Randomized prospective study of early discontinuation of antiepileptic drugs in children with epilepsy. Psychomotor development and minor anomalies in children exposed to antiepileptic drugs in utero: a prospective population-based study. Long-term neuropsychological consequences of maternal epilepsy and anticonvulsant treatment during pregnancy for school-age children and adolescents. Enhancing antiepileptic drug adherence: a randomized controlled trial. Systematic screening allows reduction of adverse antiepileptic drug effects: a randomized trial. Discontinuing antiepileptic drugs in children with epilepsy. A comparison of a six-week and a nine-month taper period. A multicenter randomized controlled trial on the clinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy. The Italian TDM Study Group in Epilepsy. Psychomotor development in preschool children exposed to antiepileptic drugs in utero. Comparison of antiepileptic drugs on cognitive function in newly diagnosed epileptic children: a psychometric and neurophysiological 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. 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. Antiepileptic drugs (AEDs) are potential teratogenic agents. The purpose of this study was to examine the long-term effects of intrauterine AED exposure on neurologic and psychological functioning.
                Of a prospective study, "Epilepsy, pregnancy, and child development," children could be retraced at school age and adolescence. Sixty-seven were born to mothers with epilepsy [no drugs during pregnancy (n = 13), monotherapy (n = 31), polytherapy (n = 23)]; 49 were nonafflicted control children. Assessments included an intelligence test (Wechsler), a neurologic examination (Touwen), and an EEG. Data analyses were performed, controlling for parental social status, type of maternal drug therapy and drug dosage, type of epilepsy, frequency of seizures during pregnancy, the original subgroups, and specific drug effects.
                Type of maternal epilepsy and type and kind of AED therapy, but not maternal seizures during pregnancy correlated with an increase in abnormal EEG patterns. Minor neurologic dysfunction was diagnosed, with increased frequency from the control to the risk/no drug or monotherapy to the polytherapy group. The compromised intelligence score of the polytherapy group was primarily due to those children who had been exposed to primidone (PRM). Level of IQ was negatively associated with PRM dosage.
                Maternal epilepsy and AED therapy during pregnancy appear to have long-term effects on the offspring well into adolescence, as evinced in EEG patterns, minor neurologic dysfunction, and intellectual performance. Severity of effects increased from control group to epilepsy/no-drug group to monotherapy group and was most marked in the polytherapy group. These group differences are assumed to reflect differential neural vulnerability to social and family factors. 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. To determine the effectiveness of systematic screening with a brief 19-item self-report instrument, the Adverse Events Profile (AEP), to reduce adverse effects of antiepileptic drugs (AEDs) and improve subjective health status.
                The authors performed a prospective randomized trial comparing the use of the AEP with usual care without the AEP. Sixty-two patients with an AEP score of >or=45 were enrolled from a consecutive group of 200 consenting adults with epilepsy.
                The mean percent improvement in AEP scores was greater in the patient group for which clinicians received the AEP compared with the usual care group (25% vs 5%; p < 0.01). Mean change in Quality of Life in Epilepsy Inventory (QOLIE)-89 total scores was not different between groups, but for the entire sample QOLIE-89 change was greater for patients having a 15-point improvement in AEP scores than for those with a 0- to 15-point improvement or a worsened score (24 vs 12 vs 3; analysis of variance, p < 0.008). More patients in the AEP group had a >15-point improvement in QOLIE-89 score (p < 0.03). Use of the AEP was associated with a 2.8-fold increase (95% CI, 1.7 to 4.8) in AED modifications. No difference in seizure rates was observed. Conclusions: Systematic screening for antiepileptic drug side effects may increase identification of toxicity and guide medication changes to reduce adverse effects and possibly improve subjective health status. 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 assess the clinical impact of monitoring serum concentrations of antiepileptic drugs (AEDs) in patients with newly diagnosed epilepsy.
                One-hundred eighty patients with partial or idiopathic generalized nonabsence epilepsy, aged 6 to 65 years, requiring initiation of treatment with carbamazepine (CBZ), valproate (VPA), phenytoin (PHT), phenobarbital (PB), or primidone (PRM) were randomly allocated to two groups according to an open, prospective parallel-group design. In one group, dosage was adjusted to achieve serum AED concentration within a target range (10-20 microg/ml for PHT, 15-40 microg/ml for PB, 4-11 microg/ml for CBZ, and 40-100 microg/ml for VPA), whereas in the other group, dosage was adjusted on clinical grounds. Patients were followed up for 24 months or until a change in therapeutic strategy was clinically indicated.
