levetiracetam and Disorders-of-Excessive-Somnolence

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

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

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

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

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

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

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

Levetiracetam (LEV) is often chosen early in the treatment of refractory epilepsy; however, its adverse effects have largely been studied as part of clinical trials. Oxcarbazepine and valproate (VPA) are the other commonly used AEDs and, hence, serve as good comparators. This study was conducted to evaluate behavioral abnormalities and somnolence among patients with epilepsy being treated with LEV and/or OXC compared with those receiving VPA.. Data of consecutive patients attending our intractable epilepsy clinic over a 2 1/2-year period were reviewed, and patients with at least one seizure a month, who had been initiated on either or a combination of LEV, VPA, or OXC, were included for analysis. Data regarding behavioral adverse effects, daytime somnolence (EDS), and weight changes were collected apart from those regarding any major effect necessitating dose reduction or discontinuation of the AED.. Among a total of 445 patients screened, 292 (93 F, median age: 21years [range: 8-54]; 237 focal and 55 generalized epilepsy) fulfilled inclusion criteria. Median epilepsy duration was 11years. Levetiracetam had been introduced in 114 patients, VPA in 134, and OXC in 151 during the study period. Twenty-three were on LEV+OXC, 27 on LEV+VPA, and 33 on VPA+OXC. Behavioral disturbances (irritability, obsessive manifestations, aggressiveness, and frank psychosis) were observed in 43 patients; 23 on introduction of LEV (20.2%); LEV was discontinued in 10 (9%). Daytime somnolence was reported by 28 patients, 15 on OXC (10%); 8 received oral modafinil for the same, while none discontinued this AED. Only one patient on LEV and 3 on VPA reported EDS. Menstrual disturbances were reported by 9, weight gain by 3, and severe hair loss by 2 females on VPA.. Behavioral disturbances with levetiracetam are common among patients with refractory epilepsy while somnolence is common with oxcarbazepine. Antiepileptic drugs should be selected with this in perspective.

Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; Child; Disorders of Excessive Somnolence; Drug Resistant Epilepsy; Female; Humans; Irritable Mood; Levetiracetam; Male; Middle Aged; Obsessive Behavior; Oxcarbazepine; Piracetam; Psychoses, Substance-Induced; Retrospective Studies; Young Adult

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

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

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

Levetiracetam-treated patients commonly report daytime drowsiness, fatique, asthenia and decreasing of motor activity. However the origin of these reported side effects are still debated, we aimed to clarify effect of levetiracetam on sleep. Therefore this prospective study was conducted to evaluate the effects of levetiracetam on motor activity, amount and continuity of sleep and napping.. Various tests were performed on twenty two patients treated with levetiracetam (10 monotherapy, 12 add-on therapy) at least three days before the initiation of treatment, and consecutively for five to eight days at the third week of treatment. These tests included sleep logs, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Modified Maintenance of Wakefulness Test and actimetric measurements. In order to evaluate the sleep behavior of these patients the following sleep parameters were estimated: bedtime, wake-up time, sleep-onset time, sleep-offset time, sleep latency, total sleep time, wake time after sleep onset, fragmentation index, total activity score, nap episodes, total nap duration and sleep efficiency. Twenty members of staff from our hospital (Doctor, nurse, secretary, civil servant etc.) were evaluated as control subjects in the study.. After three-week treatment with levetiracetam (in particular with add-on therapy), Epworth Sleepiness Scale scores, napping episodes and total nap durations increased and sleep latencies decreased. While durations of Modified Maintenance of Wakefulness Test and total activity scores decreased. However the total sleep time and the sleep efficiency did not show any difference from the pre-treatment values.. Our results suggest that levetiracetam leads to drowsiness by decreasing the daily motor activity and increasing the naps; however this agent does not have any major effects on total sleep time and sleep efficiency during night. Actimetric analyses give information about continuity of sleep and sleep/wake states however does not give satisfactory information about architecture of sleep. In order to determine the effects of levetiracetam on the sleep architecture we need similiar protocol studies by full night polysomnography.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Disorders of Excessive Somnolence; Electroencephalography; Epilepsy, Complex Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Motor Activity; Piracetam; Prospective Studies; Severity of Illness Index; Sleep; Sleep Stages; Surveys and Questionnaires; Wakefulness

The spontaneous occurrence of blepharospasm and dystonic movements in face muscles, particularly those of the perioral and mandibular regions, has been named as Meige's disease which was first described by Henry Meige in 1910. We report the case of a woman with Meige's syndrome whose symptoms improved with the use of levetiracetam.

Topics: Anticonvulsants; Botulinum Toxins, Type A; Brain; Disorders of Excessive Somnolence; Dose-Response Relationship, Drug; Electromyography; Facial Muscles; Female; Humans; Ion Channels; Levetiracetam; Meige Syndrome; Middle Aged; Molecular Chaperones; Piracetam; Treatment Outcome

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

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

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

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