Which adverse effects of antiepileptic drugs is the major concern in children?

  • Shaw PN, Houston JB, Rowland M, et al. Antipyrine metabolite kinetics in healthy human volunteers during multiple dosing of phenytoin and carbamazepine. Br J Clin Pharmacol 1985; 20: 611–8

    Article  PubMed  CAS  Google Scholar 

  • Perucca E, Richens A. General principles: biotransformation. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic Drugs. 4th ed. New York: Raven Press, 1995: 31–50

    Google Scholar 

  • Connell J, Oozeer R, De Vries L, et al. Clinical and EEG responses to anticonvulsants in neonatal seizures. Arch Dis Child 1989; 64: 459–64

    Article  PubMed  CAS  Google Scholar 

  • Bruni J. Phenytoin: toxicity. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic drugs. 4th ed. New York: Raven, 1995: 345–50

    Google Scholar 

  • Cramer JA, Mattson RH. Phenobarbital: toxicity. In Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic Drugs. 4th ed. New York: Raven, 1995: 409–20

    Google Scholar 

  • Schiff D, Chan G, Stern L. Fixed drug combinations and the displacement of bilirubin from albumin. Pediatrics 1971; 48: 139–41

    PubMed  CAS  Google Scholar 

  • Deshmukh A, Wittert W, Schnitzler E, et al. Lorazepam in the treatment of refractory neonatal seizures. Am J Dis Child 1986; 140: 1042–4

    PubMed  CAS  Google Scholar 

  • McDermott CA, Kowalczyk AL, Schnitzler ER, et al. Clinical and laboratory observations: pharmacokinetics of lorazepam in critical ill neonates with seizures. J Pediatr 1992; 120: 479–83

    Article  PubMed  CAS  Google Scholar 

  • Sinal SH, Crowe JE. Cyanosis, coughing and hypotension following intravenous administration of paraldehyde. Pediatrics 1976; 57: 158–9

    Google Scholar 

  • Dreifuss FE. Valproic acid: toxicity. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic drugs. 4th ed. New York: Raven, 1995: 641–8

    Google Scholar 

  • Leppik I. Felbamate. Epilepsia 1995; 36Suppl. 2: S66–72

    Article  PubMed  CAS  Google Scholar 

  • Holmes G. Carbamazepine: toxicity. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic drugs. 4th ed. New York: Raven, 1995: 567–79

    Google Scholar 

  • Dreifuss FE. Ethosuximide: toxicity. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic drugs. 4th ed. New York: Raven, 1995: 675–9

    Google Scholar 

  • Leppik IE, Cloyd JC. Primidone: toxicity. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic drugs. 4th ed. New York: Raven, 1995: 487–90

    Google Scholar 

  • Abu-Arafeh IA, Wallace SJ. Unwanted effects of antiepileptic drugs. Dev Med Child Neurol 1988; 30: 117–21

    Article  PubMed  CAS  Google Scholar 

  • Mattson RH. Efficacy and adverse effects of established and new antiepileptic drugs. Epilepsia 1995: 36Suppl. 2: S13–26

    Article  PubMed  CAS  Google Scholar 

  • Okuno T, Ho M, Nakano S, et al. Carbamazepine therapy and long-term prognosis in epilepsy of childhood. Epilepsia 1989; 30: 57–61

    Article  PubMed  CAS  Google Scholar 

  • Lee WM. Drug-induced hepatotoxicity. N Engl J Med 1995; 333: 1118–27

    Article  PubMed  CAS  Google Scholar 

  • Loiseau P. Sodium valproate, platelet dysfunction and bleeding. Epilepsia 1981; 22: 141–6

    Article  PubMed  CAS  Google Scholar 

  • Gidal B, Spencer N, Maly M, et al. Valproate mediated disturbances of hemostasis [letter]. Neurology 1994; 30: 354

    Google Scholar 

  • Allarakhia IN, Garofalo EA, Komarynski MA, et al. Valproic acid and thrombocytopenia in children: a case-controlled retrospective study. Pediatr Neurol 1996; 14: 303–7

