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Nervenheilkunde 2004; 23(06): 354-362
DOI: 10.1055/s-0038-1626387
Original- und Übersichtsarbeiten - Original and Review Articles
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Einsatz neuer Antiepileptika bei vorher unbehandelten Jugendlichen und Erwachsenen mit Epilepsie

Therapie-EmpfehlungenRecommendations for the use of new antiepileptic drugs for therapy of previously untreated adolescents and adults with epilepsy
D. Schmidt
1   Arbeitsgruppe Epilepsieforschung Berlin
,
C. E. Elger
2   Klinik für Epileptologie, Universität Bonn
,
B. J. Steinhoff
3   Epilepsiezentrum Kork, Kehl-Kork
,
S. R. G. Stodieck
4   Epilepsie-Zentrum Hamburg
,
H. Stefan
5   Zentrum Epilepsie, Erlangen
,
A. Hufnagel
6   Neurologische Universitätsklinik Essen
,
B. Schmitz
7   Universitätsklinik, Berlin, Campus Virchow-Klinikum
,
G. Luef
8   Universitätsklinik für Neurologie, Innsbruck
,
D. Dennig
9   Epileptologische Schwerpunktpraxis, Stuttgart
,
W. Fröscher
10   Abt. Neurologie und Epileptologie, Die Weissenau, Ravensburg
,
G. Krämer
11   Schweizerisches Epilepsie-Zentrum, Zürich
,
T. Mayer
12   Epilepsiezentrum Kleinwachau e.V., Radeberg
,
H. J. Meencke
13   Epilepsiezentrum Berlin-Brandenburg, Institut für Diagnostik der Epilepsien gGmbH
,
S. Noachtar
14   Neurologische Klinik, Universität München, Klinikum Großhadern
,
B. Pohlmann-Eden
15   Epilepsie-Zentrum Bethel, Bielefeld
,
U. Runge
16   Neurologische Universitätsklinik Greifswald
,
A. Schulze-Bonhage
17   Neurozentrum der Universität Freiburg
,
O. W. Witte
18   Klinik für Neurologie, Friedrich-Schiller-Universität Jena
› Author Affiliations
Further Information

Publication History

Publication Date:
18 January 2018 (online)

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Zusammenfassung

Die neuen, zur Monotherapie neu erkrankter jugendlicher und erwachsener Patienten mit Epilepsie in Deutschland zugelassenen Antiepileptika (AE) Gabapentin (GBP), Lamotrigin (LTG), Oxcarbazepin (OXC) und Topiramat (TPM) haben eine Reihe von Vorteilen gegenüber alten AE wie z. B. Carbamazepin (CBZ), Phenobarbital (PHB), Phenytoin (PHT), Primidon (PRM) oder Valproinsäure (VPA). Sie sind bei gleicher Wirksamkeit in Bezug auf Verträglichkeit in geeigneter Dosierung für neu erkrankte Patienten mit fokalen Epilepsien mindestens gleichwertig und zum Teil vorteilhafter als alte AE, weil sie weniger oder gar nicht enzyminduzierend sind und daher generell zu weniger Arzneimittelinteraktionen und wahrscheinlich auch zu weniger hormonell-metabolischen Nebenwirkungen führen. Die fetale Fehlbildungsrate unter LTG ist nach dem derzeitigen Wissensstand vergleichbar mit CBZ und unbehandelten Epilepsiepatientinnen und liegt deutlich niedriger als bei VPA. Daraus ergibt sich die medizinische Notwendigkeit, vor jeder Ersteinstellung sorgfältig zu prüfen, ob ein neues AE bevorzugt gegenüber einer alten Substanz einzusetzen ist. Die Auswahl zwischen den verschiedenen neuen AE sollte unter Berücksichtigung aller relevanten individuellen Faktoren erfolgen. Vor allem bei Patienten, bei denen sich unerwünschte Nebenwirkungen der alten AE besonders ungünstig auswirken könnten, sollten geeignete neue, weniger oder nicht enzyminduzierende AE bevorzugt werden.

