Vigabatrin: Clinical Evidence Supporting Rational Polytherapy in Management of Uncontrolled Seizures

Abstract

Monotherapy is the policy for management of patients with epilepsy. With increasing knowledge of the biology of epilepsy and of the modes of action of antiepileptic drugs (AEDs), this concept must be reevaluated. When monotherapy fails to control seizures, subsequent treatment should be based on "rational pharmacology," taking into consideration the mode of action of the drugs, to provide improved efficacy with maintained tolerance and ease of administration. Introduction of vigabatrin (VGB) as a new AED calls for just such a reevaluation. VGB is an enzyme-activated irreversible inhibitor of gamma-aminobutyric acid (GABA)-transaminase that increases brain and cerebrospinal (CSF) GABA concentrations in animals and humans. It has limited efficacy in the classic animal seizure screening tests, but in many clinical studies has halved the incidence of seizures in approximately 50% of patients, especially those with partial epilepsies. We evaluated the efficacy of VGB in "socially integrated and active outpatients" as a likely subset to demonstrate any advantage of rational polytherapy. The criteria for this evaluation included the effects on seizure frequency, patient tolerability, and cognitive performance in a battery of psychometric tests. Fourteen of the 19 patients (73%) completing the study had > 50% reduction in seizure frequency, and 10 of 19 (52%) had > 70% reduction in seizure frequency. Tolerability appeared good; somnolence was the most frequent adverse event. Three patients complained of a worsening of their seizures, 1 with an increase in frequency and 2 with development of myoclonic jerks not previously reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Seizures in a boy with succinic semialdehyde dehydrogenase deficiency treated with vigabatrin (γ‐vinyl‐GABA)

“…The slowing of our patient's EEG background activity within 2 weeks of onset of therapy is also a known side-effect of vigabatrin (Binnie 1982;de Bittencourt et al 1994). In 1993, two groups reported on a total of 5 patients who developed an acute encephalopathy along with slowing of the EEG due to vigabatrin (Sfilke-Kellermann et al 1993; Sharief et al 1993).…”

Epilepsia do lobo temporal: Relato de um paciente intacto após 26 anos de evolução sem tratamento

“…O caso de nosso paciente levanta a possibilidade de que drogas antiepilépticas sejam causa importante de distúrbios neuropsicológicos, neuropsiquiátricos e psico-sociais, como os encontrados em pacientes epilépticos. O uso da monoterapia com drogas eficazes para o tipo de crises e sem efeitos sedantes ou a utilização de politerapia racional -quando indicada e combinando drogas antiepilépticas com ações diferentes e que apresentem pouco risco de interações farmacológicas que levem a aumento da incidência de efeitos adversos -têm mostrado sua eficácia, evitando que o tratamento seja uma fonte a mais de complicações cognitivas e de conduta em pacientes epilépticos 9 . Um correto diagnóstico, a terapia adequada, com uso da politerapia racional quando necessário, o esclarecimento dos pacientes e seus familiares (sobre a doença, a conduta e seu prognóstico) são medidas que certamente contribuem para preservar a função cognitiva em pacientes epilépticos.…”

Epilepsy surgery without invasive EEG: early results of a new program

“…The majority of these patients were well known to the physicians; all were refractory to drug treatment, and had epilepsies which appeared to be amenable to one the surgical procedures the program was prepared to perform. As a general rule these patients were on rational antiepiletic drug regimens 3 and had their barbiturates and benzodiasepines withdrawn before surgical investigation 2 . All had clinical and laboratory screening, video moitoring and neuroimaging.…”