Clinical features of panic patients sensitive to hyperventilation or breath-holding methods for inducing panic attacks

Our aim was to compare the clinical features of panic disorder (PD) patients sensitive to hyperventilation or breath-holding methods of inducing panic attacks. Eighty-five PD patients were submitted to both a hyperventilation challenge test and a breath-holding test. They were asked to hyperventilate (30 breaths/min) for 4 min and a week later to hold their breath for as long as possible, four times with a 2-min interval. Anxiety scales were applied before and after the tests. We selected the patients who responded with a panic attack to just one of the tests, i.e., those who had a panic attack after hyperventilating (HPA, N = 24, 16 females, 8 males, mean age ± SD = 38.5 ± 12.7 years) and those who had a panic attack after breath holding (BHPA, N = 20, 11 females, 9 males, mean age ± SD = 42.1 ± 10.6 years). Both groups had similar (chi² = 1.28, d.f. = 1, P = 0.672) respiratory symptoms (fear of dying, chest/pain disconfort, shortness of breath, paresthesias, and feelings of choking) during a panic attack. The criteria of Briggs et al. [British Journal of Psychiatry, 1993; 163: 201-209] for respiratory PD subtype were fulfilled by 18 (75.0%) HPA patients and by 14 (70.0%) BHPA patients. The HPA group had a later onset of the disease compared to BHPA patients (37.9 ± 11.0 vs 21.3 ± 12.9 years old, Mann-Whitney, P < 0.001), and had a higher family prevalence of PD (70.8 vs 25.0%, chi² = 19.65, d.f. = 1, P = 0.041). Our data suggest that these two groups - HPA and BHPA patients - may be specific subtypes of PD.

Impact of alcohol intoxication and withdrawal syndrome on social phobia and panic disorder in alcoholic inpatients

PURPOSE: To investigate the impact of alcohol intoxication and withdrawal on the course of social phobia and panic disorder. METHOD: A group of 41 alcoholic inpatients undergoing detoxification therapy were interviewed using the SCID-I (DSM-IV) and questions to detect fluctuations in the course of social phobia and panic disorder as a function of the different phases in alcohol dependence (intoxication, withdrawal, and lucid interval). RESULTS: Only 1 (2.4%) patient presented panic disorder throughout life, and 9 (21.9%) had panic attacks during alcohol intoxication or during the withdrawal syndrome. Sixteen (39%) alcoholic patients showed social phobia with onset prior to drug use. However, drinking eventually became unable to alleviate social phobia symptoms or worsened such symptoms in 31.2% of social-phobic patients. While patients with social phobia reported a significant improvement in psychiatric symptoms during alcohol intoxication, patients experiencing panic attacks worsened significantly during intoxication. In the withdrawal phase, patients with social phobia tended to have more and more intense phobic symptoms. CONCLUSION: Our findings indicate that the impact of alcohol intoxication is different for social phobia as compared to panic disorder, at first decreasing the social-phobic symptoms but later aggravating them. In panic disorder, the impact of intoxication by alcohol is more harmful, at least in the short term.

Adverse life events and coping skills in panic disorder

Research literature and clinical experience shows that panic patients are often able to identify stressors that preceded the onset of their first attacks. In this study we investigated the relation between life events, coping skills, and panic disorder. METHODS: Forty-tree panic patients were compared with 29 control subjects regarding the occurrence and the impact of stressful life events in a 1-year period preceding the onset of panic attacks using the Social Readjustment Rating Scale and London Life Event and Difficulty Schedule. Coping skills were measured using the Ways of Coping Questionnaire. RESULTS: No differences were observed between panic patients and controls regarding the number of reported stressful life events in the previous year. Panic patients compared to controls reported loss of social support as the most meaningful class of events significantly more often. In response to stressful situations, panic patients more often used coping skills judged as ineffective. CONCLUSIONS: The present study suggests that the type of life event and the coping skills used in response to them, more than the occurrence of stressful events itself, may be associated with the onset of panic disorder.

Some notes on a historical perspective of panic disorder

This article aims to describe important points in the history of panic disorder concept, as well as to highlight the importance of its diagnosis for clinical and research developments. Panic disorder has been described in several literary reports and folklore. One of the oldest examples lies in Greek mythology - the god Pan, responsible for the term panic. The first half of the 19th century witnessed the culmination of medical approach. During the second half of the 19th century came the psychological approach of anxiety. The 20th century associated panic disorder to hereditary, organic and psychological factors, dividing anxiety into simple and phobic anxious states. Therapeutic development was also observed in psychopharmacological and psychotherapeutic fields. Official classifications began to include panic disorder as a category since the third edition of the American Classification Manual (1980). Some biological theories dealing with etiology were widely discussed during the last decades of the 20th century. They were based on laboratory studies of physiological, cognitive and biochemical tests, as the false suffocation alarm theory and the fear network. Such theories were important in creating new diagnostic paradigms to modern psychiatry. That suggests the need to consider a wide range of historical variables to understand how particular features for panic disorder diagnosis have been developed and how treatment has emerged.