Summary

New antiepileptic drugs (AEDs) for therapy of previously untreated adolescents and adults with epilepsy in Germany are gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OXC), and topiramate (TPM). They have a number of advantages compared to old AEDs such as carbamazepine (CBZ), phenobarbital (PHB), phenytoin (PHT), primidone (PRM), and valproate (VPA). The new AEDs show similar efficaciousness and at least similar or better tolerability at adequate dosages than old drugs for patients with partial epilepsy because they are less or not enzyme inducing at all and thus cause fewer drug interactions and are less likely to produce hormonalmetabolic disturbances. Based on current evidence, the major malformation rate associated with the use of LTG is similar to that seen during CBZ treatment or in untreated women with epilepsy and is lower than that observed with VPA treatment. These data request that a careful evaluation is needed to determine if a new AED should be preferred over an old AED when starting an AED in a previously untreated patient with epilepsy. The choice among the new AEDs will be made after careful consideration of all other individual relevant factors. In patients, in whom adverse events of the old AEDs could be particulary harmful, suitable new AEDs which are less or not at all enzyme inducing, should be preferred.

Schlüsselwörter

Gabapentin - Lamotrigin - Oxcarbazepin - Topiramat - Empfehlungen - Epilepsietherapie - Antiepileptika - Ersteinstellung

Keywords

Gabapentin - lamotrigine - oxcarbazepine - topiramate - recommendations - epilepsy treatment - antiepileptic drugs - initial epilepsy treatment
 

