Pentagastrin-induced sleep panic attacks: Panic in the absence of elevated baseline arousal

Background: It has been suggested that pharmacological challenges that induce panic attacks are confounded by effects of environmental stress, elevated baseline arousal, and expectancy bias. Methods: To control for effects of arousal and cognition on the panicogenic effects of pentagastrin, pharmacological challenges were conducted during sleep in seven patients with panic disorder or social phobia. All patients had previously experienced pentagastrin-induced panic while awake. Infusions of normal saline and pentagastrin (0.6 μg/kg) were administered in fixed order and timed so that pentagastrin infusions took place during the transition from Stage 2 to Stage 3 sleep. Long intravenous lines were placed for remote blood sampling and subsequent analysis of plasma adrenocorticotropic hormone and cortisol. Measures of anxiety and panic were obtained at baseline and upon awakening after pharmacological challenge. Results: All seven subjects awoke within seconds following pentagastrin infusion. Four patients reported symptoms that met criteria for panic. Neither baseline anxiety nor neuroendocrine measures were predictive of panic. Conclusions: These data demonstrate the ability to induce panic during a period of diminishing arousal and indicate that panic attacks can occur in the absence of elevated arousal and environmental stress.