Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Pharmacological Management of the Genetic Generalised Epilepsies in Adolescents and Adults


Common genetic generalised epilepsy syndromes encountered by clinicians include childhood and juvenile absence epilepsies, juvenile myoclonic epilepsy and generalised tonic–clonic seizures on awakening. Treatment of these syndromes involves largely the use of broad-spectrum antiseizure drugs. Those effective for the generalised epilepsies include sodium valproate, phenobarbital, ethosuximide, clobazam, clonazepam, lamotrigine, levetiracetam, topiramate, zonisamide and, more recently, perampanel and brivaracetam. Results from the few rigorous studies comparing outcomes with drugs for genetic generalised epilepsies show valproate to be the most effective. The majority of patients with genetic generalised epilepsy syndromes will become seizure free on antiseizure monotherapy; those for whom control proves elusive may benefit from combination regimens. Early counselling regarding management may assist the patient to come to terms with their diagnosis and improve long-term outcomes. Treatment can be lifelong in some individuals, although others may remain seizure free without medication. Choice of antiseizure medication depends on the efficacy for specific seizure types, as well as tolerability. For patients prescribed comedication, drug interactions should be considered. In particular, for young women taking oral hormonal contraceptives, ≥ 200 mg/day of topiramate can decrease the circulating concentration of ethinylestradiol and ≥ 12 mg/day of perampanel can induce levonorgestrel metabolism. The use of valproate in women of childbearing potential is limited by associated teratogenic and neurodevelopmental effects in offspring. Given that valproate is often the antiseizure drug of choice for genetic generalised epilepsies, this creates a dilemma for patients and clinicians. Decision making can be aided by comprehensive assessment and discussion of treatment options. Psychiatric comorbidities are common in adolescents and adults with genetic generalised epilepsies. These worsen the prognosis, both in terms of seizure control and quality of life. Attendant lifestyle issues can impact significantly on the individual and society. Frontal lobe dysfunction, which can present in patients with juvenile myoclonic epilepsy, can adversely affect the long-term outlook, regardless of the nature of seizure control. Ongoing management requires consideration of psychosocial and behavioural factors that can complicate diagnosis and treatment. An assured supportive attitude by the neurologist can be an important contributor to a positive outcome. The mechanisms underlying genetic generalised epilepsies, including genetic abnormalities, are unclear at present. As the pathophysiology is unravelled, this may lead to the development of novel therapies and improved outcomes for patients with these syndromes.

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

Fig. 1


  1. 1.

    Brodie MJ. Tolerability and safety of commonly used antiepileptic drugs in adolescents and adults: a clinician’s overview. CNS Drugs. 2017;31:135–47.

  2. 2.

    Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58:512–21.

  3. 3.

    Striano P, Nobile C. The genetic basis of juvenile myoclonic epilepsy. Lancet Neurol. 2018;17:493–5.

  4. 4.

    Glauser TA, Cnaan A, Shinnar S, et al. Ethosuximide, valproic acid and lamotrigine in childhood absence epilepsy. New Engl J Med. 2010;362:790–9.

  5. 5.

    Wallace SI. Myoclonus and epilepsy in childhood: a review of treatment with valproate, ethosuximide, lamotrigine and zonisamide. Epilepsy Res. 1998;29:147–54.

  6. 6.

    Ethosuximide; indications and dose. In: National Institute for Health and Care Excellence. British National Formulary. https://bnf.nice.org.uk/drug/ethosuximide.html#indicationsAndDoses. Accessed 15 Dec 2019.

  7. 7.

    Glauser T, Ben-Menachem E, Bourgeois B, et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia. 2013;54:551–63.

  8. 8.

    Berkovic SF, Knowlton RC, Leroy RF, et al. Placebo-controlled study of levetiracetam in idiopathic generalised epilepsy. Neurology. 2007;69:1751–60.

  9. 9.

    French JA, Krauss G, Wechsler R, et al. Adjunctive perampanel for treatment of drug-resistant primary generalized tonic-clonic seizures in patients with idiopathic generalized epilepsy: a double-blind randomized placebo-controlled phase III trial. Neurology. 2015;85:950–7.

  10. 10.

    Yamauchi T, Aikawa H. Efficacy of zonisamide: our experience. Seizure. 2004;(Suppl. 1):S41–8.

  11. 11.

    Marinas A, Villaneuva V, Giraldez BG, et al. Efficacy and tolerability of zonisamide in idiopathic generalized epilepsy. Epileptic Disord. 2009;11:61–6.

