Skip to main content
SpringerLink
Log in

Newer Anticonvulsants

Comparative Review of Drug Interactions and Adverse Effects

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

The tolerability and drug interaction profiles of 6 new anticonvulsants: oxcarbazepine, vigabatrin, lamotrigine, gabapentin, tiagabine and topiramate, are reviewed. In general, these new anticonvulsants are well tolerated and drug interaction problems are minor with the exception of the risk of failure of oral contraceptives during treatment with oxcarbazepine or topiramate.

In this review, the clinical implications of the tolerability of these drugs are discussed for different patient groups. The choice of which new anticonvulsant for which patient depends upon individual factors, in particular, seizure type, tolerability and practical administration factors.

Treating elderly patients may be complicated by an increased sensitivity to adverse effects as these patients very often receive polytherapy for accompanying diseases. Drugs with very simple pharmacokinetic properties may be preferred in this group. Women of childbearing age face specific problems related to the epilepsy and to treatment with anticonvulsants. These include impaired fertility, failure of oral contraceptives and the risk of birth defects. Some new anticonvulsants may be suggested in preference to classical drugs to avoid these problems, but the human experience with newer anticonvulsants is still limited and, therefore, so is knowledge of the risk of congenital malformations in the offspring of mothers taking anticonvulsants. Psychiatric and behavioural changes frequently complicate treatment of patients with mental retardation. Some of the new anticonvulsants, in particular those affecting the γ-aminobutyric acid (GAB A) system such as vigabatrin, seem to exacerbate this problem and should be used with caution in these patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Browne TR, Mattson RH, Penry JK, et al. Vigabatrin for refractory complex partial seizures: multicenter single-blind study with long-term follow up. Neurology 1987; 37: 184–9

    Article  PubMed  CAS  Google Scholar 

  2. Cohen AF, Land GS, Breimer DD, et al. Lamotrigine, a new anticonvulsant: pharmacokinetics in normal humans. Clin Pharm Ther 1987; 42: 535–41

    Article  CAS  Google Scholar 

  3. Busch JA, Radulovic LL, Bockbrader HN, et al. Effect of maalox TC® on single-dose pharmacokinetics of gabapentin capsules in healthy subjects. Pharm Res 1992; 9 Suppl. 10: S315

    Google Scholar 

  4. 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 

  5. Sonnen AEH. Oxcarbazepine and oral contraceptives. Acta Neurol Scand 1990; 82 Suppl.: 133–7

    Google Scholar 

  6. Rosenfeld WE, Doose DR, Walker SA, et al. Effect of topira-mate on the pharmacokinetics of oral contraceptive containing norethindrone and ethinyl estradiol in patients with epilepsy. Epilepsia 1997; 38(3): 317–23

    Article  PubMed  CAS  Google Scholar 

  7. Chadwick DW. An overview of the efficacy and tolerability of new antiepileptic drugs. Epilepsia 1997; 38 Suppl. 1: S59–S62

    Article  PubMed  CAS  Google Scholar 

  8. Marson AG, Kadir ZA, Hutton JL, et al. The new antiepileptic drugs: a systematic review of their efficacy and tolerability. Epilepsia 1997; 38(8): 859–80

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  10. May TW, Rambeck B, Jurgens U. Influence of oxcarbazepine and methsuximide on lamotrigine concentrations in epileptic patients with and without valproic acid comedication: results of a retrospective study. Ther Drug Monit 1999; 21(2): 175–81

    Article  PubMed  CAS  Google Scholar 

  11. Hossain M, Sallas W, Gasparini M, et al. Drug-drug interaction profile of oxcarbazepine in children and adults. Neurology 1999; 52 Suppl. 2: A525

    Google Scholar 

  12. Zaccara G, Gangemi PF, Bendoni L, et al. Influence of single and repeated doses of oxcarbazepine on the pharmacokinetic profile of felodipine. Ther Drug Monit 1993; 15: 39–42

    Article  PubMed  CAS  Google Scholar 

  13. Jensen PK, Saano V, Haring P, et al. Possible interaction between oxcarbazepine and an oral contraceptive. Epilepsia 1992; 33(6): 1149–52

