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 CCK(B) antagonist, in patients with panic disorder. Two different dosages (25 and 50 μg) 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 μg CCK was 44% (4/9) and 71% (5/7) with 50 μg. 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.