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Drug Treatment of Epilepsy in the 1990s

Achievements and New Developments

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Summary

There have been significant advances in the medical treatment of epilepsy in recent years. Improved formulations of several classical antiepileptic drugs (AEDs) have appeared, resulting in improved efficacy and decreased toxicity. A marked increase in the number of comparative investigations of AEDs has also made treatment choice somewhat simpler. Rational methods applied in the search for new AEDs have resulted in the introduction of several new AEDs. So far, evidence seems to indicate that progress has been made with regard to developing compounds not necessarily with superior efficacy but with simpler pharmacokinetics, avoiding enzyme induction as well as decreasing the number of interactions, and improving adverse effect profiles, in comparison to the previous generation of AEDs. A novel approach to the clinical testing of AEDs has made. it possible to demonstrate unequivocal efficacy, as well as efficacy as mono-therapy, very early in the development of novel compounds. Results of studies from developing countries seem to raise doubt with regard to the value of the old dogmatic principle that early treatment is important in terms of the long term prognosis for seizure control. Traditional ideas on the value of monotherapy have also been questioned on the basis of a novel concept of so-called ‘rational polytherapy’ which, however, still await scientific validation. On the basis of excellent epidemiological and large controlled clinical studies, our ideas of the necessary duration of AED treatment have become much more optimistic than before.

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References

  1. Locock C. Discussion of paper by EH Sieveking: analysis of 52 cases of epilepsy observed by the author. Lancet 1857; I: 527

    Google Scholar 

  2. Tomson T. Interdosage fluctuations in plasma carbamazepine concentration determine intermittent side effects. Arch Neurol 1984; 41: 830–4

    Article  PubMed  CAS  Google Scholar 

  3. Cramer J, Mattson RH, Prevey MC, et al. How often is medication taken as prescribed? A novel assessment technique. JAMA 1989; 261: 3273–7

    Article  PubMed  CAS  Google Scholar 

  4. Persson L, Ben-Menachem E, Bentsson E, et al. Differences in side effects between a conventional carbamazepine preparation and a slow release preparation of carbamazepine. Epilepsy Res 1990; 6: 134–40

    Article  PubMed  CAS  Google Scholar 

  5. Canger R, Altamura AC, Belvedere O, et al. Conventional vs controlled-release carbamazepine: a multicentre, double-blind, cross-over study. Acta Neurol Scand 1990; 82: 9–13

    Article  PubMed  CAS  Google Scholar 

  6. McKee PJW, Backlaw J, Butler R, et al. Monotherapy with conventional and controlled-release carbamazepine: a double-blind, double-dummy comparison in epileptic patients. Br J Clin Pharmacol 1991; 32: 99–104

    Article  PubMed  CAS  Google Scholar 

  7. McKee PJW, Blacklaw J, Carswell A, et al. Double dummy comparison between once and twice daily dosing with modified-release carbamazepine in epileptic patients. Br J Clin Pharmacol 1993; 36: 257–61

    Article  PubMed  CAS  Google Scholar 

  8. Gram L, Bentsen KD, Parnas H, et al. Controlled trials in epilepsy. A review. Epilepsia 1982; 23: 491–519

    Article  PubMed  CAS  Google Scholar 

  9. Mattson RH, Cramer JA, Collins JF, et al. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondary generalised tonic-clonic seizures. N Engl J Med 1985; 313: 145–51

    Article  PubMed  CAS  Google Scholar 

  10. Mattson RH, Cramer JA, Collins JE. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalised tonic-clonic seizures in adults. N Engl J Med 1992; 327: 765–71

    Article  PubMed  CAS  Google Scholar 

  11. Richens A, Davidson DLW, Cartlidge NEF, et al. A multicentre comparative trial of sodium valproate and carbamazepine in adult onset epilepsy. J Neurol Neurosurg Psychiatry 1994; 57: 682–7

    Article  PubMed  CAS  Google Scholar 

  12. Heller AJ, Chesterman P, Elwes RDC, et al. Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial. J Neurol Neurosurg Psychiatry 1995; 58: 44–50

    Article  PubMed  CAS  Google Scholar 

  13. Verity CM, Hosking G, Easter DJ. A multicentre comparative trial of sodium valproate and carbamazepine in pediatric epilepsy. Dev Med Child Neurol 1995; 37: 97–108