    Article  CAS  Google Scholar 

  14. 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 

  15. 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 

  16. 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 

  17. Aikiä M, Kälviäinen R, Sivenius J, et al. Cognitive effects of oxcarbazepine and phenytoin monotherapy in newly diagnosed epilepsy: one year follow-up. Epilepsy Res 1992; 11: 199–203

    Article  PubMed  Google Scholar 

  18. Sabers A, Møller A, Dam M, et al. Cognitive function and anticonvulsant therapy: effect of monotherapy in epilepsy. Acta Neurol Scand 1995; 92: 19–27

    Article  PubMed  CAS  Google Scholar 

  19. Nielsen OA, Johannessen AC, Bardrum B. Oxcarbazepine-induced hyponatremia, a cross-sectional study. Epilepsy Res 1988; 2: 269–71

    Article  PubMed  CAS  Google Scholar 

  20. Pendlebury SC, Moses DK, Eadie MJ. Hyponatremia during oxcarbazepine therapy. Hum Toxicol 1989; 8: 337–44

    Article  PubMed  CAS  Google Scholar 

  21. 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 

  22. Johannessen AC, Nielsen OA. Hyponatremia induced by oxcarbazepine. Epilepsy Res 1987; 1: 155–6

    Article  PubMed  CAS  Google Scholar 

  23. Isojärvi JI, Pakarinen AJ, Myllylä VV. Basic haematological parameters, serum gamma-glutamyl-transferase activity, and erythrocyte folate and serum vitamin B12 levels during carbamazepine and oxcarbazepine therapy. Scizure 1997; 6: 207–11

    Article  Google Scholar 

  24. Rimmer EM, Richens A. Interaction between vigabatrin and phenytoin. Br J Clin Pharmacol 1989; 27: 27S–33

    Article  PubMed  Google Scholar 

  25. Pedersen SA, Klosterskov P, Gram L, et al. Long-term study of gamma-vinyl GAB A in the treatment of epilepsy. Acta Neurol Scand 1985; 72: 295–8

    Article  PubMed  CAS  Google Scholar 

  26. Rémy C, Beaumont D. Efficacy and safety of vigabatrin in the long-term treatment of refractory epilepsy. Br J Clin Pharmacol 1989; 27: S125–9

    Article  Google Scholar 

  27. Tartara A, Manni R, Galimberti CA, et al. Vigabatrin in the treatment of epilepsy: a long-term follow-up study. J Neurol Neurosurg Psychiatry 1989; 52: 467–71

    Article  PubMed  CAS  Google Scholar 

  28. Sander JW, Trevisol-Bittencourt PC, Hart YM, et al. Evaluation of vigabatrin as an add-on drug in the management of severe epilepsy. J Neurol Neurosurg Psychiatry 1990; 53: 1008–10

    Article  PubMed  CAS  Google Scholar 

  29. Aldenkamp AP, Vermeulen J, Mulder OG, et al. Gamma-vinyl GABA (vigabatrin) and mood disturbances. Epilepsia 1994; 35: 999–1004

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  32. Thomas L, Trimble M, Schmidt B, et al. Vigabatrin and behaviour disorders: a retrospective survey. Epilepsy Res 1996; 25: 21–7

    Article  PubMed  CAS  Google Scholar 

  33. Ring HA, Reynolds EH. Vigabatrin and behaviour disturbances [letter]. Lancet 1990; 335: 970

    Article  PubMed  CAS  Google Scholar 

  34. Brodie MJ, McKee PJW. Vigabatrin and psychosis [letter]. Lancet 1990; 335: 1279

    Article  PubMed  CAS  Google Scholar 

  35. Gillham RA, Blacklaw J, McKee PJW, et al. Effect of vigabatrin on sedation and cognitive function in patients with refractory epilepsy. J Neurol Neurosurg Psychiatry 1993; 56: 1271–5

    Article  PubMed  CAS  Google Scholar 

  36. Dodrill CB, Arnett JL, Sommerville KW, et al. Effects of differing dosages of vigabatrin (Sabril) on cognitive abilities and quality of life in epilepsy. Epilepsia 1995; 36(2): 164–73

    Article  PubMed  CAS  Google Scholar 

  37. Provinciali L, Bartolini M, Mari F, et al. Influence of vigabatrin on cognitive performances and behaviour in patients with drug-resistant epilepsy. Acta Neurol Scand 1996; 94: 12–8

