A double-blind randomised crossover trial of low-dose flumazenil for benzodiazepine withdrawal: A proof of concept

Benzodiazepines (BZD) are a class of anxiolytics with varying uses, which primarily act on the GABAA receptor resulting in hyperpolarisation. BZDs are often a difficult drug class to cease once neuroadaptation has occurred; recommendations usually involve gradual dose reductions at variable rates. A growing body of evidence has suggested that low-dose flumazenil, a GABAA receptor antagonist, may be a useful agent to allow for rapid detoxification. To collect pilot data on the safety and efficacy of low-dose subcutaneous flumazenil to reduce BZD use, withdrawal symptoms, and craving in participants taking above and below the therapeutic maximum diazepam equivalent of 30 mg to inform on sample size for future trials. In a randomised double-blinded crossover study design, participants received low-dose flumazenil first (4 mg/24 h for approximately eight days) or placebo first. Groups were divided into those taking