    Article  PubMed  CAS  Google Scholar 

  14. Porter RJ, Cereghino JJ, Gladding GD, et al. Antiepileptic drug development program. Cleve Clin J Med 1984; 51: 293–305

    CAS  Google Scholar 

  15. Rogowski MA, Porter RJ. Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with considerations of promising developmental stage compounds. Pharmacol Rev 1990; 42: 223–6

    Google Scholar 

  16. Theodore WH, Raubertas RF, Porter RJ, et al. Felbamate: a clinical trial for complex partial seizures. Epilepsia 1991; 32: 392–7

    Article  PubMed  CAS  Google Scholar 

  17. Gram L, Wulff K, Rasmussen KE, et al. Valproate sodium: a controlled clinical trial including monitoring of serum levels. Epilepsia 1977; 18: 141–8

    Article  PubMed  CAS  Google Scholar 

  18. Leber P. Hazards of inference: the active control investigation. Epilepsia 1989; 30: S57–63

    Article  PubMed  Google Scholar 

  19. Leber P. The implicit assumption of active controlled trials (a critical examination). Control Clin Trials 1983; 14: 133

    Google Scholar 

  20. Schmidt D. Evaluation of clinical efficacy in antiepileptic drug trials. In: Pisani F, Perucca E, Avanzini G, editors. New antiepileptic drugs. Suppl. 3. Amsterdam: Elsevier, 1991: 69–78

    Google Scholar 

  21. Pledger GW, Kramer LD. Clinical trials of investigational antiepileptic drugs: monotherapy designs. Epilepsia 1991; 32: 216–21

    Article  Google Scholar 

  22. Cereghino JJ. Clinical trial design for antiepileptic drugs. Ann Neurol 1992; 32: 393–4

    Article  PubMed  CAS  Google Scholar 

  23. Gram L, Schmidt D. Innovative designs of controlled clinical trials in epilepsy. Epilepsia 1993; 34 Suppl. 7: S1–6

    Article  PubMed  Google Scholar 

  24. Pledger GW, Schmidt D. Evaluation of antiepileptic drug efficacy: a review of clinical trial design. Drugs 1994; 48: 498–509

    Article  PubMed  CAS  Google Scholar 

  25. Sachdeo R, Kramer LD, Roseberg A, et al. Felbamate monotherapy: controlled trial in patients with partial onset seizures. Ann Neurol 1992; 32: 386–92

    Article  PubMed  CAS  Google Scholar 

  26. Faught E, Sachdeo RC, Remler MP, et al. Felbamate monotherapy for partial-onset seizures: an active control trial. Neurology 1993; 43: 688–92

    Article  PubMed  CAS  Google Scholar 

  27. Bourgeois B, Leppik IE, Sackellares JC, et al. Felbamate: a double-blind controlled trial in patients undergoing presurgical evalaution of partial seizures. Neurology 1993; 43: 693–6

    Article  PubMed  CAS  Google Scholar 

  28. Kalviainen R, Keranen T, Riekkinen PJ. Place of newer antiepileptic drugs in the treatment of epilepsy. Drugs 1993; 46(6): 1009–24

    Article  PubMed  CAS  Google Scholar 

  29. Patsalos PN, Duncan JS. New antiepileptic drugs: a review of their current status and clinical potential. CNS Drugs 1994; 2(1): 40–77

    Article  Google Scholar 

  30. Sabers A, Gram L. Progress in the medical treatment of epilepsy: an overview of new antiepileptic drugs. Eur J Neurol 1995; 1: 189–202

    Article  Google Scholar 

  31. McLean MJ, Schmutz M, Wamil AW, et al. Oxcarbazepine: mechanisms of action. Epilepsia 1994; 35 Suppl. 3: S5–9

    Article  PubMed  Google Scholar 

  32. Bülau P, Stoll KD, Fröscher W. Oxcarbazepine versus carbamazepine. In: Wolf P, Dam M, Janz D, editors. Advances in epileptology. New York: Raven Press, 1987: 331–6

    Google Scholar 

  33. Reinikainen KJ, Keränen T, Halonen T, et al. Comparison of oxcarbazepine and carbamazepine: a double-blind study. Epilepsy Res 1987; 1: 284–9

