. Fatigue is more likely to be reported by females and seems to be specifically associated with LEV treatment. However, fatigue is not mediated by a negative effect of LEV on mood.

Topics: Adult; Anticonvulsants; Epilepsy; Fatigue; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam

Levetiracetam, a widely used antiepileptic drug in children, has been associated with psychosocial and behavioral problems, which are also influenced by epilepsy variables, including duration or seizure frequency.. The objective of this study is to investigate the frequency and timing of treatment-emergent psychosocial and behavioral problems in children receiving levetiracetam, irrespective of seizure variables which are possible confounders.. A prospective, case-control study with a 3-month follow-up was conducted. Consecutive children aged 6 to 16years with new-onset partial seizures were included in case of starting treatment with either levetiracetam or valproic acid. Psychosocial and behavioral functioning were assessed using a set of standardized questionnaires including Strengths and Difficulties Questionnaire (SDQ) and Children's Depression Inventory (CDI) at baseline, 1 and 3-month follow-up. Patients' baseline scores were compared to healthy subjects. The difference in the follow-up SDQ and CDI scores was evaluated in patients receiving levetiracetam and valproic acid.. A total of 101 participants were analyzed; 32 patients in levetiracetam group, 19 patients in valproic acid group and 50 healthy controls. Baseline SDQ and CDI scores were not statistically different between patients and healthy subjects (p>0.05). No statistically significant difference was observed in CDI, total and subscale SDQ scores between patients receiving levetiracetam or valproic acid during the study period (p>0.05). A girl aged 15years receiving levetiracetam had a CDI score of 18 without suicidal ideation at baseline. She developed suicidal ideation and depression, which resolved after switching of levetiracetam to valproic acid, at the 1-month follow-up. No other psychiatric or behavioral side-effects were observed in other patients.. Psychosocial and behavioral side-effects of levetiracetam treatment are not frequent and they don't emerge in most of children at lower doses. At this dose, and after 3months, using these specific instruments, we did not observe any difference between the valproic acid and levetiracetam treatment groups.

Topics: Adolescent; Anticonvulsants; Case-Control Studies; Child; Child Behavior; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Piracetam; Valproic Acid

Switching patients from a branded antiepileptic drug (AED) to a generic is often challenging. Several studies have shown that considerable proportions of patients report deteriorated seizure control or increased adverse effects, enforcing a switchback to the original drug. Since tolerability and seizure control usually correlate with AED serum concentrations, we examined the fluctuation of levetiracetam (LEV) serum concentrations in patients with epilepsy before and after generic substitution.. This was an 18-week, naturalistic, open, prospective, two-center study. After a baseline period of 10 weeks, 33 outpatients on stable treatment with branded LEV (Keppra. 16 out of 33 patients were switched to a generic LEV product. No switchbacks were seen. LEV dose, LEV serum concentrations, fluctuation index and concentration/dose-ratio (C/D-ratio) were not significantly different within-group (baseline vs. study period) or between-group. Large within-subject variability in serum concentrations was seen in both groups. None of the patients that were seizure-free before inclusion experienced seizures while on the generic LEV product.. Our results show equal fluctuation of LEV serum concentrations with branded LEV and the generic LEV. Most importantly, within-subject variability was much larger than the small, non-significant differences between brands.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Cohort Studies; Dose-Response Relationship, Drug; Drug Substitution; Drugs, Generic; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Outpatients; Piracetam; Time Factors; Treatment Outcome; Young Adult

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

Recent adverse event reports have raised the question of increased angioedema risk associated with exposure to levetiracetam. To help address this question, the Observational Health Data Sciences and Informatics research network conducted a retrospective observational new-user cohort study of seizure patients exposed to levetiracetam (n = 276,665) across 10 databases. With phenytoin users (n = 74,682) as a comparator group, propensity score-matching was conducted and hazard ratios computed for angioedema events by per-protocol and intent-to-treat analyses. Angioedema events were rare in both the levetiracetam and phenytoin groups (54 vs. 71 in per-protocol and 248 vs. 435 in intent-to-treat). No significant increase in angioedema risk with levetiracetam was seen in any individual database (hazard ratios ranging from 0.43 to 1.31). Meta-analysis showed a summary hazard ratio of 0.72 (95% confidence interval [CI] 0.39-1.31) and 0.64 (95% CI 0.52-0.79) for the per-protocol and intent-to-treat analyses, respectively. The results suggest that levetiracetam has the same or lower risk for angioedema than phenytoin, which does not currently carry a labeled warning for angioedema. Further studies are warranted to evaluate angioedema risk across all antiepileptic drugs.

Topics: Angioedema; Community Networks; Databases, Factual; Epilepsy; Female; Humans; Levetiracetam; Male; Phenytoin; Piracetam

We assessed the prevalence and magnitude of neuropsychiatric adverse events (NPAEs) associated with antiepileptic drugs (AEDs) among patients with brain tumour-related epilepsy (BTRE).. This observational, prospective, multicentre study enrolled 259 patients with BTRE after neurosurgery. All patients received AED monotherapy. Efficacy was assessed through clinical diaries, whereas NPAEs were collected using the Neuropsychiatric Inventory Test-12 questionnaire at baseline and after 5 months.. Tumour localization in the frontal lobe was associated with a higher prevalence of NPAEs (odds ratio, 7.73; P < 0.001). Independent of tumour localization, levetiracetam (LVT) treatment was associated with higher prevalence and magnitude of NPAEs (odds ratio, 7.94; P < 0.01) compared with other AEDs. Patients with oligodendroglioma reported more NPAEs than patients with other tumour types. NPAEs were not influenced by chemotherapy, radiotherapy or steroid treatment. Evaluating non-neurobehavioural adverse events of AEDs, no significant differences were found among AEDs, although patients treated with old AEDs had a higher prevalence of adverse events than those treated with new AEDs.. Both tumour localization in the frontal lobe and LVT treatment are associated with a higher risk of NPAEs in patients with BTRE. LVT is regarded as a first-line option in patients with BTRE because of easy titration and few significant drug-to-drug interactions. Thus, as NPAEs lead to poor compliance and a high dropout rate, clinicians need to accurately monitor NPAEs after AED prescription, especially in patients with frontal lobe tumours receiving LVT.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Epilepsy; Female; Humans; Italy; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Treatment Outcome; Young Adult

The approach to the use of generic antiepileptic drugs has recently evolved from major concern to general acceptance, but the evidence related specifically to the safety of switching from brand-name to generic levetiracetam (LEV) is scarce. The aim of the study was to assess the risk of increased frequency of seizures or other adverse events after replacement of a brand-name LEV with a generic one.. This retrospective analysis included 159 patients treated with LEV in a tertiary outpatient epilepsy clinic. We included all patients diagnosed with epilepsy who were treated with LEV as at March 1, 2013. Most patients were forced to switch to the generic LEV because of the sudden rise in cost of the branded LEV. We recorded data on age, sex, age at onset of epilepsy, type of epilepsy, and its treatment. We analyzed data from one visit before potential switching and from two visits after the potential switching. The interval between visits was typically 3 months. We registered an increase in the frequency of seizures and in the occurrence of adverse events.. Among 151 subjects who switched to generic LEV after March 1, 2013, increased frequency of seizures was noted in 9 patients (6%) during the first follow-up visit. Patients with increased frequency of seizures did not differ from other patients regarding sex, age, age at the onset of epilepsy, and the median dose of LEV before switching or the median duration of treatment with LEV before switching. Two patients returned to brand-name LEV. Adverse events were noted in six other patients (4%) and included somnolence, irritability, or dizziness.. Switching from brand-name to generic LEV is generally safe.

Topics: Adult; Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Retrospective Studies

A common side effect of levetiracetam is the onset of neuropsychiatric symptoms such as mood changes including depression, anxiety, agitation, and sometimes psychosis. We performed a retrospective analysis to examine the effect of sleep pattern and chronotype on individual susceptibility to levetiracetam-induced mood changes. We reviewed records of 110 adults with epilepsy presenting to our clinic during a 3-month period, and categorized them into those currently on levetiracetam, and those no longer taking it because of mood-related adverse effects. Patients were administered Morningness-Eveningness Questionnaire (MEQ), Beck's Depression Inventory-II, and Neurological Disorders Depression Inventory in Epilepsy. Using various statistical methods, we analyzed the comparison of these 3 different scales amongst one another and between those subjects who tolerated levetiracetam and those who did not. Of 110 patients, 74 (67%) tolerated levetiracetam and 36 (33%) did not tolerate it because of mood changes with chronotype being a significant determining factor. Of those who tolerated the drug, 62% were intermediate chronotypes and 20.3% and 17.6% were morning and evening chronotypes, respectively. For those intolerant, 86.1% were morning chronotypes, 13.9% were intermediate chronotypes, and none were evening chronotypes (p<0.001). Thirty-two percent of morning chronotypes, 100% of evening chronotypes, and 90.2% of intermediate chronotypes were tolerant of levetiracetam (p<0.001). Chronotype significantly affected toleration of levetiracetam. Chronotype, but not depression, was a significant factor in determining tolerability of mood-altering side effects of levetiracetam, via statistically significant trend for an increasing ability to tolerate levetiracetam as chronotype would shift from morning to intermediate to evening. Additional research may help establish if this is related to possible underreporting of poor mood with evening chronotypes, and morning chronotypes having more stringent sleep schedules, genetic factors, or other reasons.

Topics: Adult; Analysis of Variance; Anticonvulsants; Anxiety Disorders; Circadian Rhythm; Depressive Disorder; Epilepsy; Female; Humans; Incidence; Levetiracetam; Male; Middle Aged; Mood Disorders; Piracetam; Retrospective Studies; Sleep; Surveys and Questionnaires; Young Adult

To evaluate the efficacy and tolerability of levetiracetam monotherapy in dogs with structural epilepsy. Retrospective case series. Nineteen client-owned dogs with structural epilepsy. Seizure frequencies after initiation of treatment were used to evaluate the efficacy of levetiracetam monotherapy. Seizure control was considered good if no seizures occurred within three months of starting treatment or poor if seizures returned within one month of starting treatment. Tolerability was evaluated by considering the occurrence and severity of any reported side effects. Ten of the 19 dogs were considered to have a good response to treatment with 7 achieving complete seizure freedom. Nine dogs were considered to have poor response to treatment. There was a statistically significant reduction in the percentage of patients experiencing cluster seizures from 68.4% to 15.8% (p=0.002). Side effects were noted in 8 of the 19 dogs but were considered mild in all cases. Follow-up times ranged from 12 days to 426 days. When used in conjunction with other appropriate therapies, levetiracetam may be an efficacious option for monotherapy in dogs with structural epilepsy. Its tolerability makes it a suitable option for use in a wide variety of patients.

Topics: Animals; Anticonvulsants; Dog Diseases; Dogs; Epilepsy; Follow-Up Studies; Levetiracetam; Piracetam; Retrospective Studies; Seizures; Treatment Outcome

Pseudolymphoma is a drug reaction to anti-epileptics that is well recognized in humans; it has been reported in one cat but not dogs. In this report, lymphoma-like clinical signs are suspected to be secondary to phenobarbital administration in a dog. A 2.5-year-old male, neutered Shepherd mix presented for a 3-day history of progressive ataxia, dazed mentation, pyrexia, and lethargy. While hospitalized, the dog developed generalized lymphadenopathy and sustained pyrexia. The dog was receiving levetiracetam and phenobarbital for epilepsy, and serum concentrations of both were within standard therapeutic ranges. Abdominal ultrasound revealed hepatomegaly, splenomegaly, and generalized lymphadenopathy. Cytology of the peripheral lymph nodes was consistent with reactive lymph nodes, and aspirates of the liver and spleen revealed histiocytic-neutrophilic inflammation. Phenobarbital was discontinued and replaced with zonisamide. Within 24 hours, the dog was normothermic, and other clinical signs resolved within a week. This case highlights a potentially serious yet reversible adverse reaction to phenobarbital in a dog. This idiosyncratic reaction could be mistaken for neoplasia and is an important differential for lymphoma-like signs in any dog administered phenobarbital.

Topics: Animals; Anticonvulsants; Dog Diseases; Dogs; Epilepsy; Levetiracetam; Male; Phenobarbital; Piracetam; Pseudolymphoma

Topics: Anticonvulsants; Brain Neoplasms; Epilepsy; Humans; Levetiracetam; Piracetam

Long-term treatment with antiepileptic drugs (AEDs) is accompanied by reduced bone mass that is associated with an increased risk of bone fractures. Although phenytoin has been reported to adversely influence bone metabolism, little is known pertaining to more recent AEDs. The aim of this study was to evaluate the effects of gabapentin or levetiracetam on bone strength, bone mass, and bone turnover in rats. Male Sprague-Dawley rats were orally administered phenytoin (20 mg/kg), gabapentin (30 or 150 mg/kg), or levetiracetam (50 or 200 mg/kg) daily for 12 weeks. Bone histomorphometric analysis of the tibia was performed and femoral bone strength was evaluated using a three-point bending method. Bone mineral density (BMD) of the femur and tibia was measured using quantitative computed tomography. Administration of phenytoin significantly decreased bone strength and BMD, which was associated with enhanced bone resorption. In contrast, treatment with gabapentin (150 mg/kg) significantly decreased bone volume and increased trabecular separation, as shown by bone histomorphometric analysis. Moreover, the bone formation parameters, osteoid volume and mineralizing surface, decreased after gabapentin treatment, whereas the bone resorption parameters, osteoclast surface and number, increased. Levetiracetam treatment did not affect bone strength, bone mass, and bone turnover. Our data suggested that gabapentin induced the rarefaction of cancellous bone, which was associated with decreased bone formation and enhanced bone resorption, and may affect bone strength and BMD after chronic exposure. To prevent the risk of bone fractures, patients prescribed a long-term administration of gabapentin should be regularly monitored for changes in bone mass.

Topics: Administration, Oral; Amines; Animals; Anticonvulsants; Bone Density; Bone Remodeling; Bone Resorption; Cancellous Bone; Cyclohexanecarboxylic Acids; Epilepsy; Femur; Fractures, Bone; Gabapentin; gamma-Aminobutyric Acid; Humans; Levetiracetam; Male; Osteoclasts; Phenytoin; Piracetam; Rats; Rats, Sprague-Dawley; Tibia; Tomography, X-Ray Computed

This report describes the diagnosis and management of idiopathic epilepsy in a 4-yr-old intact female Reeve's muntjac ( Muntiacus reevesi). The patient was initially witnessed to have isolated paroxysmal events consistent with epileptic seizures (altered consciousness, lateral recumbency, tonic/clonic movement of limbs) lasting less than 3 min with an immediate return to normal consciousness. The seizure frequency increased to >3 seizures within 24 hr and phenobarbital 3 mg/kg orally every 12 hr was started. Because of continued epileptic seizures and low serum phenobarbital levels, the dose was increased until significant elevations of aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were detected. Levetiracetam 40 mg/kg orally every 12 hr was initiated and the phenobarbital was weaned and discontinued. One breakthrough seizure has been witnessed in the 10 mo since starting levetiracetam.

Topics: Animals; Anticonvulsants; Epilepsy; Female; Levetiracetam; Muntjacs

Topics: Administration, Oral; Anticonvulsants; Drug Overdose; Drug Packaging; Epilepsy; Humans; Levetiracetam; Medication Errors; Solutions

Levetiracetam is a new generation antiepileptic drug used in treatment of patients with epilepsy and has adverse effects on different tissues. We aimed to evaluate the apoptotic effects of levetiracetam exposure during pregnancy on liver and kidney tissues of rat pups.. We analyzed the newborn rat pups exposed to levetiracetam during prenatal period. Fifteen pregnant female rats were divided into three groups. The group 1 and 2 rats were treated with different doses of levetiracetam (25 mg/kg/d and 50 mg/kg/d, respectively) from gestational days 1-22 during pregnancy. Group 3 (control group) was treated with the same volume of saline. Apoptosis was evaluated by the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) method. Liver and kidney tissues from rat pups were used for investigation.. The percent of TUNEL positive apoptotic cells in group 1 were 22 and 17.5 for kidney and liver, respectively. The percent of TUNEL positive apoptotic cells in group 2 were 20.9 and 20.9 for kidney and liver, respectively. The percent of TUNEL positive apoptotic cells in group 3 were 18.4 and 17.1, respectively, for kidney and liver. The apoptotic index was the same in kidney and liver tissues of all groups.. Our results demonstrate that the prenatal exposure of levetiracetam has no apoptotic effects on liver and kidney of rat pups and, it has biosafety in pregnancy in terms of apoptosis. The first study evaluating the apoptotic effects on liver and kidney tissues following administration of levetiracetam during prenatal period.

Topics: Animals; Animals, Newborn; Anticonvulsants; Apoptosis; Chi-Square Distribution; DNA Nucleotidylexotransferase; Epilepsy; Female; In Situ Nick-End Labeling; Kidney; Levetiracetam; Liver; Piracetam; Pregnancy; Pregnancy Complications; Random Allocation; Rats; Rats, Sprague-Dawley

Our aim was to investigate regional difference in brain activities in response to antiepileptic drug (AED) medications in benign epilepsy with central-temporal spikes (BECTS) using resting-state functional magnetic resonance imaging (fMRI).. Fifty-seven patients with BECTS underwent resting-state fMRI scans after receiving either valproic acid (VPA) (n = 15), levetiracetam (LEV) (n = 21), or no medication (n = 21). fMRI regional homogeneity (ReHo) parameter among the three groups of patients were compared and were correlated with total doses of AED in the two medicated groups.. Compared with patients on no-medication, patients receiving either VPA or LEV showed decreased ReHo in the central-temporal region, frontal cortex, and thalamus. In particular, the VPA group showed greater ReHo decrease in the thalamus and milder in cortices and caudate heads compared with the LEV group. In addition, the VPA group demonstrated a negative correlation between ReHo values in the central-temporal region and medication dose.. Both VPA and LEV inhibit resting-state neural activity in the central-temporal region, which is the main epileptogenic focus of BECTS. VPA reduced brain activity in the cortical epileptogenic regions and thalamus evenly, whereas LEV reduced brain activity predominantly in the cortices. Interestingly, VPA showed a cumulative effect on inhibiting brain activity in the epileptogenic regions in BECTS.. • Regional differences in brain activity in response to different AEDs in BECTS. • AEDs inhibit resting-state neural activity in epileptogenic and subcortical regions in BECTS. • Valproic acid effect on the cortical epileptogenic regions and thalamus evenly. • Levetiracetam effect seen predominantly in cortices. • Valproic acid has a cumulative effect on inhibiting brain activity in epileptogenic regions.

Topics: Anticonvulsants; Brain; Child; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Female; Frontal Lobe; Humans; Image Interpretation, Computer-Assisted; Levetiracetam; Magnetic Resonance Imaging; Male; Piracetam; Temporal Lobe; Thalamus; Valproic Acid

Levetiracetam has a high tolerability and is effective against various seizure types and epilepsy syndromes. However, no study has specifically evaluated the efficacy of levetiracetam in children with refractory epilepsy based on magnetic resonance imaging (MRI) findings and the presence of intellectual disability (ID).. We retrospectively evaluated levetiracetam efficacy and safety in 49 pediatric patients who met the following inclusion criteria: (1) diagnosis of refractory epilepsy with first-line antiepileptic (AED) treatment ⩾2years, (2) younger than 20years old, and (3) received oral levetiracetam treatment for ⩾6months. We assessed the relationships of these outcomes with MRI findings and ID status.. Eighteen (37%) patients achieved a ⩾50% reduction in seizure frequency, and the majority (78%) had no remarkable side effects. Twenty-two (45%) patients had previously been treated with more than seven antiepileptic drugs prior to levetiracetam. Among 18 patients who achieved a ⩾50% reduction in seizure frequency, 13 and 5 had negative and positive MRI findings, and 9 and 9 had and did not have ID, respectively.. Our findings suggest that even for intractable pediatric cases with symptomatic etiology (i.e., MRI lesion and ID), levetiracetam has favorable efficacy for refractory epilepsy with tolerable adverse effects.

Topics: Administration, Oral; Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Resistant Epilepsy; Drug Therapy, Combination; Drug Tolerance; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Retrospective Studies; Treatment Outcome

To ascertain efficacy and tolerability of carbamazepine (CBZ), sodium valproate (VPA), lamotrigine (LTG) and levetiracetam (LEV) using the UKAED register (www.ukaed.info).. Patients on CBZ (n=91), VPA (n=61), LTG (n=105), LEV (n=72) and healthy control subjects (CTR) on no medication (n=51) were extracted. All patients had anonymously provided information on seizure type and frequency and completed the Liverpool Adverse Event Profile (LAEP).. The number of seizure-free patients in the last 4 weeks was overall CBZ/VPA/LTG/LEV=60%/79%/67%/67%, for generalized epilepsy was CBZ/VPA/LTG/LEV=67%/89%/65%/94%, and for localization-related epilepsy was CBZ/VPA/LTG/LEV=59%/71%/67%/57%. Mean LAEP scores were CBZ/VPA/LTG/LEV/CTR=42.21/39.66/39.86/43.01/29.69. The mean LAEP was significantly higher in patients reporting depression and in patients with active epilepsy than in patients without depression and remission. Central nervous system (CNS) adverse effects including memory problems, difficulty concentrating, depression, unsteadiness, restlessness, feelings of anger, shaky hands and dizziness were significantly more frequent in CBZ, VPA, LTG and LEV than in CTR. The feeling of anger was significantly more frequent in LEV, and depression was significantly more frequent in CBZ compared to the other drugs.. In this Internet-based register of self-reported efficacy and tolerability, CBZ, VPA, LTG and LEV were similar. Self-reported CNS adverse effects were significantly more frequent than in controls. In addition, anger was associated with LEV and depression with CBZ. Confounding factors were depression and uncontrolled epilepsy.

Topics: Adult; Anticonvulsants; Carbamazepine; Depression; Epilepsy; Female; Humans; Internet; Lamotrigine; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Seizures; Self Report; Treatment Outcome; Triazines; United Kingdom; Valproic Acid

Levetiracetam may induce serious behavioral disturbances, especially after surgical resection of frontal lobe low-grade glioma. Two patients, treated with levetiracetam, developed serious psychiatric complications postoperatively which completely resolved after switching to valproate. We aim to create awareness for this serious but reversible adverse effect of levetiracetam in this specific patient category.

Topics: Anticonvulsants; Brain Neoplasms; Craniotomy; Epilepsy; Frontal Lobe; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Mental Disorders; Middle Aged; Oligodendroglioma; Piracetam; Postoperative Complications; Valproic Acid

Perinatal arterial stroke is the most frequent form of cerebral infarction in children. Neonatal seizures are the most frequent symptom during the neonatal period. The current management of perinatal stroke is based on supportive care. It is currently unknown if treatment of the seizures modifies the outcome, and no clinical studies have focused on seizures during neonatal stroke. We studied the effect of phenobarbital and levetiracetam on an ischemic-reperfusion stroke model in P7 rats using prolonged electroencephalographic recordings and a histologic analysis of the brain (24h after injury). The following two types of epileptic events were observed: 1) bursts of high amplitude spikes during ischemia and the first hours of reperfusion and 2) organized seizures consisting in discharges of a 1-2Hz spike-and-wave. Both phenobarbital and levetiracetam decreased the total duration of the bursts of high amplitude spikes. Phenobarbital also delayed the start of seizures without changing the total duration of epileptic discharges. The markedly limited efficacy of the antiepileptic drugs studied in our neonatal stroke rat model is frequently observed in human neonatal seizures. Both drugs did not modify the stroke volume, which suggests that the modification of the quantity of bursts of high amplitude spikes does not influence the infarct size. In the absence of a reduction in seizure burden by the antiepileptic drugs, we increased the seizure burden and stroke volume by combining our neonatal stroke model with a lithium-pilocarpine-induced status epilepticus. Our data suggest that the reduction of burst of spikes did not influence the stroke volume. The presence of organized seizure with a pattern close to what is observed in human newborns seems related to the presence of the infarct. Further research is required to determine the relationship between seizure burden and infarct volume.

Topics: Animals; Animals, Newborn; Anticonvulsants; Brain; Brain Ischemia; Disease Models, Animal; Epilepsy; Female; Levetiracetam; Lithium Compounds; Male; Phenobarbital; Pilocarpine; Piracetam; Random Allocation; Rats, Wistar; Reperfusion Injury; Stroke

Epilepsy is one of the major neurological disorders frequently associated with psychiatric disorders such as depression. The predisposition of tryptophan metabolism towards kynurenine pathway has been reported as one of the plausible reasons for association of depression in epilepsy. Hence, this study was envisaged to evaluate the dose dependent inhibition of indoleamine 2,3-dioxygenase (IDO) enzyme employing quercetin (screened employing in vitro method) with levetiracetam for combined management of epilepsy and comorbid depression. Kindling was induced in male swiss albino mice by administration of pentylenetetrazole subconvulsive doses (35 mg/kg, i.p.) at an interval of 48 ± 2 h. Kindled animals were treated with vehicle, levetiracetam (40 mg/kg/day i.p.) levetiracetam in combination with different doses of quercetin (10 mg/kg; 20 mg/kg; 40 mg/kg)/day/p.o. for 15 days. Except naïve, all the groups were challenged with pentylenetetrazole (35 mg/kg i.p.) on day 5, 10, and 15 to evaluate the seizure severity score. Depression was evaluated in all experimental groups using the tail suspension and sucrose preference test on days 1, 5, 10 and 15, 2 h after pentylenetetrazole challenge. Results suggested that vehicle treated kindled animals were significantly associated with depression. Chronic levetiracetam treatment significantly reduced seizure severity score, but further worsened the associated depression. Quercetin supplementation with levetiracetam dose dependently ameliorated depression associated with epilepsy. Neurochemical and biochemical findings also supported the behavioural findings of the study. Thus, our results suggested that supplementation of quercetin with levetiracetam could be explored further for combined treatment of epilepsy and comorbid depression.

Topics: Animals; Anticonvulsants; Behavior, Animal; Brain; Combined Modality Therapy; Convulsants; Depression; Depressive Disorder; Disease Models, Animal; Epilepsy; Levetiracetam; Male; Mice; Pentylenetetrazole; Piracetam; Quercetin

Adult patients with Down syndrome (DS) are at higher risk of developing Alzheimer-type dementia and epilepsy. The relationship between developing dementia and the risk of developing seizures in DS is poorly characterized to date. In addition, treatment response and medication tolerability have not been rigorously studied.. We identified 220 patients with a diagnosis of DS and dementia. Those without a history of developing seizures (DD) were compared to patients with new-onset seizures (DD+S) after the age of 35. Electronic records were reviewed for demographics, seizure characteristics, cognitive status, and psychiatric comorbidities.. Of the patients included for analysis, twenty-six out of 60 patients had new-onset seizures or developed seizures during the follow-up period (the DD+S group) with a median onset of 2.0years after the dementia diagnosis. Generalized tonic-clonic seizures were the most common seizure type (61.5% of DD+S). Sixteen (61.5%) patients were reported to have myoclonus. Levetiracetam was the most commonly used initial medication, with the majority (73%) of patients treated achieving partial or complete seizure control. The DD+S patients tended to have a similar burden of new-onset neuropsychiatric symptoms compared to the DD group.. New-onset epilepsy seems to occur early in the course of dementia in DS patients. Patients generally respond to treatment. A great burden of neuropsychiatric symptoms is seen. Future studies need to explore the relationship between β-amyloid accumulation and epileptiform activity and attend to the care and needs of DS patients with dementia and seizures.

Topics: Adult; Anticonvulsants; Dementia; Disease Progression; Down Syndrome; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Myoclonus; Piracetam

Levetiracetam (LEV) is commonly used as a mono- or adjunctive therapy for treating patients with partial and generalized epilepsy. This study aimed to develop a population pharmacokinetic (PK) model of LEV, based on sparse data, and to explore LEV efficacy relative to its PK properties in patients with epilepsy. We included 483 LEV concentrations from 425 patients with epilepsy that received multiple oral LEV doses. We performed a population PK analysis, implemented in NONMEM (version 7.2). In addition, we explored the relationships between seizure control and PK variables (i.e., LEV dose, trough concentration, and the number of concomitant anti-epileptic drugs). LEV concentration-time profiles were adequately described with a one-compartment, open linear model, with first-order absorption, and additive residual error. The typical population estimates of the apparent clearance (CL/F) and the volume of distribution (V/F) were 3.9L/h and 65.3L, respectively. Body weight was a significant covariate for CL/F and V/F; the estimated glomerular filtration rate only significantly affected CL/F; and concomitant intake of other anti-epileptic drugs did not significantly affect either parameter. A cumulative percentage analysis revealed that over 95% of patients that remained seizure-free received LEV doses of 2000mg/day or lower. LEV trough concentrations were not significantly different between seizure-free and seizure groups, for each LEV dose. In conclusion, we successfully developed a population PK model of LEV, which enabled investigation of LEV efficacy, relative to its PK properties. The findings in this study can be utilized to optimize LEV dosing regimens in clinical practice.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Body Weight; Dose-Response Relationship, Drug; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Seizures; Treatment Outcome; Young Adult

To assess the impact of the new AEDs on overall outcome for patients with epilepsy.. In 2004, the effect of combination therapy on seizure frequency in adult patients with focal epilepsy was evaluated in a cross-sectional study in our center. We repeated this analysis ten years and eight new antiepileptic drugs (AED) later.. In 2014, a higher percentage of patients with polytherapy (117 out of 396; 30%) were seizure-free compared with the original analysis (22%) (p=0.042). Eighty three out of 218 (38%) subjects on duo-therapy were seizure-free (27% in 2004) (p=0.040); in the 151 receiving triple therapy there were 30 (20%) seizure-free subjects (10% in 2004). Four out of 27 subjects (15%) with four AEDs were seizure-free (0% in 2004). The most common pairing of 52 different combinations for duo-therapy was levetiracetam-oxcarbazepine. Eighty different AEDs regimens were being used in the patients administered three AEDs.. Our combined data from these two studies indicate that some patients with focal epilepsy might benefit from newer AEDs as an adjunctive therapy in the hope they could acquire seizure freedom.

Topics: Adult; Aged; Anticonvulsants; Carbamazepine; Cross-Sectional Studies; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Piracetam; Retrospective Studies; Seizures; Treatment Outcome

Objective: As a treatment for cases of developmental disorder accompanied with epilepsy, the author examined the efficacy and tolerability of combined administration of levetiracetam (LEV) on the cases. Methods: There were 21 participants (male-to-female-ratio was 16 to 5, 6 in their 10s, 7 in their 20s, 7 in their 30s and 1 in their 40s) to whom LEV was prescribed from October 2011 to December 2014. The effect was classified as loss of seizure, effective (more than 75% reduction in the number of seizures, more than 50% reduction in the number of seizures), unchanged (no change), and aggravation (increase in the number of seizures). Results: The study included 19 autistic spectrum disorder (ASD) cases (13 with profound intellectual disability, 5 with severe intellectual disability, and 1 with high functioning autism), 1 borderline intelligence case, and 1 attention deficit/hyper activity disorder (AD/HD) case. By classification of epilepsy seizure, there were 15 symptomatic localization-related epilepsy cases and 6 generalized epilepsy cases. The initial dose of LEV was an average of 488.1 mg/day, and the maintenance dose was an average of 1,714.2 mg/day. The average duration of administration was 2 years and 3 months. In terms of the response rate, there were 11 cases of loss of seizure (52.4%), 4 cases of more than 75% reduction in the number of seizures, (19.0%), and 3 cases of more than 50% reduction in the number of seizures (14.3%). The overall response rate was 85.7% (18 cases). 14.3% was unchanged (3 cases). No aggravation case was observed. There was only one case of dizziness in the initial period, but all cases continued taking LEV. The kinds of anticonvulsant agent could be adjusted from 2.5 at the beginning of LEV administration to 1.5. Emotional stability was also observed. Some cases could stop taking tranquilizers. Conclusions: LEV showed high response rate and tolerability on the cases of ASD and other developmental disorder accompanied with epilepsy. Administration of this drug led to reduction in the number of concomitant medications, which indicates the possibility that LEV may contribute to enhancing compliance.

Topics: Adult; Anticonvulsants; Drug Combinations; Epilepsy; Female; Humans; Levetiracetam; Male; Neurodevelopmental Disorders; Piracetam

The aim of this study was to assess the rate of response to long-term low-dose levetiracetam (LEV) treatment and the clinical factors associated with response.. The response to low-dose LEV of 43 patients with epilepsy (22 male, 21 female; age range, 5-39 years; median age, 13 years) was retrospectively assessed. Patients aged <15 years received <20 mg/kg/day LEV, whereas those aged ≥15 years received <1000 mg/day LEV. Clinical features were compared between responders to low-dose LEV, responders to the recommended dose, and non-responders.. Of the 43 patients who received low-dose LEV, 13 (30%) showed improvement, defined as seizure cessation or >75% seizure reduction over 6 months for patients with monthly, weekly, and daily seizures; and over 1 year for patients with yearly seizures. Efficacy was maintained for >1 year in 10 (77%) of the 13 patients. Long-term response to low-dose LEV was significantly associated with older age at onset and fewer previous treatments with ineffective anti-epileptic drugs. All patients showing long-term response to low-dose LEV developed only focal seizures.. Titration of LEV starting from a low dose may be effective in selected patients. Once patients respond to low-dose treatment, maintenance of the effective dosage may prolong response.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Piracetam; Retrospective Studies; Time Factors; Treatment Outcome; Young Adult

Syntaxin Binding Protein 1 (STXBP1) mutations determine a central neurotransmission dysfunction through impairment of the synaptic vesicle release, thus causing a spectrum of phenotypes varying from syndromic and non-syndromic epilepsy to intellectual disability of variable degree. Among the antiepileptic drugs, levetiracetam has a unique mechanism of action binding SV2A, a glycoprotein of the synaptic vesicle release machinery.. We report a 1-month-old boy manifesting an epileptic encephalopathy with clonic seizures refractory to phenobarbital, pyridoxine and phenytoin that presented a dramatic response to levetiracetam with full epilepsy control and EEG normalization. Genetic analysis identified a novel de novo heterozygous mutation (c.[922A>T]p.[Lys308(∗)]) in the STXBP1 gene that severely affects the protein.. The observation of a dramatic efficacy of levetiracetam in a case of STXBP1 epileptic encephalopathy refractory to other antiepileptic drugs and considerations regarding the specific mechanism of action of levetiracetam modulating the same system affected by STXBP1 mutations support the hypothesis that this drug may be able to reverse specifically the disease epileptogenic abnormalities. Further clinical observations and laboratory studies are needed to confirm this hypothesis and eventually lead to consider levetiracetam as the first choice treatment of patients with suspected or confirmed STXBP1-related epilepsies.

Topics: Age of Onset; Anticonvulsants; Brain; DNA Mutational Analysis; Electroencephalography; Epilepsy; Humans; Infant, Newborn; Levetiracetam; Male; Munc18 Proteins; Mutation; Piracetam; Treatment Outcome

Concerns that antiepileptic brand-to-generic interchange results in disruption of seizure control are widespread. The objective of this study was to evaluate the safety and tolerability of the brand-to-generic levetiracetam switch in patients with focal or generalized epilepsy.. A prospective study in patients with primary, cryptogenic or symptomatic epilepsy, who were taking branded levetiracetam and were switched to generic levetiracetam. Patients were consecutively recruited from January 2013 to January 2015. We evaluated efficacy, tolerability and compliance before switching (T0) and after 6 months of therapy (T1). Evaluations were scheduled as follows: baseline, 7 and 15 days, 1, 3 and 6 months. At each visit clinical diary seizures, physical and neurological examination, laboratory parameters and electroencephalogram were evaluated.. Fifty-nine patients, equally mixed by sex, were included in the study. Mean age was 26.1 years. Forty-seven per cent of the patients enrolled received levetiracetam as monotherapy. One patient was lost during the follow-up: so at T1 we had 58 patients (28 monotherapy and 30 polytherapy). At T0 and at T1, there was no statistically significant difference in terms of seizure frequency and intensity, occurrence of adverse events, laboratory parameters and electroencephalographic features. Two patients stopped treatment with the generic (both at 3 months after the switch) and restarted therapy with brand levetiracetam because of seizure increase. At the end of the study, the switchback rate was 3.4%.. No increase of seizures and adverse effects were observed when branded levetiracetam was interchanged to a generic equivalent. More studies should be conducted with a larger series of patients to confirm these results.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Drugs, Generic; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Young Adult

Topics: Anticonvulsants; Epilepsy; Female; Humans; Infant; Levetiracetam; Piracetam; Wolf-Hirschhorn Syndrome

In patients taking antiepileptic drugs (AEDs) for epilepsy, adverse effects (AEs) often lead to unfavorable quality of life, impaired adherence, and, eventually, discontinuation of pharmacological treatment. In a true-to-life sample of subjects from our academic epilepsy outpatient clinic, we aimed to identify predictors for overall high AE burden and for specific AEs focusing on patients on monotherapy.. All patients ≥16years of age with epilepsy for ≥12months were routinely asked to complete the Liverpool Adverse Event Profile (LAEP) just before their appointment. Demographic, epilepsy, and treatment variables were derived from our comprehensive outpatient database.. Out of 841 patients, 438 (61% female, mean age: 44.7±17.1years) on monotherapy were included in this study. Levetiracetam (n=151), lamotrigine (n=167), valproic acid (n=73), or controlled-release carbamazepine (n=47) were the most commonly used antiepileptic drugs (AEDs). Independent predictors for general high AE burden (LAEP score≥45) were duration of epilepsy, lack of 12-month seizure freedom, and partial epilepsy, but none of the four individual AEDs. The most frequent LAEP-defined specific AEs were sleepiness, difficulty concentrating, tiredness, and memory problems. The three most frequent independent predictors for each of the 19 AEs were lack of 12-month seizure freedom (13/19 AEs), individual AED (7/19 AEs), and partial epilepsy (6/19 AEs). Levetiracetam was independently associated with anger/aggression, nervousness/agitation, upset stomach, depression, and sleep disturbance; lamotrigine with nervousness/agitation, upset stomach, and difficulty concentrating; and valproic acid with upset stomach and shaky hands.. Individual AEDs independently predicted some specific AEs, but not overall high AE burden. Our findings may help to characterize patients with epilepsy who are at high risk for specific AEs. Dose reduction or change to another AED may reduce LAEP score and potential nonadherence.

Topics: Adult; Aged; Anticonvulsants; Anxiety; Carbamazepine; Depression; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Fatigue; Female; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Piracetam; Quality of Life; Triazines; Valproic Acid; Young Adult

Enzyme-inducing antiepileptic drugs AEDs have adverse effects on bone mineral density (BMD), whereas studies on levetiracetam (LEV), a nonenzyme-inducing agent, have showed conflicting results. The aim of this study was to further elucidate the role of LEV in bone health. A sample of forty-six patients with epilepsy (mean age: 35.7 years, range: 20.2-64.2 years, 39.1% males) on LEV monotherapy for at least one year (range: 1.5-14.5 years, median 5.5 years) underwent femoral neck (FN) and lumbar spine (LS) BMD measurements. The T- and Z-scores were calculated. Results showed that 15.2% of the patients were identified with osteopenia and none with osteoporosis. Pearson's correlations revealed a negative but not significant association of LEV duration with bone-related measurements (range of rhos: from -0.004 to -0.23), except for LS T-scores. In terms of FN BMD measurements, Z-scores, and T-scores, longer LEV therapy duration had adverse but not significant effects on bone health after adjusting for age and gender. With regard to LS BMD measurements, Z-scores, and T-scores, men taking LEV for at least 5.5 years had better, although not significant, bone health compared with men with shorter LEV exposure, after adjusting for age. The opposite was found in women, although differences did not reach significance. These preliminary results are indicative of a differential effect of LEV therapy duration in men and women, which could presumably account for the incongruity of the already published studies. Also, LS assessments were more sensitive to these gender differences. Future larger studies should validate these results.

Topics: Adult; Anticonvulsants; Bone Density; Cohort Studies; Drug Administration Schedule; Epilepsy; Female; Health Status; Humans; Levetiracetam; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis; Piracetam; Radiography; Retrospective Studies; Sex Characteristics; Treatment Outcome; Young Adult

Symptomatic epilepsy is a common complication of glioblastoma and requires pharmacotherapy. Several uncontrolled retrospective case series and a post hoc analysis of the registration trial for temozolomide indicated an association between valproic acid (VPA) use and improved survival outcomes in patients with newly diagnosed glioblastoma.. To confirm the hypothesis suggested above, a combined analysis of survival association of antiepileptic drug use at the start of chemoradiotherapy with temozolomide was performed in the pooled patient cohort (n = 1,869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (Avastin in Glioblastoma; NCT00943826), CENTRIC (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status; NCT00689221), CORE (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Unmethylated Gene Promoter Status; NCT00813943), and Radiation Therapy Oncology Group 0825 (NCT00884741). Progression-free survival (PFS) and overall survival (OS) were compared between: (1) any VPA use and no VPA use at baseline or (2) VPA use both at start of and still after chemoradiotherapy. Results of Cox regression models stratified by trial and adjusted for baseline prognostic factors were analyzed. The same analyses were performed with levetiracetam (LEV).. VPA use at start of chemoradiotherapy was not associated with improved PFS or OS compared with all other patients pooled (PFS: hazard ratio [HR], 0.91; 95% CI, 0.77 to 1.07; P = .241; OS: HR, 0.96; 95% CI, 0.80 to 1.15; P = .633). Furthermore, PFS and OS of patients taking VPA both at start of and still after chemoradiotherapy were not different from those without antiepileptic drug use at both time points (PFS: HR, 0.92; 95% CI, 0.74 to 1.15; P = .467; OS: HR, 1.10; 95% CI, 0.86 to 1.40; P = .440). Similarly, no association with improved outcomes was observed for LEV use.. The results of this analysis do not justify the use of VPA or LEV for reasons other than seizure control in patients with newly diagnosed glioblastoma outside clinical trials.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Antineoplastic Agents, Alkylating; Brain Neoplasms; Chemoradiotherapy; Clinical Trials as Topic; Dacarbazine; Epilepsy; Female; Glioblastoma; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prognosis; Survival Analysis; Temozolomide; Valproic Acid

There are limited data on the use of the antiepileptic drug (AED) levetiracetam for the treatment of infants.. To prospectively evaluate the safety of levetiracetam oral solution and its impact on epilepsy severity in infants with different seizure types.. This noninterventional post-authorization safety study included patients 1-11 months of age. Patients' treatment - levetiracetam dose, and addition, withdrawal or changes in the doses of concomitant medications and AEDs - was at the discretion of the physician. The primary variable was treatment-emergent adverse events (TEAEs).. Of 101 infants, 75 completed and 26 discontinued the study. Mean age was 6.0 months, 50 were male, most (80%) took 1 ≥ concomitant AED and had cryptogenic or symptomatic epilepsy that was focal (38.6%) or generalized (20.8%), particularly frontal lobe epilepsy (20.0%) or West syndrome/infantile spasms (20.0%). Among known aetiologies, congenital factors (22.8%) such as dysplastic lesions or perinatal events (17.8%) were predominant. Overall, 54.5% of patients had ≥ 1 TEAE. Five patients experienced drug-related TEAEs - convulsion, irritability, somnolence and hypotonia, all listed in the product label, with the exception of hypotonia, which was reported for one patient and resolved without any change in study medication. Seven patients discontinued due to TEAEs, mainly due to infantile spasms and respiratory disorders. At study end, 71.8% of patients showed improvement in epilepsy severity, 18.8% remained stable and 9.4% showed worsening. Levetiracetam did not appear to have a negative effect on growth parameters.. In this prospective study, which included the largest number of patients in this age range so far, levetiracetam was found to be well tolerated and efficacious for the treatment of infants with epilepsy.

Topics: Anticonvulsants; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Europe; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Prospective Studies; Treatment Outcome

Topics: Anticonvulsants; Benzodiazepines; Epilepsy; Humans; Levetiracetam; Liver Failure, Acute; Liver Transplantation; Male; Middle Aged; Olanzapine; Piracetam

Resistance to antiepileptic drugs (AEDs) is a major problem in epilepsy therapy, so that development of more effective AEDs is an unmet clinical need. Several rat and mouse models of epilepsy with spontaneous difficult-to-treat seizures exist, but because testing of antiseizure drug efficacy is extremely laborious in such models, they are only rarely used in the development of novel AEDs. Recently, the use of acute seizure tests in epileptic rats or mice has been proposed as a novel strategy for evaluating novel AEDs for increased antiseizure efficacy. In the present study, we compared the effects of five AEDs (valproate, phenobarbital, diazepam, lamotrigine, levetiracetam) on the pentylenetetrazole (PTZ) seizure threshold in mice that were made epileptic by pilocarpine. Experiments were started 6 weeks after a pilocarpine-induced status epilepticus. At this time, control seizure threshold was significantly lower in epileptic than in nonepileptic animals. Unexpectedly, only one AED (valproate) was less effective to increase seizure threshold in epileptic vs. nonepileptic mice, and this difference was restricted to doses of 200 and 300 mg/kg, whereas the difference disappeared at 400mg/kg. All other AEDs exerted similar seizure threshold increases in epileptic and nonepileptic mice. Thus, induction of acute seizures with PTZ in mice pretreated with pilocarpine does not provide an effective and valuable surrogate method to screen drugs for antiseizure efficacy in a model of difficult-to-treat chronic epilepsy as previously suggested from experiments with this approach in rats.

Topics: Animals; Anticonvulsants; Diazepam; Disease Models, Animal; Drug Resistance; Epilepsy; GABA Antagonists; Levetiracetam; Male; Mice; Pentylenetetrazole; Phenobarbital; Pilocarpine; Piracetam; Rats; Seizures; Status Epilepticus; Valproic Acid

Generic substitution of antiepileptic drugs (AEDs) is still a matter of controversy and concern among clinicians and patients. We aimed to assess intrasubject variation in plasma concentrations of lamotrigine (LTG), levetiracetam (LEV) and topiramate (TPM) after generic substitution compared with a stable brand-name drug regimen in a population of patients with epilepsy. A retrospective analysis was performed on prospectively collected and stored data from our therapeutic drug monitoring (TDM) database for the years 2009-2014. The main outcome variable was the proportion of patients who, after switching from branded to generic formulations, showed a greater than ±20% change in AED plasma concentrations compared to the proportion of control patients showing a change in AED plasma concentrations of the same extent while receiving stable branded formulations over repeated TDM tests. Fifty patients on LTG, 27 on LEV and 16 on TPM showing at least one TDM test while receiving generic products fulfilled the inclusion/exclusion criteria for the analysis and were compared with 200 control patients for LTG, 120 for LEV and 80 for TPM. The proportion of patients showing an intrasubject change greater than ±20% in AED plasma concentrations was similar in the brand name vs generic group compared with the control one for LTG (22% vs 33%) and LEV (44% vs 38%), while it was higher in the control group for TPM (41% vs 6%, p<0.01). These are the first data in the literature about the within-patient variation in steady-state plasma concentrations of a series of stable treatments with brand-name AEDs in a real clinical setting. In conclusion, a significant interday variability in intrapatient LTG, LEV and TPM plasma concentrations can be observed even in patients stabilized with the same brand name product over time. This suggests that any change in plasma AED concentration and possible related clinical effects after generic substitution may be not necessarily related to the switch. Our results should be confirmed by large, prospective, blinded, randomized controlled studies in people with epilepsy.

