Laszlo A. Papp

High-Dose Carbon Dioxide Challenge Test in Anxiety Disorder Patients

Many investigators have shown that panic disorder patients and possibly social phobics are hypersensitive to the anxiogenic effects of inhaled carbon dioxide (CO2). In this study we administered double-breath inhalation of 35% CO2 and 65% oxygen (O2) to panic disorder patients, social phobics, and normal controls. At baseline, panic disorder patients were characterized by higher pulse, anxiety score, and evidence of hyperventilation. Panic patients and social phobics panicked more often to 35% CO2 than to room air; normal controls did not have a higher rate of panic to CO2 than to room air. However, we did not find significant group differences in anxiety level, physiological measures, or biochemical measures in response to CO2 breathing compared with room air breathing. These results confirm earlier reports of baseline hyperventilation in panic disorder patients. However, 35% CO2 may be too high a dose to differentiate respiratory responses of patients compared with normals.

Effect of antipanic treatment on response to carbon dioxide.

BACKGROUND Disordered breathing among patients with panic disorder, including hyperventilation during attacks and increased anxiogenic response to carbon dioxide (CO2) inhalation, is well established. We wished to assess whether there is a change in the physiological response to CO2 after patients have undergone antipanic therapy with either tricyclic antidepressants or cognitive behavioral therapy (CBT). METHODS Twenty-nine patients with panic disorder underwent baseline CO2 sensitivity testing using the traditional Read rebreathing method and then received either antidepressant treatment (n = 21) or CBT (n = 8). After completing treatment, CO2 testing was repeated. A comparison sample of 14 normal volunteers also had two CO2 sensitivity tests, separated by an average of 21.6 (SD = 8.8) weeks. RESULTS Using a liberal standard, in which all CO2 sensitivity tests whose correlations between minute ventilation and end-tidal CO2 were at least .75 were used, patients, but not controls, demonstrated a significant reduction in CO2 sensitivity between the first and second test. Using a more conservative .90 correlation standard reduced the sample size available and resulted in trend reduction in patients but no significant change in controls. There was a suggestion that the change was most pronounced in treatment responders, although the number of patient nonresponders is extremely small in this sample. CONCLUSIONS These data indicate that treatment reduces CO2 sensitivity in patients with panic disorder. We speculate that manipulation of the serotonergic and noradrenergic neurotransmission systems, both known to play a role in the control of respiration, may have a specific effect in reducing respiratory hyperactivity in panic disorder.

Pretreatment patient factors predicting attrition from a multicenter randomized controlled treatment study for panic disorder

This study examined pretreatment factors associated with attrition from a clinical trial for panic disorder. The study group consisted of 162 patients who began 11-visit treatments. Six domains (demography, panic disorder severity, psychiatric comorbidity, illness/treatment attributions, coping styles, and personality styles) with 52 variables were used to predict attrition. One hundred twenty-two patients completed and 40 dropped out from treatment. Final multivariate regression analyses showed that the following two variables were independently associated with attrition: lower household income and negative treatment attitudes; attributing the panic disorder to life stressors and greater age were independently associated with attrition at the trend level. Preliminary analyses suggested, in addition, associations between attrition and lower education, shorter length of prior treatment, higher anxiety sensitivity, lower agoraphobic avoidance, and a coping style of seeking social support that were not confirmed by best predictor analysis. Psychiatric comorbidity and personality styles were unrelated to attrition. The implications of these findings for future research and clinical practice are discussed.

Fluoxetine treatment of obsessive-compulsive disorder: an open clinical trial

The selective serotonin reuptake blocker fluoxetine was administered to 49 patients with obsessive-compulsive disorder in a 12-week open clinical trial. A minimum adequate trial of at least 8 weeks of treatment was completed by 39 patients. Response rates were 62% (24/39) of adequately treated patients and 49% (24/49) of the whole sample. These uncontrolled findings suggest that fluoxetine is of significant benefit for a substantial proportion of obsessive-compulsive disorder patients. However, controlled trials comparing fluoxetine with placebo and other active agents are needed to confirm this, as are studies aimed to delineate fluoxetines full dose range, optimal length of treatment and relapse rate following discontinuation.