  12. 12.

    Stephen LJ, Kelly K, Wilson EA, Parker P, Brodie MJ. A prospective audit of adjunctive zonisamide in an everyday clinical setting. Epilepsy Behav. 2010;17:455–60.

  13. 13.

    Velizarova R, Crespel A, Genton P. Zonisamide for refractory juvenile absence epilepsy. Epilepsy Res. 2014;7:1263–6.

  14. 14.

    Janz D, Christian W. Impulsive petit mal. Deutsche Zeitschrift für Nervenheilkunde. 1957;176:346–88.

  15. 15.

    Shorvon SD, Bermejo PE, Gibbs AA, Huberfeld G, Kalviainen R. Antiepileptic drug treatment of generalized tonic-clonic seizures: an evaluation of regulatory data and five criteria for drug selection. Epilepsy Behav. 2018;82:91–103.

  16. 16.

    Striano P, Belcastro V. Treating mycolonic epilepsy in children: state of the art. Exp Opin Pharmacother. 2013;14:1355–61.

  17. 17.

    Kasteleijn-Nolst Trenite DG, Genton P, et al. Evaluation of brivaracetam, a novel SV2A ligand, in the photosensitivity model. Neurology. 2007;69:1027–34.

  18. 18.

    Matagne A, Margineau DG, Kenda B, et al. Anti-convulsive and anti-epileptic properties of brivaracetam (ucb34714), a high-affinity ligand for the synaptic vesicle protein, SV2A. Br J Pharmacol. 2008;154:1662–71.

  19. 19.

    Kwan P, Trinka E, Van Paesschen W, Rektor I, Johnson ME, Lu S. Adjunctive brivaracetam for uncontrolled focal and generalized epilepsies: results of a phase III, double-blind, randomized, placebo-controlled, flexible-dose trial. Epilepsia. 2014;55:38–46.

  20. 20.

    Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organisation of the epilepsies: report of the ILAE Commission on Classification and Terminology. Epilepsia. 2015;51:676–85.

  21. 21.

    Balagura G, Lapadre G, Verrotti A, Striano P. Moving beyond sodium valproate: choosing the right anti-epileptic drug in children. Exp Opin Pharmacother. 2019;20:1449–56.

  22. 22.

    Kwan P, Sills GJ, Brodie MJ. The mechanisms of action of commonly used antiepileptic drugs. Pharmacol Ther. 2001;90:21–34.

  23. 23.

    Tomson T, Battino D, Perucca E. Valproic acid after five decades of use in epilepsy: time to reconsider the indications of a time-honoured drug. Lancet Neurol. 2016;15:210–8.

  24. 24.

    Tomson T, Battino D, Bonizzoni E, Craig J, Lindhout D, Perucca E. Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry. Lancet Neurol. 2018;17:530–8.

  25. 25.

    Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy: interactions between antiepileptic drugs and other drugs. Lancet Neurol. 2003;2:473–81.

  26. 26.

    Machado RA, Garcia VF, Astencio AG, Cuartas VB. Efficacy and tolerability of lamotrigine in juvenile myoclonic epilepsy: a prospective, unblinded randomized controlled trial. Seizure. 2013;22:846–55.

  27. 27.

    Brodie MJ. Modern management of juvenile myoclonic epilepsy. Expert Rev Neurother. 2016;16:681–8.

  28. 28.

    Brodie MJ, Yuen AW. Lamotrigine substitution study: evidence for synergism with sodium valproate? 105 Study Group. Epilepsy Res. 1997;26:423–32.

  29. 29.

    Brodie MJ. Sodium channel blockers in the treatment of epilepsy. CNS Drugs. 2017;31:527–34.

  30. 30.

    Guberman AH, Besag FM, Brodie MJ, et al. Lamotrigine associated rash: risk benefit comorbidities in adults and children. Epilepsia. 1999;40:985–91.

  31. 31.

    Gaffield ME, Culwell KR, Lee CR. The use of hormonal contraception among women taking anticonvulsant therapy. Contraception. 2011;83:16–29.

  32. 32.

    Perucca EA. Pharmacological and clinical review on topiramate, a new antiepileptic drug. Pharmacol Res. 1997;35:241–56.

  33. 33.

    Lee S, Sziklas V, Andermann F, et al. The effect of adjunctive topiramate on cognitive function in patients with epilepsy. Epilepsia. 2003;44:339–47.

  34. 34.