Topics: Adult; Anticonvulsants; Blood Chemical Analysis; Databases, Pharmaceutical; Drug Substitution; Drugs, Generic; Epilepsy; Female; Follow-Up Studies; Fructose; Humans; Inpatients; Lamotrigine; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Retrospective Studies; Topiramate; Triazines

Although it has been reported that some antiepileptic drugs have inducing or inhibiting effects on lamotrigine (LTG) clearance, whether they have the same effects in Asian epilepsy patients as in those in other countries has not been clarified, especially in children. The aim of this study was to determine the effects of co-medications on LTG clearance in Japanese children with epilepsy.. A total of 342 routine serum concentration measurements of LTG in 102 Japanese epilepsy patients under 20years of age were reviewed. The dose-corrected concentration (DCC) of LTG was calculated as [concentration]/[dose/(body weight)], and the DCC of LTG was compared by co-medication. The difference in the DCC of LTG was compared between patients with and without valproic acid (VPA) and between those with and without drugs inducing glucuronic acid conjugation (phenytoin (PHT), carbamazepine (CBZ), and phenobarbital (PB)).. The DCC of LTG was significantly higher in patients on VPA and significantly lower in patients on drugs inducing glucuronic acid conjugation than in patients on LTG monotherapy. The DCC of LTG was significantly higher in patients on CBZ than in patients on PHT or PB. There was no correlation between the DCC of LTG and the concentration of VPA or metabolic inducers within the therapeutic range. Other antiepileptic drugs including clobazam, clonazepam, zonisamide, and levetiracetam had little effect on LTG concentration.. LTG concentration changes dramatically with concomitant antiepileptic drugs in Japanese children, as previously reported from other countries, and special attention is required. Although the dose of LTG should be adjusted when starting or discontinuing VPA or metabolic inducers, no adjustment is needed when changing the dose of VPA or metabolic inducers in the therapeutic range.

Topics: Adolescent; Anticonvulsants; Benzodiazepines; Carbamazepine; Child; Child, Preschool; Clobazam; Clonazepam; Drug Interactions; Drug Therapy, Combination; Epilepsy; Female; Humans; Infant; Infant, Newborn; Isoxazoles; Japan; Lamotrigine; Levetiracetam; Male; Phenobarbital; Phenytoin; Piracetam; Triazines; Valproic Acid; Young Adult; Zonisamide

This study aimed to evaluate the clinical characteristics of levetiracetam (LEV)-induced cutaneous adverse drug reactions (cADRs) and to explore its possible genetic association with the human leukocyte antigen (HLA) genes.. Nine cases with LEV-induced cADRs were recruited. Demographic and clinical information of these cases was summarized. Additionally, cases were matched with LEV-tolerant controls (1:4). High-resolution HLA class I and class II genotyping was performed for each participant. The allele frequencies between the cases and controls were compared.. All LEV-induced cADRs were mild skin rashes which occurred within 28 days of LEV exposure. The mean latency from LEV exposure to skin rash was (15.67±5.41) days (ranging 6-27). The carrier rates of the two alleles, HLA-DRB1*0405 and HLA-DQB1*0401, were higher in cases compared with controls (the same P=0.036, OR=13.875, 95% CI: 1.273-151.230). The association between the HLA-C*0304 allele and LEV-induced cADRs was boundary (P=0.05, OR=5.2, 95% CI: 1.086-24.897). However, the above-mentioned HLA alleles didn't reach statistical significance after multiple comparisons.. Safety monitoring was necessary within four weeks after the initiation of LEV treatment, although it has been regarded as a safe antiepileptic drug. Our study failed to show any potential link between HLA alleles and LEV-induced cADRs in Han Chinese. Further studies are needed to clarify the genetic and immunological mechanisms of LEV-induced cADRs.

Topics: Adult; Anticonvulsants; Asian People; Child; China; Epilepsy; Exanthema; Female; Gene Frequency; Genotyping Techniques; Heterozygote; HLA Antigens; Humans; Levetiracetam; Male; Middle Aged; Piracetam

Certain antiepileptic drugs (AEDs) such as valproic acid (VPA) are known to affect body weight, and lipid profile. However, evidences regarding effects of AEDs on the body composition are deficient. This cross-sectional study compared the body composition and lipid profile among patients with epilepsy on newer and conventional AEDs.. The patients with epilepsy (n=109) on treatment with conventional and newer AEDs (levetiracetam, lamotrigine and clobazam) for > 6 months were enrolled. Of these, 70 were on monotherapy: levetiracetam (n=12), VPA (n=16), carbamazepine (n=20) and phenytoin (n=22) and the remaining on polytherapy. Their body composition [body fat mass, lean dry mass (LDM), total body water (TBW), intracellular water (ICW), extracellular water (ECW) and basal metabolic rate (BMR) was estimated and biochemical parameters were assessed.. Levetiracetam group had no significant difference with VPA, carbamazepine, phenytoin and control groups, except low LDM (17.8±2.4) than VPA groups (20.2±2.7, p<0.05). In comparison with control, AEDs monotherapy groups had no significant difference, except higher LDM and ECW in VPA group. Among groups based on conventional and newer AEDs, there was no significant difference in body composition parameters except for higher LDM (as % of BW) in conventional AEDs only treated group than control (p<0.01).. The alterations observed in body composition with valproic acid in contrast to other AEDs like levetiracetam, carbamazepine and phenytoin could affect treatment response in epilepsy especially in subjects with already altered body composition status like obese and thin frail patients, which needs to be established by prospective studies (CTRI/2013/05/003701).

Topics: Adult; Anticonvulsants; Benzodiazepines; Body Composition; Body Water; Body Weight; Carbamazepine; Clobazam; Cross-Sectional Studies; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Lipids; Male; Middle Aged; Piracetam; Triazines; Valproic Acid

Topics: Administration, Oral; Anticonvulsants; Brain; Brain Waves; Drug Administration Schedule; Drug Compounding; Epilepsy; Humans; Levetiracetam; Piracetam; Tablets; Treatment Outcome

To determine prescribing patterns of antiepileptic drugs (AEDs) in pediatric patients with confirmed diagnosis of epilepsy, and to provide knowledge of general practice of physicians.. The study was a multi-center crosssectional observational study, in specialized clinics for management of epilepsy in north, central and south Jordan. This study was conducted from January 2014 to July 2014. These were 3 from university tertiary care hospitals and 4 from governmental tertiary care hospitals.. A total of 694 pediatric patients were included. Monotherapy AED use had the highest frequency 465 (67.0%), followed by dual therapy 162 (23.3%). The frequency of monotherapy in university hospitals was lower than governmental hospitals (p<0.05); however, Polytherapy was more frequent in younger children. Two old AEDs were most frequently prescribed as a monotherapy; Valproic acid 235 (50.5%) and carbamazepine 155 (33.3%). The most common combination in dual therapy was valproic acid with carbamazepine 28 (17.3%). The second most common combinations were carbamazepine with levetiracetam 21 (13.0%) or valproic acid with levetiracetam 20 (12.3%).. Older AED remain first line drugs for use in both monotherapy and combination therapy for epileptic disorders. Polytherapy is associated with younger kids and being treated in a university hospital.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Cross-Sectional Studies; Drug Therapy, Combination; Epilepsy; Female; Fructose; Humans; Jordan; Levetiracetam; Male; Phenobarbital; Piracetam; Practice Patterns, Physicians'; Topiramate; Valproic Acid

To investigate the clinical efficacy and safety of Levetiracetam (LEV) add-on therapy for child refractory epilepsy.. Levetiracetam add-on therapy was tested on 65 children who suffered refractory epilepsy, and clinical seizures. Electroencephalogram (EGG) changes and adverse reactions were observed in these children respectively in three, six and twelve months after the therapy.. The complete control rates observed after 3, 6 and 12 months were respectively: 6.9%, 10.3% and 3.4%, while the response rates were accordingly 44.8%, 58.6% and 39.6%. The ameliorative rate of EGG reached 65.5%, appearing in positive correlation with the clinical efficacy (r = 0.436, p = 0.001). The retention rate after one year was 89%. Adverse reactions were expressed in 3% of the child patients, and the symptoms were dysphoria, mental and behavior disorders.. The levetiracetam add-on therapy for child refractory epilepsy, demonstrates fast and obvious efficacy as well as fewer adverse reactions.

Topics: Anticonvulsants; Child; Epilepsy; Humans; Levetiracetam; Piracetam; Treatment Outcome

Epilepsy has an impact on the reproductive system. Males with epilepsy have lower fertility rates, hypo-sexuality and reduced potency compared with the general population. Anti-epileptic drugs and epilepsy itself are thought to be responsible for this reduced fertility. LEV is a second-generation anti-epileptic agent with low incidences of both adverse effects and drug-drug interactions. In this study, we have investigated the effects of LEV treatment on sex hormones and sperm parameters in newly diagnosed epilepsy patients.. We recruited 26 males with newly diagnosed epilepsy and introduced LEV monotherapy. Patients were divided into two groups depending on whether they had partial or generalized seizures. We acquired the results of pre- and post-treatment sperm analyses and serum sex hormone levels. We also recorded the maximum dose, daily dose and treatment duration for each individual. Pre- and post-treatment comparisons and correlations between both sperm and sex hormone parameters and both treatment duration and dose were determined.. Pre- and post-treatment sex hormone levels were not significantly different. The total sperm count, percentage of normal morphology and functional sperm count tested after treatment were significantly lower in both groups compared with pre-treatment values (p<0.05). There was a moderate correlation between daily dose and reduction in functional sperm count (r: 0.41, p: 0.034).. Our findings confirm that LEV treatment of newly diagnosed epilepsy patients decreases sperm parameters without altering sex hormone levels. Our results may guide the choice of anti-epileptic drug treatment among men with epilepsy.

Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Gonadal Steroid Hormones; Humans; Levetiracetam; Male; Piracetam; Sperm Count; Statistics as Topic; Testis; Ultrasonography, Doppler; Young Adult

Topics: Adrenoleukodystrophy; Anticonvulsants; Child; Cord Blood Stem Cell Transplantation; Epilepsy; Glomerular Filtration Rate; Humans; Levetiracetam; Male; Monitoring, Physiologic; Piracetam

To investigate the effects of prenatal exposure to monotherapy levetiracetam, topiramate, and valproate on child cognitive functioning.. This was a cross-sectional observational study. Children exposed to monotherapy levetiracetam (n = 42), topiramate (n = 27), or valproate (n = 47) and a group of children born to women who had untreated epilepsy (n = 55) were enrolled retrospectively from the UK Epilepsy and Pregnancy Register. Assessor-blinded neuropsychological assessments were conducted between 5 and 9 years of age. Information was collected on demographic and health variables and adjusted for in multiple regression analyses.. In the adjusted analyses, prenatal exposure to levetiracetam and topiramate were not found to be associated with reductions in child cognitive abilities, and adverse outcomes were not associated with increasing dose. Increasing dose of valproate, however, was associated with poorer full-scale IQ (-10.6, 95% confidence interval [CI] -16.3 to -5.0, p < 0.001), verbal abilities (-11.2, 95% CI -16.8 to -5.5, p < 0.001), nonverbal abilities (-11.1, 95% CI -17.3 to -4.9, p < 0.001), and expressive language ability (-2.3, 95% CI -3.4 to -1.6, p < 0.001). Comparisons across medications revealed poorer performance for children exposed to higher doses of valproate in comparison to children exposed to higher doses of levetiracetam or topiramate.. Preconception counseling should include discussion of neurodevelopmental outcomes for specific treatments and their doses and women should be made aware of the limited nature of the evidence base for newer antiepileptic drugs.

Topics: Adult; Anticonvulsants; Child; Cognition Disorders; Cross-Sectional Studies; Epilepsy; Female; Follow-Up Studies; Fructose; Humans; Levetiracetam; Male; Piracetam; Pregnancy; Prenatal Exposure Delayed Effects; Topiramate; Valproic Acid; Young Adult

Qatar is a small country on the Eastern coast of the Arabian Peninsula. Its population is a unique mixture of native citizens and immigrants. We aimed to describe the features of epilepsy in Qatar as such information is virtually lacking from the current literature.. We summarized information retrospectively collected from 468 patients with epilepsy seen through the national health system adult neurology clinic.. Epilepsy was classified as focal in 65.5% of the cases and generalized in 23%. Common causes of epilepsy were as follows: stroke (9%), hippocampal sclerosis (7%), infections (6%), and trauma (6%). Sixty-six percent of patients were receiving a single antiepileptic drug, with levetiracetam being the most frequently prescribed drug (41% of subjects). When the patients were divided by geographical background, remote infections caused the epilepsy in 15% of Asian patients (with neurocysticercosis accounting for 10%) but only in 1% of Qatari and 3% of Middle East/North African subjects (with no reported neurocysticercosis) (p<0.001). Cerebrovascular and neurodegenerative etiologies were the most prominent in Qataris, accounting for 14% (p=0.005) and 4% (p=0.03) of cases, respectively. The choice of antiepileptic drugs varied also according to the regional background, but the seizure freedom rate did not, averaging at 54% on the last clinic visit.. To our knowledge, this is the first detailed information about epilepsy in Qatar. The geographical origin of patients adds to the heterogeneity of this disorder. Neurocysticercosis should be in the etiological differential diagnosis of epilepsy in patients coming from Southeast Asian countries, despite the fact that it is not endemic to Qatar. The choice of antiepileptic drugs is influenced by the availability of individual agents in the patients' native countries but had no bearing on the final seizure outcome.

Topics: Adult; Anticonvulsants; Diagnosis, Differential; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Neurocysticercosis; Piracetam; Qatar; Retrospective Studies; Treatment Outcome; Young Adult

Topics: Agranulocytosis; Anticonvulsants; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Fever; Humans; Levetiracetam; Male; Piracetam

Haematological toxicity due to antiepileptic drugs is uncommon, but the increased risk of aplastic anaemia has been reported. Few case reports have been published regarding pancytopenia associated with levetiracetam treatment, and its intrinsic pathogenesis is still unknown. We describe the case of a woman aged 77 years who presented with abdominal pain and loss of appetite. She had been taking valproic acid, due to a previous episode of epileptic seizures, and presented with drowsiness and dizziness. Valproate was discontinued and therapy with levetiracetam was initiated. 2 days later, we observed severe anaemia, leucopenia and thrombocytopenia, which were attributed to levetiracetam. Although she recovered soon after the treatment was discontinued, it took 2 weeks for cell counts to return to normal.

Topics: Aged; Anticonvulsants; Epilepsy; Female; Humans; Leukocyte Count; Levetiracetam; Pancytopenia; Piracetam

A novel antiepileptic drug, levetiracetam, has been reported to cause several psychiatric adverse effects in spite of its effectiveness on epilepsy. However, a possible relationship between levetiracetam and obsessive-compulsive behavior has only been reported in a few studies with adult epilepsy patients. We treated a pediatric patient with epilepsy without past or family history of psychiatric disorder. Levetiracetam was started to control generalized tonic-clonic seizure. Two months after initiation of levetiracetam with favorable seizure control, she started to show an obsessive-compulsive behavior such as repetitive checking of her back, pants, and chair. Based on the course of its appearance, levetiracetam administration was identified as a possible cause. After termination of levetiracetam, her obsessive-compulsive behavior completely disappeared with reappearance of seizures. This case provides clear evidence that levetiracetam may cause obsessive-compulsive behavior even in a pediatric epilepsy patient without psychiatric background, possibly mediated by modulation of the glutamate system by levetiracetam.

Topics: Adolescent; Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Obsessive-Compulsive Disorder; Piracetam

Retro-chiasmal lesions almost always give rise to homonymous field defects with only one exception. The nasal visual field extends to 60% of the horizon, whereas the temporal field extends to a further 30°-40° beyond that; this part of the visual field is represented on the contralateral anterior parieto-occipital sulcus. A lesion in this area will give rise to monocular visual field defect affecting the contralateral eye. This is called the temporal crescent or the half moon syndrome. In this case report, a woman presented with seizures secondary to haemorrhagic infarction of the anterior part of the parieto-occipital sulcus. She later presented with right-sided visual disturbance; her examination confirmed temporal crescent syndrome. I explain the pathophysiology of this rare neurological syndrome in this report.

Topics: Aged; Anticonvulsants; Cerebral Infarction; Epilepsy; Female; Humans; Levetiracetam; Piracetam; Syndrome; Vision Disorders; Visual Fields

This study was a retrospective assessment of the therapeutic drug monitoring data collected for levetiracetam and lamotrigine from a clinical setting. The proportion of patients in relation to the therapeutic ranges for serum concentrations of lamotrigine and levetiracetam was estimated, and the influence of age and anticonvulsant comedications on their clearances were studied.. Information on levetiracetam (2011-2013) and lamotrigine (2008-2013) dose, trough concentration, age, sex, body weight, and anticonvulsant comedications prescribed was obtained from the therapeutic drug monitoring register and archived medical records. Patients were categorized into 4 groups based on anticonvulsant comedications and further divided into 3 subgroups based on age (a: <9 years; b: 9-17 years; c: ≥18 years). In each subgroup, the proportion of patients who achieved trough concentrations in the therapeutic range for levetiracetam and lamotrigine was computed. Apparent clearance (CL/F) was compared across subgroups by 1-way analysis of variance, and factors which significantly predicted CL/F were identified by stepwise multiple linear regression.. Overall, 348 (330 patients) and 706 (493 patients) samples for levetiracetam and lamotrigine were included in the analysis. Of these, 56.9% and 72.4% were within, 43.1% and 23.9% below, 0% and 3.7% above the therapeutic range for levetiracetam and lamotrigine, respectively. A significant difference in CL/F was noted across subgroups for levetiracetam (P < 0.001) and lamotrigine (P < 0.001). Age <9 years, age ≥18 years, and inducer comedications significantly predicted CL/F for levetiracetam. For lamotrigine, inhibitor comedications, age <9 years, inducer comedications, and age 9-17 years significantly predicted CL/F.. These findings emphasize the need to monitor relatively newer anticonvulsants, lamotrigine and levetiracetam, especially among children and when other anticonvulsant comedications are prescribed or discontinued in the treatment regimen.

Topics: Adolescent; Adult; Age Factors; Anticonvulsants; Child; Child, Preschool; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 Enzyme Inhibitors; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Epilepsy; Female; Humans; Infant; Lamotrigine; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Triazines; Young Adult

Levetiracetam (Lev) is a new antiepileptic drugs, proved to be effective and tolerance in regulatory trials, but these controlled trials do not always predict how useful a drug will be in day to day clinical practice, Retention rates can provide a better indication of efficacy and tolerability in everyday use.. Totally 124 patients with more than 3 months disease course were enrolled in the study from June 2007 to December 2007. The LEV dose ranged from 10 to 60 mg/kg per day. Follow up visit were performed at 6 months, 12 months, 24 months and 36 months, and treatment effects, adverse effects were recorded.. The LEV retention rates at 6, 12, 24, and 36 months were 93.5% (116/124), 84.7% (105/124), 65.3% (81/124), and 58.9% (73/124), respectively. The predominant causes of withdrawal were lack of efficacy (62.7%) and serious adverse effects (17.6%). In addition, 48.6% (51/105), 60.5% (49/81) and 72.6% (53/73) patients were seizure-free for 12 months, 24 months and 36 months, respectively. In this study, 75 (60.5%) patients experienced at least one side effect. The most common side effects observed were irritability 38.7% (29/75), somnolence 17.3% (13/75), learning disability 16.0% (12/75), anorexia 17.3% (13/75), somnipathy 13.3% (10/75), and abnormal behavior 13.3% (10/75).. Our study revealed the high retention rate of LEV in Chinese children and adolescents with epilepsy.

Topics: Adolescent; Anticonvulsants; Asian People; Child; Child, Preschool; Epilepsy; Female; Humans; Levetiracetam; Male; Medication Adherence; Piracetam

Cosmetic side effects (CSEs) such as weight gain and alopecia are common, undesirable effects associated with several AEDs. The objective of the study was to compare the CSE profiles in a large specialty practice-based sample of patients taking both older and newer AEDs.. As part of the Columbia and Yale AED Database Project, we reviewed patient records including demographics, medical history, AED use, and side effects for 1903 adult patients (≥16years of age) newly started on an AED. Cosmetic side effects were determined by patient or physician report in the medical record and included acne, gingival hyperplasia, hair loss, hirsutism, and weight gain. We compared the overall rate of CSEs and intolerable CSEs (ICSEs-CSEs that led to dosage reduction or discontinuation) between different AEDs in both monotherapy and polytherapy.. Overall, CSEs occurred in 110/1903 (5.8%) patients and led to intolerability in 70/1903 (3.7%) patients. Weight gain was the most commonly reported CSE (68/1903, 3.6%) and led to intolerability in 63 (3.3%) patients. Alopecia was the second most common patient-reported CSE (36/1903, 1.9%) and was intolerable in 33/1903 (1.7%) patients. Risk factors for CSEs included female sex (7.0% vs. 4.3% in males; p<0.05) and any prior CSE (37% vs. 2.9% in patients without prior CSE; p<0.001). Significantly more CSEs were attributed to valproic acid (59/270; 21.9%; p<0.001) and pregabalin (14/143; 9.8%; p<0.001) than to all other AEDs. Significantly less CSEs were attributed to levetiracetam (7/524; 1.3%; p=0.002). Weight gain was most frequently associated with valproic acid (35/270; 13.0%; p<0.001) and pregabalin (12/143; 8.4%; p<0.001). Hair loss was most commonly reported among patients taking valproic acid (24/270; 8.9%; p<0.001). Finally, gingival hyperplasia was most commonly reported in patients taking phenytoin (10/404; 2.5%; p<0.001). Cosmetic side effects leading to dosage change or discontinuation occurred most frequently with pregabalin and valproic acid compared with all other AEDs (13.3 and 5.6% vs. 2.3%; p<0.001). For patients who had been on an AED in monotherapy (n=677), CSEs and ICSEs were still more likely to be attributed to valproic acid (30.2% and 17.1%, respectively) than to any other AED (both p<0.001).. Weight gain and alopecia were the most common patient-reported CSEs in this study, and weight gain was the most likely cosmetic side effect to result in dosage adjustment or medication discontinuation. Particular attention should be paid to pregabalin, phenytoin, and valproic acid when considering cosmetic side effects. Female patients and patients who have had prior CSE(s) to AED(s) were more likely to report CSEs. Knowledge of specific CSE rates for each AED found in this study may be useful in clinical practice.

Topics: Acne Vulgaris; Adult; Alopecia; Anticonvulsants; Epilepsy; Female; gamma-Aminobutyric Acid; Gingival Diseases; Hirsutism; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Pregabalin; Risk Factors; Sex Factors; Valproic Acid; Weight Gain

Epilepsy with electrical status epilepticus in sleep (ESES) is a devastating disease, and we sought to evaluate the efficacy of levetiracetam (LEV) for the treatment of patients with this epileptic encephalopathy in China.. Clinical data from all patients with ESES who received LEV therapy at our pediatric neurology outpatient clinic between 2007 and 2014 (n=71) were retrospectively analyzed. The LEV dosage was 30-50mg/kg/day. Electroencephalography recordings and neuropsychological evaluations were performed repeatedly for 3-75months after the start of LEV therapy.. Thirty-five (70%) of 50 patients who had seizures at the start of LEV therapy had a >50% reduction in seizure frequency. Positive response on EEG was found during the first 3-4months of LEV therapy in 32 (45%) of 71 patients, with normalization of EEG in 5 patients. Relapse occurred in 8 (25%) of the initial electrical responders. Hence, 47 patients (66%) still suffered from ESES and only 13 patients regained their baseline level of function at the last follow-up. The response to LEV was significantly associated with ESES duration, age at onset of ESES, and etiology of epilepsy. Although fatigue and anorexia were the primary adverse events, LEV was well-tolerated by all patients.. Levetiracetam is safe and may be efficient when used to treat ESES syndrome; however, the efficacy EEG neuropsychological outcomes is limited on the whole.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; China; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Seizures; Sleep Wake Disorders; Status Epilepticus; Treatment Outcome

To assess the effect and tolerability of zonisamide (ZNS) as adjunctive treatment for difficult-to-treat epilepsy in adult Scandinavian patients.. 151 outpatients (mean age: 42.5 years) from 18 centres in Denmark, Sweden and Norway were recruited to the study. 81.5% had focal epilepsy, and the mean number of previously tried AEDs was 4.5. The patients were given ZNS as add-on treatment, and the ZNS dosing and the visit frequency were governed by the treating physician. The primary efficacy endpoint was the retention rate after 12-month treatment. Assessments included also responder rate, type and frequency of adverse events, healthcare resource utilization (HCRU) and quality of life (QOLIE-31).. 90 patients (59.6%) completed the study. Mean daily ZNS dose was 300.8 mg. After 12 months, 81 patients were still on ZNS, that is a retention rate of 53.6%. The mean reduction of seizure frequency at 12 months was 27%. Best effect was seen in those with focal and those with secondary generalized seizures. In the QOLIE-31, there was a mean increase from baseline of 4.8 points. The tolerability was generally good. The majority of side effects were CNS-related, dizziness, fatigue, seizure aggravation, and headache being most prevalent. 21.2% had adverse events leading to withdrawal of ZNS.. A retention rate of 53.6% after 1 year of treatment with ZNS is roughly in accordance with the retention rates found for lamotrigine, oxcarbazepine, levetiracetam and topiramate in drug-resistant patients.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Denmark; Drug Therapy, Combination; Epilepsy; Female; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Male; Middle Aged; Norway; Patient Dropouts; Piracetam; Quality of Life; Sweden; Treatment Outcome; Triazines; Young Adult; Zonisamide

The purpose of this study was to identify clinical correlates of self-reported aggressiveness (SRA) in patients with epilepsy treated with levetiracetam (LEV) with special reference to the role of depression.. A consecutive sample of adult outpatients with epilepsy was assessed with the Neurological Disorder Depression Inventory for Epilepsy, the Adverse Event Profile (AEP), and the Emotional Thermometer.. From a total sample of 163 consecutive patients treated with LEV, SRA at any level (from rarely a problem to always) was associated with a 7-fold increased risk of being depressed (95% CI: 3.0-17.5; p<0.001). Self-reported aggressiveness was reported as "always" a problem by 9.8% of the patients. In these patients, apart from depression, SRA was associated with high AEP total scores (55.1 vs. 39.3; p<0.001) and polytherapy (43.8% vs. 19.8%; p=0.034). Anxiety scores were not elevated (4.9 vs. 3.6; p=0.183).. Self-reported aggressiveness during treatment with LEV is not an isolated symptom but is associated with depressed mood. Anxiety-mediated mechanisms do not seem to be involved.

Topics: Adult; Aggression; Anticonvulsants; Depressive Disorder, Major; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Self Report; Treatment Outcome

Retrospective studies can complement information derived from double-blinded randomized trials. There are multiple retrospective studies reporting good efficacy and tolerability of the anti-epileptic drug levetiracetam (LEV) in human patients with epilepsy; however, reports of LEV's tolerability and efficacy in dogs with epilepsy remain limited. The purpose of this retrospective study was to describe the use of LEV in a canine epilepsy clinic and determine the long-term efficacy and tolerability of LEV in veterinary clinical practice. The electronic database of a UK based referral hospital was searched for LEV usage in dogs with seizures. Information and data necessary for the evaluation were obtained from a combination of electronic and written hospital records, the referring veterinary surgeons' records and telephone interviews with dog owners. Only dogs that were reportedly diagnosed with idiopathic epilepsy were included in the study.. Fifty-two dogs were included in this retrospective study. Two treatment protocols were recognised; 29 dogs were treated continuously with LEV and 23 dogs received interval or pulse treatment for cluster seizures. LEV treatment resulted in 69% of dogs having a 50% or greater reduction of seizure frequency whilst 15% of all the dogs were completely free from seizures. Seizure frequency reduced significantly in the whole population. No dog was reported to experience life-threatening side effects. Mild side effects were experienced by 46% of dogs and a significantly higher number of these dogs were in the pulse treatment group. The most common side-effects reported were sedation and ataxia.. LEV appears to be effective and well tolerated for reduction of seizures.

Topics: Animals; Anticonvulsants; Dog Diseases; Dogs; Epilepsy; Female; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures; Treatment Outcome

Hyponatremia is frequently seen in heart failure patients and has a high mortality rate. If not treated adequately, acute and chronic hyponatremia may worsen the prognosis of heart failure. Despite its high incidence in heart failure patients, other underlying conditions that possibly lead to the incidence of hyponatremia may be underestimated, thus making its treatment more difficult. In this case study, we describe a rare case of levetiracem-induced and tolvaptan-resistant hyponatremia.

Topics: Aged; Anticonvulsants; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Epilepsy; Heart Failure; Humans; Hyponatremia; Inappropriate ADH Syndrome; Levetiracetam; Male; Piracetam; Tolvaptan

TO determine neuroprotective properties of levetiracetam and simvastatin using rats with pilocaroine-induced epilepsy.. Epileptic rat models were randomly divided into 4 groups, each being exposed to saline, simvastatin, levetiracetam, or levetiracetam + simvastatin. Brain tissues of the rats were examined. Nissl staining was used to determine pilocarpine-induced neuronal loss in CA1 and CA3 of hippocampus. Western blot was used to detect calpain-1 expression of hippocampus.. Severe cell death was found 24 h after seizures, with a level significantly higher than the controls. Compared with the saline-treated cells, simvastatin did not decrease severe cell death (P>0.05), but levetiracetam and levetiracetam+simvastatin decreased severe cell death 24 h after seizures (P<0.05). No significant differences were found between those treated with levetiracetam and those with levetiracetam+simvastatin. Compared with controls, overexpressed calpain-1 was found in the rats 24 h after seizures, which indicates that calpain-1 may be involved in the pathophysiological mechanisms of epilepsy. Compared with those treated with pilocarpine + saline, simvastatin, levetiracetam and levetiracetam + simvastatin reduced the level of calpain-1 24 h after seizures (P<0.05).. Levetiracetam, not simvastatin, possesses neuroprotective properties, through changing calpain-1 expression levels. But levetiracetam plus simvastatin treatment does not have advantages over the choice of monotherapy. Simvastain does not possess neuroprotective properties at the early stage of epilepsy.

Topics: Animals; Calpain; Disease Models, Animal; Epilepsy; Hippocampus; Levetiracetam; Pilocarpine; Piracetam; Rats; Seizures; Simvastatin

Norrie disease is an X-linked recessive disorder that is characterized by congenital blindness. Although epileptic seizures are observed in some patients with Norrie disease, little is known about this phenomenon. Here, we report the manifestation of epilepsy in siblings with Norrie disease to increase our knowledge of epilepsy in this condition. Three brothers with congenital blindness were diagnosed with Norrie disease after genetic analyses indicated the deletion of exon 2 of the NDP gene. The eldest brother had suffered from epileptic seizures since the age of 11years, and his seizures were resistant to antiepileptic drugs. Although the second brother had no epileptic seizures, the youngest sibling had experiences epileptic seizures since the age of 8years. His seizures were controlled using lamotrigine and levetiracetam. An electroencephalography (EEG) revealed epileptiform discharges in the occipital areas in all three brothers. A study of these patients will increase our knowledge of epilepsy in patients with Norrie disease.

Topics: Anticonvulsants; Blindness; Chromosomes, Human, X; Electroencephalography; Epilepsy; Eye Proteins; Genetic Diseases, X-Linked; Humans; Lamotrigine; Levetiracetam; Nerve Tissue Proteins; Nervous System Diseases; Pedigree; Phenotype; Piracetam; Retinal Degeneration; Siblings; Spasms, Infantile; Triazines

Lacosamide treats partial seizures by enhancing slow inactivation of voltage-gated sodium channels. The described cardiac toxicity of lacosamide in the literature to date includes atrioventricular blockade (PR prolongation), atrial flutter, atrial fibrillation, sinus pauses, ventricular tachycardia and a single cardiac arrest. We report a second case of cardiac arrest following an intentional lacosamide overdose.. A 16 year-old female with a seizure disorder was found unresponsive in pulseless ventricular tachycardia after intentionally ingesting 4.5 g (76 mg/kg) lacosamide, 120 mg (2 mg/kg) cyclobenzaprine and an unknown amount of levetiracetam. Exact time of ingestion was unknown. Her initial electrocardiogram (ECG) demonstrated sinus tachycardia at 139 beats per minute, QRS duration 112 ms, and terminal R-wave in lead aVR > 3 mm. Despite treatment with 150 mEq of sodium bicarbonate, she had persistent EKG findings eight hours after presentation. Her serum lacosamide concentration nine hours after presentation was elevated at 22.8 μg/mL, while serum cyclobenzaprine concentration was 16 ng/mL (therapeutic: 10-30 ng/mL), and serum levetiracetam concentration was 22.7 μg/mL (therapeutic: 12-46 μg/mL). On hospital day three, ECG demonstrated resolution of the terminal R-wave with QRS of 78 ms. The patient recovered without physical or neurologic sequelae.. The patient's lacosamide, cyclobenzaprine and levetiracetam overdose was associated with QRS prolongation and terminal right axis deviation--suggesting sodium channel blockade as a likely etiology for her cardiac arrest. Cyclobenzaprine has potential for sodium channel blockade and ventricular dysrhythmias although cardiac toxicity due to cyclobenzaprine alone is rare. The combination of cyclobenzaprine with lacosamide may have resulted in cardiovascular collapse. In conclusion, overdose of lacosamide combined with therapeutic concentrations of sodium channel blocking xenobiotics may cause cardiac conduction delays and cardiac arrest.

Topics: Acetamides; Adolescent; Amitriptyline; Anticonvulsants; Drug Interactions; Drug Overdose; Electrocardiography; Epilepsy; Female; Heart Arrest; Humans; Lacosamide; Levetiracetam; Piracetam; Risk Factors; Sodium Bicarbonate; Sodium Channel Blockers; Sodium Channels; Suicide, Attempted; Tachycardia, Ventricular; Treatment Outcome

As new research has increased our understanding of epilepsy and the challenges patients with epilepsy face, the role of the nurse as an educator and advocate has grown. This article, the second in a two-part series, addresses the most important aspects of assessing and caring for patients with epilepsy-highlighting the seizure first-aid instructions that all family members of a patient with epilepsy should have; the teaching points to share with parents of young children with epilepsy; and online epilepsy resources for patients, family members, and health care professionals. The authors also discuss current medical, surgical, neurostimulatory, and dietary approaches to epilepsy treatment.

Topics: Anticonvulsants; Brain; Cognition Disorders; Consumer Health Information; Diet, Ketogenic; Drug Resistance; Epilepsy; Evidence-Based Nursing; Fructose; Humans; Internet; Levetiracetam; Medical Marijuana; Parents; Piracetam; Topiramate

Synaptic vesicle protein 2A (SV2a) is the binding site of the antiepileptic drug levetiracetam and the only known synaptic vesicle target of an epilepsy medication. To date, no pathogenic mutation in SV2A, which is the gene encoding synaptic vesicle glycoprotein 2A, has been identified in humans. We report a homozygous mutation in the SV2A gene in a patient with intractable epilepsy.. We investigated a patient with intractable epilepsy, involuntary movements, microcephaly, and developmental and growth retardation. Both parents were multiply consanguineous and an earlier-born brother of the proband had a similar course and died at 7 months of age. Detailed clinical history, imaging, electroencephalograph and metabolic testing were obtained. Full exome sequencing was performed using genomic DNA isolated from the patient and both parents.. Exome sequencing identified a homozygous arginine to glutamine mutation in amino acid position 383 (R383Q) in exon 5 of the SV2A gene. Both parents were carriers for the R383Q variant, suggesting that R383Q is a recessive mutation. There were no other candidate alterations in the exome that could explain the phenotype in the proband. The amino acid arginine at position 383 of SV2a gene is evolutionally conserved throughout vertebrates. R383Q change is not observed in known healthy cohorts, exome databases, or the Database of Single Nucleotide Polymorphisms. The R383Q mutation is located in the second adenine binding domain in SV2a protein and may alter adenine nucleotides binding to SV2a.. Our report provides the elusive evidence that an SV2A mutation can be a cause of epilepsy in humans. Levetiracetam, which binds to SV2A, was not effective as an antiepileptic medication. The location of the mutation in our patient supports an important role of adenine nucleotides binding in SV2A function.

Topics: Anticonvulsants; Child, Preschool; Developmental Disabilities; Dyskinesias; Epilepsy; Female; Growth Disorders; Humans; Levetiracetam; Membrane Glycoproteins; Microcephaly; Mutation; Nerve Tissue Proteins; Piracetam

Topics: Anticonvulsants; Dose-Response Relationship, Drug; Electrocardiography; Epilepsy; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; Female; Follow-Up Studies; Heart; Humans; Levetiracetam; Long QT Syndrome; Piracetam; Point Mutation; Young Adult

Catamenial epilepsy is a periodic increase in seizure frequency in women with epilepsy during menstruation, or at any specific point in the menstrual cycle. We present five cases who attended the epilepsy outpatient clinic at the Sichuan Provincial People's Hospital, China, and who suffered catamenial epilepsy and received intermittent Levetiracetam (LEV) treatment 1 week prior to and post-menstruation around each menstrual period. The patients responded positively and seizures were controlled with a dose of 0.5g, twice daily in 3(67%) patients, and by a dose of 0.75g twice daily in the remaining 2(33%) patients, indicating that intermittent LEV therapy could be an effective strategy for the treatment of catamenial epilepsy.

Topics: Adult; Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Menstrual Cycle; Piracetam

To evaluate the long-term effects and tolerability of levetiracetam (LEV) in refractory epilepsy.. LEV was administered to 76 patients whose seizures were inadequately controlled by their current medications. The patients were followed for a minimum of 18 months but less than 2 years. The efficacy of LEV treatment was assessed retrospectively as the proportion of patients who experienced at least a 50% reduction in the frequency of seizures (50% RR), and adverse events were analyzed.. The 50% RR in all 76 patients was 42%. The 50% RRs in the 54 patients with localization-related epilepsy and in the 20 patients with generalized epilepsy were 42% and 35%, respectively. The patients who responded most remarkably to the therapy, with at least a 75% reduction in the frequency of seizures, were more often those with localization-related epilepsy. Among adverse events, irritability and hyperactivity/impulsivity were observed more frequently in this study than in previous reports. These events were observed predominantly in patients suffering from autism or attention deficit hyperactivity disorder (AD/HD) as a comorbidity. γ-GTP values were improved in 14 of 17 patients whose values prior to beginning LEV treatment were higher than the normal range. This beneficial effect presumably resulted from a dose reduction or the discontinuation of other hepatotoxic antiepileptic drugs.. LEV was useful for the treatment of refractory epilepsy, and long-term efficacy was demonstrated. LEV also appeared to be less hepatotoxic. Behavioral changes should be monitored carefully when LEV is administered to patients with concomitant autism or AD/HD.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Levetiracetam; Long-Term Care; Male; Middle Aged; Piracetam; Treatment Outcome; Young Adult

To elucidate the mechanisms that regulate p-glycoprotein (PGP) expression and function in pharmacoresistant epilepsy, we investigated the effect of an ETB receptor antagonist (BQ788) and a p38 mitogen-activated protein kinase (p38MAPK) inhibitor (SB202190) on intractable seizures in chronic epileptic rats.. Lithium-pilocarpine-induced chronic epileptic rats were used in the present study. Animals were given levetiracetam (LEV), LEV + SB202190, LEV + BQ788, SB202190 or BQ788 over a 3-day period using an osmotic pump. Seizure activity was recorded by video-EEG monitoring with 2h of recording per day at the same time of day. We also performed western blot after EEG analysis.. Compared to control animals, PGP, ETB receptor and p38MAPK expression was increased in the hippocampus of epileptic animals. Neither SB202190 nor BQ788 affected the spontaneous seizure activity in epileptic rats. Three of ten rats were responders and achieved complete seizure control or significant reduction in seizure activity by LEV. In four of ten rats, seizure frequency was unaltered by LEV (non-responders). LEV + SB202190 reduced seizure duration, but not seizure frequency, in both responders and non-responders. LEV + BQ788 alleviated seizure frequency and seizure duration in both responders and non-responders. Compared to responders, PGP and ETB receptor expression was enhanced in the hippocampus of non-responders.. To the best of our knowledge, these findings are the first indications of the role of ETB receptor in pharmacoresistant epilepsy. Therefore, the present data suggest that the regulation of the ETB receptor-mediated signaling pathway may be important for identification of new therapeutic strategies for improving antiepileptic drug efficacy.

Topics: Animals; Anticonvulsants; Brain; Chronic Disease; Disease Models, Animal; Endothelin B Receptor Antagonists; Enzyme Inhibitors; Epilepsy; Imidazoles; Levetiracetam; Male; Oligopeptides; p38 Mitogen-Activated Protein Kinases; Piperidines; Piracetam; Pyridines; Rats, Sprague-Dawley; Receptor, Endothelin B; Seizures; Treatment Outcome

Longitudinal prescription patterns of antiepileptic drugs (AEDs) have not been described to date in Korea. Here we aimed to describe AED prescribing trends over a 12-year period and assess age differences in AED prescribing patterns in a pediatric epilepsy population.. We retrieved and analyzed all AED prescribing and dispensing data in 2001-2012 in patients aged 0-18 years with an established diagnosis of epilepsy at the largest tertiary children's hospital in Korea. AEDs included for analysis were classified as older (i.e., carbamazepine, ethosuximide, phenobarbital, phenytoin, and valproic acid) and newer (i.e., gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, topiramate, vigabatrin, zonisamide, lacosamide, and rufinamide) on the basis of market availability before versus after 1991.. A total of 5593 patients with epilepsy were prescribed an AED during the 12-year period. The proportion of newer AED prescriptions was 52.6 % in 2001 and continuously increased to 74.3 % in 2012. Oxcarbazepine was most widely used, followed by valproic acid. While carbamazepine and vigabatrin use progressively decreased over the 12-year period, those of lamotrigine and topiramate rapidly increased. Age differences in prescribing patterns were observed. Polytherapy was observed in 49.7 % of the total population, while 83.9 % of new users were prescribed monotherapy.. This study provided updated information on AED prescription trends for childhood epilepsy. We found a progressive increase in the use of newer AEDs. However, valproic acid, the only prevalent older AED, continued to be widely prescribed. A high rate of polytherapy among the prescriptions overall raises some safety concerns.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Drug Prescriptions; Epilepsy; Female; Hospitals, Pediatric; Humans; Infant; Infant, Newborn; Levetiracetam; Longitudinal Studies; Male; Oxcarbazepine; Piracetam; Republic of Korea; Tertiary Care Centers; Valproic Acid

Topics: Adolescent; Adult; Anticonvulsants; Cognition; Contraception; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsy; Female; Humans; Hungary; Insurance Coverage; Insurance, Health; Lamotrigine; Levetiracetam; Middle Aged; Piracetam; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Triazines; Valproic Acid; Young Adult

To clarify the efficacy and safety of levetiracetam (LEV) in children with localization-related epilepsy, we performed a retrospective study in our hospital.. We reviewed the cases of 70 pediatric patients (mean age, 9.4 years, range 4-15 years) who had undergone LEV add-on therapy between October 2010 and September 2014. The subjects were followed for a period of 24 weeks.. The mean starting dose was 9.9 mg/kg/day, and the mean final dose was 39.9 mg/kg/day. The LEV continuation rate was estimated to be 87%. The responder rate (based on ≥ 50% reduction in seizure frequency) was 57%. Twenty-four of the 70 patients experienced side effects, such as drowsiness, fatigue, and aggressiveness. Although most of the adverse events were mild and tolerable, it was necessary to discontinue the medication in four patients. We evaluated the effects of gender, age, duration of illness, secondarily generalized seizure, baseline seizure frequency, MRI abnormality, number of previously administered drugs, number of concomitant drugs, and final dose. MRI abnormality and final dose of LEV had a statistically significant influence on the efficacy.. LEV can be used as an effective and safe add-on treatment in children with localization-related epilepsy.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Treatment Outcome

Suicide is a major cause of premature mortality in patients with epilepsy. We aimed to identify the clinical correlates of suicide in these patients.. We conducted a matched, case-control study based on a clinical case registry of epilepsy patients (n = 35,638) treated between January 1994 and December 2011 at an academic tertiary medical center in Seoul, Korea. Each epilepsy patient in the suicide group (n = 74) was matched with three epilepsy patients in the nonsuicide group (n = 222) by age, gender, and approximate time at first treatment. The clinical characteristics of the patients in both groups were then compared.. In a univariate analysis, seizure frequency during the year before suicide, use of antiepileptic drug polytherapy, lack of aura before seizure, diagnosis of temporal lobe epilepsy, use of levetiracetam, psychiatric comorbidity, and use of antidepressants were all significantly higher in the suicide group than in the nonsuicide group. Multivariate analysis revealed that a high seizure frequency (odds ratio [OR] 3.3, 95% confidence interval [CI] 1.04-10.2), a lack of aura before seizure (OR 4.0, 95% CI 1.7-9.3), temporal lobe epilepsy (OR 3.7, 95% CI 1.6-8.6), and use of levetiracetam (OR 7.6, 95% CI 1.1-53.7) and antidepressants (OR 7.2, 95% CI 1.5-34.1) were all associated with a higher probability of suicide.. Patients with temporal lobe epilepsy who experience seizures weekly or more frequently, experience a lack of aura, use levetiracetam, or take antidepressants are all at a higher risk of suicide and should be monitored closely.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Antidepressive Agents; Case-Control Studies; Epilepsy; Epilepsy, Temporal Lobe; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Republic of Korea; Risk Factors; Suicide; Young Adult

Forced normalization has been reported in association with almost all anti-epileptic drugs.. We report on a 9-year-old girl with idiopathic epilepsy who showed forced normalization after administration of levetiracetam (LEV). She initially presented with generalized tonic-clonic seizures when she was 4 years old. Diffuse sharp and slow wave complexes (SWCs) were observed on electroencephalography (EEG). We prescribed sodium valproate (VPA) and benzodiazepines, but the seizures and EEG findings worsened gradually. Although subsequent administration of LEV stopped the seizures, the patient became subject to episodes of rage and violent behavior. Forced normalization was confirmed by the disappearance of SWCs on EEG. We reduced the dose of LEV and tried in various ways to resolve the situation, but finally we had to abandon LEV.. To the best of our knowledge, this is the first report of a patient with idiopathic epilepsy but without disabilities in everyday life showing forced normalization associated with LEV administration.

Topics: Anticonvulsants; Child; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Piracetam; Treatment Outcome

Our objective is to explore the effects of levetiracetam on the levels of neuropeptides, serum activity and concentrations of oxidative stress and inflammatory response proteins, and levels of brain injury marker in patients with refractory epilepsy. Seventy-two patients with refractory epilepsy received levetiracetam treatment. Neuropeptides galanin (GAL) and neuropeptide Y (NPY) in plasma and cerebrospinal fluid (CSF) were detected using double-antibody sandwich immunoassay and radioimmunoassay, respectively. Enzyme-linked immunosorbent assay was used to detect serum activity of paraoxonase (PON1) and serum concentrations of oxidized low-density lipoprotein (ox-LDL) and S100B. Arylesterase (ARE) activity was measured by colorimetric assay, and immune scatter turbidimetry was used to detect a high-sensitivity C-reactive protein (hs-CRP). After treatment, NPY and GAL in plasma and CSF of the patients were significantly decreased as compared to concentrations before treatment (P < 0.05). Levetiracetam reduced serum activities of PON1 and ARE (P < 0.05) and led to markedly increased serum levels of ox-LDL (P < 0.05). Serum concentrations of hs-CRP and S100B protein were significantly lower after levetiracetam administrations than before treatment (P < 0.05). Levetiracetam treatment had a clear beneficial effect on the overall quality of life (QOL) scores of the patients, as indicated by significantly improved cognitive functioning, behavior problems, emotional conditioning, physical condition, social functioning, self-assessed life quality score, self-assessed health score, and the total QOL score (P < 0.05). Levetiracetam can improve life quality of patients with refractory epilepsy, decrease NPY and GAL in plasma and cerebrospinal fluid, serum PON1 and ARE activities, and serum levels of ox-LDL, hs-CRP, and S100B. Levetiracetam therefore may be considered a drug of choice for treating refractory epilepsy.

