Efficacy Of Levetiracetam Research Articles

Levetiracetam for seizure prevention in brain tumor patients: a systematic review

Seizures are common complications for patients with brain tumors. No clear evidence exists regarding the use of antiepileptic agents for prophylactic use yet newer agents are being favoured in many clinical settings. The objective of this systematic review was to determine the efficacy of levetiracetam for preventing seizures in patients with brain tumors. A literature search was completed using the databases PubMed (1948 to December 2015), EMBASE (1980 to December 2015), Cochrane Database of Systematic Reviews, and Google Scholar. Studies were included if they reported seizure frequency data pertaining to levetiracetam use in patients with brain tumors as either monotherapy or as an add on agent. The literature search produced 21 articles (3 randomized controlled trials, seven prospective observational studies, and 11 retrospective observational studies). All studies were found to be at high risk of bias. Overall, studies show levetiracetam decreased seizure frequency in brain tumor patients with or without craniotomy. Safety outcomes were also favourable. As such, levetiracetam appears effective for reducing seizures in patients with brain tumors and may be considered a first-line agent. However, there is an urgent need for more high quality prospective data assessing levetiracetam and other antiepileptic drugs in this population.

Prevalence of Early Posttraumatic Seizures in Children With Moderate to Severe Traumatic Brain Injury Despite Levetiracetam Prophylaxis*

To evaluate the prevalence of early seizures after levetiracetam prophylaxis in children with moderate to severe traumatic brain injury. Prospective observational study. Level 1 pediatric trauma center. We enrolled 34 patients between the ages of 0-18 years with moderate to severe traumatic brain injury admitted to the PICU at a level 1 trauma center who received levetiracetam for early posttraumatic seizure prophylaxis. Primary outcome was the prevalence of early posttraumatic seizures that were defined as clinical seizures within 7 days of injury. In 6 of 34 patients (17%), clinical seizures developed despite levetiracetam prophylaxis. An additional two patients had nonconvulsive seizures. This prevalence is similar to that reported in the literature in this patient population who do not receive seizure prophylaxis (20-53%) and is higher than that in patients who receive phenytoin prophylaxis (2-15%). Patients with early posttraumatic seizures were younger (median age, 4 mo) (p < 0.001) and more likely to have suffered from abusive head trauma (p < 0.0004). Early clinical posttraumatic seizures occurred frequently in children with moderate to severe traumatic brain injury despite seizure prophylaxis with levetiracetam. Younger children and those with abusive head trauma were at increased risk of seizures. Further studies are needed to evaluate the efficacy of levetiracetam before it is routinely used for seizure prophylaxis in these children, particularly in young children and those who have suffered from abusive head trauma.

Neuroprotective effects of chronic administration of levetiracetam in a rat model of diabetic neuropathy

ObjectiveDiabetic neuropathy (DNP) is a frequent and serious complication of diabetes mellitus (DM) that leads to progressive and length-dependent loss of peripheral nerve axons. The purpose of the present study is to assess the neuroprotective effects of levetiracetam (LEV) on DNP in a streptozotocin (STZ)-induced DM model in rats. MethodsAdult Sprague-Dawley rats were administered with STZ (60mg/kg) to induce diabetes. DNP was confirmed by electromyography (EMG) and motor function test on 21st day following STZ injection. Study groups were assigned as follows; Group 1: Naïve control (n=8), Group 2: DM+1mL/kg saline (n=12), Group 3: DM+300mg/kg LEV (n=10), Group 4: DM+600mg/kg LEV (n=10). LEV was administered i.p. for 30 consecutive days. Then, EMG, motor function test, biochemical analysis (plasma lipid peroxides and total anti-oxidant capacity), histological and immunohistochemical analysis of sciatic nerves (TUNEL assay, bax, caspase 3, caspase 8 and NGF) were performed to evaluate the efficacy of LEV. ResultsTreatment of diabetic rats with LEV significantly attenuated the inflammation and fibrosis in sciatic nerves and prevented electrophysiological alterations. Immunohistochemistry of sciatic nerves showed a considerable increase in bax, caspase 3 and caspase 8 and a decrease in NGF expression in saline-treated rats whereas LEV significantly suppressed apoptosis markers and prevented the reduction in NGF expression. Besides, LEV considerably reduced plasma lipid peroxides and increased total anti-oxidant capacity in diabetic rats. ConclusionsThe results of the present study suggest that LEV may have therapeutic effects in DNP through modulation of anti-oxidant and anti-apoptotic pathways.