Cardio-respiratory symptoms in panic disorder: a contribution from cognitive-behaviour therapy

Objective: To compare patients with panic disorder with agoraphobia treated with cognitive-behavioural therapy (CBT) associated with the medication with patients treated only with medication and verify the behaviour of the cardio-respiratory symptoms of both groups. Methods: Randomized sample in the Psychiatry Institute of the Federal University of Rio de Janeiro, divided in two groups of 25 participants each. Group 1 undertook 10 weekly sessions of CBT with one hour of duration each together with medication. Group 2, Control, were administered medication that only consisted of tricyclic anti-depressants and selective inhibitors of the re-uptake of serotonin. Evaluation instruments were applied at the beginning and to the end of the interventions. Results: According to the applied scales, group 1 showed statistically more significant results than group 2, with: reduction of panic attacks, cardio-respiratory symptoms, anticipatory anxiety, agoraphobia avoidance and fear of bodily sensations. Conclusion: Exposures (in vivo and interoceptive), especially for induction symptom exercises and relaxation, were considered essential to prepare patients with panic disorder to handle future cardio-respiratory symptoms and panic attacks with agoraphobia.

Hyperventilation in panic disorder patients and healthy first-degree relatives

Our aim was to observe the induction of panic attacks by a hyperventilation challenge test in panic disorder patients (DSM-IV) and their healthy first-degree relatives. We randomly selected 25 panic disorder patients, 31 healthy first-degree relatives of probands with panic disorder and 26 normal volunteers with no family history of panic disorder. All patients had no psychotropic drugs for at least one week. They were induced to hyperventilate (30 breaths/min) for 4 min and anxiety scales were applied before and after the test. A total of 44.0% (N = 11) panic disorder patients, 16.1% (N = 5) of first-degree relatives and 11.5% (N = 3) of control subjects had a panic attack after hyperventilating (chi² = 8.93, d.f. = 2, P = 0.011). In this challenge test the panic disorder patients were more sensitive to hyperventilation than first-degree relatives and normal volunteers. Although the hyperventilation test has a low sensitivity, our data suggest that there is no association between a family history of panic disorder and hyperreactivity to an acute hyperventilation challenge test. Perhaps cognitive variables should be considered to play a specific role in this association since symptoms of a panic attack and acute hyperventilation overlap.

Fighting by sleep-deprived rats as a possible manifestation of panic: effects of sodium lactate

Increased fighting is an effect of desynchronized sleep deprivation (DSD) in rats, and recently this behavior has been suggested to be spontaneous panic and equivalent to panic disorder. In the present study we tested this hypothesis by evaluating the effect of sodium lactate on this aggressiveness, because this substance is recognized to induce spontaneous panic attacks in patients. A total of 186 male albino Wistar rats, 250-350 g, 90-120 days of age, were submitted to DSD (multiple platform method) for 0, 4, or 5 days. At the end of the deprivation period the rats were divided into subgroups respectively injected intraperitoneally with 1.86, 2.98 and 3.72 g/kg of 1 M sodium lactate, or 1.86 and 3.72 g/kg of 2 M sodium lactate. The control animals were submitted to the same procedures but received equivalent injections of sodium chloride. Regardless of DSD time, sleep-deprived animals that received sodium lactate presented a significantly higher mean number of fights (0.13 ± 0.02 fights/min) and a longer mean time spent in confrontation (2.43 ± 0.66 s/min) than the controls (0.01 ± 0.006 fights/min and 0.12 ± 0.07 s/min, respectively; P<0.01, Student t-test). For the sodium lactate group, concentration of the solution and time of deprivation increased the number of fights, with the mean number of fights and mean duration of fighting episodes being greater with the 2.98 g/kg dose using 1 M lactate concentration. These results support the hypothesis that fighting induced by DSD is probably a spontaneous panic manifestation. However, additional investigations are necessary in order to accept this as a promising animal model for studies on panic disorder.

