Respiratory panic disorder subtype: acute and long-term response to nortriptyline, a noradrenergic tricyclic antidepressant

The goal of the study was to describe with prospective methodology the therapeutic response to nortriptyline in the respiratory panic disorder (PD) subtype versus the non-respiratory subtype. A total of 118 PD outpatients (DSM-IV) were previously divided into respiratory (n=77) and non-respiratory (n=41) subtypes and then treated with nortriptyline for 1 year. Demographic and clinical features were compared in the two groups. Anxiety scales were administered before and during the treatment by raters who were blind to the subtype diagnosis. The principal instruments used to evaluate response were the Clinical Global Impression, the Sheehan Panic and Anticipatory Anxiety Scale, and the Panic Disorder Severity Scale. In the first 8 weeks of treatment (acute phase), the respiratory subtype had a significantly faster response on all the major scales. At the end of the study (week 52), there was no difference in the scale scores, and the reduction in panic attacks from baseline to end-point did not differ significantly between the two groups. In the respiratory subtype, the disorder had a later onset, was associated with a high familial history of mental disorder, and significantly more often required treatment with more than an occasional benzodiazepine. The non-respiratory subtype had significantly more previous depressive episodes. In conclusion, the respiratory PD subtype had a faster response to treatment with nortriptyline at 8 weeks than did the non-respiratory subtype, and an equivalent response after 1 year of treatment.     

Clinical features of respiratory and nocturnal panic disorder subtypes

Our aim is to compare the panic disorder (PD) respiratory subtype and the nocturnal panic subtype. A group of 193 PD patients (DSM-IV) was examined in the Laboratory of Panic and Respiration in the Institute of Psychiatry of the Federal University of Rio de Janeiro. The diagnoses were made using the SCID-I for DSM-IV. The subtypes were the respiratory (with 4 out of 5 prominent respiratory symptoms during the panic attacks [PA]) vs. non-respiratory, likewise PD with nocturnal (during sleep) PAs vs. PD with only diurnal PAs. The respiratory subtype accounted for 56.5% (n=109) of our sample; the non-respiratory subtype, 43.5% (n=84); the nocturnal subtype, 49.2% (n=95); and the non-nocturnal subtype, 50.8% (n=98). Despite a rich literature concerning correlations between the respiratory system and nocturnal panic attacks, our data do not support these findings, as the comparison of proportions in the respiratory and nocturnal groups did not differ. The non-nocturnal subtype was significantly associated with agoraphobia, and the respiratory subtype was not associated with these variables.     

Carbon dioxide test as an additional clinical measure of treatment response in panic disorder

OBJECTIVE: We aim to determine if a treatment with a dose of clonazepam--2 mg/day, for 6 weeks, blocks spontaneous panic attacks and the ones induced by the inhalation of 35% carbon dioxide (CO2) in panic disorder (PD) patients. The CO2 challenge-test may be a useful addition tool for measuring the pharmacological response during the initial phase (6 weeks) in the treatment of PD. METHOD: Eighteen PD patients drug free for a week participated in a carbon dioxide challenge test. Fourteen had a panic attack and were openly treated for a 6-week period with clonazepam. At the end of the 6-week period they were submitted again to the CO2 challenge test. RESULTS: After 6 weeks of treatment with clonazepam, 12 of 14 PD patients (85.7%) did not have a panic attack after the CO2 challenge test. Just 2 of 14 patients (14.3%) had a panic attack after the CO2 challenge test. Ten of 14 (71.4%) PD patients had panic free status after clonazepam treatment. The 2 patients who had a panic attack in the sixth week, after the CO2 test, did not have panic free status after the treatment with clonazepam. CONCLUSION: The CO2-test may be a valid tool for testing and predicting the drug response.     

Clinical Characteristics of the Respiratory Subtype in Panic Disorder Patients

Objective

Panic disorder has been suggested to be divided into the respiratory and non-respiratory subtypes in terms of its clinical presentations. The present study aimed to investigate whether there are any differences in treatment response and clinical characteristics between the respiratory and non-respiratory subtypes of panic disorder patients.

Methods

Among the 48 patients those who completed the study, 25 panic disorder patients were classified as the respiratory subtype, whereas 23 panic disorder patients were classified as the non-respiratory subtype. All patients were treated with escitalopram or paroxetine for 12 weeks. We measured clinical and psychological characteristics before and after pharmacotherapy using the Panic Disorder Severity Scale (PDSS), Albany Panic and Phobic Questionnaire (APPQ), Anxiety Sensitivity Index-Revised (ASI-R), State-Trait Anxiety Inventory (STAI-T, STAI-S), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D).

