Opinion statement
-
•For pure childhood absence epilepsy (CAE), ethosuximide (ESM) remains the drug of first choice. Although valproic acid (VPA) is of equal efficacy, it is more toxic, and is reserved for those patients with accompanying convulsions. Lamotrigine (LTG) is effective as both add-on and monotherapy for CAE. If any of these three drugs fails, one of the other two can be used as monotherapy. Rarely, when ESM, VPA, or LTG does not effectively control CAE, phenytoin (PHT), primidone (PRM), and phenobarbital (PB) may be partially effective, although carbamazepine (CBZ) may worsen absence seizures. Experience is limited with the newer AEDs. Tiagabine (TGB) may induce absence status epilepticus in PGE. Oxcarbazepine (OXC) and vigabatrin (VGB) may worsen absence seizures. Felbamate (FBM) is probably effective, but is potentially fatal. Lifelong therapy is not anticipated.
-
•For juvenile absence epilepsy (JAE), VPA is the drug of first choice. LTG is also of proven efficacy. The risks of VPA-induced teratogenicity (possibly lessened by the concurrent use of folic acid) and weight gain are potentially unacceptable in young women of childbearing age. Not enough data exists on the safety of LTG in pregnancy. A combination of VPA and LTG can be used if either drug alone is unsuccessful.
-
•For juvenile myoclonic epilepsy (JME), VPA is the traditional drug of first choice in most patients. As in JAE, side effects may make VPA an unacceptable choice in many patients, especially young women. In clinical practice, TPM is being increasingly used as monotherapy for JME. Many patients appreciate the accompanying weight loss seen with TPM, but it has potentially troubling side effects, has not been well studied as monotherapy for JME, and its safety in pregnancy has yet to be confirmed. PHT and CBZ may worsen myoclonus when used alone, but they may have a role as add-on treatment to VPA, LTG, or TPM, especially when generalized tonicclonic seizures (GTCSs) are not controlled. PB and PRM may also be useful as add-on treatment, but often have unacceptable side effects. Clonazepam may be useful as adjunctive treatment for resistant myoclonic jerks. OXC and VGB both worsen myoclonic seizures. GBP is not useful in JME and can make seizures worse. The efficacy of FBM and TGB in JME is largely unknown. Lifelong AED therapy is necessary.
-
•In epilepsy with generalized tonic-clonic seizure (GTCS) on awakening (EGA), VPA is the drug of choice, especially if other seizure types (absence and myoclonic) are present. If only GTCSs are present, then PB, PHT, and CBZ may be as effective as VPA; however, the use of PHT and CBZ may ‘unearth’ other seizure types (absence and myoclonic) in those patients with EGA, although PB is poorly tolerated. As for JME, LTG, and TPM may both be effective monotherapy for EGA, although the use of other AEDs in EGA has not been well studied. Lifelong AED treatment is necessary.
Similar content being viewed by others
References
Commission on Classification and Terminology of the International League Against Epilepsy: Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989, 30:389–399.
Delgado-Escueta AV, Medina MT, Serratosa JM, et al.: Mapping and positional cloning of common idiopathic generalized epilepsies: juvenile myoclonus epilepsy and childhood absence epilepsy. Adv Neurol 1999, 79:351–374.
Reutens DC, Berkovic SF: Idiopathic generalized epilepsy of adolescence: are the syndromes clinically distinct? Neurology 1995, 45:1469–1476.
Leppik IE: Role of new and established antiepileptic drugs. Epilepsia 1998, 39(suppl 5):2–6. Good summary of the mode of action, pharmacokinetics and clinical usefulness of some of the newer AEDs (GBP, TGB, VGB, FBM, LTG, TPM), as well as a useful cryptic summary of the role of the established AEDs.
Snead OC, Hosey LC: Exacerbation of seizures by carbamazepine. N Engl J Med 1985, 313:916–921.
Ramsey RE, Wilder BJ, Berger JR, et al.: A double blind study comparing carbamazepine with phenytoin as initial seizure therapy in adults. Neurology 1975, 33:904–910.
Treiman DM: Efficacy and safety of antiepileptic drugs: a review of controlled trials. Epilepsia 1987, 28(suppl 3):S1-S8.
Mattson FH: General principles. Selection of antiepileptic drug therapy. In Antiepileptic Drugs, edn 4. Edited by Levy RH, Mattson RH, Meldrum BS. New York: Raven Press; 1995:123–135.
