RSS-Feed abonnieren
DOI: 10.1055/s-2004-822634
© Georg Thieme Verlag KG Stuttgart · New York
Optimierung der Epilepsietherapie von Kindern und Jugendlichen mit Lamotrigin
Optimizing Epilepsy Therapy in Children and Adolescents with LamotriginePublikationsverlauf
Publikationsdatum:
18. Mai 2005 (online)
![](https://www.thieme-connect.de/media/klinpaed/200504/lookinside/thumbnails/10.1055-s-2004-822634-1.jpg)
Zusammenfassung
Lamotrigin ist ein breit wirksames Antiepileptikum zur Mono- und Zusatztherapie bei Kindern und Jugendlichen mit fokalen und generalisierten Epilepsien. Von einer Reihe von Epileptologen wird Lamotrigin wegen der guten Verträglichkeit (keine Gewichtszunahme, keine Beeinträchtigung der Kognition, nach neuen Daten wahrscheinlich keine teratogenenen Eigenschaften in Monotherapie) gerade bei älteren Schulkindern und Jugendlichen als ein Mittel der 1. Wahl angesehen. Bei zahlreichen Epilepsiekrankheiten, wie z. B. der tuberösen Hirnsklerose, der juvenilen neuronalen Ceroidlipofuszinose und dem Rett-Syndrom, ist Lamotrigin mit gutem Erfolg anwendbar. Die Wirksamkeit von Lamotrigin nimmt im Laufe der Langzeithandlung nicht ab. Erste Studien zeigen, dass Lamotrigin auch bei Kindern vor dem 2. Lebensjahr gut wirksam und verträglich ist. Bei der Behandlung schwieriger Epilepsien hat sich die Kombination von Lamotrigin mit Valproat als besonders günstig erwiesen, dieser klinischen Beobachtung entsprechen neue tierexperimentelle Ergebnisse. Als häufigste dosisabhängige Nebenwirkungen von Lamotrigin finden sich die typischen ZNS-Nebenwirkungen Schwindel, Ataxie, Übelkeit, Tremor und Doppeltsehen. Die vor 1998 besonders häufig aufgetretenen allergischen Exantheme kommen durch geänderte Eindosierungsrichtlinien heute nicht mehr häufiger vor als bei konventionellen Antiepileptika. Lamotrigin beeinflusst die kognitiven Fähigkeiten, insbesondere Gedächtnis und Sprachfunktionen nicht negativ, es hat stimmungsaufhellende und die Lebensqualität verbessernde Eigenschaften. In tierexperimentellen Untersuchungen wirkt Lamotrigin antiepileptogen und neuroprotektiv.
Abstract
Lamotrigine is a broadly effective antiepileptic drug in mono- and add-on therapy for children and adolescents with focal and generalized epilepsies. Some epileptologists consider lamotrigine as the drug of primary choice in older school children and adolescents because of its good tolerability (no increase of body weight, no impairment of cognitive functions, due to new data probably no teratogenic properties). Lamotrigine can be used with good efficacy in numerable epilepsy diseases, such as tuberous sclerosis, juvenile neuronal lipofuscinosis and Rett syndrome. The first studies show that lamotrigine is also effective in children under 2 years of age. For therapy of difficult-to-treat epilepsies the combination of lamotrigine with valproate has proved as especially useful. This clinical observation is supported by new results of animal experiments. The dose-dependant and typical CNS side effects vertigo, ataxia, nausea, tremor and diplopia are found most frequently. The rate of allergic skin rashes which was very high before 1998 has decreased markedly by new dosage guidelines and is now as low as in older antiepileptic drugs. Lamotrigine does not impair cognitive functions, especially not memory and language. It has mood-stabilizing features and may improve quality of life. In animal experiments lamotrigine shows antiepileptogenic and neuroprotective effects.