Results

The prevalence of the agoraphobia was significantly higher in the respiratory group than the non-respiratory group although there were no differences in gender and medication between the two groups. The respiratory group showed higher scores on the fear of respiratory symptoms of the ASI-R. In addition, after pharmacotherapy, the respiratory group showed more improvement in panic symptoms than the non-respiratory group.

Conclusion

Panic disorder patients with the respiratory subtype showed more severe clinical presentations, but a greater treatment response to SSRIs than those with non-respiratory subtype. Thus, classification of panic disorder patients as respiratory and non-respiratory subtypes may be useful to predict clinical course and treatment response to SSRIs.     

Psychopathological description of hyperventilation-induced panic attacks: a comparison with spontaneous panic attacks

Our aim was to describe the clinical features of hyperventilation-induced panic attacks (HPA) in panic disorder patients - DSM-IV - and to compare them with their spontaneous panic attacks and with spontaneous panic attacks in panic disorder (PD) patients not sensible to the hyperventilation challenge test. We reexamined 88 previously studied PD patients when they were submitted to a hyperventilation challenge test. They were induced to hyperventilate (30 breaths/min) for 4 min and anxiety scales were applied before and after the test. A total of 51.1% (n = 45) PD patients had a panic attack after hyperventilating - HPA (chi(2) = 13.11, d.f. = 1, p = 0.017). The clinical symptoms of the most severe panic attack were recorded by the HPA patient and by the PD patients not sensible to this test (non-HPA; n = 43, 48.9%) in a diary during a 1-week period and then compared. The HPA group had more respiratory symptoms (chi(2) = 15.26, d.f. = 1, p < 0.001), fulfilling the criteria for the respiratory PD subtype (75.6%), the disorder started later (Mann-Whitney, p < 0.001), had a higher familial prevalence of PD (chi(2) = 19.45, d.f. = 1, p = 0.036), and had more previous depressive episodes (chi(2) = 18.74, d.f. = 1, p < 0.001). The HPA group had similar symptomatology in spontaneous attacks and HPA. The HPA group may be regarded as a subgroup of the respiratory panic disorder subtype with diagnostic and therapeutic implications.     

Early carbon dioxide challenge test may predict clinical response in panic disorder

We examined whether responses to the carbon dioxide (CO(2)) challenge test were correlated with clinical response. Thirty-four panic disorder patients participated in a CO(2) test after 1 h, 2 weeks and 6 weeks of treatment with clonazepam (2 mg/day) or placebo. The clonazepam group had significantly fewer panic attacks in response to the CO(2) test and the test may predict clinical response.     

Comparison between hyperventilation and breath-holding in panic disorder: patients responsive and non-responsive to both tests

Our aim was to compare the demographic and psychopathological features of panic disorder (PD) patients who underwent hyperventilation and breath-holding challenge tests, and to describe the features of patients who had a panic attack after both tests versus those patients who did not experience panic after either test. Eighty-five PD patients were induced 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 in between. Anxiety scales were applied before and after the tests. Patients who responded with a panic attack to both tests (BPA, n = 25) were compared with patients who experienced spontaneous panic attacks but did not panic in response to the two tests (NPA, n = 16). The BPA group had a significantly higher presence of respiratory symptoms during a panic attack. The criteria for the respiratory PD subtype were fulfilled in 18 (72.0%) BPA patients and in 6 (37.5%) NPA patients. The BPA patients had a later onset of panic disorder and a higher familial prevalence of PD. Our data suggest that there is a distinction between PD patients who were sensitive to both hyperventilation and breath-holding tests and PD patients who were not affected by the challenge tests. The panic attack may be a final common pathway for different types of stimuli, and respiratory tests may characterize different PD subgroups.     