Ventilatory effects of tryptophan depletion in panic disorder: A preliminary report

On the basis of preclinical studies, we hypothesized that deficient serotonin neurotransmission may be associated with the respiratory hyperactivity and carbon dioxide sensitivity seen in panic disorder. We used the tryptophan depletion method to investigate the effects of transient reductions in serotonin on respiration in five patients with panic disorder and seven normal control subjects. During room air breathing, the patients showed significantly increased ventilation when tryptophan-depleted, while the normal subjects showed no significant changes in respiration. These preliminary data suggest that serotonergic manipulation may affect ventilatory indices, with panic disorder patients being particularly sensitive to the effect of tryptophan depletion.

How study of respiratory physiology aided our understanding of abnormal brain function in panic disorder.

There is a substantial body of literature demonstrating that stimulation of respiration (hyperventilation) is a common event in panic disorder patients during panic attack episodes. Further, a number of abnormalities in respiration, such as enhanced CO2 sensitivity, have been detected in panic patients. This led some to posit that there is a fundamental abnormality in the physiological mechanisms that control breathing in panic disorder and that this abnormality is central to illness etiology. More recently, however, evidence has accumulated suggesting that respiratory physiology is normal in panic patients and that their tendency to hyperventilate and to react with panic to respiratory stimulants like CO2 represents the triggering of a hypersensitive fear network. The fear network anatomy is taken from preclinical studies that have identified the brain pathways that subserve the acquisition and maintenance of conditioned fear. Included are the amygdala and its brain stem projections, the hippocampus, and the medial prefrontal cortex. Although attempts to image this system in patients during panic attacks have been difficult, the theory that the fear network is operative and hyperactive in panic patients explains why both medication and psychosocial therapies are clearly effective. Studies of respiration in panic disorder are an excellent example of the way in which peripheral markers have guided researchers in developing a more complete picture of the neural events that occur in psychopathological states.

Rebreathing tests in panic disorder.

In order to compare the ventilatory response of panic patients and normal controls, 21 panic disorder patients with agoraphobia and 21 normal controls underwent the Read rebreathing test. Panic patients panicked significantly more during the test, responded with more respiratory rate and less tidal volume, but showed no hypersensitivity to inhaled carbon dioxide compared to normal controls.

Arterial blood gas changes in panic disorder and lactate- induced panic

Lactate infusions were conducted in 12 male panic patients and 8 male normal controls with arterial catheters in place to reassess previously reported acid-base changes based on venous blood samples. The analysis of arterial pH, carbon dioxide pressure, and bicarbonate concentration confirmed most venous findings. At baseline, before the infusion, venous blood shows evidence of mixed chronic and acute respiratory alkalosis in patients while arterial blood gasses are most consistent with developing acute respiratory alkalosis. During the infusion both bloods are consistent with mixed metabolic and respiratory alkalosis with the patients hyperventilating more than normal controls and panicking patients hyperventilating more than nonpanicking patients. Arterial blood seems more sensitive than venous blood in detecting baseline differences between panicking and nonpanicking patients. A baseline arterial carbon dioxide pressure of 40 mmHg or higher and an arterial pH below 7.40 may predict no subsequent panic to lactate infusion.

Cognitive-behavioral therapy for management of anxiety and medication taper in older adults.

OBJECTIVE The authors hypothesized that patients with late-life anxiety undergoing cognitive-behavioral therapy plus medical management for medication taper (CBT-MM) would realize greater reduction in medication use and greater improvement in psychological symptoms than a control group undergoing medical management alone (MM). METHODS Forty-two patients (age >60) who wanted to reduce anxiolytic medication were allocated to the two groups (CBT-MM versus MM), using a randomization plus difference-minimization procedure (to equate for medication use). RESULTS CBT-MM completers significantly reduced medication use, but not at a greater rate than MM completers. At the same time, CBT-MM completers experienced significantly greater alleviation of psychological symptoms than did MM completers. Some, but not all, treatment gains were maintained at 6-month follow-up. Intention-to-treat analyses using the mixed-effects model showed similar, but weaker, treatment effects than completer analyses. CONCLUSIONS Cognitive-behavioral therapy can alleviate psychological symptoms in elderly patients with anxiety even as patients reduce anxiolytic medication.

Exercise tolerance in panic disorder patients

Sixteen panic patients and fifteen normal controls performed submaximal exercise testing on a bicycle ergometer. Only one patient subject panicked. Biochemical, physiological, and psychological data showed similar exercise tolerance in both patients and controls. Exercise-induced distress and lactate increment do not appear to cause panic attacks.