Introduction Of Vigabatrin Research Articles

Alternative Psychoses and Forced Normalization after Seizure Control by Anticonvulsants with Special Consideration of the New Anticonvulsants

In the case of alternative psychosis and forced normalization, the patient alternates between periods of clinically manifest seizures and normal behavior, and other periods of seizure freedom (or significant seizure reduction) accompanied by psychosis or behavioral disturbances. Unlike the clinically defined alternative psychosis, forced normalization is based on EEG findings. In clinical practice and in the literature, both terms are mostly used synonymously, and they also describe the same clinical pictures. This allowed a joint evaluation of the publications about alternative psychosis and forced normalization. Most often, these two disorders occur after seizure control by anticonvulsants. In the period of older anticonvulsants, the succinimides for the treatment of absence seizures were most often associated with the development of an alternative psychosis or forced normalization. In the era of newer anticonvulsants that started with the introduction of vigabatrin, mostly patients with intractable focal seizures were affected. In 1987 - 31 years ago - paranoid hallucinatory psychosis, triggered by vigabatrin in a patient with epilepsy was reported for the first time. In the following years, reports of alternative psychosis and forced normalization appeared to be related to most of the new anticonvulsants. A comprehensive literature search provided 66 cases with detailed information on such events. More than twice as many women were likely to be affected as compared to men; the reason for this phenomenon is unclear. In four retrospective studies, another 176 alternative events were reported but no details were given. The risk of alternative psychosis and forced normalization seems to be particularly low with the new anticonvulsants oxcarbazepine, eslicarbazepine, gabapentin and pregabalin.

ETP019 Efficacy of early introduction of Vigabatrin in tuberous sclerosis complex

ETP019 Efficacy of early introduction of Vigabatrin in tuberous sclerosis complex

The role of vigabatrin in childhood seizure disorders: results from a clinical audit.

The emergence of visual field defects attributed to vigabatrin (VGB) treatment and intramyelinic edema in animal experiments has raised concerns about its future role in the treatment of childhood seizures. We evaluated our experience with this antiepileptic agent with retrospective analysis of database and chart audit. Of 73 patients, 43 girls and 33 boys were treated with VGB over a 7-year period. The mean age of patients at the introduction of VGB was 87 months (range, 5-257 months). In 12 of 73 cases, VGB was used as monotherapy; in 61 of 73 cases, it was used as an add-on drug. Seizure types included secondarily generalized seizures (21), mixed seizures (21), partial seizures (18), and generalized seizures (13). Seizure etiology was idiopathic/cryptogenic in 22 patients, symptomatic in 50, and undetermined in a single patient. The mean duration of therapy was 16 months (median, 10 months; range, 1-144 months). VGB was effective in 30 (seven seizure free, 23 with >90% reduction in seizures), partially effective in four (50-90% reduction in seizures), and ineffective in 38 (<50% reduction in seizures). Nearly 50% of patients with infantile spasms responded to VGB. All patients underwent ophthalmic evaluation; two (16%) of 12 patients who could undergo static threshold perimetry were demonstrated to have the characteristic visual field constriction. VGB is effective in producing a significant reduction in seizure frequency in nearly half the patients with childhood seizures, including refractory epilepsy. Despite emerging concerns regarding visual side effects, this drug retains an important role in the medical management of childhood epilepsy.

A risk-benefit assessment of treatments for infantile spasms.

Infantile spasms are a devastating epileptic encephalopathy of the young child. The continuing spasms and hypsarrhythmia have a deleterious effect on brain maturation and further cognitive development. Corticotropin (adrenocorticotropic hormone) or corticosteroids have been the gold standard treatment for the last 40 years, but there is little agreement on the best agent to use, or the dosage and duration of the treatment. Despite this empirical approach, corticotropin or corticosteroids are effective in controlling spasms and normalising electroencephalograms in about 60% of cases. The major concern with this treatment is the occurrence of frequent and severe adverse effects. The introduction of vigabatrin in the 1990s improved the outcome of infantile spasms. Vigabatrin shows an efficacy at least equal to that of corticosteroids, and even higher in specific groups such as those with tuberous sclerosis. The major advantages of vigabatrin are the ability to initiate treatment at the full dosage. rapid efficacy, suitability for outpatient treatment and particularly good tolerability with only minor adverse effects. Recently, however, the safety of vigabatrin has caused concern since a specific visual field loss has been reported in treated adults. The current problem is determining the risk-benefit ratio of vigabatrin and corticosteroids/corticotropin in children with infantile spasms, and to specify the groups where their use could be optimal. Visual field loss is usually asymptomatic and can be detected only by perimetric visual field studies. In children, especially in the young or disabled, it is difficult if not impossible to detect the visual field loss and it is not yet known if children are at higher or lower risk for this adverse effect. Until a clear answer about the occurrence of this adverse effect in children has been established through randomised study, vigabatrin may still be considered first-line therapy in infantile spasms. Children who do not achieve a good response to vigabatrin should be switched to corticotropin/corticosteroid therapy. Despite the efficacy of corticosteroids and vigabatrin, the use of the conventional antiepileptic drugs, the newly developed antiepileptic drugs and some promising results with ketogenic diet, 25 to 30% of patients with infantile spasms continue to have spasms and experience psychomotor regression. These drug-resistant patients could be candidates for surgery.

Vigabatrin-Induced Seizures in Angelman Syndrome

Four children with Angelman syndrome (AS) showed worsening of seizures after introduction of vigabatrin (VGB), at the University Children’s Hospital, Zurich, Switzerland.