    Article  PubMed  CAS  Google Scholar 

  • Appleton R. The role of vigabatrin in the management of infantile epileptic syndromes. Neurology 1993; 43Suppl. 5: S21–3

    PubMed  CAS  Google Scholar 

  • Brodie MJ. Lamotrigine. Lancet 1992; 339: 1397–400

    Article  PubMed  CAS  Google Scholar 

  • Ramsay RE. Gabapentin: toxicity. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic Drugs. 4th ed. New York: Raven, 1995: 857–60

    Google Scholar 

  • Leppik IE. Tiagabine: the safety landscape. Epilepsia 1995; 36Suppl. 6: S10–3

    Article  PubMed  CAS  Google Scholar 

  • Reife RA, Pledger GW. Safety of topiramate in clinical use. Adv AED Ther 1995; 1(1): 24–9

    Google Scholar 

  • Tada H, Wallace SJ, Hughes IA. Height in epilepsy. Arch Dis Child 1986; 61: 1224–6

    Article  PubMed  CAS  Google Scholar 

  • Dam M, Ostergaard LH. Other Antiepileptic drugs: oxcarbazepine. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic Drugs. 4th ed. New York: Raven, 1995: 987–95

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Dodson WE. Felbamate in the treatment of Lennox-Gastaut Syndrome: results of a 12-month open-label study following a randomized clinical trial. Epilepsia 1993; 34Suppl. 7: S18–24

    Article  PubMed  Google Scholar 

  • Bebin EM, Dogis TF, Dreifuss FE. Felbamate: toxicity. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic drugs, 4th ed. New York: Raven, 1995: 823–7

    Google Scholar 

  • Dreifuss FE. Other antiepileptic drugs: bromides. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic drugs. 4th ed. New York: Raven, 1995: 949–51

    Google Scholar 

  • Pellock JM. Carbamazepine side effects in children and adults. Epilepsia 1987; 28Suppl. 3: S64–70

    Article  PubMed  Google Scholar 

  • Jeng Y-M, Tien H-F, Su I-J. Phenytoin-induced pseudolymphoma: re-evaluation using modern molecular biology techniques. Epilepsia 1996; 37(1): 104–7

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Baillie TA, Sheffels PR. Valproic acid: chemistry and biotransformation. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic Drugs. 4th ed. New York: Raven, 1995: 589–604

    Google Scholar 

  • Melegh B, Pap M, Morava E, et al. Carnitine-dependent changes of metabolic fuel consumption during long-term treatment with valproic acid. J Pediatr 1994; 125: 317–21

    Article  PubMed  CAS  Google Scholar 

  • Thurston JH, Hauhart RE. Reversal of the adverse chronic effects of the unsaturated derivative of valproic acid — 2-n-pro-pyl-4-pentenoic acid — on ketogenesis and liver coenzyme A metabolism by a single injection of pantothenate, carnitine, and acetyl-cysteine in developing mice. Pediatr Res 1993; 33: 72–6

    Article  PubMed  CAS  Google Scholar 

  • Murakami K, Sugimoto T, Nishira N, et al. Abnormal metabolism of carnitine and valproate in a case of acute encephalopathy during chronic valproate therapy. Brain Dev 1992; 14: 178–81

    Article  PubMed  CAS  Google Scholar 

  • Kuhara T, Inoue Y, Matsumoto M, et al. Markedly increased co-oxidation of valproate in fulminant hepatic failure. Epilepsia 1990; 31: 214–7

    Article  PubMed  CAS  Google Scholar 

  • Konig St A, Siemes H, Blaker F, et al. Severe hepatotoxicity during valproate therapy: an update and report of eight new fatalities. Epilepsia 1994; 35: 1005–15

    Article  Google Scholar 

  • Bryant AE, Dreifuss FE. Valproic acid hepatic fatalities III: U.S. experience since 1986. Neurology 1996; 46: 465–9

    Article  PubMed  Google Scholar 

  • Moore MR. International review of drugs in acute porphyria [letter]. Int J Biochem 1980; 12: 1089

    Article  PubMed  CAS  Google Scholar 

  • Tatum WO, Zacharian SB. Gabapentin treatment of seizures in acute intermittent porphyria. Neurology 1995; 45: 1216–7