Topics: Adolescent; Adult; Aryldialkylphosphatase; C-Reactive Protein; Enzyme-Linked Immunosorbent Assay; Epilepsy; Female; Galanin; Humans; Levetiracetam; Lipoproteins, LDL; Male; Middle Aged; Neuropeptide Y; Piracetam; Quality of Life; Radioimmunoassay; S100 Calcium Binding Protein beta Subunit; Young Adult

A series of fluorinated analogs of the potent investigative anticonvulsant agent (4S,8aS)-4-phenylperhydropyrrolo[1,2-a]pyrazine-2,6-dione 1 was prepared and characterized by IR, 1H, 13C NMR and mass spectral data. The compounds have been evaluated in the in vivo rodent models of epilepsy. They displayed high activity in the 'classical' maximal electroshock seizure (MES) and subcutaneous Metrazol (scMET) tests as well as in the 6Hz model of pharmacoresistant limbic seizures. The results showed that incorporating fluorine atoms into the phenyl ring of 1 can be beneficial for the anticonvulsant potency. The most promising meta-trifluoromethyl and meta-trifluoromethoxy derivatives (4S,8aS)-5h and (4S,8aS)-5l, respectively, displayed very broad spectra of activity across the preclinical seizure models.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Electroshock; Epilepsy; Halogenation; Hydrocarbons, Fluorinated; Male; Mice; Molecular Structure; Pentylenetetrazole; Pilocarpine; Pyrazines; Pyrroles; Rats; Rats, Sprague-Dawley; Seizures; Structure-Activity Relationship

Topics: Acute Generalized Exanthematous Pustulosis; Aged, 80 and over; Anticonvulsants; Epilepsy; Female; Fever; Humans; Levetiracetam; Piracetam

Levetiracetam is one of the new anticonvulsant drugs that has a high therapeutic index and potential antiepileptogenic effects. Herein, we report a patient with multidrug refractory epilepsy and Ohtahara syndrome who was accidentally administered 300 mg/kg/d for 35 days by her mother. To our knowledge, there are only a few cases of accidental overdose of levetiracetam in pediatric patients reported in the literature, and this case study is the first to report such a high and long-term dose in an infant who showed no adverse effects.

Topics: Anticonvulsants; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Follow-Up Studies; Humans; Infant; Levetiracetam; Piracetam

Since anticonvulsants such as valproate or oxcarbazepine have quite a disadvantageous profile of possible adverse drug events (ADEs), safer alternatives are being sought. The newer anticonvulsant levetiracetam is often considered advantageous. We performed a chart review of children and adolescents aged from 0.5 to 16.9 years, who had been started on an initial monotherapy with levetiracetam, valproate, or oxcarbazepine between 2007 and 2011, in order to analyze the therapy's failure rate during the first year. We differentiated failure of monotherapy due to a lack of effectiveness and due to ADEs. No psychometric tests were performed. Lack of effectiveness and inacceptable ADEs were assumed according to the judgment of physicians and families. Anticonvulsive monotherapy failed in 29/61 (48 %) levetiracetam patients and in 18/49 (37 %) valproate patients (for focal and generalized epilepsies; n.s.). This was caused by a lack of effectiveness in 25/61 (41 %) levetiracetam patients and in 11/49 (22 %) valproate patients (p ≤ 0.05). A modification of therapy due to ADEs was performed in 4/61 (7 %) levetiracetam patients and in 7/49 (14 %) valproate patients (n.s.). An anticonvulsive monotherapy failed in 21/42 (50 %) patients treated with levetiracetam and in 10/34 (29 %) patients treated with oxcarbazepine (for focal epilepsies; n.s.). Changes of monotherapy were caused by a lack of effectiveness in 17/42 (40 %) of levetiracetam patients and in 6/34 (18 %) of oxcarbazepine patients (p ≤ 0.05). ADEs leading to changes in therapy were reported for 4/42 (10 %) of levetiracetam and 4/34 (12 %) of oxcarbazepine patients (n.s.). An initial monotherapy of levetiracetam failed more frequently due to a lack of effectiveness than a monotherapy with valproate or oxcarbazepine. We found no significant difference in therapy failure due to ADEs.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Oxcarbazepine; Piracetam; Retrospective Studies; Treatment Failure; Treatment Outcome; Valproic Acid

Since indication extension to children data regarding the effectiveness of levetiracetam in paediatric patients remains limited.. Investigate the real-life effectiveness of levetiracetam in paediatric patients.. Epileptic children (<16 years) who had initiated levetiracetam between 1 October 2006 and 31 March 2007 were included and followed for 1 year by hospital or non-hospital neurologists practising in France.. Among the 156 identified children, 147 were analysed: 51.7% were female, and mean (SD) age was 9.2 years (4.2). Most patients had either partial symptomatic (30.6%) or partial cryptogenic (26.5%) epilepsy, 92.5% experienced seizures during the 6 months preceding levetiracetam initiation, and 19.2% were on levetiracetam alone at initiation. One-year levetiracetam continuation rate was estimated to be 72.0% (95%CI [63.8; 78.6]). Of the 104 children continuing levetiracetam treatment at end of study, 31.7% were seizure-free during the last six months of follow-up, and 23.1% on levetiracetam alone. Discontinuation of levetiracetam (n = 41) was mainly for insufficient efficacy (58.5% of those concerned).. In real-life clinical practice important treatment retention and non-negligible reduction of seizure frequency may be expected.

Topics: Anticonvulsants; Child; Epilepsy; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Levetiracetam; Male; Piracetam; Proportional Hazards Models; Treatment Outcome

Anticonvulsant hypersensitivity syndrome is an adverse drug reaction usually occurring from 1 to 8 weeks after exposure to antiepileptic drugs. It can threaten life by affecting the liver, kidneys, central nervous system or lungs. We present a 47-year-old patient treated with phenytoin, lamotrigine and clobazam for 7 years. He presented with hepatic and renal failure in relation to this syndrome demonstrated by renal biopsy. Prognosis was excellent due to an early diagnosis leading to cessation of the causative agents. Levetiracetam was started with a good response.

Topics: Anticonvulsants; Drug Hypersensitivity Syndrome; Epilepsy; Humans; Levetiracetam; Liver Failure; Male; Middle Aged; Piracetam; Renal Insufficiency

To report cases of hair loss with levetiracetam (LEV) in epilepsy patient and summarise their demographic and clinical features.. All patients reported attended the epilepsy outpatient clinic of the West China Hospital, Sichuan University. Demographic and clinical information was obtained from medical records and by interview. All the patients were under regular follow up.. Five epilepsy patients (4 females and 1 male) are reported. All developed hair loss within two months of starting LEV treatment. Three had idiopathic epilepsy, two symptomatic epilepsy. Three patients received LEV monotherapy, two combination treatment. None decided to switch away from LEV to another drug after developing hair loss, although the dose of LEV was reduced in one patient.. Hair loss may be a rare side effect of LEV treatment in patients with epilepsy. LEV-related hair loss appears reversible if the dose is reduced or treatment is stopped.

Topics: Adult; Anticonvulsants; Epilepsy; Female; Follow-Up Studies; Humans; Hypotrichosis; Levetiracetam; Male; Piracetam; Time Factors; Young Adult

To compare the cognitive and language development of children born to women with epilepsy (WWE) exposed in utero to levetiracetam (LEV) or sodium valproate (VPA) and control children born to women without epilepsy not taking medication during pregnancy.. The children, aged between 36 and 54 months, were recruited from the United Kingdom and assessed using the Griffiths Mental Development Scales and the Reynell Language Development Scale. Maternal demographic and epilepsy information was also collected for use in statistical regression. This is an observational study with researchers not involved in the clinical management of the mothers enrolled.. After controlling for confounding variables, children exposed to LEV in utero (n = 53) did not differ from unexposed control children (n = 131) on any scale administered. Children exposed to VPA (n = 44) in utero scored, on average, 15.8 points below children exposed to LEV on measures of gross motor skills (95% confidence interval [CI] -24.5 to -7.1, p < 0.001), 6.4 points below on comprehension language abilities (95% CI -11.0 to -1.8, p = 0.005), and 9.5 points below on expressive language abilities (95% CI -14.7 to -4.4, p < 0.001).. The current study indicates that children exposed to LEV in utero were superior in their language and motor development in comparison to children exposed to VPA. This information should be used collaboratively between health care professionals and WWE when deciding on women's preferred choice of antiepileptic drug.

Topics: Adult; Anticonvulsants; Child Development; Child, Preschool; Epilepsy; Female; Humans; Language Development; Levetiracetam; Male; Piracetam; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Prospective Studies; United Kingdom; Valproic Acid

 Although previous studies suggest that valproate (VPA) may induce reproductive endocrine disorders, the effects of newer antiepileptic drugs (AEDs) on reproductive endocrine health have not been widely investigated and compared with those of older AEDs. Therefore, this multicenter cross-sectional study aimed to evaluate the prevalence of reproductive endocrine dysfunctions in pubertal females with epilepsy receiving VPA, lamotrigine (LTG), or levetiracetam (LEV) monotherapy..  Pubertal girls on VPA (n = 11), LTG (n = 8), or LEV (n = 13) monotherapy for at least 6 months were recruited. Healthy sex-matched and age-matched subjects were enrolled as controls (n = 32). Each participant underwent a comprehensive physical examination concerning signs of hyperandrogenism. The Ferriman-Gallwey score of hirsutism was assessed. In addition, all patients completed a standardized questionnaire regarding epilepsy, menstrual cycle, and hirsutism features. Adiposity indices were measured and weight gain was documented for each subject..  Hirsutism score, occurrence of hyperandrogenism features, and adiposity indices were significantly higher in the VPA group when compared with LEV and control groups. VPA therapy was more frequently associated with weight gain when compared with LTG and controls, whereas no significant differences with regard to signs of hyperandrogenism were found between VPA and LTG groups. Furthermore, no differences in menstrual disorders were observed between groups..  Pubertal girls with epilepsy receiving VPA monotherapy were more likely to develop signs of hyperandrogenism, that is, hirsutism and acanthosis, than those on LEV or controls. However, no differences in occurrence of menstrual disorders and other reproductive dysfunctions were found between VPA, LTG, LEV, and control groups. These findings do not allow us to clearly determine whether or not VPA, LEV, and LTG monotherapies considerably affect reproductive endocrine health in pubertal girls with epilepsy. Therefore, further prospective studies of larger sample sizes are needed to establish if screening tests should be recommended.

Topics: Adiposity; Adolescent; Anticonvulsants; Cohort Studies; Cross-Sectional Studies; Drug Evaluation, Preclinical; Endocrine Disruptors; Epilepsy; Female; Hirsutism; Humans; Hyperandrogenism; Lamotrigine; Levetiracetam; Piracetam; Reproductive Health; Triazines; Valproic Acid

Corticosteroids are extensively used in treatment of many diseases. In neurosurgery practice, dexamethasone (DEX) is commonly used particularly in cerebral edema secondary to brain tumors, head trauma, and central nervous system infections. There are some uncertainties surrounding the secure use of DEX in patients with epilepsy or seizures induced by diseases of the central nervous system such as head trauma and brain tumors. Despite its extensive use, the effect of DEX on epileptiform activity is unclear. In this study the effect of DEX on epileptiform activity was investigated in rats. The effects of 1, 3, and 10mg/kg DEX on epileptiform activity was compared with effects of antiepileptic drugs commonly employed in treatment of epilepsy, namely phenytoin (PHT) 50mg/kg and levetiracetam (LEV) 50mg/kg that were administered intraperitoneally for 1 week. All groups were administered intracortical penicillin (500IU) to induce epileptiform activity. DEX at the doses of 3mg/kg and 10mg/kg significantly reduced spike frequencies compared to the initial values. In conclusion, we think that DEX can effectively decrease the epileptiform activity.

Topics: Animals; Anticonvulsants; Brain; Dexamethasone; Disease Models, Animal; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Glucocorticoids; Levetiracetam; Male; Penicillins; Phenytoin; Piracetam; Rats; Rats, Wistar; Time Factors; Treatment Outcome

Studies evaluating the effect of levetiracetam (LEV) on haematological parameters in patients with epilepsy are very limited. Clinical trials have also reported an unexplained increased incidence of pharyngitis and rhinitis in LEV-treated patients. The objective of this study was to evaluate prospectively the changes in haematological parameters in children treated with LEV monotherapy. White blood cell, neutrophils, lymphocytes, monocytes, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and platelets were measured in 22 children (13 females, mean age 6.70±4.23 years) with epilepsy, before and after 2 and 6 months of LEV monotherapy. Lymphocyte count was significantly decreased at 6 months (p=0.019) of treatment and this effect was not dose dependent. One child (4.5%) at 2 months and four children (18%) at 6 months of treatment had lymphocyte count below 10th percentile for age. There were no significant alterations in the other parameters evaluated during the study. LEV monotherapy may significantly decrease lymphocyte count at six months of treatment in children with epilepsy. Further prospective studies are needed to investigate the effect of LEV on haematological parameters and the possible association with the higher incidence of infections reported in children receiving LEV.

Topics: Anticonvulsants; Blood Cell Count; Child; Child, Preschool; Epilepsy; Female; Hematocrit; Humans; Leukocytes; Levetiracetam; Male; Piracetam; Prospective Studies

Topics: Adolescent; Anticonvulsants; Busulfan; Drug Therapy, Combination; Epilepsy; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Levetiracetam; Piracetam; Transplantation Conditioning; Valproic Acid

We investigated the relationship between behavioral problems, location of electroencephalogram (EEG) paroxysmal abnormalities (PA), and treatment with levetiracetam in children with pervasive developmental disorder (PDD) and epilepsy.. Twelve PDD children with epilepsy were included in the study. All patients had EEG PA (frontal spikes, 8; rolandic, 3; generalized, 1). After a 3-month baseline period, patients were given levetiracetam with an initial dose of 10 mg/kg/day for the first week, followed by increments of 5 mg/kg/day every week. Levetiracetam dosage was then adjusted up to a maximum of 60 mg/kg/day. EEG recordings were performed every 3 months, focusing on PA frequency. We counted the frequency of seizures and EEG PA, and scored instances of panic/aggressive behaviors.. Eight (66.7%) of the 12 patients were considered to be responders to clinical seizures and EEG findings (≥50% reduction in both seizures and PA frequency). Six (75%) of these eight patients were considered to be responders for behavioral problems (≥50% reduction in panic/aggressive behavior). These six patients had frontal EEG paroxysms, whereas the remaining two patients without behavioral responses had rolandic EEG paroxysms. Patients with frontal PA showed a significantly higher correlation between EEG/clinical seizures and behavioral improvements (p < 0.05).. The present data indicated the usefulness of LEV in reducing behavioral problems related to the reduction of seizures and frontal spikes in PDD for some but not all of the patients. Thus, levetiracetam represents an important addition to treatment for PDD children with epilepsy presenting with frontal EEG paroxysms.

Topics: Adolescent; Anticonvulsants; Behavioral Symptoms; Brain Waves; Child; Developmental Disabilities; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Severity of Illness Index

There is growing evidence that complex interactions between seizures and the immune system shape the course of epilepsy. However, systematic analyses of the effects of antiepileptic drugs (AED) on the immune system in humans are rare. We performed a prospective study on the influence of the widely used AED valproate and levetiracetam on interictal immunological parameters.. 36 patients were prospectively included. 15 were started on valproate (5 female (33%), age 54±27 years, 12 (80%) on monotherapy), 21 on levetiracetam (10 female (48%), age 45±19 years, 17 (81%) on monotherapy). Before treatment and after 3 months, we performed a differential blood count and analyzed the distribution of CD3(+)CD4(+)-, CD3(+)CD8(+)- and CD4(+)CD25(+)-leukocyte subsets using flow cytometry. In addition, we determined the concentrations of IL-1β, IL-6, TNF-α and MCP-1 in the peripheral blood using ELISAs.. Valproate intake resulted in a significant decrease of the total white blood count (6.96±1.23/nl vs. 6.13±1.57/nl, p=0.026) and of absolute count and percentage of neutrophils (4.60±1.05/nl vs. 3.69±1.30/nl, p=0.01; 65.4±7.9% vs. 59.5±11.5%, p=0.01, respectively). The percentage of CD3(+)CD4(+)-lymphocytes dropped significantly (50.4±10.9% vs. 45.3±12.3%, p=0.002). Levetiracetam treatment resulted in a decrease of the percentage of CD4(+)CD25(+)-lymphocytes (26.1±8.0% vs. 21.5±9.2%, p=0.01) but did not significantly alter absolute counts. Neither valproate nor levetiracetam were associated with significant changes in cytokines.. Valproate intake results in profound changes of white blood cell count and subset distribution. Cytokine levels were not influenced by valproate or levetiracetam.

Topics: Anticonvulsants; Blood Chemical Analysis; Cytokines; Enzyme-Linked Immunosorbent Assay; Epilepsy; Female; Flow Cytometry; Humans; Leukocyte Count; Levetiracetam; Lymphocytes; Male; Middle Aged; Neutrophils; Piracetam; Prospective Studies; Valproic Acid

We present a case of a 24-year-old woman with abnormal behaviour of recent onset. She had been diagnosed previously with epilepsy and had been started on antiepileptic medication. Clinical examination confirmed features of psychosis including paranoid delusions and auditory hallucination. Neurological examination showed nystagmus and dysmetria. Further evaluation revealed the underlying cause for her symptoms. She responded promptly to appropriate therapy with complete resolution of psychosis.

Topics: Adult; Anticonvulsants; Epilepsy; Female; Hallucinations; Humans; Levetiracetam; Neuropsychological Tests; Phenytoin; Piracetam; Psychotic Disorders; Seizures; Treatment Outcome

To assess the risk of teratogenicity from maternal intake of the more widely used newer antiepileptic drugs, especially lamotrigine, levetiracetam and topiramate.. Use of confidence interval and regression methods to compare risks of foetal malformation in pregnancies in women exposed (n = 1572) and in women with epilepsy not exposed (n = 153) to antiepileptic drugs in the first trimester.. Compared with the foetal malformation rate in women with epilepsy who were untreated in the first trimester (3.3%), the malformation rates for lamotrigine (4.6%), levetiracetam (2.4%) and topiramate (2.4%), all in monotherapy, were not statistically significantly different. However, the malformation rates for topiramate as part of polytherapy (14.1%) and for valproate in both monotherapy (13.8%) and polytherapy (10.2%) were statistically significantly higher. Regression analysis of combined monotherapy and polytherapy data showed no statistically significant increased risk of teratogenesis associated with lamotrigine or levetiracetam, but a statistically significant and dose-related risk for first trimester topiramate (P = 0.01) and valproate (P < 0.0001) exposure.. Evidence from this and other studies suggests that lamotrigine and levetiracetam have low risk for teratogenesis, but that topiramate exposure early in pregnancy may be associated with dose-related anatomical teratogenesis, as valproate is already known to be.

Topics: Abnormalities, Drug-Induced; Adult; Anticonvulsants; Epilepsy; Female; Fetus; Fructose; Humans; Lamotrigine; Levetiracetam; Piracetam; Pregnancy; Registries; Risk; Topiramate; Triazines; Valproic Acid

To assess the utility of retigabine (RTG) for epilepsy in clinical practice at a single UK tertiary centre.. We identified all individuals who were offered RTG from April 2011 to May 2013. We collected demographics, seizure types, previous and current antiepileptic drugs (AEDs), starting and maximum attained daily dose of RTG, clinical benefits, side effects, and reason to discontinue RTG from in- and outpatient encounters until February 28, 2014.. 145 people who had failed a median of 11 AEDs took at least one dose of RTG. One year retention was 32% and decreased following the safety alert by the US Federal Drug Administration (FDA) in April 2013. None became seizure free. 34 people (24%) reported a benefit that was ongoing at last assessment in five (3%). The most relevant benefit was the significant reduction or cessation of drop attacks or seizure-related falls in four women, this persisted at last assessment in two. The presence of simple partial seizures was associated with longer retention, as was a higher attained dose of RTG. Adverse effects were seen in 74% and largely CNS-related or nonspecific and affected the genitourinary system in 13%.. Retention of RTG was less favourable compared to data from open label extension studies of the regulatory trials. In comparison with historical data on similar retention audits retention of RTG at one year appears to be less than lamotrigine, topiramate, levetiracetam, pregabalin, zonisamide, and lacosamide, and slightly higher than gabapentin.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Carbamates; Drug Resistance; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Phenylenediamines; Piracetam; Time; Treatment Outcome; Young Adult

The aim of this study was to investigate the effects of levetiracetam (LEV) on penicillin-induced epileptiform activity in rats. Penicillin was applied intracerebroventricularly (icv) at a dose of 500 IU to induce epileptiform activity. LEV was given intraperitoneally (ip) at doses of 20, 40, 80 mg/kg before penicillin injection. This agent reduced epileptiform activity by decreasing spike frequencies. The mean spike frequencies decreased significantly in all the LEV treated groups. There was no significant change in the spike amplitudes of the LEV groups compared with the control group. 40 mg/kg of LEV was determined as the most effective dose on reducing epileptiform activity. The results of this study suggest that LEV is an effective antiepileptic agent in penicillin-induced epilepsy.

Topics: Animals; Anticonvulsants; Brain; Disease Models, Animal; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Female; Levetiracetam; Penicillins; Piracetam; Rats, Wistar

To evaluate the tolerability and clinical effects of subcutaneous (SC) levetiracetam for the treatment of epileptic seizures in a palliative care setting, we conducted a retrospective chart review of patients treated with subcutaneous levetiracetam in the Department of Palliative Medicine at the University Munich, between September 2006 and March 2013. The following parameters were extracted from the charts: reason for antiepileptic drug treatment, daily dose, concentration, infusion rate, co-administration of other drugs, and clinical effects. Furthermore, the charts were screened for signs of adverse drug reactions, e.g., irritation or pain at the infusion site. We identified 20 patients that were treated with levetiracetam SC in the inpatient (n = 7) and outpatient (n = 13) settings. Most patients (n = 17) tolerated the subcutaneous infusion well. Nineteen patients (95%) received levetiracetam in combination with other drugs. These were mainly metamizol (80%), midazolam (75%), and morphine (45%). The median dose of levetiracetam was 95.8 mg/h (SD 37 mg/h), median osmolarity of the infusion solution 2203 mOsmol/L (SD 717 mOsmol/L), and infusion rate 2 mL/h (SD 2.4 ml/h). In 16 patients (80%), seizures were controlled and status epilepticus were interrupted, respectively. We conclude that SC levetiracetam is an effective treatment and well tolerated in the palliative care setting.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Drug Therapy, Combination; Epilepsy; Female; Humans; Infusions, Subcutaneous; Levetiracetam; Male; Middle Aged; Pain; Piracetam; Retrospective Studies; Treatment Outcome

A simple liquid chromatography tandem mass spectrometry method was developed and validated according to the guidelines of the US Food and Drug Administration and the European Medicines Agency for a simultaneous quantification of levetiracetam (LEV) and its metabolite, UCB L057 in the plasma of patients. A 0.050 mL plasma sample was prepared by a simple and direct protein precipitation with 0.450 mL acetonitrile (ACN) containing 1 µg/mL of internal standard (IS, diphenhydramine), then vortex mixed and centrifuged. A 0.100 mL of the clear supernatant was diluted with 0.400 mL water and well mixed. A 0.010 mL of the resultant solution was injected into an Agilent Zorbax SB-C18 (2.1 mm×100 mm, 3.5 µm) column with an isocratic elution at 0.5 mL/min using a mixture of 0.1% formic acid in water and ACN (40:60 v/v). Detection was performed using an AB Sciex API 3000 triple quadrupole mass spectrometer, equipped with a Turbo Ion Spray source, operating in a positive mode: LEV at transition 171.1>154.1, UCB L057 at 172.5>126.1, and IS at 256.3>167.3; with an assay run time of 2 minutes. The lower limit of quantification (LLOQ) for both LEV and UCB L057 was validated at 0.5 µg/mL, while their lower limit of detection (LOD) was 0.25 µg/mL. The calibration curves were linear between 0.5 and 100 µg/mL for both analytes. The inaccuracy and imprecision of both intra-assay and inter-assay were less than 10%. Matrix effects were consistent between sources of plasma and the recoveries of all compounds were between 100% and 110%. Stability was established under various storage and processing conditions. The carryovers from both LEV and UCB L057 were less than 6% of the LLOQ and 0.13% of the IS. This assay method has been successfully applied to a population pharmacokinetic study of LEV in patients with epilepsy.

Topics: Chromatography, Liquid; Epilepsy; Humans; Levetiracetam; Limit of Detection; Piracetam; Reproducibility of Results; Tandem Mass Spectrometry

This study aimed to evaluate the effectiveness of levetiracetam (LEV) use for seizure control in patients who had undergone resective surgery for intractable epilepsy in routine clinical practice.. This was a prospective, observational study. Refractory epilepsy patients who underwent epilepsy surgery from January 2008 to December 2011 in the Department of Neurosurgery, West China Hospital were prospectively analyzed. Patients were divided into two groups according to antiepileptic drug (AED) treatment used immediately after epilepsy surgery (group A: therapy with LEV; group B: therapy without LEV). AED regimens were compared with regard to seizure-outcome for a period of more than 2 years. The International League Against Epilepsy (ILAE) classification was used to categorize seizure outcome.. A total of 319 patients (184 male and 135 female patients; mean age 28.2±13.4 years) were studied. The mean postoperative follow-up period was 3.9±1.2 years. The two groups showed was no significant difference in preoperative baseline data. At the 6-month follow-up, the proportion of patients with seizure freedom was significantly higher in group A than in group B (78.8% vs. 67.5%, p=0.03). Seizure outcomes after 2 years were assessed using the ILAE classification. The proportion of patients under ILAE seizure-outcome classification I (seizure freedom) was significantly higher in group A than in group B (74.3% vs. 60.7%, p=0.01). Seizure recurrence rates at the final assessment, after planned reduction or withdrawal, were 26.3% for group A and 40.6% for group B (p=0.04).. AED strategy after resective surgery may be a potentially modifiable prognostic indicator influencing seizure outcome in patients with intractable epilepsy. Compared to other AEDs, LEV appears to be more effective in controlling postoperative seizures in our long-term follow-up, and the advantage can be seen in early stage after surgery.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Brain; Child; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Neurosurgical Procedures; Piracetam; Prognosis; Prospective Studies; Recurrence; Treatment Outcome; Young Adult

Topics: Aged; Anticonvulsants; Brain Neoplasms; Dose-Response Relationship, Drug; Epilepsy; Female; Humans; Injections, Subcutaneous; Levetiracetam; Palliative Care; Piracetam; Treatment Outcome

Topics: Anticonvulsants; Epilepsy; Humans; Infant; Levetiracetam; Male; Munc18 Proteins; Mutation; Piracetam; Syndrome; Treatment Outcome

The effects of the antiepileptic drugs sodium valproate (VPA) and levetiracetam (LEV) on reproductive endocrine function, sexual function, and spermatozoa were explored, together with their possible etiological mechanisms, in Chinese Han men with epilepsy. Following VPA treatment (n=32), luteinizing hormone and follicle-stimulating hormone levels were significantly lower than in controls (n=30). The bioactive testosterone/luteinizing hormone ratio and the prolactin level were significantly elevated in the VPA treatment group. There were no significant differences in these hormones between the LEV treatment (n=20) and control groups. The rates of sperm morphologic abnormality (head, body, and tail) were significantly higher in the VPA treatment group than the control group but did not differ significantly between the LEV treatment and control groups. The sperm motility rate was significantly lower in the VPA treatment group (grade A sperm motility rate <25%, grade A+B sperm motility rate <50%) than in controls, as well as in the LEV treatment group (grade A sperm motility rate <25%). Patients in the VPA and LEV treatment groups had lower scores on questions 1, 2 and 3 of a simplified International Index of Erectile Function Scale than controls, but no significant difference on questions 4 or 5. The total International Index of Erectile Function Scale scores were significantly lower in the VPA and LEV treatment groups. We conclude that treatment with VPA adversely affects reproductive endocrine function, sperm parameters and sexual function to varying degrees in Chinese men with epilepsy.

Topics: Adolescent; Adult; Anticonvulsants; Asian People; Epilepsy; Erectile Dysfunction; Follicle Stimulating Hormone; Humans; Infertility, Male; Levetiracetam; Luteinizing Hormone; Male; Middle Aged; Piracetam; Spermatozoa; Testosterone; Valproic Acid; Young Adult

Although it is well documented that long-term therapy with older antiepileptic drugs (AEDs) leads to an increase in risk for atherosclerosis, there has been only limited information regarding the vascular risk in patients who are treated with new AEDs. We therefore conducted a prospective longitudinal study to assess the potential effects of new AEDs on the circulatory markers for vascular risk in patients with newly diagnosed epilepsy. We recruited adult patients with epilepsy who began to receive monotherapy with one of the new AEDs, including levetiracetam (LEV), oxcarbazepine (OXC), and topiramate (TPM). Circulatory markers of vascular risk were measured twice before and after 6 months of AED monotherapy. A total of 109 patients completed the study (LEV, n = 40; OXC, n = 40; TPM, n = 29). Six months of monotherapy resulted in significant increases in low-density lipoprotein cholesterol (LEV, from 90.2 to 98.5 mg/dl, 9.2% increase, p = 0.025; OXC, from 96.5 to 103.2 mg/dl, 7.0% increase, p = 0.049), homocysteine (LEV, from 7.9 to 10.4 μm, 31.6% increase, p = 0.001; OXC, from 8.7 to 11.5 μm, 32.2% increase, p < 0.001; TPM, from 8.3 to 12.3 μm, 48.2% increase, p < 0.001), apolipoprotein B (LEV, from 63.6 to 77.4 mg/dl, 21.7% increase; OXC, from 67.0 to 83.2 mg/dl, 24.2% increase; TPM, from 66.7 to 84.4 mg/dl, 26.5% increase; all p < 0.001), and apolipoprotein B/apolipoprotein A1 ratio (LEV, from 0.51 to 0.61, 19.6% increase; OXC, from 0.52 to 0.67, 28.8% increase; TPM, from 0.50 to 0.67, 34.0% increase; all p < 0.001). Serum apolipoprotein A1 and folate were significantly decreased in TPM (from 139.1 to 132.1 mg/dl, 5.0% decrease, p = 0.014) and OXC (from 8.1 to 6.4 ng/ml, 21.0% decrease, p = 0.046) groups, respectively. There were no significant changes in total cholesterol, triglyceride, high-density lipoprotein cholesterol, lipoprotein(a), and vitamin B12 in all three groups. Our findings suggest that treatment with some new AEDs might be associated with alterations in circulatory markers of vascular risk, which could contribute to the acceleration of atherosclerosis and increased risk of vascular diseases.

Topics: Adult; Anticonvulsants; Apolipoprotein A-I; Apolipoproteins B; Atherosclerosis; Biomarkers; Carbamazepine; Cholesterol, LDL; Epilepsy; Female; Fructose; Homocysteine; Humans; Levetiracetam; Male; Oxcarbazepine; Piracetam; Prospective Studies; Risk Factors; Topiramate

To evaluate the long-term efficacy and safety of levetiracetam based on a large population of patients in a tertiary epilepsy centre.. All patients who received levetiracetam at the Seoul National University Hospital between January 2007 and March 2009 were evaluated. Patients who underwent brain surgery for seizure control or who had associated progressive disease were excluded from this study. The electronic medical records of these patients were reviewed retrospectively.. A total of 568 patients were recruited, including 124 patients with generalised epilepsy. The mean duration of the follow-up period was 29.3 months. The seizure-free rate was 33.6% and was higher in patients with generalised epilepsy (51.6%) than patients with localisation-related epilepsy (28.6%). There was a strong correlation between initial response and dose-up response in 351 patients with increased dosage during the follow-up period. A total of 486 adverse events developed in 316 patients. The most common adverse event (24.3%) was irritability, which was associated with a high rate of drug discontinuation. Previous history of mood disorder was the only factor related to the development of irritability in patients using this medication.. Levetiracetam was effective and safe as monotherapy and add-on therapy for partial and generalised epilepsy. The initial response to levetiracetam may provide useful information for predicting the response to increased dose of levetiracetam. However, the use of this medication was associated with a rate of irritability that was higher than expected in patients with a history of mood disorders.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Drug Therapy, Combination; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Long-Term Care; Male; Middle Aged; Piracetam; Republic of Korea; Survival Analysis; Treatment Failure; Treatment Outcome; Young Adult

Pharmacoresistance to antiepileptic drugs (AEDs) is a major clinical problem in patients with mesial temporal lobe epilepsy (mTLE). Levetiracetam (LEV) represents a unique type of AED as its high-affinity binding site, the synaptic vesicle protein SV2A, is a component of the presynaptic release machinery. LEV often leads to full seizure control even in previously refractory patients. However, approximately 30% of LEV-treated mTLE patients do not show a significant response to LEV from the beginning of the pharmacotherapy and are therefore classified as a priori non-responders. This unexpected phenomenon prompted genetic studies, which failed to characterize responsible SV2A sequence alterations. Here, we followed a different approach to study the mechanisms of LEV pharmacoresistance by screening for mRNA signatures specifically expressed in LEV a priori non-responders in epileptic brain tissue and subsequent promoter analyses of highly altered transcripts. To this end, we have used our unique access to analyze hippocampal tissue from pharmacoresistant TLE patients who underwent epilepsy surgery for seizure control (n = 53) stratified according to a priori LEV responders versus patients with impaired LEV-response. Transcriptome (Illumina platform) and subsequent multimodal cluster analyses uncovered strikingly abundant synapse-associated molecule mRNA signatures in LEV a priori non-responders. Subsequent promoter characterization revealed accumulation of the single nucleotide polymorphism (SNP) rs9305614 G-allele in a priori non-responders to correlate to abundant mRNAs of phosphatidylinositol N-acetylglucosaminyltransferase (PIGP), i.e. a key component of the Wnt-signaling pathway. By luciferase assays, we observed significantly stronger activation by the LBP-1 transcription factor of the rs9305614 G-allele PIGP promoter. The present data suggest an abundance of transcripts encoding for key synaptic components in the hippocampi of LEV a priori non-responder mTLE patients, which for PIGP as proof of concept can be explained by a particular promoter variant. Our data argue for epigenetic factors predisposing for a priori LEV pharmacoresistance by transcriptional 'overexposure of targets'.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Drug Resistance; Epilepsy; Female; Hexosyltransferases; Hippocampus; Humans; Infant; Levetiracetam; Male; Membrane Proteins; Middle Aged; Piracetam; Polymorphism, Single Nucleotide; Presynaptic Terminals; Promoter Regions, Genetic; Young Adult

This paper introduces a new method for estimating the excitability of brain networks. The motivation for this research was to develop a system that can track pathological changes in excitability, in diseases such as epilepsy. The ability to track excitability may provide a method for anticipating seizures and intervening therapeutically. Four normally healthy canines were implanted with the Medtronic Activia PC+S deep brain stimulation and sensing system. The devices were used to probe the circuit of Papez, with electrical stimulation in the anterior nucleus of the thalamus to measure evoked potentials in the hippocampus. The canines were given three different dosage levels of anti-convulsant medication in an attempt to manipulate the excitability of the network. The results showed changes in the morphology of the evoked potentials, following a circadian profile and reflecting times of drug delivery.

Topics: Animals; Anticonvulsants; Brain; Brain Mapping; Circadian Rhythm; Deep Brain Stimulation; Dogs; Drug Delivery Systems; Electrodes; Electrodes, Implanted; Epilepsy; Evoked Potentials; Hippocampus; Levetiracetam; Piracetam; Seizures; Signal Processing, Computer-Assisted; Thalamus

Here we report a case of a 10-year-old female with unclassified epileptic encephalopathy who showed forced normalization after administration of levetiracetam (LEV). She initially presented with intractable tonic and myoclonic seizures that were observed about 10 times a day along with frequent multifocal sharp and slow wave complexes on electroencephalography (EEG). We were forced to decrease the topiramate dose because of the appearance of nystagmus, and her myoclonic seizures became worse. We added LEV (250 mg/day) and her tonic and myoclonic seizures disappeared one day after initiation of LEV administration. However, she showed hyporesponsiveness and akinesia. The disappearance of paroxysmal discharges on EEG confirmed the diagnosis of forced normalization. Despite continuous administration of LEV, tonic and myoclonic seizures relapsed within a month but her psychotic symptoms resolved simultaneously. To the best of our knowledge, this is the first reported case of forced normalization after LEV administration. It should be noted that LEV may cause forced normalization although it can be started at an adequate dosage.

Topics: Anticonvulsants; Brain Waves; Child; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Piracetam; Treatment Outcome

Toxic epidermal necrolysis (TEN) is rare, life-threatening skin disorder that usually is caused by an adverse drug reaction. The exact pathogenesis of TEN is still unknown. Many treatments including prednisolone, cyclosporine and intravenous immunoglobulin (IVIG) can be used to halt the disease process. We present a 12-year-old girl with epilepsy who developed TEN after about 14 days of lamotrigine treatment. Lamotrigine was immediately discontinued. After receiving systemic corticosteroid treatment, the patient had a complete recovery. Antiepileptic-induced TEN can be mortal in some cases. Thus, we would like to point out the importance of early diagnosis and treatment.

Topics: Anticonvulsants; Child; Drug Combinations; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Piracetam; Stevens-Johnson Syndrome; Triazines

The purpose of the present study was to evaluate the efficacy and safety of levetiracetam (LEV) in refractory epileptic children.. The study group included 61 outpatients (7 generalized, 48 localization-related, 3 undetermined, 3 unclassified) aged between 16 months and 18 years. LEV was given twice daily at a total dose of 10 mg/kg/day. The final mean dose was 50.7 mg/kg/day. The mean number of prior anti-epileptic drugs was 5.2. The entire treatment period was more than 6 months after LEV administration.. Fifteen children (24.6%) became seizure-free for 6 months after starting LEV, and 18 (29.5%) had a seizure reduction of more than 50% for the entire 6 months. The response rate was 33/61 (54.1%). Responders included 2/3 of patients (66.7%) with epilepsy with continuous spikes and waves during slow sleep and 13/19 (68.4%) with frontal lobe epilepsy. The effective dosage of LEV in the responders demonstrated a wide range (mean, 46.1 mg/kg/day; range, 19.4-59.1 mg/kg/day), and showed bimodal distribution. Adverse events occurred in only two patients who did not require LEV discontinuation.. LEV represents an important addition to the treatments available for refractory epileptic children.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Outpatients; Piracetam; Treatment Outcome

The aim of this study was to investigate the change of health related quality of life (HRQoL), anxiety and depression in adult patients in whom an adjunctive treatment with levetiracetam (LEV) was converted to a LEV monotherapy. A prospective, open, investigator initiated multicenter study enrolled 140 patients in whom LEV was added to the existing antiepileptic medication. A total of 65 patients who benefited from the 16-week add-on treatment with LEV (≥50% seizure reduction) were converted to LEV monotherapy (16-week follow-up). In LEV responders, HRQoL, anxiety and depression improved after add-on of LEV. The subsequent conversion to LEV monotherapy did not lead to a significant change in HRQoL, anxiety and depression. However, comparing baseline with LEV monotherapy, the improvements remained significant for most dimensions of HRQoL and for anxiety and depression. Patients' ratings of efficacy of LEV were related with their HRQoL after the conversion to monotherapy. Add-on therapy of LEV improved HRQoL, anxiety and depression in LEV responders. Conversion to a LEV monotherapy did not inevitably improve HRQoL in LEV responders, but the positive effect was maintained in the majority of the patients. The effects were highly related to seizure reduction.

Topics: Adult; Anticonvulsants; Anxiety; Depression; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Quality of Life; Treatment Outcome; Young Adult

Antiepileptic drugs (AEDs) may have adverse effects on bone metabolism and bone mineral density (BMD). The aim of this study is to determine the changes of bone metabolism and BMD in epilepsy patients who are undergoing levetiracetam (LEV) monotherapy.. Drug-naïve, sixty-one patients with recent onset epilepsy were recruited (24 female, 37 males; mean age: 31.0±13.1 years) in this study. We measured calcium, phosphate, bone alkaline phosphatase, parathyroid hormone, osteocalcin, insulin-like growth factor (IGF)-1, C-telopeptide, vitamin D3 levels and bone density measurements with DEXA method before and after LEV administration of mean duration 14.16±3.36 months.. T score in lumbar spine (L1-L4) was significantly increased with the correction of multiple T tests using Bonferroni's test across LEV monotherapy (p=0.0401). However, no significant change was observed in other parameters for BMD and T score. Repeated measures ANOVA with Bonferroni's correction of confounders such as sex, age, and treatment duration revealed significant increase in T score in lumbar spine (p=0.0164). The level of average LEV dosage itself did not reveal any significant association with BMD and bone metabolism.. We suggest that LEV monotherapy may have no harmful effect on bone strength and metabolism for 1 year.

Topics: Adolescent; Adult; Anticonvulsants; Biomarkers; Bone Density; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Treatment Outcome; Young Adult

Levetiracetam (LEV) is a widely used antiepileptic agent for partial refractory epilepsy in humans. LEV has unique antiepileptic effects in that it does not inhibit electroshock- or pentylenetetrazol-induced convulsion, but does inhibit seizures in kindling animal and spontaneously epileptic rat (SER: zi/zi, tm/tm) that shows both tonic convulsion and absence-like seizures. LEV also has unique characteristics in terms of its antiepileptic mechanism; it has no activity on Na⁺ and K⁺ channels or on glutamate and GABA(A) receptors. Recently, we found that LEV inhibits the depolarization shift and accompanying repetitive firing induced by mossy fiber stimulation in CA3 neurons of SER hippocampal slices. Therefore, this study was performed to determine whether LEV could inhibit the voltage-activated L-type Ca²⁺ current of hippocampal CA3 neurons obtained from SER and the non-epileptic Wistar rat. As previously reported, SER CA3 neurons were classified into type 1 and type 2 neurons. The application of LEV (100 μM) elevated the threshold for activation of the Ca²⁺ current, which was lowered in SER type 1 neurons and reduced the current size. Type 2 neurons of SER have a similar current-voltage relationship to Wistar rat neurons and the decay component of Ca²⁺ current during depolarization pulse in type 2 neurons was found to be smaller than that in Wistar rat neurons. LEV (100 μM) also reduced Ca²⁺ current in SER type 2 neurons. The effects of LEV were examined on such type 2 SER hippocampal CA3 neurons, compared with those on Wistar rat CA3 neurons. Application of LEV (10 μM) produced a significant decrease of amplitude of the Ca²⁺ current in SER neurons, although at this concentration of LEV there was no statistically significant decrease in the amplitude of Ca²⁺ current in Wistar rat neurons. Furthermore, LEV (100 nM-1 mM) reduced the Ca²⁺ current in a concentration-dependent manner in both SER and Wistar rat neurons, but the inhibition was much more potent in the former neurons than in the latter. Under the condition that the Ca²⁺ current had already been inhibited by LEV (10 μM), the addition of nifedipine (10 μM) did not cause further inhibition. Conversely, LEV had no effects on the current that had already been decreased by nifedipine (10 μM) given before LEV treatment (10 μM), indicating that LEV could act on the L-type Ca²⁺ channel. LEV elevated the threshold potential level for activation of the Ca²⁺ current and reduced the L-type Ca²⁺ current in typ

Topics: Animals; Anticonvulsants; Biophysics; Calcium; Calcium Channel Blockers; Dose-Response Relationship, Drug; Electric Stimulation; Epilepsy; Female; Hippocampus; In Vitro Techniques; Levetiracetam; Male; Membrane Potentials; Neural Inhibition; Neurons; Nifedipine; Patch-Clamp Techniques; Piracetam; Rats; Rats, Mutant Strains; Rats, Wistar

In epilepsy with continuous spikes and waves during slow sleep (CSWS), which is a representative epileptic syndrome of secondary bilateral synchrony (SBS), the urgent suppression of this electroencephalographic (EEG) abnormality may be necessary to prevent the progression of neuropsychological impairments. The purpose of this study was to determine the efficacy of levetiracetam (LEV) on SBS, seizure frequency, and neuropsychological impairments in children with refractory epilepsy.. Eleven (seven male and four female) patients with refractory epilepsy with SBS on EEG, aged between 4.7 years and 11.3 years, were included in this study. After a 3-month baseline period, the patients were given LEV at an initial dose of 10mg/kg/day for the first week, followed at increments of 5mg/kg/day every week, up to 20mg/kg/day. The LEV dose was then adjusted up to a maximum of 60mg/kg/day, according to the clinician's judgment. EEG recordings and clinical evaluations were performed every 3 months, focusing on SBS. The occurrence of SBS was then scored, and the relationship between the score and the response to LEV treatment was evaluated. In comparison with the baseline SBS frequency, the EEG response to LEV treatment was classified, and responders were identified as having a ≥50% reduction in SBS frequency. In addition, in comparison with the baseline seizure frequency, response to LEV treatment was classified. Responders were identified as patients with complete cessation (100% seizure control) and a response of ≥50% reduction in seizures. Furthermore, neuropsychological impairments such as hyperactivity, impulsiveness, and inattention were evaluated before and after LEV treatment.. Eight patients (72.7%) were considered responders. In addition, all eight patients were also considered responders for clinical seizures. Furthermore, 7 of 8 (87.5%) patients with response showed decreased hyperactivity and impulsivity after LEV administration.. The present data clearly indicate the usefulness of LEV in reducing both SBS on EEG and seizure frequency. LEV represents an important addition to the treatments available for refractory childhood epilepsies with SBS on EEG.

Topics: Anticonvulsants; Child; Child, Preschool; Cognition Disorders; Electroencephalography; Electroencephalography Phase Synchronization; Epilepsy; Female; Humans; Levetiracetam; Male; Neuropsychological Tests; Piracetam; Sleep Stages

Topics: Adult; Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Piracetam; Sexual Dysfunctions, Psychological; Treatment Outcome

Topics: Acute Disease; Adolescent; Anticonvulsants; Autistic Disorder; Epilepsy; Humans; Levetiracetam; Male; Pancreatitis; Piracetam; Tomography, X-Ray Computed

The efficacy and safety of the anti-convulsive drug levetiracetam (LEV) has been well documented but few clinical studies have investigated tolerance to LEV. The aim of this study was to evaluate the loss of the initial efficacy of LEV in adult patients with refractory partial-onset seizures.. We enrolled patients with refractory partial epilepsy who were started on add-on LEV treatment. The efficacy of LEV was evaluated every three months and the seizure frequency was decided by the average number of monthly seizures. A responder was defined as a patient with a ≥50% reduction in seizure frequency from the baseline. Seizure freedom was defined as a seizure-free status from the beginning of LEV treatment to the evaluation period. Loss of the initial efficacy was defined as a shift from responder status during the first three months of LEV treatment to non-responder status during the follow-up period.. A total of 95 epilepsy patients were analyzed. During the first three months of LEV treatment, 50 (52.6%) of the 95 patients were responders with a ≥50% seizure reduction. Nine patients (18.0%) showed a loss of initial efficacy during the second three-month period. In contrast, only two (4.0%) of the non-responders during the first three months became responders during the next three months. However, this difference did not reach statistical significance (P=0.054). Based on Kaplan-Meier survival estimates, 49.2% of the patients who initially responded to LEV treatment during the first three months were predicted to lose this response at 42 months. Loss of the initial efficacy of LEV treatment occurred mostly within 18 months.. This study suggests that the occurrence of tolerance is more common than late gain of efficacy of treatment although larger prospective studies would have to be carried out to prove this observation.

