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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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