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. Compliance with drug therapy by epileptic patients. Systematic screening allows reduction of adverse antiepileptic drug effects: a randomized trial. Enhancing antiepileptic drug adherence: a randomized controlled trial. Long-term neuropsychological consequences of maternal epilepsy and anticonvulsant treatment during pregnancy for school-age children and adolescents. Effect of a primary care based epilepsy specialist nurse service on quality of care from the patients' perspective: results at two-years follow-up. Treatment of epilepsy in mentally retarded patients with a slow-release carbamazepine preparation. Comparison of antiepileptic drugs on cognitive function in newly diagnosed epileptic children: a psychometric and neurophysiological study. A randomised trial of strategies to improve patient compliance with anticonvulsant therapy.
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. Fifty patients with epilepsy were randomly divided into three groups and given, respectively, oral information about the nature, purpose, appearances, functions, and unwanted effects of their medications at an initial interview; the same information supplemented by its presentation in written form for the patient to take home; and the same information by telephone contact only. Compliance with anticonvulsant therapy was assessed by interview and by drug levels. The amount of knowledge retained and the drug levels were measured again 4 weeks later. While no increase in serum levels could be detected over the mean values in the first interview, no reduction in levels could be documented either, although the drug information sheets had listed both the minor and the more serious unwanted effects of the drugs. The patients' information scores improved significantly in all three groups, but the combination of data presented at interview both orally and in written form was markedly superior to the other methods. 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. 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. 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. Epilepsy specialist nurses have the potential to improve the quality of care of community-based patients with epilepsy, although evidence of their effectiveness is limited by the lack of formal or long-term evaluation. Results of a controlled trial that assessed the effectiveness of a primary care based specialist nurse-led service suggested improvements in communication and satisfaction but not health status at one-year follow-up. A second follow-up was conducted to assess the effects after two years. Patients who reported having seen the nurse at least once in the two years ('users') were compared with those who had not ('non-users'). Comparisons between users and non-users were adjusted for baseline differences. Results were based on 40% of all 595 adult patients known to have epilepsy in 14 general practices and who answered questionnaires at baseline and two years later. The new epilepsy service was used more by those with greatest needs for care. Users of the new service were significantly more likely than non-users to have discussed 8 of 11 topics asked about epilepsy [odds ratios (ORs) ranging from 2.42 to 7.91] with their general practitioner (GP), and 2 of the 11 topics with the hospital doctor (ORs 5.59, 5. 74). Service users were significantly less likely than non-users to feel their GP knew enough about epilepsy [OR 0.27, 95% confidence intervals (CI) 0.74-0.98], and significantly more likely to report epilepsy as having an adverse impact on 3 of 10 areas of everyday life (ORs ranging from 2.09 to 2.50). Users were more likely than non-users to have seen their GP for any reason in the previous year and to change their medication from use of more than one antiepileptic drug to monotherapy, although findings were not significant. Results suggest that the epilepsy specialist nurse service is not a cost-reducing substitute, particularly for general practitioner care, but it appears to improve communication and prescribing of monotherapy, and increases access for the most needy. The service may, however, have an adverse impact on patients' perceptions of the effects of epilepsy on aspects of everyday life.
                Copyright 1999 BEA Trading Ltd. Pharmacokinetic properties and efficacy of a conventional (C) carbamazepine (CBZ) preparation divided into three daily doses and a slow-release CBZ preparation (SR) divided into two daily doses were evaluated in a randomized, double-blind, cross-over study. The trial started with a 8-week baseline period followed by the two treatment periods each 10 weeks long. At the end of each period, a 24-h blood sample series for determination of serum CBZ and carbamazepine-10,11-epoxide (CBZE) was collected. The occurrence of seizures was monitored day and night during the whole study period by experienced nurses. The mean age of the 20 evaluable patients was 24.9 and the duration of epilepsy 19.2 and carbamazepine treatment 7.0 years. The bioavailability of CBZ from the two preparations was similar. The mean fluctuation of serum CBZ concentration (Cmax-Cmin/Css) was 16% smaller during SR. The mean serum CBZ concentration in the morning samples was significantly (P less than 0.001) higher during SR treatment. The mean total number of seizures was approximately four per week and did not differ between the two treatments, but during the last 2 weeks of the study period the occurrence of seizures was significantly smaller during SR (P = 0.02). 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. Fifty-three hospital outpatients with epilepsy were randomly allocated to either a control or an intervention group. Patients in the intervention group were subjected to a combination of compliance-improving strategies: patient counselling, a special medication container, self-recording of medication intake and seizures, and mailed reminders to collect prescription refills and attend clinic appointments. Compliance with anticonvulsant therapy (as measured by plasma anticonvulsant levels and prescription refill frequencies), and seizure frequency, were evaluated in each patient prior to intervention and 6 months afterwards. Patient compliance and clinical control improved significantly in the intervention group patients. Seizure frequency was, on average, halved following intervention. Compliance and seizure frequency were unaltered in the control group. Intervention failed to improve clinic appointment keeping. Poor compliance with drug therapy commonly confounds the treatment of epilepsy. This study shows that compliance can be improved and seizure frequency lessened by strategies that are easily incorporated into the routine management of epileptic patients.
We found no clear evidence to support routine antiepileptic drug serum concentration measurement with the aim of reaching predefined target ranges for the optimisation of treatment of patients with newly-diagnosed epilepsy with antiepileptic drug monotherapy. However, this does not exclude the possible usefulness of therapeutic drug monitoring of specific antiepileptic drugs during polytherapy, in special situations or in selected patients, although evidence is lacking.