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.