Schlüsselwörter
Epilepsie - Antiepileptika - Kindesalter - Lamotrigin
Key words
Epilepsy - antiepileptic drugs - childhood - lamotrigine
Literatur
- 1 Åberg L E, Bäckman M, Kirveskari E, Santavuori P. Epilepsy and antiepileptic drug therapy in juvenile neuronal ceroid lipofuscinosis. Epilepsia. 2000; 41 1296-1302
- 2 Akman C I, Holmes G L. The effect of lamotrigine on the EEGs of children and adolescents with epilepsy. Epilepsy Behav. 2003; 4 420-423
- 3 Aldenkamp A P, Arends J, Bootsma H PR. et al . Randomized double-blind parallel-group study comparing cognitive effects of low-dose lamotrigine with valproate and placebo in healthy volunteers. Epilepsia. 2002; 43 19-26
- 4 Barron T F, Hunt S L, Hoban T F, Price M L. Lamotrigine monotherapy in children. Pediatr Neurol. 2000; 23 160-163
- 5 Bergmann L. Verträglichkeit von Lamictal. Vortrag anlässlich der Expertenkonfrenz „10 Jahre Lamictal”. Berlin 2003
- 6 Besag F MC, Dulac O, Alving J, Mullens E L. Long-term safety and efficacy of lamotrigine (Lamictal) in pediatric patients with epilepsy. Seizure. 1997; 6 51-56
- 7 Besag F MC, Ng G YT, Pool F. Successful re-introduction of lamotrigine after initial rash. Seizure. 2000; 9 282-286
- 8 Beydoun A, Kutluay E. Conversion to monotherapy. Clinical trials in patients with refractory partial seizures. Neurology. 2003; 60 (Suppl 4) S13-S25
- 9 Biton V, Levisohn P, Hoyler S, Vuong A. Lamotrigien versus valproate monotherapy-associated weight changein adolescents with epilepsy: results from a post hoc analysis of a randomized, double-blind clinical trial. J Child Neurol. 2003; 18 133-139
- 10 Brodie M J, Yuen A WC,. 105 Study Group . Lamotrigin substitution study: evidence for synergism with sodium valproate?. Epilepsy Res. 1997; 26 423-432
- 11 Cianchetti C, Pruna D, Coppola G, Pascotto A. Low-dose lamotrigine in West syndrome. Epilepsy Res. 2002; 51 199-200
- 12 Duchowny M, Pellock J M, Graf W D. et al . A placebo-controlled trial of lamotrigine add-on therapy for partial seizures in children. Neurology. 1999; 53 1724-1731
- 13 Duchowny M, Gilman J, Messenheimer J. et al. LAMICTAL Pediatric Study Group . Long-term tolerability and efficacy of lamotrigine in pediatric patients with epilepsy. J Child Neurol. 2002; 17 278-285
- 14 Eriksson A S, Knutsson E, Nergård A. The effect of lamotrigine on epileptiform discharges in young patients with drug-resistant epilepsy. Epilepsia. 2001; 42 230-236
- 15 Ettinger A B, Weisbrot D M, Saracco J. et al . Positive and negative psychotropic effects of lamotrigine in patients with epilepsy and mental retardation. Epilepsia. 1998; 39 874-877
- 16 Fayad M, Choueiri R, Mikati M. Potential hepatotoxicity of lamotrigine. Pediatr Neurol. 2000; 22 49-52
- 17 Felbamate Study Group in Lennox-Gastaut Syndrome . Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). New Engl J Med. 1993; 328 29-33
- 18 Frank L M, Enlow T, Holmes G L. et al . Lamictal (lamotrigine) monotherapy for typical absence seizures in children. Epilepsia. 1999; 40 973-979
- 19 Franz D N, Tudor C, Leonard J. et al . Lamotrigine therapy of epilepsy in tuberous sclerosis. Epilepsia. 2001; 42 935-940
- 20 Gillham R, Kane K, Bryant-Comstock L, Brodie M. A double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy with health-related quality of life as an outcome measure. Seizure. 2000; 9 375-379
- 21 Green B. Lamotrigine in mood disorders. Curr Med Res Opin. 2003; 19 272-277
- 22 Guerrini R, Dravet C, Genton P. Lamotrigine and seizure aggravation in severe myoclonic epilepsy. Epilepsia. 1998; 39 508-512
- 23 Halonen T, Nissinen J, Pittkänen A. Effect of lamotrigine treatment on status epilepticus-induced neuronal damage and memory impairment in rat. Epilepsy Res. 2001; 46 205-223
- 24 Helmstädter C. Kognitive Funktion und psychotrope Effekte unter der Therapie mit Lamictal bei Kindern. Vortrag anlässlich der Expertenkonfrenz „10 Jahre Lamictal”. Berlin 2003
