Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society.
Kanner Andres M,Ashman Eric,Gloss David,Harden Cynthia,Bourgeois Blaise,Bautista Jocelyn F,Abou-Khalil Bassel,Burakgazi-Dalkilic Evren,Llanas Park Esmeralda,Stern John,Hirtz Deborah,Nespeca Mark,Gidal Barry,Faught Edward,French Jacqueline
OBJECTIVE:To update the 2004 American Academy of Neurology (AAN) guideline for treating new-onset focal or generalized epilepsy with second- and third-generation antiepileptic drugs (AEDs). METHODS:The 2004 AAN criteria were used to systematically review literature (January 2003-November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. RESULTS:Several second-generation AEDs are effective for new-onset focal epilepsy. Data are lacking on efficacy in new-onset generalized tonic-clonic seizures, juvenile myoclonic epilepsy, or juvenile absence epilepsy, and on efficacy of third-generation AEDs in new-onset epilepsy. RECOMMENDATIONS:Lamotrigine (LTG) should (Level B) and levetiracetam (LEV) and zonisamide (ZNS) may (Level C) be considered in decreasing seizure frequency in adults with new-onset focal epilepsy. LTG should (Level B) and gabapentin (GBP) may (Level C) be considered in decreasing seizure frequency in patients ≥60 years of age with new-onset focal epilepsy. Unless there are compelling adverse effect-related concerns, ethosuximide or valproic acid should be considered before LTG to decrease seizure frequency in treating absence seizures in childhood absence epilepsy (level B). No high-quality studies suggest clobazam, eslicarbazepine, ezogabine, felbamate, GBP, lacosamide, LEV, LTG, oxcarbazepine, perampanel, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin, or ZNS is effective in treating new-onset epilepsy because no high-quality studies exist in adults of various ages. A recent Food and Drug Administration (FDA) strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years old and perampanel as monotherapy received FDA approval.
A Randomized Controlled Trial of Phenobarbital and Levetiracetam in Childhood Epilepsy.
Akter N,Rahman M M,Akhter S,Fatema K
Mymensingh medical journal : MMJ
Levetiracetam has been introduced for the control of seizures besides phenobarbital as monotherapy in children with epilepsy. This study was aimed to compare the effectiveness of these two drugs for the control of seizures in epilepsy. This randomized controlled trial was done to assess the efficacy and tolerability of levetiracetam compared to phenobarbital in childhood epilepsy and was conducted in Institute of Pediatric Neurodisorder and Autism (IPNA), Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh among children between 1 month to 15 years who were diagnosed as cases of epilepsy (idiopathic focal, generalized, focal with secondary generalization) according to ILAE to assess the effect of Levetiracetam (n=50) and Phenobarbital (n=68) from May 2015 to July 2016. The children were followed up for 12 months at 3 months interval to compare the seizure remission and side effects of Levetiracetam and Phenobarbital. The children in levetiracetam group was about 10 months older along with older age of onset of seizure (p=0.02) than those of phenobarbital group (p=0.03 and 0.02 respectively). GTCS was the most common type of seizure in both groups. During 3 months of intervention 55.8% patients of levetiracetam group achieved 50-75% seizure remission compared to 44.2% in phenobarbital group, at 6 months period 75-100% seizure remission observed among 57.4% patients of levetiracetam group compared to 42.6% of phenobarbital group (p=0.06), which continued to increase at 9 months in levetiracetam (n=33, 55.9%) compared to phenobarbital (n=26, 44.1%) and this value is statistically significant (p=0.05). No further improvement observed at 12 months follow up. Behavioral problem was reported among 4 patients of phenobarbital group without any evidence of cognitive deterioration, only 3 patients of levetiracetam experienced irritability, but no children of both group discontinued treatment due to side effects. Levetiracetam mono-therapy is more effective in controlling seizures in focal, generalized and focal with secondary generalization epilepsy compared to phenobarbital with minimum side effects.
Efficacy of levetiracetam as first-line therapy for neonatal clinical seizures and neurodevelopmental outcome at 12 months of age.
