Abstract
A single-blind, placebo-controlled multicenter trial of vigabatrin was carried out in 101 epileptic patients (mostly with partial seizures) refractory to conventional therapy. The study design included four consecutive periods: (i) an observation phase (run-in), (ii) a placebo period, (iii) fixed-dosage add-on vigabatrin (2 g/day) and (iv) dose titration (up to a maximum of 4 g/day) to optimize clinical response. Each period lasted 8 weeks, except for the titration phase, which could be extended to 16 weeks. 90 patients completed the trial. Eleven dropped out, one patient developing absence status and 4 cases showing an increased seizure frequency. In the patients completing the trial, the median number of seizures/month decreased from 16 (inter-quartile range 8–34) during placebo to 5 (2–10) during the last 8 weeks on vigabatrin (p<0.0001). Both partial and generalized tonic clonic (mostly secondary) seizures were significantly reduced. A greater than 50% reduction in seizure frequency (compared to placebo) was observed in 60 patients. Sedation and weight gain were the most frequently reported adverse events.
Sommario
Centouno pazienti affetti da epilessia farmaco-resistente (nella maggior parte dei casi con crisi parziali) sono stati inclusi in uno studio policentrico con vigabatrin somministrato in aggiunta alla terapia preesistente secondo un disegno sperimentale controllato in singolo cieco. Il protocollo prevedeva 4 fasi consecutive (osservazione basale, placebo, vigabatrin 2 g/die, vigabatrin a dose individualizzata in base alla risposta clinica, sino ad un massimo di 4 g/die), ciascuna della durata di 8 settimane ad eccezione della fase di ottimizzazione della posologia che poteva essere prolungata a 16 settimane. Novanta pazienti hanno completato lo studio, mentre 11 (tra cui 1 che ha presentato stato di piccolo male e 4 che hanno riferito un aumento della frequenza delle crisi) hanno interrotto il trattamento precocemente. Nei pazienti che hanno completato lo studio, la frequenza mensile delle crisi è diminuita da un valore mediano di 16 (range interquartile 8–34) durante placebo a 5 (2–10) durante l'ultima fase di trattamento con vigabatrin (p<0.0001). Sia le crisi parziali che le crisi generalizzate tonico-cloniche (per lo più secondariamente generalizzate) sono diminuite significativamente. Una riduzione delle crisi di oltre il 50% è stata osservata in 60 pazienti. Gli effetti collatterali più frequentemente osservati sono stati sedazione ed aumento ponderale.
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References
Ben-Menachem E., Persson L.I., Schechter P.J., et al.:The effect od different vigabatrin treatment regimens on CSF biochemistry and seizure control in epileptic patients. Brit. J. Clin. Pharmacol. 27:79S-85S, 1989.
Browne T.R., Mattson R.H., Penry J.K., et al.:Vigabatrin for refractory complex partial seizures: Multicenter single-blind study with longterm follow-up. Neurology 37:184–189, 1987.
Browne T.R., Mattson R.H., Penry J.K. et al.:Multicenter long-term safety and efficacy study of vigabatrin for refractory complex partial seizures: An update. Neurology 41:363–364, 1991.
Cannon D.J., Butler W.H., Mumford, J.P., Lewis P.J.:Neuropathologic findings in patients receiving long-term vigabatrin therapy for chronic intractable epilepsy. J. Child Neurol. 6:2S17–2S24, 1991.
Cocito L., Maffini M., Perfumo P., et al.:Vigabatrin in complex partial seizures: A long-term study. Epilepsy Res. 3:160–166, 1989.
Cosi V., Callieco R., Galimberti C.A., et al.:Effects of vigabatrin on evoked potentials in epileptic patients. Brit. J. Clin. Pharmacol. 27:61S-68S, 1989.
Graham D.:Neuropathology of vigabatrin. Brit. J. Clin. Pharmacol. 27:43S-45S, 1989.
Gram L., Klosterkov P., Dam M.:Gamma-vinyl-GABA: A double-blind placebo-controlled trial in partial epilepsy. Ann. Neurol. 17:262–266, 1985.
