Search

Objective: Previous studies have suggested that manipulations in patient instructions before inhalation of carbon dioxide (C[O.sub.2]) may blunt its anxiogenic effects. The authors examined the effects of a range of instructional types on panic rates and physiological responses to C[O.sub.2] inhalation. Method: Thirty-seven patients with panic disorder and 16 normal subjects were exposed to C[O.sub.2] inhalation under one of three instructional conditions: 1) reassurance (reiterated safety assurances), 2) control dial (patients were instructed on using an operative dial to reduce the concentration of C[O.sub.2] in the breathing canopy), and 3) basic instructions (standard information). Perceived breathlessness was measured with the Borg Scale of Respiratory Exertion. Results: Manipulation of instructional sets did not affect panic rates among patients. The reassurance condition, however, produced a significant reduction in perceived breathlessness. Conclusions: C[O.sub.2]-induced panic is a robust biological effect that occurs independent of cognitive set changes, such as illusion of control or reassurance of safety. Conclusions drawn from this study are bolstered by the fact that it is methodologically rigorous: it had a large number of subjects, used random assignment to one of three instructions, included a full array of both subjective and biological measures, and included independent ratings.

Objective: Previous studies have indicated that patients with panic disorder are more likely than normal subjects to have acute panic attacks during inhalation of CO2, but methodological objections have been raised. In this study the authors attempted to address three of these methodological problems by ensuring that raters who assessed whether panic attacks occurred were blind to subjects' diagnoses, by randomizing the order of administration of 5% CO2 and hyperventilation, and by challenging a greater number of subjects with 7% CO2. Method: Patients with panic disorder and normal subjects underwent 20-minute inhalations of 5% CO2 and 7% CO2 and 15 minutes of room-air hyperventilation. Ratings of panic/no panic during each condition were made separately by an assessor blind to diagnosis and by the subject. Scores on four panic rating scales were also recorded before and after each intervention. Results: Room-air hyperventilation caused panic attacks in a small number of patients; the difference in panic rate between patients and comparison subjects was statistically significant by the subjects' but not by the raters' assessment. Panic rates during 5% CO2 and 7% CO2 were significantly greater among the patients by both assessments; the panic rate was greatest during 7% CO2. Order of administration did not significantly affect panic rates for hyperventilation and 5% CO2. Conclusions: Panic patients were clearly more sensitive to the anxiogenic effects of CO2 than comparison subjects, and CO2 was a more potent anxiogenic stimulus than room-air hyperventilation. Seven percent CO2 discriminated best between patients and comparison subjects and should be the focus of further research.

Objective: Patients with panic disorder are behaviorally hypersensitive to CO2 inhalation and may also be biologically hypersensitive. A report by Mathew et al. showed, however, that administration of the carbonic anhydrase inhibitor acetazolamide, which is believed to increase brain CO2 level, did not cause panic in panic disorder patients. The authors of the present study noted that respiratory frequency did not increase in the earlier experiment and wondered whether respiratory stimulation occurred during acetazolamide administration, as would be expected if CO2 level increases significantly. Method: Ten patients with panic disorder and six normal control subjects received injections of acetazolamide, 1 g i.v., as per the Mathew et al. protocol, during breath by breath measurement of both tidal volume and frequency of respiration. Results: Three patients had panic attacks, one before receiving acetazolamide, one during the injection, and one 2 minutes after injection. Only the last of these attacks appeared possibly attributable to acetazolamide. None of the control subjects panicked. Neither patients nor control subjects exhibited meaningful change in tidal volume, respiratory frequency, or minute ventilation, and both groups experienced a trend toward significant decrease in overall levels of anxiety and dyspnea after acetazolamide injection. Conclusions: The authors replicated the earlier finding that acetazolamide is not panicogenic in patients with panic disorder but also showed that at the dose given, there is no meaningful effect on ventilation. If acetazolamide does affect CO2 levels it does so in a way that does not stimulate ventilation. Therefore, the acetazolamide injection results of Mathew et al. and of the present study do not challenge hypotheses linking panic attacks to hypersensitive respiratory control mechanisms.

Objective: The purpose of this article is to offer a comprehensive, data-based explanation of the relationship between hyperventilation and panic disorder linking CO2 hypersensitivity, cognitive/behavioral factors, and the respiratory effects of antipanic pharmacologic and psychological treatments. Method: The authors conducted a computerized search of MEDLINE for relevant articles. Results: Some panic patients have a chronic, subtle respiratory disturbance. Acute hyperventilation is neither necessary nor sufficient for panic to occur. Respiratory abnormalities in panic patients may adaptively aim at coping with a hypersensitive CO2 chemoreceptor system. Pharmacologic panicogens also stimulate the respiratory system, causing hyperventilation. Triggering this hypersensitive respiratory control mechanism may incite panic. Antipanic medications may reset the receptor threshold. Misattribution and catastrophic interpretation of somatic symptoms or the sense of loss of control may contribute to panic symptoms. Behavioral interventions such as desensitization or breathing retraining may block the full-blown attack. Cognitive strategies through cognitive control of respiration may supplement and accentuate these interventions. Conclusions: Panic disorder may be due to an inherently unstable autonomic nervous system, coupled with cognitive distress.