Efficacy of Levetiracetam as an Add-on Therapy in Children with Localization-related Epilepsy

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.

Blockade of endothelin B receptor improves the efficacy of levetiracetam in chronic epileptic rats

PurposeTo 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. MethodsLithium-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. ResultsCompared 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. ConclusionTo 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.

Levetiracetam: Pharmacological properties, safety and efficacy in the pediatric population with epilepsy

Age-specific distribution of epilepsy is bimodal, with the highest incidence being in childhood. Seizures can affect life as early as day one. There is a paramount variation of epilepsy in childhood and adolesence with regards to its etiology and prognosis. Antiepileptic drugs, being the mainstay of treatment, necessitates that their use in this vulnerable age group must be made after a thorough look into the available evidence. The data on levetiracetam (LEV), a second-generation antiepileptic, spans from randomized controlled trials to case reports in various pediatric epilepsy and epileptic syndromes. This review is a compilation and critical analysis of the data on the differences in the pharmacokinetic properties of LEV in children versus adults, drug-interactions, efficacy of LEV in various contexts, namely, as add-on, as monotherapy, in partial and generalized seizures, in specific epilepsy syndromes such as benign epilepsy with centrotemporal spikes, epileptic syndromes with contin- uous spike and wave during sleep, Lennox-Gastaut syndrome, Jeavons syndrome and epilepsy associated with tuberous sclerosis. LEV is an effective option for the treatment of partial-onset seizures as both an add-on in refractory epilepsy and monotherapy in newly diagnosed focal epilepsies. There are preliminary but promising data available on various epileptic syndromes and epi- leptic encephalopathies that can nudge researchers towards further work in these areas in order to generate evidences that is more substantial. The safety and tolerability profile of LEV is favorable, though, behavioral and neuropsychiatric adverse events are reportedly higher in children versus adults. The neuropsychiatric adverse events are often observed against the background of previously existing behavioral issues and neurocognitive impairments.

Lack of efficacy of levetiracetam and worsening of epileptic negative myoclonus

Epileptic negative myoclonus (ENM) is an infrequent seizure type seen in association with a variety of epileptic syndromes. It has been reported to occur inbenign focal epilepsies of childhood and can be worsened by a number of antiepileptic medications. Levetiracetam widely used to treat positive myoclonus in diverse clinical situations has also been reported as a therapeutic option. We report two children with partial epilepsy that demonstrated induction of ENM in one and worsening of ENM in the second patient on levetiracetam.

Efficacy of levetiracetam as first add-on therapy to carbamazepine and valproate sodium for children with epilepsy

We examined the effectiveness of levetiracetam (LEV) as add-on therapy after failed treatment with a first anti-epileptic drug in a prospective cohort of children with epilepsy. Eligible patients with epilepsy experienced uncontrolled seizures with the first anti-epileptic drug and were 1-15-year-old. Afte ra3m obaseline period, patients were administered LEV at an initial dose of 10 mg/kg/d, which, if needed, was incrementally increased by 5 mg/kg/d weekly up to a maximum dose of 60 mg/kg/d. Seizure frequency was defined as the mean seizure frequency per month. Clinical response to LEV over the following period of at least 6 mo was divided into five categories. A total of 37 patients were enrolled. The majority of patients (97.30%) had localization-related epilepsy. The responder rate (rate of patients with ≥50% reduction in seizure frequency) was 30/37 (81.08%). In addition, 20 of 37 (54.05%) patients showed complete seizure cessation. Mean percentage reduction in seizure frequency (all types of seizures) during the first 6 mo treatment period compared to baseline was 89.28% in responders, compared with 25.22% in non-responders. This proportion remained stable during the second 6 mo period (90.17%). Significant changes in seizure frequency were seen between before LEV administration and both the first 6 mo (P < 0.01) and second 6 mo (P < 0.01) in responders, but not in non-responders. Mean effective dose of LEV was 27.51 mg/kg/d. Somnolence was the only reported individual adverse event (5.41%), and was mild in all cases, so LEV discontinuation was not needed. LEV appears useful as a first add-on treatment in children with localization-related epilepsy.

