Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy

Abstract

To update the 2004 American Academy of Neurology (AAN) guideline for managing treatment-resistant (TR) epilepsy with second- and third-generation antiepileptic drugs (AEDs). 2004 criteria were used to systematically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. Forty-two articles were included. 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-Gastuat 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 to 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 to 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 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.

Pharmacological Treatment of Epilepsy in Elderly Patients

“… 26 According to the AES/AAN guideline, LTG (Level B) should and GBP (Level C) may be considered in patients aged ≥60 years with new-onset focal epilepsy. 27 A randomized, double-blind trial showed that the seizure-freedom rate did not differ significantly among CBZ, LTG, and LEV treatments. 35 In the Keppra vs.…”

“…The International League Against Epilepsy (ILAE) and the American Epilepsy Society/American Academy of Neurology (AES/AAN) recommended lamotrigine (LTG) and gabapentin (GBP) as efficacious monotherapies for newly diagnosed and untreated focal seizures based on strong evidence ( Table 1 ). 26 27 However, there are no guidelines for elderly patients with other types of seizures. Elderly patients are sensitive to the adverse effects of AEDs, and drug compliance in this population is affected more by the adverse effects of AEDs than by their efficacy.…”

Recommendations of the Polish Society of Epileptology for the treatment of epileptic seizure in adult patients in Poland: an update

“…Before choosing a third-line medication, it's recommended to consult with a center specializing in epilepsy to verify diagnosis, consider a different combination of AEDs, or consider other non-pharmacological treatments, including neurosurgical treatment. Allocation of the AED to first, second and third line was based on a review of the relevant latest literature on different treatment strategies, level of evidence for AEDs efficacy, international guidelines (Kanner et al, 2018a;2018b), drug status in Poland (registration, availability and reimbursement) and clinical and daily use experience. Each member of the appointed group of experts expressed his/her comments, and after reaching a consensus, recommendations were made.…”

“…The rationale of recommendation of AEDs use was strongly based upon results of recent guidelines in particular prepared by the Sub-Commission of the American Academy of Neurology (AAN) and the American Epilepsy Society (AES) (Kanner et al, 2018a(Kanner et al, , 2018b. Based on the clinical trial methodology, AAN experts identified three categories of recommendation strength (levels A, B and C) for monotherapy in new-onset epi-Joanna Jędrzejczak et al lepsy and add-on therapy in refractory epilepsy.…”

The Effect of Nitrendipine and Levetiracetam in Pentylenetetrazole Kindled Rats

“…According to The Report of the American Epilepsy Society and the Guideline Development as a result of Class I studies, levetiracetam is effective as add-on therapy for treatment of resistant generalize epilepsy with generalize tonic clonic seizures and also addon therapy for treatment of juvenile myoclonic epilepsy and juvenile absence seizures [17] . It has been known that levetiracetam binds the synaptic vesicle protein 2A [18] , the activity of which is related to the exocytosis of transmitter vesicles [19,20] .…”