Levetiracetam Versus Phenobarbital for Neonatal Seizures: A Randomized Controlled Trial.
Sharpe Cynthia,Reiner Gail E,Davis Suzanne L,Nespeca Mark,Gold Jeffrey J,Rasmussen Maynard,Kuperman Rachel,Harbert Mary Jo,Michelson David,Joe Priscilla,Wang Sonya,Rismanchi Neggy,Le Ngoc Minh,Mower Andrew,Kim Jae,Battin Malcolm R,Lane Brian,Honold Jose,Knodel Ellen,Arnell Kathy,Bridge Renee,Lee Lilly,Ernstrom Karin,Raman Rema,Haas Richard H,
BACKGROUND AND OBJECTIVES:There are no US Food and Drug Administration-approved therapies for neonatal seizures. Phenobarbital and phenytoin frequently fail to control seizures. There are concerns about the safety of seizure medications in the developing brain. Levetiracetam has proven efficacy and an excellent safety profile in older patients; therefore, there is great interest in its use in neonates. However, randomized studies have not been performed. Our objectives were to study the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment of neonatal seizures. METHODS:The study was a multicenter, randomized, blinded, controlled, phase IIb trial investigating the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment for neonatal seizures of any cause. The primary outcome measure was complete seizure freedom for 24 hours, assessed by independent review of the EEGs by 2 neurophysiologists. RESULTS:Eighty percent of patients (24 of 30) randomly assigned to phenobarbital remained seizure free for 24 hours, compared with 28% of patients (15 of 53) randomly assigned to levetiracetam ( < .001; relative risk 0.35 [95% confidence interval: 0.22-0.56]; modified intention-to-treat population). A 7.5% improvement in efficacy was achieved with a dose escalation of levetiracetam from 40 to 60 mg/kg. More adverse effects were seen in subjects randomly assigned to phenobarbital (not statistically significant). CONCLUSIONS:In this phase IIb study, phenobarbital was more effective than levetiracetam for the treatment of neonatal seizures. Higher rates of adverse effects were seen with phenobarbital treatment. Higher-dose studies of levetiracetam are warranted, and definitive studies with long-term outcome measures are needed.
Levetiracetam monotherapy for the treatment of infants with epilepsy.
Arican Pinar,Gencpinar Pinar,Cavusoglu Dilek,Olgac Dundar Nihal
PURPOSE: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. METHOD: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. RESULTS: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. CONCLUSION: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.
Effectiveness of Levetiracetam Monotherapy in Pediatric Patients With Epilepsy.
Mazur Rafal D,Wang Ba Qianyu,Kato Bs Kenneth,Buchsbaum Bs Richard,Bonito Bs Jennifer,Choi Hyunmi,Hirsch Lawrence,Detyniecki Kamil
Journal of child neurology
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.
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.