Psychopathological profile of 35% CO2 challenge test-induced panic attacks: a comparison with spontaneous panic attacks

Our aim was to describe the clinical features of 35% CO2-induced panic attacks in patients with panic disorder (PD) (Diagnostic and Statistical Manual and Mental Disorders, Fourth Edition) and compare them with the last spontaneous panic attack in patients with PD who had not had a panic attack after the 35% CO2 challenge test. We examined 91 patients with PD submitted to the CO2 challenge test. The test consisted of exhaling as fully as possible, took a fast vital capacity breath, held their breath for 8 seconds, exhaled, and then repeated the fast vital capacity breath, again holding for 8 seconds. The patients inhaled the 35% CO2/65% O2 mixture or atmospheric compressed air, randomly selected in a double-blind design. Scales were applied before and after the test. A total of 68.1% (n = 62) patients with PD had a panic attack (responders) after the CO2 test (chi2(1) = 25.87, P = .031). The last spontaneous panic attack and the symptom profile from the patients with PD who had not had a panic attack after the test (n = 29, 31.9%) were described to compare. The responders had more respiratory symptoms (chi2(1) = 19.21, P < .001), fulfilling the criteria for respiratory PD subtype (80.6%); the disorder started earlier (Mann-Whitney, P < .001), had a higher familial prevalence of PD (chi2(1) = 20.45, P = .028), and had more previous depressive episodes (chi2(1) = 27.98, P < .001). Our data suggest that there is an association between respiratory PD subtype and hyperreactivity to a CO2 respiratory challenge test. The responders may be a subgroup of respiratory PD subtype with future diagnostic and therapeutic implications.     

Differences in symptom structure between panic attack and limited symptom panic attack: A study using cluster analysis

Abstract We had investigated the clinical characteristics of panic disorder (PD) in a Japanese outpatient population comprised of more than 250 patients diagnosed as having PD during a 13-year study period and observed that some PD patients had both panic attacks (PA) and limited symptom panic attacks (LPA). In the criteria for PD based on the Diagnostic and Statistics Manual of Mental Disorders , third edition-revised ( DSM-III-R ), episodes involving four or more symptoms are classified as PA, while those involving fewer than four symptoms are described as LPA. Therefore, LPA is identified as part of an episode of PA, since the difference between the two episodes is only in the number of symptoms. However, some recent research suggests that there is a distinct subgroup of individuals who suffer LPA. Using cluster analysis, we investigated the differences between PA and LPA groups in terms of the structures of several panic symptoms, which included anticipatory anxiety, agoraphobia and 13 clinical symptoms based on the DSM-III-R at the time of panic attacks, in 247 patients with PD. Cluster analysis revealed clusters of three and four panic symptoms in the PA group and LPA group, respectively, and there were also differences in symptom structure between the two groups. These results suggest that there may be a subgroup of individuals who show LPA among PD patients.     

Double-blind clonazepam vs placebo in panic disorder treatment

OBJECTIVE: To assess the effectiveness of clonazepam, in a fixed dose (2 mg/day), compared with placebo in the treatment of panic disorder patients. METHOD: 24 panic disorder patients with agoraphobia were randomly selected. The diagnosis was obtained using the structured clinical interview for DSM-IV. All twenty-four subjects were randomly assigned to either treatment with clonazepam (2 mg/day) or placebo, during 6 weeks. Efficacy assessments included: change from baseline in the number of panic attacks; CGI scores for panic disorder; Hamilton rating scale for anxiety; and panic associated symptoms scale. RESULTS: At the therapeutic endpoint, only one of 9 placebo patients (11.1%) were free of panic attacks, compared with 8 of 13 (61.5%) clonazepam patients (Fisher exact test; p=0,031). CONCLUSION: the results provide evidence for the efficacy of clonazepam in panic disorder patients.     

Respiratory and cognitive subtypes of panic. Preliminary validation of Ley's model

A review of the panic disorder literature strongly suggests subtypes of panic attacks, including a respiratory subtype. This study empirically tested several aspects of Ley's panic subtype theory, measuring end-tidal carbon dioxide (ETCO2) levels at baseline, during psychologic and respiratory stressors, and at recovery. As predicted, Type 1 (classic or respiratory) panickers had significantly lower resting ETCO2 compared to Type 3 (cognitive) and to controls. Type 3 panickers did not differ from controls. Physiologic findings support the existence of respiratory and other subtypes of panic attacks in panic disorder. More complex measures of respiration and other physiology are likely required to elicit full subtype profiles. Distinguishing between chronic (compensated) hyperventilators and acute hyperventilators will likely be useful in clarifying the subtypes. Recognizing the need for differential diagnosis of panic attacks can facilitate developing more specific treatment plans and interventions (e.g., restoration of normal ETCO2 in Type 1), improving treatment success rates.     