Topics: Adult; Anticonvulsants; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Retreatment; Treatment Failure; Treatment Outcome

A new series of chiral pyrido[1,2-a]pyrazine derivatives was synthesised and evaluated in in vivo animal models of epilepsy. A significant influence of the stereochemistry of the pyrido[1,2-a]pyrazine framework on the pharmacological activity was observed. Compounds with (4R,9aS) absolute configuration proved inactive, whereas other stereoisomers exhibited markedly dissimilar spectra of anti-seizure efficacy in the maximal electroshock seizure (MES), subcutaneous Metrazol seizure (scMET) and Pilocarpine-induced status prevention (PISP) tests. Importantly, the investigated agents revealed high potency in the 6Hz model, with the ED(50) values comparable to the reference drug Levetiracetam. Derivatives (4S,9aR)-6 and (4R,9aR)-6 emerged as promising new lead structures, the former having a broad spectrum of anticonvulsant activity and the latter showing high potency in 6Hz and PISP models.

Topics: Animals; Anticonvulsants; Biological Assay; Diketopiperazines; Electroshock; Epilepsy; Magnetic Resonance Spectroscopy; Male; Mice; Molecular Structure; Optical Rotation; Pyrazines; Rats; Rats, Sprague-Dawley; Spectrometry, Mass, Electrospray Ionization; Spectroscopy, Fourier Transform Infrared; Stereoisomerism; Structure-Activity Relationship

We aimed to compare apparent steady-state oral clearance (CL/F) of the antiepileptic drug levetiracetam (LEV) in elderly (66-80 years, n=105) and very elderly (81-96 years, n=70) vs nonelderly (30-65 years, n=97) patients with epilepsy. Median weight-normalized CL/F (mLmin(-1)kg(-1)) decreased from 1.23 (nonelderly) to 0.83 (elderly) and 0.59 (very elderly) (p<0.001). LEV CL/F significantly declines with aging, elderly and very elderly patients requiring an about 30% and 50% lower dose, respectively, compared to nonelderly adults to achieve a given LEV plasma concentration.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Epilepsy; Female; Geriatrics; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Retrospective Studies

To investigate the cognitive effect of levetiracetam (LEV) monotherapy with quantitative electroencephalogram (EEG) analysis and neuropsychological (NP) tests.. Twenty-two drug-naïve epilepsy patients were enrolled. EEG recordings were performed before and after LEV therapy. Relative power of discrete frequency bands was computed, as well as alpha peak frequency (APF) at occipital electrodes. Eighteen patients performed a battery of NP tests twice across LEV treatment.. LEV therapy decreased the power of delta (1-3 Hz, p<0.01) and theta (3-7 Hz, p<0.05) bands and increased that of alpha-2 (10-13 Hz, p<0.05) and beta-2 (19-24 Hz, p<0.05) bands. Region-specific spectral change was observed: delta power change was significant in fronto-polar region, theta in anterior region, alpha-2 in broad region, and beta-2 in left fronto-central region. APF change was not significant. Improvement in diverse NP tests requiring attention, working memory, language and executive function was observed. Change in theta, alpha-2, and beta-2 power was correlated with improvement in several NP tests.. Our data suggest LEV is associated with acceleration of background EEG frequencies and improved cognitive function. Change in frequency band power could predict improvement in several cognitive domains across LEV therapy.. Combined study of quantitative EEG analysis and NP tests can be useful in identifying cognitive effect of antiepileptic drugs.

Topics: Adolescent; Adult; Anticonvulsants; Brain Mapping; Brain Waves; Cognition; Electroencephalography; Epilepsy; Executive Function; Female; Follow-Up Studies; Fourier Analysis; Humans; Levetiracetam; Linear Models; Male; Middle Aged; Neuropsychological Tests; Piracetam; Retrospective Studies; Verbal Learning; Young Adult

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, and is highly resistant to medication with up to 40% of patients continuing to experience seizures whilst taking oral antiepileptic drugs. Recent research suggests that this may be due to abnormalities in the blood-brain barrier, which prevent the passage of therapeutic substances into the brain. We sought to develop a drug delivery material that could be implanted within the brain at the origin of the seizures to release antiepileptic drugs locally and avoid the blood brain barrier. We produced poly-lactide-co-glycolide drop-cast films and wet-spun fibers loaded with the novel antiepileptic drug Levetiracetam, and investigated their morphology, in vitro drug release characteristics, and brain biocompatibility in adult rats. The best performing structures released Levetiracetam constantly for at least 5 months in vitro, and were found to be highly brain biocompatible following month-long implantations in the motor cortex of adult rats. These results demonstrate the potential of polymer-based drug delivery devices in the treatment of epilepsy and warrant their investigation in animal models of focal epilepsy.

Topics: Animals; Anticonvulsants; Brain; Epilepsy; Glial Fibrillary Acidic Protein; Lactic Acid; Levetiracetam; Male; Materials Testing; Microscopy, Electron, Scanning; Piracetam; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats, Sprague-Dawley; Time Factors

The effect of an antiepileptic drug on cognitive function is of primary importance with respect to the patient's quality of life. Levetiracetam (LEV) is a novel antiepileptic drug used to treat epilepsy, but its effects on spatial and emotional learning and memory are not yet well understood. The goal of our study was to establish the effects of LEV (17 and 54 mg/kg, intraperitoneally (IP)) on spatial memory retrieval in the Morris water maze test and on acquisition and memory formation in the passive avoidance (PA) test in naive mice.. The subjects were adult male BALB/c mice. Spatial learning and memory was established with the Morris water maze (MWM) test. The 'time spent in escape platforms quadrant' and the 'distance to platform' analyses were measured using a video tracking system to determine spatial memory function. Emotional learning and memory were determined with a one-trial, step-through passive avoidance test.. In the MWM test, LEV (17 and 54 mg/kg) neither affected the time spent in the target quadrant nor altered the distance to platform. Moreover, LEV had no effect on swim speed. In the PA task, LEV (17 and 54 mg/kg) significantly prolonged retention latency.. Our results indicate that LEV did not alter spatial memory retrieval in the MWM test, but it did show some ameliorating effects on acquisition and memory formation in the PA test in naive mice.

Topics: Analysis of Variance; Animals; Anticonvulsants; Avoidance Learning; Behavior, Animal; Epilepsy; Humans; Levetiracetam; Male; Maze Learning; Memory; Mice; Mice, Inbred BALB C; Piracetam; Reaction Time

In young children presenting drug-resistant epilepsy, the number of approved antiepileptic drugs is limited. Levetiracetam (LEV) is one of the most recent antiepileptic drugs (AED) introduced on the market and data on its effectiveness and tolerance in children are scarce.. The objective of this retrospective study was to report our experience with the use of levetiracetam as an adjuvant therapy in a population of 42 children presenting a drug-resistant epilepsy. The study was conducted over a 5-year-period (from 1 January 2004 to 30 June 2007).. The patients' mean age was 10.8 years (range, 2.1-19 years). The mean duration of epilepsy was 6.6 years (range, 1.5-19 years). After the administration of LEV, 10 patients (23.8%) became seizure-free and 16 (38.1%) had more than 50% seizure reduction. A reduction of less than 50% was observed in 13 patients (31%). Three patients (7.1%) presented an increase in seizure frequency. The effectiveness of LEV was similar in partial and generalized epilepsy. LEV was well tolerated by these patients. The main adverse effects were anorexia, asthenia, and behavioral disorders, and drowsiness was encountered in 17% of the patients. All persistent adverse events were noted. In children under 4 years of age, LEV was particularly well tolerated.. This study confirms the effectiveness and tolerance of LEV used as an adjuvant therapy in children presenting drug-resistant epilepsy, particularly in the very young ones.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Quality of Life; Retrospective Studies; Time Factors; Treatment Outcome; Young Adult

Topics: Aged; Anticonvulsants; Cognition; Disease Progression; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Follow-Up Studies; Humans; Levetiracetam; Male; Motor Activity; Piracetam; Stroke

This paper demonstrates the analysis of levetiracetam, a new chiral antiepileptic drug, at ng/mL levels using an ultra-high-performance liquid chromatography (UHPLC)-photodiode absorbance (PDA) method. Three different sample preparation methods, liquid-liquid extraction with Extrelut, solid phase extraction (SPE) with Oasis HLB and Oasis MAX SPE cartridges, and protein precipitation with organic solvents were carried out. The last preparatory method is the simplest and provides the best recoveries: between 97.1% and 100.4% with RSD value below 5%. The column for separation is BEH C18 column (1.7 µm particle size and 100 × 2.1 mm i.d.) and acetonitrile-phosphate buffer (pH = 6.6; 0.01 M) (10/90 v/v) is the mobile phase. The results obtained are compared to analysis conducted by the HPLC method. The UHPLC method was validated in the range of 2-100 µg/mL levetiracetam concentration (R(2) = 0.9997). LOD and LOQ are 10 ng/mL and 33 ng/mL, respectively. The developed UHPLC method was applied to plasma samples of patient with epilepsy.

Topics: Blood Proteins; Chromatography, High Pressure Liquid; Epilepsy; Humans; Hydrogen-Ion Concentration; Levetiracetam; Limit of Detection; Linear Models; Liquid-Liquid Extraction; Piracetam; Reproducibility of Results; Sensitivity and Specificity; Solid Phase Extraction; Temperature

To study the prognostic implications of antiepileptic drug (AED) use on seizure freedom following temporal lobe resections for intractable epilepsy.. Seizure outcome implications of epilepsy characteristics and AED use were studied in patients who underwent temporal lobectomy patients at the Cleveland Clinic between September 1995 and December 2006. Survival analysis and multivariate regression with Cox proportional hazard modeling were used. Complete seizure freedom was defined as a favorable outcome.. Records of 312 patients were analyzed (mean ± standard deviation follow-up 3.5 ± 1.7 years). The estimated probability of complete seizure freedom was 69% at 12 months (95% confidence interval [CI] 66-72%), and 48% at 36 months (95% CI 45-52%). The mean number of AEDs used per patient at the time of surgery was 1.78 (range 1-4), dropping to 1.02 at last follow-up (range 0-4). Following multivariate analysis, a lower preoperative seizure frequency and perioperative use of levetiracetam predicted a favorable outcome (risk ratio [RR] 0.62, 95% CI 0.43-0.89, and RR = 0.57, 95% CI 0.39-0.83, respectively), whereas nonspecific pathology (RR 1.71, 95% CI 1.15-2.47) and a higher number of AEDs used at the time of surgery correlated with higher rates of seizure recurrence (whole-model log-rank test p-value < 0.0001). Better outcomes within the levetiracetam group were seen despite a higher proportion of several poor prognostic indicators within this patient group, and started as early as 4 months after surgery, gradually increasing to a 15-20% survival advantage by 5 years. No similar outcome correlations were identified with another AED.. AED use may be a potential new modifiable seizure-outcome predictor after temporal lobectomy. This possible prognostic indicator is discussed in light of proposed seizure recurrence mechanisms.

Topics: Adolescent; Adult; Aged; Anterior Temporal Lobectomy; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Humans; Levetiracetam; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Piracetam; Positron-Emission Tomography; Postoperative Complications; Recurrence; Retrospective Studies; Seizures; Statistics, Nonparametric; Survival Analysis; Treatment Outcome; Young Adult

Levetiracetam (LEV), a new anticonvulsant agent primarily used to treat epilepsy, has been used in pain treatment but the cellular mechanism of this action remains unclear. This study aimed to investigate effects of LEV on the excitability and membrane depolarization-induced calcium signaling in isolated rat sensory neurons using the whole-cell patch clamp and fura 2-based ratiometric Ca(2+)-imaging techniques. Dorsal root ganglia (DRG) were excised from neonatal rats, and cultured following enzymatic and mechanical dissociation. Under current clamp conditions, acute application of LEV (30 µM, 100 µM and 300 µM) significantly increased input resistance and caused the membrane to hyperpolarize from resting membrane potential in a dose-dependent manner. Reversal potentials of action potential (AP) after hyperpolarising amplitudes were shifted to more negative, toward to potassium equilibrium potentials, after application of LEV. It also caused a decrease in number of APs in neurons fired multiple APs in response to prolonged depolarization. Fura-2 fluorescence Ca(2+) imaging protocols revealed that HiK(+) (30 mM)-induced intracellular free Ca(2+) ([Ca(2+)](i)) was inhibited to 97.8 ± 4.6% (n = 17), 92.6 ± 4.8% (n = 17, p < 0.01) and 89.1 ± 5.1% (n = 18, p < 0.01) after application of 30 µM, 100 µM and 300 µM LEV (respectively), without any significant effect on basal levels of [Ca(2+)](i). This is the first evidence for the effect of LEV on the excitability of rat sensory neurons through an effect which might involve activation of potassium channels and inhibition of entry of Ca(2+), providing new insights for cellular mechanism(s) of LEV in pain treatment modalities.

Topics: Action Potentials; Analgesics; Animals; Anticonvulsants; Calcium; Dose-Response Relationship, Drug; Electrophysiology; Epilepsy; Fluorescent Dyes; Fura-2; Ganglia, Spinal; Levetiracetam; Neurons; Pain; Patch-Clamp Techniques; Piracetam; Rats; Sensory Receptor Cells

To examine the relationship of three alternative measures of adherence with seven negative outcomes associated with epilepsy for development of a quality measure in epilepsy.. Retrospective cohort analysis.. PharMetrics national claims database.. Patients in the PharMetrics database for the years 2004-08 taking antiepileptic drugs.. None.. For each definition of adherence, the odds ratios (ORs) comparing non-adherent with adherent groups were assessed for consistency and direction for the number of hospital admissions, emergency room (ER) visits, head injuries including traumatic brain injuries, falls, motor vehicle accidents (MVAs), fractures and a 'seizure' outcome defined as hospital admissions or ER visits with a primary diagnosis of epilepsy or convulsions.. The inclusion criteria were met by 31 635 individuals. In the multivariate analysis, the adherent group had lower odds of hospital admissions with ORs for the eight specifications ranging from 0.729 to 0.872 and ER visits where ORs for the eight specifications ranged from 0.750 to 0.893. The eight ORs for head injuries ranged from 0.647 to 0.888. For fractures, the ORs ranged from 0.407 to 0.841. Our proxy for seizure was inconsistently associated with adherence status.. All the adherence measures defined non-adherent groups that were associated with negative outcomes in epilepsy.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Carbamazepine; Cohort Studies; Epilepsy; Female; Follow-Up Studies; Hospitalization; Humans; Levetiracetam; Male; Medication Adherence; Mental Disorders; Middle Aged; Odds Ratio; Phenytoin; Piracetam; Quality Indicators, Health Care; Retrospective Studies; Treatment Outcome; Young Adult

Nationwide analyses of drug use can provide a prevalence estimate of the underlying disease and can help in understanding the characteristics of treatment. This study aimed for such analyses regarding the utilization of antiepileptic drugs (AED) for epilepsy in Germany. In 2009, all 4,115,705 AED prescriptions of all German patients with statutory health insurance (70,011,508 persons) were retrospectively analyzed. The IMS(®) LRx database served as data source, which accesses nationwide pharmacy data centers processing all German prescription data. To establish the age and sex-specific percentage of patients taking AED because of epilepsy, we used a second database, Disease Analyzer(®), which covered a representative sample of the German population (7.2 million patients) and contained ICD10 codes alongside with prescription data. The period prevalence of patients taking AED because of epilepsy was 9.1/1,000 (children/adolescents: 5.2/1,000; elderly: 12.5/1,000). Of the patients, 83.1 % took at least one of four AED: valproate (29.8 %), carbamazepine (26.4 %), lamotrigine (21.4 %), and levetiracetam (16.9 %). Oxcarbazepine and sultiame were popular with pediatricians. Elderly patients frequently received phenytoin and primidone. More than half of the patients were treated by family physicians; 68 % took AED in monotherapy and 7.9 % received >2 AED (children/adolescents: 12.5 %). The costs for AED prescribed for epilepsy amounted to €285.1 Mio (median AED costs/patient: €158/a). The German 2009 prevalence of epileptic patients taking AED was 9.1/1,000. Family physicians cared for the majority of patients. Prevalence and prescribing patterns changed with age. Costs of AED against epilepsy added up to 1 % of total medication costs in Germany.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Carbamazepine; Child; Databases, Factual; Epilepsy; Germany; Humans; Lamotrigine; Levetiracetam; Middle Aged; Piracetam; Population Surveillance; Prevalence; Retrospective Studies; Triazines; Valproic Acid; Young Adult

Levetiracetam, a broad spectrum antiepileptic drug, binds to membrane protein SV2A. The protein coding region of SV2A was sequenced in 158 patients with focal or generalized epilepsies divided into three groups based on their response to levetiracetam: responders (>75% decrease), exacerbators (50% increase) and non-responders. Nonsynonymous coding variation within SV2A was extremely rare, suggesting that rare variation is not likely to account for the individual differences in response to levetiracetam.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Genetic Variation; Humans; Levetiracetam; Male; Membrane Glycoproteins; Middle Aged; Nerve Tissue Proteins; Pharmacogenetics; Piracetam

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

To establish a population pharmacokinetics (PPK) model of levetiracetam in Chinese children with epilepsy.. A total of 418 samples from 361 epileptic children in Peking University First Hospital were analyzed. These patients were divided into two groups: the PPK model group (n=311) and the PPK validation group (n=50). Levetiracetam concentrations were determined by HPLC. The PPK model of levetiracetam was established using NONMEM, according to a one-compartment model with first-order absorption and elimination. To validate the model, the mean prediction error (MPE), mean squared prediction error (MSPE), root mean-squared prediction error (RMSPE), weight residues (WRES), and the 95% confidence intervals (95% CI) were calculated.. A regression equation of the basic model of levetiracetam was obtained, with clearance (CL/F)=0.988 L/h, volume of distribution (V/F)=12.3 L, and K(a)=1.95 h(-1). The final model was as follows: K(a)=1.56 h(-1), V/F=12.1 (L), CL/F=1.04×(WEIG/25)(0.583) (L/h). For the basic model, the MPE, MSPE, RMSPE, WRES, and the 95%CI were 9.834 (-0.587-197.720), 50.919 (0.012-1286.429), 1.680 (0.021-34.184), and 0.0621 (-1.100-1.980). For the final model, the MPE, MSPE, RMSPE, WRES, and the 95% CI were 0.199 (-0.369-0.563), 0.002082 (0.00001-0.01054), 0.0293 (0.001-0.110), and 0.153 (-0.030-1.950).. A one-compartment model with first-order absorption adequately described the levetiracetam concentrations. Body weight was identified as a significant covariate for levetiracetam clearance in this study. This model will be valuable to facilitate individualized dosage regimens.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; China; Epilepsy; Humans; Infant; Levetiracetam; Models, Biological; Models, Statistical; Piracetam

Levetiracetam is a commonly prescribed antiepileptic drug, and is generally well tolerated, but can eventually cause behavioral disturbances. These disturbances seem more frequent in children and in patients with a previous psychiatric history. We report on reversible autistic regression induced by levetiracetam in a 6-year-old girl with spastic cerebral palsy, mild cognitive deficiency, and focal epilepsy. She was diagnosed with pervasive developmental disorder, and demonstrated mild to moderate impairment in pragmatic language and interactions with peers. After the introduction of levetiracetam, she developed stereotypies, and her social and communicative skills deteriorated severely. She also exhibited mood lability. When the medication was discontinued, a dramatic response occurred, with a complete resolution of new abnormal findings. Levetiracetam can provoke unusual behavioral adverse effects in certain patients who are biologically more vulnerable.

Topics: Anticonvulsants; Autistic Disorder; Cerebral Palsy; Child; Cognition Disorders; Epilepsy; Female; Humans; Levetiracetam; Paraplegia; Piracetam; Regression, Psychology

Topics: Anticonvulsants; Brain; Carbamazepine; Choristoma; Consciousness Disorders; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Electroencephalography; Epilepsy; Female; Fluorodeoxyglucose F18; Frontal Lobe; Headache; Humans; Levetiracetam; Middle Aged; Oxcarbazepine; Piracetam; Positron-Emission Tomography; Radiopharmaceuticals; Status Epilepticus

Newer antiepileptic drugs (AEDs) are widely used in patients with epilepsy. There is still insufficient documentation regarding pharmacokinetic variability of these AEDs in different patient groups.. The purpose of this study was to compare age and comedication as factors contributing to pharmacokinetic variability between 4 newer AEDs (lamotrigine, levetiracetam, oxcarbazepine, and topiramate) among patients with refractory epilepsy.. Data regarding age, gender, use of AEDs, daily doses, and serum concentration measurements were retrieved from a therapeutic drug monitoring database, from patients admitted to the National Center for Epilepsy, Norway, 2007-2008.. In total, 1050 patients were included, 111 younger children (2-9 years), 137 older children (10-17 years), 720 adults (18-64 years), 82 elderly (65-93 years). Fifty percent of the patients were prescribed polytherapy, in 88 different combinations. The interindividual pharmacokinetic variability was extensive, as illustrated by a 10-fold variability in serum concentration compared with dose. Age affected the apparent clearance of levetiracetam to the largest extent, as shown by a 60% increase in younger children and a 40% reduction in the elderly, respectively, compared with adults. Comedication altered the clearance of lamotrigine to the greatest extent ±70% because it is affected by both enzyme inducers and inhibitors. Hepatic enzyme inducers increased the clearance of levetiracetam and topiramate by 25% and oxcarbazepine by 75%. Valproic acid reduced the clearance of topiramate by 25%.. Age and comedication are important contributors to pharmacokinetic variability. Age had the greatest impact on levetiracetam, and comedication affected the clearance of each of the 4 AEDs investigated in this study. Pharmacokinetic drug interactions must be carefully considered when multidrug therapies are prescribed. Therapeutic drug monitoring is a valuable tool for individualizing AED therapy.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Drug Monitoring; Drug Therapy, Combination; Epilepsy; Female; Fructose; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Piracetam; Topiramate; Triazines; Young Adult

Newer anti-epileptic drugs (nAEDs) have been introduced in Japan, including zonisamide (ZNS), gabapentine (GBP), topiramate (TPM), lamotrigine (LTG), and levetiracetam (LEV). Because nAEDs have different properties from older AEDs, they may provide a better control of the seizures and a more favorable safety and tolerability profile. Indeed, the systematic meta-analyses of randomized control trials demonstrated that the odds ratios for 50% responder rate were ZNS 2.7-2.99, GBP 2.02-2.29, TPM 4.07-5.22, LTG 2.32-2.87, and LEV 3.75-5.33, indicating their clinical efficacy. These studies also showed that the odds ratios for discontinuation were ZNS 1.78-4.23, GBP 0.99-1.36, TPM 2.38-2.56, LTG 1.16-1.19, and LEV 0.97-1.26, indicating their good tolerability. In the guidelines and the expert opinions, it was demonstrated that nAEDs can be used as the second-line drugs for both partial and generalized seizures. Furthermore, because nAEDs may have fewer drug-interactions, fewer adverse effects, and different mechanisms, it was also demonstrated that nAEDs are rather ideal as an add-on drug. It was also reported that nAEDs are less harmful for females of reproductive age.

Topics: Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Epilepsy; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Piracetam; Pregnancy; Pregnancy Complications; Topiramate; Triazines; Zonisamide

An open pilot study to evaluate the effect of pregabalin (PGB) as add-on therapy on seizure control, quality of life, and anxiety in patients with brain tumour-related epilepsy (BTRE).. We recruited 25 consecutive patients with BTRE and uncontrolled seizures. At baseline and during follow-up, patients underwent a complete physical and neurological examination and were evaluated using the QOLIE 31P (V2), EORTC QLQ C30, Adverse Events Profile, and Hamilton Anxiety Rating Scale (HAM-A). At baseline, a seizure diary was given.. During follow-up, 17 patients underwent chemotherapy, none underwent radiotherapy, 9 had disease progression, and 3 died. Mean duration of follow-up was 4.1 months. Mean PGB dosage was 279 mg/day. At baseline, mean weekly seizure frequency was 5.3 (±10) and at last available follow-up visit was 2.8±5. This difference was statistically significant (p=0.016). The responder rate was 76%. Ten patients dropped out; 4 as a result of seizure worsening, 1 as a result of unchanged seizure frequency, 3 as a result of a lack of compliance, and 2 as a result of side effects. Based on the QOLIE-31-P, a significant improvement of the subscale "seizure worry" (p=0.004) and a significant decrease in distress scores related to AEDs and social life (p=0.009 and p=0.008, respectively) were observed. A significant decrease in HAM-A score (p=0.002) was documented. CONCLUSIONS; These data indicate that PGB may represent a valid alternative as add-on treatment in this patient population, based on its efficacy on seizure control and anxiety.

Topics: Adult; Aged; Anticonvulsants; Anxiety; Benzodiazepines; Brain Neoplasms; Carbamazepine; Clobazam; Drug Therapy, Combination; Epilepsy; Female; Fructose; gamma-Aminobutyric Acid; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Phenobarbital; Pilot Projects; Piracetam; Pregabalin; Quality of Life; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Young Adult

Epilepsy is a common manifestation of mitochondrial disease associated with mutations of the mitochondrial polymerase γ (POLG). Prognosis of mitochondrial epilepsy is often poor and there are few reports of successful treatment of POLG-related epilepsy. We describe a 26-year-old woman who experienced severe headache during a three-day period, followed by symptoms of visual flashing, speech difficulty, and generalised seizures. EEG recording showed non-convulsive status epilepticus (left occipital area) and brain MRI revealed parieto-occipital T2-hyperintensities. Visual aura and aphasia persisted despite antiepileptic medication with phenytoin, oxcarbazepine, and levetiracetam. Mitochondrial disorder was clinically suspected and a homozygous c.2243G>C mutation (p.Trp748Ser) was discovered in the POLG1 gene. The patient was then set on a low glycaemic index treatment (LGIT) variant of the ketogenic diet, after which the headaches, aphasia, and visual aura progressively improved and disappeared. She returned home two weeks after onset of symptoms and has not had further seizures. She continues to receive levetiracetam monotherapy and LGIT. We conclude that, at least for this patient, the combination of three antiepileptic drugs and LGIT is effective and well tolerated as treatment for severe episodes of POLG-related mitochondrial epilepsy.

Topics: Anticonvulsants; Diet, Ketogenic; DNA Polymerase gamma; DNA-Directed DNA Polymerase; Epilepsy; Female; Glycemic Index; Humans; Levetiracetam; Mitochondrial Diseases; Piracetam; Young Adult

In order to assess the efficacy of modern antiepileptic drug (AED) therapy, we collected data from 517 consecutive adult outpatients referred to our centre between March and August 2011. In total, 211 patients (40.8%) were treated with monotherapy, 208 patients (40.2%) with a combination of two AEDs, and for the remaining patients (n=98; 19%) more than two AEDs were combined. The most common AEDs were valproate, lamotrigine, carbamazepine, and levetiracetam. Of the recent AEDs, levetiracetam was the leading drug with regards to drug combinations. Freedom of seizures for more than one year was achieved in 291 patients (56.3%). Under monotherapy, 168 patients (32.5% of all patients; 79.6% of patients with monotherapy) became seizure-free. Seizure-freedom with two AEDs was achieved in 103 patients (19.9% of all patients; 49.5% of patients with two AEDs) and in 20 patients with three AEDs (3.9% of all patients; 25.3% of patients with three AEDs). We conclude from this cross-sectional survey in a large patient group that combinations may still lead to treatment success in a considerable proportion of patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ambulatory Care; Anticonvulsants; Carbamazepine; Cross-Sectional Studies; Drug Therapy, Combination; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Piracetam; Treatment Outcome; Triazines; Valproic Acid; Young Adult

A number of novel pyrrole[1,2-a]pyrazine derivatives were synthesized and evaluated in in vivo animal models of epilepsy. Among them, several compounds displayed promising seizure protection in the maximal electroshock seizure (MES), subcutaneous metrazol seizure (scMET), 6 Hz and pilocarpine-induced status prevention (PISP) tests, with ED(50) values comparable to the reference anticonvulsant drugs (AEDs). A critical influence of the stereochemistry and conformational preferences of the pyrrole[1,2-a]pyrazine core on in vivo pharmacological activity was observed. The mechanism of the anticonvulsant action of the agents synthesized is most probably not via inhibition of the voltage-dependent sodium (Na(+)) currents.

Topics: Animals; Anticonvulsants; Diketopiperazines; Electroshock; Epilepsy; Humans; Male; Mice; Models, Molecular; Pentylenetetrazole; Rats; Rats, Sprague-Dawley; Rats, Wistar; Seizures; Sodium Channel Blockers; Sodium Channels

To assess the efficacy and tolerability of levetiracetam (Lev) in children with epilepsy.. Open-label observational, prospective, single arm, non-interventional study examining patients (≤14 years) with epilepsy, receiving mono- or combination therapy with levetiracetam. Levetiracetam was started at a dose of approximately 10mg/kg/day. The dose was titrated up with 10mg/kg increments if seizures were poorly controlled but the maximum daily dose could not be more than 60 mg/kg/day. Documented were seizure type and frequency, levetiracetam dose and side effects.. 120 patients (39.3% females, mean age 4.5 ± 3.9 years) were enrolled. Average duration of follow-up was 10.3 ± 3.5 months. At study endpoint, 64.8% of patients got seizure free and 83.0% got a seizure reduction of ≥50%. Observed side effects were somnolence, dysphoria, nervousness, dystrophy, somnipathy, asitia, debilitation, etc. and the incidence rate in the study was 47.5%. Four (3.3%) of 120 patients withdrew because of intolerance of side effects. The estimated one year retention rate of levetiracetam was 73.3%. Poor effect was the most common reason for withdrawal.. In our study, it seemed that levetiracetam was safe and effective for a wide range of epileptic seizures in children with epilepsy.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Levetiracetam; Male; Piracetam; Retrospective Studies; Time Factors

utilization of antiepileptic drugs (AEDs) has long been associated with bone deleterious effects. Furthermore, the BsmI restriction fragment polymorphism of the vitamin D receptor (VDR) has been associated with reduced bone mineral density (BMD), mostly in postmenopausal women. This study evaluates the association between bone metabolism of patients with epilepsy and the BsmI VDR's polymorphism in chronic users of AEDs.. this study evaluated 73 long-term users of antiepileptic drug monotherapy, in a cross-sectional design. Fasting blood samples were obtained to estimate the circulating serum levels of calcium, magnesium, phosphorus, parathormone, 25 hydroxyvitamin D as well as the VDR's genotype. Bone mineral density at the lumbar spine was measured with Dual Energy X-Ray Absorptiometry.. bone mineral density was significantly associated with the genotype of VDR (mean BMD: Bb genotype 1.056 ± 0.126 g/cm(2) ; BB genotype 1.059 ± 0.113 g/cm(2) ; bb genotype 1.179 ± 0.120 g/cm(2) ; P < 0.05). Additionally, the presence of at least one B allele was significantly associated with lower bone mineral density (B allele present: BMD = 1.057 ± 0.12 g/cm(2) , B allele absent: BMD = 1.179 ± 0.119 g/cm(2) ; P < 0.01). Patients with at least one B allele had lower serum levels of 25 hydroxyvitamin D when compared with bb patients (22.61 ng/ml vs. 33.27 ng/ml, P < 0.05), whilst they tended to have higher levels of parathyroid hormone.. vitamin D receptor polymorphism is associated with lower bone mass in patients with epilepsy. This effect might be mediated through the vitamin D-parathormone pathway.

Topics: Absorptiometry, Photon; Adolescent; Adult; Alleles; Anticonvulsants; Bone Density; Calcium, Dietary; Carbamazepine; Cross-Sectional Studies; Epilepsy; Female; Genotype; Humans; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Piracetam; Polymorphism, Genetic; Premenopause; Receptors, Calcitriol; Regression Analysis; Statistics, Nonparametric; Valproic Acid

Systemic injection of high doses of 11-deoxycortisol succinate had been reported to induce status epilepticus in rats and cats that was associated with paroxysmal epileptiform activity refractory to first generation antiepileptic drugs (AEDs). Using patch clamp recordings we have investigated the mechanisms of 11-deoxycortisol-induced excitability and we have discovered that this molecule accelerates the decay time of the inhibitory postsynaptic currents (IPSCs) mediated by GABA(A) receptors, both in neuronal cultures and in hippocampal slices. In addition, it reduces the amplitude and frequency of IPSCs. Thus, 11-deoxycortisol action on GABAergic neurotransmission may be one of the underlying causes of convulsive seizures that had been observed in rats. In the present study, we have reproduced the ability of 11-deoxycortisol to induce convulsive seizures after intravenous infusion in mice. The threshold dose of 11-deoxycortisol necessary for seizure induction was also determined (0.95 mmol/kg). Furthermore, we have established that these seizures are completely refractory to several AEDs such as phenytoin (up to 100 mg/kg), carbamazepine (up to 56 mg/kg), and valproate (up to 300 mg/kg). Levetiracetam and diazepam afforded only limited protection at high doses, 540 and 3-10 mg/kg, respectively. Interestingly, long-lasting seizures induced by 11-deoxycortisol in mice were not associated with typical neuropathological changes observed in other models of status epilepticus. We propose that 11-deoxycortisol-induced seizures may be an advantageous experimental model of drug-resistant epilepsy. Finally, better understanding of the pro-epileptic properties of 11-deoxycortisol is very important, because this endogenous steroid precursor may play a role in the pathophysiology of epilepsy. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.

Topics: Animals; Anticonvulsants; Cerebellum; Cortodoxone; Dose-Response Relationship, Drug; Drug Resistance; Electroencephalography; Epilepsy; Hippocampus; Inhibitory Postsynaptic Potentials; Levetiracetam; Male; Mice; Mice, Inbred C57BL; Piracetam; Receptors, GABA-A; Status Epilepticus

Trimethylaminuria is a metabolic disorder characterized by the excessive excretion of trimethylamine in bodily secretions, which confers a very unpleasant odour resembling that of dead fish. Literature reports only two cases affected by trimethylaminuria and epilepsy. We describe a third patient who, from the age of seven, was affected by temporal focal seizures with nocturnal episodes of nausea, vomiting, anxiety and autonomic activation followed by headache. EEG showed focal paroxysmal abnormalities prevailing on the right temporo-parieto-occipital regions. We began administering levetiracetam and seizures stopped. Our patient also showed learning disabilities despite a normal intelligence quotient (IQ), while another described patient had an IQ varying from borderline to mild mental retardation. We discuss the association between trimethylaminuria and epilepsy, and formulate some hypotheses on the relationship between trimethylamine convulsive effect and the anticonvulsive role of levetiracetam.

Topics: Anticonvulsants; Child; Comorbidity; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Metabolism, Inborn Errors; Methylamines; Neuropsychological Tests; Piracetam

We describe the case of a 22-year-old male affected by NFLE reporting paroxysmal RLS-like symptoms. The patient was referred to our Sleep Center due to nocturnal paresthesias and cramps involving the left leg and leading to sleep fragmentation. At age 4, the patient presented with secondary generalized seizures preceded by left leg discomfort, controlled on CBZ. After successive therapy discontinuation, leg symptoms built up in frequency and duration until a secondary generalized seizure re-occurred. On CBZ prompt resumption no further GM seizures occurred albeit persistence of night-time frequent cramps and paraesthesia. Sleep EEG demonstrated asymmetric interictal sharp theta on the right posterior frontal areas, whereas brain MRI results were consistent with a Taylor type right frontal cortical dysplasia. CBZ augmentation and add on therapy with LEV led to further frequency reduction of sensory symptoms.

Topics: Anticonvulsants; Brain Diseases; Carbamazepine; Electroencephalography; Epilepsy; Epilepsy, Frontal Lobe; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Malformations of Cortical Development; Malformations of Cortical Development, Group I; Piracetam; Restless Legs Syndrome; Young Adult

Levetiracetam has shown good safety/tolerability and efficacy in regulatory trials. This was confirmed in observational investigations performed soon after marketing by using continuation or retention rates as a composite measure. When an anti-epileptic drug first becomes available; however, there is evidence of channelling to more severe patients than thereafter.. This study was performed several years after marketing of levetiracetam and found high rates of continuation. It also further explores this measure by determining the continuation in the absence of initiation of additional anti-epileptic drugs.. To investigate real-life effectiveness of levetiracetam in patients initiating treatment in a stable market situation.. Epileptic adults who had initiated levetiracetam between 1 January and 31 August in 2005 or 2006 were included and followed for 1 year by hospital or nonhospital neurologists practising in France. One-year continuation rates were estimated using Kaplan-Meier analysis. Among those still treated at end of study, treatment goals were investigated. Factors associated with discontinuation were investigated using Cox proportional hazards regression.. A total of 794 subjects were included in the cohort, and 753 subjects were followed up and included in the analysis. Among these, mean (SD) age was 42.6 (±17.0) years, 51.1% were female, 76.6% had partial epilepsy, 93.5% had seizures in the 6 months preceding levetiracetam initiation and 82.9% had at least one concomitant anti-epileptic drug when starting levetiracetam. One-year levetiracetam continuation rate was 83.5% (95% confidence interval, 80.5-86.0%). Of the 579 patients still using levetiracetam at end of study, 46.8% were seizure free during the last 6 months, and 24% were on levetiracetam monotherapy. Reasons for discontinuation (n= 122) were adverse events (45%), lack of efficacy (38%) or both (9%). Levetiracetam discontinuation was most strongly associated with previous exposure to more than four anti-epileptic drugs, whereas continuation was most strongly associated with presence of seizure-related falls in the 6 months preceding levetiracetam initiation.. This population-based cohort study in a stable market situation found a high 1 year levetiracetam continuation rate compared with previous studies done sooner after market introduction.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Cohort Studies; Epilepsy; Female; France; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Time Factors; Treatment Outcome; Young Adult

To monitor the effect of adding levetiracetam in paediatric patients with hemiplegic cerebral palsy and uncontrolled epilepsy.. A case series of eight patients with hemiplegic cerebral palsy whose focal seizures were not adequately controlled by their current anticonvulsants were monitored after levetiracetam was added to their medications. If there was a 50% reduction in seizure frequency, then the other anticonvulsants were discontinued. Prolonged follow-up occurred for a minimum of 2 years.. There were seven males and one female whose ages ranged from 4 years to 17 years. All had focal onset seizures, while seven also had secondarily generalised tonic clonic seizures. Levetiracetam resulted in at least a 50% reduction in seizure frequency in seven, with no change in one. Three were able to wean successfully to monotherapy and remained seizure free for over 2 years. They had a prior history of infrequent seizures, one to six per year. Those who continued to require multiple anticonvulsants had a prior history of more frequent seizures, 6-50/year. Levetiracetam was well tolerated, and none ceased this because of side effects.. Levetiracetam is likely to be an effective anticonvulsant in children and adolescents with hemiplegic cerebral palsy and infrequent but persistent focal seizures.

Topics: Adolescent; Anticonvulsants; Cerebral Palsy; Child; Child, Preschool; Drug Therapy, Combination; Epilepsy; Female; Hemiplegia; Humans; Levetiracetam; Male; Outcome Assessment, Health Care; Piracetam

Children born to women with epilepsy (WWE), exposed in utero to levetiracetam (LEV, n = 51), were assessed for early cognitive development and compared to children exposed to sodium valproate in utero (VPA, n = 44) and a group of children representative of the general population (n = 97).. Children were recruited prospectively from 2 cohorts in the United Kingdom and assessed using the Griffiths Mental Development Scale (1996), aged <24 months. Information regarding maternal demographics were collected and controlled for. This is an observational study with researchers not involved in the clinical management of the WWE.. On overall developmental ability, children exposed to LEV obtained higher developmental scores when compared to children exposed to VPA (p < 0.001). When compared, children exposed to LEV did not differ from control children (p = 0.62) on overall development. Eight percent of children exposed to LEV in utero fell within the below average range (DQ score of <84), compared with 40% of children exposed to VPA. After controlling for maternal epilepsy and demographic factors using linear regression analysis, exposure to LEV in utero was not associated with outcome (p = 0.67). Conversely, when compared with VPA exposure, LEV exposure was associated with higher scores for the overall developmental quotient (p < 0.001).. Children exposed to LEV in utero are not at an increased risk of delayed early cognitive development under the age of 24 months. LEV may therefore be a preferable drug choice, where appropriate, for WWE prior to and of childbearing age.

Topics: Anticonvulsants; Child Development; Child, Preschool; Cognition; Epilepsy; Female; Humans; Infant; Levetiracetam; Maternal Exposure; Maternal-Fetal Exchange; Piracetam; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Retrospective Studies; Valproic Acid

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Carbamazepine; Contraindications; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Piracetam; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Triazines

A 4.5-year-old spayed female domestic shorthair cat was evaluated because of a generalized seizure disorder that developed after an anesthesia-related hypoxic event.. Following administration of phenobarbital, the seizures stopped but the cat developed severe generalized lymphadenopathy. Results of a CBC and serum biochemical analysis were unremarkable. Cytologic examination of the lymph nodes revealed a reactive lymphocyte population. Differential diagnoses included neoplasia and infection, but results of related diagnostic tests were all negative.. Treatment was changed from phenobarbital to levetiracetam. Ten days following discontinuation of phenobarbital, the lymph node enlargement resolved, and the cat remained free of seizures with levetiracetam as treatment.. Pseudolymphoma and anticonvulsant hypersensitivity syndrome are recognized potential sequelae to anticonvulsant administration in humans. However, a pseudolymphoma-like reaction to anticonvulsants in veterinary species has not previously been reported. This case highlighted a potentially serious yet reversible sequela to phenobarbital treatment that may have been mistaken for more severe illness such as neoplasia.

Topics: Animals; Anticonvulsants; Cat Diseases; Cats; Epilepsy; Female; Levetiracetam; Phenobarbital; Piracetam; Pseudolymphoma

Effects of the "VID-82925" kinase inhibitor molecule were investigated both during the developing phase as well as during the stable phase of the focus with spontaneous recurrent seizures using the 4-AP-induced in vivo epilepsy model in anesthetized rats.. In electrophysiologic experiments, VID-82925 (0.85 mg/kg) was injected intravenously either before the induction (pretreatment) or after the development of the stable focus (treatment). Reference drugs carbamazepine (4.8 mg/kg) and levetiracetam (50 mg/kg) were employed using the same experimental paradigm. The antiepileptic effect of VID-82925 was also compared to those of the broad-spectrum gap junction channel blocker carbenoxolone (10 mm).. Pretreatment with VID-82925 revealed an antiepileptogenic effect as it suppressed significantly the manifestation of the epileptiform activity not only during the developing phase, but also for a considerable long period during the stable phase of the focus. The current data do not allow us to differentiate an antiictal treatment effect from an antiepileptogenic effect of the compound during the stable phase of the focus. Treatment with VID-82925 was also effective against ictogenesis during the stable phase of the focus. Pretreatment with levetiracetam failed to exert any antiepileptogenic effect. The antiepileptic effects of VID-82925 and of the reference drugs on the epileptiform activity of the stable focus were comparable in intensity; however, the effect of VID-82925 was 2-3 times longer. The effects of VID-82925 and of carbenoxolone overlapped one another to some extent, suggesting that VID-82925 may exert its effects at least partially through blocking of gap junctional communication.. Our results indicate that inhibition of protein kinases may also provide an effective strategy for the development of a drug that is not only antiepileptic but also depresses the course of epileptogenesis.

Topics: 4-Aminopyridine; Animals; Anticonvulsants; Carbamazepine; Carbenoxolone; Cerebral Cortex; Electroencephalography; Epilepsy; Female; Heart Rate; Levetiracetam; Male; Piracetam; Premedication; Protein Kinase Inhibitors; Rats; Rats, Wistar; Signal Processing, Computer-Assisted

To describe the clinical outcomes of a compulsory switch from branded to generic levetiracetam (LEV) among people with epilepsy (PWE) in an outpatient setting.. We conducted a retrospective chart review of 760 unduplicated consecutive adult patients attending a tertiary care epilepsy clinic at Ben Taub General Hospital. On November 1, 2008 hospital policy required all patients receiving branded LEV to be automatically switched to generic LEV. We calculated the proportion of patients switching back to branded LEV and reasons for the switch back.. Of the 260 patients (34%) being prescribed LEV (generic and brand name) during the study period, 105 (42.9%) were switched back to brand name LEV by their treating physicians. Reasons for switch back included increase in seizure frequency (19.6% vs. 1.6%; p < 0.0001) and adverse effects (AEs) (3.3%). AEs included headache, fatigue, and aggression. Patient age was associated with switchback when controlling for gender, epilepsy classification, and treatment characteristics [relative risk (RR) 2.44; 95% confidence interval (CI) 2.09-2.84; p < 0.05)]. An increase in seizure frequency subsequent to generic substitution was associated with polytherapy compared to monotherapy (3.225; 1.512-6.880; p < 0.05).. A significant proportion of patients in our cohort on generic LEV required switch back to the branded drug. Careful monitoring is imperative because a compulsory switch from branded to generic LEV may lead to poor clinical outcomes, with risk of AEs and increased seizure frequency.

Topics: Adult; Anticonvulsants; Cohort Studies; Drug Substitution; Drugs, Generic; Epilepsy; Female; Hospitalization; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures; Treatment Failure

Topics: Anticonvulsants; Epilepsy; Humans; Incidence; Levetiracetam; Phenytoin; Piracetam; Subarachnoid Hemorrhage

The optimal regimen for seizure prophylaxis after subarachnoid hemorrhage (SAH) remains uncertain. Based on data suggesting that a short course may be adequate, coupled with an association between phenytoin exposure and poor cognitive outcome, our institution modified their seizure prophylaxis protocol for patients with SAH from an extended course of phenytoin to 3 days of levetiracetam. This study sought to compare the incidence of seizures before and after this change to evaluate whether a short course of levetiracetam would be as effective in preventing in-hospital seizures.. This study analyzed 442 consecutive patients admitted with SAH between January 2003 and January 2008, including 297 patients treated before the protocol change (PHT group) and 145 treated afterward (LEV group). Occurrence of all seizures was extracted from a prospectively collected intensive care unit database and further review of medical records. In-hospital seizures were divided into early (occurring on or before day 3, all patients on prophylaxis) and those occurring late (after day 3, LEV group off prophylaxis).. In-hospital seizures occurred in 3.4% of the PHT group and 8.3% of the LEV group (P = 0.03). Although the rate of early seizures was not different (1.4% PHT vs. 2.8% LEV, P = 0.45), there was a higher rate of late seizures (2% PHT vs. 5.5% LEV, P = 0.05).. The use of short-duration levetiracetam for seizure prophylaxis after SAH was associated with a higher rate of in-hospital seizures than an extended course of phenytoin, mainly related to an increase in late seizures, when the levetiracetam had been discontinued. This suggests that a longer duration of prophylaxis may be required to minimize seizures in patients with SAH, although confirmatory studies are required.

