Prediction of Panicogenic Effects of Caffeine and Yohimbine in Patients with Panic Disorder and Healthy Controls

Abstract

Biological challenge agents have been found to induce panic symptoms and/or a panic attack in patients with Panic Disorder (PD) within a controlled laboratory setting. In contrast to other agents used to induce panic symptoms, yohimbine, an alpha-2 adrenoreceptor antagonist, and caffeine, a central adenosine receptor antagonist, have peak effects within a subscribed time frame after administration. To date, no studies have compared these agents directly in patients with PD or examined the psychological mechanisms that may moderate a panic response. The present study was the first to examine patients with PD and healthy controls' self-reported psychological and physiological responses to these agents under controlled laboratory conditions. Twenty-two patients with PD and 20 healthy controls completed the yohimbine challenge, while 41 patients with PD and 33 healthy controls completed the caffeine challenge; 14 completed both challenges. The challenge agent and placebo were administered on two separate days in a randomized, double-blind procedure. Results indicated that yohimbine was a more potent panicogenic substance than was caffeine, as evidenced by participants reporting a more severe panic response during the former challenge. The relationship between panic severity and both agoraphobic cognitions and fear of publicly observable anxiety was stronger in patients with PD compared to controls in the yohimbine challenge, while there were no group differences in the caffeine challenge. Importantly, patients with PD who had more compared to less agoraphobic cognitions, fear of anxiety-related symptoms, and avoidance-oriented coping strategies reported more of a panic response during the yohimbine challenge condition, with a smaller effect during the placebo. Few effects were found for heart rate response to the biological challenge agents. The results indicate that findings may be dependent upon the type of challenge substance administered. It appears that for psychological variables to play a role, there has to be a sufficient panicogenic response to the challenge agent, as there was in the yohimbine but not in the caffeine challenge.