The panic-inducing properties of the cholecystokinin tetrapeptide CCK4 in patients with panic disorder.
We studied the effect of the cholecystokinin tetrapeptide (CCK4), a potent CCKB antagonist, in patients with panic disorder. Two different dosages (25 and 50 micrograms) of CCK4 and saline were tested in 12 patients who were randomly allocated to 2 of the 3 possible treatment groups. Patients were tested on 2 separate occasions, 1 week apart, using an unbalanced single-blind incomplete block design. A total of 24 intravenous injections were carried out. The panic rate with 25 micrograms CCK was 44% (4/9) and 71% (5/7) with 50 micrograms. None of the patients panicked with saline (0/8). Patients' symptom responses were very similar to their spontaneous panic attacks. Taking the Panic Symptom Scale (PSS) as outcome variable, we found that CCK4 provoked symptoms of panic in a dose-dependent fashion. The behavioral response to CCK4 was not accompanied by activation of the hypothalamic-pituitary-adrenal (HPA) axis as measured by the prolactin and cortisol responses. Moreover, CCK4-induced panic symptoms were not correlated with plasma increases in the principal noradrenergic metabolite, 3-methoxy-4-hydroxy-phenylglycol (MHPG), suggesting that activation of the locus coeruleus may not be critical for CCK4-induced panic.
van Megen
H J
HJ
Rudolf Magnus Institute for Neurosciences, Department of Psychiatry, University Hospital Utrecht, The Netherlands.
Westenberg
H G
HG
Den Boer
J A
JA
Kahn
R S
RS
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D008875:Middle Aged; D016584:Panic Disorder / Q000188:drug therapy*; D013758:Tetragastrin / Q000494:pharmacology*
D013758:Tetragastrin; D008734:Methoxyhydroxyphenylglycol