Topics: Adult; Aged; Anticonvulsants; Databases, Factual; Delayed-Action Preparations; Disease-Free Survival; Epilepsy; Female; Humans; Incidence; Inpatients; Intensive Care Units; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Subarachnoid Hemorrhage

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Meta-Analysis as Topic; Piracetam

Levetiracetam (LEV) is a broad spectrum antiepileptic drug (AED) with a unique mechanism of action. This retrospective audit explores outcomes in patients commenced on LEV monotherapy at the Epilepsy Unit at the Western Infirmary, Glasgow, Scotland from 1st January 2001 until 30th June 2009.. LEV monotherapy was started in 228 patients (89 men, 139 women, aged 12-81 years [median 28 years]). Of these, 161 (70.6%) had partial-onset seizures, 59 (25.9%) had idiopathic generalized epilepsies (35 primary generalized tonic-clonic seizures [PGTCS], 20 juvenile myoclonic epilepsy, 4 juvenile absence epilepsy), and 8 (3.5%) had unclassified GTCS. Initial dosing was 250 mg twice daily for 2 weeks, followed by 500 mg twice daily. Patients were reviewed every 6-8 weeks. If required, the LEV dose was titrated in 500 mg increments to a maximum tolerated or effective dose.. In total, 112 (49.1%) patients remained seizure-free for ≥1 year on a median LEV dose of 1000 mg/day (range 500-3000 mg/day). Patients were more likely to achieve seizure freedom with LEV as a first monotherapy (81 of 149 [54.4%]), as opposed to switching from another AED (31 of 79 [39.2%]; p=0.03). In this latter group, seizure freedom was more likely in those who switched after failing their 1st or 2nd AED (n=39 of 64 [60.9%]), compared to later in the treatment schedule (n=2 of 15 [13.3%]; p=0.029). Patients reporting <5 seizures (70 of 118) prior to starting LEV were more likely to become seizure-free than those with ≥5 seizures (42 of 110; p=0.001). Thirty-six (15.8%) patients had a ≥50% seizure reduction over 1 year; 43 (18.9%) were classified as having a <50% improvement, but elected to continue on LEV. The drug was withdrawn in 37 (16.2%) patients (30 side effects, 7 lack of efficacy). Eighteen (7.9%) patients reported intolerable neuropsychiatric symptoms (7 aggression, 7 mood swings, 2 irritability, 2 depression). Other side effects leading to drug withdrawal included sedation (n=5) and lethargy (n=4).. Seizure freedom was achieved in around half the patients on a median LEV dose of 1000 mg/day. This was more likely to occur in those taking the drug as first monotherapy, and in those with <5 pre-treatment seizures. Around 50% of those who discontinued LEV due to side effects developed neuropsychiatric symptoms.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Child; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Scotland; Treatment Outcome

The effect on clearance of levetiracetam (LEV) was estimated in women with epilepsy of childbearing potential using oral contraceptives (OCs). The estimated clearance (plasma concentration/daily dose) was 39 nmol/L/mg (range 14-88 nmol/L/mg) among women who did not use OC (n=30) and 38 nmol/L/mg (range 18-103 nmol/L/mg) among OC users (n=23) (p=0.8). In conclusion, combing LEV and OCs seems safe from a pharmacokinetic perspective.

Topics: Adolescent; Adult; Anticonvulsants; Contraceptives, Oral; Dose-Response Relationship, Drug; Epilepsy; Female; Humans; Levetiracetam; Middle Aged; Piracetam; Pregnancy; Young Adult

This study explored the effects of levetiracetam (LEV) on the expression of nerve cell adhesion molecule (NCAM) and growth-associated protein 43 (GAP-43) mRNA in the hippocampus of rats with epilepsy induced by lithium-pilocarpine (Li-PILO) in order to provide a basis for investigating the antiepileptic mechanism of LEV and its doseresponse.. Forty-eight Wistar rats were randomly divided into a normal control, a Li-PILO model and two LEV treatment groups (LEV: 150 and 300 mg/kg) (n=12 each). The LEV treatment groups received LEV by intragastric administration 6 hrs after status epilepticus (once daily for 2 two weeks). The expressions of NCAM and GAP-43 mRNA in the hippocampus was determined by real-time PCR.. The expression of NCAM and GAP-43 mRNA in the Li-PILO model group was significantly higher than in the normal control group (P<0.05). LEV treatment of 150 and 300 mg/kg significantly decreased the expression of NCAM and GAP-43 mRNA compared with the Li-PILO model group (P<0.05). The LEV treatment group at the dose of 300 mg/kg showed significantly lower expression of NCAM and GAP-43 mRNA than the 150 mg/kg LEV treatment group (P<0.05).. Li-PILO can up-regulate the expressions of NCAM and GAP-43 mRNA in the hippocampus of rats with epilepsy. LEV can inhibit the expression of NCAM and GAP-43 mRNA and the effect is associated with the dose of LEV.

Topics: Animals; Anticonvulsants; Epilepsy; GAP-43 Protein; Hippocampus; Levetiracetam; Male; Neural Cell Adhesion Molecules; Piracetam; Rats; Rats, Wistar; RNA, Messenger

Symptoms of attention deficit hyperactivity disorder (ADHD) are more common in children with epilepsy than in the general paediatric population. Epileptiform discharges in EEG may be seen in children with ADHD also in those without seizure disorders. Sleep enhances these discharges which may be suppressed by levetiracetam.. To assess the effect of levetiracetam on focal epileptiform discharges during sleep in children with ADHD.. In this retrospective study a new semi-automatic quantitative method based on the calculation of spike index in 24-h ambulatory EEG recordings was applied. Thirty-five ADHD children, 17 with focal epilepsy, one with generalised epilepsy, and 17 with no seizure disorder were evaluated. Follow-up 24-h EEG recordings were performed after a median time of four months.. Mean spike index was 50 prior to levetiracetam treatment and 21 during treatment. Seventeen children had no focal interictal epileptiform discharges in EEG at follow-up. Five children had a more than 50% reduction in spike index. Thus, a more than 50% reduction in spike index was found in 22/35 children (63%). Out of these an improved behaviour was noticed in 13 children (59%).. This study shows that treatment with levetiracetam reduces interictal epileptiform discharges in children with ADHD. There is a complex relationship between epilepsy, ADHD and epileptiform activity, why it is a need for prospective studies in larger sample sizes, also to ascertain clinical benefits.

Topics: Anticonvulsants; Attention Deficit Disorder with Hyperactivity; Child; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Retrospective Studies; Sleep Stages; Wakefulness

Both valproic acid and levetiracetam are anti-epileptic drugs, often used either alone or in combination. The present study compares valproate (VPA) with levetiracetam (LEV) as an intravenous (i.v.) anticonvulsant treatment in intensive care patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) with a high risk of seizures.. A prospective, single-center patient registry of 35 intensive care unit (ICU) patients with onset seizure and/or high risk of seizures underwent an anticonvulsive, first-line single treatment regimen either with VPA or LEV. Plasma concentrations (pc), interactions between drugs in the ICU context, adverse effects and seizure occurrences were observed and recorded.. A significant decrease in the pc in patients treated with LEV was observed after changing from intravenous (160±51μmol/l) to enteral liquid application (113±58μmol/l), corresponding to a 70.3% bioavailability for enteral liquid applications. The pc in VPA patients decreased significantly, from (491±138μmol/l) to (141±50μmol/l), after adding meropenem to the therapy (p<0.05). Three epileptic seizures occurred during anticonvulsive therapy in the LEV group, and two in the VPA group, including one non-convulsive status epilepticus (NCSE).. Though this finding needs further verification, the enteral liquid application of levetiracetam seems to be associated with lower bioavailability than the common oral application of levetiracetam. The use of the antibiotic drug meropenem together with valproic acid leads to lower pc levels in patients treated with of valproic acid. For clinical practice, this indicates the need to monitor the levels of valproic acid in combination with meropenem.

Topics: Administration, Oral; Aged; Aneurysm, Ruptured; Anti-Bacterial Agents; Anticonvulsants; Biological Availability; Brain Ischemia; Critical Care; Drug Interactions; Enteral Nutrition; Epilepsy; Female; Humans; Intensive Care Units; Levetiracetam; Male; Meropenem; Middle Aged; Piracetam; Prospective Studies; Seizures; Subarachnoid Hemorrhage; Thienamycins; Valproic Acid

Little is known about the haematological side effects of the newer antiepileptic drugs (AEDs), but recent case reports have raised concerns regarding the possibility of altered thrombocyte counts or function in some patients during levetiracetam (LEV) treatment. The aim of our study was to investigate haematological changes in patients treated with the newer AEDs, LEV and lamotrigine (LTG), compared with the older AEDs, valproate (VPA) and carbamazepine (CBZ).. This cross-sectional study included 251 patients with epilepsy of both genders, aged 18-45 years, using AED monotherapy: 52 patients on LEV (31 men, 21 women), 80 on LTG (37 men, 43 women), 90 on CBZ (61 men, 29 women), 29 on VPA (15 men, 14 women), and 79 healthy controls (36 men, 43 women). Haemoglobin (Hb), white blood cells (WBC) and platelet (thrombocyte) counts were estimated. The subjects were recruited from hospitals in south-eastern Norway and Innsbruck, Austria.. Significantly lower platelet counts were recorded in both men and women on LEV monotherapy. In the LEV group, platelets were 14% lower (40.68 × 10(9) /l lower) than in the control group. There was no difference according to sex or age of the patients. Only minor changes in haematological parameters were observed for the other drugs investigated.. Both men and women treated with LEV monotherapy have lower blood platelet counts than healthy controls, with no difference in Hb or WBC. Haematological changes observed with the other AEDs were minor.

Topics: Adolescent; Adult; Anticonvulsants; Blood Platelets; Carbamazepine; Cross-Sectional Studies; Epilepsy; Female; Humans; Lamotrigine; Leukocytes; Levetiracetam; Male; Middle Aged; Piracetam; Platelet Count; Triazines; Valproic Acid

To evaluate the add-on effect of levetiracetam (LEV) treatment on the EEG and clinical status of children with continuous spikes-waves during slow sleep (CSWS).. 20 children with CSWS refractory to other conventional antiepileptic drugs (AEDs) received LEV 45-50 mg/kg/day as add-on treatment, and were prospectively followed for a minimum period of 18 months. The patient population comprised seven cryptogenic, seven symptomatic and six idiopathic cases (atypical benign partial epilepsy, aBECTs). The electrographic evaluation included 24 h EEG recordings taken every six months (minimum of three per child). Electrographically children were categorised as responders, partial responders or non-responders by comparing changes in the spike index (SI) during NREM-sleep with baseline SI before initiation of LEV. The clinical efficacy of LEV was assessed by comparing seizure frequency at the end of follow up with the baseline. The follow up duration varied from 18 to 53 months.. Electrographic response was observed in 11 patients. Eight patients demonstrated a lasing response (more than 12 months): five from symptomatic, two--cryptogenic and one--idiopathic group respectively. Three children showed a partial response (6-12 months): one from symptomatic and two from idiopathic group. Eleven out of the 20 children were seizure free at baseline and during the whole follow up. The rest, six-symptomatic and three-cryptogenic patients, had seizures prior to LEV treatment initiation. Six became seizure free after add-on therapy with LEV, and in three children a significant reduction of seizure frequency was observed.. This study suggests that add-on therapy with LEV is more effective in children with CSWS resulting from a known underlying structural brain lesion (the symptomatic group).

Topics: Action Potentials; Adolescent; Anticonvulsants; Brain Waves; Child; Child, Preschool; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Piracetam; Prospective Studies; Sleep; Syndrome; Treatment Outcome

To correlate SV2A expression in surgically removed tumor and peritumoral tissue of glioma patients with epilepsy with the clinical response to levetiracetam in a prospective cohort.. Forty glioma patients with epilepsy were recruited. All patients had undergone surgery and were on levetiracetam monotherapy. Clinical characteristics were documented. Follow-up visits were scheduled at 3 and 6 months. Patients who responded to levetiracetam were compared to those who did not respond. Expression of SV2A was determined by means of immunohistochemistry in the surgically removed tumor and peritumoral tissue. Optical density (OD) was used to measure SV2A expression.. In total, 34 patients were eligible for analysis. Patients with a good response to treatment had significantly stronger SV2A expression as demonstrated by OD in tumor tissue (mean 44.5, SD 17.3) as well as in peritumoral tissue (mean 67.5, SD 7.8) than patients who did not show such a response (mean 8.1, SD 7.7, p < 0.01 and 45.6, SD 11.2, p < 0.01). SV2A expression predicted efficacy of levetiracetam monotherapy with an accuracy of 91%.. Our results suggest that expression of SV2A in tumor and peritumoral tissue is correlated to the clinical response to levetiracetam and predicts levetiracetam efficacy.

Topics: Adult; Aged; Blotting, Western; Brain Neoplasms; Cohort Studies; Epilepsy; False Positive Reactions; Female; Follow-Up Studies; Glioma; Humans; Immunohistochemistry; Levetiracetam; Male; Membrane Glycoproteins; Middle Aged; Nerve Tissue Proteins; Nootropic Agents; Piracetam; Predictive Value of Tests; Prospective Studies; Treatment Outcome; Young Adult

Antiepileptic drugs (AEDs) are frequently used off-label for the treatment of psychiatric, pain, and other neurological disorders. Off-label AED use may confound the diagnosis for acute neuropsychiatric changes associated with delirium by fortuitously treating, or partially treating, underlying seizure disorders while masking ictal electrographic patterns on EEGs. Standard video/EEG monitoring includes weaning from AEDs to maximize ictal activity and better determine seizure focus. We report a case of off-label gabapentin use masking ictal electrographic activity, the neuropsychiatric and electrographic consequences of discontinuing gabapentin, and the therapeutic response when gabapentin was re-initiated and titrated to a total daily dose greater than that at time of admission. Weaning from AEDs with concurrent video/EEG monitoring is an important diagnostic tool in these complex cases.

Topics: Administration, Oral; Aged; Amines; Anticonvulsants; Brain Waves; Cyclohexanecarboxylic Acids; Electroencephalography; Epilepsy; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Levetiracetam; Piracetam; Psychotic Disorders

To ascertain the frequency of self-reported symptoms in patients taking antiepileptic drugs (AED).. We included patients on carbamazepine (CBZ) n = 36, valproate (VPA) n = 21, levetiracetam (LEV) n = 12, phenytoin (PHT) n = 11, lamotrigine (LTG) n = 20, patients not taking anticonvulsive drugs n = 19, and healthy control subjects (CTRL) n = 41 to complete the Liverpool Adverse Event Profile (LAEP).. The mean LAEP scores were CBZ/PHT/LEV/VPA/LTG/noAED/CTRL = 44.97/42.00/41.00/40.33/32.42/42.00/30.80. LEV scored overall in the same range as the older AED but had a different adverse effect profile with self-reported anger (33%) and shaky hands (42%) particularly frequent. Patients with depression or uncontrolled epilepsy had significantly higher LAEP scores than patients without depression or uncontrolled epilepsy.. Our unblinded observational study of self-reported symptoms suggested LTG was overall the drug with the least self-reported symptoms. Larger studies are needed to determine whether this was a truly significant difference. LEV had a different side effect profile to older AED. Confounding factors were depression and uncontrolled epilepsy. This observation should be further tested with randomized studies.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Outcome Assessment, Health Care; Piracetam; Self Report; Triazines; Young Adult

Octreotide is a synthetic somatostatin analogue which has been suggested for use in the management of acute pancreatitis, though its safety and effectiveness in the pediatric setting has not been extensively studied.. we present a rare case of a 6.5-year-old female with acute lymphoblastic leukemia (ALL) and L-asparaginase (L-asp) induced pancreatitis, who developed epileptic seizures, possibly associated with octreotide administration. Her imaging and laboratory findings ruled out a leukemic involvement or infection of CNS. The EEG revealed repetitive sharp waves maximal on the frontal and temporal areas of the right hemisphere. The child was treated with diazepam and she continued with systemic anticonvulsant treatment with levetiracetam. After 2 weeks of conservative treatment, pancreatitis resolved and she continued her chemotherapy protocol. Levetiracetam treatment lasted 8 months. 7 months after the first episode, EEG was reported as normal, and the child completed the chemotherapy protocol without any further severe complications.. Larger and well designed studies are needed to warrant the safety of octreotide in pediatric population.

Topics: Acute Disease; Anticonvulsants; Asparaginase; Child; Diagnosis, Differential; Drug Interactions; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Octreotide; Pancreatitis; Piracetam; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Levetiracetam (LEV) is a novel antiepileptic drug (AED) which was discovered in early 1980s and soon, in 1999 FDA approved LEV for the management of partial onset seizure. In India, LEV tablet was approved in April 2005. It acts by binding to the synaptic vesicle protein SV2A, which is present on synaptic vesicles and some neuroendocrine cells. Pharmacokinetics of LEV such as, less protein binding and lack of hepatic metabolism makes LEV less susceptible to drug interactions with other anticonvulsants. Evidence also suggests that LEV is much better than other AEDs in the way of broad therapeutic window, convenient dosing and less adverse effect. Besides the pharmacological effects, pharmacoeconomically also, LEV is a beneficial drug. All these valuable pharmacological and pharmacoeconomic aspect makes LEV an important option in management of various types of epilepsy.

Topics: Anticonvulsants; Drug Interactions; Epilepsy; Humans; India; Levetiracetam; Piracetam; Treatment Outcome

The objective was to retrospectively study the efficacy and safety of levetiracetam (keppra) as an add-on treatment of pharmacoresistant forms of epilepsy in children. We have analyzed medical histories of 192 patients with pharmacoresistant epilepsy admitted to a neurological department of the Research and Treatment Center of Children's Medical Care over the period of 2008-2011. The patient's age varied in the range from 6 months to 19 years (mean age 5.7 years). The results of the study revealed the high efficacy of levetiracetam as an add-on treatment of pharmacoresistant epilepsy in children. The efficacy of > 50%, including patients in the remission, was found in 60.2%, the remission of more than 6 months was observed in 20.3% of patients. The efficacy of levetiracetam was higher in the treatment of the following variants of pharmacoresistant epilepsy: seizures caused by brain defects (the efficacy of > 50% was seen in 66.7% of patients), atypical rolandic epilepsy (the efficacy of > 50% was seen in 100% of patients). The efficacy of levetiracetam was not correlated with the priority of prescription of the drug that might be explained by the unique mechanism of the action of this anticonvulsant. Levetiracetam is well tolerated in the children age. Side-effects that were not life threatening were noted only in 6.2% of patients and the retention rate was 75.5%. The aggravation of seizures and EEG abnormalities, regardless of the epilepsy form, type of seizure, drug dose or the combination of anticonvulsants were seen in 5.7% of patients.

Topics: Adolescent; Anticonvulsants; Brain; Child; Child, Preschool; Drug Resistance; Drug Therapy, Combination; Electroencephalography; Epilepsy; Humans; Infant; Levetiracetam; Male; Piracetam; Retrospective Studies; Treatment Outcome; Young Adult

Tolerance to drug treatment is a serious problem in the treatment of epilepsy. We previously showed that tolerance to levetiracetam (LEV) developed within 4 days after the start of the treatment in a rat model for spontaneous seizures after electrically induced status epilepticus. In the current study we tested whether the development of tolerance to LEV could be prevented by alternating between LEV and valproate (VPA) treatment.. Before starting the alternating therapy with LEV and VPA (3 day LEV-3 day VPA, two cycles), we assessed the efficacy of VPA monotherapy by administering VPA to chronic epileptic rats via osmotic minipumps during 7 days. The anticonvulsive effects were determined by continuous video-EEG (electroencephalography) monitoring, and the concentration of VPA and LEV was measured in plasma using gas chromatography.. VPA significantly suppressed spontaneous seizures in chronic epileptic rats for 5 days. Hereafter, seizure frequency increased to pretreatment values despite adequate VPA blood levels. Seizure duration was reduced for 6 days during treatment. Seizure severity was reduced throughout the 7-day treatment period. Alternating treatment of LEV and VPA did not prevent development of tolerance; however, seizures were suppressed significantly longer compared to VPA and LEV monotherapy.. Because alternating treatment with LEV and VPA led to a prolonged effective seizure control in the animal model, it would be worthwhile to explore the possibilities of using an alternating treatment protocol in pharmacoresistant patients in whom an effective treatment is hampered by tolerance to antiepileptic drugs.

Topics: Animals; Anticonvulsants; Dentate Gyrus; Disease Models, Animal; Drug Administration Schedule; Drug Resistance; Drug Tolerance; Electric Stimulation; Electroencephalography; Epilepsy; Epilepsy, Temporal Lobe; Humans; Levetiracetam; Male; Piracetam; Rats; Rats, Sprague-Dawley; Status Epilepticus; Treatment Outcome; Valproic Acid

Lacosamide (Vimpat) is a newly licensed novel antiepileptic drug. We report a case of refractory convulsive status epilepticus (CSE) that was successfully controlled with lacosamide. The 38-year-old male patient was admitted for a series of complex partial seizures with secondary generalization leading to refractory CSE. During the transport to the hospital the patient was given 22.5 mg diazepam, 12.5 mg etomidate, and 5 mg midazolam without success. An additional dose of 4 mg lorazepam and a dose of 1,500 mg levetiracetam after admission were yet without clinical effect. A further treatment with lacosamide (300 mg via percutaneous gastric fistula) resulted in complete clinical remission of the epileptic activity within 30 min. The application of lacosamide resulted in cessation of CSE and was well tolerated. To our knowledge, this is the first case of successful treatment of refractory CSE with lacosamide. Further studies are needed to evaluate the safety and efficacy of lacosamide in treatment of SE.

Topics: Acetamides; Adult; Anticonvulsants; Diazepam; Drug Resistance; Drug Therapy, Combination; Epilepsy; Etomidate; Humans; Lacosamide; Levetiracetam; Male; Midazolam; Piracetam; Practice Guidelines as Topic; Status Epilepticus; Treatment Outcome

In the past decade, most studies on levetiracetam were conducted on patients aged > or = 4 years of age. The authors sought to assess the efficacy and safety of levetiracetam as an adjunctive treatment of children <4 years of age with refractory epilepsy. The mean levetiracetam dosage used on the 24 patients in this study was 38.85 mg/kg per day, and the mean duration of treatment was 40 weeks. During the study, levetiracetam was tapered off in 2 patients due to seizure worsening and was discontinued in other 2 patients due to unacceptable adverse effects. Levetiracetam therapy was effective in 58.3% of patients, with 20.8% achieving seizure freedom. Eight patients showed no obvious response and the remaining 2 patients showed divergent responses. Although adverse effects were seen in 37.5% of patients, all adverse effects were tolerable or resolved with time or discontinuation. Therefore, the authors conclude that levetiracetam treatment is effective and safe in young children with refractory epilepsy.

Topics: Anticonvulsants; Child, Preschool; Drug Therapy, Combination; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Seizures; Time Factors; Treatment Outcome

In order to clarify the seizure susceptibility of Noda epileptic rat (NER) and the antiepileptic effects of levetiracetam (LEV), we performed electrical hippocampal kindling in NERs compared with Wistar rats (experiment 1), and hippocampal kindling in NERs with LEV administration (experiment 2). In experiment 1, electrical stimulation was administered to the right dorsal hippocampus of NERs and Wistar rats once per day. In experiment 2, NERs were randomly assigned to group L (LEV administration) and C (saline administration). Following daily administration of LEV (240 mg/kg, i.p.) to group L and saline to group C, hippocampal kindling was performed from the 5th day of consecutive LEV or saline administration. As a result of experiment 1, all NERs exhibited stage 5 (falling) or stage 6 seizure (running/jumping, subsequent seizure) from the first electrical stimulation. In experiment 2, LEV suppressed development of hippocampal kindling, increased the afterdischarge threshold of the hippocampus and inhibited stage 6 seizures in NER. Although LEV prolonged the afterdischarge duration at the first stage 5 seizure significantly, there was a tendency to prolong the latency to generalization by LEV. These findings indicate that NER is susceptible not only to limbic seizures but also to brainstem seizures. Furthermore, LEV may have inhibitory effects not only on the hippocampus but also on other neuronal pathways to secondary generalization in this rat model.

Topics: Animals; Anticonvulsants; Brain Stem; Disease Models, Animal; Disease Progression; Drug Administration Schedule; Electric Stimulation; Epilepsy; Functional Laterality; Genetic Predisposition to Disease; Hippocampus; Kindling, Neurologic; Levetiracetam; Male; Neural Inhibition; Neural Pathways; Piracetam; Rats; Rats, Mutant Strains; Rats, Wistar; Treatment Outcome

To assess the long-term efficacy and tolerability of levetiracetam in routine clinical practice.. We retrospectively analysed 218 patients, mostly adults, presenting mostly with localisation-related epilepsy, treated with levetiracetam as adjunctive therapy or monotherapy for up to 36 months. The primary points evaluated were: long-term retention rate, reasons for discontinuing levetiracetam and the percentage of seizure-free patients.. The retention rate at 6, 12, 24 and 36 months following the commencement of levetiracetam treatment was 91.7, 75.2, 60.1 and 53.7% respectively. Sixty-seven (30.7%) patients discontinued levetiracetam treatment. During the clinical audit evaluation period, surgical resection or implantation of VNS was performed in 31 (14.3%) patients. In 53 of the 67 patients (79.1%), the treatment was discontinued due to lack of efficacy; in 14 patients (20.9%) treatment was discontinued due to adverse events. In total, 24 of 218 patients (11.0%) were seizure-free for 36 months.. Levetiracetam is an effective and well-tolerated option for long-term treatment of epilepsy in adults.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Chemotherapy, Adjuvant; Cohort Studies; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures; Time Factors; Treatment Outcome; Young Adult

The influence of levetiracetam (LEV) and valproic acid (VPA) monotherapy on sex-steroid hormone profile was investigated in thirty prepubertal children. VPA-treated children showed greatest androstendione concentrations when compared to LEV treated children (p=0.016) and to controls (p=0.011). All other reproductive endocrine hormones were similar among groups. In conclusion, LEV does not seem to induce changes in reproductive endocrine functions as well as clinically relevant endocrine side effects in prepubertal children.

Topics: Analysis of Variance; Anticonvulsants; Child; Cohort Studies; Cross-Sectional Studies; Epilepsy; Female; Gonadal Steroid Hormones; Gonadotropins, Pituitary; Humans; Levetiracetam; Male; Pilot Projects; Piracetam; Sex Factors; Valproic Acid

A drug holiday seems to produce seizure interval prolongation (SIP) after reinstitution of antiepileptic drugs (AEDs). This effect was demonstrated mainly with carbamazepine. We evaluated SIP with newer AEDs and tested the relationship of SIP to history of AED tolerance.. We prospectively studied patients with refractory epilepsy admitted to the Vanderbilt epilepsy monitoring unit (EMU) over a period of 12 months. We included only patients on levetiracetam, lamotrigine, or oxcarbazepine who had their AEDs withdrawn on admission and reinstituted without change upon discharge. We defined SIP as the interval from EMU discharge to first seizure minus the interval between the last two seizures before EMU admission.. A total of 43 patients completed the study; 15 were on monotherapy. SIP was greater than zero in this patient group (p < 0.0001), with a mean prolongation of 19.4 +/- 28.0 days. The average SIP was higher (p = 0.01) in patients on monotherapy (29.7 +/- 23.8 days) than patients on polytherapy (13.9 +/- 29.0 days). SIP tended to be greater in patients with a prior history of AED tolerance (25.7 +/- 36.8 days) compared to patient with no prior history of AED tolerance (14.0 +/- 16.3 days).. SIP does occur after brief AED withdrawal. This effect is greater in patients on monotherapy and tends to be larger in patients with a history of AED tolerance. The SIP effect may be related to the phenomenon of tolerance, clinically seen as resistance to AED therapeutic effect.

Topics: Adult; Anticonvulsants; Carbamazepine; Drug Administration Schedule; Drug Resistance; Drug Tolerance; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Humans; Lamotrigine; Levetiracetam; Male; Oxcarbazepine; Piracetam; Severity of Illness Index; Substance Withdrawal Syndrome; Treatment Outcome; Triazines

Levetiracetam (LEV, 2S-(oxo-1-pyrrolidinyl)butanamide, Keppra, UCB Pharma) is a new anti-epileptic drug used to treat certain types of seizures in epilepsy patients. However, the pharmacodynamics of LEV is still controversial. Recently, interleukin-1 beta (IL-1 beta) has been reported to involve in epileptic phenomena. Therefore, we investigated the effects of LEV on IL-1 beta system in the hippocampus and piriform cortex of chronic epileptic rats. As compared to controls, typical reactive astrogliosis and microgliosis were observed in the hippocampus and piriform cortex of epileptic animals. In addition, both reactive astrocytes and reactive microglia showed strong IL-1 beta and interleukin-1 receptor subtype 1 (IL-1R1) immunoreactivities. LEV reduced reactive gliosis and expression levels of IL-1 beta system in the hippocampus and the piriform cortex, while valproic acid did not. These findings suggest that the LEV may have, at least in part, anti-inflammatory effect, particularly against IL-1 beta system in neuroglia within epileptic brains.

Topics: Animals; Anticonvulsants; Astrocytes; Chronic Disease; Epilepsy; Gliosis; Hippocampus; Interleukin-1beta; Levetiracetam; Male; Microglia; Olfactory Pathways; Pilocarpine; Piracetam; Rats; Rats, Sprague-Dawley; Receptors, Interleukin-1 Type I; Valproic Acid

We evaluated factors possibly influencing serum concentrations of levetiracetam (LEV-SC). The study included 163 patients with epilepsy (91 men, 72 women; mean age 39.6 years). The duration of treatment on first analysis was 226 days; the mean daily dose amounted to 2,434 mg. In each patient between one and seven measurements were carried out (mean 2.2). LEV-SC significantly depended on daily dosage and the interval between the time the medication was taken and the time of blood extraction. A marked drop in LEV-SC was observed 4-5 h following ingestion. Carbamazepine, oxcarbazepine and clobazam reduced LEV-SC, whereas valproate elevated LEV-SC significantly. When assessing evaluation of compliance these factors have to be taken into consideration when comparing intraindividual LEV-SC.

Topics: Adult; Analysis of Variance; Anticonvulsants; Biological Availability; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Linear Models; Male; Metabolic Clearance Rate; Piracetam; Statistics as Topic

To investigate the efficacy and safety of levetiracetam adjunctive therapy in childhood intractable epilepsy, data were reviewed for 130 children who had >or=4 seizures per month, whose seizures were intractable to an initial >or=2 antiepileptic drugs, and who could be monitored for at least 6 months after levetiracetam add-on. Reduction in seizure frequency and related variables were investigated. Sixty-two of the 130 patients (48%) showed a seizure reduction of >or=50%, and 28 patients (22%) became seizure-free. A reduction in seizures by >or=50% was observed in 33/64 in children with partial seizures (52%) and in 29/66 children with generalized seizures (44%). Efficacy did not differ significantly among seizure types. Overall efficacy was unaffected by abnormalities evident from magnetic resonance imaging, by mental retardation, or by maintenance dose of levetiracetam. The mean maintenance dose of levetiracetam was 47.0mg/kg per day (S.D. = +/- 29.7), and mean follow-up duration was 13.4 months (S.D. =+/- 8.7). No demographic features differed significantly between patients with seizure freedom and without seizure remission. Levetiracetam was discontinued in 24 children at last visit (retention rate, 82%). The most common complaint was irritability (5%), and none of the adverse events were life threatening. In conclusion, levetiracetam adjunctive therapy is effective and safe for childhood intractable epilepsy.

Topics: Adolescent; Age Factors; Aggression; Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Irritable Mood; Levetiracetam; Male; Piracetam; Retrospective Studies; Treatment Outcome

We review our experience with high-dose intravenous levetiracetam (IV-LEV) for acute seizure exacerbations in nine children with medically intractable epilepsy. All children had acute repetitive seizures-while on chronic antiepileptic drugs-that either led to hospitalization (eight) or occurred during hospitalization (one), and received doses of IV-LEV of 150 mg/kg/day or greater, with a mean dose of 228 +/- 48 mg/kg/day. Eight of nine children had resolution of the acute repetitive seizures. Seizure frequency was reduced to less than baseline in seven children (seizure-free in two, >/=80% reduction in four, and 50% reduction in one). Except for one child with increased seizures, IV-LEV was well tolerated in all children without complications.

Topics: Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Injections, Intravenous; Levetiracetam; Male; Piracetam; Seizures; Time Factors; Treatment Outcome

To evaluate the efficacy and safety of levetiracetam in the management of epilepsy in patients with glioma.. A prospective study in hospitalized patients with a new diagnosis of glioma.. Department of Neurological Sciences and Visions, Spedali Civili of Brescia.. From March 1, 2006, until January 1, 2009, 176 consecutive patients (101 men and 75 women) with a first diagnosis of glioma were enrolled in the study. All patients with a diagnosis of epilepsy were treated with levetiracetam.. Clinical, histological, and magnetic resonance imaging findings were analyzed.. Age at the diagnosis of glioma ranged from 22 to 79 years (mean [SD], 57 [15] years; median, 59 years). Duration of the disease ranged from 27 days to 2(1/2) years (mean [SD], 13.7 [7.8] months; median, 13 months). Eighty-two patients received levetiracetam because of a diagnosis of epilepsy. At the last evaluation (May 1, 2009), 75 of 82 patients (91%) treated with levetiracetam were seizure free; in 2 of these patients, levetiracetam was withdrawn because of intolerable adverse effects. Prompt and long-lasting control of seizures was obtained in 49 of 82 patients (60%) with a dose of levetiracetam that ranged from 1500 to 3000 mg/d, and 9 (11%) of the treated patients needed an increase of levetiracetam dosage to 4000 mg/d to become seizure free. No laboratory abnormalities were observed in patients with concomitant chemotherapy.. The results of this study provide good evidence that levetiracetam is efficacious and safe in patients with epilepsy due to glioma.

Topics: Adult; Aged; Anticonvulsants; Brain Neoplasms; Dose-Response Relationship, Drug; Epilepsy; Female; Glioma; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Severity of Illness Index

To compare the effectiveness of antiepileptic drugs (AEDs) for use in older adults with epilepsy.. Retrospective review.. Columbia Comprehensive Epilepsy Center, New York, New York.. Four hundred seventeen outpatients 55 years and older newly taking any of the 10 most commonly prescribed AEDs between 2000 and 2005.. The percentage of patients who remained taking the AED for 12 or more months (12-month "retention"). We also measured efficacy (12-month seizure freedom) and adverse effects leading to dose change. Retention and seizure-freedom rates were analyzed by pairwise comparisons using chi(2) for the overall group and patients with refractory and nonrefractory disease as well as patients newly taking their first AED.. The 10 AEDs newly taken by 10 or more patients were analyzed. There were no significant non-AED predictors of retention. Without controlling for severity, lamotrigine had the highest 12-month retention rate (79%), significantly higher than carbamazepine (48%), gabapentin (59%), oxcarbazepine (24%), phenytoin (59%), and topiramate (56%). The retention rate for levetiracetam (73%) was second highest and significantly higher than carbamazepine and oxcarbazepine. Oxcarbazepine had the lowest retention rate, significantly lower than all other AEDs. Lamotrigine had the highest 12-month seizure-freedom rate (54%), followed by levetiracetam (43%). When stratified into patients with nonrefractory and refractory disease, relative rates of seizure freedom and retention remained comparable with the overall group. Imbalance, drowsiness, and gastrointestinal symptoms were the most common intolerable adverse effects.. In this study of older adults with epilepsy, lamotrigine was the most effective AED as measured by 12-month retention and seizure freedom, with levetiracetam a close second. Oxcarbazepine was consistently less effective than most other AEDs.

Topics: Adult; Aged; Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Drug Resistance; Epilepsy; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Phenytoin; Piracetam; Retrospective Studies; Topiramate; Treatment Outcome; Triazines

In 2006, intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy, 16 years or older. We have established the safety, tolerability, and dosage of intravenous levetiracetam in children. This prospective study included 30 children (6 months to <15 years of age). Patients were administered a single dose of intravenous levetiracetam (50 mg/kg, maximal dose 2500 mg) over 15 minutes. A blood level of levetiracetam was performed 10 minutes after the infusion. The treated children's average age was 6.3 years (range 0.5-14.8 years). The mean levetiracetam level was 83.3 microg/mL (range 47-128 microg/mL). There were no serious adverse reactions. Minor reactions included sleepiness, fatigue, and restlessness. An apparent decrease in seizure frequency across all seizure types was noted. The dose of 50 mg/kg was well tolerated by the patients and is a safe, appropriate loading dose.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Humans; Infant; Infusions, Intravenous; Levetiracetam; Male; Piracetam; Prospective Studies; Regression Analysis; Seizures; Time Factors; Treatment Outcome

To evaluate of the efficacy and safety of adjunctive levetiracetam (LEV) in children younger than 4 years with refractory epilepsy.. One hundred and twelve children at age of 4 months to 4 years with refractory epilepsy received LEV as adjunctive therapy. LEV was administered in two equal daily doses of 10 mg/kg. The dose was increased by 10 mg/kg every week up to the target dose (20-40 mg/kg). The efficacy and tolerability were evaluated.. At an average follow-up period of 13 months (6-22 months), LEV administration was found to be effective in 43 children (38.4%) (responders showing more than a 50% decrease in seizure frequency) and 14 children (12.5%) became seizure-free. Fifty-three children (47.3%) did not respond to the treatment and 2 children (1.8%) worsened. The therapy-related adverse events were mild, including restlessness, reduction in sleep time, night terrors, debility, somnolence, nausea and vomiting. The adverse events were either tolerable or resolved in time with dosage reduction in most of children, and only 3 cases required discontinuation.. LEV as adjunctive therapy is effective and well-tolerated in children younger than 4 years with refractory epilepsy, suggesting that it represents a valid option for the treatment of refractory epilepsy in this age group.

Topics: Anticonvulsants; Child, Preschool; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Piracetam

Phenylketonuria (PKU) is one of the most common inherited metabolic disorders, which is characterized by excessive accumulation of phenylalanine (Phe) in tissues. Generalized seizures occur in 25% of the patients. Little is known about seizures and their treatment in adult PKU patients, and information with newer antiepileptic drugs is lacking. Here we report an adult patient who developed generalized seizures later in life, despite strict dietary control, and whose seizures were aggravated by levetiracetam (LEV). Convulsions ceased after discontinuation of LEV and the patient has been seizure free on topiramate 125 mg/day.

Topics: Anticonvulsants; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Female; Fructose; Humans; Levetiracetam; Phenylalanine; Phenylketonurias; Piracetam; Topiramate; Treatment Outcome; Young Adult

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Piracetam; Treatment Outcome

The aim of this study was to evaluate efficacy and tolerability of levetiracetam (LEV) in patients with different epilepsy syndromes.. We evaluated epileptic patients seen in the previous 18 months, including all patients with present or past exposure to LEV. Tolerability of LEV therapy was evaluated in all patients; efficacy was evaluated only in patients who had received LEV for at least six months. Two hundred and two patients were included in the study. Patients were considered responsive when showing a > 50% reduction in seizures frequency and non-responders when seizure frequency was unchanged, worsened or showed a reduction < 50%.. Thirty patients did not complete six months of LEV treatment and dropped out. 57.4% of the patients with uncontrolled seizures treated for at least six months were responders, with 27.7% seizure free. Adverse effects were observed in 46 patients (23%) and were responsible for early drop out in 26. Adverse effects occurred significantly more often in females than in males (30.6% vs 13.2%); moreover, nearly 30% of women with adverse effects complained of more than one adverse effect, while this was never observed in male patients.. Our study shows LEV as a well tolerated and effective treatment, both in monotherapy and as an add-on. Further investigations on larges samples are needed to investigate the issue of gender-related tolerability.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Child; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Logistic Models; Male; Middle Aged; Piracetam; Retrospective Studies; Treatment Outcome; Young Adult

Different neuroimaging techniques (fMRI, spectroscopy, PET) are being used to evaluate candidate drugs in pharmacological development. In patients with epilepsy fast propagation of the epileptiform activity between different brain areas occurs. Electric Source Imaging (ESI), in contrast to the aforementioned techniques, has a millisecond time resolution, allowing visualization of this fast propagation. The purpose of the current project was to use ESI to investigate whether introduction of an antiepileptic drug (levetiracetam, LEV) would change the propagation patterns of the interictal epileptiform activity. Thirty patients with epilepsy were subject to an EEG recording before (pre-LEV) and after (in-LEV) introduction of LEV. Interictal spikes with similar topographic distribution were averaged within each subject, and a distributed source model was used to localize the EEG sources of the epileptiform activity. The temporal development of the activity within 20 regions of interest (ROIs) was determined, and source propagation between different regions was compared between the pre-LEV and in-LEV recordings. Patients with epileptic seizures showed propagation in 22/24 identified spike types in the pre-LEV recordings. In the in-LEV recordings only 7/15 spike types showed propagation, and six of these seven propagating spikes were recorded in patients with poor effect of treatment. Also in patients without seizures LEV tended to suppress propagation. We conclude that the observed suppression of source propagation can be considered as an indicator of effective antiepileptic treatment. ESI might thus become a useful tool in the early clinical evaluation of new candidate drugs in pharmacological development.

Topics: Anticonvulsants; Brain Mapping; Child; Child, Preschool; Diagnostic Imaging; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Time Factors

The aim of the study was to investigate risk factors for cardiovascular disease in patients with epilepsy using the new antiepileptic drug levetiracetam (LEV), compared with patients taking carbamazepine (CBZ) or lamotrigine (LTG).. Two hundred and twelve patients and 80 controls (age: 18-45 years) of both genders were included. The patients had been treated with either LEV (n = 52), CBZ (n = 87) or LTG (n = 73) monotherapy for at least 6 months. Total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were measured. Smoking, drinking habits and physical activity were recorded and body mass index (BMI) was calculated.. Neither LEV nor LTG altered TC, LDL or HDL. Both men and women using CBZ had higher TC, HDL and LDL than controls. LDL/HDL and TC/HDL ratios were unchanged. Women on CBZ and LTG had a greater BMI when compared with the control group. Patients with epilepsy recorded less physical activity and lower alcohol use than the controls.. Neither LEV nor LTG affected blood lipid levels, while patients treated with CBZ have higher cholesterol, HDL and LDL than controls. The patients were less physically active, and women on CBZ and LTG had higher BMI.

Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; Cardiovascular Diseases; Comorbidity; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Piracetam; Risk Factors; Triazines; Young Adult

Epilepsy is a common disease of childhood, in which almost 25% of cases are resistant to common antiepileptic drugs. Uncontrolled epilepsy increases morbidity and mortality rates, adversely affects growth and development in these children and imposes heavy psychological stress and financial burdens on parents, health care and society, making it mandatory to find effective therapies for the condition. Our aim was to study the efficacy of levetiracetam, as an add-on therapy, in children suffering from refractory epilepsy.. In this prospective add-on study, 45 children aged 0.6-15 years (median 5.9 years) with epilepsy not responding to most conventional or new antiepileptic drugs were treated by adding levetiracetam to their present antiepileptic regimen and followed for a minimum period of 12 weeks. The starting dose of 20mg/kg/day was increased at intervals of 1 week by 10mg/kg/day, if necessary, up to a maximum dose of 60mg/kg/day.. Four children (8.7%) became seizure free, in 4 (8.7%), seizure frequency increased, and in 8 (17.4%) and 13 (28.3%) patients, seizure frequency decreased by 75-99% and 50-74% respectively. Overall levetiracetam was effective in 54.3% of patients, decreasing seizure frequency to at least 50% of baseline seizure frequency. Variables such as sex, age, duration of disease, type and cause of seizure, EEG and imaging data, also type of epileptic syndrome showed no statistically significant correlations with these results.. Levetiracetam can be used as an effective add-on treatment in children with refractory epilepsy.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Prospective Studies; Treatment Outcome

Despite the advent of new antiepileptic drugs, many children continue to have refractory seizures. We sought to determine whether oral LEV is helpful in seizure control and tolerable at doses higher than 60mg/kg/day in the pediatric outpatient population.. A retrospective chart review over a 1.5-year period was performed at the Columbia Comprehensive Epilepsy Center to identify children who were treated with levetiracetam doses titrated above the usual 40-60mg/kg/day. Data was collected on seizure semiology, epilepsy type, seizure frequency, concomitant antiepileptic drugs, and adverse effects.. Thirty-two children, ranging in age from 1 to 19 years, required high dose levetiracetam. The median dosage of levetiracetam was 146mg/kg/day (range, 70-275mg/kg/day), and the median maximum serum trough level was 43mcg/ml (range, 20-121mcg/ml). All but one patient were taking one or more other antiepileptic drugs. A more than 50% reduction in seizure frequency was observed in 14 children (44%), with 5 achieving seizure freedom (16%). No response to high dose levetiracetam was found in 14 children (44%), and worsening of seizure frequency occurred in 4 (12%). Adverse effects were observed in 4 patients (12%), and were behavioral.. Not only do some children tolerate high doses and serum levels of levetiracetam, but they may also benefit from them, suggesting that doses higher than 60mg/kg/day may be considered in children who partially respond to the lower doses.

Topics: Administration, Oral; Adolescent; Age Factors; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Mental Disorders; Piracetam; Retrospective Studies; Treatment Outcome; Young Adult

The pharmacokinetics of many antiepileptic drugs differs between adults and children. The influence of age and concomitant medications on the dose/concentration ratio of levetiracetam was examined in 103 children with epilepsy. Dosing and plasma levels of levetiracetam and concomitant antiepileptic drugs were reviewed retrospectively. The dose/concentration ratio was calculated as the weight-normalized dose (mg/kg/day) divided by the steady-state trough plasma drug level, which was used as a measure of apparent oral clearance of levetiracetam. Children were classified into age groups and treatment groups: levetiracetam given with enzyme inducers (n = 24) or nonenzyme inducers (n = 69), or as monotherapy (n = 10). Levetiracetam clearance differed significantly between age groups (0-4, 5-11, and 12-17 years), i.e., the younger the child, the higher the clearance. The increase was 1.7-fold between the youngest and oldest age groups. Children on enzyme inducers exhibited significantly higher clearance (1.3-fold), compared with those on nonenzyme inducers and monotherapy. Levetiracetam did not influence the clearance of lamotrigine, valproate, topiramate, or clonazepam. In conclusion, younger age and comedication with an enzyme inducer increased levetiracetam clearance. This finding should be taken into account when treating individual patients.

Topics: Adolescent; Age Factors; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Drug Interactions; Drug Therapy, Combination; Epilepsy; Female; Humans; Infant; Lamotrigine; Levetiracetam; Male; Metabolic Clearance Rate; Oxcarbazepine; Phenytoin; Piracetam; Retrospective Studies; Triazines; Valproic Acid

We sought to determine whether the testosterone increase found with levetiracetam exposure in animal studies also occurs in patients. Adult male patients were evaluated for reproductive hormone levels before and 1 month after levetiracetam therapy. Eight subjects met inclusion/exclusion criteria (mean age 46 years, range 29-75 years). Total testosterone prior to starting levetiracetam ranged from 206-787 ng/dl [mean 445, standard deviation (SD) 227]. The mean total testosterone after levetiracetam therapy increased to 592 ng/dl (range 216-981, SD 297), an increase of 16% (p = 0.036). The free testosterone increased from a mean of 64 pg/ml (range 36-115, SD 30) to a mean of 76 pg/ml (range 35-155, SD 44), an increase of 19% (p = 0.080). The magnitude of change in testosterone levels correlated with the initial testosterone level (p = 0.038, r = 0.734). These results suggest that levetiracetam increases testosterone levels and that an initial testosterone level may predict the magnitude of increase.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Epilepsy; Follicle Stimulating Hormone; Humans; Levetiracetam; Luteinizing Hormone; Middle Aged; Piracetam; Reference Values; Sex Hormone-Binding Globulin; Testosterone; Young Adult

Topics: Aged; Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Diagnostic Imaging; Electroencephalography; Epilepsy; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Levetiracetam; Patient Education as Topic; Piracetam; Social Support; Triazines

We evaluated long-term retention rates of newer antiepileptic drugs (AED) in adults with localization-related epilepsy retrospectively.. We estimated retention rates by Kaplan-Meier method in all 222 patients (age > or = 16) with localization-related epilepsy exposed to new AED at the Tampere University Hospital.. There were 141 patients exposed to lamotrigine, 78 to levetiracetam, 97 to topiramate, 68 to gabapentin, and 69 to tiagabine. Three-year retention rate for lamotrigine was 73.5%, levetiracetam 65.4%, topiramate 64.2%, gabapentin 41.7%, and tiagabine 38.2%. The most common cause for withdrawal of these AED was lack of efficacy.. Our study suggests that there are clinically significant differences among gabapentin, lamotrigine, levetiracetam, tiagabine, and topiramate as treatment for focal epilepsy in everyday practice. Gabapentin and tiagabine seem to be less useful than the other three AED. Furthermore, our study supports the value of retention rate studies in assessing outcome of the drugs in clinical practice.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amines; Anticonvulsants; Child; Cyclohexanecarboxylic Acids; Epilepsy; Female; Finland; Fructose; Gabapentin; gamma-Aminobutyric Acid; Half-Life; Humans; Lamotrigine; Levetiracetam; Licensure, Pharmacy; Male; Middle Aged; Nipecotic Acids; Piracetam; Retrospective Studies; Tiagabine; Topiramate; Treatment Outcome; Triazines; Young Adult

To assess the long-term usefulness of 'new anti-epileptic drugs (AEDs)' (lamotrigine, topiramate, levetiracetam, gabapentin and pregabalin) in institutionalized intellectually disabled patients. Information from RCTs is lacking in this population with severe intellectual and behavioural disabilities.. Retrospective study. Data from the medical files and the pharmacy databases of 118 institutionalized intellectually disabled patients who had ever used at least one of the new AEDs were analyzed. The main evaluation parameters were the duration of use (using Kaplan-Meier survival estimates) and the reason for discontinuation (lack of efficacy, occurrence of adverse events, or both) of the new AEDs. Drug continuation was based on the evaluation of treatment results by experienced epileptologists, and not on fixed criteria.. New AEDs were generally tried only after a substantial number of other regimens (with classic AEDs) had failed. The most frequently used new AEDs were lamotrigine (68%) and levetiracetam (58%), followed by topiramate (28%) and gabapentin (8%). The 3-year retention rates were 70% (lamotrigine), 52% (levetiracetam), 51% (topiramate) and 33% (gabapentin). Discontinuation due to "lack of efficacy" occurred in 61% (topiramate), 60% (lamotrigine) and 42% (levetiracetam) of the cases. Discontinuation due to adverse events occurred in 42% (levetiracetam), 33% (topiramate) and 28% (lamotrigine).. Treatment of epilepsy with new AEDs was quite often successful in this very therapy-resistant population.