    Mula M, Trimble MR, Lhatoo SD, Sander JW. Topiramate and psychiatric adverse events in patients with epilepsy. Epilepsia. 2003;44:659–63.

  35. 35.

    Veiby G, Daltveit AK, Engelsen BA, Gilhus NE. Fetal growth restriction and birth defects with newer and older antiepileptic drugs during pregnancy. J Neurol. 2014;261:579–88.

  36. 36.

    Brodie MJ, Mintzer S, Pack AM, Gidal BE, Vecht CJ, Schmidt D. Enzyme induction with antiepileptic drugs: cause for concern? Epilepsia. 2013;54:11–27.

  37. 37.

    Rosenfield WE, Doose DR, Walker SA, Nayak RK. Effect of topiramate on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyloestradiol. Epilepsia. 1997;38:317–23.

  38. 38.

    Kwan P, Brodie MJ. Emerging drugs for epilepsy. Expert Opin Emerg Drugs. 2007;12:407–22.

  39. 39.

    White JR, Walczak TS, Leppik IE, et al. Discontinuation of levetiracetam because of behavioural side effects. Neurology. 2003;61:1218–21.

  40. 40.

    Hirsch LJ, Arif H, Buchsbaum R, et al. Effect of age and comedication on levetiracetam pharmacokinetics and tolerability. Epilepsia. 2007;48:1351–9.

  41. 41.

    Brodie MJ. Perampanel. In: Shorvon S, Perucca E, Engel J, editors. The treatment of epilepsy. 4th ed. Hoboken: Wiley-Blackwell; 2016. p. 546–54.

  42. 42.

    Steinhoff BJ, Ben-Menachem E, Ryvlin P, et al. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies. Epilepsia. 2013;54:1481–9.

  43. 43.

    Brodie MJ, Stephen LJ. Prospective audit with adjunctive perampanel: preliminary observations in focal epilepsy. Epilepsy Behav. 2016;54:100–3.

  44. 44.

    Ettinger AB, Lopresti A, Yang H, et al. Psychiatric and behavioural adverse events in randomized clinical studies of the non-competitive AMPA receptor antagonist perampanel. Epilepsia. 2015;56:1252–63.

  45. 45.

    Gidal BE, Laurenza A, Hussein Z, et al. Perampanel efficacy and tolerability with enzyme-inducing AEDs in patients with epilepsy. Neurology. 2015;84:1–9.

  46. 46.

    Rock DM, Macdonald RL, Taylor CP. Blockade of sustained repetitive action potentials in cultured spinal cord neurons by zonisamide (AD 810, CI 912), a novel anticonvulsant. Epilepsy Res. 1989;3:138–43.

  47. 47.

    Kito M, Machara M, Watanabe K. Mechanisms of T-type calcium channel blockade by zonisamide. Seizure. 1996;5:115–9.

  48. 48.

    Piedad J, Rickards H, Besag FG, Cavana AE. Beneficial and adverse psychotropic effects of antiepileptic drugs in patients with epilepsy. CNS Drugs. 2012;26:319–35.

  49. 49.

    Wroe S. Zonisamide and renal calculi in patients with epilepsy: how big an issue? Curr Med Res Opin. 2007;23:1765–73.

  50. 50.

    Low PA, James S, Peschel T, Leon R, Rothstein A. Zonisamide and associated oligohydrosis and hypothermia. Epilepsy Res. 2004;62:27–34.

  51. 51.

    Goren MJ, Onat F. Ethosuximide: from bench to bedside. CNS Drugs. 2007;13:224–39.

  52. 52.

    Brodie MJ, Kwan P. Current position of phenobarbital in epilepsy and its future. Epilepsia. 2012;53(Suppl. 8):40–6.

  53. 53.

    Zaccara G, Perucca E. Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs. Epileptic Disord. 2014;16:403–32.

  54. 54.

    Pernea M, Sutcliffe AG. Clobazam and its use in epilepsy. Pediatr Rep. 2016;8:34–8.

  55. 55.

    Sankar R. GABA (A) receptor physiology and its relationship to the mechanism of action of the 1,5-benzodiazepine clobazam. CNS Drugs. 2012;26:229–44.

  56. 56.

    Ng Y, Collins SD. Clobazam. Neurotherapeutics. 2007;4:138–44.

  57. 57.

    Gauthier AC, Mattson RH. Clobazam: a safe, efficacious and newly rediscovered therapeutic for epilepsy. CNS Neurosci Ther. 2015;21:543–8.

  58. 58.

