Panic-related responses to pentagastrin, flumazenil, and thyrotropin-releasing hormone in healthy volunteers

Thyrotropin‐releasing hormone ( TRH) induces some somatic symptoms that resemble those of a panic attack, without being considered to be a laboratory panicogen in panic disorder (PD) patients. This study aimed to identify doses of TRH and the laboratory panicogens, pentagastrin and flumazenil, that would produce a similar intensity of panic‐related somatic symptoms in healthy volunteers because comparison of the effects of these doses in PD patients could be used to test the hypothesis that these agents have specific panicogenic effects that are not explained solely by cognitively mediated reactions to somatic symptoms. Nine subjects were administered pentagastrin (0.2 μg/kg) and TRH (600 or 1,200 μg) in a double‐blind, randomized order, within‐subjects design. Fifteen subjects received pentagastrin (0.1 μg/kg), TRH (600 or 1200 μg) and flumazenil (2 mg) in a double‐blind, randomized order within‐subjects design. Although low dose pentagastrin (0.1 μg/kg) induced comparable cardiorespiratory responses to those of TRH, it induced greater anxiety, suggesting that TRH would not be a credible comparator for pentagastrin in challenge studies in PD. However, TRH produced equal or greater symptom and physiological responses compared with flumazenil, suggesting that flumazenil may act as a panicogen in PD via a GABAergic mechanism rather than via a cognitively mediated response to somatic symptoms. This now requires confirmation in PD patients. Depression and Anxiety 17:78–87, 2003. © 2003 Wiley‐Liss, Inc.