levetiracetam and Sleep-Wake-Disorders

Electric Status Epilepticus during Sleep (ESES) occurs in children with and without epilepsy. It may be related to disturbances as autism spectrum disorder, attention-deficit hyperactivity disorder and acquired aphasia (Landau-Kleffner syndrome). Antiepileptic drug (AED) treatment has been reported in small studies without placebo control. This study was designed to assess AED effect in a placebo-controlled double-blind cross-over study. Levetiracetam (LEV) was chosen based on clinical evidence. Eighteen patients fulfilled the inclusion criteria. The mean spike index at baseline was 56, falling to a mean of 37 at the end of the LEV treatment period. Assessed with a 2-way ANOVA, there is a significant treatment effect (p<0.0002). To the best of our knowledge, this is the first placebo-controlled double-blind cross-over study for any AED in patients with ESES. The effect of LEV is comparable with its effect in treatment of epileptic seizures.

Topics: Analysis of Variance; Anticonvulsants; Child; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Electroencephalography; Epilepsies, Myoclonic; Female; Humans; Levetiracetam; Male; Piracetam; Sleep Wake Disorders; Treatment Outcome

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

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

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

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

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

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

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

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

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

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

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

Topics: Adult; Anticonvulsants; Epilepsy, Frontal Lobe; Humans; Levetiracetam; Male; Piracetam; Polysomnography; Sleep Wake Disorders; Tourette Syndrome

We studied 52 patients with electric status epilepticus in slow sleep (EESSS) during 3-5 years. Age-dependent peculiarities of clinical course of the disease, risk factors for EESSS and rational approaches to antiepileptic treatment for these cases were singled out. Symptomatic and idiopathic EESSS variants were revealed. Combinations of valproates, levetiracetam and ethosuximidum were the most effective antiepileptic drugs in the treatment of EESSS.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Drug Resistance; Electricity; Electroencephalography; Ethosuximide; Female; Humans; Levetiracetam; Male; Piracetam; Sleep Stages; Sleep Wake Disorders; Status Epilepticus; Syndrome; Valproic Acid

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

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