Randomized prospective study of early discontinuation of antiepileptic drugs in children with epilepsy. Enhancing antiepileptic drug adherence: a randomized controlled trial. Outcomes of add-on treatment with lamotrigine in partial epilepsy. Efficacy and cognitive side effects of tiagabine and topiramate in patients with epilepsy. Influence of surgery and antiepileptic drugs on seizures symptomatic of cerebral tumours. Systematic screening allows reduction of adverse antiepileptic drug effects: a randomized trial. Lamotrigine therapy for partial seizures: a multicenter, placebo-controlled, double-blind, cross-over trial. Evaluation of acceptance and commitment therapy for drug refractory epilepsy: a randomized controlled trial in South Africa--a pilot study. Long-term neuropsychological consequences of maternal epilepsy and anticonvulsant treatment during pregnancy for school-age children and adolescents. A randomized, double-blind, placebo-controlled trial of topiramate in adults with epilepsy and intellectual disability: impact on seizures, severity, and quality of life. A randomized, double-blind, placebo-controlled, clinical trial of D-alpha-tocopheryl acetate (vitamin E), as add-on therapy, for epilepsy in children.
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. 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 need for new antiepileptic drugs (AEDs) and more sensitive methods of assessing their efficacy is well recognized. This study was designed to evaluate the efficacy and safety of lamotrigine (LTG), a potential new AED and to develop and test new outcome measures. A health-related quality of life (HRQL) model was developed which contains previously validated measures of anxiety, depression, happiness, overall mood, self-esteem, and mastery and a specifically designed seizure severity scale with patient- and caregiver-based components. This HRQL model was used in a randomized, placebo-controlled, double-blind, cross-over study of LTG in 81 patients with refractory partial seizures. Seizure frequency was the primary measure and seizure severity and the HRQL were secondary measures of efficacy. The reduction in seizure frequency with LTG, relative to placebo, was 29.7% [95% confidence interval (CI) 17.8%, 39.9%] for total seizure count, 33.4% (95% CI 14.8%, 47.9%) for complex partial seizures (CPS) and 20.3% (95% CI 0.3%, 36.2%) for secondarily generalized tonic-clonic seizures (GTCS). However, although 41 patients elected to continue with LTG, only 11 experienced at least 50% reduction in total seizures, indicating that other factors influenced their decision. The score with LTG, relative to placebo, was significantly lower for the ictal (p = 0.017) and caregivers (p = 0.035) subscales of the seizure severity scale and significantly higher for happiness (p = 0.003) and mastery (p = 0.003). Simple correlation and multiple-regression analyses indicate that the effects on seizure frequency, seizure severity, and psychological variables appear to be independent of each other. This study indicates that LTG is effective in reducing seizure frequency and has additional favorable effects on seizure severity, mood, and perceived internal control. Some of the scales used indicate the potential of secondary measures of efficacy to enhance the sensitivity of trials of new AEDs. Whereas the efficacy of the newer antiepileptic drugs (AEDs) is well established, there remain questions regarding their cognitive side effects. Therefore, we performed a comparative open randomized trial with TPM and TGB as add-on therapy, with particular consideration of cognition, mood, and health-related quality of life (HRQOL).
                Forty-one patients with refractory epilepsy were randomly assigned to one of the two treatment groups (TPM vs TGB) and received neuropsychological testing at baseline (T1), after titration (3 months, T2), and during the maintenance phase (another 3 months, T3). Tests included measures of intelligence, attention, working memory, episodic memory, language, and self-report questionnaires regarding mood and HRQOL. Twenty patients (8 TPM, 12 TGB) discontinued the trial for different reasons (no group difference).
                Seizure outcome (intention-to-treat analysis) was comparably good in both groups (8.1% seizure free, 29.7% seizure reduction>50%). From baseline to after the titration paired sample t tests revealed significant deterioration in verbal fluency, language comprehension, working memory, and visual block tapping under TPM and a deterioration in verbal memory (delayed free recall) in the TGB group. These functions remained stable in the maintenance phase. Self-report measures initially indicated concerns about AED side effects in both groups and concerns about worse cognitive functioning and depression under TPM. In the maintenance phase the TGB group reported feeling a lack of energy, whereas patients on TPM demonstrated improvement on all QOLIE scales on a descriptive level.
