Lamotrigine as an Add-On Drug in the Management of Lennox-Gastaut Syndrome

442

270

Summary: Purpose:In severe myoclonic epilepsy of infancy (SME), multiple drug-resistant focal and generalized seizure types occur. Lamotrigine (LTG), found effective in many generalized and partial seizures, has been little used in severe childhood epilepsy syndromes with multiple seizure types. We studied the effects of LTG in SME.Methods: Twenty-one patients with SME, aged 2-18 years, were treated with LTG, 20 in add-on and one in monotherapy. LTG was started at 0.2-2.5 mg/kg/day and increased to 2.5-12.5 mg/kg/day. For each seizure type, excluding atypical absences, >50% variations compared with the 2 months preceding LTG were considered indicators of response, also taking into account the degree of disability each seizure type produced.Results: LTG induced worsening in 17 (80%) patients, noSevere myoclonic epilepsy (SME) in infants (1) is one of the most disabling epileptic syndromes. Seizures begin during the first year of life in previously normal children as generalized or unilateral attacks, facilitated by fever, and often occurring in the form of status epilepticus. Such seizures are followed later, between ages 1 and 4 years, by myoclonus, atypical absences, and complex partial seizures, accompanied in some children by clinical photosensitivity. Often coinciding with the onset of myoclonus, there is a slowing in psychomotor development, patients being variably mentally retarded from school age on. All seizure types are extremely resistant to drug treatment. Although SME is diagnosed only in -1% of patients with epilepsy (2), the management of these patients is particularly time demanding and costly, as they undergo multiple periods of hospitalization and antiepileptic drug (AED) trials in which almost all combinations of available drugs are tried.Lamotrigine (LTG) has proven to be effective in the

Section: Results Are Summarizd Inmentioning

confidence: 99%

Lamotrigine and Seizure Aggravation in Severe Myoclonic Epilepsy

Guerrini

Dravet²,

Genton³

et al. 1998

442

270

“…Vigabatrin (VGB) has appeared to be most effective in partial seizures in children ( 17), reflecting the adult experience, but may worsen seizures in some pediatric populations (1 8). LTG has been studied primarily in open trials in children (8), with some positive findings reported in LennoxGastaut syndrome ( 19,20) and in atypical absence seizures (8,2 1). Gabapentin (GBP) was not shown to have an effect on absence seizures in children in a shortterm EEG monitoring trial (22).…”

Section: Discussionmentioning

confidence: 99%

Preliminary Observations on Topiramate in Pediatric Epilepsies

Glauser

1997

Summary:Preliminary results of studies of topiramate (TPM) in children are now available. In a pharmacokinetic study among 18 male and female children, target daily dosages of up to 9 mg/kg/day were evaluated. TPM pharmacokinetics in children were linear. Mean TPM oral clearance (CL/F) was 44-54% higher in children [depending on concomitant antiepileptic drugs (AEDs)] compared with historical data from adults, and steady-state plasma TPM concentrations for the same mg/kg dose were 33% lower in children compared with historical adult data. In a long-term, open-label pilot study of adjunctive TPM therapy in 18 patients with Lennox-Gastaut syndrome, six of the eight patients (75%) still receiving TPM report a greater than 50% reduction in total seizures, with the best results observed in tonic-atonic, atypical absence, and generalized tonic-clonic seizures. Subsequent large double-blind, placebo-controlled trials of adjunctive TPM therapy in Lennox-Gastaut syndrome and refractory partial-onset pediatric epilepsy are ongoing, with high percentages of enrolled patients in both studies completing double-blind treatment and entering long-term TPM open extension trials. A small TPM monotherapy substitution trial in children with well controlled partial onset seizures showed that TPM monotherapeutic substitution can be achieved successfully with an acceptable amount of adverse experiences with a weekly increase of 1 mg/kg/day to a maximal dose of 3 mg/kg/day. These preliminary results suggest that TPM may be a useful new AED in pediatric patients with a variety of seizure disorders.

“…With the exception of a single patient, the seizure count was lower during the LTG phase (p < In uncontrolled studies, LTG (up to 15 mgkglday, 400 mg/day) has shown efficacy as add-on therapy in children and adolescents with refractory multiple seizure types (including those with accompanying neurologic or developmental abnormalities), with approximately 40% of patients showing a reduction of 50% or better in seizure frequency and approximately 10% achieving total control of seizures after 3 months of treatment. Generalized seizures, including atypical and typical absence seizures, atonic and tonic seizures, and Lennox-Gastaut syndrome, were more responsive (26)(27)(28)(29)(30)(31)(32). A retrospective analysis of 285 children with refractory epilepsy (frequently accompanied by neurologic impairment) who responded to short-to medium-term (up to 12 months) adjunctive LTG therapy indicated that efficacy was maintained in long-term ( 1 4 .…”

Section: Additional Clinical Studiesmentioning

confidence: 99%

Lamotrigine

Matsuo

1999

Summary: Clinical use of the antiepileptic drug (AED) lamotrigine (LTG) has dramatically increased since its introduction in Europe in 1991 and in the United States in 1994. This article surveys the English-language literature of LTG published before 1998. This literature is concerned with the molecular mechanisms of LTG's antiepileptic action, evaluation of its clinical antiepileptic efficacy, adverse experiences associated with its clinical use, and current guidelines for its initiation. LTG's efficacy has been extensively confirmed in multiple postmarketing studies, and its applications are broad. The most serious adverse experiences have involved skin rash. Valproic acid affects LTG metabolism, and a specific set of guidelines for the concurrent use of valproic acid and LTG has been developed. Unique issues are also associated with its pediatric use. LTG has a significant place in clinical management of a wide range of epilepsy syndromes, and the scope of its use is expanding. Accumulating clinical data enable the clinician to maximize its efficacy and minimize adverse experiences. Guidelines for its pediatric use must be followed diligently.