Vigabatrin in Pediatric Epilepsy—An Open Study

Abstract

The antiepileptic effect of vigabatrin in adults has been demonstrated in a number of controlled studies. In children, the effect of vigabatrin has been investigated only to a limited extent. In order to assess the long-term effect and safety of vigabatrin in patients with severe epilepsy, an open, add-on, dose-ranging study was initiated. To date, 27 children with partial epilepsy, two with generalized epilepsy, two with Lennox-Gastaut syndrome, and one with nonclassifiable epilepsy have been enrolled in the trial. Fifty-four percent of patients have experienced a greater than 50% reduction in seizure frequency, and four patients have become seizure free. A significant reduction in seizures was noted across the patient population, although patients who were recorded as seizure free at 3 and 6 months did suffer some recurrence of seizures. However, when seizures recurred, they did so at much lower frequency than recorded at the start of the study. Thirteen patients (39%) reported adverse events attributable to vigabatrin; one was immediately withdrawn from the study, and six had their vigabatrin dose reduced. No physiologic effects were noted on normal growth or clinical physical examination. ( J Child Neurol 1991;6(Suppl):2S38-2S44).he neurotransmitter y-aminobutyric acid (GABA) is broken down by the enzyme GABA aminotransferase. Vigabatrin (y-vinyl-GABA) is a specific and irreversible inhibitor of this enzyme. Administration of vigabatrin leads to dose-related increases in the levels of GABA in brain and cerebrospinal fluid in humans. 1 Vigabatrin has been extensively evaluated as an anticonvulsant drug, and its efficacy as add-on therapy in the treatment of drug-resistant epilepsies has been confirmed in several double-blind, placebocontrolled studieS2-7 and one double-blind parallel study.8 Approximately half the patients in these studies experienced a 50% or greater reduction in seizure frequency. Efficacy appeared to be greater in adult patients with partial epilepsies. In children, it has been shown that vigabatrin is active in a wider range of seizure types, and its efficacy is not confined to partial seizures.9,10 Long-term follow-up studies in adults have demonstrated good tolerability and continued efficacy for periods of up to 4 years,11 but few such studies have been carried out in children. This study assesses the long-term effect, tolerability, and safety of vigabatrin in children with intractable epilepsy. Materials and Methods Study DesignThis was an open, add-on, dose-ranging study. Patients were recruited consecutively provided they fulfilled the entry criteria, ie, they were regular attenders at the study center clinic, aged between 2 and 15 years, had uncontrolled epilepsy with at least four documented seizures per month, and were on at least one other antiepileptic drug but not more than three. Informed consent was obtained from parents or guardians in all cases. Vigabatrin DosingFor the first month of treatment, the initial dose of vigabatrin for patients more than 8 years of age was 2 g da...

Psychotic and severe behavioural reactions with vigabatrin: a review

“…A further open study of 33 patients reported aggression in 9.1 % and hyperkinesia in 6.1% of children treated with vigabatrin. The majority continued on vigabatrin (47). The overall incidence of behavioural disturbances in these studies was 14.2%.…”

“…In contrast, Sander et al (8) reported a single patient who developed a schizo-manic reaction after 32 weeks of therapy and another patient who developed aggressive outbursts after 6 months of treatment. The studies in children considered earlier (44)(45)(46)(47) included long-term follow-up data, but the timing of adverse events was generally not given. However, the impression is that they tended to occur early in treatment.…”

A Risk-Benefit Assessment of Vigabatrin in the Treatment of Neurological Disorders

“…Vigabatrin was found to be most effective in partial seizures, but no clear dose-response relationship was found. An open-labelled, add-on study (Uldall et al 1991) in 33 children with epilepsy found a >50% reduction of seizures in 54% of patients, with 21 % being seizure free . However, seizures recurred in some patients, which may have been related to the reduction in number or dosage of concomitant drugs.…”

Changes in the electroretinogram resulting from discontinuation of vigabatrin in children

“…Vigabatrin (γ-vinyl-GABA) is an antiepileptic drug successful in the management of childhood seizures including infantile spasms [1][2][3][4][5][6][7]. The anticonvulsant effect of vigabatrin is achieved by irreversible inhibition of the enzyme GABA-transaminase used to break down the inhibitory neurotransmitter GABA.…”