THE PANIC-INDUCING PROPERTIES OF THE CHOLECYSTOKININ TETRAPEPTIDE CCK4 IN PATIENTS WITH PANIC DISORDER

We studied the effect of the cholecystokinin tetrapeptide (CCK4), a po tent CCKB antagonist, in patients with panic disorder. Two different d osages (25 and 50 mu g) of CCK4 and saline were tested in 12 patients who were randomly allocated to 2 of the 3 possible treatment groups. P atients were tested on 2 separate occasions, 1 week apart, using an un balanced single-blind incomplete block design. A total of 24 intraveno us injections were carried out. The panic rate with 25 mu g CCK was 44 % (4/9) and 71% (5/7) with 50 mu g. 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 out come variable, we found that CCK4 provoked symptoms of panic in a dose -dependent fashion. The behavioral response to CCK4 was not accompanie d by activation of the hypothalamic-pituitary-adrenal (HPA) axis as me asured by the prolactin and cortisol responses. Moreover, CCK4-induced panic symptoms were not correlated with plasma increases in the princ ipal noradrenergic metabolite, 3-methoxy-4-hydroxy-phenylglycol (MHPG) , suggesting that activation of the locus coeruleus may not be critica l for CCK4-induced panic.