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Anxiolyticlike Effects of Atrial Natriuretic Peptide on Cholecystokinin Tetrapeptide–Induced Panic Attacks
Preliminary Findings
Klaus Wiedemann, MD;
Holger Jahn, MD;
Alexander Yassouridis, PhD;
Michael Kellner, MD
Arch Gen Psychiatry. 2001;58:371-377.
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.
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.
Corresponding author and reprints: Klaus Wiedemann, Department of
Psychiatry and Psychotherapy, University of Hamburg, Martinistrasse 52, 20246
Hamburg, Germany (e-mail: wiedeman{at}uke.uni-hamburg.de).
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