Anxiolyticlike Effects of Atrial Natriuretic Peptide on Cholecystokinin Tetrapeptide–Induced Panic Attacks: Preliminary Findings | Anxiety Disorders | JAMA Psychiatry | JAMA Network
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Original Article
April 2001

Anxiolyticlike Effects of Atrial Natriuretic Peptide on Cholecystokinin Tetrapeptide–Induced Panic Attacks: Preliminary Findings

Author Affiliations

From the Department of Psychiatry and Psychotherapy, University of Hamburg, Hamburg (Drs Wiedemann, Jahn, and Kellner), and Max Planck Institute of Psychiatry, Munich (Drs Wiedemann, Yassouridis, and Kellner), Germany.

Arch Gen Psychiatry. 2001;58(4):371-377. doi:10.1001/archpsyc.58.4.371

Background  Panic attacks induced by administration of cholecystokinin tetrapeptide (CCK-4) have been evaluated as a valuable tool to investigate the neurobiological mechanisms involved in panic anxiety. The rationale to study the effects of natriuretic peptides on the CCK-4 response is derived from observations that atrial natriuretic peptide (ANP) is released during panic attacks in humans and has anxiolyticlike actions in various animal models.

Methods  A double-blind, placebo-controlled design was conducted in 9 patients with panic disorder and 9 similar healthy control subjects. After pretreatment with an infusion of 150 µg of ANP or placebo in random order, each subject received 50 µg of CCK-4. Psychopathological parameters as well as physiological measures were sampled before and after CCK-4 administration.

Results  After pretreatment with ANP, the number of CCK-4–induced panic attacks decreased from 8 to 6 in patients and from 5 to 2 in controls. Acute Panic Inventory ratings were significantly reduced in patients after ANP vs placebo pretreatment. Infusion of ANP significantly curtailed the CCK-4–induced release of corticotropin in patients. Heart rate variability analysis indicated a sympathetic stimulation by CCK-4 that was inhibited by ANP in patients and controls.

Conclusions  The present study indicates that ANP exerts anxiolyticlike effects on CCK-4–stimulated anxiety attacks in patients with panic disorder. In addition, ANP produced an inhibition of the hypothalamopituitary-adrenocortical system and sympatholytic effects.