In a double-blind, placebo-controlled, parallel-group study in 30 healthy volunteers treated with 1 mg alprazolam 1 hour prior to a 50-μg CCK-4 challenge, a significant reduction of API and PSS scores
and of the number of reported symptoms compared to placebo pretreatment were found.49 A recent study (following an unbalanced, three-arm, two-period, crossover, double-blind, placebo-controlled design) in 21 male volunteers Inhibitors,research,lifescience,medical who received 1 mg of lorazepam 2 hours before CCK-4 did not show an attenuated panic signal in any PSS parameter.50 However, this dose of lorazepam was considerably lower than in the two previous studies reported above. Concerning Inhibitors,research,lifescience,medical anti-panic non-selective Epigenetics inhibitor serotonin reuptake inhibitors (imipramine or clomipramine) no study on CCK-4 panic in healthy volunteers has been published. With an SSRI, Kellner
et al51 could not demonstrate an inhibitory effect of escitalopram (6 weeks of 10 mg/d) on a 50-μg CCK-4 challenge in a double-blind, placebo-controlled, randomized, within-subject crossover design in 30 healthy young men. Induced panic under escitalopram was even significantly more pronounced in the subgroup of subjects with the short/short genotype for the serotonin transporter Inhibitors,research,lifescience,medical linked polymorphic Inhibitors,research,lifescience,medical region in this study. Another investigation with an identical dose and duration of escitalopram pretreatment also failed to show a significant inhibitory effect on CCK-4 panic in healthy man (I. Tőru, personal communication). Investigational anti-panic drugs and CCK-4 panic in healthy volunteers To test the effectiveness of a single oral 100 mg dose of the cholecystokinin
B antagonist CI-988 in attenuating panic symptoms induced by CCK-4 a randomized, placebo-controlled, double-blind, three-way crossover design was used in 30 healthy Inhibitors,research,lifescience,medical men.52 A small (14%), but significant decrease of sum intensity scores of panic symptoms was observed under CI-988. However, there was no marked difference in the number of panic symptoms. In contrast, a subsequent study in 14 patients with panic disorder who were given 50 also or 100 mg of CI-988 in a double-blind, two-period incomplete block design 2 hours before injection of CCK-4 failed to show a statistically significant treatment effect on the total intensity score on the PSS (the primary efficacy parameter), as well as on the number of panic symptoms, time to and occurrence of the first panic symptoms, duration of symptoms, intensity of apprehension, and the percentage of patients who did not have a panic attack.