Nervenheilkunde 2014; 33(11): 816-821
DOI: 10.1055/s-0038-1627747
Übersichtsartikel
Schattauer GmbH

Prognose der Umstellung einer antikonvulsiven Medikation

Anfallsfreiheit oder Reduktion der AnfallsfrequenzPrognosis of changes of anticonvulsive pharmacotherapyseizure freedom or reduction of seizure frequency
J. Rösche
1   Klinik für Neurologie und Poliklinik, Universitätsmedizin Rostock
,
W. Fröscher
2   Epilepsiezentrum Bodensee, Zentrum für Psychiatrie Südwürttemberg, Ravensburg-Weissenau
› Author Affiliations
Further Information

Publication History

eingegangen am: 08 August 2014

angenommen am: 29 August 2014

Publication Date:
24 January 2018 (online)

Zusammenfassung

Gegenstand und Ziel

Da wenigstens 25% aller Menschen mit Epilepsie auf eine erste Antiepileptikatherapie nicht anfallsfrei werden, sollen die Erfolgsaussichten weiterer Pharmakotherapien bezüglich mindestens einjähriger Anfallsfreiheit oder zumindest mehr als 50%iger Reduktion der Anfallsfrequenz anhand publizierter Kohortenstudien herausgearbeitet werden.

Methoden

In einer PubMed Recherche gefundene Kohortenstudien an Menschen mit Epilepsie, aus denen der Prozentsatz der Behandlungserfolge bezüglich mindestens einjähriger Anfallsfreiheit oder zumindest mehr als 50%iger Reduktion der Anfallsfrequenz, nach erfolgloser Vorbehandlung mit mindestens einem Antiepileptikum ablesbar war, wurden ausgewertet.

Ergebnisse

Auch nach mehrjährigem therapierefraktärem Verlauf kann noch bei 20% bis 30% der Patienten eine mindestens einjährige Anfallsfreiheit durch Medikamentenumstellungen erzielt werden. Bei vermutlich weiteren 30% lassen sich Reduktionen der Anfallsfrequenz von mehr als 50% erreichen.

Schlussfolgerungen

Es gibt bei Patienten mit therapierefraktärer Epilepsie keine Situation, in welcher der Versuch der weiteren Optimierung der antiepileptischen Medikation grundsätzlich zwecklos wäre.

Klinische Relevanz

Entsprechend internationaler Empfehlungen sollten Patienten mit Epilepsie, bei denen zwei adäquate medikamentöse Therapieversuche nicht zu Anfallsfreiheit geführt haben, einer prächirurgischen Epilepsiediagnostik zugeführt werden. Führt dies nicht zu einem epilepsiechirurgischen Eingriff, sind weitere Medikamentenumstellungen erfolgversprechend.

Summary

Objective

Since at least 25% of patients with epilepsy are not becoming seizure free on a first antiepileptic treatment the efficacy of further pharmacologic treatment concerning seizure freedom for at least one year or reduction of seizure frequency of more than 50% was evaluated according to the cohort studies on patients with epilepsy published so far.

Methods

We evaluated all studies found in PubMed presenting data from which the percentage of patients who achieved seizure freedom for more than one year or the percentage of patients who achieved a reduction in seizure frequency of more than 50% after at least one unsuccessful antiepileptic treatment could be obtained.

Results

Even after a long term refractory course of epilepsy 20% to 30% of the patients can achieve seizure freedom for more than one year by changes in their antiepileptic medication. In probably another 30% of the patients a reduction in seizure frequency of at least 50% can be achieved.

Conclusions

In patients with refractory epilepsy there is always a chance to reduce the seizure frequency by changing the antiepileptic medication.

Clinical relevance

According to international recommendations patients with epilepsy, who are not seizure free despite treatment with two appropriate medical regimens should be transferred to presurgical evaluation. If this does not result in surgical treatment further medical treatment attempts by changing and combining the antiepileptic drugs should be performed.