35% Carbon dioxide and breath-holding challenge tests in panic disorder: a comparison with spontaneous panic attacks

Respiration and its control mechanisms may represent an important system involved in abnormal anxiety. Our aim was to compare the demographic and clinical features of patients with panic disorder (PD) with agoraphobia (DSM-IV) who had a panic attack after both the 35% carbon dioxide (CO(2)) test and the breath-holding test (CPA group), and compare them with PD patients who did not have a panic attack after both tests (NPA group). We examined 76 patients with PD who were administered a 35% CO(2)test and a breath-holding test within a 1-week interval. Anxiety scales were applied before and after each test. A panic attack was induced in 50 (65.8%) patients during the CO(2)test (chi(2) = 28.44, df = 1, P<.001) and in 40 (52.6%) patients during the breath-holding test (chi(2) = 15.35, df = 1, P = .036). All patients who had a panic attack during the breath-holding test also had a panic attack during the CO(2)test (n = 40; CPA group). Twenty-six (34.2%) patients with PD did not have a panic attack after both respiratory tests (NPA group). The CPA group had more (chi(2) = 21.67, df = 1, P = .011) respiratory PD subtype. In the CPA group, the disorder started earlier (Mann-Whitney, P<.001), had a higher familial prevalence of PD (chi(2) = 18.34, df = 1, P = .028), and had more previous depressive episodes (chi(2) = 23.59, df = 1, P<.001). Our data suggest that there is an association between respiratory PD subtype and the response to respiratory challenge tests: CO(2)and breath-holding. The CPA may be confirmed as a subgroup of respiratory PD subtype.     

Successful use of clonazepam in patients with treatment-resistant panic disorder

Ten cases are presented--two in detail--in which clonazepam was used successfully in patients with treatment-resistant panic disorder with or without agoraphobia. Seven of 10 patients who had been resistant to standard pharmacological treatments of panic attacks and agoraphobia achieved cessation of their attacks while three had mild to moderate symptom persistence. These data underscore other reports of clonazepam's usefulness in the treatment of panic disorder. Clinical use of clonazepam is discussed.     

Panic disorder respiratory subtype: a comparison between responses to hyperventilation and CO2 challenge tests

In this study 117 panic disorder patients were divided into a respiratory subtype group and a non-respiratory subtype group. The respiratory subtype patients were observed to be more sensitive to the 35% CO(2) inhalation challenge test and the hyperventilation test than the non-respiratory subtype patients.     

Low doses of clonazepam in the treatment of panic disorder

In order to assess the efficacy of a high-potency benzodiazepine in the treatment of panic disorder, an open trial was conducted with clonazepam. Clonazepam was administered in relatively low doses and, after four weeks, was shown to be effective in reducing the number of panic attacks and associated features of the disorder.     

Efficacy, safety, and gradual discontinuation of clonazepam in panic disorder: a placebo-controlled, multicenter study using optimized dosages.

BACKGROUND: The purpose of this multicenter, double-blind, placebo-controlled study was to evaluate the efficacy and safety of optimized dosages of clonazepam for the treatment of panic disorder and assess the tolerability of a schedule for gradual discontinuation. METHOD: Adult patients with panic disorder with or without agoraphobia (DSM-III-R criteria) were randomly assigned to receive either placebo or clonazepam in individually adjusted doses over 3 weeks to approximate an optimal dosage, which was then maintained for an additional 3 weeks, amounting to a 6-week therapeutic phase. The daily dose range was 0.25 to 4.0 mg administered in 2 divided doses. In the following 7-week discontinuance phase, the doses were tapered gradually to cessation. RESULTS: At the therapeutic endpoint, clonazepam (N = 222) proved clinically and statistically superior to placebo (N = 216) in change in the number of panic attacks and in Clinical Global Impressions-Severity of Illness (CGI-S) and CGI-Change scores, Patient's Global Impression of Change scores, amount of fear and avoidance associated with phobic symptoms, and duration of anticipatory anxiety. The gradual tapering of clonazepam was not associated with symptoms suggestive of withdrawal syndrome. Although patients taking clonazepam experienced some clinical worsening compared with the status achieved at endpoint, particularly in terms of number of panic attacks, no deterioration was observed using their condition at baseline as point of reference. No overall evidence of rebound was found. All regimens were generally well tolerated. Somnolence was the main adverse event associated with clonazepam therapy. The percentage of patients who reported adverse events was higher in the clonazepam group than in the placebo group, as was the mean number of adverse events per patient. CONCLUSION: In this placebo-controlled trial, clonazepam was an efficacious and safe shortterm treatment of the symptoms of panic disorder. Discontinuance during and after slow tapering was well tolerated.     