    Article  PubMed  CAS  Google Scholar 

  38. Marciani MG, Maschio M, Spanedda F, et al. Development of myoclonus in patients with partial epilepsy during treatment with vigabatrin: an electroencephalographic study. Acta Neurol Scand 1995; 91: 1–5

    PubMed  CAS  Google Scholar 

  39. Jongsma MJ, Laan LA, van Emde Boas W, et al. Reversible motor disturbances induced by vigabatrin [letter]. Lancet 1991; 338: 893

    Article  PubMed  CAS  Google Scholar 

  40. Eke T, Talbot JE, Lawden MC. Severe persistent visual field constrictions associated with vigabatrin. BMJ 1997; 314: 180–1

    Article  PubMed  CAS  Google Scholar 

  41. Kälviäinen R, Nousiainen I, Mantyjarvi M, et al. Vigabatrin, a gabaergic antiepileptic drug causes concentric visual fields defects. Neurology 1999; 53(5): 922–6

    Article  PubMed  Google Scholar 

  42. Wild JM, Martinez C, Reinshagen G, et al. Characteristics of unique visual field defect attributed to vigabatrin. Epilepsia 1999; 40(12): 1784–94

    Article  PubMed  CAS  Google Scholar 

  43. Hardus P, Verduin WM, Postma G, et al. Concentric contraction of the visual field in patients with temporal lobe epilepsy and its association with the use of vigabatrin medication. Epilepsia 2000; 41(5): 581–7

    Article  PubMed  CAS  Google Scholar 

  44. Arndt CF, Derambure P, Defoort-Dhellemmes S, et al. Outer retinal dysfunction in patients treated with vigabatrin. Neurology 1999; 52: 1201–5

    Article  PubMed  CAS  Google Scholar 

  45. Manuchehri K, Goodman S, Siviter L, et al. Acontrolled study of vigabatrin and visual abnormalities. Br J Ophthalmol 2000; 84(5): 499–505

    Article  PubMed  CAS  Google Scholar 

  46. Wong IC, Mawer GE, Sander JW. Severe persistent visual field constriction associated with vigabatrin: reaction might be dose dependent. BMJ 1997; 314: 1693–4

    PubMed  CAS  Google Scholar 

  47. Versino M, Veggiotti P. Reversibility of vigabatrin-induced visual field defects [letter]. Lancet 1999; 354(9177): 486

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  49. 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 

  50. Yuen AWC, Land G, Weatherley BC, et al. Sodium valproate acutely inhibits lamotrigine metabolism. Br J Clin Pharmacol 1992; 33: 511–3

    Article  PubMed  CAS  Google Scholar 

  51. Gidal BE, Kanner A, Maly M, et al. Lamotrigine pharmacokinetics in patients receiving felbamate. Epilepsy Res 1997; 27: 1–5

    Article  PubMed  CAS  Google Scholar 

  52. Peck AW. Clinical pharmacology of lamotrigine. Epilepsia 1991;32 Suppl. 2: S9–12

    Article  PubMed  Google Scholar 

  53. Holdich T, Whiteman P, Orme M, et al. Effect of lamotrigine on the pharmacology of the combined oral contraceptive pill. Epilepsia 1991; 32 Suppl. 1: 96

    Article  Google Scholar 

  54. Warner T, Patsalos PN, Prevett M, et al. Lamotrigine induced carbamazepine toxicity: an interaction with carbamazepine-10,11-epoxide. Epilepsy Res 1992; 11(2): 147–50

    Article  PubMed  CAS  Google Scholar 

  55. Schapel GT, Dollman W, Beran RG, et al. No effect of LTG on CBZ and CBZ-E concentrations. Epilepsia 1991; 32 Suppl. 1: S58

    Google Scholar 

  56. Gidal BE, Rutecki P, Shaw R, et al. Effect of lamotrigine on carbamazepine epoxide/carbamazepine serum concentration ratios in adult patients with epilepsy. Epilepsy Res 1997; 28: 207–11

    Article  PubMed  CAS  Google Scholar 

  57. Besag FM, Berry DJ, Pool F, et al. Carbamazepine toxicity with lamotrigine: pharmacokinetic or pharmacodynamic interaction. Epilepsia 1998; 39(2): 183–7

