Dose-dependent effects of flumazenil on cognition, mood, and cardio-respiratory physiology in healthy volunteers

Objectives: To assess the possible effects of flumazenil on cognitive processing, physiology, and mood. Design: A double-blind, placebo controlled, four-way cross-over study, using healthy volunteers. Methods: On each of 4 separate visits, 16 participants received 0.5mg, 2.5mg, 5.0mg of flumazenil, or normal saline. They then performed a computerised test battery assessing cognitive function. Measures of pulse rate, arterial oxygen saturation and mean arterial pressure were also taken. Finally, participants completed visual analogue scales assessing their subjective mood state. Results: The majority of cognitive tasks showed dose-dependent declines in performance. Mean arterial pressure was significantly reduced, as was pulse rate. Subjective alertness showed a similar decline. Conclusions: Flumazenil has been clinically described as an agent with few intrinsic properties, whose primary effect lies in its ability to reverse benzodiazepine-induced states. This study has shown that flumazenil does possess intrinsic activity which have a significant effect on cognition, cardiovascular physiology and mood. Clinicians need to be aware of these effects.