Lamotrigine monotherapy for newly diagnosed typical absence seizures in children

Gregory L Holmes, L Matthew Frank, Raj D Sheth, Bryan Philbrook, John D Wooten, Alain Vuong, Susan Kerls, Anne E Hammer, John Messenheimer, Gregory L Holmes, L Matthew Frank, Raj D Sheth, Bryan Philbrook, John D Wooten, Alain Vuong, Susan Kerls, Anne E Hammer, John Messenheimer

Abstract

Purpose: To evaluate the efficacy, tolerability, and effects on behavior and psychosocial functioning of lamotrigine monotherapy in children with newly diagnosed typical absence seizures.

Patients and methods: Children meeting enrollment criteria (n=54) received a confirmatory 24-h ambulatory electroencephalogram (EEG) and then entered a Escalation Phase of up to 20-weeks during which lamotrigine was titrated until seizures were controlled or maximum dose (10.2mg/kg) was reached. Seizure freedom was assessed by diary review and clinic hyperventilation (clinic HV) and then confirmed by EEG with hyperventilation (HV/EEG). Patients who maintained seizure freedom for two consecutive weekly visits were entered into the Maintenance Phase (n=30). Diary, clinic HV, and HV/EEG data were supplemented with 24-h ambulatory EEG at baseline and the ends of the Escalation and Maintenance Phases. Health outcome assessments were completed at screening and at the end of the Maintenance Phase.

Results: By the end of the Escalation Phase, seizure-free rates (responders) were 59% by seizure diary (n=51), 56% by HV/EEG (n=54) (primary endpoint), and 49% by 24-h ambulatory EEG (n=49). During the Maintenance Phase, 89% (week 24) and 86% (week 32) remained seizure free by diary (n=28), 78% by clinic HV (n=27), and 81% by 24-h ambulatory EEG (n=26). Seizure freedom was first observed beginning at the fifth week of the Escalation Phase. The most frequent adverse events were headache and cough. Health outcome scores were either improved or unchanged at the end of the Maintenance Phase.

Conclusions: Lamotrigine monotherapy results in complete seizure freedom in a substantial number of children with typical absence seizures. Lamotrigine was well tolerated in this study.

Trial registration: ClinicalTrials.gov NCT00144872.

