Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: meta-analysis of controlled trials

Epilepsia. 2001 Apr;42(4):515-24. doi: 10.1046/j.1528-1157.2001.28900.x.


Purpose: To synthesize evidence concerning the effect of antiepileptic drugs (AEDs) for seizure prevention and to contrast their effectiveness for provoked versus unprovoked seizures.

Methods: Medline, Embase, and The Cochrane Clinical Trials Register were the primary sources of trials, but all trials found were included. Minimal requirements: seizure-prevention outcome given as fraction of cases; AED or control assigned by random or quasi-random mechanism. Single abstracter. Aggregate relative risk and heterogeneity evaluated using Mantel-Haenszel analyses; random effects model used if heterogeneity was significant.

Results: Forty-seven trials evaluated seven drugs or combinations for preventing seizures associated with fever, alcohol, malaria, perinatal asphyxia, contrast media, tumors, craniotomy, and traumatic brain injury. Effective: Phenobarbital for recurrence of febrile seizures [relative risk (RR), 0.51; 95% confidence interval (CI), 0.32-0.82) and cerebral malaria (RR, 0.36; CI, 0.23-0.56). Diazepam for contrast media-associated seizures (RR, 0.10; CI, 0.01-0.79). Phenytoin for provoked seizures after craniotomy or traumatic brain injury (craniotomy: RR, 0.42; CI, 0.25-0.71; TBI: RR, 0.33; CI, 0.19-0.59). Carbamazepine for provoked seizures after traumatic brain injury (RR, 0.39; CI, 0.17-0.92). Lorazepam for alcohol-related seizures (RR, 0.12; CI, 0.04-0.40). More than 25% reduction ruled out valproate for unprovoked seizures after traumatic brain injury (RR, 1.28; CI, 0.76-2.16), and carbamazepine for unprovoked seizures after craniotomy (RR, 1.30; CI, 0.75-2.25).

Conclusions: Effective or promising results predominate for provoked (acute, symptomatic) seizures. For unprovoked (epileptic) seizures, no drug has been shown to be effective, and some have had a clinically important effect ruled out.

Publication types

  • Meta-Analysis
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anticonvulsants / therapeutic use*
  • Brain Diseases / complications
  • Brain Injuries / complications
  • Carbamazepine / therapeutic use
  • Controlled Clinical Trials as Topic / statistics & numerical data
  • Diazepam / therapeutic use
  • Epilepsy / etiology
  • Epilepsy / prevention & control*
  • Humans
  • Lorazepam / therapeutic use
  • Models, Statistical
  • Phenobarbital / therapeutic use
  • Phenytoin / therapeutic use
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Risk
  • Seizures / etiology
  • Seizures / prevention & control*
  • Treatment Outcome
  • Valproic Acid / therapeutic use


  • Anticonvulsants
  • Carbamazepine
  • Valproic Acid
  • Phenytoin
  • Lorazepam
  • Diazepam
  • Phenobarbital