Does withdrawal of different antiepileptic drugs have different effects on seizure recurrence? Further results from the MRC Antiepileptic Drug Withdrawal Study

Brain. 1999 Mar;122 ( Pt 3):441-8. doi: 10.1093/brain/122.3.441.


One thousand and thirteen patients, in remission of epilepsy for at least 2 years, were randomized to continued therapy or slow withdrawal over 6 months and were followed up for a median period of 5 years. At the time of randomization 83% of patients were receiving monotherapy with carbamazepine (237 patients), phenobarbitone/primidone (72 patients), phenytoin (184 patients) or valproate (228 patients) in low doses, and plasma levels were below the usual optimal range. The most important factor determining seizure recurrence was continued therapy, which was the case for barbiturates, phenytoin and valproate. There was no significant difference for patients taking carbamazepine at randomization, because of a low rate of recurrence in those withdrawing treatment. The difference between carbamazepine and other drugs was not explained by differences in covariate prognostic factors. There was no evidence that withdrawal of phenobarbitone was associated with withdrawal seizures. These data provide unique evidence for the effectiveness of standard antiepileptic drugs as monotherapy. The results for carbamazepine may be open to a number of interpretations.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Anticonvulsants / adverse effects*
  • Anticonvulsants / therapeutic use
  • Carbamazepine / adverse effects
  • Carbamazepine / therapeutic use
  • Child
  • Drug Combinations
  • Epilepsy / drug therapy*
  • Epilepsy / physiopathology
  • Female
  • Humans
  • Male
  • Phenobarbital / adverse effects
  • Phenobarbital / therapeutic use
  • Phenytoin / adverse effects
  • Phenytoin / therapeutic use
  • Primidone / adverse effects
  • Primidone / therapeutic use
  • Proportional Hazards Models
  • Recurrence
  • Risk Assessment
  • Seizures / epidemiology*
  • Seizures / physiopathology
  • Substance Withdrawal Syndrome / epidemiology*
  • Substance Withdrawal Syndrome / physiopathology
  • Valproic Acid / adverse effects
  • Valproic Acid / therapeutic use


  • Anticonvulsants
  • Drug Combinations
  • Primidone
  • Carbamazepine
  • Valproic Acid
  • Phenytoin
  • Phenobarbital