Brodie MJ, French JA: Management of epilepsy in adolescents and adults. Lancet 2000, 356:323–329. This summarizes the optimal clinical approach to epilepsy management in adolescents and adults, with equal emphasis on correct diagnosis, rational pharmacotherapy, and nonpharmacologic treatments. While addressing both localization-related epilepsy and PGE, the section on special populations (especially teenagers and women) is particularly relevant to PGE.
Brodie MJ: Monostars: an aid to choosing an antiepileptic drug as monotherapy. Epilepsia 1999, 40(suppl 6):17–22. This is a helpful review, which offers good guidance to rational AED monotherapy.
Bourgeois B, Beaumanoir A, Blajev B, et al.: Monotherapy with valproate in primary generalized epilepsies. Epilepsia 1987, 28(suppl):S8-S11.
Wallace SJ: Myoclonus and epilepsy in childhood: a review of treatment with valproate, ethosuximide, lamotrigine and zonisamide. Epilepsy Res 1998, 29(2):147–154.
Chadwick DW: Valproate monotherapy in the management of generalized and partial seizures. Neurology 1987, 28(suppl 2):S12-S17.
Delgado-Escueta AV, Serratosa JM, Medina MT: Juvenile myoclonic epilepsy. In The Treatment of Epilepsy: Principles and Practice, edn 2. Edited by Wyllie E. Baltimore: Williams and Wilkins; 1996:484–501.
Berkovic SF, Andermann F, Guberman A, et al.: Valproate prevents the recurrence of absence status. Neurology 1989, 39:1294–1297.
Andermann F, Robb P: Absence status: a reappraisal following review of thirty eight patients. Epilepsia 1972, 13:177–187.
Porter RJ, Penry JK: Petit mal status. In Advances in Neurology, vol 34: Status Epilepticus. Edited by Delgado-Escueta AV, Wasterlain CG, Treiman DM, Porter RJ. New York: Raven Press; 1983:61–67.
Rowan AJ, Meijer JW, de Beer-Pawlikowski N, et al.: Valproate-ethosuximide combination therapy for refractory absence seizures. Arch Neurol 1983, 40:797–802.
Zahn CA, Morrell MJ, Collins SD, et al.: Management issues for women with epilepsy: a review of the literature. Neurology 1998, 51(4):949–956. This is a good review of the literature on this potentially difficult area.
Brodie MJ, Richens A, Yuen AW: Double blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. Lancet 1995, 345:476–479.
Pellock JM: The clinical efficacy of lamotrigine as an antiepileptic drug. Neurology 1994, 44(suppl 8):29–35.
Buchanan N: Lamotrigine: clinical experience in 200 patients with epilepsy with follow up to four years. Seizure 1996, 5(3):209–214.
Buchanan N: The use of lamotrigine in juvenile myoclonic epilepsy. Seizure 1996, 5(2):149–151.
Frank LM, Enlow T, Holmes GL, et al.: Lamictal (lamotrigine) monotherapy for typical absence seizures in children. Epilepsia 1999, 40(7):973–979.
Munn R, Farrell K: Open study of clobazam in refractory epilepsy. Pediatr Neurol 1993, 9(6):465–469.
Buchanan N: Clobazam in the treatment of epilepsy: prospective follow up to 8 years. J R Soc Med 1993, 86:378–380.
Canadian Clobazam Cooperative Group: Clobazam in treatment of refractory epilepsy. Epilepsia 1991, 32:407–416.
Naito H, Wachi M, Nishida M: Clinical effects and plasma concentrations of long term clonazepam monotherapy in previously untreated epileptics. Acta Neurol Scand 1987, 76:58–63.
Obeid T, Panayiotopoulos CP: Juvenile myoclonic epilepsy: a study in Saudi Arabia. Epilepsia 1988, 29:280–282.
Brodie MJ, Dichter MA: Antiepileptic drugs. N Engl J Med 1996, 334(3):168–175. This is an excellent summary of the indications for, pharmacokinetics, interactions, and side effects of, the established AEDs. It also addresses the issues of refractory epilepsy, AED treatment during pregnancy, drug monitoring, discontinuing AEDs, and when to refer patients to an epilepsy center.
Bourgeois BFD: Phenobarbital and primidone. In The Treatment of Epilepsy: Principles and Practice, edn 2. Edited by Wyllie E. Baltimore: Williams and Wilkins; 1996:845–855.
Leroy RF, Castian T: Pilot study of felbamate in adult medically refractory primary generalized seizure patients. Epilepsia 1991, 32(suppl 3):13.