    Article  PubMed  Google Scholar 

  • McLean MJ. Gabapentin. Epilepsia 1995; 36Suppl. 2: S73–86

    Article  PubMed  CAS  Google Scholar 

  • Dreifuss FE, Santilli N, Langer DH, et al. Valproic acid hepatic fatalities: a retrospective review. Neurology 1987; 37: 379–85

    Article  PubMed  CAS  Google Scholar 

  • Scheffner D, Konig S, Rauterberg-Rutland I, et al. Fatal liver failure in 16 children with valproate therapy. Epilepsia 1988; 29: 530–42

    Article  PubMed  CAS  Google Scholar 

  • Herranz JL, Armijo JA, Artego R. Clinical side effects of phenobarbitone primidone, phenytoin, carbamazepine and valproate during monotherapy in children. Epilepsia 1988; 29: 794–804

    Article  PubMed  CAS  Google Scholar 

  • Dulac O, Chiron C, Luna D, et al. Vigabatrin in childhood epilepsy. J Child Neurol 1991; 6Suppl. 2: S30–7

    Google Scholar 

  • Feucht M, Brantner-Inthaler S. γ-vinyl GABA (vigabatrin) in the therapy of Lennox-Gastaut syndrome: an open study. Epilepsia 1994; 35(5): 993–8

    Article  PubMed  CAS  Google Scholar 

  • Alving J. Case of severe acute intoxication with oxcarbazepine combined with lamotrigine [abstract]. Epilepsia 1994; 35Suppl. 7: 72

    Google Scholar 

  • Aman MG, Werry JS, Paxton JW, et al. Effects of phenytoin on cognitive motor performance in children as a function of drug concentration, seizure type, and time of medication. Epilepsia 1994; 35: 172–80

    Article  PubMed  CAS  Google Scholar 

  • Aman MG, Werry JS, Paxton JW, et al. Effect of sodium valproate on psychomotor performance in children as a function of dose, fluctuations in concentration, and diagnosis. Epilepsia 1987; 28: 115–28

    Article  PubMed  CAS  Google Scholar 

  • Steinhoff BJ, Kruse R. Bromide treatment of pharmaco-resistant epilepsy with generalised tonic-clonic seizures: a clinical study. Brain Dev 1992; 14: 144–9

    Article  PubMed  CAS  Google Scholar 

  • Corbett JA, Trimble MR, Nichol RC. Behavioural and cognitive impairments in children with epilepsy: the long-term effects of anticonvulsant therapy. J Am Acad Child Psychiatry 1985; 24: 17–23

    Article  PubMed  CAS  Google Scholar 

  • Vining EPG, Mellits ED, Dorsen MM, et al. Psychologic and behavioural effects of antiepileptic drugs in children: a double-blind comparative comparison between phenobarbital and valproic acid. Pediatrics 1987; 80: 165–74

    PubMed  CAS  Google Scholar 

  • Ounsted C. The hyperkinetic syndrome in epileptic children. Lancet 1955; II: 303–11

    Article  Google Scholar 

  • Wolf SM, Shinnar S, Hang H, et al. Gabapentin toxicity in children manifesting as behavioural changes. Epilepsia 1995; 36(12): 1203–5

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Camfield CS, Chaplin S, Doyle AB, et al. Side effects of phenobarbital in toddlers; behavioural and cognitive aspects. J Pediatr 1979; 95: 361–5

    Article  PubMed  CAS  Google Scholar 

  • Canovas Martinez A, Ordovas Baines JP, Escriva Asparisi A, et al. Vigabatrin — associated reversible acute psychosis in a child. Ann Pharmacother 1995; 29: 1115–7

    PubMed  CAS  Google Scholar 

  • Aldridge Smith J, Wallace SJ. Febrile convulsions: intellectual progress in relation to anticonvulsant therapy and recurrence of fits. Arch Dis Child 1982; 57: 104–7

    Article  Google Scholar 

  • Chen Y, Kang W, Chin-Min So W. Comparison of antiepileptic drugs on cognitive function in newly diagnosed epileptic children: a psychometric and neurophysiological study. Epilepsia 1996; 37(1): 81–6