PP02.11 – 2668: Efficacy of levetiracetam in a neonatal intensive care cohort

Objective Neonatal seizures are the most common neurological emergency in newborns. Up to date, phenobarbitone (Pb) is the recommended first-line antiepileptic drug (AED), although animal and human studies have reported neuronal damage (apoptosis and even cell death) and consecutive impairment after its use. Levetiracetam (LEV) seems to have a more favorable profile, but only few data are available concerning its use in newborns. Methods We retrospectively analyzed data from all neonates treated with LEV at our institution 2009–2014 as second line treatment following treatment with Pb. Response was defined as being seizure free (SF) or ≥50% reduction in seizure frequency (SR). Results Data from 35 neonates (21 males) were analyzed. The mean gestational age at birth was 37+1 weeks, birth weight 3060 g. LEV was administered at a mean postnatal age of 16 days. Etiologies were vascular insults in 20 (57.1%), brain malformation in 9 (25.7%), genetic/metabolic disorders in 5 (14.3%) and CNS infections in 1 (2.9%) patients. Duration of LEV treatment was Conclusion Our results illustrate that treatment with LEV is effective and safe in newborn infants. Prospective controlled studies and long-term evaluation of developmental outcome are warranted to further assess efficacy and safety of LEV in newborn infants.

P9 – 2231: The efficacy of Levetiracetam for the treatment of neonatal seizures

Objective Neonatal seizures are often refractory to treatment with the standard antiseizure medications. Current therapeutic options for treatment of neonatal seizures, such as phenobarbital and phenytoin lack efficacy, and potentially harmful to the developing brain. Thus, we tried any alternatives to achieve controls in neonatal seizures that were refractory to standard antiseizure agents. Despite the lack of published data regarding the safety, tolerability and efficacy of Levetiracetam (LVT) in the neonatal age group. Methods We report a retrospectively identified cohort of 17 neonates who received Levetiracetam. They were thoroughly investigated including EEGs and neuroimaging. Levetiracetam was considered effectives if administration associated with more than 50 reduction in seizures within 48 hours. Levetiracetam was initiated to full term babies only. The mean initial dose was 20 mg/kg and the mean maintenance dose was 40 mg/kg in two divided doses. Results No respiratory or cardiac side effects were detected. Levetiracetam was associated with a greater than 50% seizure reduction in 8 out of the 17 neonates (47%) including seizure termination in 5 (29%). Conclusion Further multicenter larger studies is recommended to determine the safety and the optimal dosing of Levetiracetam in neonates and to compare it is efficacy to other antiseizure medications in order to assess whether this medication deserve widespread use in clinical practice.

Efficacy of generic levetiracetam (epiterra) in monotherapy for epilepsy in adult patients: preliminary results

Objective : to evaluate the efficacy and tolerability of levetiracetam (LEV) (epiterra, TEVA) in adult patients with focal epilepsy (FE) or juvenile myoclonic epilepsy (JME) who took the drug for і6 months as of December 15, 2014. Patients and methods. The efficacy of LEV as a generic (epiterra) used in monotherapy was analyzed in 23 patients with FE and in 4 female patients with JME who had taken the drug for ≥6 months. In FE, LEV was switched to epiterra because of the high cost of the former and inadequate efficacy/poor tolerability of initial antiepileptic drugs (AEDs) in 17 and 6 cases, respectively. In JMA, epiterra was prescribed as initial therapy in 2 cases and, with the diagnosis being changed, in 2 more patients. Results and discussion. When LEV was switched to its generic, the indicators of efficacy, tolerability, quality of life, and a plain electroencephalogram (EEG) were significantly unchanged. When epiterra was substituted for other AEDs, the efficiency of its therapy was also significantly unchanged and tolerance, quality of life, and EEG characteristics were improved. Epiterra’s adverse reactions as sleepiness (n = 1) and a higher rate of mental processes (n=1) were observed exclusively when it was switched from another AED. However, they were transient (for 2–3 weeks) and seen during either dose adjustment or at the stage of transitional combined therapy. Dual therapy (valproate + epiterra) had to be used in only 1 female patient. Thus, the 6-month use of epiterra in adult patients with FE as an alternative to brand LEV did not deteriorate the clinical picture of the disease (remission rates and injury frequency and severity were significantly unchanged) baseline tolerability, quality of life, or plain EEG values. The findings suggest that the use of epiterra is highly promising in epileptology, particularly in FE and JME in adult patients.

Intravenous levetiracetam in Thai children and adolescents with status epilepticus and acute repetitive seizures.