Objective: The authors assessed the substance and diagnostic specificity of carbon-dioxide-induced panic since, in addition to the specific biochemical effects of inhaled carbon dioxide (CO2), simple physiologic distress is also frequently implicated as a panicogenic factor during respiratory challenge studies with CO2 in patients with anxiety disorders. Method: Eighteen patients with panic disorder, 20 with social phobia, and 23 psychiatrically normal subjects inhaled a mixture of 35% CO2 and 65% O2 for 30 seconds through a face mask. They also breathed for 30 seconds through a valve reducing the diameter of the airway. A double-blind, counterbalanced, randomized design was used. Results: In spite of important similarities between the two interventions, including the induction of equal amounts of subjective respiratory distress, carbon dioxide inhalation was significantly more potent than increased airway resistance in provoking panic in the anxiety disorder patients. The patients with panic disorder were significantly more sensitive to CO2 than were the patients with social phobia or the normal subjects. Conclusions: Carbon dioxide inhalation appears to have a specific panicogenic effect in panic patients that goes beyond simple breathlessness. (Am J Psychiatry 1993; 150:250-257)

Objective: The behavioral response to [CO.sub.2] inhalation has been used to differentiate panic disorder patients from normal subjects and other clinical populations. This study extended examination of the diagnostic specificity of [CO.sub.2]-induced anxiety by testing panic disorder patients and clinical populations with reported low and high sensitivity to [CO.sub.2] inhalation (patients with major depression and patients with premenstrual dysphoric disorder, respectively). Method: The behavioral responses to inhalation of 5% and 7% [CO.sub.2], administered by means of a respiratory canopy, were studied in 50 patients with panic disorder, 21 with major depression, and 10 with premenstrual dysphoric disorder and in 34 normal comparison subjects. Occurrence of panic attacks was judged with DSM-IV criteria by a blind rater. Subjects were rated on three behavioral scales at baseline and after each [CO.sub.2] inhalation. Results: Panic disorder patients had a higher rate of [CO.sub.2]-induced panic attacks than depressed patients and normal subjects, whose panic rates were not distinguishable. The panic rate for patients with premenstrual dysphoric disorder was similar to that for panic disorder patients and higher than that for normal subjects. Subjects with [CO.sub.2]-induced panic attacks had similarly high ratings on the behavioral scales, regardless of diagnosis, including the small number of panicking normal subjects. Seven percent [CO.sub.2] was a more robust panicogen than 5%, and response to 7% [CO.sub.2] better distinguished panic disorder patients from normal subjects than response to 5% [CO.sub.2]. Conclusions: Patients with panic disorder and patients with premenstrual dysphoric disorder are highly susceptible to [CO.sub.2]-induced panic attacks, and depressed patients appear to be insensitive to [CO.sub.2] inhalation. The symptoms of [CO.sub.2]-induced panic attacks have a similar intensity regardless of the subject's diagnosis. (Am J Psychiatry 2001; 158:58-67)

Twenty panic disorder patients with mitral valve prolapse showed amelioration of prolapse on repeat echocardiogram after treatment for panic disorder. This effect was significant when compared to repeat echocardiograms in eight psychiatrically normal control subjects with mitral valve prolapse. (Am J Psychiatry 1992; 149:1587-1588)

Studies have shown that inhalation of carbon dioxide can induce panic in panic disorder patients, the point of panic coinciding with high carbon dioxide concentrations in the blood. Panic patients may be hypersensitive to carbon dioxide. Patients with a history of panic attacks and control subjects were placed under a clear plastic canopy and told that carbon dioxide would be added to the air they were breathing and that they might experience anxiety. The patients were given room air for 20 minutes; five percent carbon dioxide was added to the room air for another 20 minutes without their knowledge. Blood samples were monitored for carbon dioxide concentrations, and the patients were told to report any symptoms as soon as they occurred. The male panic patients were significantly more sensitive to carbon dioxide than the male control subjects, but anxiety levels in both groups were low and did not differ significantly. The data also suggested that there may be sex differences in panic disorder and that female panic patients may not be hypersensitive to carbon dioxide. Psychological factors known to affect carbon dioxide sensitivity were not controlled, but all subjects received the same instructions and experienced the same degree of anxiety. The physiologic differences that were recorded did not seem to be related to the levels of anxiety experienced by the subjects. (Consumer Summary produced by Reliance Medical Information, Inc.)