    Article  PubMed  CAS  Google Scholar 

  • American Academy of Pediatrics’ Committee on Drugs. Behavioural and cognitive effects of anticonvulsant therapy. Pediatrics 1985; 76: 644–7

    Google Scholar 

  • Stores G, Williams PL, Styles E, et al. Psychological effects of sodium valproate and carbamazepine in epilepsy. Arch Dis Child 1992; 67: 1330–7

    Article  PubMed  CAS  Google Scholar 

  • Aldenkamp AP, Alpherts WCJ, Blennow G, et al. Withdrawal of antiepileptic medication in children — effects on cognitive function: the multicentre Holmfrid study. Neurology 1993; 43: 41–50

    Article  PubMed  CAS  Google Scholar 

  • Forsythe I, Butler R, Berg I, et al. Cognitive impairment in new cases of epilepsy randomly assigned to carbamazepine, phenytoin and sodium valproate. Dev Med Child Neurol 1991; 33: 524–35

    Article  PubMed  CAS  Google Scholar 

  • Shields WD, Saslow E. Myoclonic, atonic and absence seizures following institution of carbamazepine therapy in children. Neurology 1983; 33: 1487–9

    Article  PubMed  CAS  Google Scholar 

  • Snead OC, Hosey LC. Exacerbation of seizures in children by carbamazepine. N Engl J Med 1985; 313: 916–21

    Article  PubMed  Google Scholar 

  • Marciani MG, Gigli GL, Maschio CE, et al. Vigabatrin-induced myoclonus in four cases of partial epilepsy [abstract]. Epilepsia 1995; 36Suppl. 3: 107

    Google Scholar 

  • Lortie A, Chiron C, Mumford J, et al. The potential for increasing seizure frequency, relapse and appearance of new seizure types with vigabatrin. Neurology 1993; 43Suppl. 5: S24–7

    PubMed  CAS  Google Scholar 

  • Ceuleman B, Boel M. Lamotrigine: add on therapy in children with refractory epilepsies [abstract]. Epilepsia 1995; 36Suppl. 3: 110

    Google Scholar 

  • Roussounis SH, Rudolf N de M. Clonazepam in the treatment of children with intractable seizures. Dev Med Child Neurol 1977; 19: 326–34

    Article  PubMed  CAS  Google Scholar 

  • Piatella L, Zamponi N, Cardinali C. Vigabatrin versus carbamazepine in newly diagnosed partial epilepsy in childhood [abstract]. Epilepsia 1995; 36Suppl. 3: S103

    Google Scholar 

  • Herranz JL, Campos J, Casas C, et al. Spanish experience with efficacy and tolerability of vigabatrin in 197 children with refractory epilepsy [abstract]. Epilepsia 1995; 36Suppl. 3: S103

    Google Scholar 

  • Besag FMC, Wallace SJ, Dulac O, et al. Lamotrigine in the treatment of epilepsy in childhood. Pediatr Pharmacol Ther 1995; 127: 991–7

    CAS  Google Scholar 

  • What is the most common adverse effect associated with anti seizure drugs?

    Some common side effects that may occur in the first few weeks of taking seizure medicines include feeling tired, stomach upset or discomfort, dizziness, or blurred vision. Some of these may not occur or are tolerated okay if the medication is started at a low dose and increased slowly.

    What are the side effects of seizure medication in children?

    Therefore, all seizures medications have some risk of side effects. Most children have few or no problems with side effects from seizure medications..
    Feeling sleepy..
    Mood changes..
    Irritability..
    Stomach problems..

    What antiepileptics cause birth defects?

    Studies have shown that valproic acid presents the most risk to the developing baby. Along with valproic acid, carbamazepine might increase the risk for spina bifida (a major birth defect of the baby's spine) and cleft palate (a birth defect of the baby's mouth).

    Which antiepileptic is most teratogenic?

    Valproate is the drug with the highest risk, whereas prevalence of MCMs is lowest with lamotrigine, levetiracetam, and oxcarbazepine. For valproate, phenobarbital, phenytoin, carbamazepine, and lamotrigine, the risk of MCMs is dose-dependent.