Topics: Adolescent; Adult; Amines; Anticonvulsants; Child; Cyclohexanecarboxylic Acids; Drug Utilization Review; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Institutionalization; Intellectual Disability; Lamotrigine; Levetiracetam; Middle Aged; Piracetam; Retrospective Studies; Topiramate; Triazines

Quantitative analysis of epileptiform discharges (EDs) before and after the initiation of an antiepileptic treatment is a useful tool to objectively documentate the efficacy of an antiepileptic drug (AED). Aim of this study was to evaluate the effect of levetiracetam (LEV) on EDs, monitored with ambulatory EEG (A/EEG), in a limited series of patients with generalized epilepsy.. We performed 24h A/EEG recording in basal condition and at follow-up after LEV therapy in 21 adult epileptic patients. Eleven received LEV as monotherapy and 10 as add-on. For each patient we quantified total epileptic activity considering the following parameters: total number, total duration, maximal duration and median duration of EDs. Self-reported information on the effect of LEV on clinical seizures was also collected, to determine the electro-clinical correlation.. A high variability of the response to LEV was observed in the monotherapy group, without statistical differences for all the parameters investigated. A significant reduction of the total number of seizures (113.6 vs. 41.2; p=.01) was observed in patients in add-on therapy. The modifications of epileptiform EEG abnormalities did not necessarily correlate with the self-reported clinical impressions.. The quantification of EDs monitored by A/EEG provides a useful objective support for evaluating the neurophysiologic profile and the real efficacy of an antiepileptic treatment. In our patients LEV was able to significantly reduce the EDs only in add-on therapy. Further larger studies are necessary to clarify the effects of LEV on electro-clinical features of generalized epilepsy.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Drug Therapy, Combination; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Monitoring, Ambulatory; Piracetam

Clinical experience with intravenous levetiracetam (LEV IV) is still very limited, especially in elderly subjects. The primary objective of this retrospective observational study was to describe the efficacy and tolerability of LEV IV in older patients presenting with epileptic seizure emergencies.. Medical records of 14 older people treated with LEV IV were analysed retrospectively. All patients suffered from series of complex partial seizures or convulsive or non-convulsive status epilepticus needing emergent intravenous (IV) antiepileptic drug (AED) treatment. Nine patients were taking AED therapy when LEV IV was administered.. Mean age was 73.9 years (range 61-97). Mean dosage was 1,643 mg/day (range 500-4,000). Seizure control could be achieved in 11/14 patients (78.6%). No significant adverse events were noted besides sedation.. LEV IV was effective and well tolerated in these critically ill older patients. LEV IV seems to be a reasonable practical alternative in multimorbid older patients who need IV treatment with an AED.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Drug Tolerance; Emergencies; Epilepsy; Epilepsy, Complex Partial; Female; Humans; Infusions, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Status Epilepticus

Levetiracetam (LEV), a newer antiepileptic drug (AED) useful for several epilepsy syndromes, binds to SV2A. Identifying genetic variants that influence response to LEV may allow more tailored use of LEV. Obvious candidate genes are SV2A, SV2B and SV2C, which encode the only known binding site, synaptic vesicle protein 2 (SV2), with LEV binding to the SV2A isoform. SV2A is an essential protein as homozygous SV2A knockout mice appear normal at birth but fail to grow, experience severe seizures and die by 3 weeks. We addressed characterising AED response issues in pharmacogenetics and whether variation in these genes associates with response to LEV in two independent cohorts with epilepsy. We also investigated whether variation in these three genes associated with epilepsy predisposition in two larger cohorts of patients with various epilepsy phenotypes. Common genetic variation in SV2A, encoding the actual binding site of LEV, was fully represented in this study whereas SV2B and SV2C were not fully covered. None of the polymorphisms tested in SV2A, SV2B or SV2C influence LEV response or predisposition to epilepsy. We found no association between genetic variation in SV2A, SV2B or SV2C and response to LEV or epilepsy predisposition. We suggest this study design may be used in future pharmacogenetic work examining AED or LEV efficacy. However, different study designs would be needed to examine common variation with minor effect sizes, or rare variation, influencing AED or LEV response or epilepsy predisposition.

Topics: Adult; Anticonvulsants; Cohort Studies; Epilepsy; Epilepsy, Temporal Lobe; Female; Genetic Predisposition to Disease; Genetic Variation; Genotype; Hippocampus; Humans; Ireland; Levetiracetam; Male; Membrane Glycoproteins; Nerve Tissue Proteins; Piracetam; Polymorphism, Genetic; Synaptic Vesicles; United Kingdom

Quantification of epileptiform activity in EEG has been applied for decades. This has mainly been done by visual inspection of the recorded EEG. There have been many attempts using computers to quantify the activity, usually with moderate success. In a row of contexts, including Landau-Kleffner syndrome and the syndrome of epilepsy with continuous spike wave during slow sleep, the spike index (SI) has been applied to quantify [Symbol: see text]interictal nocturnal focal epileptiform activity', which is suggested as a general term for the epileptiform activity enhanced by sleep. However, the SI has been implemented differently by different authors and has usually not been well described and never properly defined. This study suggests a definition of SI that gives a semiautomatic and relatively robust algorithm for assessment. The method employs spike detection by means of template matching of the current source density estimate. The percentage of time within an epoch with interspike interval (ISI) below a given limit, usually 3 s, is returned as the SI. This is calculated during daytime and in non-REM sleep. The standard epoch length is 10 min. The parameter selection is discussed in the context of the influence of spikes and bursts on cognition. The described method gives reproducible results in routine use, gives clinical valuable information, and is easily implemented in a clinical setting. There is only a minor added workload for the electroencephalographer.

Topics: Algorithms; Anticonvulsants; Brain; Child; Cognition; Electroencephalography; Epilepsy; Humans; Levetiracetam; Linear Models; Piracetam; Reproducibility of Results; Signal Processing, Computer-Assisted; Sleep; Time Factors

To develop a population pharmacokinetic model to evaluate the demographic and physiologic determinants of levetiracetam (LEV) pharmacokinetics (PK) and to suggest recommended doses of LEV in children.. LEV PK were investigated in a prospective open trial of LEV as adjunctive therapy using a population approach performed with NONMEM (Nonlinear Mixed Effects Model) on 170 LEV concentration-time records and covariate information from 44 children between 4 and 16 years of age. Possible associations between pharmacokinetic parameters and age, gender, body weight, creatinine clearance, and concomitant antiepileptic drugs (AEDs) were assessed. The final model was used to perform Monte Carlo simulations in order to identify the dosing regimens that should achieve the same nominal target concentration range as in adults.. LEV PK were well described by a one-compartment model with first-order absorption and elimination. Both LEV apparent clearance and distribution volume were related to body weight, and no pharmacokinetic interaction was observed. Monte Carlo simulations showed that a 10mg/kg twice daily (b.i.d.) regimen provides a plasma concentration similar to that obtained in adults for the recommended 500 mg b.i.d. starting dose, and that a 20 mg/kg b.i.d. regimen would achieve the previously described 6-20 mg/L target range for the trough concentration.. Our results support the use of a weight-based LEV dosing regimen and provide a basis for a recommended pediatric dosage regimen. The relationship between LEV plasma concentrations and clinical effect has not been evaluated fully and could differ between adults and children. Clinical studies should be able to validate these dosing recommendations.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Electrochemistry; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Models, Biological; Piracetam; Population; Prospective Studies; Reference Values; Reproducibility of Results; Time Factors

In intensive care unit (ICU) patients, seizure or status epilepticus treatment with intravenous benzodiazepines or conventional antiepileptic drugs (AEDs), such as phenytoin, may be accompanied by cardiovascular depression or hypotension. Levetiracetam (LVM) is a novel AED that does not undergo extensive liver metabolism, does not require drug level monitoring, and is not associated with hemodynamic instability. We retrospectively analyzed the use, safety, and efficacy of LVM in ICU patients.. Collected data included age, sex, therapy indication and duration, dosing regimen, documented seizure activity, ICU admission diagnoses, length of ICU stay, serum creatinine, liver function tests, adverse reactions, concomitant use of other AEDs, and drug interactions.. Fifty-one patients were identified (26 males; mean (SD) age, 58.2 (19.8) years). Most patients (65%) did not receive a loading dose; the most common loading dose was 1,500 mg (50% of 18 patients). The most common maintenance dose was 500 mg twice daily (59% of 51 patients), and average duration of therapy was 13.6 (12.7) days. Approximately 47% of patients had preexisting liver disease, and 25% had elevated serum creatinine. Twenty-two patients received LVM therapy for seizure prophylaxis; 29 for acute seizure treatment. Ninety-three percent of patients treated with LVM for acute seizure had no subsequent seizures; the remaining patients (7%) required additional AEDs. One patient receiving LVM for seizure prophylaxis had documented seizures requiring additional AEDs. No adverse hemodynamic events or cardiac arrhythmias were reported.. LVM appears to be safe for ICU patients when dosing is adjusted for renal function.

Topics: Adult; Aged; Anticonvulsants; Critical Care; Critical Illness; Epilepsy; Female; Humans; Kidney; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies

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

With an apparently first epileptic seizure in a young female patient, we propose a diagnostic and therapeutic discussion on a common clinical problem. Due to the large number of available antiepileptic drugs, choosing the best treatment is not an easy task. One must take into consideration the type of epilepsy, the pharmacological properties of the antiepileptic drug, and the clinical profile of the patient. Besides drug prescription, specific recommendations must also be made.

Topics: Adult; Anticonvulsants; Carbamazepine; Drug Therapy, Combination; Epilepsy; Female; Fructose; Humans; Lamotrigine; Levetiracetam; Piracetam; Topiramate; Treatment Outcome; Triazines; Valproic Acid

Variations in the plasma concentration of levetiracetam during pregnancy and postpartum were prospectively monitored in five women to investigate their potential implications in epilepsy management and child outcome. Under unchanged levetiracetam dosages, the mean concentrations of levetiracetam during the third trimester were 62% of the baseline late (12 month) postpartum levels, but only 47% of the baseline early postpartum (2 month) levetiracetam levels. In dual therapy with lamotrigine, baseline late postpartum levetiracetam clearance was 63.2%, whereas in early postpartum it was 45% of the maximal second-trimester clearance. However, the number of seizures remained unchanged once lamotrigine dose was increased. No woman had adverse effects during the puerperium. The mean umbilical cord/maternal plasma concentration ratio was 1.21. None of the newborns had malformations, with the anthropometric data being normal for their gestational age. The decline in gestational levetiracetam plasma concentration does not seem to be hazardous, but differs according to whether early or late postpartum levels are chosen as baseline levels.

Topics: Adult; Anticonvulsants; Epilepsy; Female; Follow-Up Studies; Humans; Lamotrigine; Levetiracetam; Maternal-Fetal Exchange; Piracetam; Postpartum Period; Pregnancy; Pregnancy Complications; Triazines

Topics: Acetamides; Aged; Anti-Infective Agents; Epilepsy; Epilepsy, Complex Partial; Humans; Levetiracetam; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Oxazolidinones; Piracetam; Staphylococcal Infections; Ulcer

The aim of this pilot study was to investigate the effects of levetiracetam monotherapy on seizure control, quality of life and neurocognitive performance in patients with brain tumor-related epilepsy. We present here preliminary data from 18 patients with follow-up of 6 months. We evaluated seizure frequency at baseline. We used administered Mini Mental State Examination (MMSE), Karnofsky Performance Status (KPS), Barthel index (BI), QOLIE 31P (V2), EORTC QLQ-C30 and Adverse Events Profile. After 6 months, 16 patients were seizure free (88.9%), 2 (11.1%) had reduction in seizure frequency >50%. Compared to baseline, we observed a worsening of performance (KPS p = 0.011; BI = 0.008) and global lower cognitive performance (MMSE p = 0.011); distress related to seizure frequency (p = 0.003) and medication effects (p = 0.046) were significantly lower. Levetiracetam caused mild and reversible side effects. These preliminary data on LEV monotherapy in patients with brain tumor-related epilepsy show that this antiepileptic drug is efficacious and well tolerated.

Topics: Activities of Daily Living; Adult; Aged; Anticonvulsants; Blood Cell Count; Brain Neoplasms; Combined Modality Therapy; Epilepsy; Female; Humans; Karnofsky Performance Status; Levetiracetam; Logistic Models; Male; Middle Aged; Neuropsychological Tests; Personal Autonomy; Piracetam; Quality of Life; Seizures; Surveys and Questionnaires; Young Adult

An 18-year-old woman presented with epileptic negative myoclonus (ENM) as her major seizure pattern for 4years. Her seizures were characterized by intermittent postural lapse of the right limbs for a period of hours to 2 days. Ictal electroencephalography (EEG)-electromyography showed a silent period that was time-locked to generalized spike-wave discharges. Video/EEG monitoring demonstrated marked improvement of ENM after oral administration of levetiracetam. Cranial magnetic resonance imaging was normal, but 2-deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography during frequent ENM showed hypometabolism in the left frontoparietal cortex. Technetium-99m-ethyl cysteinate dimer single-photon emission computed tomography revealed hyperperfusion over the left parietal cortex and putamen. Here, we document the short-term effects of levetiracetam in this subject with nearly isolated ENM and the neuroimaging results during ENM. Long-term follow-up is in progress to evaluate the clinical evolution and long-term effects of levetiracetam on ENM.

Topics: Adolescent; Anticonvulsants; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Piracetam; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon

Angelman syndrome (AS) commonly presents with epilepsy (>80%). The goal of this study was to examine the natural history and various treatments of epilepsy in AS in a large population.. A detailed electronic survey containing comprehensive questions regarding epilepsy in AS was conducted through the Angelman Syndrome Foundation.. There were responses from 461 family members of individuals with AS, of whom 86% had epilepsy (60% with multiple seizure types), the most common being atonic, generalized tonic-clonic, absence, and complex partial. Partial-onset seizures only were reported in 11% of those with epilepsy. Epilepsy was most common among those with maternal deletions and unknown subtypes, with catastrophic epilepsies present in only these two subtypes. These epilepsies were refractory to medication, with only 15% responding to the first antiepileptic drug (AED). The most commonly prescribed AED were valproic acid and clonazepam, but lamotrigine and levetiracetam appeared to have similar efficacy and tolerability.. This is the largest study to date assessing epilepsy in AS. Although epilepsy in AS is considered a generalized epilepsy, there was a high prevalence of partial seizures. There are few previous data regarding the use of newer AED in AS, and the results of this study suggest that these newer agents, specifically levetiracetam and lamotrigine, may have efficacy similar to that of valproic acid and clonazepam, and that they appear to have similar or better side-effect profiles. Nonpharmacologic therapies such as dietary therapy and vagus nerve stimulation (VNS) also suggest favorable efficacy and tolerability, although further studies are needed.

Topics: Adolescent; Adult; Angelman Syndrome; Anticonvulsants; Child; Child, Preschool; Clonazepam; Comorbidity; Drug Administration Schedule; Drug Resistance; Epilepsy; Epilepsy, Generalized; Female; Humans; Infant; Lamotrigine; Levetiracetam; Male; Middle Aged; Piracetam; Surveys and Questionnaires; Syndrome; Treatment Outcome; Triazines; Vagus Nerve Stimulation; Valproic Acid

Synaptic vesicle protein 2A (SV2A) constitutes a distinct binding site for an antiepileptic drug levetiracetam (Keppra). In the present study we characterized SV2A (+/-) heterozygous mice in several seizure models and tested if the anticonvulsant efficacy of levetiracetam is reduced in these mice.. Seizure thresholds of male SV2A (+/-) mice and their wild-type littermates were assessed in pilocarpine (i.p.), kainic acid (s.c.), pentylenetetrazol (i.v.), 6-Hz and maximal electroshock models. Kindling development was compared in amygdala and corneal kindling models. Ex vivo binding of levetiracetam to SV2A was also performed.. Long-term electroencephalography (EEG) monitoring and behavioral observations of SV2A (+/-) mice did not reveal any spontaneous seizure activity. However, a reduced seizure threshold of SV2A (+/-) mice was observed in pilocarpine, kainic acid, pentylenetetrazol, and 6-Hz models, but not in maximal electroshock seizure model. Accelerated epileptogenesis development was also demonstrated in amygdala and corneal kindling models. Anticonvulsant efficacy of levetiracetam, defined as its ability to increase seizure threshold for 6 Hz electrical stimulation, was significantly reduced (approx. 50%) in the SV2A (+/-) mice, consistently with reduced binding to SV2A in these mice. In contrast, valproate produced the same anticonvulsant effect in both SV2A (+/+) and SV2A (+/-) mice.. The present results evidence that SV2A is involved in mediation of the in vivo anticonvulsant activity of levetiracetam, in accordance with its previously proposed mechanism of action. Furthermore, the present data also indicate that even partial SV2A deficiency may lead to increased seizure vulnerability and accelerated epileptogenesis.

Topics: Amygdala; Animals; Anticonvulsants; Binding Sites; Brain; Disease Models, Animal; Electroshock; Epilepsy; Kainic Acid; Kindling, Neurologic; Levetiracetam; Male; Membrane Glycoproteins; Mice; Mice, Knockout; Nerve Tissue Proteins; Pentylenetetrazole; Pharmacogenetics; Phenotype; Piracetam

The aim of this study was to characterize the anticonvulsant effects of levetiracetam (LEV) in combination with the various antiepileptic drugs (clonazepam [CZP], oxcarbazepine [OXC], phenobarbital [PB], tiagabine [TGB], and valproate [VPA]), in the mouse 6 Hz psychomotor seizure model. Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3s stimulus duration) delivered via ocular electrodes and isobolographic analysis for parallel and non-parallel dose-response effects was used to characterize the consequent anticonvulsant interactions between the various drug combinations. Potential concurrent adverse-effect profiles of interactions between LEV and CZP, OXC, PB, TGB, and VPA at the fixed-ratio of 1:1 were evaluated in the chimney (motor performance), passive avoidance (long-term memory), and grip-strength (muscular strength) tests. LEV administered singly was associated with a dose-response relationship curve (DRRC) that was parallel to that for CZP and non-parallel to that for OXC, PB, TGB and VPA. With isobolography for parallel DRRCs, the combination of LEV with CZP at three fixed-ratios of 1:3, 1:1 and 3:1 was additive in nature. With isobolography for non-parallel DRRCs the combinations of LEV with OXC, TGB and VPA at the fixed-ratio of 1:1 were also additive. In contrast, the isobolography for non-parallel DRRCs revealed that the interaction for the combination of LEV with PB at the fixed-ratio of 1:1 was supra-additive (synergistic). None of the combinations were associated with any concurrent adverse effects with regards to motor coordination, long-term memory or muscular strength. LEV is associated with favorable anticonvulsant synergism with PB and is additive with regards to CZP, OXC, TGB and VPA in the mouse 6 Hz psychomotor seizure model.

Topics: Animals; Anticonvulsants; Clonazepam; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Drug Synergism; Drug Therapy, Combination; Electroshock; Epilepsy; Levetiracetam; Male; Mice; Phenobarbital; Piracetam; Psychomotor Performance; Valproic Acid

To determine the utility and tolerability of levetiracetam (LEV) compared to phenytoin (PHT) in preventing clinical seizures in patients with subarachnoid hemorrhage (SAH).. Utility and tolerability of PHT and LEV in patients with SAH were determined by the occurrence of breakthrough clinical seizures or adverse events necessitating a change of medication. Comparisons were performed with Chi-square tests.. All 176 patients were initially treated with PHT. No breakthrough clinical seizures occurred. In 70 (39.8%) patients, PHT was replaced with LEV due to adverse events including elevation of transaminases, thrombocytopenia, unexplained fever, rash, gastrointestinal disturbance, and worsening mental status. After switching to LEV, all adverse effects resolved except gastrointestinal disturbance and worsening mental status in 4 patients. Adverse events occurred more often in patients taking PHT.. In patients with SAH, LEV appears to have superior tolerability compared to PHT.

Topics: Adult; Aged; Anticonvulsants; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Subarachnoid Hemorrhage; Treatment Outcome

Topics: Anticonvulsants; Brain; Child; Cognition; Cognition Disorders; Developmental Disabilities; Electroencephalography; Epilepsy; Evoked Potentials; Humans; Levetiracetam; Neuropsychological Tests; Nootropic Agents; Piracetam; Recovery of Function

One hundred and thirty-eight patients (76 women and 62 men, aged from 16 to 65 years) with symptomatic partial epilepsy (n=128) and idiopathic generalized epilepsy (n=10) have been studied. All patients received keppra on regiments of monotherapy (n=30) and polytherapy (n=108). The study included evaluation of anamnesis, clinical and neurophysiological examination, routine EEG and/or video-EEG-monitoring, MRI of the brain, assessment of effectiveness, tolerability and quality of life (QUALIE-31, version 1). The period of observation was 1-4 years (on average 2,5 years). The high effectiveness and tolerability, good characteristics of therapy duration, the early appearance of clinical effect after the therapy has been started and positive cognitive effect are noted. The effectiveness, tolerance and clinical features of keppra treatment in different epileptic syndromes are analyzed.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Piracetam; Quality of Life; Syndrome; Treatment Outcome; Young Adult

Levetiracetam is one of the newer anti-epileptic medications, which is now widely used in the treatment of childhood epilepsy. Thrombocytopenia is not a well-known adverse effect of this medication. There have only been two adult case reports describing this feature as an adverse effect of levetiracetam. We describe this feature in a child. A six and half-year-old boy developed symptomatic epilepsy secondary to cerebral venous sinus thrombosis. He was treated with levetiracetam. He made a good recovery from his primary illness, but five weeks after he started taking levetiracetam, he presented with thrombocytopenia requiring platelet transfusion. Extensive investigations for known causes of thrombocytopenia were negative. Withdrawal of levetiracetam led to the resolution of thrombocytopenia. Levetiracetam-induced thrombocytopenia is a rare, but significant adverse effect.

Topics: Anticonvulsants; Child; Epilepsy; Humans; Levetiracetam; Male; Piracetam; Sinus Thrombosis, Intracranial; Thrombocytopenia

The objective of this study was to determine what contraindications to phenytoin exist in Emergency Department (ED) patients with a medical history of seizures. We conducted a retrospective chart review using ED medical records from 2005 at two network health care EDs. We identified potential patients through ICD-9 (International Classification of Diseases, Ninth Revision) codes, selected only adult patients with a prior documented history of seizures, and reviewed these charts. From 201 charts reviewed, the three most common antiepileptic drugs taken by patients were: phenytoin (38%), levetiracetam (17%), and valproic acid (15%). For absolute contraindications to phenytoin, 4.5% of seizure patients had a known hypersensitivity to phenytoin and 1.5% were pregnant; however, no pregnant patients were taking phenytoin and only 1 person with hypersensitivity to phenytoin was taking phenytoin. For relative contraindications, 6% of seizure patients had liver disease, 8% had kidney disease, 9% had alcohol use/dependence, and 16% had diabetes. However, 55% of those with liver disease, 44% with kidney disease, 77% with alcohol use/dependence, and 53% with diabetes were currently taking phenytoin. Very few seizure patients in the ED have absolute contraindications to the use of phenytoin, and most with absolute contraindications are taking other antiepileptic drugs. Conversely, a greater proportion of seizure patients have relative contraindications and many are continuing to use phenytoin.

Topics: Anticonvulsants; Contraindications; Emergency Service, Hospital; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Pregnancy; Retrospective Studies; Valproic Acid

Topics: Adult; Epilepsy; Female; Hemodiafiltration; Humans; Levetiracetam; Piracetam; Renal Dialysis; Valproic Acid

Levetiracetam, the alpha-ethyl analogue of the nootropic piracetam, is a widely used antiepileptic drug (AED) that provides protection against partial seizures and is also effective in the treatment of primary generalized seizure syndromes including juvenile myoclonic epilepsy. Levetiracetam was discovered in 1992 through screening in audiogenic seizure susceptible mice and, 3 years later, was reported to exhibit saturable, stereospecific binding in brain to a approximately 90 kDa protein, later identified as the ubiquitous synaptic vesicle glycoprotein SV2A. A large-scale screening effort to optimize binding affinity identified the 4-n-propyl analogue, brivaracetam, as having greater potency and a broadened spectrum of activity in animal seizure models. Recent phase II clinical trials demonstrating that brivaracetam is efficacious and well tolerated in the treatment of partial onset seizures have validated the strategy of the discovery programme. Brivaracetam is among the first clinically effective AEDs to be discovered by optimization of pharmacodynamic activity at a molecular target.

Topics: Animals; Anticonvulsants; Binding Sites; Disease Models, Animal; Drug Delivery Systems; Drug Design; Epilepsy; Humans; Levetiracetam; Piracetam

A rapid, selective, reliable, precise, accurate, and reproducible tandem mass spectrometric (MS-MS) method for the quantification of levetiracetam (LEV) in human plasma using adenosine as an internal standard (IS) has been developed and validated. The drug and IS were extracted by solid phase extraction (SPE) technique and analyzed on Symmetry((R)) C(18) column (5 microm, 3.9 mm x 50 mm) using a mobile phase of methanol-water-formic acid (97:03:0.25, v/v/v) at a flow rate of 0.2 ml/min. Quantitation was achieved using a positive electrospray ionization (ESI+) interface employing multiple reaction monitoring (MRM) mode at MRM transitions m/z 171>126 and m/z 268>136 for LEV and IS, respectively. The method was validated over the concentration range of 1.0-40 microg/ml (r>0.99) with a limit of quantification of 1.0 microg/ml (R.S.D.%; 4.1 and Bias%; -9.0 to + 11.0%). Intra- and inter-run precision of LEV assay at three concentrations ranged from 0.6 to 8.9% with accuracy (bias) varied from -4.0 to 8.6% indicating good precision and accuracy. Analytical recoveries of LEV and IS from spiked human plasma were in the range of 91.7-93.4% and 80.2-84.1%, respectively. Stability of LEV in human plasma samples at different conditions showed that the drug was stable under the studied conditions. Matrix effect study showed a lack of matrix effect on mass ions of LEV and IS. The described method compared well with the commercial HPLC-UV method of Chromsystem (r(2)=0.99). The suitability of the developed method for therapeutic drug monitoring was demonstrated by measuring LEV in human plasma samples of epileptic patients treated with LEV.

Topics: Adenosine; Anticonvulsants; Calibration; Chromatography, Liquid; Drug Monitoring; Drug Stability; Drug Storage; Epilepsy; Freezing; Humans; Levetiracetam; Metabolic Clearance Rate; Piracetam; Quality Control; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Solid Phase Extraction; Tandem Mass Spectrometry; Time Factors

Antiepileptic drugs are routinely given after craniotomy. Though phenytoin (PHT) is still the most commonly used agent, levetiracetam (LEV) is increasingly administered for this purpose. This retrospective study compared the use of LEV and PHT as monotherapy prophylaxis following supratentorial neurosurgery.. Patients receiving LEV monotherapy after supratentorial craniotomy were reviewed and compared to a control group of patients receiving PHT monotherapy.. One of 105 patients taking LEV and 9/210 patients taking PHT had seizures within 7 days of surgery (p = 0.17). Adverse drug reactions requiring change in therapy during hospitalization occurred in 1/105 patients taking LEV and 38/210 patients taking PHT (p < 0.001). Among patients followed for at least 12 months, 11/42 (26%) treated with LEV vs 42/117 (36%) treated with PHT developed epilepsy (p = 0.34); 64% remained on LEV, while 26% remained on PHT (p = 0.03).. Both levetiracetam (LEV) and phenytoin (PHT) were associated with a low risk of early postoperative seizures and a moderate risk of later epilepsy. LEV was associated with significantly fewer early adverse reactions than PHT and with a higher retention rate in patients who were followed for at least 1 year and developed epilepsy.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain; Brain Injuries; Drug Tolerance; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Neurosurgical Procedures; Phenytoin; Piracetam; Postoperative Complications; Retrospective Studies; Supratentorial Neoplasms; Treatment Outcome

Topics: Adult; Anticonvulsants; Brain; Epilepsy; Humans; Levetiracetam; Liver; Liver Failure, Acute; Liver Function Tests; Liver Transplantation; Male; Neurocysticercosis; Phenytoin; Piracetam; Treatment Outcome

In the treatment of seizures and epilepsy associated with central nervous system (CNS) infections, drug-drug interactions may significantly and unexpectedly impact outcome not only of epilepsy but also of the infectious disorders in both emergent and chronic care situations. A case is described in whom, the administration of the antimicrobial agent, meropenem presumably reduced serum valproate concentrations resulting in impaired seizure control. Other situations are reviewed in which interactions between antiepileptic drugs (AEDs) and antimicrobial agents may be of clinical significance. These include: (1) seizure management in individuals with neurocysticercosis, (2) management of seizures in patients with lobar tuberculomas, (3) management of seizures due to cerebral abscess, and (4) management of seizures in HIV-seropositive individuals.

Topics: Aged; Anti-Infective Agents; Anticonvulsants; Brain Abscess; Drug Interactions; Epilepsy; Female; Heart Block; HIV Infections; Humans; Levetiracetam; Neurocysticercosis; Piracetam; Valproic Acid

We present a simple, fast and validated method for the determination of the new generation antiepileptic drug (AED) levetiracetam (LEV) in plasma of patients with epilepsy using high performance liquid chromatography (HPLC) with UV detection. Plasma sample (500 microL) pretreatment was based on simple deproteinization by methanol spiked with the internal standard (I.S.). HPLC analysis was carried out on a Synergi 4-microm Hydro-RP, 150 mm x 4 mm I.D. column. The mobile phase was a mixture of potassium dihydrogen phosphate buffer (50 mM, pH 4.5) and acetonitrile (94:6, v/v) at an isocratic flow rate of 1.5 mL/min. The UV detector was set at 205 nm. Calibration curves were linear (mean correlation coefficient=0.999) over a range of 4-80 microg/mL. The quantitation limit was 2 microg/mL and the absolute recovery was >90% for LEV and the I.S. Both intra and interassay precision and accuracy were lower than 7.5%. The chromatographic run lasted 13 min. The present procedure omitting expensive solid phase or time-consuming liquid-liquid extraction and drying steps is cheaper, faster and simpler than mostly published analytical methods for levetiracetam. Applied to a large population of patients with epilepsy this assay proved very practical in our therapeutic drug monitoring setting (TDM).

Topics: Chromatography, High Pressure Liquid; Epilepsy; Humans; Levetiracetam; Piracetam; Reproducibility of Results; Sensitivity and Specificity

The authors report a patient with Lennox-Gastaut syndrome who was a fraternal twin. The twins encountered myoclonic seizures at the age of 4 years, but the seizures in the other patient were controlled very quickly without intellectual development damage. With the disease evolving, other characteristic seizures of Lennox-Gastaut syndrome appeared and failed to be controlled by multiple antiepileptic drugs, so levetiracetam was added on. At this time, frequent partial seizures from the left occipital and posterior temporal regions occurred, which always intermixed with atypical absence seizures in a single ictal event. To control the status epilepticus, levetiracetam was withdrawn immediately, and clonazepam, midazolam, and corticotropin in turn were used. The partial seizures were gradually alleviated. The results obtained in this study suggest that there might be some correlative mechanisms between partial seizures and atypical absence seizures in a single event. There is a temporal relationship between the occurrence of partial seizures and the introduction of levetiracetam.

Topics: Adolescent; Epilepsy; Epilepsy, Absence; Humans; Intellectual Disability; Levetiracetam; Male; Piracetam

Efficacy of keppra was studied in 52 patients, aged 10-55 years, after the surgical treatment of gliomas of the brain hemispheres. The medication was used (in combination with other anticonvulsant drugs and hormones) during the radiotherapy. In 30 (57,8%) of cases epileptic seizures were before the surgery. In 22 (42,2%) of patients they developed during the radiotherapy. Keppra was used in the regiment of "urgent aid" in relation to the appearance of seizures and increase of their frequency during the radiotherapy. Doses of keppra varied from 500 to 2500 mg (30-50 mg/kg/day) in a single dose. Then patients received the drug 2 times daily under the control of clinical and EEG presentations. A clinical effect, including the decrease of seizures frequency by 48,3% (p<0,001), positive changes of quality of seizures (more simple structure, reduced time of seizures), was observed for the first 24 h and in future the state of patients was stable. All patients have completed the course of radiotherapy. The choice of dose was depended on age, body mass and dynamics of clinical and EEG data.

Topics: Administration, Oral; Adolescent; Adult; Anticonvulsants; Brain Neoplasms; Child; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Glioma; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Piracetam; Postoperative Period; Treatment Outcome; Young Adult

The purpose of the study was to assess changes in cognitive functions and quality of life in patients with epilepsy over one year of treatment with levetiracetam (LEV) as add-on therapy.. Thirty-two patients (16 women; 16 men) who received LEV as an add-on treatment were included, and 27 completed the one-year follow-up period. Extensive neuropsychological assessments, together with a quality-of-life questionnaire were administered at baseline and at one, three, six and twelve months after beginning the add-on treatment. Patients received LEV starting with 500 mg/day in the first week, increasing by a further 500 mg/day per week until a target dose of 2 000 mg/day was reached by the end of the first month.. At the one-year follow-up, a significant improvement was observed in measurements of prospective memory, working memory, motor functions, verbal fluency, attention and quality of life. Performance for neuropsychological and quality-of-life tests was not affected by external variables such as seizure reduction or changes in previous anti-epileptic treatment. Slight changes between patients were observed, but these were not clinically significant.The limited sample size and the lack of a control group should be mentioned as limitations of the study. No control group was evaluated as in our clinical practice it was difficult to establish a comparable group of patients. Changes in the different variables were assessed by comparing baseline information with follow-up results.Despite the study limitations, we consider that the one-year treatment period provides valuable information regarding the drug's long-term effects in this setting.. Results of the present study suggest that long-term LEV treatment as add-on therapy does not interfere with cognitive function and improves quality of life.

Topics: Adult; Aged; Anticonvulsants; Cognition; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Piracetam; Prospective Studies; Quality of Life; Seizures; Young Adult

Topics: Anticonvulsants; Drug Approval; Drug Labeling; Epilepsy; Humans; Levetiracetam; Piracetam; United States; United States Food and Drug Administration

To evaluate the efficacy and tolerability of levetiracetam (LEV) in the treatment of epilepsy as a monotherapy in children.. Thirty-two children with epilepsy (age ranged from 8 months to 12 years) and who had received LEV monotherapy were investigated by a self-controlled and open-label research. LEV was administered at a dose of 10 mg/kg.d, and increased by 10 mg/kg.d per week till to the target dose (20-40 mg/kg.d), with a mean dose of 35 mg/kg.d.. Thirty-one patients were followed up for more than three months. Twenty-five patients (80.6%) had at least 50% reduction in seizures, 22 cases (70.9%) became seizure-free, and LEV therapy was discontinued in 5 patients (16.1%) due to either an inadequate seizure control or aggravated seizures. The therapy-related adverse events included mood and behavioral changes (6/31, 19.4%), asthenia (2/31, 6.5%), somnolence (2/31, 6.5%), and skin rashes (1/31, 3.2%). The adverse effects were spontaneously disappeared or disappeared after reducing the LEV dose.. LEV monotherapy is effective and safe for the control of partial and generalized tonic-clonic seizures in children with epilepsy. LEV appears to be a promising anti-epileptic drug for monotherapy in children with epilepsy.

Topics: Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Follow-Up Studies; Humans; Infant; Levetiracetam; Male; Piracetam

Twenty-two dogs with idiopathic epilepsy which were pharmacoresistant to phenobarbitone and bromide were treated with levetiracetam as an add-on medication. Records of eight dogs were used retrospectively to determine a safe, efficient levetiracetam dosage. Fourteen dogs were entered into a prospective, open label, non-comparative study. After 2 months of levetiracetam oral treatment (10 mg/kg TID), 8/14 dogs responded significantly to the treatment and seizure frequency was reduced by 50%. In dogs that remained refractory, the dosage was increased to 20 mg/kg TID for 2 months. One further dog responded to levetiracetam treatment. Levetiracetam responders had a significant decrease in seizure frequency of 77% (7.9+/-5.2 to 1.8+/-1.7 seizures/month) and a decrease in seizure days per month of 68% (3.8+/-1.7 to 1.2+/-1.1 seizure days/month). However, 6/9 responders experienced an increase in seizure frequency and seizure days after 4-8 months continuing with the levetiracetam treatment at the last effective dosage. Levetiracetam was well tolerated by all dogs and sedation was the only side-effect reported in just one of the 14 dogs.

Topics: Animals; Anticonvulsants; Bromides; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsy; Female; Levetiracetam; Male; Phenobarbital; Piracetam; Retrospective Studies; Treatment Outcome

Two of the most commonly prescribed new antiepileptic drugs as add-on therapy for patients with chronic refractory epilepsies are topiramate and levetiracetam. In regulatory trials, both drugs were characterized as very promising new antiepileptic drugs. However, results from these highly controlled short-term clinical trials cannot simply be extrapolated to everyday clinical practice, also because head-to-head comparisons are lacking. Therefore, results from long-term open label observational studies that compare two or more new AEDs are crucial to determine the long-term performance of competing new antiepileptic drugs in clinical practice.. We analyzed all patients referred to a tertiary epilepsy centre who had been treated with topiramate from the introduction of the drug in spring 1993 up to a final assessment point mid-2002 and all patients who had been treated with LEV in the same centre from the introduction of the drug in early 2001 up to a final assessment point end-2003 using a medical information system.. Three hundred and one patients were included for levetiracetam and 429 patients for TPM. Retention rate after 1 year was 65.6% for LEV-treated patients and 51.7% for TPM-treated patients (p=0.0015). Similarly, retention rates for LEV were higher at the 24-month mark: 45.8% of LEV-treated patients and 38.3% of TPM-treated patients were still continuing treatment (p=0.0046). Adverse events led to drug discontinuation in 21.9% of TPM-treated patients compared to 6.0% of LEV-treated patients (p<0.001). The number of patients discontinuing treatment because of lack of efficacy was similar for both groups. Seizure freedom rates varied between 11.6 and 20.0% for TPM and between 11.1 and 14.3% for LEV per 6-months interval. Several important AED specific adverse events leading to drug discontinuation were identified, including neurocognitive side effects from TPM and mood disorders from LEV.. The retention rate for LEV is significantly higher than for TPM. LEV had a more favourable side effect profile than TPM with comparable efficacy. Patients on TPM discontinued treatment mainly because of neurocognitive side effects. In the treatment with LEV, the effects on mood must not be underestimated.

Topics: Adolescent; Adult; Age of Onset; Aged; Anticonvulsants; Child; Child, Preschool; Cognition; Epilepsy; Female; Fructose; Humans; Infant; Levetiracetam; Long-Term Care; Magnetic Resonance Imaging; Male; Middle Aged; Piracetam; Tomography, X-Ray Computed; Topiramate

Levetiracetam is considered a "weight-neutral" drug. We report 19 cases of significant weight loss associated with levetiracetam at a dose ranging from 500 to 2000 mg/day.. The population was divided into two groups. Group 1 includes patients in whom levetiracetam was the only possible cause of weight loss and Group 2 those in whom other factors may have played a role. Similar cases reported by the French national drug safety center were added (Group 3).. Group 1 included 9 females and 3 males (weight loss ranging from 8.1% to 28.6%). Three patients had levetiracetam in monotherapy. Prior levetiracetam only three were overweight. One patient was hospitalized for a thorough assessment of weight loss. Seven patients reported reduced caloric intake due to decreased pleasure with food. The other five did not report any changes in feeding behavior. Group 2 included seven females with a weight loss ranging from 10% to 26.6%. One patient was on topiramate since two years prior to levetiracetam. Weight loss started with the introduction of levetiracetam. In 4 patients, there was a decreased dosage or cessation of a previous drug known to produce weight gain in some cases simultaneously to the introduction of levetiracetam, but in two of these patients these drugs had not produced any weight gain. Group 3 included only two patients (weight loss: 7 and 20 kg).. This study provides evidence that levetiracetam can cause significant weight loss. Women are at higher risk while initial weight is not a factor.

Topics: Adult; Age of Onset; Anticonvulsants; Body Mass Index; Epilepsy; Feeding Behavior; Female; Humans; Levetiracetam; Male; Middle Aged; Obesity; Overweight; Piracetam; Risk Factors; Sex Factors; Weight Loss

We report on the manifestation of a levetiracetam (LEV)-induced encephalopathy.. A 28-year-old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high-amplitude discharges.. Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased.

Topics: Adult; Anticonvulsants; Brain Diseases; Electroencephalography; Epilepsy; Humans; Levetiracetam; Male; Piracetam; Valproic Acid

To investigate changes in levetiracetam (LEV) serum concentration/dose ratio (C/D-ratio) in relation to pregnancy.. Altogether 21 consecutive pregnancies in 20 women with epilepsy receiving LEV during gestation were studied retrospectively. The main target variable was the C/D-ratio before and during pregnancy, and in the post partum period. Secondary target variables were changes in LEV dose, concomitant use of other antiepileptic drugs and seizure frequency. Student's paired t-test and two-sample t-test for independent samples were used to test for statistically significant changes in C/D-ratio means.. Mean C/D-ratio in the third trimester was 50% of the mean C/D-ratio at baseline (p<0.001, n=11). Baseline levels were reached within the first weeks after pregnancy. The interindividual variability was pronounced.. Serum concentrations of LEV declined significantly in the third trimester of pregnancy and increased rapidly after delivery.

Topics: Adult; Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Piracetam; Pregnancy; Retrospective Studies; Time Factors

Topics: Acute Disease; Adult; Dose-Response Relationship, Drug; Epilepsy; Epilepsy, Complex Partial; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Piracetam

Cerebral cavernous malformations (CCM) are vascular malformations causing seizures and cerebral hemorrhages. They occur in sporadic and familial forms. Familial cases are associated with a high frequency of multiple lesions, which are less frequently associated with sporadic cases.. We report a 46-year-old woman presenting with epilepsy with multiple cerebral cavernomatosis on MRI. Because she had had a previous liver transplantation operation, and received immunosuppressants, she was not advised to have a brain operation. However, she had to be operated as a result of a bleeding in one of her cerebral cavernomas. The histologic diagnosis was cavernoma. She has been seizure free after the operation with levetiracetam therapy for the last 17 months. She had no positive family history for both epilepsy and cavernomatosis.. When multiple cerebral cavernomatosis are identified in a patient, a detailed neurologic family history should be sought despite the possibility of its being a sporadic case. Our main intention is to present a patient who is surgically controversial and to point out the importance of genetic heredity.

Topics: Adult; Anticonvulsants; Brain; Cerebral Hemorrhage; Chromosomes, Human, Pair 7; Epilepsy; Family Health; Female; Genetic Predisposition to Disease; Hemangioma, Cavernous, Central Nervous System; Humans; KRIT1 Protein; Levetiracetam; Magnetic Resonance Imaging; Male; Microtubule-Associated Proteins; Middle Aged; Mutation; Neoplasms, Multiple Primary; Neurosurgical Procedures; Piracetam; Proto-Oncogene Proteins; Tomography, X-Ray Computed; Treatment Outcome

To report our experience with rapid titration of levetiracetam regimens in children and adolescents who were unresponsive to or intolerant of other antiepileptic drugs.. A retrospective chart review was performed to identify patients with childhood epilepsy who underwent a rapid titration to full doses of levetiracetam in 2 weeks or less. Data regarding demographics, disease characteristics, previous use of antiepileptics, levetiracetam dosage titration schedule, and clinical outcomes were collected and analyzed.. Eight children (seven girls, one boy) aged 19 months-17 years were identified. The levetiracetam dosage was titrated to full maintenance doses over 2-14 days (mean 10 days). All patients demonstrated greater than 50% reduction in seizure frequency, with six patients (75%) becoming seizure free. Only one patient experienced a clinically significant adverse event.. Rapid dosage titration of levetiracetam is feasible and well tolerated in children who require rapid escalation to therapeutic doses.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Demography; Drug Administration Schedule; Epilepsy; Female; Humans; Infant; Levetiracetam; Magnetic Resonance Imaging; Male; Piracetam; Retrospective Studies; Treatment Outcome

New antiepileptic drugs (AEDs), introduced since 1993, provide more diverse options in the treatment of epilepsy. Despite the equivalent efficacy and better tolerability of these drugs, more than 25% of patients remain refractory to treatment. Moreover, the issues for pediatric patients are different from those for adults, and have not been addressed in the development and application of the new AEDs. Recently published evidence-based treatment guidelines have helped physicians to choose the most reasonable AED, although they cannot fully endorse new AEDs because of the lack of well-designed, randomized controlled trials. We review the mechanisms of action, pharmacokinetic properties, adverse reactions, efficacy, and tolerability of eight new AEDs (felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin, and zonisamide), focusing on currently available treatment guidelines and expert opinions regarding pediatric epilepsy.

Topics: Amines; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Cyclohexanecarboxylic Acids; Epilepsy; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Levetiracetam; Pediatrics; Phenylcarbamates; Piracetam; Practice Guidelines as Topic; Propylene Glycols; Topiramate; Triazines; Vigabatrin

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

To characterize levetiracetam pharmacokinetics, identify significant covariate relationships and identify doses in children that achieve blood concentrations similar to those observed in adults.. Nonlinear mixed-effects modelling was used to analyse pooled data collected from 228 children with epilepsy aged 3 months to 18 years in five trials of adjunctive levetiracetam therapy. Simulations were used to identify dosing regimens achieving levetiracetam steady-state peak and trough plasma concentrations similar to those attained in adults receiving the recommended starting dose for adjunctive therapy (500 mg twice daily). The covariates considered for inclusion in the base model were age, bodyweight, gender, race, body surface area (BSA), body mass index (BMI), creatinine clearance (CL(CR)), levetiracetam dose, concomitant antiepileptic drug (AED) by category (neutral, enzyme inducer, inhibitor, combination of inducer and inhibitor), and benzodiazepines.. A one-compartment model with first-order absorption and elimination best characterized the data. The following significant covariates were identified: (i) age on the absorption rate constant (k(a)); (ii) bodyweight, dose, CL(CR) and concomitant enzyme-inducing AED on plasma oral clearance (CL/F); and (iii) bodyweight on the apparent volume of distribution after oral administration (V(d)/F). The main explanatory covariates were age on k(a), bodyweight on CL/F and V(d)/F, and enzyme-inducing AED on CL/F, of which bodyweight was the most influential covariate. Dosing can be carried out with either 10 mg/kg of oral solution twice daily in children weighing <50 kg and a 500-mg tablet twice daily in those weighing >50 kg or, when patients favour a solid formulation, 10 mg/kg of oral solution twice daily in children weighing <20 kg, a 250-mg tablet twice daily in those weighing 20-40 kg, and a 500-mg tablet twice daily in those weighing >40 kg. All of these doses achieved steady-state peak and trough plasma concentrations similar to those observed in adults following the recommended starting dose for adjunctive therapy (500 mg twice daily).. The most influential covariate of levetiracetam pharmacokinetics in children is bodyweight. A starting dose of levetiracetam 10 mg/kg twice daily ensures the same exposure in children as does 500 mg twice daily in adults.