  • Literatur

  • 1 Arroyo S, Squires L, Wang S. for the EPMN 106 Study Investigators. Topiramate (TPM) Monotherapy in Newly Diagnosed Epilepsy: Effectiveness in Dose-Response Study. Epilepsia 2002; 43 (Suppl. 08) 47-8.
    CrossrefPubMedGoogle Scholar
  • 2 Bazil CW, Pedley TA. Clinical pharmacology of antiepileptic drugs. Clin Neuropharmacol 2003; 26 (01) 38-52.
    CrossrefPubMedGoogle Scholar
  • 3 Ben-Menachem E, Axelsen M, Johanson EH. et al. Predictors of weight loss in adults with topiramate-treated epilepsy. Obes Res 2003; 11 (04) 556-62.
    CrossrefPubMedGoogle Scholar
  • 4 Bill PA, Vigonius U, Pohlmann H. et al. A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in adults with previously untreated epilepsy. Epilepsy Research 1997; 27: 195-204.
    CrossrefPubMedGoogle Scholar
  • 5 Biton V. Effect of antiepileptic drugs on bodyweight. Overview and clinical implications for the treatment of epilepsy. CNS Drugs 2003; 17 (11) 781-91.
    PubMedGoogle Scholar
  • 6 Blum DE. New drugs for persons with epilepsy. Adv Neurol 1998; 76: 57-87.
    Google Scholar
  • 7 Brodie MJ, Anhut H, Murray G. et al. Gabapentin versus Lamotrigine monotherapy: a doubleblind comparison. Epilepsia 2002; 43 (09) 993-1000.
    CrossrefPubMedGoogle Scholar
  • 8 Brodie MJ, Overstall PW, Giorgi L. Multicentre, double-blind, randomised comparison between lamotrigine and carbamazepine in elderly patients with newly diagnosed epilepsy. Epilepsy Research 1999; 37: 81-7.
    CrossrefPubMedGoogle Scholar
  • 9 Brodie MJ, Richens A. et al. Double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. Lancet 1995; 345: 476-9.
    CrossrefPubMedGoogle Scholar
  • 10 Chadwick DW, Anhut H, Greiner MJ. et al. A double -blind trial of gabapentin monotherapy for newly diagnosed partial seizures. Neurology 1998; 51: 1282-8.
    CrossrefPubMedGoogle Scholar
  • 11 Christe W, Krämer G, Vigonius U. et al. A double-blind controlled clinical trial: oxcarbazepine versus sodium valproate in adults with newly diagnosed epilepsy. Epilepsy Research 1997; 26: 451-60.
    CrossrefPubMedGoogle Scholar
  • 12 Cozza KL, Armstrong SC, Oesterheld JR. Concise Guide to Drug Interaction Principles for Medical Practice. 2nd ed.. Washington: American Psychiatric Publishing; 2003
    Google Scholar
  • 13 Curran HV, Java R. Memory and psychomotor effects of oxcarbazepine in healthy human volunteers. Eur J Clin Pharmacol 1993; 44 (06) 529-33.
    CrossrefPubMedGoogle Scholar
  • 14 Dam M, Ekberg R, Lóyning Y. et al. A doubleblind study comparing oxcarbazepine and carbamazepine in patients with newly diagnosed, previously untreated epilepsy. Epilepsy Research 1989; 03: 70-6.
    CrossrefPubMedGoogle Scholar
  • 15 Devinsky O, Vuong A, Hammer A, Barrett PS. Stable weight during lamotrigine therapy: A review of 32 studies. Neurology 2000; 54: 973-5.
    CrossrefPubMedGoogle Scholar
  • 16 Dimond KR, Pande AC, Lamoreaux L, Pierce MW. Effect of gabapentin on mood and wellbeing in patients with epilepsy. Prog NeuroPsychopharmacol 1996; 20: 407-17.
    Google Scholar
  • 17 Doose DR, Wang SS, Padmanabhan M. et al. Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects. Epilepsia 2003; 44 (04) 540-9.
    CrossrefPubMedGoogle Scholar
  • 18 Edwards KR, Sackellares JC. et al. Lamotrigine monotherapy improves depressive symptoms in epilepsy: a double-blind comparison with valproate. Epilepsy and Behavior 2001; 02: 28-36.
    CrossrefPubMedGoogle Scholar
  • 19 Elger CE, Schmidt D. Aktuelle Epilepsietherapie: kurzgefasst. München: Zuckschwerdt 2003
    PubMedGoogle Scholar
  • 20 Engel Jr. J, Wiebe S, French J. et al. Practice parameter. Temporal lobe and localized neocortical resections for epilepsy. Report of the Quality standards Subcommittee with the American Academy of Neurology, in Association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology 2003; 60: 538-47.
    Google Scholar