    Article  PubMed  CAS  Google Scholar 

  34. Dam M, Ekberg R, Løyning Y, et al. A double-blind study comparing oxcarbazepine and carbamazepine in patients with newly diagnosed, previously untreated epilepsy. Epilepsy Res 1989; 3: 70–6

    Article  PubMed  CAS  Google Scholar 

  35. Houtkooper MA, Lammertsma A, Meyer JWA, et al. Oxcarbazepine (GP 47.680): a possible alternative to carbamazepine. Epilepsia 1987; 28(6): 693–8

    Article  PubMed  CAS  Google Scholar 

  36. Friis ML, Kristensen O, Boas J, et al. Therapeutic experiences with 947 epileptic out-patients in oxcarbazepine treatment. Acta Neurol Scand 1993; 87: 224–7

    Article  PubMed  CAS  Google Scholar 

  37. van Parys JPA, Meinardi H. Survey of 260 epileptic patients treated with oxcarbazepine (Trileptal®) on a named-patient basis. Epilepsy Res 1994; 19: 79–85

    Article  PubMed  Google Scholar 

  38. Grant SM, Faulds D. Oxcarbazepine: a review of its pharmacology and therapeutic potential in epilepsy, trigeminal neuralgia and affective disorders. Drugs 1992; 43(6): 873–88

    Article  PubMed  CAS  Google Scholar 

  39. Schechter PJ, Hanke NFJ, Grove J, et al. Biochemical and clinical effects of gamma-vinyl GAB A in patients with epilepsy. Neurology 1984; 34: 182–6

    Article  PubMed  CAS  Google Scholar 

  40. Ben-Menachem E. Pharmacokinetic effects of vigabatrin on cerebrospinal fluid amino acids in humans. Epilepsia 1989; 30 Suppl. 3:S12–4

    Article  PubMed  Google Scholar 

  41. Mumford JP, Dam M. Meta-analysis of European placebo controlled studies of vigabatrin in drug resistant epilepsy. Br J Clin Pharmacol 1989; 27 Suppl. 1: S101–7

    Article  Google Scholar 

  42. Chiron C, Dulac O, Beaumont D, et al. Therapeutic trial of vigabatrin in refractory infantile spasms. J Child Neurol 1991; 6 Suppl. 2:S52–9

    Google Scholar 

  43. Kalviainen R, Aikia M, Saukkonen AM, et al. Vigabatrin vs carbamazepin monotherapy in patients with newly diagnosed epilepsy. Arch Neurol 1995; 52: 989–96

    Article  PubMed  CAS  Google Scholar 

  44. Michelucci R, Tassinari CA. Response to vigabatrin in relation to seizure type. Br J Clin Pharmacol 1989; 27 Suppl. 1: 119S–24S

    Article  PubMed  Google Scholar 

  45. Remy C, Beaumont D. Efficacy and safety of vigabatrin in the long-term treatment of refractory epilepsy. Br J Clin Pharmacol 1989; 27 Suppl. 1: 125S–9S

    Article  PubMed  Google Scholar 

  46. Dodrill CB, Arnett JL, Sommerville KW, et al. Evaluation of the effects of vigabatrin on cognitive abilities and quality of life in epilepsy. Neurology 1993; 43: 2501–7

    Article  PubMed  CAS  Google Scholar 

  47. Ring HA, Crellin R, Reynolds EH. Vigabatrin and depression. J Neurol Neurosurg Psychiatry 1993; 56: 925–8

    Article  PubMed  CAS  Google Scholar 

  48. Sander JWAS, Hart YM, Trimble MR, et al. Vigabatrin and psychosis. J Neurol Neurosurg Psychiatry 1991; 54: 435–9

    Article  PubMed  CAS  Google Scholar 

  49. Grant SM, Heel RC. Vigabatrin: a review of its pharmacodynamic and pharmacokinetic proberties, and therapeutic potential in epilepsy and disorders of motor control. Drugs 1991; 41: 889–926

    Article  PubMed  CAS  Google Scholar 

  50. Leach MJ, Marden CM, Miller AA. Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: II. Neurochemical studies on the mechanism of action. Epilepsia 1986; 27(5): 490–7

