In a double-blind placebo-controlled prospective clinical trial we studied the 
efficacy and safety of the benzodiazepine antagonist, flumazenil. In 23 patients 
admitted to the Intensive Care Unit with coma due to overdose with 
benzodiazepines or other sedatives, flumazenil i.v. (up to 2 mg or placebo) was 
given. In 13 patients given flumazenil the Glasgow Coma Scale (GCS) increased 
significantly from 4.9 to 7.8 (p less than 0.05). Six of these 13 patients, 
including mainly benzodiazepine mono-intoxications, needed only one series of 
injections (up to 1.0 mg flumazenil); the GCS increased thereby from 4.5 to 10.7 
within a maximum of 5 min (p less than 0.01). In the remaining 7 patients, 
needing two series of injections of flumazenil (up to 2.0 mg), GCS did not rise 
significantly and coma was related to intoxications with nonbenzodiazepine 
sedatives, flunitrazepam and in one patient, encephalitis. In the 10 patients 
receiving placebo, the GCS did not change. A significant increase in the GCS 
from 5.5 to 10.8 (p less than 0.001) was, however, observed when flumazenil (up 
to 1.0 mg) was given after placebo. In patients with EEG monitoring the changes 
in waveform pattern paralleled the clinical response. Effects could be detected 
within 1-2 min after flumazenil injection and lasted up to 45 min. There were no 
adverse reactions or benzodiazepine withdrawal symptoms. We conclude that 
flumazenil is an effective and safe drug in the treatment of benzodiazepine 
overdose. The use of flumazenil is of diagnostic value in mixed-drug 
intoxications or coma of unknown origin and is of therapeutic importance for 
reversal of benzodiazepine intoxications.