Battaglia · Archives of general psychiatry 2001 · double-blind randomized crossover trial · n=12

Modulation by muscarinic antagonists of the response to carbon dioxide challenge in panic disorder.

Cited 41 times in the scientific literature.

Level 2 - randomized trial

Individual randomized crossover trial

PubMed 11177112 · doi:10.1001/archpsyc.58.2.114 · record verified 2026-08-29

What was done

Twelve patients with panic disorder participated in a double-blind, randomized crossover study across three separate days. Two hours before a respiratory challenge with a 35% carbon dioxide / 65% oxygen mixture (versus air as control), participants 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.

What was found

The abstract reports no numerical values or statistics. Self-rated subjective anxiety increased significantly and intensely following carbon dioxide inhalation after pretreatment with placebo and pirenzepine. In contrast, after biperiden administration, subjective anxiety during carbon dioxide challenge remained similar to preinhalation baseline levels, resembling the response to air.

Why it matters

This suggests that central muscarinic cholinergic mechanisms play a role in mediating the hypercapnia-induced panic response in panic disorder.

Limits

The study had a very small sample size (n = 12). The abstract provides no exact quantitative scores, effect sizes, or physiological measurements, and acute laboratory carbon dioxide challenges may not capture the full complexity of natural panic attacks.

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