The effect of 6-week treatment with escitalopram on CCK-4 challenge: A placebo-controlled study in CCK-4-sensitive healthy volunteers

Cholecystokinin-tetrapeptide (CCK-4)-induced panic attacks are reportedly attenuated by effective treatment with antipanic antidepressants in patients with panic disorder, but in healthy volunteers such effects are not well studied. The aim of this study was to assess the effect of 6-week treatment with an SSRI escitalopram on CCK-4-induced symptoms in healthy volunteers, who previously responded with a panic attack to CCK-4 challenge. A total of 18 healthy subjects (10 males and eight females, mean age 22.5±5.8) received a 6-week treatment with escitalopram (10 mg/day) and placebo followed by CCK-4 challenge (50 μg) in a double-blind crossover design. The panic rate was 67% after treatment with escitalopram and 56% after treatment with placebo (p=0.7). Thus, the results showed a significant reduction in CCK-4-induced panic rates without significant differences between escitalopram and placebo conditions. There were no significant effects of either treatment on any other variable of anxiety or cardiovascular indices. Secondary analysis showed no effect of gender or 5-HTTLPR polymorphism on response to CCK-4 challenge. This study demonstrated that in contrast to the findings in patients with panic disorder, in CCK-4-sensitive healthy volunteers the treatment with an antipanic SSRI did not cause a reduction of CCK-4-induced panic attacks beyond the effect of placebo. The mechanisms behind this discrepancy and the reasons of the decrease in sensitivity to CCK-4 challenge on repeated administration remain to be clarified in future studies.