    Article  PubMed  CAS  Google Scholar 

  58. Kaufman KR, Gerner R. Lamotrigine toxicity secondary to sertraline. Scizure 1998; 7: 163–5

    CAS  Google Scholar 

  59. Messenheimer J, Mullens EL, Giorgi L, et al. Safety review of adult clinical trial experience with lamotrigine. Drug Saf 1998; 18(4): 281–96

    Article  PubMed  CAS  Google Scholar 

  60. Sadler M. Lamortigine associated with insomnia. Epilepsia 1999; 40(3): 322–5

    Article  PubMed  CAS  Google Scholar 

  61. Schlienger RG, Shapiro LE, Shear NH. Lamotrigine-induced severe cutaneous adverse reactions. Epilepsia 1998; 39 Suppl. 7: S22–6

    Article  PubMed  CAS  Google Scholar 

  62. Guberman AH, Besag FMC, Brodie MJ, et al. Lamotrigine-associated rash: risk/benefit considerations in adults and children. Epilepsia 1999; 49(7): 985–91

    Article  Google Scholar 

  63. Nicholson RJ, Kelly KP, Grant IS. Leucopenia associated with lamotrigine. BMJ 1995; 310: 504

    Article  PubMed  CAS  Google Scholar 

  64. De Camargo OA, Bode H. Agranulocytosis associated with lamotrigine. BMJ 1999; 318(7192): 1179

    Article  PubMed  Google Scholar 

  65. Makin AT, Fitt S, Williams R. Fulminant hepatic failure induced by lamotrigine. BMJ 1995; 311: 292

    Article  PubMed  CAS  Google Scholar 

  66. Schaub JE, Williamson PJ, Barnes EW, et al. Multisystem adverse reaction to lamotrigine [letter]. Lancet 1994; 344: 481

    Article  PubMed  CAS  Google Scholar 

  67. Smith D, Baker G, Davis G, et al. Outcomes of add-on treatment with lamotrigine in partial epilepsy. Epilepsia 1993; 34: 312–22

    Article  PubMed  CAS  Google Scholar 

  68. Betts T, Goodwin G, Winthers RM, et al. Human safety of lamotrigine. Epilepsia 1991; 32 Suppl. 2: S17–21

    Article  PubMed  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

  71. 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: 795–801

    Article  PubMed  CAS  Google Scholar 

  72. Ramsay RE. Clinical efficacy and safety of gabapentin. Neurology 1994; 44 Suppl. 5: S23–30

    PubMed  CAS  Google Scholar 

  73. Beydoun A, Fischer J, Labar DR, et al. Gabapentin monotherapy: II. A 26-week, double-blind, dose-controlled, multicenter study of conversion from polytherapy in outpatients with refractory complex partial or secondarily generalized seizures. Neurology 1997; 49: 746–52

    PubMed  CAS  Google Scholar 

  74. Chadwick DW, Anhut H, Greiner MJ, et al. A double-blind trial of gabapentin monotherapy for newly diagnosed partial epilepsy. Neurology 1998; 51: 1282–8

    Article  PubMed  CAS  Google Scholar 

  75. Asconapé J, Collins T. Weight gain associated with the use of gabapentin. Epilepsia 1995; 36 Suppl. 4: S72

    Google Scholar 

  76. Beydoun A, Fakhoury T, Nasreddine W, et al. Conversion to high dose gabapentin monotherapy in patients with medically refractory partial epilepsy. Epilepsia 1998; 39(2): 188–93

    Article  PubMed  CAS  Google Scholar 

  77. Vossler DG. Exacerbation of seizures in Lennox-Gastaut syndrome by gabapentin. Neurology 1996; 46: 852–3

    Article  PubMed  CAS  Google Scholar 

  78. Asconapé J, Diedrich A, DellaBadia J. Gabapentin-associated myoclonus. Neurology 1995; 45 Suppl. 4: A249–50

    Google Scholar 

  79. Scheyer RD, Assaf AA, Spencer SS, et al. Gabapentin-related myoclonus. Epilepsia 1996; 37 Suppl. 5: 203

    Google Scholar 

  80. Chudnow RS, Dewey RB, Lawson CR. Choreoathetosis as a side effect of gabapentin therapy in severely neurologically impaired patients. Arch Neurol 1997; 54: 910–2

