Andres M Kanner1, Eric Ashman1, David Gloss1, Cynthia Harden1, Blaise Bourgeois1, Jocelyn F Bautista1, Bassel Abou-Khalil1, Evren Burakgazi-Dalkilic1, Esmeralda Llanas Park1, John Stern1, Deborah Hirtz1, Mark Nespeca1, Barry Gidal1, Edward Faught1, Jacqueline French1. 1. From Miller School of Medicine (A.M.K.), University of Miami, FL; Bronson Methodist Hospital (E.A.), Kalamazoo, MI; Charleston Area Medical Center (D.G.), Charleston, WV; Mount Sinai Beth Israel (C.H.), New York, NY; Children's Hospital, Harvard Medical School (B.B.), Boston, MA; Cleveland Clinic Foundation (J.F.B.), OH; Department of Neurology (B.-A.K.), School of Medicine, Nashville, TN; Cooper Medical School (E.B.-D.), Rowan University, Cherry Hill, NJ; Alexian Brothers Medical Group (E.L.P.), Hoffman Estates, IL; School of Medicine (J.S.), University of California in Los Angeles; University of Vermont Medical Center (D.H.), Burlington; Children's Hospital (M.N.), University of California San Diego School of Medicine; School of Pharmacy (B.G.), University of Wisconsin, Madison; Emory University School of Medicine (E.F.), Atlanta, GA; and New York University (J.F.), New York.
Abstract
OBJECTIVE: To update the 2004 American Academy of Neurology guideline for managing treatment-resistant (TR) epilepsy with second- and third-generation antiepileptic drugs (AEDs). METHODS: 2004 criteria were used to systemically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. RESULTS: Forty-two articles were included. RECOMMENDATIONS: The following are established as effective to reduce seizure frequency (Level A): immediate-release pregabalin and perampanel for TR adult focal epilepsy (TRAFE); vigabatrin for TRAFE (not first-line treatment); rufinamide for Lennox-Gastaut syndrome (LGS) (add-on therapy). The following should be considered to decrease seizure frequency (Level B): lacosamide, eslicarbazepine, and extended-release topiramate for TRAFE (ezogabine production discontinued); immediate- and extended-release lamotrigine for generalized epilepsy with TR generalized tonic-clonic (GTC) seizures in adults; levetiracetam (add-on therapy) for TR childhood focal epilepsy (TRCFE) (1 month-16 years), TR GTC seizures, and TR juvenile myoclonic epilepsy; clobazam for LGS (add-on therapy); zonisamide for TRCFE (6-17 years); oxcarbazepine for TRCFE (1 month-4 years). The text presents Level C recommendations. AED selection depends on seizure/syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. This evidence-based assessment informs AED prescription guidelines for TR epilepsy and indicates seizure types and syndromes needing more evidence. A recent Food and Drug Administration (FDA) strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years of age and perampanel as monotherapy received FDA approval.
OBJECTIVE: To update the 2004 American Academy of Neurology guideline for managing treatment-resistant (TR) epilepsy with second- and third-generation antiepileptic drugs (AEDs). METHODS: 2004 criteria were used to systemically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. RESULTS: Forty-two articles were included. RECOMMENDATIONS: The following are established as effective to reduce seizure frequency (Level A): immediate-release pregabalin and perampanel for TR adult focal epilepsy (TRAFE); vigabatrin for TRAFE (not first-line treatment); rufinamide for Lennox-Gastaut syndrome (LGS) (add-on therapy). The following should be considered to decrease seizure frequency (Level B): lacosamide, eslicarbazepine, and extended-release topiramate for TRAFE (ezogabine production discontinued); immediate- and extended-release lamotrigine for generalized epilepsy with TR generalized tonic-clonic (GTC) seizures in adults; levetiracetam (add-on therapy) for TR childhood focal epilepsy (TRCFE) (1 month-16 years), TR GTC seizures, and TR juvenile myoclonic epilepsy; clobazam for LGS (add-on therapy); zonisamide for TRCFE (6-17 years); oxcarbazepine for TRCFE (1 month-4 years). The text presents Level C recommendations. AED selection depends on seizure/syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. This evidence-based assessment informs AED prescription guidelines for TR epilepsy and indicates seizure types and syndromes needing more evidence. A recent Food and Drug Administration (FDA) strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years of age and perampanel as monotherapy received FDA approval.
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