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. Discontinuation of anticonvulsant therapy in children with partial epilepsy. Psychomotor development and minor anomalies in children exposed to antiepileptic drugs in utero: a prospective population-based study. Influence of surgery and antiepileptic drugs on seizures symptomatic of cerebral tumours. Adjunctive lamotrigine for partial seizures in patients aged 1 to 24 months.
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. 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 aim of this study was to assess psychomotor development, using Griffiths' test, and the incidence of minor anomalies at birth in children who had been exposed to antiepileptic drugs (AEDs) in utero. The study sample comprised 100 children of mothers who were treated with AEDs during pregnancy and 100 matched control children. Women with epilepsy were recruited from a pregnant urban population (450 000 inhabitants). The lowest possible dose of the fewest AEDs to maintain seizure control was used. Drug levels were controlled on a monthly basis. The children were assessed at 9 months of age. The study children had a significant increase in the number of minor anomalies (31 compared with 18 control children; odds ratio 2.4, CI 1.15 to 5.02, P=0.02 McNemars test), and an increased number of facial anomalies after carbamazepine exposure (11 compared with six control children). Drug exposure did not influence the Griffiths' score at 9 months of age. Even a meticulous AED treatment strategy during pregnancy increases the number of minor anomalies. However, treatment with AEDs does not necessarily influence short-term psychomotor development. One hundred and twenty-eight adult patients presenting with and operated on for supratentorial neoplasms were studied. Sixty-five had preoperative seizures and were treated with antiepileptic drugs (AEDs). Among the 63 patients without preoperative epileptic fits, 41 were given AEDs (either phenobarbital or phenytoin) as prophylactic treatment and 22 were not treated. The preoperative epilepsy course was considered with respect to tumour site and histological type. Early and late postoperative seizure occurrence was considered in the different groups of patients. The results suggest the usefulness of a short term preventive treatment with AEDs after surgery in patients without preoperative seizures. In patients with preoperative epilepsy, AEDs should be continued after surgery. However long-term AEDs treatment should not be recommended in patients without preoperative epilepsy. In fact, no significant difference in late seizure occurrence was found between preventively treated and untreated patients. This randomized, double-blind, placebo-controlled trial was conducted to assess the efficacy and tolerability of adjunctive lamotrigine for the treatment of partial seizures in infants aged 1 to 24 months.
                The study used a responder-enriched design in which all patients received adjunctive lamotrigine during an open-label phase (n = 177; maximum maintenance dose 5.1 mg/kg/day for those on non-enzyme-inducing antiepileptic drugs [AEDs] or valproate and 15.6 mg/kg/day for those on enzyme-inducing AEDs). Patients meeting response criteria were randomly assigned to double-blind treatment for up to 8 weeks with continued lamotrigine (n = 19) or to withdrawal from lamotrigine (placebo; n = 19) while background AEDs were maintained.
                The proportion of treatment failures (patients who met escape criteria or withdrew before completing the double-blind phase) was lower with lamotrigine (58%) than with placebo (84%). This finding was not significant in the primary analysis (two-sided chi(2) test [primary endpoint]). A post hoc sensitivity analysis of the primary endpoint was also performed (p = 0.045 by one-sided, mid-p corrected Fisher exact test). The median time to meet escape criteria was longer with lamotrigine (42 days) than with placebo (22 days) (p = 0.059). During the last 28 days of the open-label phase, 53% of the patients had a >or=50% reduction in frequency of partial seizures with lamotrigine. Additional reduction in partial seizure frequency was observed during the double-blind phase compared with the last 4 weeks of the open-label phase among those randomly assigned to lamotrigine (32% with a >or=25% reduction) but not those randomly assigned to placebo (5% with a >or=25% reduction). Lamotrigine was well tolerated, with an adverse event profile comparable to that observed in older pediatric patients.
                Lamotrigine was well tolerated, and the data indicate that it may be efficacious in the treatment of partial seizures in infants aged 1 to 24 months.
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.