- 25 Huber B, May T, Seifel M. Lamotrigine in multi-handicapped therapy-resistant epileptic patients. Clin Drug Invest. 1998; 16 263-277
- 26 Kwan P, Brodie M J. Clinical trials of antiepileptic medications in newly diagnosed patients with epilepsy. Neurology. 2003; 60 (Suppl 4) S2-S12
- 27 Kumandas S, Caksen H, Ciftei A. et al . Lamotrigine in two cases of Rett syndrome. Brain Dev. 2001; 23 240-242
- 28 Löscher W. Animal models of epilepsy for the development of antiepileptogenic and disease-modifying drugs. A comparison of the pharmacology of kindling and post-status epilepticus models of temporal lobe epilepsy. Epilepsy Res. 2002; 50 105-123
- 29 Luszczki J J, Czuczwar M, Kis J. et al . Interactions of lamotrigine with topiramate and first-generation antiepileptic drugs in the maximal electroshock test in mice: an isobolographic analysis. Epilepsia. 2003; 44 1002-1013
- 30 Manonmani V, Wallace S J. Epilepsy with myoclonic absences. Arch Dis Child. 1994; 70 288-290
- 31 Meador K J, Loring D W, Ray P G. et al . Differential cognitive and behavioural effects of carbamazepine and lamotrigine. Neurology. 2001; 56 1177-1182
- 32 Messenheimer J. Efficacy and safety of lamotrigine in pediatric patients. J Child Neurol. 2002; 17 S34-S42
- 33 Mikati M A, Fayed M, Kolielat M. et al . Efficacy, tolerability, and kinetics of lamotrigine in infants. J Pediatr. 2002; 141 31-35
- 34 Motte J, Trevathan E, Arvidsson J FV. et al . Lamotrigine for generalized seizures associated with the Lennox-Gastaut syndrome. New Engl J Med. 1997; 337 1807-1812
- 35 Piňa-Garca J E, Gucuyener K, Warnock C. et al . Safety and efficacy of lamotrigine in infants age 1-24 months with partial seizures - updated preliminary open-label results. Epilepsia. 2003; 44 (Suppl 8) 111
- 36 Pisani F, Oteri G, Russo. et al . The efficacy of valproate-lamotrigine comedication in refractory complex partial seizures: evidence for a pharmacodynamic interaction. Epilepsia. 1999; 40 1141-1146
- 37 Pitkänen A, Sutula T P. Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. Lancet Neurol. 2002; 1 173-181
- 38 Sabers A, Ohman I, Christensen J, Tomson T. Oral contraceptives reduce lamotrigine plasma levels. Neurology. 2003; 61 570-571
- 39 Sachdeo R C, Glauser T A, Ritter F. et al . A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Neurology. 1999; 52 1882-1887
- 40 Sälke-Kellermann R A. Lamotrigin-neuroprotektive Wirkung?. Vortrag anlässlich der Expertenkonfrenz „10 Jahre Lamictal”. Berlin 2003
- 41 Siemes H. Lamotrigin als Zusatztherapie bei schwierig zu behandelnden Epilepsien des Kindes- und Jugendalters. Pädiat Prax. 1999; 56 254-256
- 42 Sotero de Menezes M A, Rho J M, Murphy P, Cheyette S. Lamotrigine-induced tic disorder: report of five pediatric cases. Epilepsia. 2000; 41 862-867
- 43 Stenbom Y, Tonnby B, Hagberg B. Lamotrigine in Rett syndrome: treatment experience from a pilot study. Eur Child Adolescent Psychiat. 1998; 7 49-52
- 44 Stephen L J, Brodie M J. Seizure freedom with more than one antiepileptic drug. Seizure. 2002; 11 349-351
- 45 Thomé-Souza S, Freitas A, Fiore L A, Valente K D. Lamotrigine and valproate: efficacy of co-administration in a pediatric population. Ped Neurol. 2003; 28 360-364
- 46 Überall M A. Normal growth during lamotrigine monotherapy in pediatric epilepsy patients - a prospective evaluation of 103 children and adolescents. Epilepsy Res. 2001; 46 63-67
- 47 Überall M A. Neues aus der Kinderepileptologie. Vortrag, gehalten im März 2001 in Essen. 2001
- 48 Veggiotti P, Cieuta C, Rey E, Dulac O. Lamotrigine in infantile spasms. Lancet. 1994; 344 1375-1376
Prof. Dr. med. Hartmut Siemes
Holbeinstr. 39
12203 Berlin
Telefon: 0 30/84 47 10 79
Fax: 0 30/84 47 10 79
eMail: hartmut.siemes@t-online.de