                Baseline characteristics did not differ between the two groups. Most patients with partial epilepsy were treated with CBZ, whereas generalized epilepsies were most commonly managed with PB or VPA. PHT was used only in a small minority of patients. A total of 116 patients completed 2-year follow-up, and there were no differences in exit rate from any cause between the monitored group and the control group. The proportion of assessable patients with mean serum drug levels outside the target range (mostly below range) during the first 6 months of the study was 8% in the monitored group compared with 25% in the control group (p < 0.01). There were no significant differences between the monitored group and the control group with respect to patients achieving 12-month remission (60% vs. 61%), patients remaining seizure free since initiation of treatment (38% vs. 41%), and time to first seizure or 12-month remission. Frequency of adverse effects was almost identical in the two groups.
                Only a small minority of patients were treated with PHT, the drug for which serum concentration measurements are most likely to be useful. With the AEDs most commonly used in this study, early implementation of serum AED level monitoring did not improve overall therapeutic outcome. and the majority of patients could be satisfactorily treated by adjusting dose on clinical grounds. Monitoring the serum levels of these drugs in selected patients and in special situations is likely to be more rewarding than routine measurements in a large clinic population. The aim of this study was to assess psychomotor development with the Griffiths' test in preschool children exposed to antiepileptic drugs (AED) in utero. The study sample consisted of 76 children exposed to AED in utero and 71 unexposed children. The children (exposed and unexposed) have since birth been included in a population-based longitudinal follow-up study of children born to women with meticulously treated epilepsy during pregnancy, initiated in 1985. In total, 67 exposed and 66 unexposed children were tested with the Griffiths' test, which consists of 6 subsets: locomotor function, personal and social behaviour, hearing and speech, eye and hand coordination, performance, and practical reasoning. There was no significant difference in the global scores of the Griffiths' test between the two groups of children. Children exposed to phenytoin in utero (n = 16) showed a significant but subtle reduction in the scores for locomotor development compared with the unexposed children (mean scores: 98 vs 106: 95% confidence interval for the difference in mean scores: -14.0 to -0.4). There was no such difference for the children exposed to carbamazepine in utero (n = 35). The exposed children had significantly fewer siblings (p < 0.01). A significant number of the mothers with AED treatment had no higher level of education than compulsory school (p < 0.01). No other differences in socioeconomic status were observed between the groups. Conclusion: The subtle delay in locomotor development evaluated with the Griffiths' test at 4.5-5 y of age in children exposed to phenytoin may indicate a subtle influence on psychomotor development, which may be more obvious at school age: thus, larger studies and further follow-up are warranted. Using a randomized parallel group study design, we compared the cognit ive effects of carbamazepine (CBZ), phenobarbital (PB), and valproate (VPA) in children with epilepsy. Seventy-three children with newly diagnosed epilepsy were tested with the Wechsler Intelligence Scale for Children-Revised (WISC-R), Bender-Gestalt test, and auditory event-related potentials (P 300) before and 6 and 12 months after antiepileptic drug (AED) treatment. There were no significant differences in WISC-R IQs and Bender-Gestalt scores for children in any group at any of the three sessions. P 300 latencies were increased in the children receiving PB but not in children receiving CBZ and VPA. P 300 amplitudes were significantly reduced in treated children in all three groups, but amplitudes were not significantly different among the three groups. These findings suggest that PB may affect cognitive function of epileptic children and that the P 300 may be a sensitive additional procedure that can be used to assess the cognitive effect of AEDs.
In view of methodological deficiencies and small sample size, in the solitary study identified, we cannot derive any reliable conclusions regarding the optimal rate of tapering of AEDs. Further studies are needed in adults as well as in children to investigate the rate of withdrawal of AEDs and to study the effects of variables such as seizure types, its aetiology, mental retardation, EEG abnormalities, presence of neurological deficits and other co-morbidities on the rate of tapering.