Discontinuing antiepileptic drugs in patients who are seizure free on monotherapy

Abstract

Objectives: To assess the recurrence rate of epilepsy attributable to discontinuation of treatment in seizure free patients and to identify the risk factors for recurrence. Methods: 330 patients referred to an epilepsy centre who were seizure free for at least 2 years while on stable monotherapy were the study population. Discontinuation of antiepileptic drugs (AEDs) was proposed to all eligible patients or to their carers after discussion of the risks and benefits. Depending on whether they accepted or refused treatment withdrawal, the patients were stratified into two cohorts and followed up until seizure relapse or 31 March 1999, whichever came first. For each patient, records were taken of the main demographic and clinical variables. Results: The sample comprised 225 patients who entered the discontinuation programme and 105 who decided to continue treatment. Twenty nine patients (28%) continuing treatment had a relapse, compared with 113 (50%) of those entering the withdrawal programme. For patients continuing treatment, the probability of remission was 95% at 6 months, 91% at 12 months, 82% at 24 months, 80% at 36 months, and 68% at 60 months. The corresponding values for patients discontinuing treatment were 88%, 74%, 57%, 51%, and 48%. After adjusting for the principal prognostic factors, in patients discontinuing AEDs the risk of seizure relapse was 2.9 times that of patients continuing treatment. A relation was also found between relapse and duration of active disease, number of years of remission while on treatment, and abnormal psychiatric findings. Conclusions: Seizure free referral patients on stable monotherapy who elect to withdraw drug treatment are at higher risk of seizure relapse compared with patients continuing treatment. Severity of disease and seizure free period are significant prognostic factors. I n patients with epilepsy who are seizure free for a period while on antiepileptic drugs (AEDs), the question arises whether treatment can be withdrawn. The decision to discontinue AEDs is based on the chance of remaining seizure free after drug withdrawal, the presence of factors predictive of a higher risk of seizure recurrence, and the medical and social consequences of the withdrawal compared with continuation of treatment. The risk of seizure relapse after withdrawal of AEDs has been estimated at from 10% to 70% depending on the method and design of the studies. Based on a meta-analysis of the literature, 1 the risk of relapse after drug withdrawal was 25% at 1 year and 29% at 2 years. Several factors have been implicated in the risk of relapse, including age at onset of seizures, 2-7 age at treatment withdrawal, The risk of seizure relapse attributable to drug discontinuation is less well defined. The only study comparing continued antiepileptic treatment and drug withdrawal showed that 78% of patients continuing and 59% of those stopping AEDs remained seizure free two years after randomisation. 11 In that study the patients were enrolled regardless of whether they were taking one or mor...

Early withdrawal of non-anesthetic antiepileptic drugs after successful termination of nonconvulsive seizures and nonconvulsive status epilepticus

“…While some studies show that within the NCS/NCSE group, subjects with generalized ictal discharges had a worse prognosis compared to subjects with unilateral ictal discharges [34], others did not find any prognostic correlation with abnormal or epileptiform EEG [31]. In the context of AED withdrawal, a number of studies have identified factors associated with increased risk of relapse including multiple seizure types, focal epileptiform abnormalities on EEG, and worsening EEG patterns after AED discontinuation [29,[35][36][37]. While we did not analyze outcomes based on NCS/NCSE subtypes, we did find that the primary background EEG abnormality was similar to previously published studies and did not differ between the wean and non-wean groups.…”

“…In these instances, the bias is toward an increased risk of seizure recurrence following AED discontinuation [28]. Both randomized controlled trials and prospective studies have demonstrated that adult patients with known epilepsy who continue AED treatment have relapse rates of 22-28%, compared with 41-50% in withdrawal groups [29,30] although lower seizure relapse rates of 15% have been reported in AED withdrawal groups [31]. Our study found a relapse rate of approximately 15% overall (17% and 13% in wean and non-wean groups, respectively) during the remainder of hospitalization after a seizure-free interval of at least 24 h. This lower rate compared to outpatient studies may be due, in part, to the shorter monitoring period which, by default, does not account for the long-term follow up times that were used in the outpatient population.…”

Changes in medication associated with epilepsy‐related hospitalisation: a case‐crossover study

“…Based on a metaanalysis, the risk of relapse after AED withdrawal was 25% after 1 year and 29% at 2 years. 21 Specchio et al 22 found that the risk of seizure relapse after discontinuing treatment was 2.9 times that of patients continuing treatment. Our study supports the evidence of the difficulties that are associated with discontinuing AEDs.…”

Stay, Hit, or Fold? What Do you Do If the Treatment May be as Bad as the Problem—Results of a Q-PULSE Survey

“…Complications from longstanding treatment with some AEDs are well described, but relatively few studies exist to establish the risks of tapering AEDs in medically managed seizure-free adults (1)(2)(3)(4)(5). A systematic meta-analysis has identified a relapse rate of 29% (5), whereas the prospective studies have identified relapse rates of 27 to 52 percent (1)(2)(3)(4).…”

“…A systematic meta-analysis has identified a relapse rate of 29% (5), whereas the prospective studies have identified relapse rates of 27 to 52 percent (1)(2)(3)(4). Literature reviews on this topic have occurred in the past (6)(7)(8), and the relative safety of withdrawal of AEDs in the setting of 2 or more years of seizure freedom has been reported.…”