Mirtazapine versus fluoxetine in the treatment of panic disorder

Mirtazapine is an antidepressant whose side effect profile differs from that of first-line agents (selective serotonin reuptake inhibitors) used in the treatment of panic disorder. The present study compared the effect of mirtazapine and fluoxetine in the treatment of panic disorder in a double-blind, randomized, flexible-dose trial conducted with outpatients. After a 1-week single-blind placebo run-in, 27 patients entered an 8-week double-blind phase in which they were randomly assigned to treatment with either mirtazapine or fluoxetine. Both groups improved significantly in all but one efficacy measure (P<=0.01). ANOVA showed no significant differences between the two treatment groups in number of panic attacks, Hamilton Anxiety Scale or Sheehan Phobic Scale, whereas measures of patient global evaluation of phobic anxiety were significantly different between groups (F1,20 = 6.91, P = 0.016) favoring mirtazapine. For the 22 patients who completed the study, the mean daily dose of mirtazapine was 18.3 ± 1.3 vs 14.0 ± 1.0 mg for fluoxetine at the endpoint. Weight gain occurred more frequently in the mirtazapine group (50 vs 7.7%, P = 0.04) and nausea and paresthesia occurred more often in the fluoxetine group (P = 0.01). Results suggest that mirtazapine has properties that make it attractive for the treatment of panic disorder.

Respiratory panic disorder subtype and sensitivity to the carbon dioxide challenge test

The aim of the present study was to verify the sensitivity to the carbon dioxide (CO2) challenge test of panic disorder (PD) patients with respiratory and nonrespiratory subtypes of the disorder. Our hypothesis is that the respiratory subtype is more sensitive to 35% CO2. Twenty-seven PD subjects with or without agoraphobia were classified into respiratory and nonrespiratory subtypes on the basis of the presence of respiratory symptoms during their panic attacks. The tests were carried out in a double-blind manner using two mixtures: 1) 35% CO2 and 65% O2, and 2) 100% atmospheric compressed air, 20 min apart. The tests were repeated after 2 weeks during which the participants in the study did not receive any psychotropic drugs. At least 15 of 16 (93.7%) respiratory PD subtype patients and 5 of 11 (43.4%) nonrespiratory PD patients had a panic attack during one of two CO2 challenges (P = 0.009, Fisher exact test). Respiratory PD subtype patients were more sensitive to the CO2 challenge test. There was agreement between the severity of PD measured by the Clinical Global Impression (CGI) Scale and the subtype of PD. Higher CGI scores in the respiratory PD subtype could reflect a greater sensitivity to the CO2 challenge due to a greater severity of PD. Carbon dioxide challenges in PD may define PD subtypes and their underlying mechanisms.

Effects of reversible inactivation of the dorsomedial hypothalamus on panic- and anxiety-related responses in rats

The medial hypothalamus is part of a neurobiological substrate controlling defensive behavior. It has been shown that a hypothalamic nucleus, the dorsomedial hypothalamus (DMH), is involved in the regulation of escape, a defensive behavior related to panic attacks. The role played by the DMH in the organization of conditioned fear responses, however, is less clear. In the present study, we investigated the effects of reversible inactivation of the DMH with the GABA A agonist muscimol on inhibitory avoidance acquisition and escape expression by male Wistar rats (approximately 280 g in weight) tested in the elevated T-maze (ETM). In the ETM, inhibitory avoidance, a conditioned defensive response, has been associated with generalized anxiety disorder. Results showed that intra-DMH administration of the GABA A receptor agonist muscimol inhibited escape performance, suggesting an antipanic-like effect (P < 0.05), without changing inhibitory avoidance acquisition. Although a higher dose of muscimol (1.0 nmol/0.2 µL; N = 7) also altered locomotor activity in an open field when compared to control animals (0.2 µL saline; N = 13) (P < 0.05), the lower dose (0.5 nmol/0.2 µL; N = 12) of muscimol did not cause any motor impairment. These data corroborate previous evidence suggesting that the DMH is specifically involved in the modulation of escape. Dysfunction of this regulatory mechanism may be relevant in the genesis/maintenance of panic disorder.