    Browne T. Clonazepam. N Engl J Med. 1978;299:812–6.

  59. 59.

    Brodie MJ, Chung S, Wade A, et al. Clobazam and clonazepam use in epilepsy: results from a UK database incident user cohort study. Epilepsy Res. 2016;123:68–74.

  60. 60.

    Grabowska-Grzb A, Jedrzcejczak J, Naganska E, Fizer U. Risk factors for depression in people with epilepsy. Epilepsy Behav. 2006;8:411–7.

  61. 61.

    Stephen LJ, Brodie MJ. Brivaracetam: a novel antiepileptic drug for focal-onset seizure. Therap Adv Neurol Dis. 2017;11:1–10.

  62. 62.

    Gillard M, Fuks B, Leclercq K, Matagne A. Binding characteristics of brivaracetam, a selective, high affinity SV2A ligand in rat, mouse and human brain: relationship to anticonvulsant properties. Br J Pharmacol. 2011;664:34–44.

  63. 63.

    Yates SL, Fakhoury T, Lang W, Eckhardt K, Borghs S, D’Souza J. An open-label, prospective, exploratory study of patients with epilepsy switching from levetiracetam to brivaracetam. Epilepsy Behav. 2015;52:165–8.

  64. 64.

    Zhu L, Chen D, Tao C, Xu D, Chen S, Liu L. The adverse event profile of brivaracetam: a meta-analysis of randomized controlled trials. Seizure. 2017;45:7–16.

  65. 65.

    D’Souza J, Perucca E. Brivaracetam. In: Shorvon S, Perucca E, Engel J, editors. The treatment of epilepsy. 4th ed. Chichester: Wiley; 2015. p. 418–30.

  66. 66.

    Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369:1016–26.

  67. 67.

    Rosenow F, Schade-Brittinger C, Burchardi N, et al. The LaLiMo Trial: lamotrigine compared with levetiracetam in the initial 26 weeks of monotherapy for focal and generalised epilepsy: an open-label, prospective, randomised controlled multicenter study. J Neurol Neurosurg Psychiatry. 2012;83:1093–8.

  68. 68.

    Coppola G, Piccorossi A, Operto FF, Verrotti A. Anticonvulsant drugs for generalized tonic-clonic epilepsy. Exp Opin Pharmacother. 2017;18:925–36.

  69. 69.

    Glauser TA, Cnaan A, Shinnar S, et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy: initial monotherapy outcomes at 12 months. Epilepsia. 2013;54:141–55.

  70. 70.

    Brigo F, Igwe SC, Lattanzi S. Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents. Cochrane Database Syst Rev. 2019;2:CD003032.

  71. 71.

    Nolan D, Lester S, Rau S, et al. Clinical use and efficacy of levetiracetam for absence epilepsies. J Child Neurol. 2018;34:94–8.

  72. 72.

    Levy A, Chen R. Myoclonus: pathophysiology and treatment options. Curr Treat Options Neurol. 2016;18:21.

  73. 73.

    Zhang Y, Chen J, Ren J, et al. Clinical features and treatment outcomes of juvenile myoclonic epilepsy patients. Epilepsia Open. 2019;4:302–8.

  74. 74.

    Velizarova R, Crespel A, Genton P, Serafini A, Gelisse P. Zonisamide for refractory juvenile absence epilepsy. Epilepsy Res. 2014;108:1263–6.

  75. 75.

    Steinig I, von Podwils F, Möddel G, et al. Postmarketing experience with brivaracetam in the treatment of epilepsies: a multicenter cohort study from Germany. Epilepsia. 2017;58:1208–16.

  76. 76.

    Grande-Martin A, Sopelana-Garay D, Pardal-Fernandez J, et al. Exceptional response to brivaracetam in a patient with refractory idiopathic generalized epilepsy and absence seizures. Epileptic Disord. 2018;20:60–4.

  77. 77.

    Strzelczyk A, Kay L, Bauer S, et al. Use of brivaracetam in genetic generalized epilepsies and for acute, intravenous treatment of absence status epilepticus. Epilepsia. 2018;59:1549–56.

  78. 78.

    Reif PS, Männer A, Willems LM, et al. Intravenous lacosamide for treatment of absence status epilepticus in genetic generalized epilepsy: a case report and review of literature. Acta Neurol Scand. 2018;138:259–62.

  79. 79.

    Camfield CS, Striano P, Camfield PR. Epidemiology of juvenile myoclonic epilepsy. Epilepsy Behav. 2013;28(Suppl. 1):S15–7.

