A dose-ranging study of the behavioral and cardiovascular effects of CCK-tetrapeptide in panic disorder

Recent animal studies have shown that pretreatment with centrally active cholecystokinin (CCK) anatagonists blocks the anxiogenic effects of CCK-tetrapeptide (CCK-4). In order to determine whether pretreatment with these antagonists can block the anxiogenic effects of CCK-4 in patients with panic disorder, a suitable challenge dose of CCK-4 must be selected. Thus, we conducted a dose range study in which patients with panic disorder ( n = 29) were challenged with CCK-4 (10, 15, 20, or 25 μg) or placebo on two separate occasions, in a balanced incomplete block design. Patients received in random order 10 μg ( n = 12), 15 μg ( n = 11), 20 μg ( n = 12), or 25 μg ( n = 12) of CCK-4 or placebo ( n = 11). CCK-4 induced anxiety and panic responses in a dose-dependent fashion. The incidence of panic attacks following the CCK-4 challenge was 17% (10 μg), 64% (15 μg), 75% (20 μg), and 75% (25 μg). None of the patients panicked with placebo. Moreover, a strong linear relationship between CCK-4 and increases in heart rate and diastolic blood pressure was found. The findings of this study suggest that a dose of 20 μg of CCK-4 (ED 75) might be suitable for efficacy studies of CCK B antagonists and other potential antipanic drugs in patients with panic disorder.