Psychopharmacotherapy of panic disorder: 8-week randomized trial with clonazepam and paroxetine

The objective of the present randomized, open-label, naturalistic 8-week study was to compare the efficacy and safety of treatment with clonazepam (N = 63) and paroxetine (N = 57) in patients with panic disorder with or without agoraphobia. Efficacy assessment included number of panic attacks and clinician ratings of the global severity of panic disorders with the clinical global impression (CGI) improvement (CGI-I) and CGI severity (CGI-S) scales. Most patients were females (69.8 and 68.4% in the clonazepam and paroxetine groups, respectively) and age (mean ± SD) was 35.9 ± 9.6 years for the clonazepam group and 33.7 ± 8.8 years for the paroxetine group. Treatment with clonazepam versus paroxetine resulted in fewer weekly panic attacks at week 4 (0.1 vs 0.5, respectively; P < 0.01), and greater clinical improvements at week 8 (CGI-I: 1.6 vs 2.9; P = 0.04). Anxiety severity was significantly reduced with clonazepam versus paroxetine at weeks 1 and 2, with no difference in panic disorder severity. Patients treated with clonazepam had fewer adverse events than patients treated with paroxetine (73 vs 95%; P = 0.001). The most common adverse events were drowsiness/fatigue (57%), memory/concentration difficulties (24%), and sexual dysfunction (11%) in the clonazepam group and drowsiness/fatigue (81%), sexual dysfunction (70%), and nausea/vomiting (61%) in the paroxetine group. This naturalistic study confirms the efficacy and tolerability of clonazepam and paroxetine in the acute treatment of patients with panic disorder.

New perspective on the pathophysiology of panic: merging serotonin and opioids in the periaqueductal gray

Panic disorder patients are vulnerable to recurrent panic attacks. Two neurochemical hypotheses have been proposed to explain this susceptibility. The first assumes that panic patients have deficient serotonergic inhibition of neurons localized in the dorsal periaqueductal gray matter of the midbrain that organize defensive reactions to cope with proximal threats and of sympathomotor control areas of the rostral ventrolateral medulla that generate most of the neurovegetative symptoms of the panic attack. The second suggests that endogenous opioids buffer normal subjects from the behavioral and physiological manifestations of the panic attack, and their deficit brings about heightened suffocation sensitivity and separation anxiety in panic patients, making them more vulnerable to panic attacks. Experimental results obtained in rats performing one-way escape in the elevated T-maze, an animal model of panic, indicate that the inhibitory action of serotonin on defense is connected with activation of endogenous opioids in the periaqueductal gray. This allows reconciliation of the serotonergic and opioidergic hypotheses of panic pathophysiology, the periaqueductal gray being the fulcrum of serotonin-opioid interaction.

Dorsal periaqueductal gray stimulation facilitates anxiety-, but not panic-related, defensive responses in rats tested in the elevated T-maze

The escape response to electrical or chemical stimulation of the dorsal periaqueductal gray matter (DPAG) has been associated with panic attacks. In order to explore the validity of the DPAG stimulation model for the study of panic disorder, we determined if the aversive consequences of the electrical or chemical stimulation of this midbrain area can be detected subsequently in the elevated T-maze. This animal model, derived from the elevated plus-maze, permits the measurement in the same rat of a generalized anxiety- and a panic-related defensive response, i.e., inhibitory avoidance and escape, respectively. Facilitation of inhibitory avoidance, suggesting an anxiogenic effect, was detected in male Wistar rats (200-220 g) tested in the elevated T-maze 30 min after DPAG electrical stimulation (current generated by a sine-wave stimulator, frequency at 60 Hz) or after local microinjection of the GABA A receptor antagonist bicuculline (5 pmol). Previous electrical (5, 15, 30 min, or 24 h before testing) or chemical stimulation of this midbrain area did not affect escape performance in the elevated T-maze or locomotion in an open-field. No change in the two behavioral tasks measured by the elevated T-maze was observed after repetitive (3 trials) electrical stimulation of the DPAG. The results indicate that activation of the DPAG caused a short-lived, but selective, increase in defensive behaviors associated with generalized anxiety.

Piranha attacks in dammed streams used for human recreation in the State of São Paulo, Brazil

In recent years, attacks by piranhas have become a common problem in dammed portions of rivers and streams in the State of Sao Paulo, Southeastern Brazil. In two outbreaks recorded in two neighboring counties in the Northwest region of the state, 74 bathers were bitten. Only one bite per person was recorded during a short period of the year. The bites were related to parental care and/or defense of spawning territory, which confirms previous studies and demystify the attacks by these legendary fish, as they are perceived by most people. Placement of fine mesh nets and removal of aquatic vegetation stopped the attacks.

Hormonal response during a fenfluramine-associated panic attack

Secretion curves for prolactin, cortisol, TSH, and GH from a 37-year old woman with dysthymia and panic disorder with agoraphobia were determined one day prior to (day I), and during a panic attack (day II) associated with an oral dose of 60 mg dl-fenfluramine, a drug known to increase anticipatory anxiety. The increased cortisol secretion observed is discussed in relation to the hormonal correlates of anxiety and the possible role of depression, dl-fenfluramine, and serotonergic receptor sensitivity