  80. 80.

    Maguire M, Marson AG, Ramaratnam S. Epilepsy (generalised). Clin Evid. 2012;2:1201.

  81. 81.

    Covanis A, Gupta AK, Jeavons PM. Sodium valproate: monotherapy and polytherapy. Epilepsia. 1982;23:693–720.

  82. 82.

    Calleja S, Salas-Puig J, Ribacoba R, et al. Evolution of juvenile myoclonic epilepsy treated from the outset with sodium valproate. Seizure. 2001;10:424–7.

  83. 83.

    Hitiris N, Brodie MJ. Evidence based treatment of idiopathic generalized epilepsies with older antiepileptic drugs. Epilepsia. 2005;4(Suppl. 9):149–53.

  84. 84.

    Mendriatta MM, Aggarwal P. Clinical expression and EEG features of patients with juvenile myoclonic epilepsy (JME) from North India. Seizure. 2002;11:431–6.

  85. 85.

    Chowdhury A, Brodie MJ. Pharmacological outcomes in juvenile myoclonic epilepsy over a 30 year period: support for sodium valproate. Epilepsy Res. 2016;119:62–6.

  86. 86.

    Gelisse P, Genton P, Thomas P, et al. Clinical factors of drug resistance in juvenile myoclonic epilepsy. J Neurol Neurosurg Psychiatry. 2001;70:240–3.

  87. 87.

    Jayalakshmi S, Vooturi S, Bana AK, et al. Factors associated with lack of response to valproic acid monotherapy in juvenile myoclonic epilepsy. Seizure. 2014;23:527–32.

  88. 88.

    Silvennoinen K, de Lange N, Zagaglia S, et al. Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy. Epilepsia Open. 2019;4:420–30.

  89. 89.

    Levisohn PM, Holland KD. Topiramate or valproate in patients with juvenile myoclonic epilepsy: a randomized open-label comparison. Epilepsy Behav. 2007;10:547–52.

  90. 90.

    Park KM, Kim SH, Nho SK, et al. A randomized open-label observational study to compare the efficacy and tolerability between topiramate and valproate in juvenile myoclonic epilepsy. J Clin Neurosci. 2013;20:1079–82.

  91. 91.

    Liu J, Wang LN, Wang YP. Topiramate for juvenile myoclonic epilepsy. Cochrane Database Syst Rev. 2019;1:CD010008. https://doi.org/10.1002/14651858.cd010008.pub4.

  92. 92.

    Noachter S, Andermann E, Meyisck P, et al. Levetiracetam for the treatment of idiopathic generalised epilepsy with myoclonic seizures. Neurology. 2008;70:607–16.

  93. 93.

    Rosenfeld WE, Benbadis S, Edrich P, et al. Levetiracetam as add on therapy for idiopathic generalized epilepsy syndromes with onset during adolescence: analysis of two randomized double-blind placebo-controlled studies. Epilepsy Res. 2009;85:72–80.

  94. 94.

    Specchio LM, Gambardella A, Giallonardo AT, et al. Open label, long-term pragmatic study of levetiracetam in the treatment of juvenile myoclonic epilepsy. Epilepsy Res. 2006;17:32–9.

  95. 95.

    Stephen LJ, Kelly K, Parker P, et al. Levetiracetam monotherapy outcomes from an epilepsy clinic. Seizure. 2011;20:554–7.

  96. 96.

    Biton V, Bourgeois BF; YTC/YTCE Study Investigators. Topiramate in patients with juvenile myoclonic epilepsy. Arch Neurol. 2005;62:170–8.

  97. 97.

    De Araujo Filho GM, Pascalicchio TF, Lin K, Sousa PS, Yacubian MT. Neuropsychiatric profiles of patients with juvenile myoclonic epilepsy treated with valproate or topiramate. Epilepsy Behav. 2006;3:606–9.

  98. 98.

    Stephen LJ, Sills GJ, Brodie MJ. Topiramate in refractory epilepsy: a prospective, observational study. Epilepsia. 2000;41:977–80.

  99. 99.

    Kothare SV, Valencia I, Khurana DS, et al. Efficacy and tolerability of zonisamide in juvenile myoclonic epilepsy. Epileptic Disord. 2004;6:267–70.

  100. 100.

    Afra P, Adamolekum B. Lacosamide treatment of juvenile myoclonic epilepsy. Seizure. 2012;21:202–4.

  101. 101.

