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. Discontinuation of anticonvulsant therapy in children with partial epilepsy. Comparison between one and three years of treatment in uncomplicated childhood epilepsy: a prospective study. I. Outcome in different seizure types. The late prognosis of epilepsy in childhood: results of a prospective follow-up study.
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). To evaluate when it is possible to discontinue anticonvulsant treatment in children with cryptogenic partial epilepsy, the authors studied 89 epileptic children divided into two groups: Group A, 45 children whose therapy was discontinued after 1 year from the last seizure; and Group B, 44 children whose therapy was stopped after 2 years from the last seizure. After 5 years of follow-up, the recurrence rate was similar in the two groups of patients (Group A, 28.8%; Group B, 25%). It is safe to discontinue the anticonvulsant therapy in children with cryptogenic partial epilepsy who were seizure free for only 1 year. The main purpose of this prospective study was to analyze whether 1 year of treatment was as effective as 3 years with respect to remission rate in children with idiopathic epilepsy.
                Treatment for epileptic seizures was started in 207 children aged 2-16 years. They were randomized to treatment for 1 or 3 years. At the end of the predetermined treatment period, 161 children had been seizure-free for 6 months and the treatment could be gradually withdrawn.
                The overall remission rate in our group of patients was significantly higher (71%) in the group treated for 3 years than in the group treated for 1 year (53%). However, comparison of remission rates between patients with different seizure types showed statistically significant differences in outcome depending on duration of treatment only in children with complex partial seizures (CPS).
                Our results show that 1 year of treatment can be recommended in children with benign partial epilepsy with rolandic spikes (BECT) and in children with simple partial seizures (SPS) but is clearly insufficient in children with CPS. A proper seizure classification is one important tool, although not sufficient, in offering recommendations concerning the duration of treatment in children with idiopathic epilepsy. 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.
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.