Sachdeo RC, Wagner ML: Felbamate in generalized tonic-clonic seizures. Epilepsia 1991, 32(suppl 3):54.
Sachdeo RC, Murphy JV, Kamin M: Felbamate in juvenile myoclonic epilepsy. Epilepsia 1992, 33 (suppl 3):118.
Biton V: Preliminary open-label experience with topiramate in primary generalized seizures. Epilepsia 1997, 38 (suppl 1):42–44.
Biton V, Montouris GD, Ritter F, et al.: A randomized, placebo controlled study of topiramate in primary generalized tonic-clonic seizures. Neurology 1999, 52:1330–1337.
Crawford P: An audit of topiramate use in a general neurology clinic. Seizure 1998, 7(3):207–211.
Trenite DGAKN, Marescaux C, Stodieck S, et al.: Photosensitive epilepsy: a model to study the effects of antieplieptic drugs. Evaluation of the piracetam analogue, levetiracetam. Epilepsy Res 1996, 25(3):225–230.
Smith K, Betts T: The effect of add-on therapy with levetircetam (UCBL059) on patients with resistant juvenile myoclonic epilepsy. Abstract presented at: Fourth Eilat Conference on New Antiepileptic Drugs; September 6–10, 1998; Eilat, Israel.
Peters DH, Sorkin EM: Zonisamide: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy. Drugs 1993, 45:760–787.
Dichter MD, Brodie MJ: New antiepileptic drugs. N Engl J Med 1996, 334(24):1583–1590. This is an excellent review of the evidence of efficacy in some of the most recently available AEDs. It also summarizes the pharmacokinetics, drug-drug interactions and side effects of these newer AEDs.
Shimizu M, Uno H, Ito T, et al.: Research and development of zonisamide, a new type of antiepileptic drug. Yakugaku Zasshi 1996, 116(7):533–547.
Kotani H, Hirai K, Nishiki T, et al.: Zonisamide monotherapy against absence attacks: report of two cases. No To Hattatsu 1994, 26(4):349–354.
Brodie MJ: Established anticonvulsants and treatment of refractory epilepsy. Lancet 1990, 336:350–354.
Graves NM, Ramsey RE: Phenytoin and fosphenytoin. In The Treatment of Epilepsy: Principles and Practice, edn 2. Edited by Wyllie E. Baltimore: Williams and Wilkins; 1996:833–844.
Perucca E, Gram L, Avenzini G, et al.: Antiepileptic drugs as a cause of worsening seizures. Epilepsia 1998, 39:5–17.
Carbamazepine update. Lancet 1989, 2:595–597.
Liporace JD, Sperling MR, Dichter MA: Absence seizures and carbamazepine in adults. Epilepsia 1994, 35:1026–1028.
Hosford DA, Wang Y: Utility of the lethargic (1h/1h) mouse model of absence seizures in predicting the effects of lamotrigine, vibabatrin, tiagabine, gabapentin and topiramate against human absence seizures. Epilepsia 1997, 38:408–414.
Eckardt KM, Steinhoff BJ: Nonconvulsive status epilepsy in two patients receiving tiagabine treatment. Epilepsia 1998, 39:671–674.
Knake S, Hamer HM, Schomburg U, et al.: Tiagabineinduced absence status in idiopathic epilepsy. Seizure 1999, 8(5):314–317.
Chadwick D, Leiderman DB, Sauermann W, et al.: Gabapentin in generalized seizures. Epilepsy Res 1996, 25:191–197.
Schacter SC, Saper CB: Vagus nerve stimulation. Epilepsia 1998, 39:677–686.
Tecoma E, Iraqui V, Wetzel K, et al.: Vagus nerve stimulation in refractory primary generalized epilepsy: clinical and electrographic findings [abstract]. Epilepsia 1996, 37(suppl 5):83.
Labar D, Murphy J, Tecoma E: Vagus nerve stimulation for medication resistant generalized epilepsy. Neurology 1999, 52(7):1510–1512.
Stephen LJ, McLellan AR, Harrison JH, et al.: Bone density and antiepileptic drugs: a case controlled study. Seizure 1999, 8:339–342.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Murphy, K., Delanty, N. Primary generalized epilepsies. Curr Treat Options Neurol 2, 527–541 (2000). https://doi.org/10.1007/s11940-000-0031-0
Issue Date:
DOI: https://doi.org/10.1007/s11940-000-0031-0