    Zangaladze A, Skidmore C. Lacosamide use in refractory idiopathic refractory primary generalized epilepsy. Epilepsy Behav. 2012;23:79–80.

  102. 102.

    Wechsler RT, Yates SL, Messenheimer J, Leroy R, Beller C, Doty P. Lacosamide for uncontrolled primary generalized tonic-clonic seizures: an open-label study with 59-week extension. Epilepsy Res. 2017;130:13–20.

  103. 103.

    Sodemann U, Moller HS, Blaabjerg M, Beier CP. Successful treatment of refractory absence status epilepticus with lacosamide. J Neurol. 2014;261:2025–7.

  104. 104.

    D’Orsi G, Pacillo T, Trivisano M, Pascarella MG, Ferrara MA, Specchio LM. Lacosamide in absence status epilepticus. Seizure. 2014;23:397–8.

  105. 105.

    Obeid T, Panayiotopoulos CP. Clonazepam in juvenile myoclonic epilepsy. Epilepsia. 1989;30:603–6.

  106. 106.

    Resor SR, Resor LD. Chronic acetazolamide monotherapy in the treatment of juvenile myoclonic epilepsy. Neurology. 1990;40:1677–81.

  107. 107.

    Ng M, Devinsky O. Vagus nerve stimulation for refractory idiopathic generalised epilepsy. Seizure. 2004;13:176–8.

  108. 108.

    Holmes MD, Silbergeld DL, Drouhard D, Wilensky JA, Ojemann L. Effect of vagus nerve stimulation on adults with pharmacoresistant generalized epilepsy syndromes. Seizure. 2004;13:340–5.

  109. 109.

    Biraben A, Allain H, Scarabin JM, et al. Exacerbation of juvenile myoclonic epilepsy with lamotrigine. Neurology. 2000;55:1757–8.

  110. 110.

    Scottish Intercollegiate Guideline Network. Epilepsy and women’s health. In: Diagnosis and management of epilepsy in adults (SIGN publication no 143). May 2015. http://www.sign.ac.uk/assets/sign143.pdf. Accessed 15 Dec 2019.

  111. 111.

    National Institute for Health and Care Excellence. Epilepsies: diagnosis and management. Clinical guideline. January 2012. https://www.nice.org.uk/guidance/cg137/resources/epilepsies-diagnosis-and-management-pdf-35109515407813. Accessed 15 Dec 2019.

  112. 112.

    Gayatri NA. Aggravation of epilepsy by anti-epileptic drugs. Dev Med Child Neurol. 2006;48:394–8.

  113. 113.

    Hamano S-I, Mochizuki M, Monikawa T. Phenobarbital-induced atypical absence seizure in benign childhood epilepsy with centrotemporal spikes. Seizure. 2002;11:201–4.

  114. 114.

    Sazgar M, Bourgeois B. Aggravation of epilepsy by antiepileptic drugs. Pediatr Neurol. 2005;4:227–34.

  115. 115.

    Stephen LJ, Forsyth M, Kelly K, Brodie MJ. Antiepileptic drug combinations: have newer agents altered clinical outcomes? Epilepsy Res. 2012;98:194–8.

  116. 116.

    Cacao G, Parra J, Mannan S, Sisodiya S, Sander J. Juvenile myoclonic epilepsy refractory to treatment in a tertiary referral centre. Epilepsy Behav. 2018;82:81–6.

  117. 117.

    Trinka E, Baumgartner S, Unterberger I, Unterrainer J, Luef G, Haberlandt E, et al. Long-term prognosis for childhood and juvenile absence epilepsy. J Neurol. 2004;251:1235–41.

  118. 118.

    Danhofer P, Brazdil M, Oslejskova H, Kuba R. Long-term seizure outcome in patients with juvenile absence epilepsy: a retrospective study in a tertiary referral center. Seizure. 2014;23:443–7.

  119. 119.

    Yacubian EM. Juvenile myoclonic epilepsy: challenges on its 60th anniversary. Seizure. 2017;44:48–52.

  120. 120.

    Burneo JG. SUDEP: let’s talk about it. Neurology. 2019;93:1–2.

  121. 121.

    Covanis A. Photosensitivity in idiopathic generalized epilepsies. Epilepsia. 2005;46(Suppl. 9):67–72.

  122. 122.

    Asadi-Pooya AA, Hashemzehi Z, Emami M. Predictors of seizure control in patients with juvenile myoclonic epilepsy (JME). Seizure. 2014;23:889–91.

  123. 123.