Kanmaz Seda,Altun Köroğlu Özge,Terek Demet,Serin Hepsen Mine,Simsek Erdem,Dokurel Cetin İpek,Yilmaz Sanem,Yalaz Mehmet,Aktan Gul,Akisu Mete,Kultursay Nilgun,Gokben Sarenur,Tekgul Hasan
Acta neurologica Belgica
Appropriate treatment of neonatal seizures with an effective therapy is important in reducing long-term neurologic disabilities. Sixty-seven neonates, who received intravenous (IV) levetiracetam (LEV) as first-line therapy for treating seizures between 2013 and 2017 were evaluated retrospectively to investigate the efficacy of LEV and its neurodevelopmental outcome at 12 months of age. Of the 67 neonates (44 preterm and 23 term babies) evaluated for seizures, 55 (82%) had a defined etiology. EEG confirmation was obtained in 36 (57.1%) of the neonates with clinical seizures. On the 7th day of the treatment (mean seizure control time 7.4 ± 15.1 days), LEV was effective as monotherapy in 43 (64%), whereas add-on therapy was required in 24 (36%) neonates. At the 1-year follow-up, 76% of infants achieved drug-free state, nine (18%) infants remained on LEV monotherapy and three (6%) needed add-on therapy. Neurodevelopmental outcome of the infants was assessed with Ankara Development Screening Inventory and results suggested favorable neurodevelopmental outcome in 69.7% of the infants with at the end of the 1-year follow-up with LEV monotherapy. In conclusion, this retrospective cross-sectional study demonstrated that IV LEV is an effective first-line therapy for treating neonatal clinical seizures and LEV monotherapy effect was sustained during the first year follow-up.
Comparative Effectiveness of Levetiracetam vs Phenobarbital for Infantile Epilepsy.
Grinspan Zachary M,Shellhaas Renée A,Coryell Jason,Sullivan Joseph E,Wirrell Elaine C,Mytinger John R,Gaillard William D,Kossoff Eric H,Valencia Ignacio,Knupp Kelly G,Wusthoff Courtney,Keator Cynthia,Ryan Nicole,Loddenkemper Tobias,Chu Catherine J,Novotny Edward J,Millichap John,Berg Anne T
Importance: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. Objective:To compare the effectiveness of levetiracetam vs phenobarbital for nonsyndromic infantile epilepsy. Design, Setting, and Participants: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. Exposures:Use of levetiracetam or phenobarbital as initial monotherapy within 1 year of the first seizure. Main Outcomes and Measures: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. Results: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]). Conclusions and Relevance: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.
Vitamin D deficiency in children with epilepsy taking valproate and levetiracetam as monotherapy.
Durá-Travé Teodoro,Gallinas-Victoriano Fidel,Malumbres-Chacón María,Moreno-Gónzalez Paula,Aguilera-Albesa Sergio,Yoldi-Petri María Eugenia
OBJECTIVE: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. MATERIAL & METHODS: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. CONCLUSIONS: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.
Long-term effect of levetiracetam monotherapy on haematological parameters in children with epilepsy: A prospective study.
Attilakos Achilleas,Dinopoulos Argirios,Paschalidou Maria,Tsirouda Maria,Karalexi Maria,Prasouli Alexia,Garoufi Anastasia
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.
Effect of Levetiracetam Monotherapy in Nonlesional Focal Childhood Epilepsy.
Kanemura Hideaki,Sano Fumikazu,Ohyama Tetsuo,Sugita Kanji,Aihara Masao
This article compares the efficacy and tolerability of carbamazepine (CBZ) and levetiracetam (LEV) when used as initial monotherapy in children with nonlesional focal epilepsy. Patients with nonlesional focal epilepsy were subdivided into two groups according to the initial monotherapy: a LEV group administered LEV at an initial dose of 5 mg/kg/day and a CBZ group. Seizure response, adverse events, medication dose, reasons for discontinuing medication, adherence, and random serum levels were recorded. The overall percentage of patients who failed initial treatment and reasons for each treatment failure were determined. Data were analyzed from 183 children who received CBZ monotherapy and 46 children who received LEV monotherapy for ≥12 months. Overall, 126 patients (68.9%) became seizure-free with CBZ, compared with 37 patients (80.4%) with LEV. Moreover, four patients in CBZ and four patients in LEV groups showed a >50% reduction in seizure frequency. The efficacy rate was significantly higher and the adverse event rate was significantly lower in the LEV group than in the CBZ group ( = 0.0129 and = 0.0039, respectively). LEV may offer superior efficacy and a lower risk of adverse effects compared with CBZ. LEV as initial monotherapy may represent a valuable treatment option for children with nonlesional focal childhood epilepsy.
Comparison of the neurocognitive outcomes in term infants treated with levetiracetam and phenobarbital monotherapy for neonatal clinical seizures.
Arican Pinar,Olgac Dundar Nihal,Mete Atasever Neslihan,Akkaya Inal Mine,Gencpinar Pinar,Cavusoglu Dilek,Akbay Sinem,Tekgul Hasan
PURPOSE: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. METHODS: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. RESULTS: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. CONCLUSION: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.
The Efficacy and Tolerability of Levetiracetam as a First Line Monotherapy in Childhood Epilepsy.
Connolly A,Quirke M,Crowley S,Hayes E,Hurley C,Keegan M,Griffin G,Webb D
Irish medical journal
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.