The clinical anti-convulsant effects of flumazenil, a benzodiazepine antagonist.

The clinical anti-convulsant effect of flumazenil in epilepsy has been demonstrated: (i) by acute i.v. administration under EEG control in an epileptic patient who had been previously heavily sedated with diazepam; (ii) in patients undergoing pharmaco-EEG studies whereby spike and wave counts were diminished following oral administration of 10 mg of flumazenil; and (iii) in a series of 27 epileptic patients treated chronically for periods of up to 42 months with flumazenil as monotherapy or as addition to basic therapy. The daily dose ranged from 10-90 mg. Before treatment all patients presented with frequent seizures and had an abnormal EEG. In these patients the anti-convulsant effect was good or very good in 70% of the previously untreated (naive) patients and in about half of the patients who had epilepsy of long duration and had been treated already with standard anti-convulsants. Side-effects with flumazenil were generally mild in nature and rarely led to discontinuation. About one-third of the patients expressed a feeling of well-being while under therapy with flumazenil. A possible mechanism of action is discussed.