    Gűrer R, Aydin S, Őzkara C. Outcomes of low dose valproic acid treatment in patients with juvenile myoclonic epilepsy. Seizure. 2019;70:43–8.

  124. 124.

    Giorgi FS, Guida M, Caciagli L, et al. Social cognition in juvenile myoclonic epilepsy. Epilepsy Res. 2016;128:61–7.

  125. 125.

    Somayajula S, Vooturi S, Jayalakshmi S. Psychiatric disorders among 165 patients with juvenile myoclonic epilepsy in India and association with clinical and sociodemographic variables. Epilepsy Behav. 2015;53:37–42.

  126. 126.

    Almane DN, Jones JE, McMillan T, et al. The timing, nature and range of neurobehavioral comorbidities in juvenile myoclonic epilepsy. Pediatr Neurol. 2019;101:47–52.

  127. 127.

    Kanner AM. Most antidepressant drugs are safe for patients with epilepsy at therapeutic doses: a review of the evidence. Epilepsy Behav. 2016;61:282–6.

  128. 128.

    FDA Drug Safety Communication. Valproate antiseizure products contraindicated for migraine prevention in pregnant women due to decreased IQ scores in exposed children. https://www.fda.gov/Drugs/DrugSafety/ucm350684.htm. Accessed 15 Dec 2019.

  129. 129.

    European Medicines Agency. Valproate and related substances. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Valproate_and_related_substances/human_referral_prac_000032.jsp&mid=WC0b01ac05805c516f. Accessed 15 Dec 2019.

  130. 130.

    Hernández-Diaz S, Smith CR, Shen A, et al.; North American AED Pregnancy Registry; North American AED Pregnancy Registry. Comparative safety of antiepileptic drugs during pregnancy. Neurology. 2012;78:1692–9.

  131. 131.

    Campbell E, Kennedy F, Russell A, et al. Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers. J Neurol Neurosurg Psychiatry. 2014;85:1029–34.

  132. 132.

    Baker GA, Bromley RL, Briggs M, et al. IQ at 6 years after in utero exposure to antiepileptic drugs: a controlled cohort study. Neurology. 2015;84:382–90.

  133. 133.

    Weston J, Bromley R, Jackson CF, et al. Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. Cochrane Database Syst Rev. 2016;11:CD010224. https://doi.org/10.1002/14651858.cd010224.pub2.

  134. 134.

    Veroniki AA, Rios P, Cogo E, et al. Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis. BMJ Open. 2017;7:e017248. https://doi.org/10.1136/bmjopen-2017-017248.

  135. 135.

    Lacey AS, Pickrell WO, Thomas RH, Kerr MP, White CP, Rees MI. Educational attainment of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry. 2018;89:736–40.

  136. 136.

    Bromley RL, Weston J, Adab N. Treatment for epilepsy in pregnancy: neurodevelopmental outcomes in the child. Cochrane Database Syst Rev. 2014;10;CD010236.

  137. 137.

    Christensen J, Gronborg TK, Sorensen MJ, et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA. 2013;309:1696–703.

  138. 138.

    Bromley RL, Baker GA. Fetal antiepileptic drug exposure and cognitive outcomes. Seizure. 2017;44:225–31.

  139. 139.

    Mostacci B, Bisulli F, Poluzzi E, et al. Emilia-Romagna study on pregnancy and exposure to antiepileptic drugs (ESPEA): a population-based study on prescription patterns, pregnancy outcomes and fetal health. J Neurol Neurosurg Psychiatry. 2018;89:983–8.

  140. 140.

    Bech LF, Polcwiartek C, Kragholm K, et al. In utero exposure to antiepileptic drugs is associated with learning disabilities among offspring. J Neurol Neurosurg Psychiatry. 2018;89:1324–31.

  141. 141.

    Christensen J, Pedersen L, Sun Y, et al. Association of prenatal exposure to valproate and other antiepileptic drugs with risk for attention-deficit/hyperactivity disorder in offspring. JAMA Network Open. 2019;2(1):e186606.

  142. 142.

    Angus-Leppan H, Liu R. Weighing the risks of valproate in women who could become pregnant. BMJ. 2018;361:53–5.

  143. 143.

    Tomson T, Battino D, Perucca E. Teratogenicity of antiepileptic drugs. Curr Opin Neurol. 2019;32:246–52.

  144. 144.

    Tomson T, Battino D, Bromley R, Kochen S, Meador K, Pennell P, et al. Management of epilepsy in pregnancy: a report from the International League Against Epilepsy Task Force on Women and Pregnancy. Epileptic Disord. 2019;21:1–21.