    PubMed  CAS  Google Scholar 

  81. Leach JP, Girvan J, Paul A, et al. Gabapentin and cognition: a double blind, dose ranging, placebo controlled study in refractory epilepsy. J Neurol Neuropsych Psychiatry 1997; 62: 372–6

    Article  CAS  Google Scholar 

  82. Dodrill CB, Arnett JL, Hayes AG, et al. Cognitive abilities and adjustment with gabapentin: results of a multisite study. Epilepsy Res 1999; 35: 109–21

    Article  PubMed  CAS  Google Scholar 

  83. So EL, Wolff D, Graves NM, et al. Pharmacokinetics of tiagabine as add-on therapy in patients taking enzyme-inducing anti-epileptic drugs. Epilepsy Res 1995; 22: 221–6

    Article  PubMed  CAS  Google Scholar 

  84. Samara EE, Gustavson LE, El-Shourbagy T, et al. Population analysis of the pharmacokinetics of tiagabine in patients with epilepsy. Epilepsia 1998; 39(8): 868–73

    Article  PubMed  CAS  Google Scholar 

  85. Schachter SC, Cahill WT, Wannamaker BB, et al. Open label dosage and tolerability study of tiagabine monotherapy in patients with refractory complex partial seizures. J Epilepsy 1998; 11: 248–55

    Article  Google Scholar 

  86. Kälviäinen R, Brodie MJ, Duncan J, et al. A double-blind, placebo-controlled trial of tiagabine given three-times daily as add-on therapy for refractory partial seizures. Epilepsy Res 1998; 30: 31–40

    Article  PubMed  Google Scholar 

  87. Sachdeo RC, Leroy RF, Krauss GL, et al. Tiagabine therapy for complex partial seizures. Arch Neurol 1997; 54: 595–601

    Article  PubMed  CAS  Google Scholar 

  88. Eckardt KM, Steinhoff BJ. Nonconvulsive status epilepticus in two patients receiving tiagabine treatment. Epilepsia 1998; 6: 671–4

    Article  Google Scholar 

  89. Sveinbjornsdottir S, Sander JW, Patsalos PN, et al. Neuropsychological effects of tiagabine, a potential new antiepi-leptic drug. Scizure 1994; 3: 29–35

    Article  CAS  Google Scholar 

  90. Dodrill CB, Arnett JL, Sommerville KW, et al. Cognitive and quality of life effects of differing dosages of tiagabine in epilepsy. Neurology 1997; 48: 1025–31

    Article  PubMed  CAS  Google Scholar 

  91. Dodrill CB, Arnett JL, Shu V, et al. Effects of tiagabine monotherapy on abilities, adjustment, and mood. Epilepsia 1998; 39(1): 33–42

    Article  PubMed  CAS  Google Scholar 

  92. Kälviäinen R, Nousiainen I, Mäntyjärvi M, et al. Absence of concentric visual field defects in patients with initial tiagabine monotherapy [abstract]. Epilepsia 1999; 40 Suppl. 2: 259

    Google Scholar 

  93. Sachdeo RC, Sachdeo SK, Walker SA, et al. Steady-state pharmacokinetics of topiramate and carbamazepine in patients with epilepsy during and concomitant therapy. Epilepsia 1996; 37: 774–80

    Article  PubMed  CAS  Google Scholar 

  94. Gisclon LG, Curtin CR, Kramer LD. The steady-state (SS) pharmacokinetics (PK) of phenytoin (Dilantin) and topiramate (Topamax®) in epileptic patients on monotherapy and during combination therapy [abstract]. Epilepsia 1994; 35 Suppl. 8: 54

    Google Scholar 

  95. Privitera M, Fincham R, Penry J, et al. Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 600-, 800-, and 1,000-mg daily dosages. Neurology 1996; 46: 1678–83

