Withdrawal of antiepileptic drugs: Guidelines of the Italian League Against Epilepsy

Abstract

SUMMARYThe Italian League Against Epilepsy has issued evidence-based guidelines to help practicing physicians in their decision to stop or withhold antiepileptic drugs (AEDs) in patients achieving a prolonged period of seizure freedom. Six adult and two child neurologists, divided into four pairs, critically appraised 128 published reports and provided graded recommendations answering 15 key questions: length of the seizure-free period after treatment initiation, difference in seizure-free periods in children and adults, electroencephalography (EEG) pattern at the time of discontinuation, etiology of epilepsy, seizure type(s), patient's age and sex, family history of epilepsy, history of febrile seizures, epilepsy syndrome, seizure frequency before entering remission, duration of active epilepsy, tapering period, number and type of AEDs taken at time of discontinuation, combination of risk factors for recurrence, and length of patient monitoring after treatment discontinuation. Based on the available data, the following recommendations can be outlined: (1) antiepileptic treatment might be discontinued after a minimum period of 2 years of seizure freedom; shorter seizure-free periods are associated to a higher risk of relapse; (2) in children, AED discontinuation could be considered after less than two seizurefree years because of a marginally higher risk of relapse for early withdrawal; (3) factors, such as abnormal EEG (including epileptiform abnormalities) at the time of treatment discontinuation, a documented etiology of seizures (including mental retardation, perinatal insults, and abnormal neurologic examination), partial seizures, or an older age at disease onset, enhance the risk of relapse; however, patients should not be encouraged to withhold treatment unless a combination of two or more of these factors is present; (4) female sex, family history of epilepsy, history of febrile seizures, disease length/severity, and number and type of drugs taken should not influence the decision to stop treatment; (5) epilepsy syndrome should be always included in the decision process; (6) slow (at least 6 months) AED discontinuation should be encouraged; in any case the duration of the tapering period should be tailored to the patient's needs and preference; and (7) patient discontinuing treatment should be followed for no <2 years. As a general habit, the decision to stop treatment should be discussed and shared with each patient, taking into account social and personal complications of a seizure relapse and the medical complications of chronic AED treatment.

Seponering av antiepileptika ved anfallsfrihet – når og hvordan?

“…Når man skal vurdere seponering, er det viktig å ta hensyn til faktorer som øker risikoen og til faktorer som reduserer risikoen for tilbakefall -alder ved epilepsidebut, epilepsiårsak, epilepsiform, EEG-funn og nevrologiske og utviklingsmessige tilleggsvansker, jf. ramme 1 -4 (14,22,27).…”

Practice Current: When do you stop antiepileptic drugs in patients with genetic generalized epilepsies and in those with focal epilepsies?

“…17 It is widely accepted in the literature that the presence of focal seizures carries a higher risk of recurrence after AED withdrawal. 18 Most studies, though, describe a heterogeneous population of patients with localization-related epilepsy and do not exclude patients with a known cause (either structural or genetic) from their analysis.…”

EEG in children, in the laboratory or at the patient's bedside

“…The timing of an EEG before and after eventual AED withdrawal depends on the epileptic syndrome (e.g. no systemic EEG follow-up in benign epilepsy with centrotemporal spikes in the absence of new clinical signs; EEG performed 3 to 6 months after AED withdrawal in childhood absence epilepsy) [8].…”