Grant S.M., Heel R.C.:Vigabatrin- A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy and disorders of motor control. Drugs 41:889–926, 1991.
Hammond E.J., Wilder B.J.:Gamma-vinyl-GABA: A new antiepileptic drug. Clin. Neuropharmacol. 8:1–12, 1985.
Italian Collaborative Study Group On Vigabatrin:Studio multicentrico con vigabatrin nell' epilessia farmaco-resistente. Boll. Lega It. Epil. 70/71:121–123, 1990.
Loiseau P., Hardenberg J.P., Pestre M. et al.:Double-blind, placebo-controlled study of vigabatrin (gamma-vinyl-GABA) in drug-resistant epilepsy. Epilepsia 27:115–120, 1986.
Matilainen R., Pitkanen A., Ruutiainen T., et al.:Effect of vigabatrin on epilepsy in mentally retarded patients: a 7-month follow-up study. Neurology 38:743–747, 1988.
Michelucci R., Tassinari C.A., Iudice A., Mumford J.P.:Efficacia a lungo termine del vigabatrin nell' epilessia farmaco-resistente. Boll. Lega It. Epil. 62/63:393–394, 1988.
Mumford J.P., Dam M.:Meta-analysis of European placebo-controlled studies of vigabatrin in drug resistant epilepsy. Brit. J. Clin. Pharmacol. 27:101S-107S, 1989.
Mutani R., Cantello R., Gianelli M., Bettucci D.:Rational basis for the development of new antiepileptic drugs. In: Pisani F., Perucca E., Avanzini G., Richens A. (Eds), New Antiepileptic Drugs, Elsevier B.V., Amsterdam, pp. 23–28, 1991.
Pedersen S.A., Klosterkov P., Gram L., Dam M.:Long-term study of gamma-vinyl-GABA in the treatment of epilepsy. Acta Neurol. Scand. 72:295–298, 1985.
Remy C., Favel P., Tell G., et al.:Etude en double-aveugle contre placebo en permutations croisées du vigabatrin dans l'épilepsie de l'adulte résistant a la thérapeutique. Boll. Lega It. Epil. 54/55:241–243, 1986.
Remy C., Beaumont D.:Efficacy and safety of vigabatrin in the long-term treatment of refractory epilepsy. Brit. J. Clin. Pharmacol. 27:125S-129S, 1989.
Reynolds E.H., Ring H., Heller A.:A controlled trial of gamma-vinyl-GABA in drug resistant epilepsy. Brit. J. Clin. Pract. 42 (Suppl. 61):33, 1988.
Rimmer E.M., Richens A.:Double-blind study of gamma-vinyl-GABA in patients with refractory epilepsy. Lancet 1:189–190, 1984.
Rimmer E., Richens A.:Interaction between vigabatrin and phenytoin. Brit. J. Clin. Pharmacol. 27:27S-33S, 1989.
Sivenius J., Ylinen A., Murros K. et al.:Vigabatrin in drug-resistant partial epilepsy: A 5-year follow-up study. Neurology 41:562–565, 1991.
Tartara A., Manni R., Galimberti C.A., et al.:Vigabatrin in the treatment of epilepsy: A doubleblind, placebo-controlled study. Epilepsia 27:717–723, 1986.
Tartara A., Manni R., Galimberti C.A., et al.:Vigabatrin in the treatment of epilepsy: A longterm follow-up study. J. Neurol. Neurosurg. Psychiatry. 52:467–471, 1989.
Tassinari C.A., Michelucci R., Ambrosetto G., Salvi F.:Double-blind study of vigabatrin in the treatment of drug resistant epilepsy. Arch. Neurol. 44:907–910, 1987.
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The Italian Study Group on Vigabatrin., Loeb, C., Iudice, A. et al. Single-blind, placebo-controlled multicenter trial of vigabatrin in the treatment of epilepsy. Ital J Neuro Sci 13, 741–747 (1992). https://doi.org/10.1007/BF02229159
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DOI: https://doi.org/10.1007/BF02229159