  • 21 Farhat G, Yamout B, Mikati MA. et al. Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology 2002; 58: 1348-53.
    CrossrefPubMedGoogle Scholar
  • 22 Faught E, Squires L, Wang S, Thienel U. Topiramate Monotherapy in Newly/Recently Diagnosed Epilepsy: Adverse Event Profile in 1000+ Participating in Double-Blind Trials Neurology. 2003; 60 (Suppl. 01) A475.
    Google Scholar
  • 23 Faught E. Clinical trials for treatment of primary generalized epilepsies. Epilepsia 2003; 44 (Suppl. 07) 44-50.
    PubMedGoogle Scholar
  • 24 Gilliam FG, Veloso F, Bomhof MA. et al. A dose-comparison trial of Topiramate as monotherapy in recently diagnosed partial epilepsy. Neurology 2003; 60: 196-202.
    CrossrefPubMedGoogle Scholar
  • 25 Gil-Nagel A. Review of new antiepileptic drugs as initial therapy. Epilepsia 2003; 44 (Suppl. 04) 3-10.
    PubMedGoogle Scholar
  • 26 Guerreiro MM, Vigonius U, Pohlmann H. et al. A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in children and adolescents with epilepsy. Epilepsy Research 1997; 27: 205-13.
    CrossrefPubMedGoogle Scholar
  • 27 Hancock E, Cross H. Treatment of LennoxGastaut Syndrome. Cochrane Database. Syst Rev 2003; 03: CD003277.
    Google Scholar
  • 28 Harden CL. The co-morbidity of depression and epilepsy:epidemiology, etiology, and treatment. Ann Clin Psychiatry 2003; 15 (02) 95-108.
    CrossrefPubMedGoogle Scholar
  • 29 Herzog AG, Coleman AE, Jacobs AR. et al. Interictal EEG discharges, reproductive hormones, and menstrual disorders in epilepsy. Ann Neurol 2003; 54 (05) 625-37.
    CrossrefPubMedGoogle Scholar
  • 30 Herzog AG, Drislane FW, Schomer Dl. et al. Differential antiepileptic drug effects on sex hormones and reproductive hormones: a comparison between lamotrigine and enzyme-inducing antiepileptic drugs. Epilepsia 2003; 44 (Suppl. 09) 107.
    CrossrefPubMedGoogle Scholar
  • 31 Hufnagel A. Erstmaliger epileptischer Anfall. In: Diener HC. (Hrsg.). Leitlinien für Diagnostik und Therapie in der Neurologie. Stuttgart: Thieme Verlag 2003: 2-3.
    Google Scholar
  • 32 Hufnagel A. Oxcarbazepin ein neues Antiepileptikum. Arzneimitteltherapie 2000; 18: 299-301.
    Google Scholar
  • 33 Isojaervi J, Rättyä J, Myllyla VV. et al. Valproate, lamotrigine and insulin-mediated risks in women with epilepsy. Ann Neurol 1998; 43 (04) 446-51.
    CrossrefPubMedGoogle Scholar
  • 34 Isojaervi JIT, Löfgren E, Juntunen KST. et al. Effect of epilepsy and antiepileptic drugs on male reproductive health. Neurology 2004; 62: 247-53.
    CrossrefPubMedGoogle Scholar
  • 35 Isojaervi JIT, Pakarinen AJ, Rautio A. et al. Liver enzyme induction and serum lipid levels after replacement of carbamazepine with oxcarbazepine. Epilepsia 1994; 35 (06) 1217-20.
    CrossrefPubMedGoogle Scholar
  • 36 Isojaervi JIT, Pakarinen AJ, Rautio A, Pelkonen O, Myllylae VV. Serum sex hormone levels after replacing carbamazepine with oxcarbazepine. Europ J Clin Pharmacol 1995; 47 (05) 461-4.
    PubMedGoogle Scholar
  • 37 Isojärvi JIT, Repo M, Pakarinen AJ, Lukkarinen O, Myllylä VV. Carbamazepine, phenytoin, sex hormones, and sexual function in men with epilepsy. Epilepsia 1995; 36: 366-70.
    CrossrefPubMedGoogle Scholar
  • 38 Isojärvi JI, Laatikainen TJ, Knip M. et al. Obesity and endocrine disorders in women taking valproate for epilepsy. Ann Neurol 1996; 39: 579-84.
    CrossrefPubMedGoogle Scholar
  • 39 Kalogjera-Sackellares D, Sackellares JC. Improvement in depression associated with partial epilepsy in patients treated with lamotrigine. Epilepsy and Behavior 2002; 03: 510-6.
    CrossrefPubMedGoogle Scholar
  • 40 Koskiniemi M, Van Vleymen B, Hakamies L. et al. Piracetam relieves symptoms in progressive myoclonus epilepsy: a multicentre, randomised, double-blind, crossover study comparing the efficacy and safety of three dosages of oral piracetam with placebo. J Neurol Neurosurg Psychiat 1998; 64 (03) 344-8.
    CrossrefPubMedGoogle Scholar