Topics: Adolescent; Algorithms; Anticonvulsants; Child; Child, Preschool; Databases, Factual; Epilepsy; Humans; Infant; Levetiracetam; Nonlinear Dynamics; Piracetam; Population; Retrospective Studies

Incidental paradoxical antiepileptic effect of levetiracetam has been described. The aim of the present study was to identify the epilepsy patients at risk.. We performed a retrospective analysis in 207 patients treated with levetiracetam. This entailed evaluation of patient notes and patient interviews. A paradoxical effect was defined as an increased seizure frequency or the experience of more severe seizures including generalized tonic-clonic seizures (GTCS) within 1 month after starting levetiracetam (LEV).. Thirty patients (14%) experienced a paradoxical effect. Eight of them (4%) developed de novo GTCS. We could not demonstrate any association between the paradoxical effect of levetiracetam and type of epilepsy or the antiepileptic comedication used. However we found that the paradoxical effect developed preferentially (p < 0.001) in mentally retarded patients.. Because there is an increased risk of worsening epilepsy when starting levetiracetam treatment of mentally retarded epileptic patients, there is a need for caution and close observation during the first weeks of therapy.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Disorders of Excessive Somnolence; Dizziness; Drug Interactions; Epilepsy; Female; Humans; Intellectual Disability; Irritable Mood; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Risk Factors

Screening of 12,000 compounds for binding affinity to the synaptic vesicle protein 2A (SV2A), identified a high-affinity pyrrolidone derivative, brivaracetam (ucb 34714). This study examined its pharmacological profile in various in vitro and in vivo models of seizures and epilepsy, to evaluate its potential as a new antiepileptic drug.. The effects of brivaracetam and levetiracetam on epileptiform activity and seizure expression were examined in rat hippocampal slices, corneally kindled mice, audiogenic seizure-susceptible mice, maximal electroshock and pentylenetetrazol seizures in mice, hippocampal-kindled rats, amygdala-kindled rats and genetic absence epilepsy rats.. Brivaracetam and levetiracetam reduced epileptiform responses in rat hippocampal slices, brivaracetam being most potent. Brivaracetam also differed from levetiracetam by its ability to protect against seizures in normal mice induced by a maximal electroshock or maximal dose of pentylenetetrazol. In corneally kindled mice and hippocampal-kindled rats, brivaracetam induced potent protection against secondarily generalized motor seizures and showed anti-kindling properties superior to levetiracetam. In amygdala-kindled rats, brivaracetam induced a significant suppression in motor-seizure severity and, contrary to levetiracetam, reduced the after-discharge at a higher dose. Audiogenic seizure-susceptible mice were protected more potently against the expression of clonic convulsions by brivaracetam than by levetiracetam. Brivaracetam induced a more complete suppression of spontaneous spike-and-wave discharges in genetic absence epilepsy rats than levetiracetam.. Brivaracetam has higher potency and efficacy than levetiracetam as an anti-seizure and anti-epileptogenic agent in various experimental models of epilepsy, and a wide therapeutic index.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Electroshock; Epilepsy; Hippocampus; Levetiracetam; Ligands; Male; Membrane Glycoproteins; Mice; Nerve Tissue Proteins; Piracetam; Pyrrolidinones; Rats; Rats, Sprague-Dawley; Seizures

Levetiracetam (LEV) is a novel antiepileptic drug (AED) that has recently obtained marketing authorisation for use in children. The purpose of this study was to assess the efficacy, tolerability and retention rate of LEV in children with refractory epilepsies. It is a retrospective multicentre observational study reporting the use of LEV in 200 children, aged 0.3-19 years (median 9-years-old) over a 4-year period. All of the patients included in the study had refractory epilepsy with a median age of onset of epilepsy of 3 years (range 0-13 years). The 38% had failed and withdrawn 3 or more AEDs previously and 24% were taking at least 2 other AEDs in addition to LEV. The 47% had focal, and 58% had symptomatic epilepsies. The LEV dose ranged from 8 to 100 mg/kg/day (mean 39 mg/kg). The study comprised 215 person years of LEV exposure.. LEV was well tolerated with a retention rate of 49% at 1 year. No serious adverse events were reported with possibly related adverse events reported in only 24% of patients (mainly emotional or behavioural changes). At more than 2, 6 and 12 months, worthwhile improvement (>50% seizure reduction) was noted in 60, 40 and 32%, including seizure freedom in 14, 14 and 5%, respectively.. Our results confirm the efficacy and tolerability of LEV in children with refractory epilepsies and demonstrate good response and retention rates at 12 months. It represents the largest cohort of paediatric patients published so far on LEV with a 1-year follow-up.

Topics: Adolescent; Adolescent Behavior; Anticonvulsants; Child; Child Behavior; Child, Preschool; Drug Therapy, Combination; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Outcome Assessment, Health Care; Patient Compliance; Patient Dropouts; Piracetam; Retrospective Studies

Polytherapy with two or more antiepileptic drugs (AEDs) is generally required for approximately 30% of patients with epilepsy, who do not respond satisfactorily to monotherapy. The potential usefulness of AED combinations, producing synergistic anticonvulsant efficacy and minimal adverse effects, is therefore of significant importance. The present study sought to ascertain the potential usefulness of levetiracetam (LEV) and felbamate (FBM) in combination in the mouse maximal electroshock (MES)-induced seizure model.. The anticonvulsant interaction profile between LEV and FBM in the mouse MES-induced seizure model was determined using type II isobolographic analysis. Acute adverse effects (motor performance) were ascertained by use of the chimney test. LEV and FBM brain concentrations were measured by HPLC in order to determine any pharmacokinetic contribution to the observed antiseizure effect.. LEV in combination with FBM, at the fixed ratios of 1:2, 1:1, 2:1, and 4:1, were supraadditive, whereas at the fixed ratio of 1:4, additivity was observed in the mouse MES model. Furthermore, none of the investigated combinations altered motor performance in the chimney test. Brain FBM concentrations were unaffected by concomitant LEV administration. In contrast, FBM significantly increased LEV brain concentrations.. LEV in combination with FBM was associated with pharmacodynamic supraadditivity in the MES test. However, this anticonvulsant supraadditivity was associated with a concurrent increase in brain LEV concentrations indicating a pharmacokinetic contribution to the observed pharmacodynamic interaction between LEV and FBM.

Topics: Animals; Anticonvulsants; Behavior, Animal; Brain; Chromatography, High Pressure Liquid; Disease Models, Animal; Drug Synergism; Electroshock; Epilepsy; Felbamate; Humans; Levetiracetam; Male; Mice; Motor Activity; Phenylcarbamates; Piracetam; Propylene Glycols; Seizures

For the treatment of patients with chronic refractory epilepsies, development of new antiepileptic drugs is crucial. Three regulatory trials have demonstrated that add-on levetiracetam is efficacious in patients with localization-related epilepsy. However, results from these highly controlled short-term clinical trials cannot simply be extrapolated to everyday clinical practice. Therefore, more information is needed about the long-term profile of a new antiepileptic drug in clinical practice.. We analyzed all patients who had been treated with levetiracetam in the Epilepsy Centre Kempenhaeghe from the introduction of the drug in early 2001 up to a final assessment point, at the end of 2003, using a medical information system.. In total, 301 patients were included. One hundred thirty-eight patients (45.8%) discontinued LEV treatment during the 24-month follow-up period. Reasons for discontinuation were lack of efficacy in 15.9% of patients, adverse events in 6.0% of patients, and a combination of lack of efficacy and adverse events in 16.3% of patients. By Kaplan-Meier survival analysis, the continuation rate was 65.6% after 1 year and 45.8% after 2 years. About 15% of patients in this highly refractory group had a 3-month remission, whereas 10% of patients became seizure-free for longer periods. The most frequently reported side effects at the time of discontinuation were mood disorders, tiredness, and sleepiness. Variables predicting (dis)continuation of levetiracetam treatment could not be identified.. Levetiracetam is a new antiepileptic drug that appears to be a useful add-on treatment in patients with refractory epilepsy. Its side effect profile is mild, with mood disorders being the most dominant adverse event.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Child, Preschool; Drug Resistance; Drug Therapy, Combination; Epilepsy; Female; Follow-Up Studies; Humans; Infant; Levetiracetam; Male; Mental Disorders; Middle Aged; Piracetam; Referral and Consultation; Seizures; Survival Analysis

The aim of this multicentric, retrospective, and uncontrolled study was to evaluate the efficacy and safety of levetiracetam (LEV) in 81 children younger than 4 years with refractory epilepsy. At an average follow-up period of 9 months, LEV administration was found to be effective in 30% of patients (responders showing more than a 50% decrease in seizure frequency) of whom 10 (12%) became seizure free. This efficacy was observed for focal (46%) as well as for generalized seizures (42%). In addition, in a group of 48 patients, we compared the initial efficacy (evaluated at an average of 3 months of follow-up) and the retention at a mean of 12 months of LEV, with regard to loss of efficacy (defined as the return to the baseline seizure frequency). Twenty-two patients (46%) were initial responders. After a minimum of 12 months of follow-up, 9 of 48 patients (19%) maintained the improvement, 4 (8%) of whom remained seizure free. A loss of efficacy was observed in 13 of the initial responders (59%). Maintained LEV efficacy was noted in patients with focal epilepsy and West syndrome. LEV was well tolerated. Adverse events were seen in 18 (34%) patients. The main side effects were drowsiness and nervousness. Adverse events were either tolerable or resolved in time with dosage reduction or discontinuation of the drug. We conclude that LEV is safe and effective for a wide range of epileptic seizures and epilepsy syndromes and, therefore, represents a valid therapeutic option in infants and young children affected by epilepsy.

Topics: Anticonvulsants; Child, Preschool; Epilepsy; Female; Humans; Infant; Infant, Newborn; Levetiracetam; Male; Piracetam; Retrospective Studies

To study pharmacokinetics of levetiracetam (LEV) during pregnancy, delivery, lactation, and in the neonatal period.. Fourteen women with epilepsy receiving LEV treatment during pregnancy and lactation contributed with 15 pregnancies to this prospective study in which LEV concentrations in plasma and breast milk were determined. Trough maternal plasma samples were collected each trimester, and at baseline after delivery. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from newborns during 2 days after delivery. LEV concentration was also determined in breast milk and in plasma collected from 11 of the mothers and their suckling infants after birth.. The umbilical cord/maternal plasma concentration ratios ranged from 0.56-2.0 (mean 1.15, n=13). LEV plasma concentrations in the neonates declined with an estimated half-life of 18 h (n=13). The mean milk/maternal plasma concentration ratio was 1.05 (range, 0.78-1.55, n=11). The infant dose of LEV was estimated to 2.4 mg/kg/day, equivalent to 7.9% of the weight-normalized maternal dose. Plasma concentrations in breastfed were approximately 13% of the mother's plasma levels. Maternal plasma concentrations during third trimester were only 40% of baseline concentrations outside pregnancy (p<0.001, n=7). Our observations suggest considerable transplacental transport of LEV and fairly slow elimination in the neonate. Plasma concentrations of LEV in nursed infants are low despite an extensive transfer of LEV into breast milk. Pregnancy appears to enhance the elimination of LEV resulting in marked decline in plasma concentration, which suggests that therapeutic monitoring may be of value.

Topics: Anticonvulsants; Breast Feeding; Delivery, Obstetric; Epilepsy; Female; Fetal Blood; Half-Life; Humans; Infant, Newborn; Lactation; Levetiracetam; Maternal-Fetal Exchange; Milk, Human; Piracetam; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Prospective Studies; Puerperal Disorders

Topics: Acoustic Stimulation; Anticonvulsants; Brain Stem; Dose-Response Relationship, Drug; Epilepsy; Female; Humans; Levetiracetam; Middle Aged; Muscle, Skeletal; Neural Pathways; Noise; Piracetam; Reflex, Abnormal; Reflex, Startle; Treatment Outcome

Levetiracetam (LEV) and topiramate (TPM) are considered highly effective novel antiepileptic drugs (AEDs) in the treatment of focal epilepsies. To explore potential side effects, this study investigated their influence on cognitive functions comparatively by means of a standardized neuropsychological test battery assessing several cognitive domains. In this observational study, cognitive changes were explored in 30 consecutively recruited patients with focal epilepsy treated with LEV and in 21 patients treated with TPM, comparing functions assessed prior to gradual initiation and after reaching steady state of the individual target dosage. Before titration, patient groups did not differ significantly with respect to cognitive performance. Whereas the LEV group manifested no change in cognitive performance after AED titration, the TPM group worsened in the cognitive domains of cognitive speed and verbal fluency, as well as short-term memory. These findings suggest that TPM, unlike LEV, may impair frontal lobe functions. The lack of cognitive side effects related to LEV treatment may be relevant for treatment decisions.

Topics: Adult; Anticonvulsants; Case-Control Studies; Cognition; Electroencephalography; Epilepsy; Female; Fructose; Humans; Intelligence; Levetiracetam; Male; Memory, Short-Term; Middle Aged; Multivariate Analysis; Neuropsychological Tests; Piracetam; Topiramate; Visual Perception

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

To assess the single-dose pharmacokinetics of levetiracetam and its major metabolite ucb L057 in infants and young children with epilepsy.. Eligible patients with a stable regimen of antiepileptic medications received a single oral dose of levetiracetam 20 mg/kg administered as a 10% oral solution followed by a 24-hour pharmacokinetic evaluation.. Thirteen subjects (age 2.3-46.2 months) enrolled and received levetiracetam; 12 provided evaluable pharmacokinetic data. Levetiracetam was rapidly absorbed and reached peak plasma concentration (t(max)) 1.4 +/- 0.9 hours after dosing. The mean half-life (t(1/2)) of levetiracetam was 5.3 +/- 1.3 hours, and the apparent clearance was 1.46 +/- 0.42 mL/min/kg. Graphical differences were observed among three age subgroups (1 to <6 months, 6 to <24 months, and 24 to <48 months); however, statistical analysis was limited due to each subgroup's small sample size. No significant gender differences were detected. Treatment-emergent adverse events were seen in three patients (23.1%) but were not considered to be related to levetiracetam.. The mean t(1/2) of levetiracetam was shorter and its apparent clearance was more rapid for infants and young children than that previously reported for adults. When determining dosage, age-dependent drug clearance should be considered; these findings suggest that a larger dose of levetiracetam (corrected for body weight) needs to be considered for infants and young children with epilepsy than that given to adults with epilepsy. A single dose of levetiracetam was well tolerated in this study population.

Topics: Administration, Oral; Age Factors; Anticonvulsants; Child, Preschool; Dose-Response Relationship, Drug; Epilepsy; Female; Half-Life; Humans; Infant; Levetiracetam; Male; Piracetam

Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Female; Humans; Intellectual Disability; Levetiracetam; Male; Piracetam

There is little literature on a possible link between the use of antiepileptic drugs (AEDs) and the occurrence of suicidal ideation. Nevertheless, its occurrence needs to be promptly recognized because it may trigger suicidal attempts. We retrospectively evaluated a case registry of 517 patients taking levetiracetam (LEV) for suicidal ideation, looking at possible clinical variables involved. Suicidal ideation was reported by four patients (0.7%). All cases occurred in the context of a mood disorder presenting early during LEV therapy. Psychopathological characteristics of suicidal ideation were consistent in all subjects and similar to some features that are described as typical of the so-called interictal dysphoric disorder of epilepsy.

Topics: Adult; Affective Symptoms; Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Male; Mood Disorders; Piracetam; Retrospective Studies; Self-Injurious Behavior; Suicide, Attempted

To compare pharmacokinetics and tolerability of levetiracetam (LEV) in older versus younger adults.. As part of the Columbia Antiepileptic Drug Database, we retrospectively studied the pharmacokinetics and tolerability of LEV in patients who had been seen as an outpatient at our center during a 4-year period. We compared apparent clearance (CL) of LEV in the youngest (16-31 years; n=151) and oldest (55-88 years; n=157) quartile of 629 adult outpatients who had taken LEV. We also analyzed the frequency of adverse effects leading to dose change or discontinuation ("intolerability") and specific adverse effects in the younger versus older adults. One-year retention was determined for younger and older adults newly started on LEV at our center.. Mean LEV CL differed significantly between older (46.5 ml/h/kg) and younger adults (78.3 ml/h/kg). On average, older patients had a 40% lower LEV CL than younger patients. Comedication with an enzyme-inducing antiepileptic drug (EIAED; mostly carbamazepine) was associated with a 24% higher clearance of LEV compared to those who were not on EIAEDs. This difference was 37% in a subgroup of patients whose LEV CL was compared while they were on and off EIAEDs. Stepwise linear regression identified younger age and comedication with an EIAED as significant predictors of increased LEV CL. A total of 34.3% of the 629 patients (31.7% of younger vs. 40.7% of older patients; p=0.16) reported intolerability to LEV on at least one occasion. This difference in tolerability reached significance in the group of patients newly started on LEV (26.3% vs. 41.0%; p=0.017). Drowsiness and psychiatric/behavioral side effects were the most common adverse effects associated with LEV use in both age groups. One-year retention was 72% in the older group vs. 54% in the younger group (not significant).. Older adults have lower CL than younger adults and require a mean 40% lower dose of LEV to achieve the same serum level. Comedication with an EIAED increases LEV CL by 24-37%. Younger adults tolerate LEV better than older adults, but 1-year retention was (nonsignificantly) higher in the older group.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Ambulatory Care; Anticonvulsants; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enzyme Induction; Epilepsy; Female; Humans; Levetiracetam; Male; Metabolic Clearance Rate; Middle Aged; Piracetam; Retrospective Studies

Levetiracetam (LEV) is used in the setting of acute brain injury for seizure treatment or prophylaxis but its safety and efficacy in this setting is unknown.. We retrospectively analyzed the patterns of use and safety/efficacy of LEV in 379 patients treated in the neuroscience intensive care unit (NSICU). We extracted from the charts clinical data including diagnosis, AED therapy before and during stay in the NSICU, complications of treatment, length of stay, and clinical outcomes (improvement, Glasgow Coma Scale, and death). We analyzed the data using binary and ordered (multi-category) logistic regression.. Overall, our findings are that phenytoin used prior to the NSICU admission was frequently replaced with LEV monotherapy (P < 0.001). Patients treated with LEV monotherapy when compared to other AEDs had lower complication rates and shorter NSICU stays. Older patients and patients with brain tumors or strokes were preferentially treated with LEV for prevention and/or management of seizures (all P < or = 0.014).. The results of this study suggest that LEV is a frequently used AED in the setting of acute brain injury and that it may be a desirable alternative to phenytoin. Prospective studies evaluating the long-term safety, efficacy and outcomes of LEV in this setting are indicated.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Diseases; Brain Neoplasms; Cerebral Hemorrhage; Comorbidity; Critical Illness; Epilepsy; Humans; Intensive Care Units; Length of Stay; Levetiracetam; Middle Aged; Piracetam; Retrospective Studies; Stroke; Treatment Outcome

Levetiracetam is a new antiepileptic drug reported to be effective and well-tolerated in adults and children affected by epilepsy. Its lack of hepatic cytochrome metabolism is the theoretic basis for the absence of interactions with other drugs that follow this pathway. We present a 14-year-old girl who underwent orthotopic heart transplantation, followed by antirejection therapy including cyclosporine. Symptomatic occipital lobe epilepsy developed that was successfully treated with oxcarbazepine, but cyclosporine plasma levels decreased to below the antirejection threshold. Oxcarbazepine was replaced by levetiracetam. Levetiracetam did not affect the metabolism of cyclosporine, and cyclosporine plasma levels have remained in the therapeutic range up to now. The patient is still seizure-free and does not complain of any side effects after a 1-year follow-up. Further studies are necessary to confirm the lack of interactions between these drugs, which would make levetiracetam a useful therapeutic option in managing seizure control during antirejection therapy with cyclosporine.

Topics: Adolescent; Anticonvulsants; Cardiomyopathy, Dilated; Cyclosporine; Enzyme Inhibitors; Epilepsy; Female; Heart Transplantation; Humans; Levetiracetam; Piracetam

Topics: Anticonvulsants; Dose-Response Relationship, Drug; Epilepsy; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Psychoses, Substance-Induced

The authors report the first case of levetiracetam-induced diffuse interstitial lung disease. The patient is a 9-year-old girl who was admitted to the pediatric intensive care unit for aspiration pneumonia. She has a history of epilepsy, cerebral palsy, mental retardation, asthma, and repeated hospitalizations for presumed aspiration pneumonia, which resolved with conventional medical treatment. She has been on low-dose levetiracetam for her epilepsy over the past 2 years, and the dosage was increased just prior to this admission. However, this time, with conventional treatment, the patient's aspiration pneumonia did not improve, which led to a lung biopsy. The biopsy demonstrated a diffuse interstitial process of relatively recent onset, with features consistent with diffuse lung disease. Levetiracetam was implicated in the pathogenesis of the interstitial pneumonitis. The patient improved clinically after the discontinuation of levetiracetam and with the treatment of steroids.

Topics: Anticonvulsants; Child; Epilepsy; Female; Humans; Levetiracetam; Lung Diseases, Interstitial; Piracetam

To investigate the hypothesis that some patients with epilepsy are generally prone to develop psychiatric adverse events (PAEs) during antiepileptic drug (AED) therapy irrespective of the mechanism of action of the drugs.. From a large case registry of patients prescribed topiramate (TPM) and levetiracetam (LEV), data of patients who had a trial with both drugs were analyzed. Demographic and clinical variables of those who developed PAEs with both drugs (group 1) were compared with those who did not (group 2). Subsequently, from the whole case registry, psychopathological features, demographic, and clinical variables of patients developing PAEs with TPM were compared with those of patients developing PAEs with LEV.. The case registry included over 800 patients. Among 108 patients having a trial with both drugs, we identified 9 patients in group 1 and 71 in group 2. Previous psychiatric history, family psychiatric history and history of febrile convulsions showed to be significant clinical correlates. Comparing patients who developed PAEs with LEV with those who developed PAEs with TPM, there were no differences in epilepsy related variables. Well-defined DSM-IV disorders were more frequent with TPM than with LEV. Seizure freedom was associated with psychosis.. This study suggests that a subgroup of patients is generally prone to develop PAEs during AED therapy, despite different pharmacological properties of the AEDs. A particular clinical profile and relevant variables have been identified.

Topics: Adult; Anticonvulsants; Comorbidity; Diagnostic and Statistical Manual of Mental Disorders; Epilepsy; Female; Fructose; Humans; Levetiracetam; Male; Mental Disorders; Netherlands; Piracetam; Psychiatric Status Rating Scales; Psychoses, Substance-Induced; Registries; Retrospective Studies; Seizures, Febrile; Topiramate

Topics: Anticonvulsants; Bias; Carbamazepine; Clinical Trials as Topic; Conflict of Interest; Disclosure; Drug Industry; Epilepsy; Humans; Levetiracetam; Neurology; Neuropharmacology; Piracetam; Reproducibility of Results; Treatment Outcome

Levetiracetam is a new antiepileptic drug prescribed for the treatment of patients with refractory partial seizures with or without secondary generalization as well as for the treatment of juvenile myoclonic epilepsy. A rapid and specific method by high-performance liquid chromatography diode array detection was developed to measure the concentration of levetiracetam in human plasma. The trough plasma concentrations measured in 69 epileptic patients treated with 500 to 3000 mg/d of levetiracetam ranged from 1.1 to 33.5 microg/mL. The mean (range) levetiracetam plasma concentrations in responders and nonresponders were 12.9 microg/mL (4.6-21 microg/mL) and 9.5 microg/mL (1.1-20.9 microg/mL), respectively. A wide variability in concentration-response relationships was observed in patients. Using a receiver operating characteristic curve, the threshold levetiracetam concentration for a therapeutic response was 11 microg/mL. The sensitivity and specificity for this threshold levetiracetam concentration were 73% and 71%, respectively. According to chi analysis, this finding was not significant probably because of the small number of patients and because of their refractory seizure type. Nevertheless, the levetiracetam plasma concentration could be used to help clinicians detect severe intoxication or to verify compliance by repeating the measurement in patients.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Chromatography, High Pressure Liquid; Drug Monitoring; Drug Resistance; Epilepsy; Female; Humans; Levetiracetam; Male; Medical Records; Middle Aged; Piracetam; Predictive Value of Tests; Retrospective Studies; ROC Curve; Severity of Illness Index; Spectrophotometry, Ultraviolet

Topics: Adult; Anticonvulsants; Ataxia; Carbamazepine; Drugs, Generic; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Magnetic Resonance Imaging; Piracetam

A comparative analysis of treatment with keppra and topamax of various types of epilepsy has been carried out in 37 patients aged from 1 to 35 years. Symptomatic temporal-frontal-lobe epilepsy was diagnosed in 22 patients, symptomatic temporal lobe epilepsy in 15 including "urgent aid" cases with previous antiepileptic therapy being ineffective. Effect of the drugs on the cerebral blood flow was studied with the single proton emission CT. Keppra treatment was assigned to 20 patients in dosages varying from 500 to 2,500 mg (30-50 mg/kg/daily) for single intake. Then the patients received the drug two times daily under the clinical and EEG control. The drug was tested for using in the "urgent care mode". The clinical effect by 43% decreasing (p<0,001) of seizures was observed in the first 12 h. The "stability state" was 80% after 8 months of the treatment. Topamax was administered to 17 patients in two dosages depending on patient's age and weight starting with 25-50 mg (from 3 to 12,5 mg/kg/daily) with the dose adjustment during 2 days. The latter was depended on the dynamics of clinical data and EEG. For the first 2 days, patients revealed changes in seizures quality: the seizure structure became less complex, without generalized seizures, and period of a seizure was shorter. Reduction of seizures frequency was observed on the 7-10th day and made up on average 73,9% (p<0,01). Comparing to keppra, topamax did not cause signs of autonomic and psychological discomfort. Generalized seizures became less frequent by the 3rd day.

Topics: Adolescent; Adult; Anticonvulsants; Blood Flow Velocity; Cerebrovascular Circulation; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Fructose; Humans; Infant; Levetiracetam; Male; Neuroprotective Agents; Piracetam; Tomography, Emission-Computed, Single-Photon; Topiramate; Treatment Outcome

Levetiracetam (Lev) is a new antiepileptic drug with a distinct mechanism of action, shown in regulatory trials to be effective. These controlled trials do not always predict how useful a drug will be in day to day clinical practice. Retention rates can provide a better indication of efficacy and tolerability in everyday use. Patients attending a tertiary referral centre for epilepsy and who received Lev in the first 2 years of its marketing were assessed (n = 811) to determine continuation rates of treatment with this drug. At the last follow up, 65% of patients were still taking Lev, and the estimated 3 year retention rate was 58%. In total, 11% attained seizure freedom of at least 6 months. Patients taking greater numbers of concurrent antiepileptic drugs (AEDs) were more likely to discontinue Lev, and those reaching higher maximum daily dosages were less likely to discontinue Lev. The retention rate for Lev compares favourably with that of other new AEDs.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Cohort Studies; Dose-Response Relationship, Drug; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Time Factors

Approximately 30% of patients with epilepsy do not experience satisfactory seizure control with antiepileptic drug (AED) monotherapy and often require polytherapy. The potential usefulness of AED combinations, in terms of efficacy and adverse effects, is therefore of major importance. The present study sought to identify potentially useful AED combinations with levetiracetam (LEV) METHODS: With isobolographic analysis, the mouse maximal electroshock (MES)-induced seizure model was investigated with regard to the anticonvulsant effects of carbamazepine (CBZ), phenytoin, phenobarbital (PB), valproate, lamotrigine, topiramate (TPM), and oxcarbazepine (OXC), administered singly and in combination with LEV. Acute adverse effects were ascertained by use of the chimney test evaluating motor performance and the step-through passive-avoidance task assessing long-term memory. Brain AED concentrations were determined to ascertain any pharmacokinetic contribution to the observed antiseizure effect.. LEV in combination with TPM, at the fixed ratios of 1:2, 1:1, 2:1, and 4:1, was supraadditive (synergistic) in the MES test. Likewise, the combination of LEV with CBZ (at the fixed ratio of 16:1) and LEV with OXC (8:1 and 16:1) were supraadditive. In contrast, all other LEV/AED combinations displayed additivity. Furthermore, none of the investigated LEV/AED combinations altered motor performance and long-term memory. LEV brain concentrations were unaffected by concomitant AED administration, and LEV had no significant effect on brain concentrations of concomitant AEDs.. These preclinical data would suggest that LEV in combination with TPM is associated with beneficial anticonvulsant pharmacodynamic interactions. Similar, but less profound effects were seen with OXC and CBZ.

Topics: Animals; Anticonvulsants; Behavior, Animal; Brain; Carbamazepine; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Electroshock; Epilepsy; Humans; Levetiracetam; Male; Memory; Mice; Motor Activity; Oxcarbazepine; Piracetam; Seizures

An observational longitudinal design was employed to evaluate whether treatment with the antiepileptic drug levetiracetam (LEV) adversely impacts behavior in people with intellectual disabilities and/or acquired brain damage. Thirty-five adults were assessed once off the drug and once when on LEV therapy, with a 2-month interval between assessments. Behaviors were rated using an adaptation of the Yale-Brown Obsessive Compulsive Scale and the Challenging Behaviour Scale. Challenging behaviors were rated as more frequent and severe when individuals were taking LEV. Behavioral worsening was not related to better seizure control or increased levels of engagement in activities. Families and professionals need to be aware of the potential reversible adverse effects of this drug.

Topics: Adult; Anticonvulsants; Behavior; Epilepsy; Female; Humans; Intellectual Disability; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Surveys and Questionnaires

To assess the anticonvulsant activity of the novel antiepileptic drug, levetiracetam (LEV) in a model of self-sustaining limbic status epilepticus, and to measure the consequence of LEV treatment on the pattern of mitochondrial dysfunction known to occur after status epilepticus (SE).. The rat perforant pathway was stimulated for 2 h to induce self-sustaining status epilepticus (SSSE). Stimulated rats were assigned to one of three treatment groups, receiving intraperitoneal injections of saline, 200 mg/kg LEV, or 1,000 mg/kg LEV, 15 min into SSSE and at 3 times over the next 44-h period. All animals received diazepam after 3-h SSSE to terminate seizures. Forty-four hours later, the hippocampi were extracted and prepared for electrochemical high-performance liquid chromatography (HPLC), to measure reduced glutathione levels, and for spectrophotometric assays to measure activities of mitochondrial enzymes (aconitase, alpha-ketoglutarate dehydrogenase, citrate synthase, complex I, and complex II/III). These parameters were compared between treatment groups and with sham-operated rats.. LEV administration did not terminate seizures or have any significant effect on spike frequency, although rats that received 1,000 mg/kg LEV did exhibit improved behavioral seizure parameters. Significant biochemical changes occurred in saline-treated stimulated rats compared with shams: with reductions in glutathione, alpha-ketoglutarate dehydrogenase, aconitase, citrate synthase, and complex I activities. Complex II/III activities were unchanged throughout. Rats that received 1,000 mg/kg LEV had significantly improved biochemical parameters, in many instances, comparable to sham control levels.. Despite continuing seizures, administration of LEV (1,000 mg/kg) protects against mitochondrial dysfunction, indicating that in addition to its antiepileptic actions, LEV may have neuroprotective effects.

Topics: Aconitate Hydratase; Animals; Anticonvulsants; Chromatography, High Pressure Liquid; Citrate (si)-Synthase; Disease Models, Animal; Dose-Response Relationship, Drug; Electric Stimulation; Electroencephalography; Epilepsy; Glutathione; Hippocampus; Levetiracetam; Male; Mitochondria; Mitochondrial Diseases; Neurons; Neuroprotective Agents; Perforant Pathway; Piracetam; Rats; Rats, Sprague-Dawley; Status Epilepticus

To evaluate the efficacy and tolerability of levetiracetam in children with drug resistant epilepsy from a retrospective study.. We report the result of a study of 85 pediatric patients (mean 10.5 years, range: 1-24) with refractory generalized and focal epilepsy, who received levetiracetam as add-on treatment. The average duration of epilepsy was eight years, and the patient were treated with mean of 6.0 antiepileptic drugs before levetiracetam was introduced.. Ten patients (12%) became seizure-free, three (3%) responded with seizure reduction of more than 90%, 32 (38%) responded with seizure reduction of more than 50% following introduction of levetiracetam. No response to levetiracetam was reported in 34% (n: 29). Positive psychotropic effect was observed in 26 patient (30%). Mild to moderate side effects were reported in 11 patients (13%), consisting most frequently general behavioral changes, aggression, sleep disturbances, but they ceased after decreasing the dose of levetiracetam. Mental retardation was associated with poor response and associated with more side effects.. Levetiracetam is a well tolerated new antiepileptic drug that may effectively improve seizures control as an add-on drug in resistant epilepsy in childhood with good tolerability.

Topics: Adolescent; Adult; Age of Onset; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Intellectual Disability; Levetiracetam; Male; Piracetam; Retrospective Studies; Treatment Outcome

Keppra (levetiracetam) was used as a part of the complex therapy in 87 patients with partial epilepsy and in 17 patients with adult idiopathic generalized epilepsy. Most of the cases were pharmacoresistant. Remission was observed in 25.3% of patients for the period over 12 months. Therapeutic efficacy by a decrease of seizures frequency by 75% and more has been reached in 12.6% of cases; by 50% and more--in 43.7%. The absence of drug effect and insufficient efficacy were detected only in 18.4% of cases. The therapeutic effect was stable and did not decrease after 12 and 24 months. The drug was well tolerated and was withdrawn in 5 cases (4.8%) because of side effects. The results obtained hold promise for using keppra in epileptology, in particular in treatment of pharmacoresistant epilepsy.

Topics: Adult; Anticonvulsants; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prognosis; Time Factors

The long-term efficacy and tolerability of levetiracetam (LEV) was analysed in 218 epilepsy patients. One hundred and ninety-nine patients were treated for at least 6 months. We evaluated LEV efficacy for all types of seizures together, and for simple partial, complex partial and secondary generalized seizures individually.. A significant decrease in the number of seizures occurred after 6 months of treatment (p<0.001). Mean seizure frequency (irrespective of type) before LEV was 19.2 a month. The mean monthly frequency at 6, 12, 24 and 36 months dropped to 12.7, 10.5, 9.7 and 7.1 seizures a month, respectively. The mean percentage reduction in seizures at these times was 45.7, 52.1, 59.1 and 64.2% and the number of responding patients was 51.3, 54.2, 59.8 and 62.2%. The number of patients completely seizure free was 18.6, 16.7, 15.2 and 16.2%. We found similar results in the last three categories for partial simple, complex and secondary generalized seizures individually. Side effects in 18.3% of patients caused treatment discontinuation in 6.4%. The most frequent were somnolence, moodiness and dizziness. The retention rate at 6, 12, 24 and 36 months was 0.848, 0.72, 0.62 and 0.5, respectively.. LEV is effective and well tolerated for long-term treatment of epilepsy.

Topics: Anticonvulsants; Chi-Square Distribution; Drug Therapy, Combination; Epilepsy; Humans; Kaplan-Meier Estimate; Levetiracetam; Piracetam; Retrospective Studies; Statistics, Nonparametric

Neurocognitive complaints may interfere with long-term antiepileptic drug (AED) treatment and are an important issue in clinical practice. Most data about drug-induced cognitive problems are derived from highly controlled short-term clinical trials. We analyzed such cognitive complaints for the two most commonly used AEDs in a clinical setting using patient perceived problems as primary outcome measure.. All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment.. Four hundred and two patients used either TPM (n = 260) or LEV (n = 142); 18 months retention showed a statistically significant difference, revealing 15% more patients that continued LEV compared to TPM: 18 months retention 46% for TPM and 61% for LEV [F (1.400) = 3.313, p = 0.043]. Neurocognitive complaints accounted for a significant number of drug discontinuations and especially the high frequency of neurocognitive complaints in the first period of TPM treatment appeared to be significant different from LEV [F(2,547) = 3.192, p = 0.042]. In the remaining patients, the difference in neurocognitive complaints was not statistically significant.. cognitive complaints are common in TPM treatment and frequently lead to drug withdrawal. The impact of LEV on cognitive function is only mild. This leads to a much higher (15%) drug discontinuation rate for TPM compared to LEV.

Topics: Adult; Anticonvulsants; Attitude to Health; Child; Cognition Disorders; Drug Utilization; Epilepsy; Female; Follow-Up Studies; Fructose; Humans; Levetiracetam; Male; Patient Dropouts; Piracetam; Topiramate

Although levetiracetam undergoes minimum metabolism, B-esterases have been identified in whole blood that are capable of metabolising levetiracetam. The present study was designed to ascertain any variability in levetiracetam blood concentrations that could be attributed to in situ metabolism and which could impact on the utility of such concentration measurements in guiding therapeutic management.. Blood samples were collected from 40 patients that were prescribed levetiracetam. Sera (Groups 1 and 2) or whole blood (Groups 3 and 4) were compared. Paraoxan, an inhibitor of B-esterase activity, was added to samples assigned to Groups 2 and 4. Samples within each group were assigned to Time 0 (frozen within 30 min of sample collection), Time 2 days and Time 7 days (samples kept at ambient temperature for 2 and 7 days).. For serum samples, mean levetiracetam concentrations at Time 2 days and Time 7 days were indistinguishable from Time 0, regardless of whether B-esterase activity was inhibited on not. In contrast, for whole blood, in the absence of B-esterase inhibition, mean levetiracetam concentrations declined over time (11% and 29%; 2 and 7 days) compared to baseline values. In the presence of B-esterase inhibitor, mean levetiracetam concentrations at 2 days were indistinguishable from baseline values, although at 7 days values declined by 4%.. If therapeutic monitoring of levetiracetam is to be undertaken, serum should be the matrix of choice and that whole blood should be separated as soon as possible after patient sampling so as to minimize in situ levetiracetam metabolism which could result in spuriously low concentrations and substantial intrapatient variability.

Topics: Adult; Aged; Anticonvulsants; Blood Specimen Collection; Chromatography, High Pressure Liquid; Drug Monitoring; Enzyme Inhibitors; Epilepsy; Esterases; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Time Factors

It is not known whether the antiepileptic drug (AED) levetiracetam can be used safely in human pregnancy. As part of a study to determine the risks of major congenital malformations (MCMs) for infants exposed to AEDs in utero, we identified all cases exposed to levetiracetam. Three of 117 exposed pregnancies had an MCM (2.7%; 95% CI 0.9% to 7.7%); all 3 were exposed to other AEDs.

Topics: Abnormalities, Drug-Induced; Adult; Anticonvulsants; Body Weight; Epilepsy; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Levetiracetam; Piracetam; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies; Registries; United Kingdom

We here present a method for the routine quantification of the novel antiepileptic drug levetiracetam in human serum by HPLC-UV. The procedure is very easy, quick, inexpensive and rugged. The sample preparation consists only in the precipitation of serum proteins by perchloric acid and extraction of unpolar components by cyclohexane. The aqueous phase containing the analyte levetiracetam is injected onto a porous graphitic carbon analytical HPLC-column and separated by gradient elution with diluted phosphoric acid/acetonitrile. Detection is carried out at a wavelength of 205 nm. The calibration function is linear in the range of 1-75 microg/ml. The detection limit is 0.1 microg/ml. Using four quality control sample concentrations, the inter-day relative standard deviations (R.S.D.) are lower than 3% and the accuracies are better than 6%. The respective inter-day values are: R.S.D. < 4% and accuracies better than 2%. Frequently co-administered antiepileptic drugs do not interfere with the assay. The method has been successfully applied to patient samples.

Topics: Anticonvulsants; Chromatography, High Pressure Liquid; Drug Therapy, Combination; Epilepsy; Humans; Lamotrigine; Levetiracetam; Phenobarbital; Piracetam; Primidone; Triazines

To study the pharmacokinetics of levetiracetam (LEV) at birth, during lactation, and in the nursed infant.. Eight consecutive breast-feeding women with epilepsy treated with LEV twice daily and their infants were studied.. The mean umbilical cord serum/maternal serum ratio was 1.14 (range, 0.97-1.45) (n = 4). The mean milk/maternal serum concentration ratio was 1.00 (range, 0.76-1.33) at 3 to 5 days after delivery (n = 7). At sampling 2 weeks to 10 months after delivery (n = 5), it was similar (range, 0.85-1.38). At 3 to 5 days after delivery, the infants had very low LEV serum concentrations (<10-15 microM), a finding that persisted during continued breast-feeding. No malformations were detected, and in none of the infants did signs of adverse effects develop.. Our data indicate an extensive transfer of LEV from mother to fetus and into breast milk. However, breast-fed infants had very low LEV serum concentrations, suggesting a rapid elimination of LEV.

Topics: Anticonvulsants; Breast Feeding; Epilepsy; Female; Fetal Blood; Humans; Infant, Newborn; Lactation; Levetiracetam; Maternal-Fetal Exchange; Milk, Human; Parturition; Piracetam; Pregnancy; Pregnancy Complications

This study provides the results of a cost-effectiveness analysis of levetiracetam as an adjunctive treatment for refractory epilepsy from the Canadian Ministry of Health perspective. The main objective is to estimate the expected cost-effectiveness ratio expressed as the incremental cost per seizure-free day gained when using levetiracetam. In addition, this study examines the potential savings that might result by reducing the number of surgical evaluations and surgery when using levetiracetam.. A 1-year dose escalation decision-tree model comparing levetiracetam plus standard therapy with standard therapy alone was designed in order to combine probability, resource use and unit cost data (1999 Canadian dollars [$Can]). The short-term outcomes were derived from three phase III randomised, double-blind, placebo-controlled trials performed in 904 patients, aged 16-70 years, with at least 1 year history of epilepsy, two to four partial seizures per month, and receiving a maximum of two classic antiepileptic drugs.. The average gain in seizure-free days attributed to levetiracetam was 19 days per patient per year and the incremental cost-effectiveness ratio (ICER) for levetiracetam add-on in the base-case scenario was $Can80.7 per seizure-free day gained per patient per year. Moreover, when surgical investigation and surgery are considered in the model, the use of levetiracetam may be dominant, with substantial savings to the overall healthcare budget. All univariate sensitivity analyses show that the model was robust to the assumptions made.. The economic analysis presented in this paper suggests, given a wide range of assumptions, that the increased cost of treating patients (with refractory epilepsy) with levetiracetam may be partially offset by a reduction in other direct medical costs (from the Canadian Ministry of Health perspective), as a consequence of an increase in the number of seizure-free days. Moreover, potential cost savings may be foreseen when it is assumed that levetiracetam may reduce the number of candidates for surgical evaluation and surgery through a reduction of seizure frequency.

Topics: Anticonvulsants; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Resistance; Drug Therapy, Combination; Epilepsy; Humans; Levetiracetam; Models, Economic; Piracetam

Levetiracetam (LEV) is increasingly used as adjunctive anticonvulsant therapy because of apparent low toxicity. Somnolence, asthenia, headache, dizziness, and nervousness are the most frequently reported side effects (1). We describe a patient, predisposed to the development of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), in whom hyponatremia developed after two challenges of LEV.

Topics: Aged; Anticonvulsants; Carbamazepine; Drug Therapy, Combination; Epilepsy; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Levetiracetam; Piracetam; Sodium

Seizures arising from acetylcholinesterase inhibition are a feature of organophosphate anticholinesterase intoxication. Although benzodiazepines are effective against these seizures, alternative anticonvulsant drugs may possess greater efficacy and fewer side-effects. We have investigated in the guinea-pig hippocampal slice preparation the ability of a series of anticonvulsants to suppress epileptiform bursting induced by the irreversible organophosphate anticholinesterase, soman (100 nM). Carbamazepine (300 microM), phenytoin (100 microM), topiramate (100-300 microM) and retigabine (1-30 microM) reduced the frequency of bursting but only carbamazepine and phenytoin induced a concurrent reduction in burst duration. Felbamate (100-500 microM) and clomethiazole (100-300 microM) had no effect on burst frequency but decreased burst duration. Clozapine (3-30 microM) reduced the frequency but did not influence burst duration. Levetiracetam (100-300 microM) and gabapentin (100-300 microM) were without effect. These data suggest that several compounds, in particular clomethiazole, clozapine, felbamate, topiramate and retigabine, merit further evaluation as possible treatments for organophosphate poisoning.

Topics: Amines; Animals; Anticonvulsants; Carbamates; Carbamazepine; Chlormethiazole; Clozapine; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Epilepsy; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Guinea Pigs; Hippocampus; In Vitro Techniques; Levetiracetam; Male; Phenylcarbamates; Phenylenediamines; Piracetam; Propylene Glycols; Soman; Topiramate

The long-lasting antiseizure effects of levetiracetam (LEV) have been observed in the spontaneously epileptic rat (SER) that expresses both tonic and absence-like seizures. Furthermore, the antiepileptogenic effects of LEV in addition to antiseizure effects have been reported in the amygdala-kindling model in rats. This suggests that the long-lasting seizure protection of LEV may be at least partly due to its antiepileptogenic effects. Therefore this study aimed to differentiate the antiseizure and potential antiepileptogenic effects of LEV by administering LEV continuously to SERs before the appearance of any seizure expression.. LEV was administered to the SERs at 80 mg/kg/day (i.p.) from postnatal weeks 5 to 8. The period of observation for tonic convulsions was from postnatal week 5 to 13. Absence-like seizures were recorded by using conventional EEG in weeks 12 and 13.. After age 7-8 weeks, SERs exhibit spontaneous tonic convulsions. Development of tonic convulsions was significantly inhibited in the LEV group, compared with the control group, by the middle of week 9. A significant reduction of tonic convulsions also was observed in the LEV group until week 13 (5 weeks after termination of the administration). In week 12, the absence-like seizures were significantly lower in the LEV group, compared with the control group.. This study demonstrates a significant inhibition of seizures after prolonged treatment with LEV before the developmental expression of seizure activity in SERs. This effect is suggested to be due to an antiepileptogenic effect and not an antiseizure effect of LEV, because the half-life of the drug in plasma is short (2-3 h in rats) after single and long-term administration. Furthermore, the inhibition of seizure expression in SERs was still apparent 5 weeks after termination of LEV treatment. These results further suggest that LEV possesses not only antiseizure effects but also antiepileptogenic properties.

Topics: Animals; Animals, Newborn; Anticonvulsants; Disease Models, Animal; Drug Administration Schedule; Electrodes, Implanted; Electroencephalography; Epilepsy; Female; Frontal Lobe; Hippocampus; Injections, Intraperitoneal; Levetiracetam; Male; Piracetam; Rats; Rats, Mutant Strains; Seizures

The aim of this audit was to ascertain outcomes for people who had taken or who were still taking three "new generation" broad-spectrum antiepileptic drugs (AEDs), namely lamotrigine, levetiracetam and topiramate. Thirteen percent of people became seizure free and approximately, one-third had a reduction of greater than 50% in their seizures. Two-thirds of people were still taking their audit AED. In addition, approximately one-third of people with a learning disability derived substantial benefit, although the rate of seizure freedom was lower. All three AEDs were most successful at treating primary generalised epilepsy and least successful with symptomatic generalised epilepsy. With some reservations the data suggests that levetiracetam and topiramate are the most efficacious AEDs, but topiramate is the least well tolerated. These results mean consideration of a "general prescribing policy" is important when using and choosing these AEDs. We conclude that lamotrigine, levetiracetam and topiramate are useful additions to the armamentarium of AEDs.