Intravenous levetiracetam is an option for treatment of status epilepticus (SE) and acute repetitive seizures (ARS). However, there have been relatively few studies with children and adolescents. Also, an appropriate dosage has yet to be determined. This study investigated the safety and the efficacy of levetiracetam for intravenous treatment of convulsive status epilepticus and acute repetitive seizures in children and adolescents. Retrospectively, the study reviewed the medical records of 19 male and 31 female patients under 18 years of age who had received intravenous levetiracetam treatment either for acute repetitive seizures or for convulsive status epilepticus. The patients were admitted between April 1st, 2010 and December 31st, 2011 to the Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Data were collected on underlying illnesses, etiology of seizures, indication for levetiracetam therapy, initial dosage, rate of infusion, untoward effects during infusion and emerged complications. Efficacy of treatment was defined as the termination of seizure within 30 min of completing levetiracetam infusion and no seizure recurrence within 6 h of initial treatment. The age range of the 50 patients was from one day to 18 years (mean 79.6 months). The analysis included 52 episodes of 34 acute repetitive seizures (63.4%) and 18 convulsive status epilepticus (34.6%). Infusion rates ranged from 2 to 66 mg/kg/min (mean 29.6). Cessation of seizure was obtained in 59.6% of 52 episodes. Patients with underlying drug resistant epilepsy did not respond to levetiracetam therapy as well as patients with other etiology of seizures. There were no adverse drug reactions or untoward effects observed during the therapy. Intravenous administration of levetiracetam is safe and effective for treatment of acute repetitive seizures and convulsive status epilepticus in children and adolescents. Failure of treatment may be related to underlying drug resistant epilepsy. Further study of appropriate initial dosage and pharmacokinetic variations in the patients is needed as possible explanation of the unresponsiveness.

Correlation Between Efficacy of Levetiracetam and Serum Levels Among Children With Refractory Epilepsy

BackgroundLevetiracetam is used as adjunctive therapy in various types of seizures. Studies evaluating the effect of levetiracetam on children with refractory epilepsy are scarce. The aim of this study was to evaluate the correlation between serum concentration of levetiracetam and either efficacy or tolerability in children with refractory epilepsy, and to determine the value of levetiracetam blood level monitoring. MethodsMedical records of 50 children with refractory epilepsy treated with levetiracetam and regularly followed at Assaf Harofeh Medical Center were retrospectively reviewed. Trough serum levetiracetam concentration was determined using high-performance liquid chromatography and correlated with the administered dose and clinical report. ResultsNo correlation between levetiracetam serum levels and clinical efficacy, tolerability or administered dosage was found. The average dose of levetiracetam was 43.7 ± 20.0 (range 14-100) mg/kg/day and the average serum concentration was 16.0 ± 9.5 (range 2.5-38.5) μg/mL. Forty-five patients (95%) had more than a 50% reduction of seizure frequency, with 22 (44%) patients becoming seizure-free for at least 6 months. Adverse events related to levetiracetam were reported in 15 (30%) patients. No correlation between serum concentrations and adverse events was found. These results were not affected by gender, age, type of seizure, and other drugs. ConclusionsDetermination of serum concentration is not needed in all children treated with levetiracetam. Serum concentrations may be valuable either in patients with refractory epilepsy for compliance evaluation or in patients with satisfactory control of seizures for determination of their therapeutic baseline.

Levetiracetam efficacy in children with epilepsy with electrical status epilepticus in sleep

PurposeEpilepsy 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. MethodsClinical 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. ResultsThirty-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. ConclusionsLevetiracetam is safe and may be efficient when used to treat ESES syndrome; however, the efficacy EEG neuropsychological outcomes is limited on the whole.

Comparison of Levetiracetam and sodium Valproate in migraine prophylaxis: A randomized placebo-controlled study.

