Angelo Bertani

Carbon dioxide/oxygen challenge test in panic disorder.

The effects of a single inhalation of a 35% CO2/65% O2 gas mixture were examined in 71 patients with panic disorder with or without agoraphobia and 44 normal control subjects. Compared with the placebo condition, inhalation of air, the CO2/O2 mixture elicited a clear anxiety reaction only in panic disorder patients, who experienced a sudden rise of subjective anxiety as well as of several panic symptoms. Respiratory symptoms and the fear of dying best distinguished the patients from the control subjects. Baseline anxiety was not the key factor in explaining this differential reaction. The clinical features of panic disorder (namely, frequency of panic attacks, agoraphobia, anticipatory anxiety, and duration of illness) were not significantly related to the response to the challenge test, suggesting that CO2 reactivity might be a trait marker of panic disorder.

Asthma and panic attacks

Panic disorder (PD) and asthma share many common characteristics and have been found in epidemiological studies to be significantly comorbid. To investigate possible reasons for this overlapping, the authors evaluated 51 patients with asthma, assessing the prevalence of PD and sporadic panic attacks, the temporal relationship between these two disorders, and the familial risk for PD in the families of asthmatics. The results showed significantly higher prevalences of PD, sporadic panic attacks, and social phobia in asthmatics than those reported for the general population. In 9 (90%) of the asthmatics with PD, asthma appeared first. Finally, the morbidity risk for PD in families of asthmatics with PD (13.5%) was significantly higher than in families of asthmatics without evidence of panic (2%). Our results suggest that the high prevalence of PD in asthmatics might be related to a facilitating effect of asthma on the development of PD in subjects with familial predisposition to PD.

The 35% CO2 challenge test in patients with social phobia

Panic disorder (PD) and social phobia (SP) share many clinical, demographic and biological characteristics. To investigate the relationships between the two disorders, the responses to inhalation of a 35% carbon-dioxide (CO2) and 65% oxygen (O2) gas mixture were assessed. Sixteen patients with PD, 16 patients with SP, 13 patients with both SP and PD, seven patients with SP who experienced sporadic unexpected panic attacks and 16 healthy control subjects inhaled one vital capacity of 35% CO2 or compressed air. A double-blind, randomized, crossover design was used. PD patients and SP patients showed similar anxiogenic reactions to 35% CO2, both stronger than seen in control subjects. Patients with both disorders and SP patients with sporadic unexpected panic attacks reacted similarly to subjects with PD or SP alone. These results suggest that PD and SP share a common hypersensitivity to CO2 and thus might belong to the same spectrum of vulnerability.

Pharmacologic effect of imipramine, paroxetine, and sertraline on 35% carbon dioxide hypersensitivity in panic patients: a double-blind, random, placebo-controlled study.

The effects of short treatment (7 days) with the tricyclic antidepressant imipramine and the two selective serotonin reuptake inhibitors paroxetine and sertraline on the reactivity to inhalation of 35% CO2/65% O2 were compared in 70 panic patients who had positive responses to 35% CO2 inhalations. A double-blind, random, placebo-controlled design was applied. Each patient was given the 35% CO2 challenge on days 0 (before starting the treatment), 3, and 7. In the placebo group, there were no significant changes in the reactivity to 35% CO2 in the three sessions whereas there were significant similar reductions of reactivity to 35% CO2 in all three drug-treated groups. These results confirm the good reproducibility of 35% CO2 reactivity and the negligible effects of placebo on reactivity to CO2 and suggest that short treatments with imipramine, paroxetine, and sertraline decrease reactivity to 35% CO2, possibly as an expression of their antipanic properties.

Modification of 35% carbon dioxide hypersensitivity across one week of treatment with clomipramine and fluvoxamine: a double-blind, randomized, placebo-controlled study.

The effects of short treatments (7 days) with clomipramine and fluvoxamine on the reactivity to inhalations of 35% CO2/65% O2 were compared in 39 panic patients who had positive responses to 35% CO2 inhalations. A double-blind, randomized, placebo-controlled design was applied. Each patient was given the 35% CO2 challenge on days 0 (before starting treatment), 3, and 7. Patients on placebo did not report any significant changes in their reactivity to 35% CO2 across the three sessions, whereas patients on clomipramine and fluvoxamine reported a significant attenuation of the reactivity on day 7. These results indicate that treatments with clomipramine and fluvoxamine decrease hypersensitivity to 35% CO2 after a few days, suggesting a relevant role of the modulation of CO2 sensitivity by the serotonergic system in antipanic properties of these compounds.

Plasma interleukin-1 beta concentrations in panic disorder

Plasma interleukin-1 beta (IL-1 beta) concentrations were measured in 10 outpatients with panic disorder before and on days 30 and 32 of treatment with alprazolam (2-2.5 mg/day). IL-1 beta concentrations were found to be significantly higher in patients than in control subjects both before and during therapy. Thus, IL-1 beta levels may be a marker of panic disorder that is not related to the current level of symptomatology.

