Randomised comparative monotherapy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy

Lancet. 1996 Mar 16;347(9003):709-13. doi: 10.1016/s0140-6736(96)90074-4.


Background: The medical treatment of childhood epilepsy is largely influenced by clinical trials in adult patients. We know of only one randomised comparative trial (of two drugs) in newly diagnosed childhood epilepsy. We have undertaken a long-term, prospective, randomised, unmasked, pragmatic trial of the comparative efficacy and toxicity of four standard antiepileptic drugs used as monotherapy in children with newly diagnosed epilepsy.

Methods: Between 1981 and 1987, 167 children aged 3-16 years, who had had at least two previously untreated tonic-clonic or partial seizures, with or without secondary generalisation, were randomly allocated treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform to standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to achieving 1-year remission.

Findings: The overall outcome with all four drugs was good. 20% of children remained free of seizures and 73% had achieved 1-year remission by 3 years of follow-up. We found no significant differences between the drugs for either measure of efficacy at 1, 2, or 3 years of follow-up. The overall frequency of unacceptable side-effects necessitating withdrawal of the randomised drug was 9%. This total included six of the first ten children assigned phenobarbitone; no further children were allocated this drug. Of the other three drugs, phenytoin (9%) was more likely to be withdrawn than carbamazepine (4%) or sodium valproate (4%). INTERPRETATION Our data will inform choice of drug and outcome with four of the standard drugs available for newly diagnosed tonic-clonic or partial seizures with or without secondary generalisation in children.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Carbamazepine / adverse effects
  • Carbamazepine / therapeutic use*
  • Child
  • Child, Preschool
  • Epilepsies, Partial / drug therapy
  • Epilepsy / drug therapy*
  • Epilepsy, Tonic-Clonic / drug therapy
  • Humans
  • Phenobarbital / adverse effects
  • Phenobarbital / therapeutic use*
  • Phenytoin / adverse effects
  • Phenytoin / therapeutic use*
  • Prospective Studies
  • Treatment Outcome
  • Valproic Acid / adverse effects
  • Valproic Acid / therapeutic use*


  • Anticonvulsants
  • Carbamazepine
  • Valproic Acid
  • Phenytoin
  • Phenobarbital