References

    1. Achenbach T.M. University of Vermont; Burlington: 1991. Integrative Guide to the 1991 CBCL/4-18, YSR, and TRF Profiles.
    1. Adams D.J., Lueders H. Hyperventilation and six-hour EEG recording in evaluation of absence seizures. Neurology. 1981;31:1175–1177.
    1. Bird H.R., Canino G., Rubio-Stipec M., Ribera J.C. Further measures of the psychometric properties of the Children's Global Assessment Scale. Arch. Gen. Psychiatry. 1987;44:821–824.
    1. Brodbeck V., Jansen V., Fietzek U., Muehe C., Weber G., Heinen F. Long-term profile of lamotrigine in 119 children with epilepsy. Eur. J. Paediatr. Neurol. 2006;10:135–141.
    1. Browne T.R., Dreifuss F.E., Penry J.K., Porter R.J., White B.G. Clinical and EEG estimates of absence seizure frequency. Arch. Neurol. 1983;40:469–472.
    1. Browne T.R., Penry J.K., Porter R.J. Responsiveness before, during, and after spike-wave paroxysms. Neurology. 1974;24:659–665.
    1. Buoni S., Grosso S., Fois A. Lamotrigine in typical absence epilepsy. Brain Dev. 1999;21:303–306.
    1. Coppola G., Auricchio G., Federico R., Carotenuto M., Pascotto A. Lamotrigine versus valproic acid as first-line monotherapy in newly diagnosed typical absence seizures: an open-label, randomized, parallel-group study. Epilepsia. 2004;45:1049–1053.
    1. Coppola G., Licciardi G., Sciscio N., Russo F., Carotenuto M., Pascotto A. Lamotrigine as first-line drug in childhood absence epilepsy: a clinical and neurophysiological study. Brain Dev. 2004;26:26–29.
    1. Duchowny M., Gilman J., Messenheimer J., Womble G., Risner M. Long-term tolerability and efficacy of lamotrigine in pediatric patients with epilepsy. J. Child Neurol. 2002;17:278–285.
    1. Ferrie C.D., Robinson R.O., Knott C., Panayiotopoulos C.P. Lamotrigine as an add-on drug in typical absence seizures. Acta Neurol. Scand. 1995;91:200–202.
    1. Frank L.M., Enlow T., Holmes G.L., Manasco P., Concannon S., Chen C., Womble G., Casale E.J. Lamictal (lamotrigine) monotherapy for typical absence seizures in children. Epilepsia. 1999;40:973–979.
    1. Granleese J., Joseph S. Reliability of the Harter self-perception profile for children and predictors of global self-worth. J. Genet. Psychol. 1994;155:487–492.
    1. Grosso S., Galimberti D., Vezzosi P., Farnetani M., di Bartolo R.M., Bazzotti S., Morgese G., Balestri P. Childhood absence epilepsy: evolution and prognostic factors. Epilepsia. 2005;46:1796–1801.
    1. Guberman A.H., Besag F.M., Brodie M.J., Dooley J.M., Duchowny M.S., Pellock J.M., Richens A., Stern R.S., Trevathan E. Lamotrigine-associated rash: risk/benefit considerations in adults and children. Epilepsia. 1999;40:985–991.
    1. Harter S. Guilford Publications, Inc.; New York: 1999. The Construction of the Self. A Developmental Perspective.
    1. Harter S. University of Denver; Denver, Colorado: 1985. The Self-Perception Profile for Children: Revision of the Perceived Competence Scale for Children.
    1. Hirsch L.J., Weintraub D.B., Buchsbaum R., Spencer H.T., Straka T., Hager M., Resor S.R., Jr. Predictors of lamotrigine-associated rash. Epilepsia. 2006;47:318–322.
    1. Kluger G., Berz K., Holthausen H. The long-term use of vigabatrin and lamotrigine in patients with severe childhood onset epilepsy. Eur. J. Paediatr. Neurol. 2001;5:37–40.
    1. Marson A.G. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369:1016–1026.
    1. Messenheimer J.A. Rash in adult and pediatric patients treated with lamotrigine. Can. J. Neurol. Sci. 1998;25:S14–S18.
    1. Panayiotopoulos C.P. Treatment of typical absence seizures and related epileptic syndromes. Paediatr. Drugs. 2001:379–403.
    1. Pearl P.L., Holmes G.L. Absence seizures. In: Pellock J.M., Dodson W.E., Bourgeois B.F.D., editors. Pediatric Epilepsy. Diagnosis and Treatment. Demos; New York: 2001. pp. 219–231.
    1. Pearl P.L., Holmes G.L. Childhood absence epilepsies. In: Pellock J.M., Bourgeois B.F.D., Dodson W.E., editors. Pediatric Epilepsy. Demos; New York: 2008. pp. 323–334.
    1. Penry J.K., Porter R.J., Dreifuss F.E. Simultaneous recording of absence sizures with videotape and electroencephalography. Brain. 1975;98:427–440.
    1. Porter R.J., Penry J.K., Dreifuss F.E. Responsiveness at the onset of spike-wave bursts. Electroencephalogr. Clin. Neurophysiol. 1973;34:239–245.
    1. Posner E. Absence seizures in children. Clin. Evid. 2005:221–226.
    1. Posner E. Pharmacological treatment of childhood absence epilepsy. Expert Rev. Neurother. 2006;6:855–862.
    1. Posner E.B., Mohamed K., Marson A.G. A systematic review of treatment of typical absence seizures in children and adolescents with ethosuximide, sodium valproate or lamotrigine. Seizure. 2005;14:117–122.
    1. Posner, E.B., Mohamed, K., Marson, A.G., 2005b. Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents. Cochrane Database Syst. Rev. CD003032.
    1. Shaffer D., Gould M.S., Brasic J., Ambrosini P., Fisher P., Bird H., Aluwahlia S. A children's global assessment scale (CGAS) Arch. Gen. Psychiatry. 1983;40:1228–1231.
    1. Tovia E., Goldberg-Stern H., Shahar E., Kramer U. Outcome of children with juvenile absence epilepsy. J. Child Neurol. 2006;21:766–768.
    1. Wirrell E.C. Natural history of absence epilepsy in children. Can. J. Neurol. Sci. 2003;30:184–188.
    1. Wirrell E.C., Camfield C.S., Camfield P.R., Dooley J.M., Gordon K.E., Smith B. Long-term psychosocial outcome in typical absence epilepsy. Sometimes a wolf in sheeps’ clothing. Arch. Pediatr. Adolesc. Med. 1997;151:152–158.
    1. Wirrell E.C., Camfield C.S., Camfield P.R., Gordon K.E., Dooley J.M. Long-term prognosis of typical childhood absence epilepsy: remission or progression to juvenile myoclonic epilepsy. Neurology. 1996;47:912–918.
    1. Wirrell E.C., Camfield P.R., Camfield C.S., Dooley J.M., Gordon K.E. Accidental injury is a serious risk in children with typical absence epilepsy. Arch. Neurol. 1996;53:929–932.

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