Antipanic drug modulation of 35% CO2 hyperreactivity and short-term treatment outcome

Carbon dioxide (CO2) inhalation induces acute anxiety and panic attacks in patients with Panic Disorder (PD). Anti-panic drugs decrease CO2 reactivity after the first days of treatment; however, the clinical meaning of this finding has not yet been established. This study investigated the effects of treatment with tricyclic antidepressants and selective serotonin re-uptake inhibitors (SSRIs) on CO2 reactivity and compared the relationships between 35% CO2 hyperreactivity modulation and short-term clinical outcome. One hundred twenty-three patients with PD with or without agoraphobia who were hyperreactive to CO2 were randomly assigned to treatment groups with imipramine, clomipramine, paroxetine, sertraline, or fluvoxamine. A double-blind, randomized design was applied. Each patient received the 35% CO2 challenge on days 0, 7, and 30. The severity of clinical symptomatology was measured on days 0 and 30. Decreased hyperreactivity to 35% CO2 in all five treatment groups was already evident after the first week. The decrease in CO2 reactivity at the end of treatment was proportional to the degree of clinical improvement. Multiple regression analyses showed that the decrease in CO2 reactivity after the first week was a significant predictor for good clinical outcome after one month. The results of this study confirm evidence that psychoactive drugs effective in the treatment of PD decrease CO2 hyperreactivity. They also suggest that precocious modulation of CO2 reactivity might fairly reliably predict short-term clinical outcome in patients with “respiratory” PD.

Dopamine function in obsessive—compulsive disorder: Growth hormone response to apomorphine stimulation

Indirect observations suggest that the dopaminergic system may be involved in the pathophysiology of obsessive-compulsive disorder (OCD). The dopaminergic function of 15 patients with OCD and 15 age/sex-matched controls was evaluated by measuring the growth hormone (GH) responses to stimulation with the dopaminergic agonist apomorphine (APO), which increases growth hormone-releasing hormone (GHRH), GH, and somatomedine C (SMD-C) secretions. Therefore, we measured basal plasma GH and SMD-C concentrations and GH responses to GHRH stimulation to exclude that a downstream pathology of the somatotropic axis could obscure the significance of the results of the APO test. The response of prolactin (PRL) to APO inhibition were also measured. Basal plasma levels of GH, SMD-C, and PRL, GH responses to GHRH stimulation, and PRL responses to APO inhibition did not differ in the two groups of subjects. GH responses to APO stimulation were blunted in obsessive-compulsive (OC) patients. The emetic response to the same stimulation was stronger in patients than in controls. These responses suggest that in our OC patients there is a dysregulation of the dopaminergic system, which is possibly expressed in different ways in the various areas of the central nervous system.

Pharmacologic effect of toloxatone on reactivity to the 35 % carbon dioxide challenge : a single-blind, random, placebo-controlled study

The effect of a short treatment (7 days) with the reversible monoamine oxidase type A inhibitor toloxatone on the reactivity to the inhalation of 35% CO2 was evaluated in 18 panic patients who responded to 35% CO2 inhalation with panic before treatment. A single-blind, placebo-controlled design was applied. Panic patients were randomly assigned to the toloxatone (N = 10) or placebo (N = 8) groups and were given the 35% CO2 challenge on days 1 (before starting the treatment), 3, and 7. Patients on placebo did not report any significant changes in their reactivity to 35% CO2 during the three sessions, whereas patients on toloxatone reported a significant attenuation of the reactivity on day 7. These results indicate that (1) anxiety provoked by the inhalation of 35% CO2 is reproducible; (2) placebo has a negligible effect on 35% CO2 reactivity; and (3) reactivity to 35% CO2 is significantly attenuated by short treatment with toloxatone, possibly related to its antipanic activity.

The 35% CO2 hyperreactivity and clinical symptomatology in patients with panic disorder after 1 week of treatment with citalopram: an open study.

The effect of a short treatment (7 days) with citalopram on the reactivity to inhalations of 35% CO 2 and 65% oxygen and on clinical symptomatology was investigated in 15 patients with panic disorder who had a positive response to 35% CO 2 inhalation. An open study design was applied. On day 0, before starting drug treatment, and after 1 week of treatment, each patient underwent the 35% CO 2 challenge, and clinical symptomatology was evaluated with psychometric scales. The results showed a significant reduction of CO 2 reactivity and of scores on the anticipatory anxiety subscale of Panic Associated Symptoms Scale. These results confirm that the serotonergic system plays an important role in the modulation of CO 2 hyperreactivity and suggest an early anxiolytic effect of citalopram in patients who have panic disorder and are hyperreactive to CO 2 .