    Article  PubMed  CAS  Google Scholar 

  96. Shorvon SD. Safety of topiramate: adverse events and relationships to dosing. Epilepsia 1996; 37 Suppl. 2: S18–22

    Article  PubMed  CAS  Google Scholar 

  97. Crawford P. An audit of topiramate use in a general neurology clinic. Scizure 1998; 7: 207–11

    Article  CAS  Google Scholar 

  98. Wasserstein AG, Rak I, Reife RA. Nephrolithiasis during treatment with topiramate. Epilepsia 1995; 36 Suppl. 3: S153

    Google Scholar 

  99. Ben-Menachem E, Henriksen O, Dam M, et al. Double-blind, placebo-controlled trial of topiramate as add-on therapy in patients with refractory partial seizures. Epilepsia 1996; 37(6): 539–43

    Article  PubMed  CAS  Google Scholar 

  100. Burton LA, Harden C. Effect of topiramate on attention. Epilepsy Res 1997; 27: 29–32

    Article  PubMed  CAS  Google Scholar 

  101. Marson AG, Kadir AZ, Charwick DW. New antiepileptic drugs: a systematic review of their efficacy and tolerability. BMJ 1996; 313: 1169–74

    Article  PubMed  CAS  Google Scholar 

  102. LeLorier J, Gregoire G, Benhaddad A, et al. Discrepancies between meta-analyses and subsequent large randomized, controlled trials. N Engl J Med 1997; 337: 536–42

    Article  PubMed  CAS  Google Scholar 

  103. Bailar JC. The promise and problems of meta-analyses. N Engl J Med 1997; 337: 559–60

    Article  PubMed  Google Scholar 

  104. Brodie MJ. New antiepileptic drugs: the drugs are not all the same. BMJ 1997; 314: 602–3

    Article  PubMed  CAS  Google Scholar 

  105. Elferink JA, Van Zwieten-Boot BJ. New anti-epiletic drugs: analysis based on number needed to treat shows differences between drugs studied [letter]. BMJ 1997; 314: 603

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  107. Tanganelli P, Regesta G. Vigabatrin vs carbamazepine monotherapy in newly diagnosed focal epilepsy: a randomized response conditional cross-over study. Epilepsy Res 1996; 25(3): 257–62

    Article  PubMed  CAS  Google Scholar 

  108. Sachdeo RC, Reife RA, Lim P, et al. Topiramate monotherapy for partial onset seizures. Epilepsia 1997; 38(3): 294–300

    Article  PubMed  CAS  Google Scholar 

  109. Buchanan N. The use of lamotrigine in juvenile myoclonic epilepsy. Scizure 1996; 5: 149–51

    CAS  Google Scholar 

  110. Buchanan N. Lamotrigine use in twelve patients with the Lennox-Gastaut syndrome. Eur J Neurol 1995; 2: 501–3

    Article  Google Scholar 

  111. Motte J, Trevathan E, Arvidsson JFV, et al. Lamotrigine for generalized seizures associated with the Lennox-Gastaut syndrome. N Engl J Med 1997; 337: 1807–12

    Article  PubMed  CAS  Google Scholar 

  112. Ferrie CD, Robinson RO, Knott C, et al. Lamotrigine as add-on drug in typical absences. Acta Neurol Scand 1995; 91: 200–2

    Article  PubMed  CAS  Google Scholar 

  113. Frank LM, Enlow T, Holmes GL, et al. Lamictal (lamotrigine) monotherapy for typical absence seizures in children. Epilepsia 1999; 40(7): 973–9

    Article  PubMed  CAS  Google Scholar 

  114. Sander JW, Patsalos PN, Oxley JR, et al. A randomized double-blind placebo-controlled add-on trial of lamotrigine in patients with severe epilepsy. Epilepsy Res 1990; 6: 221–6

    Article  PubMed  CAS  Google Scholar 

  115. Genton P, Dravet C, Bureau M, et al. Aggravation of severe myoclonic epilepsy of infancy by lamotrigine. Epilepsia 1997; 38 Suppl. 3: 32

    Google Scholar 

  116. Biton V, Montouris GD, Ritter F, et al. A randomized, placebo-controlled study of topiramate in primary generalized tonic clonic seizures. Neurology 1999; 52: 1330–7

    Article  PubMed  CAS  Google Scholar 

  117. Sachdeo RC, Glauser TA, Ritter F, et al. A double blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Neurology 1999; 52: 1882–7

    Article  PubMed  CAS  Google Scholar 

  118. Brodie MJ, Overstall PW, Giorgi L. Multicenter, double-blind, randomised comparison between lamotrigine and carbamazepine in elderly patients with newly diagnosed epilepsy. Epilepsy Res 1999; 37: 81–7

