In healthy volunteers responses to challenge with cholecystokinin tetrapeptide differ between administration during...

This study was designed to examine the sensitivity of different sleep stages to the pharmacological provocation of nocturnal panic attacks by cholecystokinin tetrapeptide (CCK-4). In a balanced cross-over design, healthy participants were challenged with identical doses of CCK-4 both during REM sleep and during delta sleep. In nine subjects, stimulation with 50 microg CCK-4 during REM sleep failed to elicit a full-blown panic awakening, while the same dose, administered during delta sleep, produced full-blown panic attacks in two participants. Similarly, stimulation of six subjects with 100 microg CCK-4 during REM sleep resulted in only one panic response, whereas four of nine subjects awoke experiencing a panic attack following stimulation with the identical dose during delta sleep. Severity of panic symptomatology, as measured by the self-rated Acute Panic Inventory, was also significantly increased when CCK-4 was administered during delta sleep. CCK-4 can be used as a challenge agent with an abrupt onset of action making it possible to provoke panic attacks precisely during a particular sleep stage. Sensitivity to the panicogenic effects of CCK-4 seems to be higher during delta sleep than REM sleep.