Topics: Adult; Aged; Anticonvulsants; Cohort Studies; Drug Utilization; Epilepsy; Epilepsy, Generalized; Female; Fructose; Hospitals, General; Humans; Knowledge Bases; Lamotrigine; Learning Disabilities; Levetiracetam; Male; Medical Audit; Middle Aged; Patient Dropouts; Piracetam; Topiramate; Triazines; United Kingdom

In Genetic Absence Epilepsy Rats from Strasbourg (GAERS), age-related absence seizures start to appear from postnatal day (PN) 30 concomitant with 'spike and wave discharges' (SWDs) appearing on cortical EEG recordings. The aim of this study was to investigate the effect of early chronic levetiracetam (LEV) treatment on the development of SWDs in young and adult GAERS.. From PN 23 until PN 60, LEV (54 mg/kg, i.p.) was administered once daily to GAERS (n=8), while control GAERS (n=7) received saline (0.9% NaCl, i.p.). All animals were implanted with four epidural EEG electrodes at PN 51. EEG was recorded for 3h daily, during the last 4 days of the treatment (PN 57-PN 60) and during 4 additional days after treatment had been terminated (PN 61-PN 64). The animals were monitored again at the age of 4 months (PN 120-PN 124), about 2 months after the last administration of LEV.. During treatment, epileptiform events in the LEV group were significantly reduced (62%, P<0.05) in comparison with the control group. During the following 4 days, epileptiform events were reduced in the LEV group, with an average difference of 53% (P=0.064). Once the animals had reached adult age, there was no difference in epileptiform events between the LEV group and controls.. In this study, chronic LEV administration induced a reduction in epileptiform events in young GAERS. This effect persisted to some extent after treatment cessation (PN 61-PN 64), which might indicate a slowing down of epileptogenic processes. However, at the age of 4 months all animals revealed a similar expression of epileptiform discharges.

Topics: Aging; Animals; Anticonvulsants; Brain; Electrodes, Implanted; Electroencephalography; Epilepsy; Levetiracetam; Piracetam; Rats; Rats, Inbred Strains

Some evidence suggests that levetiracetam (LEV) possesses antiepileptogenic characteristics. The purpose of this study was to investigate the time course of seizure protection by LEV compared with that of phenytoin (PHT), phenobarbital (PB), valproate (VPA), and carbamazepine (CBZ) in the spontaneously epileptic rat (SER). The SER is a double mutant (tm/tm, zi/zi) showing both tonic convulsions and absence-like seizures.. The effect of single (40, 80, and 160 mg/kg, i.p.) and 5-day (80 mg/kg/day, i.p.) administration of LEV on tonic convulsions and absence-like seizures in SERs were studied. Tonic convulsions induced by blowing air onto the animal's head at 5-min intervals for 30 min and spontaneous absence-like seizures characterized by 5- to 7-Hz spike-wave-like complexes in the cortical and hippocampal EEG were recorded for 30 min. In the single-administration study, observations for seizure activity were performed once before and 3 times (45, 75, and 135 min) after drug administration. In the 5-day administration study, seizure observation was performed 4 times for 30 min (once before and 3 times after drug administration) during the 5-day drug-administration period, and continued once a day until 8 days after the final administration. The antiepileptic effects of 5-day administration of conventional AEDs (PHT, PB, VPA, and CBZ) were examined by using similar methods.. Tonic convulsions and absence-like seizures were inhibited by a single administration of LEV at 80 and 160 mg/kg, i.p., but not significantly at 40 mg/kg, i.p. When LEV was repeatedly administered at 80 mg/kg/day, i.p., for 5 days to SERs, the inhibitory effects on seizures increased with administration time. The number of tonic convulsions and absence-like seizures were significantly reduced to 39.1% and 38.4% compared with previous values, respectively, after 5-day LEV administration. Furthermore, significant inhibition of tonic convulsions was detected

Topics: Animals; Anticonvulsants; Behavior, Animal; Cerebral Cortex; Disease Models, Animal; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Epilepsy, Absence; Epilepsy, Generalized; Female; Injections, Intraperitoneal; Levetiracetam; Male; Piracetam; Rats; Rats, Mutant Strains; Time Factors

Most large-scale clinical trials of antiepileptic drugs (AEDs) are undertaken for regulatory purposes and generate basic data supporting the efficacy and safety of a new treatment. They do not, however, provide all the information required for physicians to know how well the drug will work in clinical practice. One valuable approach to generating more clinically meaningful information is to assess AED treatment retention rates, which reflect the combination of efficacy and tolerability in the real world, and have historically been low. Long-term retention rate data are available for levetiracetam (LEV), topiramate, gabapentin, and lamotrigine, and these data suggest that LEV is more likely to retain patients than other new AEDs. In a recent tertiary care study involving mainly refractory patients, 11% of participants became seizure-free on LEV and nearly two-thirds were retained on long-term treatment. High seizure freedom rates and good tolerability reported with LEV in clinical trials thus appear to translate into improved treatment retention rates in clinical practice.

Topics: Amines; Anticonvulsants; Controlled Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Levetiracetam; Long-Term Care; Patient Dropouts; Piracetam; Topiramate; Treatment Outcome; Triazines

Historically, most antiepileptic drugs (AEDs) have been discovered either by serendipity, or the screening of compounds using acute seizure models. However, an increasing understanding of the molecular mechanisms underlying epileptogenesis has led to more rational approaches to drug discovery, which have focused on either enhancing inhibitory gamma-amino butyric acid (GABA)-ergic, or antagonizing excitatory glutamatergic, neurotransmission. Unfortunately, AEDs generated using such strategies have poor efficacy and safety profiles, as they interfere with normal cell processes, while ignoring the complex underlying pathophysiology of epilepsy. Recently, however, the use of new epilepsy models has led to the discovery of levetiracetam, an AED with a truly unique mechanism of action, devoid of anticonvulsant activity in normal animals, but with potent seizure suppression in genetic and kindled chronic epilepsy models, and an unusually high safety margin. The recent identification of brivaracetam and seletracetam, which optimize this unique mechanism of action, may further improve the medical management of epilepsy. The experience with levetiracetam, brivaracetam and seletracetam reveals that new experimental epilepsy models can detect AEDs possessing a unique mechanism of action and thereby target the future challenge of providing clinicians novel additions to the current armamentarium of AEDs.

Topics: Animals; Anticonvulsants; Brain; Dose-Response Relationship, Drug; Epilepsy; Forecasting; GABA Agonists; Humans; Levetiracetam; Membrane Glycoproteins; Nerve Tissue Proteins; Piracetam; Synapses; Treatment Outcome

The authors examined sodium concentrations from 97 oxcarbazepine-treated (OXC) and 451 carbamazepine-treated (CBZ) patients with epilepsy using cross-section and follow-up studies. The frequency of hyponatremia (Na+ < or = 134 mEq/L) was 29.9% among OXC-treated patients and 13.5% among CBZ-treated patients (p < 0.0001). Hyponatremia (Na+ < or = 128 mEq/L) was severe: 12.4% of OXC-treated patients and 2.8% of CBZ-treated patients (p < 0.001). Advanced age was a risk factor for hyponatremia. Hyponatremia, once present, persisted in both groups.

Topics: Adult; Age Factors; Aging; Anticonvulsants; Carbamazepine; Databases, Factual; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Epilepsy; Female; Humans; Hyponatremia; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Piracetam; Prevalence; Sex Factors; Sodium

To investigate the prevalence and psychopathological features of psychiatric adverse events (PAEs) in patients with learning disabilities (LD) in therapy with levetiracetam (LEV).. From a population of 517 consecutively patients with epilepsy started on LEV, we identified 118 patients with epilepsy and LD.. Fifteen patients (12.7%) experienced PAEs during LEV therapy. Two (1.7%) developed an affective disorder, nine (7.6%) aggressive behaviour, two (1.7%) emotion lability and two (1.7%) other personality changes such as agitation, anger and hostile behaviour. We observed a significant association with a previous history of status epilepticus and a previous psychiatric history. We did not find a statistically significant association with epilepsy diagnosis, age at onset or duration of the epilepsy, EEG or MRI features. The titration schedule of LEV appeared not to be relevant.. LEV therapy was well tolerated in patients with epilepsy and LD and the main problems were related to aggressive behaviour. The titration schedule of LEV was not relevant and a subgroup of patients appeared to be biologically more vulnerable.

Topics: Adult; Analysis of Variance; Anticonvulsants; Behavioral Symptoms; Chi-Square Distribution; Epilepsy; Female; Humans; Learning Disabilities; Levetiracetam; Male; Piracetam; Prevalence; Regression Analysis

We retrospectively identified 14 elderly patients with a history of partial seizures who received levetiracetam (LEV) monotherapy. Patients began LEV either as first line therapy (n=5) or were converted to LEV monotherapy (n=9) after failing prior antiepileptic medications (AEDs). Thirteen patients continued on LEV monotherapy for at least 6 months. One patient was lost to follow-up. Eight patients (61.5%) became seizure free. Four patients who began LEV as a first line therapy became seizure free, whereas the remaining four patients who converted to LEV after they failed their previous AEDs became seizure free. Four patients (30.7%) had more than a 50% seizure reduction of seizures. Only one patient had no significant change in seizure frequency after started on LEV. The total dosages used to control seizures were 500-3000 mg/day, (mean 1839.2 mg/day). LEV monotherapy can be effective and well tolerated in this group of patients. A prospective, larger, double blind monotherapy study is needed to confirm this finding.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Dose-Response Relationship, Drug; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies

Levetiracetam is a new anti-epileptic drug that is currently not licensed for use in children. Studies in adults suggest that it may be a useful adjunctive treatment both in partial onset and generalised epilepsy. A retrospective case notes review of 26 children age 10 years and under with refractory epilepsy was undertaken to evaluate the efficacy and safety of the drug. The drug appeared to be most effective in children with partial onset seizures and least effective in those with myoclonic seizures. Sixty-one percent of patients showed a good response to levetiracetam with at least a 50% reduction in seizure frequency with two of these 26 children with previously refractory epilepsy becoming seizure-free. Levetiracetam was also found to be well-tolerated with very few reported side-effects.

Topics: Age Factors; Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Retrospective Studies

The purpose was to evaluate the effects of levetiracetam (LEV) in routine therapy in learning disabled patients with therapy-resistant epilepsy.. In an open observational add-on study design, 46 patients (residents of the Bethel Epilepsy Centre) with severe therapy-resistant epilepsy and different degrees of learning disabilities, who were treated with LEV between its introduction in Autumn 2000 and February 2002, were evaluated retrospectively. Information on monthly seizure frequencies, seizure severity and psychiatric status was extracted from the current patient case records. A 3 months baseline and a 3 months LEV treatment period (after 3 months of titration) were compared. Responders were defined as having a 50% reduction in seizure frequency and being evaluated as good or very good in an ad hoc global clinical efficacy scale. When only one criterion was positive, a careful individual decision was made based on the impact on the patients' daily activities.. The responder rate was 41.3% (34.8 for 50% seizure reduction). It was higher in focal and multifocal epilepsy as compared to symptomatic generalised epilepsy/Lennox Gastaut Syndrome (P<0.05). Antiepileptic response occurred in doses between 500 and 4000 mg/day. Changes in seizure severity were rare. Nine patients experienced positive psychotropic effects (mostly improved vigilance and mood); six of these patients had antiepileptic effects as well. Twelve patients had adverse effects, mostly mild; in three cases, however, more severe effects led to discontinuation.. LEV is an effective and generally well-tolerated drug for this patient group, especially in focal and multifocal epilepsy.

Topics: Adolescent; Adult; Aged; Epilepsy; Female; Humans; Learning Disabilities; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies

Levetiracetam (LEV) is a recently marketed novel anti-epileptic drug with a promising efficacy and safety profile. In this report we describe two patients who presented with enterocolitis and discuss the possible relationship with concurrent LEV intake.. In two patients. LEV was initiated to control refractory complex partial seizures (CPS). The first patient was treated with 1500 mg/day and complained of abdominal pain and weight loss 6 months later. Internal examination and colonoscopy revealed a punctate colitis. The second patient presented with bloody stool 1 month after LEV initiation. Colonoscopy showed punctate colitis. In both patients gastrointestinal symptoms disappeared following tapering of LEV.. There are no reports in the literature describing colitis related to LEV intake. Three possible mechanisms of action are discussed. Colitis may be part of a hypersensitivity syndrome caused by LEV. Pharmacodynamic interactions with other anti-epileptic drugs, for example, carbamazepine may play a role. A haematological adverse event is another possibility since piracetam, a related molecule, has a known impact on erythrocytes and platelets.. The close temporal relationship between initiation of LEV intake, symptomatic colitis and clinical improvement following LEV tapering, suggests that colitis may be a possible and previously undescribed adverse effect of LEV.

Topics: Adult; Anticonvulsants; Electroencephalography; Enterocolitis; Epilepsy; Female; Hippocampus; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Piracetam

To evaluate the efficacy and safety of levetiracetam (LEV) in refractory crypto/symptomatic, partial or generalised epilepsy in children, adolescents and young adults.. We performed a prospective open label add-on study in 99 patients (age 12 months to 32 years, mean 14 years) with partial or generalised, crypto/symptomatic seizures. Levetiracetam was added to no more than two baseline AEDs and the efficacy was rated according to seizure type and frequency.. LEV was initiated at the starting dose of 10mg/kg/day with 5-day increments up to 50 mg/kg/day, unless it was not tolerated. Concomitant therapy was generally not modified throughout the study. After a mean follow-up period of 6.7 months (range 3 weeks to 29 months), 11 patients (11.1%) were free of seizures (cryptogenic partial epilepsy, 5; symptomatic partial epilepsy, 6). A more than 75% seizure decrease was found in 14 patients (14.1%) and >50% in 8 (8.1%). Seizures were unchanged in 38 (38.4%), and worsened in 23 (23.2%). Mild and transient adverse side effects were found in 17 patients (17.2%), mostly represented by irritability and drowsiness.. LEV appears to be well tolerated in children and adolescents with severe epilepsy and seems to be a broad spectrum AED, though in our experience, it was more effective against partial seizures with or without secondarily generalisation. LEV efficacy in other epilepsy syndrome should be evaluated further in homogeneous, more selected patients.

Topics: Adolescent; Adult; Chi-Square Distribution; Child; Child, Preschool; Epilepsy; Female; Follow-Up Studies; Humans; Infant; Levetiracetam; Male; Piracetam; Prospective Studies; Statistics, Nonparametric

Alterations in neuronal calcium (Ca2+) homeostasis are believed to play an essential role in the generation and propagation of epileptiform events. Levetiracetam (LEV) and lamotrigine (LTG), novel antiepileptic drugs (AEDs), were tested on epileptiform events and the corresponding elevations in intracellular Ca2+ concentration ([Ca2+]i) recorded from rat neocortical slices.. Electrophysiological recordings were performed from single pyramidal neurons from a slice preparation. Spontaneous epileptiform events consisting of long-lasting, repetitive paroxysmal depolarization shifts (PDSs) and interictal spike activity were induced by reducing the magnesium concentration from the solution and by adding bicuculline and 4-aminopyridine. Simultaneously, microfluorimetric measurements of [Ca2+]i were performed. Optical imaging with Ca2+ indicators revealed a close correlation between Ca2+ transients and epileptiform events.. Both LEV and LTG were able to reduce both amplitude and duration of PDSs, as well as the concomitant elevation in [Ca2+]i, in a dose-dependent fashion. Whole-cell patch-clamp recordings from isolated neocortical neurons revealed that LEV significantly reduced N-, and partially P/Q-type high-voltage-activated (HVA) Ca2+ currents, whereas sodium currents were unaffected. Interestingly, the inhibitory effects of LEV were mimicked and occluded by LTG or by a combination of omega-conotoxin GVIA and omega-agatoxin IVA, selective blockers of N- and P/Q-type HVA channels, respectively, suggesting a common site of action for these AEDs.. These results demonstrate that large, transient elevations in neuronal [Ca2+]i correlate to epileptiform discharges. The antagonistic effects of LEV and LTG on [Ca2+]i overload might represent the basis for their anticonvulsant efficacy and could preserve neuronal viability.

Topics: 4-Aminopyridine; Animals; Anticonvulsants; Bicuculline; Calcium; Calcium Channel Blockers; Calcium Channels; Calcium Channels, N-Type; Dose-Response Relationship, Drug; Epilepsy; Lamotrigine; Levetiracetam; Male; Membrane Potentials; Neocortex; Patch-Clamp Techniques; Piracetam; Pyramidal Cells; Rats; Rats, Wistar; Triazines

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Sweden; Thrombocytopenia

The purpose of this study was to assess the efficacy and safety of levetiracetam in a diverse pediatric epilepsy population. A retrospective chart review of 52 consecutive children age 8 months to 16 years who were treated with levetiracetam was performed. The data include patients with partial and generalized seizures, monotherapy, and concomitant antiepileptic drug use. Levetiracetam was dosed to efficacy or unacceptable side effects, with a range of 8 to 315 mg/kg/day. Two patients discontinued levetiracetam prior to assessment of efficacy owing to side effects. Of the remaining 50 patients, 12 had > or =75% seizure reduction, 3 had > or =50% and <75% seizure reduction, 8 had > or =25% and <50% seizure reduction, and 27 had < 25% seizure reduction. A variety of pediatric epilepsy syndromes and seizure types were represented. Adverse events, seen in 17 patients, were determined to be tolerable or resolved over time with continued dosing, dosage reduction, or discontinuation. This open-label, retrospective study of 52 consecutive pediatric patients treated with levetiracetam indicates at least partial efficacy in a variety of pediatric epilepsy syndromes. Tolerability was surprisingly favorable, even at doses far exceeding 40 mg/kg/day.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Retrospective Studies; Treatment Outcome

The effect of the novel antiepileptic drug levetiracetam on caffeine (10 mM)-induced intracellular calcium ([Ca2+]i) response was investigated in rat hippocampal neurons in culture, with the aim of exploring the cellular mechanisms of this new drug. Levetiracetam significantly reduced caffeine-induced [Ca2+]i) response, with maximum inhibition at 32 microM. The R-enantiomer of levetiracetam, ucb L060, which is devoid of anticonvulsant activity, at 32 microM had no effect on caffeine-induced [Ca2+]i) response. Caffeine 10 mM also induced epileptiform field potentials in rat hippocampal slices : single stimuli evoked repetitive population spikes and spontaneous field bursts regularly occurred. Levetiracetam (32 microM) significantly inhibited the amplitudes and the number of caffeine-induced repeated population spikes and delayed the appearance of spontaneous bursts, while ucb L060 (32 microM) completely lacked anti-caffeine activity. These results suggest that the inhibition of caffeine-induced Ca release from intra-neuronal stores might be an excitability-reducing effect of levetiracetam, contributing to its antiepileptic activity.

Topics: Animals; Anticonvulsants; Caffeine; Calcium; Cells, Cultured; Central Nervous System Stimulants; Electrophysiology; Epilepsy; Hippocampus; In Vitro Techniques; Levetiracetam; Neurons; Piracetam; Rats; Rats, Sprague-Dawley

Topics: Aged; Anticonvulsants; Carbamazepine; Drug Antagonism; Drug Therapy, Combination; Epilepsy; Humans; Lamotrigine; Levetiracetam; Male; Piracetam; Treatment Outcome; Triazines

We retrospectively reviewed the charts of all of our patients with a history of partial seizures, with and without secondarily generalisation, who received levetiracetam (LEV; Keppra) for treatment of their seizures during the years 2000-2002. Forty-five patients were identified, 13 of whom began LEV as first line therapy. Eleven patients continued on LEV for at least 6 months; six of whom became seizure free and five had >50% reduction in their seizures. The remaining two patients discontinued LEV because of adverse effects. LEV monotherapy can be effective and well tolerated in adults with new onset seizures. A prospective, large, double-blind monotherapy study for newly diagnosed patients is needed to confirm this finding.

Topics: Adolescent; Adult; Age of Onset; Aged; Anticonvulsants; Drug Therapy, Combination; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Middle Aged; Piracetam; Retrospective Studies; Treatment Outcome

A proportion of patients with epilepsy are still without seizure control. This open study aims to evaluate the effect and tolerability in consecutive patients treated with the new antiepileptic drug levetiracetam.. 184 adult patients were followed up for an average period of 8.1 months. 166 patients (90%) had refractory epilepsy, defined as having seizures more than once a month despite having tried at least two antiepileptic drugs.. 64 (39%) of the patients with refractory epilepsy had at least a 50% reduction of seizure frequency. Of these, 16 (10%) became seizure free. 24 (15%) had at least a 25% increase in seizure frequency. The overall effect was not significantly different for patients with and without learning disability. Levetiracetam also had promising effects in patients with juvenile myoclonic epilepsy and Lennox-Gastaut syndrome. Side effects were reported by 88 (44%) of all patients. Only 10 (5%) discontinued levetiracetam because of side effects. Behavioural effects were more frequent in patients with learning disability.. Levetiracetam was well tolerated and effective as add-on treatment in partial and generalised seizures. Some patients experienced an increase in seizure. A possible favourable pharmacodynamic interaction between levetiracetam and carbamazepine should be further explored.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Drug Interactions; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Myoclonic Epilepsy, Juvenile; Piracetam

The safety and efficacy of novel anticonvulsants during pregnancy in women with epilepsy are not well established. Although there are a variety of pregnancy registries accruing data on various outcomes, health care professionals managing women of childbearing age are interested in any information that may assist with clinical decisions. This case series summarizes the clinical outcomes of three women with epilepsy, all of whom took levetiracetam as monotherapy during pregnancy.

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Epilepsy; Female; Humans; Infant, Newborn; Levetiracetam; Piracetam; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Treatment Outcome

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Neuroprotective Agents; Piracetam

Levetiracetam (LEV) was shown to be very efficacious and well tolerated as add-on therapy for refractory epilepsy. Here we report 33 patients with longstanding histories of epilepsy who experienced aggressive episodes during LEV therapy. This corresponds to 3.5% of LEV-treated patients as compared with less than 1% of patients not on LEV. Among these cases, 24 showed only moderate, partly transient irritability, with 10 patients requiring reduction or discontinuation of LEV. More strikingly, 9 patients displayed severe symptoms of aggression with physical violence and, in 2 cases, the need for psychiatric emergency treatment. One patient developed additional psychotic symptoms. We suggest that, specifically in patients with a previous history of aggression, behavioral tolerability of LEV should be carefully monitored.

Topics: Adult; Aged; Aggression; Anticonvulsants; Drug Resistance; Drug Therapy, Combination; Epilepsy; Female; Humans; Irritable Mood; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Patient Compliance; Piracetam; Retrospective Studies

Topics: Adult; Anticonvulsants; Body Weight; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Weight Loss

Levetiracetam (LEV) is a recently approved anticonvulsant with proven efficacy and safety in the treatment of partial seizures. LEV may cause behavioral abnormalities that can be severe and require discontinuation of this drug. Risk factors for discontinuing LEV have not been established.. To determine incidence of behavioral abnormalities severe enough to require discontinuation of LEV and identify risk factors for such behavioral abnormalities.. All patients treated with LEV at MINCEP between January 2000 and February 2002 constituted the study population (n = 553). Patients who had discontinued LEV for behavioral reasons were selected as index cases. Case controls were patients starting LEV immediately after the index case. Potential risk factors for LEV discontinuation included age, gender, cognitive function, history of psychiatric diagnosis, epilepsy syndrome, number of antiepileptic drugs, titration rate, maximum dose of LEV, and LEV level at maximum dose.. Thirty-eight patients (6.9%) discontinued LEV because of behavioral abnormalities. Variables associated with LEV discontinuation included faster titration rate to maximal dose, history of a psychiatric disorder, and diagnosis of symptomatic generalized epilepsy. Patients who discontinued LEV owing to behavioral reasons had significantly lower maximum LEV doses than controls.. This study identified variables associated with discontinuation of LEV due to behavioral abnormalities. Slower titration of LEV should be considered in those patients at higher risk of discontinuing LEV for behavioral reasons.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Behavioral Symptoms; Case-Control Studies; Child; Dose-Response Relationship, Drug; Epilepsy; Female; Humans; Incidence; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Risk Factors; Sex Factors

This prospective observational study explored the efficacy and tolerability of levetiracetam (LEV) in a prospective series of 200 patients with refractory epilepsy attending a single epilepsy service. Patients were started on adjunctive LEV using one of two titration schedules (slow and fast) and patients were studied for at least 6 months after commencing LEV. Fifty-three patients had severe learning disabilities. 14.3% became seizure free, 57.7% showed >50% reduction, 15.4% showed seizure increase. Patients with learning disability showed less positive but still very worthwhile results. A highly significant improvement in clinical outcomes overall is shown (P<0.0001). 56.6% showed no adverse effects, 27.4% showed minor adverse effects, 16% were withdrawn. The most common adverse effect causing drug withdrawal was seizure exacerbation (12%) which was much commoner in primary generalised epilepsies (P=0.00035). LEV appears to be an effective and well-tolerated anti-epileptic drug in drug resistant partial epilepsies.

Topics: Adolescent; Adult; Aged; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Residential Facilities

Levetiracetam (LEV) is a new antiepileptic drug approved as add-on therapy. Previous studies indicated that LEV has no relevant interactions with other antiepileptic drugs. The aim of this study was to investigate the influence of LEV dose, age, and co-medication on the serum concentration of LEV. In total, 363 samples of 297 inpatients who fulfilled the inclusion criteria (e.g., trough concentration, body weight available) were investigated. A patient was considered twice only if his co-medication had been changed. The LEV serum concentration in relation to LEV dose/body weight [level-to-dose ratio, LDR, (microgram/mL)/(mg/kg)] was calculated and compared for the most frequent drug combinations. Analysis of covariance (using age as covariate) carried out on the log-transformed data showed that co-medication had a highly significant (P < 0.001) effect on LEV serum concentrations. The median LDR of LEV was 0.32 for LEV + phenytoin, 0.32 for LEV + carbamazepine, 0.34 LEV + oxcarbazepine, 0.45 for LEV + lamotrigine, 0.46 for LEV + phenobarital, 0.52 for LEV monotherapy, 0.53 for LEV + valproic acid, and 0.54 LEV + valproic acid + lamotrigine. In co-medication with phenytoin (P < 0.001), carbamazepine (P < 0.001), and oxcarbazepine (P < 0.004), the LDR of LEV was significantly lower than it was with LEV monotherapy, whereas the LDR of LEV of patients on co-medication with valproic acid or lamotrigine did not differ significantly from the LDR of LEV of patients on LEV monotherapy (P > 0.05). Regression analysis including all 363 samples confirmed that other drugs (e.g., phenytoin, carbamazepine) lower LEV concentrations. In addition to co-medication, age had a significant effect on clearance of LEV. Children had lower LEV concentrations than adults on the same LEV dose per body weight. In contrast to other studies, our data point out that other enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine) can moderately decrease LEV serum concentrations (by 20-30%). However, our observations should be confirmed by prospective pharmacokinetic studies.

Topics: Adolescent; Adult; Age Factors; Aged; Anticonvulsants; Body Weight; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Regression Analysis

The purpose of this analysis was to compare treatment-emergent adverse events (TEAE) related to use of levetiracetam (LEV) reported by young and elderly patients with anxiety and cognitive disorders, and young epilepsy patients. The LEV database includes reports of TEAE from trials of patients with diagnoses of a cognitive disorder (N=719), an anxiety disorder (N=1510), or localization-related epilepsy (N=1023) who participated in clinical trials lasting up to 16 weeks. Patients were grouped as young (<65 years) or elderly (> or = 65 years). The most common TEAE occurring most frequently in the LEV-treated groups were abdominal pain, asthenia, headache, anorexia, weight loss, dizziness, insomnia, somnolence, and tremor. The only significant differences in TEAE were seen between young and elderly groups with anxiety disorders (>3% higher for LEV than for placebo-treated patients) in headache (5.2% elderly, -0.9% young, P=0.041), and tremor (5.2 and -0.5%, respectively, P=0.022) and between young anxiety patients and young epilepsy patients for somnolence (-0.7 and 5.4%, respectively, P=0.036). For the other TEAEs there was no evidence for consistent differences between young and elderly patients and between patients with different CNS disorders. Overall, LEV was well tolerated by all patient groups. The favorable adverse event profile suggests that LEV might be suitable for use by elderly patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Anticonvulsants; Anxiety Disorders; Central Nervous System Diseases; Cognition Disorders; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam

The anticonvulsant effects of the novel antiepileptic drug (AED) levetiracetam (LEV) were tested in neocortical slice preparations from 23 patients who underwent surgery for the treatment of refractory epilepsy.. Slices were used to evaluate the effects of LEV on two different models of epilepsy: low-Mg2+-induced untriggered and bicuculline-evoked stimulus-triggered epileptiform burst discharges and spontaneously appearing rhythmic sharp waves.. LEV (0.1-1 mM) did not influence spontaneously appearing rhythmic sharp waves or Mg2+-free aCSF-induced epileptiform field potentials. LEV affected neither the amplitudes or duration nor the repetition rates of burst discharges in these epilepsy models. However, LEV (100-500 microM) significantly suppressed the ictal-like discharges elicited by the gamma-aminobutyric acid subtype A (GABAA)-receptor antagonist bicuculline. A marked reduction of the amplitude and duration of bicuculline-evoked field response in the presence of LEV was observed.. The results indicate the potential for LEV to inhibit epileptiform burst discharges in human neocortical tissue, which is consistent with its effects in animal models of epilepsy. These results also support the seizure reduction observed in clinical trials and support that this may, in part, be related to the ability of LEV to inhibit epileptiform discharges.

Topics: Adolescent; Adult; Anticonvulsants; Bicuculline; Child; Child, Preschool; Culture Media; Culture Techniques; Electric Stimulation; Electroencephalography; Epilepsy; Evoked Potentials; Female; Humans; Infant; Levetiracetam; Magnesium; Male; Middle Aged; Neocortex; Piracetam

We investigated the effect of the new antiepileptic drug (AED) levetiracetam (LEV) on different types of high-voltage-activated (HVA) Ca2+ channels in freshly isolated CA1 hippocampal neurons of rats.. Patch-clamp recordings of HVA Ca2+ channel activity were obtained from isolated hippocampal CA1 neurons. LEV was applied by gravity flow from a pipette placed near the cell, and solution changes were made by electromicrovalves. Ca2+ channel blockers were used for separation of the channel subtypes.. The currents were measured in controls and after application of 1-200 microM LEV. LEV irreversibly inhibited the HVA calcium current by approximately 18% on the average. With a prepulse stimulation protocol, which can eliminate direct inhibition of Ca2+ channels by G proteins, we found that G proteins were not involved in the pathways underlying the LEV inhibitory effect. This suggested that the inhibitory effect arises from a direct action of LEV on the channel molecule. The blocking mechanism of LEV was not related to changes in steady-state activation or inactivation of Ca2+ channels. LEV also did not influence the rundown of the HVA Ca2+ current during experimental protocols lasting approximately 10 min. Finally, LEV at the highest concentration used (200 microM) did not influence the activity of L-, P- or Q-type Ca2+ channels in CA1 neurons, while selectively influencing the activity of N-type calcium channels. The maximal effect on these channels separated from other channel types was approximately 37%.. Our results provide evidence that LEV selectively inhibits N-type Ca2+ channels of CA1 pyramidal hippocampal neurons. These data suggest the existence of a subtype of N-type channels sensitive to LEV, which might be involved in the molecular basis of its antiepileptic action.

Topics: Animals; Anticonvulsants; Calcium Channel Blockers; Calcium Channels, N-Type; Dose-Response Relationship, Drug; Electric Stimulation; Epilepsy; Hippocampus; Kinetics; Levetiracetam; Neurons; Nifedipine; omega-Conotoxin GVIA; Patch-Clamp Techniques; Piracetam; Rats; Rats, Wistar

Levetiracetam is a novel antiepileptic drug with an unknown mechanism of action. To-date levetiracetam is not known to be associated with any clinically significant pharmacokinetic interaction. Similarly, levetiracetam has not been associated with any pharmacodynamic interactions. We present four patients with severe refractory epilepsy in whom introduction of levetiracetam led to disabling symptoms compatible with carbamazepine toxicity requiring either carbamazepine dose reduction or levetiracetam withdrawal. As carbamazepine and carbamazepine-epoxide blood levels were not altered during levetiracetam co-medication, a pharmacodynamic interaction is suggested. Therefore, during levetiracetam co-medication with carbamazepine, patients should be monitored closely for symptoms of carbamazepine toxicity.

Topics: Adult; Anticonvulsants; Carbamazepine; Drug Interactions; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam

The effect of the new antiepileptic drug levetiracetam (LEV; KEPPRA) on the neuronal high-voltage-activated (HVA) Ca(2+) current was investigated on pyramidal neurones, visually identified in the CA1 area of rat hippocampal slices. Nystatin-perforated patch clamp recordings were made under experimental conditions designed to study HVA Ca(2+) currents. The HVA current, activated by steadily increasing voltage-ramps, was reversibly eliminated by Cd(2+) and depressed by either nimodipine, or omega-Conotoxin GVIA. After 30 min perfusion of the slices with LEV 32 microM, the current decayed to 55+/-9% (mean+/-SEM; n=9) of the initial value, which is significantly (P<0.05, two-tailed t-test) lower than the rundown to 84+/-10% in a control group (n=10) of neurones. The limited, but significant depression of the neuronal HVA Ca(2+) current, produced by LEV at a clinically relevant concentration, might contribute to the antiepileptic action of the drug.

Topics: Animals; Anticonvulsants; Cadmium; Calcium Channel Blockers; Calcium Channels; Calcium Signaling; Epilepsy; Hippocampus; Levetiracetam; Male; Membrane Potentials; Nimodipine; omega-Conotoxin GVIA; Organ Culture Techniques; Patch-Clamp Techniques; Piracetam; Pyramidal Cells; Rats

Topics: Acetates; Amines; Anticonvulsants; Carbamazepine; Cognition; Cognition Disorders; Cyclohexanecarboxylic Acids; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Piracetam; Tiagabine; Topiramate; Triazines; Triazoles; Vigabatrin

The long-term continuation (retention) rate, efficacy, and safety data of the new antiepileptic drug levetiracetam (LEV) was evaluated in all patients with epilepsy exposed to the drug during its developmental program (n = 1,422). The retention rate was estimated to be 60% after 1 year and 32% after 5 years. Thirty-nine percent (512/1,325) of patients had a seizure reduction of > or =50%, and 13% (183/1,422) became seizure-free for at least 6 months. LEV seems an effective and well tolerated new antiepileptic drug.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Time Factors

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

Levetiracetam is a new anticonvulsant (AED) with a novel mechanism of action. Although it is generally well tolerated with a good cognitive profile, irritability and hostility have been reported in some adults taking levetiracetam. Observations in children are limited; levetiracetam is not yet approved by the Food and Drug Administration for use in children.. In four young patients, acute psychosis developed within days to months of initiation of levetiracetam for seizures.. A 5-year-old girl began having visual hallucinations of spiders in her room 14 days after starting levetiracetam. A 13-year-old boy began having auditory hallucinations, insomnia, and screaming behavior 3 months after initiation of levetiracetam. A 16-year-old girl became acutely agitated, hyperreligious, and had persecutory delusions within 7 days of starting levetiracetam. A 17-year-old girl had auditory hallucinations telling her to sing and yell after 30 days of taking the drug. All four children had dramatic improvement within days of either discontinuing or decreasing the dose of levetiracetam. The three adolescents had historical findings consistent with mild behavioral problems before initiating levetiracetam, and all four patients had prior cognitive deficits.. Reversible treatment-emergent psychosis associated with levetiracetam therapy was observed in four children and adolescents. Whether rapid initiation or prior neurobehavioral problems predispose to this side effect is not established.

Topics: Acute Disease; Adolescent; Anticonvulsants; Child, Preschool; Comorbidity; Drug Administration Schedule; Epilepsy; Female; Humans; Learning Disabilities; Levetiracetam; Male; Mental Disorders; Piracetam; Psychoses, Substance-Induced; Remission, Spontaneous

Topics: Adult; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Clinical Trials as Topic; Drug Interactions; Epilepsy; Humans; Intestinal Absorption; Isoxazoles; Levetiracetam; Nootropic Agents; Oxcarbazepine; Piracetam; Sodium Channel Blockers; Zonisamide

Levetiracetam has recently been approved as an adjunctive medication for partial seizures and frequently will be added to phenytoin. The objective of this study was to determine the presence or absence of a pharmacokinetic drug interaction of levetiracetam with phenytoin. A stable isotope tracer technique using deuterium-labeled (D10) phenytoin and high-performance liquid chromatography with ultraviolet detection (rather than mass spectrometric detection) was employed. Tracer doses of D10-phenytoin were administered i.v. before and 12 weeks after adding levetiracetam to the regimen of 6 subjects on phenytoin monotherapy for epilepsy. Blood was collected for 96 hours after each infusion. The following pharmacokinetic parameters were determined for phenytoin: Cmax, Cmin, Cavo, AUC, CL, t 1/2, VD, and free (nonprotein bound) fraction. The ratio and the 90% confidence interval of the ratio of log-transformed mean values for phenytoin pharmacokinetic parameters before (denominator) and after (numerator) adding levetiracetam all fell within the range of 0.85 to 1.17 (two one-sided test). The authors conclude that the addition of levetiracetam did not bring about clinically important changes in phenytoin pharmacokinetic parameters and that it is not necessary to change the phenytoin dosing rate when levetiracetam is added to phenytoin.

Topics: Adult; Anticonvulsants; Drug Interactions; Drug Therapy, Combination; Epilepsy; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam

Field potentials were recorded from rat hippocampal slices in order to compare the electrophysiological action of the new antiepileptic drug (AED), levetiracetam (LEV), with that of the classical AEDs, valproate, clonazepam and carbamazepine, on epileptiform responses induced by a 'high K(+)-low Ca(2+)' perfusion fluid. Increasing [K(+)] from 3 to 7.5 mM and decreasing [Ca(2+)] from 2.4 to 0.5 mM, in the bathing fluid, produced population spikes (PSs) of increasing amplitudes in the CA3 area of the slices, repetitive PSs evoked by single stimuli, and spontaneous bursts. Clinically relevant concentrations of LEV, 32 and 100 micro M, consistently reduced the second (PS(2)) and third (PS(3)) population spikes, and the number (N) of repetitive PSs per evoked response. Levetiracetam 32 micro M also opposed the increase in amplitude of the first PS (Delta PS(1)). Neither valproate 1 mM, nor clonazepam 1 micro M, nor carbamazepine 50 micro M, produced any decrease in Delta PS(1)and in PS(2), but all decreased N. These results show that LEV contrasts to reference AEDs by its ability to antagonize neuronal (hyper)synchronization, in the highly seizure-prone CA3 area of rat hippocampal slices.

Topics: Animals; Anticonvulsants; Calcium; Carbamazepine; Clonazepam; Electrophysiology; Epilepsy; Evoked Potentials; Hippocampus; In Vitro Techniques; Levetiracetam; Male; Neurons; Piracetam; Potassium; Rats; Rats, Sprague-Dawley; Valproic Acid

Since the beginning of the 1990's, a dozen of new anti-epileptic drugs have been on the market or will be soon. This article reviews the daily clinical utilisation of new anti-epileptic drugs. It considers, without being complete, the current opinions and tendencies. The new anti-epileptic substances are generally as efficient as conventional medications. However, they are better tolerated and are more easily used in combination with conventional anti-epileptic drugs. Polytherapy is certainly the form of treatment, which is used in the most cases of resistant epilepsies. The surgical treatment can be used in only a very limited number of cases. The objective of treatment is the complete control of seizures, with minimum secondary effects. Though this objective is rarely reached, the NAE significantly improves the quality of life of patients suffering from severe epilepsy. The utilisation of NAE is not without risk. Increase in the frequency and severity of seizures may occur; we should remember that severe adverse effects appeared in the post-marketing period of the use of Vigabatrine and Felbamate. Therefore, we must remain vigilant in the clinical use of the anti-epileptic drugs.

Topics: Acetates; Amines; Anemia, Aplastic; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Drug Tolerance; Epilepsy; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Phenylcarbamates; Piracetam; Propylene Glycols; Tiagabine; Topiramate; Triazines; Vigabatrin; Visual Fields

We have previously shown that the novel anticonvulsant levetiracetam exerts potent anticonvulsant activity against both focal and secondarily generalized seizures in fully amygdala-kindled rats, i.e. , a model of temporal lobe epilepsy. We examined whether levetiracetam also exhibits antiepileptogenic activity, i.e., prevents or retards acquisition or development of amygdala-kindling in rats. Before the experiments with chronic administration of levetiracetam at different doses, we determined the pharmacokinetics of the drug after i.p. injection. Levetiracetam had a relatively short half-life (about 2-3 hr) in rats, so that any lasting effects of the drug after chronic administration were certainly not due to drug accumulation. When rats were treated with levetiracetam during kindling acquisition at daily i.p. doses of 13, 27 or 54 mg/kg, the drug dose-dependently suppressed the increase in seizure severity and duration induced by repeated amygdala stimulation. After termination of daily treatment with 54 mg/kg, duration of behavioral seizures and of afterdischarges recorded from the amygdala remained to be significantly shorter compared to vehicle controls, although amygdala stimulations were continued in the absence of drug. These data thus indicate that levetiracetam not simply masked the expression of kindled seizures through an anticonvulsant action, but exerted a true antiepileptogenic effect. Adverse effects were not observed at any dose of levetiracetam tested in kindled rats. The powerful antiepileptogenic activity of levetiracetam in the kindling model indicates that levetiracetam is not only an interesting novel drug for symptomatic treatment of epilepsy but might be suited for pharmacological prevention of this disease in patients with a high prospective risk of the development of epilepsy.

Topics: Animals; Anticonvulsants; Behavior, Animal; Epilepsy; Female; Kindling, Neurologic; Levetiracetam; Piracetam; Rats; Rats, Wistar

The protective and adverse effect potentials of levetiracetam ((S)-alpha-ethyl-2-oxo-pyrrolidine acetamide) in rodent models of seizures and epilepsy were compared with the profile of several currently prescribed and newly developed antiepileptic drugs. Levetiracetam was devoid of anticonvulsant activity in the acute maximal electroshock seizure test and in the maximal pentylenetetrazol seizure test in mice (up to 540 mg/kg, i.p.) but exhibited potent protection against generalised epileptic seizures in electrically and pentylenetetrazol-kindled mice (ED50 values = 7 and 36 mg/kg, respectively, i.p.). This differs markedly from established and most new antiepileptic drugs which induce significant protection in both the acute seizure tests and the kindling models. Furthermore, levetiracetam was devoid of anticonvulsant activity in several maximal chemoconvulsive seizure tests although an interesting exception was the potent protection observed against secondarily generalised activity from focal seizures induced by pilocarpine in mice (ED50 value = 7 mg/kg, i.p.), pilocarpine and kainic acid in rats (minimum active dose = 17 and 54 mg/kg, respectively, i.p.). The protection afforded by levetiracetam on the threshold for methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM)-induced seizures persisted after chronic administration (17-170 mg/kg, i.p., twice daily/14 days) and levetiracetam did not lower the seizure threshold for the proconvulsant action of the inverse benzodiazepine receptor agonist, N-methyl-beta-carboline-3-carboxamide (FG 7142). The main metabolite of levetiracetam (ucb L057; (S)-alpha-ethyl-2-oxo-1-pyrrolidine acetic acid) was found to be inactive in sound-sensitive mice after acute administration of doses up to 548 mg/kg, i.p. Levetiracetam induced only minor behavioural alterations in both normal and amygdala-kindled rats (54-1700 mg/kg, i.p.) resulting in an unusually high safety margin between rotarod impairment and seizure suppression of 148 in corneally kindled mice and 235 in Genetic Absence Epilepsy Rats from Strasbourg. In comparison, existing antiepileptic drugs have ratios between 2 and 17 in the corneally kindled mouse model. These studies reveal a unique profile of levetiracetam in rodent models. Characteristics are a general lack of anticonvulsant activity against maximal, acute seizures and selective protection with a very high safety margin in genetic and kindled animals and against chemoconvulsants producing par

Topics: Amygdala; Animals; Anticonvulsants; Behavior, Animal; Carbolines; Convulsants; Diazepam; Disease Models, Animal; Electroconvulsive Therapy; Epilepsy; Excitatory Amino Acid Agonists; Flumazenil; GABA-A Receptor Antagonists; Kindling, Neurologic; Levetiracetam; Male; Mice; Pentylenetetrazole; Piracetam; Rats; Rats, Sprague-Dawley; Seizures

Previous behavioural and electrophysiological studies have indicated that levetiracetam (ucb LO59) acts as an anticonvulsant drug in vivo. The purpose of the present study was to investigate the effects of levetiracetam on normal synaptic transmission and epileptiform activity in vitro. Intracellular recordings were obtained from the CA3 subfield of the rat hippocampal slice preparation. Levetiracetam in a concentration of 10 microM did not influence basic cell properties or normal synaptic transmission evoked by subthreshold and suprathreshold stimuli to the commissural pathway. However, it strongly inhibited the development of epileptiform bursting by the gamma-aminobutyric acid (GABA)A-receptor antagonist bicuculline (1-30 microM). Levetiracetam also decreased the size of bursts previously established by bicuculline. In experiments in which the glutamate-receptor agonist N-Methyl-D-Aspartate (NMDA) was used to generate spontaneous bursting, levetiracetam had no effect on the size of the bursts but decreased bursting frequency. The difference in effects of levetiracetam on bicuculline- and NMDA-induced bursting appeared to be dependent on the convulsant used, since in the presence of 10 microM bicuculline, levetiracetam decreased the size of NMDA-bursts to the same extent as the size of synaptically evoked bicuculline-bursts but had little effect on bursting frequency. The results show that under our experimental conditions, levetiracetam did not alter the components of normal synaptic transmission. However, levetiracetam at the concentrations studied inhibited epileptiform bursting induced by bicuculline and NMDA in vitro in a manner consistent with the profile of an antiepileptogenic drug.

Topics: Animals; Anticonvulsants; Bicuculline; Drug Interactions; Electric Stimulation; Epilepsy; GABA Antagonists; Levetiracetam; Male; Membrane Potentials; Models, Biological; Piracetam; Pyramidal Cells; Rats; Rats, Sprague-Dawley; Synaptic Transmission

The Third Eilat Conference on New Antiepileptic Drugs was held at the Royal Beach Hotel from May 27 to May 30, 1996. Epileptologists and scientists from 20 countries attended the conference, which was held to discuss critical issues in drug development, new antiepileptic drugs (AEDs) in development, progress reports and recent findings of newly marketed AEDs, the use of AEDs in special populations and their utilization in non-epileptic disorders. Over the last seven years, six new AEDs have been introduced worldwide and new information on their safety and efficacy has become available. These include felbamate, gabapentin, lamotrigine, oxcarbazepine, topiramate and vigabatrin. Drugs in development include those at an advanced stage, such as remacemide and tiagabine, as well as those just entering clinical trials, such as rufinamide (CGP 331010) and levetiracetam (ucb LO59). The following is a summary of the presentations for drugs in development and recent findings on newly marketed drugs.

Topics: Acetamides; Animals; Anticonvulsants; Azetidines; Carbamates; Drug Evaluation, Preclinical; Drugs, Investigational; Epilepsy; Humans; Israel; Levetiracetam; Nipecotic Acids; Phenylenediamines; Piracetam; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; Thiazoles; Tiagabine; Triazoles

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