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Vigabatrin: Clinical Evidence Supporting Rational Polytherapy in Management of Uncontrolled Seizures
Author(s) -
Bittencourt P. R. M.,
Mazer S.,
Marcourakis T.,
Bigarella M. M.,
Ferreira Z. S.,
Mumford J. P.
Publication year - 1994
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1994.tb02447.x
Subject(s) - tolerability , vigabatrin , adverse effect , epilepsy , gabapentin , somnolence , medicine , anesthesia , anticonvulsant , psychology , pediatrics , pharmacology , psychiatry , pathology , alternative medicine
Summary: 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 γ‐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 ∼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% réduction in seizure frequency, and 10 of 19 (52%)had >70% réduction 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. No deleterious effect of VGB on cognitive function was noted, and performance in late recognition tests showed significant improvement by the end of the maintenance period, which may have been due to the réduction in seizure frequency. The efficacy of VGB in this study in controlling seizures as compared with results of earlier published studies of refractory epilepsy may be related to selection of patients with more benign partial epilepsy, but does support the need for further studies in such patients to evaluate the hypothesis of rational polytherapy.