  • 41 Krämer G. Oxcarbazepin (Trileptal®) ein neues Antiepileptikum zur Monound Kombinationstherapie. Aktuelle Neurologie 2000; 27: 59-71.
    Article in Thieme ConnectGoogle Scholar
  • 42 Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000; 342: 314-9.
    CrossrefPubMedGoogle Scholar
  • 43 Leach JP, Girvin J, Paul A, Brodie MJ. Gabapentin and cognition: a double-blind, dose ranging, placebo controlled study in refractory epilepsy. J Neurol Neurosurg Psychiat 1997; 62: 372-6.
    CrossrefPubMedGoogle Scholar
  • 44 Liporace J, D’Abreu A. Epilepsy and women’s health: family planning, bone health, menopause, and menstrual-related seizures. Mayo Clin Proc 2003; 78 (04) 497-506.
    CrossrefPubMedGoogle Scholar
  • 45 Liporace J, Ward S, Nei M. et al. Metabolic bone disease in young adults (younger 40 years) with epilepsy. Epilepsia 2001; 42 (Suppl. 07) 154.
    Google Scholar
  • 46 Luef G, Abraham I, Trinka E. et al. Hyperandrogenism, postprandial hyperinsulinism and the risk of PCOS in a cross sectional study of women with epilepsy treated with valproate. Epilepsy Research 2002; 48 (1-2) 91-102.
    CrossrefPubMedGoogle Scholar
  • 47 Martin R, Kuzniecky R, Ho S. et al. Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults. Neurology 1999; 52 (02) 321-7.
    CrossrefPubMedGoogle Scholar
  • 48 Meador KJ, Loring DW, Ray PG. et al. Differential cognitive effects of carbamazepine and gabapentin. Epilepsia 1999; 40: 1279-85.
    CrossrefPubMedGoogle Scholar
  • 49 Mattson RH, Cramer JA, Collins JF. et al. Comparison of carbamazepine, phenobarbital, phenytoin and primidone in partial and secondarily generalized toni-clonic epileptic seizures. New Engl J Med 1985; 313: 145-51.
    CrossrefPubMedGoogle Scholar
  • 50 Matalon S, Schechtman S, Goldzweig G, Ornoy A. The teratogenic effect of carbamazepine: a meta-analysis of 1255 exposures. Reprod Toxicol 2002; 16 (01) 9-17.
    CrossrefPubMedGoogle Scholar
  • 51 McKee PJ, Blacklaw J, Forrest G. et al. A double-blind, placebo-controlled interaction study between oxcarbazepine and carbamazepine, sodium valproate and phenytoin in epileptic patients. British J Clin Pharmacol 1994; 37 (01) 27-32.
    CrossrefPubMedGoogle Scholar
  • 52 Meador KJ, Loring DW, Ray PG. et al. Differential cognitive effects of carbamazepine and gabapentin. Epilepsia 1999; 40: 1279-85.
    CrossrefPubMedGoogle Scholar
  • 53 Morrell M. Reproductive and metabolic disorders in women with epilepsy. Epilepsia 2003; 44 (Suppl. 04) 11-20.
    CrossrefPubMedGoogle Scholar
  • 54 Morrell MJ, Isojärvi J, Taylor AE. et al. Higher androgens and weight gain with valproate compared with lamotrigine for epilepsy. Epilepsy Research 2003; 54: 189-99.
    CrossrefPubMedGoogle Scholar
  • 55 Morrow JI, Craig JJ. Russell et al. Which antiepileptic drugs are safest in pregnancy?. Epilepsia 2003; 44 (Suppl. 08) PO96.
    Google Scholar
  • 56 Motamedi G, Meador K. Epilepsy and cognition. Epilepsy and Behavior 2003; 04: S25-38.
    Google Scholar
  • 57 Nicolson A, Appleton RE, Chadwick DW, Smith DF. The relationship between treatment with valproate, lamotrigine and topiramate and the prognosis of the idiopathic generalized epilepsies. J Neurol Neurosurg Psychiat 2004; 75: 75-9.
    PubMedGoogle Scholar
  • 58 Pack AM, Morrell MJ. Adverse Effects of Antiepileptic Drugs on Bone Structure. Epidemiology, Mechanisms and Therapeutic Implications. CNS Drugs 2001; 15 (08) 633-42.
    PubMedGoogle Scholar
  • 59 Pack AM, Olarte LS, Morell MJ. et al. Bone mineral density in an outpatient population receiving enzyme-inducing antiepileptic drugs. Epilepsy and Behavior 2003; 04: 169-74.
    CrossrefPubMedGoogle Scholar
  • 60 Pedersen B, D’Souza J. Oxcarbazepine therapy results in no clinically significant changes in weight. Epilepsia 2002; 43 (Suppl. 08) 149.
    Google Scholar
  • 61 Penney S. et al. Effect of carbamazepine and valproate on bone mineral density. J Pediatr 1995; 127: 256-62.
    CrossrefPubMedGoogle Scholar
