title: Topiramate: efficacy and tolerability in children according to epilepsy syndromes.
abstract: To evaluate the efficacy and tolerability of topiramate (TPM) as add-on therapy in children less than 12 years of age with refractory epilepsy, according to epilepsy syndromes, we conducted an open, prospective, pragmatic and multicenter study in France. Efficacy was assessed, especially according to epilepsy syndromes, as well as tolerability. We included 207 children (41 of whom were less than 4 years of age). TPM was effective (responders with >50% decrease in seizure frequency) in 50% of 128 patients with partial epilepsy, and in 44% of 79 patients with generalized epilepsy. In case of generalized epilepsy, responders more frequently had generalized symptomatic epilepsy, severe myoclonic epilepsy and myoclono-astatic epilepsy, whereas response rate was mild in both infantile spasms and Lennox-Gastaut syndrome (LGS). Improvement was well maintained in all patients during the treatment period (median 5.6 months). Seizure frequency/severity increased (worsening) in 13% of patients with partial epilepsy and 17% with generalized epilepsy (particularly in those with infantile spasms), and resulted in withdrawal of TPM for 8%. The most frequently reported adverse events were moderate neurobehavioral and gastrointestinal disorders. Adverse events led to withdrawal of TPM from 13.5% of patients. Children less than 4 years of age had particularly good tolerability. Results confirm that TPM is effective and well tolerated in children under 12 years of age in a broad range of epilepsy syndromes, including refractory partial epilepsy, and symptomatic and myoclonic generalized epilepsy. Use of TPM should be considered in children under 4 years of age, and slow and progressive titration is important.
authors.affiliation: Neuropediatric Department, Cochin-Saint-Vincent de Paul University Hospital, 82 Bd Denfert-Rochereau, 75014 Paris, France. yann.mikaeloff@free.fr
authors.forename: Yann
authors.initials: Y
authors.lastname: Mikaeloff
authors.forename: Anne
authors.initials: A
authors.lastname: de Saint-Martin
authors.forename: Josette
authors.initials: J
authors.lastname: Mancini
authors.forename: Sylviane
authors.initials: S
authors.lastname: Peudenier
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pedespan
authors.forename: Louis
authors.initials: L
authors.lastname: Vallée
authors.forename: Jacques
authors.initials: J
authors.lastname: Motte
authors.forename: Marie
authors.initials: M
authors.lastname: Bourgeois
authors.forename: Alexis
authors.initials: A
authors.lastname: Arzimanoglou
authors.forename: Olivier
authors.initials: O
authors.lastname: Dulac
authors.forename: Catherine
authors.initials: C
authors.lastname: Chiron
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use*; D002648:Child; D002653:Child Behavior Disorders / Q000139:chemically induced; D002675:Child, Preschool; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007223:Infant; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced; D011446:Prospective Studies; D013577:Syndrome; D000077236:Topiramate; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose