Vigabatrin vs. carbamazepine monotherapy in newly diagnosed focal epilepsy: a randomized response conditional cross-over study. A comparative study of vigabatrin vs. carbamazepine in monotherapy of newly diagnosed partial seizures in children. A randomised open multicentre comparative trial of lamotrigine and carbamazepine as monotherapy in patients with newly diagnosed or recurrent epilepsy. Multicentre, double-blind, randomised comparison between lamotrigine and carbamazepine in elderly patients with newly diagnosed epilepsy. The UK Lamotrigine Elderly Study Group. Comparison of antiepileptic drugs on cognitive function in newly diagnosed epileptic children: a psychometric and neurophysiological study. Effect of a primary care based epilepsy specialist nurse service on quality of care from the patients' perspective: results at two-years follow-up. Adjuvant vigabatrin in refractory epilepsy: a ceiling to effective dosage in individual patients? 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. Vigabatrin as add-on therapy for adult complex partial seizures: a double-blind, placebo-controlled multicentre study. The Canadian Vigabatrin Study Group.
The clinical efficacy and safety of vigabatrin (VGB) as add-on therapy for pharmaco-resistant focal epilepsies is well established. However, for an objective evaluation, the effects of the drug in the monotherapy of newly diagnosed subjects should be determined. With this aim, VGB was compared, in a randomized, response conditional cross-over study, with carbamazepine (CBZ), the most widely prescribed drug in focal epilepsies. Fifty-one patients with complex partial (CP) seizures were randomly assigned to either the VGB or the CBZ group and evaluated after an initial 4 month period. The cross-over to the alternative drug was carried out, for an analogous period, only in cases with persisting seizures or in the presence of intolerable side effects. Patients who did not respond to either drug were subsequently treated with a combination of VGB and CBZ. No significant difference was revealed in the efficacies of VGB and CBZ; a complete control of seizures was obtained in 17/37 patients (45.9%) treated with VGB and in 20/39 patients (51.3%) treated with CBZ. The side effects were somewhat more frequent (41%) and severe with CBZ than with VGB (21.6%). The power to detect a 20% difference between the two drugs was 75%. The combination of the two drugs suppressed the seizures in 5 out of 14 resistant cases. The preliminary results in this small number of patients are encouraging and suggest that VGB may be considered as a first-line drug for epilepsy with CP seizures and as a valid alternative when other monotherapies are ineffective or poorly tolerated. Carbamazepine (CBZ) is a drug of choice for the treatment of simple or complex partial seizures and secondary generalized seizures in adults and children. Vigabatrin (VGB) is a relatively new second line antiepileptic drug and was first registered for use in Poland more than ten years ago. Few reports have been published on the comparison of efficacy of VGB in children with epilepsy. The objective of this study is to evaluate the safety, efficacy and EEG effects of initial VGB monotherapy compared with initial CBZ monotherapy in children with newly diagnosed epilepsy. We present results of a prospective, outpatient and open study carried out in the University Hospital Center in Białystok. Twenty-six children with partial epilepsy treated with VGB and 28 patients treated with CBZ were studied. The evaluation of the efficacy of the two drugs did not reveal any significant differences. Very good (reduction > 75%) seizure control was achieved in 22 out of 26 patients (84.6%) in the VGB group. One patient had a 50-75% decrease of seizures (good effect), similarly one child had a 25-50% reduction of seizures (mild effect). In two patients, we observed increased seizures (myoclonic jerks). Very good seizure control was achieved in 17 out of 28 patients (60.7%) in the CBZ group. Good seizure control was achieved in 5 out of 28 patients (17.8%) and mild control was seen in two children. No improvement was observed in 4 (14%) of the patients. The EEG background activity was improved in VGB-treated patients. No effect on the EEG background activity was observed in CBZ-treated children. VGB seems to be a safe and effective antiepileptic drug as primary monotherapy for epilepsy in children with similar proportion of side effects as CBZ. The efficacy and safety of lamotrigine and carbamazepine as monotherapy in patients with untreated, newly diagnosed or recurrent partial and/or generalised tonic-clonic seizures, were compared in a randomised, open, multicentre study. Patients received 24 weeks' treatment with oral lamotrigine 100 mg (LTG 100, n = 115) or 200 mg (LTG 200, n = 111) or carbamazepine 600 mg (CBZ 600, n = 117). Efficacy measurements were comparable between the three treatment groups, although the higher lamotrigine dose was possibly most effective, with 60.4% completing seizure free compared with 51.3% (LTG 100) and 54.7% (CBZ 600). Both dosage regimens of lamotrigine were well tolerated. More patients on CBZ 600 reported adverse experiences, 66% versus 53% (LTG 100) and 58% (LTG 200), and of these a greater proportion were attributed to CBZ 600 treatment, 53% versus 23% (LTG 100) and 28% (LTG 200). Similarly, a greater proportion of the CBZ 600 group required a change in dose, 47% versus 20% (LTG 100) and 17% (LTG 200) or withdrew completely due to adverse experiences, 10.3% versus 4.3% (LTG 100) and 4.5% (LTG 200). The most common adverse experience leading to withdrawal was rash, with approximately double the proportion of reports occurring in patients on CBZ 600 (5.1%) compared with lamotrigine (1.7% on LTG 100 and 2.7% on LTG 200). Overall lamotrigine appeared equally effective but better tolerated compared with carbamazepine. In a multicentre, double-blind trial 150 elderly patients (mean age 77 years) with newly diagnosed epilepsy were randomised in a 2:1 ratio to treatment with lamotrigine (LTG) or carbamazepine (CBZ). Following a short titration