Effect of Levetiracetam Monotherapy in Nonlesional Focal Childhood Epilepsy

Abstract

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 (p = 0.0129 and p = 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.

Keywords

levetiracetam (LEV) - epilepsy - antiepileptic drug (AED) - initial monotherapy - child

• References

• 1 Fejerman N. [Benign focal epilepsies in infancy, childhood and adolescence]. Rev Neurol 2002; 34 (01) 7-18
• 2 Fejerman N, Caraballo RH, Bernardina BD. Benign childhood epilepsy with centrotemporal spikes. In: Fejerman N, Caraballo RH. , eds. Benign Focal Epilepsies in Infancy, Childhood and Adolescence. Montrouge: John Libbey Eurotext; 2007: 77-113
• 3 Sillanpaa M. Carbamazepine. In: Shorvon S, Perucca E, Fish D, Dodson E. , eds. The Treatment of Epilepsy, 2nd ed. Malden, Massachusetts: Blackwell Science Ltd; 2004: 345-357
• 4 Konishi T, Naganuma Y, Hongo K, Murakami M, Yamatani M, Okada T. Carbamazepine-induced skin rash in children with epilepsy. Eur J Pediatr 1993; 152 (07) 605-608
• 5 Keppra prescribing information. Smyrna, GA: UCB Pharma, Inc.; 2000: 30080
• 6 French J. Use of levetiracetam in special populations. Epilepsia 2001; 42 (Suppl. 04) 40-43
• 7 Fejerman N. Benign childhood epilepsy with centrotemporal spikes. In: Engel Jr J, Pedley TA. , eds. Epilepsy A Comprehensive Textbook, 2nd ed. Philadelphia, Pennsylvania: Lippincott Williams & Wilkins; 2008: 2369-2377
• 8 Kanemura H, Sano F, Tando T, Sugita K, Aihara M. Efficacy and safety of add-on levetiracetam in refractory childhood epilepsy. Brain Dev 2013; 35 (05) 386-391
• 9 Yılmaz U, Yılmaz TS, Dizdarer G, Akıncı G, Güzel O, Tekgül H. Efficacy and tolerability of the first antiepileptic drug in children with newly diagnosed idiopathic epilepsy. Seizure 2014; 23 (04) 252-259
• 10 Alsaadi TM, Thieman C. Levetiracetam monotherapy for newly diagnosed epilepsy patients. Seizure 2003; 12 (03) 154-156
• 11 Bello-Espinosa LE, Roberts SL. Levetiracetam for benign epilepsy of childhood with centrotemporal spikes-three cases. Seizure 2003; 12 (03) 157-159
• 12 Papazoglou A, King TZ, Burns TG. Active seizures are associated with reduced adaptive functioning in children with epilepsy. Seizure 2010; 19 (07) 409-413
• 13 Kanemura H, Sano F, Aoyagi K, Sugita K, Aihara M. Do sequential EEG changes predict atypical clinical features in rolandic epilepsy?. Dev Med Child Neurol 2012; 54 (10) 912-917
• 14 Kanemura H, Sano F, Ohyama T, Aoyagi K, Sugita K, Aihara M. Sequential prefrontal lobe volume changes and cognitive dysfunctions in children with Panayiotopoulos syndrome presenting with status epilepticus. Epilepsy Res 2015; 112: 122-129
• 15 Nanba Y, Maegaki Y. Epileptic negative myoclonus induced by carbamazepine in a child with BECTS. Pediatr Neurol 1999; 21 (03) 664-667
• 16 Kikumoto K, Yoshinaga H, Oka M. , et al. EEG and seizure exacerbation induced by carbamazepine in Panayiotopoulos syndrome. Epileptic Disord 2006; 8 (01) 53-56
• 17 Fejerman N. Early-onset benign childhood occipital epilepsy (Panayiotopoulos type). In: Engel Jr J, Pedley TA. , eds. Epilepsy: A Comprehensive Textbook, 2nd ed. Philadelphia, Pennsylvania: Lippincott Williams & Wilkins; 2008: 2379-2386
• 18 Kanemura H, Sano F, Sugita K, Aihara M. Effects of levetiracetam on seizure frequency and neuropsychological impairments in children with refractory epilepsy with secondary bilateral synchrony. Seizure 2013; 22 (01) 43-47
• 19 Tekgül H, Gencpinar P, Çavuşoğlu D, Dündar NO. The efficacy, tolerability and safety of levetiracetam therapy in a pediatric population. Seizure 2016; 36: 16-21
• 20 Reunanen M, Dam M, Yuen AW. A randomised open multicentre comparative trial of lamotrigine and carbamazepine as monotherapy in patients with newly diagnosed or recurrent epilepsy. Epilepsy Res 1996; 23 (02) 149-155
• 21 Piña-Garza JE, Nordli Jr DR, Rating D, Yang H, Schiemann-Delgado J, Duncan B. ; Levetiracetam N01009 Study Group. Adjunctive levetiracetam in infants and young children with refractory partial-onset seizures. Epilepsia 2009; 50 (05) 1141-1149
• 22 Bootsma HP, Aldenkamp AP, Diepman L. , et al. The effect of antiepileptic drugs on cognition: patient perceived cognitive problems of topiramate versus levetiracetam in clinical practice. Epilepsia 2006; 47 (Suppl. 02) 24-27
• 23 Gomer B, Wagner K, Frings L. , et al. The influence of antiepileptic drugs on cognition: a comparison of levetiracetam with topiramate. Epilepsy Behav 2007; 10 (03) 486-494
• 24 Meador KJ, Gevins A, Loring DW. , et al. Neuropsychological and neurophysiologic effects of carbamazepine and levetiracetam. Neurology 2007; 69 (22) 2076-2084
• 25 Levisohn PM, Mintz M, Hunter SJ, Yang H, Jones J. ; N01103 Levetiracetam Study Group. Neurocognitive effects of adjunctive levetiracetam in children with partial-onset seizures: A randomized, double-blind, placebo-controlled, noninferiority trial. Epilepsia 2009; 50 (11) 2377-2389
• 26 Kanemura H, Sano F, Ohyama T, Sugita K, Aihara M. Efficacy of levetiracetam as first add-on therapy to carbamazepine and valproate sodium for children with epilepsy. J Pediatr Epilepsy 2014; 3: 77-83
• 27 Cereghino JJ, Biton V, Abou-Khalil B, Dreifuss F, Gauer LJ, Leppik I. Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology 2000; 55 (02) 236-242
• 28 Iwasaki T, Toki T, Nonoda Y, Ishii M. The efficacy of levetiracetam for focal seizures and its blood levels in children. Brain Dev 2015; 37 (08) 773-779
• 29 Glauser TA, Ayala R, Elterman RD. , et al; N159 Study Group. Double-blind placebo-controlled trial of adjunctive levetiracetam in pediatric partial seizures. Neurology 2006; 66 (11) 1654-1660
• 30 French J, Arrigo C. Rapid onset of action of levetiracetam in refractory epilepsy patients. Epilepsia 2005; 46 (02) 324-326
• 31 Rating D, Wolf C, Bast T. ; Sulthiame Study Group. Sulthiame as monotherapy in children with benign childhood epilepsy with centrotemporal spikes: a 6-month randomized, double-blind, placebo-controlled study. Epilepsia 2000; 41 (10) 1284-1288