    Article  PubMed  CAS  Google Scholar 

  51. Binnie CD, Debets RMC, Engelsman M, et al. Double-blind crossover trial of lamotrigine (Lamictal) as add-on therapy in intractable epilepsy. Epilepsy Res 1989; 4: 222–9

    Article  PubMed  CAS  Google Scholar 

  52. Jawad S, Richens A, Goodwin G, et al. Controlled trial of lamotrigine (Lamictal®) for refractory partial seizures. Epilepsia 1989; 30(3): 356–63

    Article  PubMed  CAS  Google Scholar 

  53. Sander JWAS, Patsalos PN, Oxley JR, et al. A randomised dou ble-blind placebo-controlled add-on trial of lamotrigine in patients with severe epilepsy. Epilepsy Res 1990; 6: 221–6

    Article  PubMed  CAS  Google Scholar 

  54. Sander JWAS, Trevisol-Bittencourt PC, Hart YM, et al. The efficacy and long term tolerability of lamotrigine in the treatment of severe epilepsy. Epilepsy Res 1990; 7: 226–9

    Article  PubMed  CAS  Google Scholar 

  55. Loiseau P, Yuen AWC, Duché B, et al. A randomised double-blind placebo-controlled crossover add-on trial of lamotrigine in patients with treatment-resistant partial seizures. Epilepsy Res 1990; 7: 136–45

    Article  PubMed  CAS  Google Scholar 

  56. Timmings PL, Richens A. Lamotrigine in primary generalized epilepsy. Lancet 1992; 339: 1300–1

    Article  PubMed  CAS  Google Scholar 

  57. Smith D, Baker G, Davies G, et al. Outcomes of add-on treatment with lamotrigine in partial epilepsy. Epilepsia 1993; 34(2): 312–22

    Article  PubMed  CAS  Google Scholar 

  58. Messenheimer J, Ramsay RE, Willmore LJ, et al. Lamotrigine therapy for partial seizures: a multicenter, placebo-controlled, double-blind, crossover trial. Epilepsia 1994; 35: 113–21

    Article  PubMed  CAS  Google Scholar 

  59. Bisgaard C, Dalby M, Mai J. Lamictal as add-on antiepileptic drug in 210 patients with resistant epilepsy [abstract]. Epilepsia 1994; 35 Suppl. 7: 98

    Google Scholar 

  60. Schlumberger E, Chavez F, Palacios L, et al. Lamotrigine in treatment of 120 children with epilepsy. Epilepsia 1994; 35(2): 359–67

    Article  PubMed  CAS  Google Scholar 

  61. Hirsch E, Dutoya V, Strumia S, et al. Lamotrigine and generalized epileptic syndromes [abstract]. Epilepsia 1995; 36 Suppl. 3: S112

    Google Scholar 

  62. Mai J, Sørensen T. Experience with lamotrigine in mentally retarded epilepsy patients [abstract]. Epilepsia 1995; 36 Suppl. 3: S115

    Google Scholar 

  63. Brodie MJ, Richens A, Yuen AWC, et al. Double-blind comparison of lamotrigine and carbamazepine in newly-diagnosed epilepsy. Lancet 1995; 345: 476–9

    Article  PubMed  CAS  Google Scholar 

  64. Binnie CD, van Emde Boas W, Kasteleijn-Nolste-Trenite DGA, et al. Acute effect of lamotrigine (BW430C) in persons with epilepsy. Epilepsia 1986; 27: 248–54

    Article  PubMed  CAS  Google Scholar 

  65. Jawad S, Yuen WC, Peck AW, et al. Lamotrigine: single dose pharmacokinetics, and initial one week experience in refractory seizures. Epilepsy Res 1987; 1: 194–201

    Article  PubMed  CAS  Google Scholar 

  66. Besag FMC, Subel B, Pool F, et al. Carbamazepine toxicity with lamotrigine: a pharmacokinetic or pharmacodynamic interaction [abstract]. Epilepsia 1994; 35 Suppl. 7: 73

    Google Scholar 

  67. Fitton A, Goa K. Lamotrigine: an update of its pharmacology and its therapeutic use in epilepsy. Drugs 1995; 50(4): 691–713

    Article  PubMed  CAS  Google Scholar 

  68. Taylor CP. Emerging perspectives on mechanism of action of gabapentin. Neurology 1994; 44 Suppl. 5: S10–6

    PubMed  CAS  Google Scholar 

  69. Goa KL, Sorkin EM. Gabapentin: a review of its pharmacological properties and clinical potential in epilepsy. Drugs 1993; 46(3): 409–27