                This study demonstrates the comparable efficacy of TPM and TGB. Consistent with previous reports, TPM but not TGB appears to be associated with persistent negative cognitive side effects on frontal lobe-associated functions, the degree of which may be estimated by the fact that this effect was observed with a very small sample size. In contrast, in patients taking TPM, initially negatively affected HRQOL returns to baseline in the long run on a descriptive level. The latter finding may be interpreted in accordance with the observation that objective performance and subjective self-report under TPM can be dissociated. 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. 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 efficacy and safety of lamotrigine (LTG), a new antiepileptic drug (AED), were evaluated in a multicenter, randomized, double-blind, placebo-controlled, cross-over study of 98 patients with refractory partial seizures. Each treatment period lasted 14 weeks. Most patients were titrated to a LTG maintenance dose of 400 mg/day. Seizure frequency with LTG decreased by > or = 50%, as compared with placebo, in one fifth of patients. Overall median seizure frequency decreased by 25% with LTG as compared with placebo (p < 0.001). With LTG, the number of seizure days decreased by 18% as compared with placebo (p < 0.01), and investigator global evaluation of overall patient clinical status favored LTG by 2:1 (p = 0.013). Plasma LTG concentrations appeared to be linearly related to dosage. LTG had no clinically important effects on the plasma concentrations of concomitant AEDs. Adverse experiences were generally minor and most frequently were CNS-related (e.g., ataxia, dizziness, diplopia, headache). Most were transient and resolved without discontinuing treatment. Five patients withdrew as a result of adverse experiences while receiving LTG, including 3 patients with rash. One placebo patient was also withdrawn because of rash. The addition of twice-daily LTG to an existing AED regimen was safe, effective, and well tolerated in these medically refractory partial seizure patients. Psychological interventions in the treatment of epilepsy have been developed and evaluated for many years but the amount of research has hardly made an impact on how epilepsy is treated. The purpose of this study was to develop and evaluate a psychological treatment program consisting of acceptance and commitment therapy (ACT) together with some behavioral seizure control technology shown to be successful in earlier research.
                The method consisted of a randomized controlled trial group design with repeated measures (n=27). All participants had an EEG verified epilepsy diagnosis with drug refractory seizures. Participants were randomized into one of two conditions, ACT or supportive therapy (ST). Therapeutic effects were measured by examining changes in quality of life (SWLS and WHOQOL) and seizure index (frequency x duration). Both treatment conditions consisted of only nine hours of professional therapy distributed in two individual and two group sessions during a four-week period.
                The results showed significant effects over all of the dependent variables for the ACT group as compared to the ST group at six- and twelve-month follow-ups.
                The results from this study suggest that a short-term psychotherapy program combined with anticonvulsant drugs may help to prevent the long-term disability that occurs from drug refractory seizures. 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. This randomized, double-blind, placebo-controlled UK trial evaluated the effect of topiramate as add-on therapy on seizure frequency, seizure severity, and quality of life in patients with epilepsy and intellectual disability. There were three phases: 4 weeks baseline, 18 weeks titration to 200-400 mg topiramate/day (adults) or 5-9 mg/kg/day (children), 12 weeks maintenance. Recruitment was low (88/120); analyses were underpowered. Seizure frequency varied enormously (median 17.7, maximum 1706.2). There was no significant difference in reduction in mean total seizure frequency or number of responders between the groups. Topiramate reduced seizure frequency by >30% from baseline (placebo 1%); post hoc analyses showed a trend toward significance (R ratio, P=0.052). There were no significant differences between the groups with respect to mean seizure severity or other outcome measures. Topiramate was generally well tolerated; body weight (P=0.015) and systolic blood pressure (P=0.043) were reduced. The study suggests that topiramate reduces seizure frequency in patients with epilepsy and intellectual disability without the added burden of behavior effects, and was potentially advantageous to physical well-being. In 24 epileptic children refractory to antiepileptic drugs (AEDs) with generalized tonic-clonic and other types of seizures, addition of D-alpha-tocopheryl acetate (Vitamin E 400 IU/day) to existing AEDs was accompanied by a significant reduction of seizures in 10 of 12 cases. This was significantly different from controls given placebo (0 of 12, p less than 0.05). This result did not appear to be due to the effects of changes in the plasma levels of the comedication. There were no adverse side effects. The Vitamin E levels steadily increased in the responders in the trial phase but this did not occur in two clinically noncompliant subjects or in 12 patients receiving placebo. No other clinically significant alterations in hematologic or biochemical test results were observed. No treatment-related changes in plasma concentration of concomitant AEDs were noted. These findings justify further clinical controlled trials of Vitamin E as adjunctive therapy for childhood epilepsy intractable to the usual antiepileptic therapy.
This review broadly supports the use of AEDs to reduce seizure frequency in people with refractory epilepsy and intellectual disability. The evidence suggests that side effects are similar to those in the general population and that behavioural side effects leading to discontinuation are rare, but that other effects are under-researched.