İnatçı Epilepsili Çocuklarda Ek Tedavi Olarak Topiramat Etkinliğinin ve Yan Etkilerinin Değerlendirilmesi

Yıl 2010, Cilt: 8 Sayı: 1, 125 - 129, 01.06.2010

Özlem Özdemir Mehmet S. Okan Aysun Nedime Beyazıt

Öz

Giriş: Bu çalışmada çocukluk çağında dirençli epileptik vakalarda ek ilaç olarak topiramat tedavisinin etkinliğinin ve yan etkilerinin değerlendirilmesi amaçlanmıştır. Gereç ve Yöntem: Çalışmaya alınan 166 hasta 67 kız, 99 erkek topiramat etkinliği ve yanetkiler açısından retrospektif olarak incelendi. Hastaların 82’si %49,4 parsiyel, 8’i %4,8 generalize, 6’sı %3,8 sekonder generalize, 24’ü %14,5 myoklonik epilepsi tanısı alırken,34 hasta %27,7 epileptik sendrom sınıfında yer aldı. Topiramat dozu 0,5 mg/kg/g dozunda başlanarak ortalama 9 mg/kg/g’e çıkıldı. Hastalar her kontrol sırasında nöbet sıklığı,süresi ve yan etkiler açısından değerlendirildi. İlacın etkinliği iyi tam, >%75 , kısmi ve kötü şeklinde sınıflandırıldı. Bulgular: Çalışmaya alınan 166 hastanın 85’inde %51,2 iyi, 39’unda %23,5 kısmi ve42’sinde %25,5 kötü yanıt elde edildi. Topiramat tedavisi ile parsiyel epilepsili hastaların 45’inde %54,9 iyi, 22’sinde %26,8 kısmi, 15’inde %18,3 kötü yanıt, generalizeepilepsili hastaların ise tümünde n=8 iyi yanıt alınırken myoklonik epilepsili hastaların10’unda %41,7 iyi, 4’ünde %16,7 kısmi ve 10’unda %41,7 kötü yanıt elde edildi. Genel olarak topiramat tedavisi parsiyel epilepsili hastalarda generalize ve myoklonikepilepsiye göre daha etkin bulundu p=0,008, p=0,024 . Topiramata bağlı yan etki 33hastada %19,9 saptandı. En sık görülen yan etki somnolans n=9, %5,4 idi. Topiramattedavisi 33 hastada %19,9 yanıt alınamaması, 4 hastada %2,4 ciddi yan etkinin görülmesi, 3 hastada %1,8 nöbet artışı ve 2 hastada da %1,2 uzun süreli nöbetsiz izlemnedeniyle sonlandırıldı. Sonuç: Topiramatın inatçı epileptik vakalarda ek tedavi olarak etkinliğinin yüksek, ciddi yan etkilerinin olmaması nedeniyle güvenilir olduğu görülmüştür. İnatçı epilepsilerde ek tedavi olarak tercih edilebileceği, ancak ilacın kendine özgü yan etkileri açısından yakın takip edilmesi gerektiği düşünüldü

Anahtar Kelimeler

Topiramat, çocukluk çağı, dirençli epilepsi, ilaç yan etki

The Efficacy and Adverse Effects of Topiramate in Add on Therapy in Children with Intractable Epilepsy

Öz

Introduction: The aim of this study was to evaluate the efficacy and adverse effects of topiramate add on therapy in children with intractable epilepsy. Materials and Method: The efficacy and adverse events of topiramate were evaluated in 166 children 67 girls, 99 boys . The classification of the epilepsies were as follows: partial 82 49.4% , generalized 8 4.8% , secondarily generalized 6 3.8% , myoclonic24 14.5% and epileptic syndromes 34 27.7% . Topiramate was initiated at a daily dose of0.5-1 mg/kg, up to an approximate daily dose of 9 mg/kg. The patients were assessed for theseizure frequency, duration and adverse events during the follow-up. Response to treatment was classified as good complete, >75% , moderately 25-75% and poor 0-25% . Results: Response to treatment among 166 patients were as follows: 85 51.2% good, 39 23.5% moderately and 42 25.3% poor. The efficacy rates according to the seizuretypes were 45 54.9% good, 22 26.8% moderately, 15 18.3% poor for partial seizures; 8 100% good for generalized whereas 10 41.7% good, 4 16.7% moderately and 10 41.7% poor for myoclonic seizures. Generally topiramate appeared to be more effective in partial epilepsy than generalized and myoclonic epilepsy p=0.008 and p=0.024 . Adverse events were presentin 33 patients 19.9% , mostly as somnolence n=9, 5.4% . Topiramate was discontinued because of poor response in 33 patients 19.9% , severe adverse events in 4 2.4% , increase in the frequency of seizures in 3 1.8% and long term seizure freefollow-up in 2 1.2% . Conclusion: Topiramate seems to be highly effective and safe in intractable epileptic patients. However, the drug