    Article  PubMed  CAS  Google Scholar 

  70. UK Gabapentin Study Group. Gabapentin in partial epilepsy. Lancet 1990; 335: 1114–7

    Article  Google Scholar 

  71. Bruni J, Saunders M, Anhut H, et al. Efficacy and safety of gabapentin (Neurontin): a multicenter, placebo-controlled, double-blind study [abstract]. Neurology 1991; 41 Suppl. 1: 330–1

    Google Scholar 

  72. Leppik IE, Shellenberger MK, Anhut H. Two open-label, multicenter studies of safety and efficacy of gabapentin as add-on therapy in patients with refractory partial seizures [abstract]. Epilepsia 1992; 33 Suppl. 3: 117

    Google Scholar 

  73. Ojemann LM, Wilensky AJ, Temkin NR, et al. Long-term treatment with gabapentin for partial epilepsy. Epilepsy Res 1992; 13: 159–65

    Article  PubMed  CAS  Google Scholar 

  74. US Gabapentin Study Group No. 5. Gabapentin as add-on therapy in refractory partial epilepsy: a double-blind, placebo-controlled, parallel-group study. Neurology 1993: 43: 2292–8

    Article  Google Scholar 

  75. US Gabapentin Study Group. The long-term safety and efficacy of gabapentin (Neurontin®) as add-on therapy in drug resistent partial epilepsy. Epilepsy Res 1994; 18: 67–73

    Article  Google Scholar 

  76. Anhut H, Ashman P, Feuerstein TJ, et al. Gabapentin (Neurontin) as add-on therapy in patients with partial seizures: a double-blind, placebo-controlled study. Epilepsia 1994; 35(4): 795–801

    Article  PubMed  CAS  Google Scholar 

  77. Anhut H, Greiner M, Mockel V, et al. Gabapentin (Neurontin) as monotherapy in newly diagnosed patients with partial epilepsy [abstract]. Epilepsia 1995; 36 Suppl. 3: S119

    Google Scholar 

  78. Garofalo E, Hayes A, Greeley C, et al. Gabapentin (Neurontin) monotherapy in patients with medically refractory partial seizures: an open-label extension study [abstract]. Epilepsia 1995; 36: S119

    Google Scholar 

  79. Gram L. Tiagabine: a novel drug with a GABAergic mechanism of action. Epilepsia 1994; 35 Suppl. 5: S85–7

    Article  PubMed  Google Scholar 

  80. Braestrup C, Nielsen EB, Sonnenwald U, et al. (R)-N-[4, 4-bis(3-metyl-2-thienyl) but-3-en-1-yl]nipecotic acid binds with high affinity to the brain GABA uptake carrier. J Neurochem 1990; 54: 639–43

    Article  PubMed  CAS  Google Scholar 

  81. Nielsen EB, Suzdak PD, Andersen KE, et al. Characterization of tiagabine (NO-328), a new potent and selective GABA uptake inhibitor. Eur J Pharmacol 1991; 196: 257–66

    Article  PubMed  CAS  Google Scholar 

  82. Fink-Jensen A, Suzdak PD, Swedberg MDB, et al. The gammaaminobutyric acid (GABA) uptake inhibitor, tiagabine, increases extracellular brain levels of GABA in awake rats. Eur J Pharmacol 1992; 220: 197–201

    Article  PubMed  CAS  Google Scholar 

  83. Richens A, Chadwick DW, Duncan JS, et al. Adjunctive treatment of partial seizures with tiagabine: a placebo-controlled trial. Epilepsy Res 1995; 21: 37–42

    Article  PubMed  CAS  Google Scholar 

  84. Lassen LC, Sommerville K, Mengel HB, et al. Summary of five controlled trials with tiagabine as adjunctive treatment [abstract]. Epilepsia 1995; 36 Suppl. 3: S148

    Google Scholar 

  85. Shank RP, Gardocki JF, Vaught JL, et al. Topiramate: preclinical evaluation of a structually novel anticonvulsant. Epilepsia 1994; 35(2): 450–60