    Article  PubMed  CAS  Google Scholar 

  119. Eldon MA, Underwood B A, Randinitis EJ, et al. Lack of effect of gabapentin on the pharmacokinetics of a norethindrone acetat/ethinyl estradiol-containing oral contraceptive [abstract]. Neurology 1993; 43: A307

    Google Scholar 

  120. Webber MP, Hauser WA, Ottman R, et al. Fertility in persons with epilepsy: 1935–1974. Epilepsia 1986; 27(6): 746–52

    Article  PubMed  CAS  Google Scholar 

  121. Isojärvi JIT, Laatikainen TJ, Pakarinen AJ, et al. Polycystic ovaries and hyperandrogeism in women taking valproate for epilepsy. N Engl J Med 1993; 329: 1383–8

    Article  PubMed  Google Scholar 

  122. Isojärvi J, Rättyä J, Knip M, et al. Replacing valproate with lamotrigine reduces cardiovascular risks and insulin mediated hyperandrogenism in women with epilepsy [abstract]. Epilepsia 1997; 38 Suppl. 3: 279

    Article  Google Scholar 

  123. Ogawa Y, Kaneko S, Otani K, et al. Serum folic acid levels in epileptic mothers and their relationship to congenital malformations. Epilepsy Res 1991; 8: 75–8

    Article  PubMed  CAS  Google Scholar 

  124. Wegner C, Nau H. Alteration of embryonic folate metabolism by valproic acid during organogenesis: implications for mechanism of teratogenesis. Neurology 1992; 42 Suppl. 5: 17–24

    PubMed  CAS  Google Scholar 

  125. Sander JW, Patsalos PN. An assessment of serum and red blood cell folate concentrations in patients with epilepsy on lamotrigine therapy. Epilepsy Res 1992; 13: 89–92

    Article  PubMed  CAS  Google Scholar 

  126. Ettinger AB, Weisbrot DM, Saracco J, et al. Positive and negative psychotropic effects of lamotrigine in patients with epilepsy and mental retardation. Epilepsia 1998; 39(8): 874–7

    Article  PubMed  CAS  Google Scholar 

  127. Beran RG, Gibson RJ. Aggressive behaviour in intellectually challenged patients with epilepsy treated with lamotrigine. Epilepsia 1998; 39(3): 280–2

    Article  PubMed  CAS  Google Scholar 

  128. Mullens L, Gallagher J, Manasco P. Improved neurological function accompanies effective control of the Lennox-Gastaut syndrome with Lamictal: results of a multinational, placebo-controlled trial. Epilepsia 1996; 37 Suppl. 5: S163

    Google Scholar 

  129. Jacoby A, Baker G, Bryant-Comstock L, et al. Lamotrigine add-on therapy is associated with improvement in mood in patients with severe epilepsy. Epilepsia 1996; 37 Suppl. 5: S202

    Google Scholar 

  130. Uldall P, Hansen FJ, Tonnby B. Lamotrigine in Rett syndrome. Neuropediatrics 1993; 24: 339–40

    Article  PubMed  CAS  Google Scholar 

  131. Lee DO, Steingard RJ, Cesena M, et al. Behavioral side effects of gabapentin in children. Epilepsia 1996; 37(1): 87–90

    Article  PubMed  CAS  Google Scholar 

  132. Tallian KB, Nahata MC, Lo W, et al. Gabapentin associated with aggressive behaviour in pediatric patients with seizures. Epilepsia 1996; 37(5): 501–2

    Article  PubMed  CAS  Google Scholar 

  133. Bhaumik S, Branford D, Duggirala C, et al. A naturalistic study of the use of vigabatrin, lamotrigine and gabapentin in adults with learning disabilities. Scizure 1997; 6(2): 127–33

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dianalund Epilepsy Hospital, DK-4293, Dianalund, Denmark

    Anne Sabers & Lennart Gram

Authors
  1. Anne Sabers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lennart Gram
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne Sabers.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sabers, A., Gram, L. Newer Anticonvulsants. Drugs 60, 23–33 (2000). https://doi.org/10.2165/00003495-200060010-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200060010-00003

Keywords

Search

Navigation