Behavioral, neuroendocrine, and cardiovascular response to flumazenil: no evidence for an altered benzodiazepine receptor sensitivity in panic disorder

Background: Flumazenil is a benzodiazepine receptor antagonist thought to be panicogenic in patients with panic disorder but not in control subjects. The present study was undertaken to compare the effects of flumazenil in patients with panic disorder and those in healthy control subjects, and also to determine whether panic disorder is characterized by a hypothesized shift in the benzodiazepine receptor “set-point” and a differential response to flumazenil. Methods: Eight patients with panic disorder and 8 matched control subjects were given infusions of saline and flumazenil in randomized order. Psychopathological changes, cardiovascular parameters, together with adrenocorticotropic hormone (ACTH) and cortisol secretion were recorded. Results: Patient and control subjects responded to flumazenil uniformly; there was no evidence for an anxiogenic activity of flumazenil in control subjects or panic disorder patients. ACTH and cortisol levels were also not differentially influenced by flumazenil or panic disorder diagnosis. Heart rate and systolic blood pressure in both groups were slightly but significantly reduced by flumazenil compared to saline. Conclusions: These findings do not support the view that panic disorder patients and control subjects respond differentially to flumazenil or that the suggested shift in the benzodiazepine receptor “set-point,” which leads to an inverse agonistic activity of flumazenil, characterizes panic disorder.