Anahtar Kelimeler

Topiramate, childhood, intractable epilepsy, adverse event

Kaynakça

• 1. Commission on Antiepileptic drugs of the International League Against Epilepsy. Guidelines for antiepileptic drug trails in children. Epilepsia 1994; 35:94-100.
• 2. Binnie CD. Cognitive impairment: is it inevitable? Seizure 1994; 3:17-22.
• 3. Y›lmaz K, Tatl› B, Ayd›nl› N, Çal›flkan M, Özmen M. Çocukluk ça¤› epilepsilerinde topiramat›n etkinli¤i. Epilepsi 2003; 9:151-4.
• 4. Ritter F, Glauser TA, Elterman RD, Wyllie E. Effectiveness, tolerability, and safety of topiramate in children with partial-onset seizures. Topiramate YP Study Group. Epilepsia 2000; 41:82-5.
• 5. Levisohn PM. Safety and tolerability of topiramate in children. J Child Neurol 2000; 15:22-6.
• 6. Glauser TA. Topiramate use in pediatric patients. Can J Neurol Sci 1998; 25:8-12.
• 7. Sachdeo RC, Glauser TA, Ritter F, Reife R, Lim P, Pledger G. A double blind, randomized trial of topiramate in LennoxGastaut syndrome. Topiramate YL Study Group. Neurology 1999; 52:1882-7.
• 8. Aykutlu E, Baykan B, Gürses C, Bebek N, Büyükbabani N, Gökyi¤it A. Add-on therapy with topiramate in progressive myoclonic epilepsy. Epilepsy Behav 2005; 6:260-3.
• 9. Faught E, Wilder BJ, Ramsay RE. Topiramate placebocontrolled dose-ranging trial in refractory partial epilepsy using 200-,400-, and 600-mg daily dosages. Topiramate YD Study Group. Neurology 1996; 46:1684-90.
• 10. Christensen J, Andreasen F, Poulsen JH, Dam H. Randomized, concentration-controlled trial of topiramate in refractory partial epilepsy. Neurology 2003; 61:1210-8.
• 11. Biton V, Montouris GD, Ritter F. Randomized, placebocontrolled study of topiramate in primary generalized tonicclonic seizures. Topiramate YTC Study Group. Neurology 1999; 22:1330-7.
• 12. Rosenfeld WE, Doose DR, Walker SA. A study of topiramate pharmacokinetics and tolerability in children with epilepsy. Pediatr Neurol 1999; 20:339-44.
• 13. Mikaeloff Y, de Saint Martin A, Mancini J, Peudenier S, Pedespan JM, Vallee L. Topiramate: efficacy and tolerability in children according to epilepsy syndromes. Epilepsy Res 2003; 53:225-32.
• 14. Jette N, Hemming K, Hutton JL, Marson AG. Topiramate add-on for drug-resistant partial epilepsy. Cochrane Database Syst Rev 2008; (3):CD001417.
• 15. Pledger G, Reife RA, Lim P, Karim R. Overview of topiramate efficacy from adjunctive therapy trials. Epilepsia 1995; 35:150.
• 16. Glauser TA. Preliminary observations on topiramate in pediatric epilepsies. Epilepsia 1997: 38:37-41.
• 17. Moreland EC, Griesemer DA, Holden KR. Topiramate for intractable childhood epilepsy. Seizure 1999; 8:38-40.
• 18. Glauser TA, Clark PO, Strawsburg R. A pilot study of topiramate in the treatment of infantile spasms. Epilepsia 1998; 39:1324-8.
• 19. Garcia-Penas JJ. Antiepileptic drugs in the treatment of autistic regression syndromes. Rev Neurol 2005; 40:173-6.
• 20. Coppola G, Caliendo G, Terracciano MM, Buono S, Pellegrino L, Pascotto A. Topiramate in refractory partialonset seziures in children, adolescents and young adults: a multicentric open trial. Epilepsy Research 2001; 43:255-60.
• 21. Natsch S, Hekster YA, Keyser A, Dekers CL, Meinardi H, Renier WO. Newer anticonvulsant drugs: role of pharmacology, drug interactions and adverse reactions in drug choice. Drug Safety 1997; 17:228-40.
• 22. Ben-Zeev B, Watemberg N, Augarten A, Brand N, Yahav Y, Efrati O, et al. Oligohydrosis and hyperthermia: pilot study of a novel topiramate adverse effect. J Child Neurol 2003; 18:254-7.