EFFECTIVENESS OF FLUMAZENIL (RO 15-1788) IN THE TREATMENT OF BENZODIAZEPINE WITHDRAWAL

Flumazenil (RO 15-1788) was used to treat benzodiazepine (BZD) withdra wal after abrupt cessation of chronic abuse of high-dose flunitrazepam or lormetazepam. Thirty-six patients (18 flunitrazepam and 18 lormeta zepam abusers) were randomly divided into 4 groups of 9 subjects: grou p A: flunitrazepam abusers treated with flumazenil; group B: flunitraz epam abusers treated with placebo; group C: lormetazepam abusers treat ed with flumazenil; group D: lormetazepam abusers treated with placebo . Fifteen withdrawal symptoms were measured on a four-point scale from 0 (not present) to 3 (severe) every 6 hours. Saline solution was used as the placebo. Mean withdrawal score was significantly higher (P < 0 .05) on the first day after cessation of lormetazepam in group D. Duri ng the following 2 days the two groups treated with placebo showed a s ignificant increase in mean withdrawal scores (P < 0.001). No rise in mean withdrawal symptom scores was seen in the groups treated with flu mazenil. One patient in group B and 2 patients in group D needed diaze pam medication 72 hours after withdrawal of BZD. No seizures or other side effects were seen after flumazenil infusion. Our data suggest tha t high doses of BZD for a prolonged period may induce functional chang es in the gamma-aminobutyric acid (GABA)-BZD receptor complex. Flumaze nil appears to up-regulate GABA-BZD-receptors and exert a weak agonist action that suppresses BZD withdrawal symptoms.