Flumazenil-precipitated withdrawal symptoms in chronic users of therapeutic doses of diazepam

Abstract

A prototype benzodiazepine (BDZ) antagonist, flumazenil (1 mg, i.v.) or placebo was administered to eight chronic users (5-15 years) of therapeutic doses of diazepam (10-25 mg/d), in a double-blind, placebo-controlled design in order to evaluate the presence of physiological dependence. The three patients receiving flumazenil developed anxiety reactions, with significant increases in bodily and psychological symptoms, as measured by rating scales. In two these amounted to a panic attack. Subjects on placebo tended to show decreases in measures of anxiety. The severity of precipitated reactions was not related to the total cumulative exposure to diazepam, but to a history of panic attacks. Previous panic may increase the vulnerability to severe reactions to flumazenil.