    Article  PubMed  CAS  Google Scholar 

  86. Mikkelsen M, Dam M, Ostergaard L. Topiramate as add-on therapy in refractory partial epilepsy [abstract]. Seizure 1992; 1 Suppl. A: 7–31

    Google Scholar 

  87. Engelskjon T, Johannessen SI, Kloster R, et al. Topiramate in the treatment of refractory partial epilepsy — an efficacy and tolerance study [abstract]. Seizure 1992; 1 Suppl. A: 7–16

    Google Scholar 

  88. Faught E, Kuzniecky R, Richardson D, et al. The dose-response relationship for topiramate in partial onset seizures [abstract]. Seizure 1992; 1 Suppl. A: 7–17

    Google Scholar 

  89. Sharief MK, Sander JW, Patsalos PN, et al. Adjuvant topiramate treatment in intractable partial epilepsy. Epilepsia 1993; 34 Suppl. 6: 41

    Google Scholar 

  90. Noyer M, Gillard M, Matagne A, et al. The novel antiepileptic drug levetiracetam (ubc L059) appears to act via a specific binding site in CNS membranes. Eur J Pharmacol 1995; 286: 137–46

    Article  PubMed  CAS  Google Scholar 

  91. Gower AJ, Noyer M, Verloes R, et al. Ubc L059, a novel anticonvulsant drug: pharmacological profile in animals. Eur J Pharmacol 1992; 222: 193–203

    Article  PubMed  CAS  Google Scholar 

  92. Gower AJ, Hirch E, Boehrer A, et al. Effect of levetiracetam, a novel antiepileptic drug, on convulsant activity in two genetic rat models of epilepsy. Epilepsy Res 1995; 22: 207–13

    Article  PubMed  CAS  Google Scholar 

  93. Singh P, Sharief MK, Sander JWA, et al. A pilot study of the efficacy and tolerability of L059 in patients with refractory epilepsy [abstract]. Seizure 1992; 1 Suppl. A: 7–46

    Google Scholar 

  94. Chevalier Y, Grant R, Sander WAS, et al. Twelve-week add-on, increasing dose (1,000-4,000 mg/day) multicenter pilot study of ubc L059 in epileptic patients [abstract]. Epilepsia 1995; 36 Suppl. 3: S153

    Google Scholar 

  95. De Deyn PP, Bielen E, Saxena V, et al. Assessment of the safety of orally administered UBC L059 as add-on therapy in patients treated with antiepileptic drugs [abstract]. Seizure 1992; 1 Suppl. A: 7–15

    Google Scholar 

  96. Leppik IE, Wolff DL. The place of felbamate in the treatment of epilepsy. CNS Drugs 1995; 4: 294–301

    Article  CAS  Google Scholar 

  97. Reynolds EH. Early treatment and prognosis of epilepsy. Epilepsia 1987; 28: 97–106

    Article  PubMed  CAS  Google Scholar 

  98. Elwes RDC, Chesterman P, Reynolds EH. Prognosis after a first untreated tonic-clonic seizure. Lancet 1985; II: 752–3

    Article  Google Scholar 

  99. Shorvon SD. The temporal aspects of prognosis in epilepsy. J Neurol Neurosurg Psychiatry 1984; 47: 1157–65

    Article  PubMed  CAS  Google Scholar 

  100. Feksi AT, Kaamugisha J, Sander JWA, et al. Comprehensive health care antiepileptic drug treatment programme in rural and semi-urban Kenya. Lancet 1991; 337: 406–9

    Article  PubMed  CAS  Google Scholar 

  101. Placencia M, Sander JWAS, Shorvon SD, et al. Antiepileptic drug treatment in a community health care setting in norther Ecuador: a prospective 12-month assessment. Epilepsy Res 1993; 14: 237–44

    Article  PubMed  CAS  Google Scholar 

  102. Sander JWAS. Some aspects of prognosis in the epilepsies: a review. Epilepsia 1993; 34: 1007–16

    Article  PubMed  CAS  Google Scholar 

  103. Watts AE. The natural history of untreated epilepsy in a rural community in Africa. Epilepsia 1992; 33: 464–8

    Article  PubMed  CAS  Google Scholar 

  104. Reynolds EH, Chadwick D, Galbraith AW. One drug (phenytion) in the treatment of epilepsy. Lancet 1976; I: 924–6

    Google Scholar 

  105. Schmidt D, Gram L. Monotherapy versus polytherapy in epilepsy: a reappraisal. CNS Drugs 1995; 3(3): 194–208

    Article  Google Scholar 

  106. Bourgeois BFD. Combination of valproate and ethosuximide: antiepileptic and neurotoxic interaction. J Pharmacol Exp Ther 1988; 247: 1128–32

