Effects of the cholecystokinin agonist pentagastrin in patients with generalized anxiety disorder

Objective: The anxiogenic and panicogenic effects of peripheral administration of the cholecystokinin-B receptor agonist pentagastrin and placebo were evaluated in patients with generalized anxiety disorder and normal comparison subjects. Method: Seven patients with generalized anxiety disorder and seven age- and sex-matched normal subjects received an intravenous bolus of placebo and pentagastrin. Results: Panic attacks occurred in five patients with generalized anxiety disorder (71%) and in one normal subject (14%). Patients with generalized anxiety disorder were more likely to report more nonpanic anxiety than were normal subjects. Conclusions: Patients with generalized anxiety disorder appear to exhibit greater subjective sensitivity to pentagastrin than do normal subjects. (Am J Psychiatry 1997; 154:700‐702) C holecystokinin tetrapeptide (CCK-4) is a neurotransmitter that has high affinity for the cholecystokinin-B (CCK-B) receptors in the central nervous system and may play a role in the modulation of anxiety in animals and humans (1). Specifically, in patients with panic disorder, an intravenous bolus of CCK-4 or the synthetic analog pentagastrin reliably provokes panic attacks in the majority of subjects (2‐4). Since the administration of CCK-4 to healthy normal subjects also induces panic attacks at substantially higher doses than in patients with panic disorder, it is hypothesized that enhanced sensitivity to CCK stimulation may be present in panic disorder (4). To explore whether CCK sensitivity may be present in anxiety disorders other than panic disorder, we compared the panicogenic and anxiogenic effects of pentagastrin and placebo infusion in patients with generalized anxiety disorder and in normal subjects.