period, the dosage was individualised for each patient while maintaining the blind over the next 24 weeks. The main difference between the groups was the rate of drop-out due to adverse events (LTG 18% versus CBZ 42%). This was in part a consequence of the lower rash rate with LTG (LTG 3%, CBZ 19%; 95% CI 7-25%). LTG-treated patients also complained less frequently of somnolence (LTG 12%, CBZ 29%; 95% CI 4-30%). Although there was no difference between the drugs in time to first seizure, a greater percentage of LTG-treated patients remained seizure-free during the last 16 weeks of treatment (LTG 39%, CBZ 21%; P = 0.027). Overall, more patients continued on treatment with LTG than CBZ (LTG 71%, CBZ 42%; P < 0.001) for the duration of the study. The hazard ratio for withdrawal was 2.4 (95% CI 1.4-4.0) indicating that a patient treated with CBZ was more than twice as likely to come off medication than one taking LTG. In conclusion, LTG can be regarded as an acceptable choice as initial treatment for elderly patients with newly diagnosed epilepsy. 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. 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. A double-blind, randomized, cross-over study of additional vigabatrin (gamma-vinyl-GABA, VGB, 1.0 g twice daily for 6 weeks, followed by 1.5 g twice daily for 6 weeks) and matched placebo was undertaken in 24 patients with refractory epilepsy. Nineteen completed the trial satisfactorily. Fewer seizure days were reported during VGB treatment [placebo 41, VGB 23, p < 0.05, 95% confidence interval (CI) -1.5 to -14]. An overall reduction in median seizure numbers failed to reach statistical significance (n = 19; placebo 52, VGB 32, NS, 95% CI -18 to +24). Subgroup analysis, however, showed a significant reduction in partial seizures (n = 17) with 2 g VGB daily (placebo 22, VGB 13, p < 0.05, 95% CI -0.5 to -16.5), but not with higher dosage (placebo 28, VGB 22, NS, 95% CI -18 to +11). A deterioration in control of partial seizures as compared with the equivalent placebo phase was observed when patients were changed from 2 to 3 g/day VGB (2 g VGB 13, 3 g VGB 22, p = 0.05, 95% CI 0 to +20). Loss of efficacy was noted in 3 patients, and seizure control worsened slightly in 5 others. One previously resistant patient developed a therapeutic response, and 2 other patients reported an additional useful reduction in seizures. In the remaining 8 patients, seizure frequency did not change. VGB did not appear to benefit tonic-clonic seizures. Serum VGB concentrations were higher during treatment with 3 g (15.5 +/- 8.9 mg/L) daily than with 2 g (13.5 +/- 11.2 mg/L). No important alterations were noted in the concentrations of concomitantly administered antiepileptic drugs (AEDs) throughout the trial. VGB is useful adjuvant therapy for treatment of partial seizures. There may be a ceiling to effective dosage. This demands individual dose titration for each patient. 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. Vigabatrin (VGB) is a novel antiepileptic drug effective as adjunctive therapy in patients with partial seizures. In this study, the efficacy and tolerability of VGB as adjunctive therapy were evaluated in patients with refractory epilepsy. Adult patients with a definite diagnosis of complex partial seizures and/or partial seizures secondarily generalized were recruited from 10 Canadian centres. Patients were randomized to receive either active medication or placebo in a double- blind fashion and entered a 36-week titration and maintenance phase with regularly scheduled visits. Both efficacy parameters and safety assessments were monitored. Clinical laboratory, evoked potential studies, MRI, and neuropsychological tests were also performed. Forty-eight percent of VGB-treated patients vs. 26 percent of placebo-treated patients had a 50 percent or greater reduction in the frequency of complex partial seizures and partial seizures secondarily generalized. Vigabatrin was well tolerated by the majority of patients. Minor neurological side effects were observed in a number of patients in both treatment groups. No serious systemic toxicity was observed. No changes in evoked potential studies or MRI findings were noted. Vigabatrin was found to be an effective and well-tolerated antiepileptic drug when used as adjunctive therapy in patients with difficult to control complex partial seizures and for partial seizures secondarily generalized. Vigabatrin is a selective irreversible inhibitor of the GABA- degradating enzyme GABA transaminase and has shown efficacy in a number of clinical trials in patients with difficult to control partial seizures. Vigabatrin has been found most effective against complex partial and secondarily generalized tonic-clonic seizures in both adults and children. Vigabatrin has also been shown to reduce infantile spasms secondary to various aetiologies and is most effective in spasms associated with tuberous sclerosis. The aim of this study was to further extend the clinical experience with VGB as adjunctive therapy in the treatment of adult patients with difficult to control complex partial seizures and/or partial seizures secondarily generalized. In addition to the assessments of efficacy and tolerability to VGB, neuropsychological evaluations were also carried out.
                Copyright 2000 BEA Trading Ltd.
There is currently insufficient data to address the risk-benefit balance of using VGB versus CBZ monotherapy for epilepsy. Considering the high prevalence of visual field defects, reported in an existing systematic review of observational studies (Maguire 2010), the prescribing of VGB monotherapy for epilepsy should be used with caution and not considered as a first-line choice. If necessary, a frequent assessment of visual field is needed. Future research should focus on investigating the reasons for visual field defects and exploring the potential prevention strategies. Moreover, future monotherapy studies of epilepsy should report results according to the recommendation of International League Against Epilepsy (ILAE) Commission, and methodological quality should be improved.