Depersonalization in panic disorder: a clinical study

Panic disorder (PD) has been hypothesized to be a heterogeneous entity, with distinct clinical subgroups. The presence of depersonalization during panic attacks may distinguish a specific subgroup of PD. We sought to analyze the differential features of a subgroup of PD patients with depersonalization. A total of 274 patients with PD were assessed and divided into 2 groups according to the presence or absence of depersonalization. The Structured Clinical Interview for DSM-III-R (SCID-UP-R) was used to assess PD and comorbid disorders. The clinical scales administered included the Hamilton Anxiety and Depression Rating Scale (HARS and HDRS), the Marks and Mathews Fears and Phobia Scale, Panic-Associated Symptom Scale (PASS), and a panic attack symptoms inventory. A total of 66 patients (24.1%) exhibited depersonalization during the attacks. Patients with depersonalization appeared to be younger and had an earlier age at onset. PD was more severe in the depersonalization group (greater number of attacks, worse level of functioning, and higher scores on most self-rating scales). Also, depersonalization patients showed more comorbidity with specific phobia. Our results support the view that PD with depersonalization may be considered a distinct and more severe subcategory of PD.     

Physiological changes during carbon dioxide inhalation in patients with panic disorder, major depression, and premenstrual dysphoric disorder: evidence for a central fear mechanism

BACKGROUND: Inhalation of carbon dioxide (CO(2)) has been shown to produce more anxiety in patients with panic disorder (PD) than in healthy comparison subjects or patients with most other psychiatric illnesses tested, although premenstrual dysphoric disorder (PMDD) may be an exception. Several reasons have been proposed to explain CO(2) breathing effects in PD. We examined differences in respiratory response to CO(2) breathing in 4 groups to address these issues. METHODS: Patients with PD (n = 52), healthy controls (n = 32), patients with PMDD (n = 10), and patients with major depression without panic (n = 21) were asked to breathe 5% and 7% CO(2). Continuous measures of respiratory physiological indices were made. RESULTS: Carbon dioxide breathing produced the expected increases in all 4 respiratory variables measured. More patients with PD and PMDD had panic attacks than did controls or patients with major depression. Subjects who experienced panic during 5% or 7% CO(2) inhalation had the most extreme increases regardless of diagnostic group. Among patients with PD, baseline end-tidal carbon dioxide levels were significantly lower in those who subsequently had a panic attack during 5% CO(2) breathing than those who did not. CONCLUSIONS: Although CO(2) breathing causes a higher rate of panic attacks in patients with PD than other groups (except PMDD), the physiological features of a panic attack appear similar across groups. Once a panic attack is triggered, minute ventilation and respiratory rate increase regardless of whether the subject carries a PD diagnosis. These findings are compatible with preclinical fear conditioning models of anxiogenesis.     

Nocturnal panic and recent life events

Recent research has hypothesized an association between traumatic events and nocturnal panic (NP). The purpose of this study was to investigate whether the onset of nocturnal panic attacks is associated with a higher frequency of and/or greater severity of stressful or traumatic life events than that of patients with panic disorders (PDs) who experience daytime panic attacks (DPs) while awake. A secondary aim was to investigate whether NP is associated with specific life events at the onset of the disorder. Our sample comprised 129 subjects with PD (DSM-IV). We investigated the number and types of stressful life events that occurred in the year prior to PD onset using a semistructured interview. Of the sample, 28.7% had recurrent nocturnal panic attacks (NP group). Subjects with and without recurrent NP did not differ on any sociodemographic or clinical characteristic. Neither the number nor type of life event distinguished those with or without NP. The subgroup of patients with PD with recurrent NP appears to represent a variant of PD with a possible increased vulnerability to conditions of diminished arousal as a trigger of panic attacks. However, the hypothesis that this vulnerability might be determined by life events that occur in the period preceding PD onset was not supported by the findings of this study.     

Clonazepam in the treatment of obsessive compulsive disorder associated with panic disorder in one patient

The authors present the case of a 21-year-old man with obsessive compulsive disorder (OCD) complicated by panic disorder, whose OCD and panic symptoms resolved during clonazepam treatment. Prior treatment with an equivalent dose of lorazepam had ameliorated his panic attacks without affecting his obsessions or compulsions. Clonazepam worked with a rapidity and completeness uncharacteristic of more established treatments for OCD.