Background:Migraine is a chronic and disabling disorder. Treatment of migraine often comprises of symptomatic (abortive) and preventive (prophylactic) treatment. The current drugs used in migraine prophylaxis include antidepressant drugs (Serotonin Reuptake Inhibitors, Tricyclic antidepressants), and anti-epileptic drugs (valproate, gabapentin, etc).Objective:The objective of our study was to assess the efficacy and tolerability of levetiracetam in adult migraine prophylaxis, compared to valproate and placebo.Materials and Methods:We conducted a prospective, randomized, placebo-controlled study. A total of 85 patients were randomized to receive levetiracetam 500 mg/d (n = 27), valproate 500 mg/d (n = 32) or placebo (n = 26). The patients were evaluated for treatment efficacy after 6 months. Efficacy was assessed as a more than 50% decrease in headache frequency.Results:In levetiracetam group, 17 (63.0%) patients experienced a more than 50% decrease in headache frequency, while this efficacy number was 21 (65.6%) for valproate group and 4 (15.4%) for placebo group. The difference was not statistically significant between levetiracetam and valproate, while it was significant when comparing either levetiracetam or valproate to placebo.Conclusion:Compared to placebo, levetiracetam offers improvement in headache frequency in patients with migraine. The efficacy of levetiracetam in migraine prophylaxis is comparable to currently used drugs such as valproate.

Levetiracetam (Keppra) efficacy and safety in the prevention of early-onset seizures following traumatic brain injuries in pediatric patients

AbstractIntroductionApproximately half a million emergency department visits for traumatic brain injury (TBI) by children and adolescents occur each year. One of the complications of TBI is early-onset seizure. Current guidelines recommend the use of phenytoin for prevention of seizures following a TBI; however, several drug interactions and adverse reactions are associated with its use. Despite studies demonstrating efficacy of levetiracetam in adult patients, the efficacy and safety of levetiracetam in children with TBI is unknown. The purpose of this study was to determine the efficacy and safety of levetiracetam for the prevention of early-onset seizures in pediatric patients following TBI.MethodsA retrospective evaluation was conducted, which included children, ages 0 to 17 years, admitted secondary to a nonpenetrating TBI and who received levetiracetam for seizure prophylaxis for up to 7 days. The primary outcome was the number of children who had a seizure within the first 7 days following a TBI, and secondary outcomes included the number of adverse drug reactions.ResultsA total of 89 pediatrics patients with nonpenetrating TBI were identified and included in the study. Forty-seven patients received a mean dose of 10 mg/kg (SD ± 4.22) of levetiracetam twice a day, and 42 patients received 500 mg 2 times per day (based on adult dosing). Seizure activity was observed in only two patients (2.2%) within the first 7 days following TBI. A total of 13 patients (14.6%) experienced anemia, agitation, and elevation of liver enzymes during levetiracetam therapy.DiscussionThe study suggests that levetiracetam appears to be an effective and safe agent for early-onset seizure prophylaxis in pediatric patients with TBI as indicated by the low number of patients with seizures. The reported adverse reactions may have resulted from the trauma rather than the use of levetiracetam.

Evaluation of levetiracetam as a pre-operative anxiolytic: A randomized, double-blind, placebo-controlled study.

Pre-operative anxiety has been described as a subjective feeling of apprehension, fear, and nervousness.[1] Many pharmacological and non-pharmacological methods have been used to allay anxiety in the pre-operative period. Anticonvulsants such as gabapentin and pregabalin are used effectively to attenuate pre-operative anxiety. Levetiracetam that is a novel antiepileptic drug has also shown anxiolysis property in various studies.[2,3] To date, no clinical study has evaluated the efficacy of levetiracetam in reducing pre-operative anxiety. We conducted this study to assess the effects of levetiracetam on attenuating pre-operative anxiety.

Clinical efficacy of levetiracetam on bone mineral density and bone metabolism in middle-aged and elderly patients with generalized tonic-clonic seizures

