Effectiveness of Low Dose of Topiramate Following Rapid Titration in Multiply Handicapped Children and Difficult-to-Treat Epilepsy

Abstract

This prospective, observational, single arm, monocentric study explored efficacy and tolerability outcomes of rapid oral initiation of topimarate in children with difficult to treat epilepsy. The study population consisted of 19 multiply handicapped children (mean age 4.4 years, range 0.6–15.3 years). The observation period was 12 weeks and included 7 visits. The mean initial dose of topiramate was 1.1 mg/kg body weight/d (range: 0.66–2.67 mg/kg/d) following rapid titration. The mean final dose was 3.3 mg/kg/d (range 0.5–6.7 mg/kg/d). An at least 50% reduction of seizure frequency compared to baseline was observed in 9 of 19 patients (47.4%). Six patients (31.6%) had a slight reduction of seizure frequency (<50%) and 4 patients (21.1%) experienced an increase of seizure frequency. A total number of 29 adverse events were documented in 17 of 19 patients. Most frequently captured were fatigue (26.3% of patients), decreased appetite (15.8%) and psychiatric disturbances (15.8%). No serious adverse events were reported. These data might suggest that in certain clinical circumstances rapid dose escalation with topiramate followed by a low maintenance dose might be a good therapeutic option for pediatric patients with difficult to treat epilepsy.

topiramate - difficult to treat epilepsy - children - rapid titration - low dose - focal seizures - generalized seizures

References

• 1 Al AS, Shorman A, Daoud AS. The efficacy and side effects of topiramate on refractory epilepsy in infants and young children: a multi-center clinical trial.  Seizure. 2005;  14 459-463
• 2 Bialer M, Doose DR, Murthy B. et al . Pharmacokinetic interactions of topiramate.  Clin Pharmacokinet. 2004;  43 763-780
• 3 Coppola G, Caliendo G, Terracciano MM. et al . Topiramate in refractory partial-onset seizures in children, adolescents and young adults: a multicentric open trial.  Epilepsy Res. 2001;  43 255-260
• 4 Cramer JA, Hammer AE, Kustra RP. Quality of life improvement with conversion to lamotrigine monotherapy.  Epilepsy Behav. 2004;  5 224-230
• 5 Elterman RD, Glauser TA, Wyllie E. et al . A double-blind, randomized trial of topiramate as adjunctive therapy for partial-onset seizures in children. Topiramate YP Study Group.  Neurology. 1999;  52 1338-1344
• 6 Glauser TA, Clark PO, Strawsburg R. A pilot study of topiramate in the treatment of infantile spasms.  Epilepsia. 1998;  39 1324-1328
• 7 Glauser TA, Levisohn PM, Ritter F. et al . Topiramate in Lennox-Gastaut syndrome: open-label treatment of patients completing a randomized controlled trial. Topiramate YL Study Group.  Epilepsia. 2000;  41 ((Suppl 1)) 86-90
• 8 Glauser TA, Clark PO, McGee K. Long-term response to topiramate in patients with West syndrome.  Epilepsia. 2000;  41 ((Suppl 1)) 91-94
• 9 Glauser TA. Topiramate in the catastrophic epilepsies of childhood.  J Child Neurol. 2000;  15 ((Suppl 1)) 14-21
• 10 Glauser TA, Dlugos DJ, Dodson WE. et al . Topiramate monotherapy in newly diagnosed epilepsy in children and adolescents.  J Child Neurol. 2007;  22 693-699
• 11 Grosso S, Galimberti D, Farnetani MA. et al . Efficacy and safety of topiramate in infants according to epilepsy syndromes.  Seizure. 2005;  14 183-189
• 12 Grosso S, Franzoni E, Iannetti P. et al . Efficacy and safety of topiramate in refractory epilepsy of childhood: long-term follow-up study.  J Child Neurol. 2005;  20 893-897
• 13 Holland KD, Wyllie PE. Use of topiramate in localization-related epilepsy in children.  J Child Neurol. 2000;  15 ((Suppl 1)) 3-6
• 14 Kahriman M, Minecan D, Kutluay E. et al . Efficacy of topiramate in children with refractory status epilepticus.  Epilepsia. 2003;  44 1353-1356
• 15 Levisohn PM. Safety and tolerability of topiramate in children.  J Child Neuro. 2000;  15 ((Suppl 1)) 22-26
• 16 Mikaeloff Y, de Saint-Martin A, Mancini J. et al . Topiramate: efficacy and tolerability in children according to epilepsy syndromes.  Epilepsy Res. 2003;  53 225-232
• 17 Ormrod D, McClellan K. Topiramate: a review of its use in childhood epilepsy.  Paediatr Drugs. 2001;  3 293-319
• 18 Perry MS, Holt PJ, Sladky JT. Topiramate loading for refractory status epilepticus in children.  Epilepsia. 2006;  47 1070-1071
• 19 Ritter F, Glauser TA, Elterman RD. et al . Effectiveness, tolerability, and safety of topiramate in children with partial-onset seizures. Topiramate YP Study Group.  Epilepsia. 2000;  41 ((Suppl 1)) 82-85
• 20 Shank RP, Gardocki JF, Streeter AJ. et al . An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action.  Epilepsia. 2000;  41 ((Suppl 1)) 3-9
• 21 Spencer SS, Berg AT, Vickrey BG. et al . Health-related quality of life over time since resective epilepsy surgery.  Ann Neurol. 2007;  62 327-334
• 22 Veggiotti P, Longaretti F, Signorini S. et al . Topiramate efficacy in an infant with partial seizures refractory to conventional antiepileptic drugs.  Seizure. 2004;  13 241-243
• 23 Wheless JW, Neto W, Wang S. Topiramate, carbamazepine, and valproate monotherapy: double-blind comparison in children with newly diagnosed epilepsy.  J Child Neurol. 2004;  19 135-141
• 24 Winner P, Pearlman EM, Linder SL. et al . Topiramate for migraine prevention in children: a randomized, double-blind, placebo-controlled trial.  Headache. 2005;  45 1304-1312
• 25 Winner P, Gendolla A, Stayer C. et al . Topiramate for migraine prevention in adolescents: a pooled analysis of efficacy and safety.  Headache. 2006;  46 1503-1510

Correspondence