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Modulation by Muscarinic Antagonists of the Response to Carbon Dioxide Challenge in Panic Disorder
Marco Battaglia, MD;
Silvana Bertella, MD;
Anna Ogliari, MD;
Laura Bellodi, MD;
Enrico Smeraldi, MD
Arch Gen Psychiatry. 2001;58:114-119.
Background Panic attacks can be induced in persons with panic disorder by inhalation
of carbon dioxide. Hypercapnia also elicits a reflex hyperventilation, which
is controlled in part by cholinergic mechanisms. This study investigated whether
the exaggerated response to carbon dioxide in panic disorder (PD) can be modulated
by antagonists of muscarinic cholinergic receptors.
Methods Twelve patients with PD received biperiden hydrochloride (a muscarinic
antagonist that crosses the blood-brain barrier), pirenzepine hydrochloride
(a muscarinic antagonist that does not cross the blood-brain barrier), or
placebo 2 hours before a 35% carbon dioxide–65% oxygen respiratory challenge
(vs air as a placebo) on 3 separate days, in a double-blind, random crossover
design.
Results According to patients' self-ratings of subjective anxiety, inhalation
of the carbon dioxide/oxygen mixture provoked a significant and intense response
after treatment with pirenzepine and placebo. After biperiden treatment, however,
hypercapnia elicited a response profile similar to that elicited by air, whereby
subjective anxiety remained similar to preinhalation levels.
Conclusions Consistent with the hypothesis of the study, a centrally active muscarinic
antagonist can block the response to carbon dioxide commonly observed in subjects
with PD.
From the Developmental Psychopathology Unit, Department of Psychology,
University Vita-Salute San Raffaele (Drs Battaglia and Ogliari), and the Department
of Neuropsychiatric Sciences, Istituto Scientifico San Raffaele Hospital (Drs
Battaglia, Ogliari, Bellodi, and Smeraldi), Milan, and the Department of Child
Psychiatry, Istituto Scientifico Eugenio Medea, Bosisio Parini, Lecco (Dr
Bertella), Italy.
Corresponding author and reprints: Marco Battaglia, MD, Department
of Neuropsychiatric Sciences, Istituto Scientifico San Raffaele Hospital,
29 via Prinetti, 20127 Milan, Italy (e-mail: marco.battaglia{at}hsr.it).
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