Multicentre clinical evaluation of vigabatrin (Sabril ®) in mild to moderate partial epilepsies

Vigabatrin (VGB) has been shown through several studies to be safe and effective as add-on therapy, particularly for the treatment of partial seizures in patients with severe epilepsies followed for years in hospital-based clinics. We now report additional clinical experience with VGB arising from an open trial of add-on VGB therapy in patients with relatively few seizures followed by qualified neurologists in private practice (the French Neurologists Sabril Study Group). VGB was administered to 397 patients aged 12-74 years (mean age = 37.5 +/- 13.8 years) who presented with no more than seven partial seizures of any type per month during a 3-month baseline period (mean number of seizures = 3.7 +/- 1.9/month). Simple partial seizures were reported in 121 (30.5%) patients, complex partial seizures in 282 (71.0%) and seizures with secondary generalization were reported in 111 (28.0%). The mean number of associated antiepileptic drugs (AEDs) was 1.9 +/- 0.9 and the mean dose of VGB was 2.21 +/- 0.64 g/day. Following introduction of VGB, 53 (13.4%) became seizure-free and remained so during the whole trial. During the fourth month of treatment, 158 patients (39.8%) had no seizures at all and a further 69 (17.4%) had their seizure frequency reduced by more than 50%. Secondary generalization was controlled during the whole period of treatment in 55 out of 97 patients (56.7%), 17 of which remained free of all types of partial seizures. VGB showed a good tolerability profile; adverse experiences more frequently reported were drowsiness and sleep disturbances. No action was necessary in the great majority of cases; the dose was reduced in 26 (6.5%) and VGB was discontinued in 32 (8%) patients. These data provide additional evidence that VGB can be used safely early on to treat patients with mild to moderate partial epilepsies. Secondary generalization was controlled in the majority of patients. Factors associated with the everyday clinical use of VGB, that resulted from a series of organized meetings with the investigators, are discussed.

The economic effects of introducing vigabatrin, a new antiepileptic medication.

Epilepsy is a common disorder, the prevalence of which is estimated at between 0.1 and 1% of the population. Although there are a number of medications available for treating the disorder, 20 to 35% of affected individuals are resistant to standard treatments. Many of these patients could benefit from a new anti-epileptic, vigabatrin. Because the current indication for vigabatrin is as an adjunct in a specific subgroup of epileptic patients, which implies an increased cost of drug therapy, an ex ante economic appraisal of the expected consequences of its introduction in the treatment of epilepsy is valuable. This would provide decision makers with information to complement standard clinical data. Using administrative records of healthcare services utilisation by epileptic patients, we performed a simulation of the expected economic repercussions of vigabatrin use on direct costs related to disease management. The results show that whether or not the introduction of vigabatrin results in an increase or a reduction in costs to the healthcare system depends largely on 3 factors: (i) the administered dosage of vigabatrin; (ii) the effect that vigabatrin has on hospital admissions; and (iii) the proportion of epileptic patients who take the drug. Moreover, this study underlines the usefulness of administrative data in forecasting the economic impact of new health technologies.

Vigabatrin-induced psychosis—management problems

A 22-year-old patient with partial seizures developed schizophreniform psychosis following the introduction of vigabatrin. She stopped her anticonvulsant medication as a consequence of her persecutory delusions. She subsequently suffered status epilepticus with severe brain damage. It is essential to outline a management plan for patients to detect and treat vigabatrin-induced psychosis.

The discovery of anti-epileptic drugs.

The general history of epilepsy is well documented, there being detailed accounts from ancient times in Babylonia (Wilson et al., 1990), ancient India (Bharucha & Bharucha, 1989), and China (Lai & Lai, 1991), up until the end of the 19th century (Tempkin, 1971). But relatively little has been written about its medical treatment, (Melville, 1982). The subject of this article is the history of potassium bromide, phenobarbitone and phenytoin, how their use in epilepsy was discovered, and in particular the surprisingly large part played by chance, luck and serendipity, in their introduction to the pharmacopaeia. The advance in this field has been one of sudden leaps forward, followed by periods of apparent inactivity, until the next discovery emerged, a pattern repeated many times, since medical treatment of epilepsy began with potassium bromide in 1857, until the introduction of vigabatrin in 1990.

Vigabatrin in Childhood Epilepsy

Sixty-six children with various types of severe drug-resistant epilepsy were entered into a long-term, dose-rising study of vigabatrin after a 4-week run-in placebo period. All the children were receiving one to three other antiepileptic drugs, the doses of which were not changed during the 6-month dose titration phase. Following the introduction of vigabatrin, 11 patients became seizure free, and 28 responded with a greater than 50% reduction in seizure frequency. The following types of epilepsy responded favorably in order of decreasing efficacy: cryptogenic and symptomatic partial epilepsy, other symptomatic generalized epilepsy, and Lennox-Gastaut syndrome. However, three of nine patients with myoclonic epilepsy showed an increase in seizure frequency. Optimal responses were found with vigabatrin doses of 40 to 80 mg/kg/day, although no significant adverse effects were noted with doses of higher than 100 mg/kg/day. Thirty-eight responders continued on vigabatrin, 19 of whom have been treated for more than 1 year, with generally good efficacy. As a result of discontinuing concomitant antiepileptics, six patients are on monotherapy with vigabatrin, four of whom are seizure free. Vigabatrin tolerability was good, with 39 of 66 children reporting no adverse effects. Hyperkinesia was reported in 17 patients (26%), and two had to drop out of the study. All these patients had a history of hyperkinesia or mental retardation. In patients in whom vigabatrin dose was reduced because of hyperkinesia, a dose increase could later be instituted without recurrence of symptoms. There was no change in neurologic examination and no drug-related abnormalities in clinical laboratory data.(ABSTRACT TRUNCATED AT 250 WORDS)