 
  • Literatur

  • 1 Mattson RH. Drug treatment of partial epilepsy. Adv Neurol 1992; 57: 643-50.
  • 2 Heller AJ, Chesterman P, Elwes RD, Crawford P, Chadwick D, Johnson AL, Reynolds EH. Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomized comparative monotherapy trial. J Neurol Neurosurg Psychiatry 1995; 58: 44-50.
  • 3 Brodie MJ, Perucca E, Ryvlin P, Ben-Menachem E, Meencke HJ. Comparison of levetiracetam and controlled release carbamazepine in newly diagnosed epilepsy. Neurology 2007; 68: 402-8.
  • 4 Baulac M, Brodie MJ, Patten A, Segieth J, Giorgi L. Efficacy and tolerability of zonisamide versus controlled-release carbamazepine for newly diagnosed partial epilepsy: a phase 3, randomized, doubleblind, non-inferiority trial. Lancet Neurol 2012; 11: 579-88.
  • 5 Kwan P, Brodie MJ, Kälviäinen R, Yurkewicz L, Weaver J, Knapp LE. Efficacy and safety of pregabalin versus lamotrigin in patients with newly diagnosed partial seizures: a phase 3, double-blind, randomised, parallel-group trial. Lancet Neurol 2011; 10: 881-90.
  • 6 Marson AG. et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet 2007; 369: 1000-15.
  • 7 Trinka E. et al. KOMET: an unblinded, randomized, two parallel-group, stratified trial comparing the effectiveness of levetiracetam with controlled-release carbamazepine and extended-release sodium valproate as monotherapy in patients with newly diagnosed epilepsy. J Neurol Neurosurg Psychiatry 2013; 84: 1138-47.
  • 8 Groenewegen A, Tofighy A, Ryvlin P, Steinhoff BJ, Dedeken P. Measures for improving treatment outcomes for patients with epilepsy – Results from a large multinational patient-physician survey. Epilepsy & Behav 2014; 34: 58-67.
  • 9 Fröscher W, Rösche J. Kombinationstherapie bei Epilepsie. Fortschr Neurol Psychiat 2013; 81: 9-20.
  • 10 Fröscher W, Auner M, Kirschbaum J. Behandlungsergebnisse bei pharmakoresistent erscheinenden Epilepsie-Patienten. Akt Neurol 1989; 16: 1-8.
  • 11 Wolf P. Treatment of epeilepsy following rejection of epilepsy surgery. Seizure 1998; 07: 25-29.
  • 12 Engel Jr J, van Ness PC, Rassmussen TB, Ojemann LM. Outcome with respect to epileptic seizures. In: Engel Jr J. (Hrsg.) Surgical treatment of the epilepsies. New York: Raven Press; 1993: 609-621.
  • 13 Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Eng J Med 2000; 342: 314-9.
  • 14 Lhatoo SD, Sander JWAS, Shorvon SD. The dynamics of drug treatment in epilepsy: an observational study in an unselected population based cohort with newly diagnosed epilepsy followed up prospectively over 11–14 years. J Neurol Neurosurg Psychiatry 2001; 71: 632-7.
  • 15 Beghi E. et al. Adjunctiv therapy versus alternative monotherapy in patients with partial epilepsy failing on a single drug: a multicentre, randomized, pragmatic controlled trial. Epilepsy Res 2003; 57: 1-13.
  • 16 Mohanraj R, Brodie MJ. Diagnosing refractory epilepsy: response to sequential treatment schedules. Eur J Neurol 2006; 13: 277-282.
  • 17 Stephen LJ, Forsyth M, Kelly K, Brodie MJ. Antiepileptic drug combinations – Have newer agents altered clinical outcomes?. Epilepsy Res 2012; 98: 194-8.
  • 18 Stephen LJ, Brodie MJ. Seizure freedom with more than one antiepileptic drug. Seizure 2002; 11: 349-51.
  • 19 Selwa LM, Schmidt SL, Malow BA, Beydoun A. Long-term outcome of nonsurgical candidates with medically refractory localization-related epilepsy. Epilepsia 2003; 44: 1568-72.
  • 20 Luciano AL, Shorvon SD. Results of treatment changes in patients with apparently drug-resistant chronic epilepsy. Ann Neurol 2007; 62: 375-81.
  • 21 Neligan A, Bell GS, Elsayed M, Sander JW, Shorvon SD. Treatment changes in a cohort of people with apparently drug-resistant epilepsy: an extended follow-up. J Neurol Neurosurg Psychiatry 2012; 83: 810-3.
  • 22 Callaghan BC, Anand K, Hesdorffer D, Hauser WA, French JA. Likelihood of seizure remission in an adult population with refractory epilepsy. Ann Neurol 2007; 62: 382-9.
  • 23 Callaghan B, Schlesinger M, Rodemer W, Pollard J, Hesdorffer D, Hauser WA, French J. Remission and relapse in a drug-resistant epilepsy population followed prospectively. Epilepsia 2011; 52: 619-26.
  • 24 Choi H, Heiman G, Pandis D, Cantero J, Resor SR, Gilliam FG, Hauser WA. Seizure remission and relapse in adults with intractable epilepsy: A cohort study. Epilepsia 2008; 49: 1440-5.
  • 25 Choi H, Heiman GA, Munger HClary, Etienne M, Resor SR, Hauser WA. Seizure remission in adults with long-standing intractable epilepsy: An extended follow-up. Epilepsy Res 2011; 93: 115-9.
  • 26 Steinhoff BJ, Staack AM, Wisniewski I. Seizure control with antiepileptic drug therapy in 517 consecutive adult outpatients at the Kork Epilepsy Centre. Epileptic Disord 2012; 14: 379-87.
  • 27 Schiller Y, Najjar Y. Quantifying the response to antiepileptic drugs. Effect of past treatment history. Neurology 2008; 70: 54-65.
  • 28 Gilioli I, Vignoli A, Visani E, Casazza M, Canafoglia L, Chiesa V, Gardella E, La Briola F, Panzica F, Avanzini G, Canevini MP, Fraqnceschetti S, Binelli S. Focal epilepsies in adult patients attending two epilepsy centers: Classification of drug-resistance, assessment of risk factors, and usefulness of “new” antiepileptic drugs. Epilepsia 2012; 53: 733-40.
  • 29 Bonnet LJ, Smith CT, Donegan S, Marson AG. Treatment outcome after failure of a first antiepileptic drug. Neurology 2014; 83: 1-9.
  • 30 Neligan A, Bell GS, Sander JW, Shorvon SD. How refractory is refractory epilepsy? Patterns of relapse and remission in people with refractory epilepsy. Epilepsy Research 2011; 96: 225-30.
  • 31 Beyenburg St, Stavern K, Schmidt D. Placebo corrected efficacy of modern antiepileptic drugs for refractory epilepsy: Systematic review and meta-analysis. Epilepsia 2011; 51: 7-26.
  • 32 Schiller Y. Seizure relapse and development of drug resistance following long-term sizure remission. Arch Neurol 2009; 66: 1233-9.
  • 33 Fröscher W. Drug resistant epilepsy. Epileptologia 2012; 20: 23-9.
  • 34 Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Hauser WA, Mathern G, Moshé SL, Perucca E, Wiebe S, French J. Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on therapeutic Strategies. Epilepsia 2010; 51: 1069-77.