Randomized prospective study of early discontinuation of antiepileptic drugs in children with epilepsy. Discontinuing anti-epileptic medication(s) in epileptic children: 18 versus 24 months. The late prognosis of epilepsy in childhood: results of a prospective follow-up study. Enhancing antiepileptic drug adherence: a randomized controlled trial. Discontinuing antiepileptic drugs in children with epilepsy. A comparison of a six-week and a nine-month taper period.
We studied recurrence rate, risk factors for recurrence, and outcome after recurrence in children after early withdrawal of antiepileptic drugs (AEDs). One hundred sixty-one children with newly diagnosed epilepsy who had become seizure free within 2 months after starting treatment and remained so for 6 months were randomly assigned to immediate withdrawal of AEDs (n = 78) or continuation of treatment for another 6 months followed by withdrawal (n = 83). The probability of remaining seizure free at 24 months after randomization was 51% (95% CI, 40 to 62) in Group A and 52% (41 to 63) in Group B. Significant predictive factors for relapse were partial epilepsy, seizure onset at 12 years or older, defined etiology, and epileptiform EEG before randomization. At the end of follow-up (median, 41.9 months), 129 children (80.6%) had a terminal remission of at least 1 year, 88 without AEDs and 41 with AEDs. No significant difference in outcome was found between Groups A and B. In children with epilepsy and an early response to therapy, AED withdrawal after 6 or 12 months of treatment leads to seizure recurrence in approximately half of all patients regardless of the duration of therapy. More than 60% of those with one or more recurrences reach a terminal remission of at least 1 year after long-term follow-up with or without AEDs. For a period of slightly over 4 years, 80 children who had been seizure-free for at least 18 months while on anti-convulsant medication were prospectively collected. These 80 children were randomly assigned to either the 18-months seizure-free group (n = 41) or to the group where anti-convulsant medications were continued for another 6 months before they were gradually tapered off and stopped, i.e. the 24-months seizure-free group (n = 39). Twelve (29%) of the 41 children who had been seizure-free for 18 months and 14 (36%) of the 39 children who had been seizure-free for 24 months had seizure recurrence during the follow-up period. Log-rank test of the recurrence experience of the two groups of patients showed no statistically significant difference between the groups (p > 0.50). Similarly, when both groups were combined and other risk variables likely to influence the rate of seizure recurrence were tested, only EEG abnormality at discontinuation of anti-convulsant medication had a significant association with the risk of seizure recurrence (p < 0.001). By means of a prospective study, relapse after discontinuation of antiepileptic drug treatment in 433 children with epilepsy and 40 patients who were treated after the first seizure was investigated. Independent of the electroencephalographic findings, the age of the patients, and other factors, the antiepileptic drugs were reduced during 1, 3, 6, and 12 months after 2, 3, and 4 seizure-free years; and in children with absences after 1, 2, 3, and 4 seizure-free years. The observation period after stopping therapy was at least 3 (on average, 5-6) years. In 157 of 433 children (36.3%) and 5 of 40 patients (12.5%), relapses occurred during this time. More than half (61.8%) of the relapses occurred during the withdrawal period or within 3 months: altogether, 86% within 1 year after discontinuation of therapy. Eighty-six percent of these patients again became free from seizures on administration of the original therapy. The dependence on predictive factors of the rate of relapse was tested by multivariate statistical analysis. There was a pronounced significant dependence on the duration of the seizure-free period, the duration of the withdrawal period, the length of illness, the frequency and duration of seizures, and the presence of paroxysmal activity in the EEG at the start of the discontinuation of antiepileptic drug treatment. The stopping of therapy during the pubertal period did not present a higher risk. Suboptimal adherence to antiepileptic drug (AED) treatment is commonplace, and increases the risk of status epilepticus and sudden unexplained death in epilepsy. This randomized controlled trial was designed to demonstrate whether an implementation intention intervention involving the completion of a simple self-administered questionnaire linking the intention of taking medication with a particular time, place, and other activity can improve AED treatment schedule adherence. Of the 81 patients with epilepsy who were randomized, 69 completed a 1-month monitoring period with an objective measure of tablet taking (electronic registration of pill bottle openings, Medication Event Monitoring System [MEMS]). Intervention participants showed improved adherence relative to controls on all three outcomes: doses taken in total (93.4% vs. 79.1%), days on which correct dose was taken (88.7% vs. 65.3%), and doses taken on schedule (78.8% vs. 55.3%) (P<0.01). The implementation intention intervention may be an easy-to-administer and effective means of promoting AED adherence. The optimal regimen for discontinuing antiepileptic medications in children with epilepsy is unknown.
                We randomly assigned 149 children to either a six-week or a nine-month period of drug tapering, after which therapy was discontinued. Each group was composed of patients who had been seizure-free for either two or four years before drug tapering was begun. Most patients were receiving one antiepileptic drug; none were taking more than two. The children were evaluated periodically during and after the taper period. Sixteen patients were lost to follow-up before the beginning of the taper period. Proportional-hazards regression analysis was used to assess the risk of seizure recurrence among the remaining 133 patients.
                Seizures recurred in 53 patients (40 percent). The mean duration of follow-up was 39 months (range, 11 to 105) for the patients who did not have a recurrence of seizures. Neither the length of the taper period (six weeks vs. nine months, P = 0.38) nor the length of time the patients were free of seizures before the taper period was begun (two years vs. four years, P = 0.20) significantly influenced the risk of seizure recurrence. The presence of mental retardation (relative risk, 3.1, 95 percent confidence interval, 1.5 to 6.2) or spikes in the electroencephalogram at the time of tapering (relative risk, 1.9, 95 percent confidence interval, 1.0 to 3.4) increased the risk of seizure recurrence.
                The risk of seizure recurrence during drug tapering and after the discontinuation of antiepileptic drug therapy in children with epilepsy is not different whether the medications are tapered over a six-week or a nine-month period.
There is evidence to support waiting for at least two or more seizure free years before discontinuing AEDs in children, particularly if individuals have an abnormal EEG and partial seizures. There is insufficient evidence to establish when to withdraw AEDs in children with generalized seizures. There is no evidence to guide the timing of withdrawal of AEDs in seizure free adults. Further blinded randomized controlled trials are needed to identify the optimal timing of AED withdrawal and risk factors predictive of relapse.