The new antiepileptic drugs: scientific review

JAMA. 2004 Feb 4;291(5):605-14. doi: 10.1001/jama.291.5.605.


Context: The past decade has brought many advances to the treatment of epilepsy, including many new pharmacological agents. Primary care physicians often care for patients with epilepsy and therefore should be familiar with the new options available.

Objective: To review data regarding the efficacy and tolerability of antiepileptic drugs introduced in the past decade.

Data sources: A search of the Cochrane Central Register of Controlled Trials was performed to identify all published human and English-language randomized controlled trials evaluating the efficacy and tolerability of the antiepileptic drugs that have been approved for use in the United States since 1990. Additional reports evaluating pharmacokinetic properties were identified through a MEDLINE search as well as review of article bibliographies.

Study selection and data extraction: Search terms included felbamate, gabapentin, lamotrigine, topiramate, tiagabine, levetiracetam, oxcarbazepine, and zonisamide. Studies were selected if efficacy and tolerability were reported as major outcome measures. Included studies (n = 55) enrolled a minimum of 20 adult subjects and had a treatment period of at least 6 weeks.

Data synthesis: Eight new antiepileptic drugs have been approved for use in the United States in the past decade. Each new antiepileptic drug is well tolerated and demonstrates statistically significant reductions in seizure frequency over baseline. No randomized controlled trials have compared the new antiepileptic drugs with each other or against the traditional antiepileptic drugs. Although there is no evidence to suggest that the newer medications are more efficacious, several studies have demonstrated broader spectrum of activity, fewer drug interactions, and overall better tolerability of the new agents.

Conclusions: New antiepileptic drugs offer many options in the treatment of epilepsy, each with unique mechanisms of action as well as adverse effect profiles. The new antiepileptic drugs are well tolerated with few adverse effects, minimal drug interactions, and a broad spectrum of activity.

Publication types

  • Review

MeSH terms

  • Acetates / therapeutic use
  • Amines*
  • Anticonvulsants / pharmacology*
  • Anticonvulsants / therapeutic use*
  • Carbamazepine / analogs & derivatives*
  • Carbamazepine / therapeutic use
  • Cyclohexanecarboxylic Acids*
  • Felbamate
  • Fructose / analogs & derivatives*
  • Fructose / therapeutic use
  • Gabapentin
  • Humans
  • Isoxazoles / therapeutic use
  • Lamotrigine
  • Levetiracetam
  • Nipecotic Acids / therapeutic use
  • Oxcarbazepine
  • Phenylcarbamates
  • Piracetam / analogs & derivatives*
  • Piracetam / therapeutic use
  • Propylene Glycols / therapeutic use
  • Tiagabine
  • Topiramate
  • Triazines / therapeutic use
  • Zonisamide
  • gamma-Aminobutyric Acid*


  • Acetates
  • Amines
  • Anticonvulsants
  • Cyclohexanecarboxylic Acids
  • Isoxazoles
  • Nipecotic Acids
  • Phenylcarbamates
  • Propylene Glycols
  • Triazines
  • Topiramate
  • Fructose
  • Carbamazepine
  • Levetiracetam
  • Zonisamide
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Lamotrigine
  • Oxcarbazepine
  • Felbamate
  • Tiagabine
  • Piracetam