  145. 145.

    Rohracher A, Brigo F, Hofler J, et al. Perampanel for the treatment of primary generalized tonic-clonic seizures in idiopathic generalized epilepsy. Expert Opin Pharmacother. 2016;17:1403–11.

  146. 146.

    Stephen LJ, Harden C, Tomson T, Brodie MJ. Management of epilepsy in women. Lancet Neurol. 2019;18:481–91.

  147. 147.

    Bromley RL, Weston J, Marson AG. Maternal use of antiepileptic agents during pregnancy and major congenital malformations in children. JAMA. 2017;318:1700–1.

  148. 148.

    Voinescu PE, Park S, Chen IQ, et al. Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy. Neurology. 2018;91:e1228–36.

  149. 149.

    Pennell PB, Peng L, Newport DJ, Ritchie JC, Koganti A, Holley DK, et al. Lamotrigine in pregnancy: clearance, therapeutic drug monitoring and seizure frequency. Neurology. 2008;70:2130–6.

  150. 150.

    Baykan B, Martinez-Juarez IE, Altindag EA, Camfield CS, Camfield PR. Lifetime prognosis of juvenile myoclonic epilepsy. Epilepsy Behav. 2013;28:S18–24.

  151. 151.

    Höfler J, Unterberger I, Dobesberger J, Kuchukhidze G, Walser G, Trinka E. Seizures outcome in 175 patients with juvenile myoclonic epilepsy: a long-term observational study. Epilepsy Res. 2014;108:1817–24.

  152. 152.

    Healy L, Moran M, Singhal S, et al. Relapse after treatment withdrawal of antiepileptic drugs for juvenile absence epilepsy and juvenile myoclonic epilepsy. Seizure. 2018;59:116–22.

  153. 153.

    Vorderwulbecke BJ, Kirschbaum A, Merkle H, Senf P, Holtkamp M. Discontinuing antiepileptic drugs in long-standing idiopathic generalised epilepsy. J Neurol. 2019;266(10):2554–9.

  154. 154.

    Holtkamp M, Kowski AB, Merkle H, Janz D. Long-term outcome in epilepsy with grand mal on awakening: forty years of follow-up. Ann Neurol. 2014;75:298–302.

  155. 155.

    Senf P, Schmitz B, Holtkamp M, Janz D. Prognosis of juvenile myoclonic epilepsy 45 years after onset: seizure outcome and predictors. Neurology. 2013;81:2128–33.

  156. 156.

    Keezer M, Sisodiya S, Sander J. Comorbidities of epilepsy: current concepts and future perspectives. Lancet Neurol. 2016;15:106–15.

  157. 157.

    O’Muircheartaigh J, Vollmar C, Barker GJ, et al. Focal structural changes and cognitive dysfunction in juvenile myoclonic epilepsy. Neurology. 2011;76:34–40.

  158. 158.

    Yogarajah M, Mula M. Social cognition, psychiatric comorbidities and quality of life in adults with epilepsy. Epilepsy Behav. 2019;100:106321.

  159. 159.

    Rauchenzauner M, Hagn C, Walch R, Baumann M, Haberlandt E, Frühwirth M, Rostasy K. Quality of life and fitness in children and adolescents with epilepsy (EpiFit). Neuropediatrics. 2017;48:161–5.

  160. 160.

    Gupta S, Kwan P, Faught E, Tsong W, Forsythe A, Ryvlin P. Understanding the burden of idiopathic generalised epilepsy in the United States, Europe and Brazil: an analysis for the National Health and Wellness Survey. Epilepsy Behav. 2016;55:146–56.

  161. 161.

    Panayiotopolous CP. Epilepsy with GTCS only. A clinical guide to tpileptic syndromes and their treatment. 2nd ed. London: Springer; 2007. p. 343–5.

Download references

Author information

Correspondence to Linda J. Stephen.

Ethics declarations


No sources of funding were received for the preparation of this article.

Conflict of interest

Linda J. Stephen has received personal fees from Eisai, outside of the submitted work. Martin J. Brodie has received personal speaker and/or consultancy fees from UCB, Eisai, Xenon and Arvelle Therapeutics outside of the submitted work.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Stephen, L.J., Brodie, M.J. Pharmacological Management of the Genetic Generalised Epilepsies in Adolescents and Adults. CNS Drugs 34, 147–161 (2020). https://doi.org/10.1007/s40263-020-00698-5

Download citation