Updated AAN Guidelines on New Antiepileptic Drugs: 6 Key Recommendations

February 8, 2019

Guidelines from the American Academy of Neurology now cover the use of third-generation antiepileptic drugs for patients with new-onset focal or generalized epilepsy.

The American Academy of Neurology (AAN) has updated its 2004 practice guidelines on the efficacy and tolerability of second- and third-generation antiepileptic drugs (AEDs) in the treatment of new-onset focal or generalized epilepsy.1

The 2004 AAN recommendations covered only seven second-generation AEDs and no third-generation AEDs. The updated guidelines include review of relevant research on the following drugs: clobazam, lacosamide, perampanel, topiramate, eslicarbazepine, lamotrigine, pregabalin, vigabatrin, felbamate, levetiracetam, rufinamide, zonisamide, gabapentin, oxcarbazepine, and tiagabine.

The guidelines also cover recently FDA-approved AEDs, including two older AEDS (clobazam and vigabatrin), which have been used in other countries for some time and were recently approved in the United States for treating some types of epilepsy. Because of a new FDA policy that allows extrapolation of efficacy across populations, eslicarbazepine and lacosamide (oral only for children) were approved as monotherapy for focal epilepsy in individuals aged 4 years and over, while perampanel was approved as monotherapy.

To update the guidelines, the AAN brought together an expert panel that reviewed recent studies and analyzed the evidence.

Key recommendations

Key recommendations for patients with new-onset focal epilepsy or unclassified tonic-clonic seizures include:

• Consider lamotrigine as monotherapy in adults with new-onset focal epilepsy (level B)

• Consider lamotrigine (level B) and gabapentin (level C) in individuals ≥ 60 yrs

- In pediatric absence seizures, consider ethosuximide or valproic acid before lamotrigine, unless there are over-riding concerns about adverse effects (level B)

Levetiracetam may be considered (level C)

• Zonisamide may be considered (level C)

• Vigabatrin appears to be less efficacious than immediate-release carbamazepine and may not be offered (level C)

- Do not use vigabatrin as first-line therapy because of serious adverse effects

• 150 mg/d of pregabalin may be less efficacious than 100 mg/d of lamotrigine (level C)

In addition, the committee found insufficient evidence to consider gabapentin, oxcarbazepine, or topiramate over carbamazepine (level U); and topiramate over phenytoin (level U). Not enough data are available to make a recommendation regarding third-generation AEDs, clobazam, felbamate, or vigabatrin in treating new-onset epilepsy (level U), or newer AEDs in unclassified generalized tonic-clonic seizures (level U).

The committee concluded: “Felbamate and vigabatrin are not recommended in new-onset epilepsy for clinical use due to serious adverse events, as there are other agents that are both safe and efficacious.”1

Take-home points

• The AAN has updated 2004 guidelines on the use of new AEDs in new-onset epilepsy

• In this setting, lamotrigine can be considered as monotherapy in adults; lamotrigine and gabapentin should be considered in individuals aged 60 and over

• Levetiracetam and zonisamide may also be considered

• In pediatric absence seizures, ethosuximide or valproic acid should be considered before lamotrigine, unless adverse effects are a concern

• Felbamate and vigabatrin should not be used in new-onset epilepsy because of serious adverse events


1. Kanner AM, Ashman E, Gloss D, et al. Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2018;91:74-81. doi: 10.1212/WNL.0000000000005755.