    PubMed  CAS  Google Scholar 

  107. Rowan J, Meijer JWA, de Beer-Pawlikowski N. Valproate-ethosuximide combination therapy for refractory absence seizures. Arch Neurol 1983; 40: 797–802

    Article  PubMed  CAS  Google Scholar 

  108. Froscher W, Fiaux A, Rothmeier J, et al. Combination of lamotrigine with gamma-Vinyl GABA (vigabatrin) in the management of intractable seizures [abstract]. Epilepsia 1993; 43 Suppl. 2: 158

    Google Scholar 

  109. Robinson MK, Black AB, Schapel GS, et al. Combined gammaVinyl GABA (vigabatrin) and lamotrigine therapy in the management of refractory epilepsy [abstract]. Epilepsia 1993; 43 Suppl. 2: 109

    Google Scholar 

  110. Stolarec I, Blacklaw J, Forrest G, et al. Vigabatrin and lamotrigine in refractory epilepsy. J Neurol Neurosurg Psychiatry 1994; 57: 921–4

    Article  Google Scholar 

  111. Pisani F, Di Perri R, Perucca E, et al. Interaction of lamotrigine with sodium valproate [letter]. Lancet 1993; 341: 1224

    Article  PubMed  CAS  Google Scholar 

  112. Panayiotopoulos CP, Ferrie CD, Knott C, et al. Interaction of lamotrigine with sodium valproate [letter]. Lancet 1993; 341: 445

    Article  PubMed  CAS  Google Scholar 

  113. Besag FMC, Panayiotopoulos C, Chivers F, et al. Therapeutic interaction of lamotrigine with valproate and suximides [abstract]. Epilepsia 1995; 36 Suppl. 3: 116

    Google Scholar 

  114. Leach JP, Brodie MJ. Synergism with GABAergic drugs in refractory epilepsy [letter]. Lancet 1994; 343: 1650

    Article  PubMed  CAS  Google Scholar 

  115. Richens A. Rational polypharmacy. Seizure 1995; 4: 211–4

    Article  PubMed  CAS  Google Scholar 

  116. Rodin EA. The prognosis of patients with epilepsy. Springfield (IL): Charles Thomas Publishers, 1968

    Google Scholar 

  117. Hauser WA, Kurland LT. The epidemiology of epilepsy in Rochester, Minnesota, 1935 through 1967. Epilepsia 1975; 16: 1–66

    Article  PubMed  CAS  Google Scholar 

  118. Annegers JF, Hauser WA, Elvesback LR. Remission of seizures and relapse in patients with epilepsy. Epilepsia 1979; 20: 729–37

    Article  PubMed  CAS  Google Scholar 

  119. Goodridge DMG, Shorvon SD. Epileptic seizures in a population of 6000: II. Treatment and prognosis. BMJ 1983; 287: 645–7

    Article  PubMed  CAS  Google Scholar 

  120. MRC Antiepileptic Drug Withdrawal Study Group. Randomised study of antiepileptic drug withdrawal in patients in remission. Lancet 1991; 337: 1175–80

    Google Scholar 

  121. Liu QR, Lopez-Gorcuera B, Mandiyan S, et al. Molecular characterization of four pharmacologically distinct gammaaminobutyric acid transporters in mouse brain. J Biol Chem 1993; 268: 2106–12

    PubMed  CAS  Google Scholar 

  122. Barinaga M. Antibodies linked to rare epilepsy. Science 1995; 268: 362–3

    Article  PubMed  CAS  Google Scholar 

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  1. Hvidovre Hospital, University Clinic of Neurology, Kettegård Alle 30, DK-2650, Hvidovre, Denmark

    Anne Sabers &  Lennart Gram

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Sabers, A., Gram, L. Drug Treatment of Epilepsy in the 1990s. Drugs 52, 483–493 (1996). https://doi.org/10.2165/00003495-199652040-00002

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