Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment

CNS Drugs. 2017 Nov;31(11):959-974. doi: 10.1007/s40263-017-0480-6.


Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

Publication types

  • Review

MeSH terms

  • Acetamides / adverse effects
  • Acetamides / therapeutic use*
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Dibenzazepines / adverse effects
  • Dibenzazepines / therapeutic use*
  • Drug-Related Side Effects and Adverse Reactions / etiology*
  • Follow-Up Studies
  • Humans
  • Lacosamide
  • Longitudinal Studies
  • Medication Adherence
  • Nitriles
  • Product Surveillance, Postmarketing
  • Pyridones / adverse effects
  • Pyridones / therapeutic use*
  • Pyrrolidinones / adverse effects
  • Pyrrolidinones / therapeutic use*
  • Seizures / drug therapy


  • Acetamides
  • Anticonvulsants
  • Dibenzazepines
  • Nitriles
  • Pyridones
  • Pyrrolidinones
  • Lacosamide
  • eslicarbazepine acetate
  • perampanel
  • brivaracetam