  • 62 Privitera MD. et al. Topiramate, carbamazepine, and valproate monotherapy: double-blind comparison in newly diagnosed epilepsy. Acta Neurol Scand 2003; 107: 165-75.
    CrossrefPubMedGoogle Scholar
  • 63 Ramsay RE. et al. Treatment of seizures in the elderly: Final analysis from DVA cooperative study 428. Epilepsia 2003; 44 (Suppl. 09) 170.
    Google Scholar
  • 64 Rättyä J. et al. The effects of valproate, carbamazepine, and oxcarbazepine on growth and sexual maturation in girls with epilepsy. Pediatrics 1999; 103 (03) 588-93.
    CrossrefPubMedGoogle Scholar
  • 65 Rättyä J. et al. Reproductive effects of valproate, carbamazepine, and oxcarbazepine in men with epilepsy. Neurology 2001; 56 (01) 31-6.
    CrossrefPubMedGoogle Scholar
  • 66 Ray JG, Papaioannou A, Ioannidis G, Adachi JD. Anticonvulsant use and low bone mass in adults with neurodevelopmental disorders. Q J Med 2002; 95: 219-23.
    CrossrefPubMedGoogle Scholar
  • 67 Rhoden EL, Morgentaler A. Risks of testosterone replacement therapy and recommendations for monitoring New Engl J Med. 2004; 350: 482-92.
    PubMedGoogle Scholar
  • 68 Sabers A, Buchholt JM, Uldall P, Hansen EL. Lamotrigine plasma levels reduced by oral contraceptives. Epilepsy Research 2001; 47: 151-4.
    CrossrefPubMedGoogle Scholar
  • 69 Salgado M, Santos D, Bathel H, Santiago R. Sexual hormone profile in young women with epilepsy treated with topiramate monotherapy. Epilepsia 2002; 43 (S8): 157.
    Google Scholar
  • 70 Sato Y. et al. Decreased bone mass and increased bone turnover with valproate therapy in adults with epilepsy. Neurology 2001; 57: 445-9.
    CrossrefPubMedGoogle Scholar
  • 71 Schmidt D, Sachdeo R. Oxcarbazepine for Treatment of Partial Epilepsy: A Review and Recommendations for Clinical Use. Epilepsy and Behavior 2000; 01: 396-405.
    CrossrefPubMedGoogle Scholar
  • 72 Schmidt D, Elger CE. Praktische Epilepsiebehandlung. Stuttgart: Thieme 2002
    PubMedGoogle Scholar
  • 73 Schmidt D, Elger CE, Steinhoff BJ, Stefan H. Wann ist Gabapentin zur Behandlung von Epilepsien vorteilhafter als Carbamazepin? Nervenheilkunde. 2003; 22: 520-4.
    PubMedGoogle Scholar
  • 74 Schmidt D, Elger CE. Oxcarbazepin (Trileptal): Ein wirksames und gut verträgliches neues Medikament der ersten Wahl zur Behandlung fokaler Anfälle. Nervenarzt 2000; 71 (10) 849-55.
    CrossrefPubMedGoogle Scholar
  • 75 Schmidt D, Elger CE. Worin unterscheidet sich Oxcarbazepin von Carbamazepin? Nervenarzt. 2004 (im Druck).
    PubMedGoogle Scholar
  • 76 Seale CG. et al. Bone health in women with epilepsy. Epilepsia 2000; 41 (Suppl. 07) 198.
    Google Scholar
  • 77 Shank RP. et al. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia 2000; 41 (Suppl. 01) S3-S9.
    PubMedGoogle Scholar
  • 78 Stefan H. Epilepsien – Diagnosen und Behandlung. 3. Aufl. Stuttgart: Thieme 1999
    PubMedGoogle Scholar
  • 79 Stefan H. Neue Antikonvulsiva 2. Generation. Arzneimitteltherapie 2003; 21: 373-83.
    Google Scholar
  • 80 Steiner TJ, Dellaportas CI. et al. Lamotrigine monotherapy in newly diagnosed untreated epilepsy: a double-blind comparison with phenytoin. Epilepsia 1999; 40 (05) 601-7.
    CrossrefPubMedGoogle Scholar
  • 81 Stephen LJ, Kwan P. et al. Hormone profiles in young adults with epilepsy treated with sodium valproate or lamotrigine monotherapy. Epilepsia 2001; 42 (08) 1002-6.
    CrossrefPubMedGoogle Scholar
  • 82 Strolin-Benedetti M. Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies. Fundamental and Clinical Pharmacology 2000; 14 (04) 301-9.
    CrossrefPubMedGoogle Scholar
  • 83 Vicenzini E. et al. A randomized placebo controlled study of clinical and neurophysiological effects of carbamazepine, oxcarbazepine and levetiracetam in healthy volunteers. Epilepsia 2002; 43 (Suppl. 08) 47.
    CrossrefPubMedGoogle Scholar
  • 84 Wellington K, Goa KL. Oxcarbazepine – an update of its efficacy in the management of epilepsy. CNS Drugs 2001; 15 (02) 137-63.
    CrossrefPubMedGoogle Scholar