To explore the effects of levetiracetam (LEV) on the changes of bone mineral density (BMD) and bone metabolism in the treatment of middle-aged and elderly patients with generalized tonic-clonic seizures. A total of 112 patients with generalized tonic-clonic seizures from October 2012 to March 2014 were selected and divided into LEV and non-medication groups according to therapeutic methods (n = 56 each). LEV was administered to LEV group at an initial dosage of 500 mg twice daily. The same dose of LEV could be added every 2 or 3 weeks based on clonic seizure condition and tolerance. And the maximal dosage was 2 000 mg. The therapeutic duration was ≥ 6 months. No anti-seizure drug was offered for non-medication group. Another 50 healthy subjects served as control group. After 6-month treatment the clinical efficacy of LEV group was evaluated. BMD was detected with bone sonometer (DPX-L) and serum levels of blood calcium (Ca), blood phosphorus (P), alkaline phosphatase and parathyroid hormone were also detected in control group, pre-treatment in non-medication group and post-treatment in LEV group. The rate of abnormal bone volume in non-medication (28.6%) and LEV groups (48.2%) were evidently higher than that in control group (4.0%) (P < 0.05). And it was apparently higher in LEV group than that in non-medication group (P < 0.05). BMD decreased obviously at post-treatment than pre-treatment (P < 0.05). And the post-treatment levels of Ca and P decreased markedly [(2.12 ± 0.19) vs (2.32 ± 0.23) mmol/L; (0.96 ± 0.01) vs (1.23 ± 0.12) mmol/L] while serum levels of alkaline phosphatase and parathyroid hormone increased significantly in LEV group than pre-treatment [(66 ± 6) vs (33 ± 3) µg/L; (62 ± 5) vs (34 ± 3) pmol/L, P < 0.05]. The clinical efficacy of LEV treatment at 1 month was similar to that at 6 months (both 98.21%). And the difference was insignificant (P > 0.05). Single use of LEV is efficacious in the treatment of middle-aged and elderly patients with generalized tonic-clonic seizures. However, both disease and anti-seizure drugs have certain effects on BMD. And long-term application of LEV may lead to bone metabolism dysfunction to some extent.

Levetiracetam as adjunctive therapy for acute alcohol withdrawal syndrome in hospitalized patients.

Benzodiazepines are often considered the standard of care for managing symptoms of acute alcohol withdrawal syndrome. Because of potential adverse effects, other agents have been evaluated in this patient population. Previous studies have produced mixed results on the efficacy of levetiracetam in alcohol withdrawal. The objective of this study was to determine whether adjunctive levetiracetam reduces the amount of symptom-triggered benzodiazepines required by patients experiencing symptoms of alcohol withdrawal. We conducted a retrospective chart review of patients who experienced symptoms of alcohol withdrawal while hospitalized. The outcomes of patients who received adjunctive levetiracetam were compared with those of patients who received only the standard of care (control group). Two hundred fifty patients (125 in each cohort) were included. No significant differences were found in the benzodiazepine requirements of the 2 cohorts. The control group required a median average daily dose of 2.0 mg of lorazepam (range, 0.1-17 mg/d) compared with the levetiracetam group, which required a median average daily dose of 1.3 mg of lorazepam (range, 0.0-53.5 mg/d) (P = 0.09). The patients in the control group required a median total of 6 mg of lorazepam during their hospitalization compared with a median total of 5.5 mg in the levetiracetam group. Both cohorts had a median length of stay of 3 days, although those in the levetiracetam group had a shorter length of intensive care unit stay and spent less time mechanically ventilated. The adjunctive use of levetiracetam does not significantly reduce the benzodiazepine requirements of patients experiencing symptoms of alcohol withdrawal in the inpatient setting.

Profile of anticonvulsant action of levetiracetam, tiagabine and phenobarbital against seizures evoked by DMCM (methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate) in neonatal rats

Levetiracetam (LEV) and tiagabine (TGB) are utilized for the treatment of seizures, including neonatal seizures. However, relatively little is known about the preclinical therapeutic profile of these drugs during brain development. The relative paucity of information regarding these drugs in neonatal animals may be due to their unusual profile of anticonvulsant action in experimental models. LEV and TGB are without effect against seizures in several common screening models (e.g., the maximal electroshock test, maximal pentylenetetrazole seizures), instead showing preferential efficacy against models of partial seizures. We have recently described a method for reliably evoking partial seizures in neonatal animals by systemic administration of the chemoconvulsant, DMCM (Kulick et al., 2014, Eur. J. Pharmacol., doi:10.1016/j.ejphar.2014.06.012). DMCM is a negative allosteric modulator of GABAA receptors, and offers a wide separation between doses required to evoke complex partial as compared to tonic–clonic seizures. Here we used DMCM to evaluate the effect of LEV and TGB against seizures in postnatal day (P) 10 rat pups. We compared the profile of LEV and TGB to that of phenobarbital (PB), the most widely utilized anticonvulsant in neonates. We found that LEV significantly protected against DMCM seizures when administered in doses of 10mg/kg and greater. TGB protected against DMCM-evoked seizures when administered in doses of 1mg/kg or greater. PB protected against DMCM-evoked seizures when administered in doses of 5mg/kg or greater. These data provide preclinical evidence for the efficacy of LEV and TGB in neonates and underscore the utility of DMCM for screening anticonvulsant action in neonatal animals.