Fabiana L. Lopes

Psychiatric disorders in asthmatic outpatients

It has been reported that the lifetime prevalence of panic disorder in patients with pulmonary disease is higher than epidemiologic estimates of population prevalence. We evaluated the frequency of anxiety disorders in 86 subjects from the Outpatient Asthma Clinic. Psychiatric diagnoses were assessed with the Mini-International Neuropsychiatric Interview 4.4 Version (MINI). Forty-five asthmatic patients (52.3%) reported at least one current anxiety disorder. The frequency of panic disorder with or without agoraphobia was 13.9% (n=12) and that of agoraphobia without panic disorder was 26.8% (n=23). Social anxiety and generalized anxiety disorders occurred in 9.3% (n=8) and 24.4% (n=21) of the sample, respectively. Twenty-nine patients (33.7%) reported a major depressive episode. The psychiatric morbidity of the sample was 61.6% (n=53). Our results tend to support the high morbidity of anxiety disorders, particularly panic/agoraphobic spectrum disorders, in asthmatic outpatients.

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 (χ2 = 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 (χ2 = 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 (χ2 = 19.45, d.f. = 1, p = 0.036), and had more previous depressive episodes (χ2 = 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.

Panic disorder and social anxiety disorder subtypes in a caffeine challenge test

Studies have demonstrated the vulnerability of anxiety disorder patients to challenge tests. Our aim was to observe if panic disorder (PD) patients and generalized social anxiety disorder (GSAD) and performance social anxiety disorder (PSAD) patients respond in a similar way to the induction of anxiety symptoms and panic attacks by an oral caffeine challenge test. We compared 28 PD patients, 25 GSAD patients, 19 PSAD, and 26 control subjects after a 480-mg caffeine test. The patients had not received psychotropic drugs for at least a 4-week period. In a randomized double-blind experiment performed in two occasions 7 days apart, 480 mg of caffeine and a caffeine-free solution were administered and anxiety scales were administered before and after each test. A panic attack was induced in 17 (60.7%) PD patients, 4 (16.0%) GSAD patients, and 10 (52.6%) PSAD patients, during the caffeine test. None of the control subjects had a panic attack after the caffeine intake. Neither patients nor any control subject had a panic attack after drinking the caffeine-free solution. Our data suggest that there is an association between PD and PSAD hyperreactivity to an oral caffeine challenge test. The PD and PSAD patients had a higher number of induced panic attacks, some specific anxiety symptoms, and a more severe anxiety response than GSAD patients and normal volunteers.

Smoking and psychiatric disorders: a comorbidity survey

Epidemiological and clinical studies have shown a positive correlation between smoking and psychiatric disorders. To investigate the prevalence of cigarette smoking, 277 psychiatric outpatients with anxiety or depressive disorders (DSM-IV) answered a self-evaluation questionnaire about smoking behavior and were compared with a group of 68 control subjects. The diagnoses (N = 262) were: 30.2% (N = 79) major depressive disorder, 23.3% (N = 61) panic disorder, 15.6% (N = 41) social anxiety disorder, 7.3% (N = 19) other anxiety disorders, and 23.7% (N = 62) comorbidity disorders. Among them, 26.3% (N = 69) were smokers, 23.7% (N = 62) were former smokers and 50.0% (N = 131) were nonsmokers. The prevalence of nicotine dependence among the smokers was 59.0% (DSM-IV). The frequency of cigarette smoking did not show any significant difference among the five classes of diagnosis. The social anxiety disorder patients were the heaviest smokers (75.0%), with more unsuccessful attempts to stop smoking (89.0%). The frequency of former smokers was significantly higher among older subjects and nonsmokers were significantly younger (chi2 = 9.13, d.f. = 2, P = 0.01). Our data present some clinical implications suggesting that in our psychiatric outpatient sample with anxiety disorder, major depression and comorbidity (anxiety disorder and major depression), the frequency of cigarette smoking did not differ from the frequency found in the control group or in general population studies. Some specific features of our population (outpatients, anxiety and depressive disorders) might be responsible for these results.

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.

A three-year follow-up study of patients with the respiratory subtype of panic disorder after treatment with clonazepam.

The demographic, clinical and therapeutic features of the respiratory subtype of panic disorder (PD) versus the non-respiratory subtype were studied in a prospective design. Sixty-seven PD outpatients (DSM-IV), who had previously been categorized into respiratory (n=35) and non-respiratory (n=32) subgroups, were openly treated with clonazepam for a 3-year period. The principal measure of efficacy was the number of panic attacks, obtained from the Sheehan Panic and Anticipatory Anxiety Scale. In the first 8 weeks of treatment (acute phase), the respiratory subtype group had a significantly faster response to clonazepam. During the follow-up (weeks 12-156), the two subgroups did not differ significantly in the number of panic attacks experienced from baseline to end point. Patients in the respiratory subtype were characterized by a later onset of disorder and a family history of PD. Patients in the non-respiratory subgroup had a significantly higher number of past depressive episodes than those in the respiratory subgroup. The respiratory subgroup had a faster response after 8 weeks of treatment and an equivalent response in the 3-year follow-up period. Clonazepam had a sustained therapeutic effect over the entire treatment period.

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.

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.

Tapering clonazepam in patients with panic disorder after at least 3 years of treatment.

High-potency benzodiazepines, such as clonazepam, are frequently used in the treatment of panic disorder (PD) because of their rapid onset of action and good tolerability. However, there is concern about their potential to cause withdrawal symptoms. We aimed to develop a protocol for safely tapering off clonazepam in patients with PD who had been receiving treatment for at least 3 years. A specific scale for judging withdrawal was also developed, the Composite Benzodiazepine Discontinuation Symptom Scale. We selected 73 patients with PD who had been asymptomatic for at least 1 year and who wished to discontinue the medication. The trial consisted of a 4-month period of tapering and an 8-month follow-up period. The dosage of clonazepam was decreased by 0.5 mg per 2-week period until 1 mg per day was reached, followed by a decrease of 0.25 mg per week. The mean dosage at the start of tapering was 2.7 ± 1.2 mg/d. In total, 51 (68.9%) of the patients were free of the medication after the 4 months of tapering according to the protocol, and 19 (26.0%) of the patients needed another 3 months to be free of medication. Clonazepam discontinuation symptoms were mostly mild and included mainly: anxiety, shaking/trembling/tremor, nausea/vomiting, insomnia/nightmares, excessive sweating, tachycardia/palpitations, headache, weakness, and muscle aches. The improvement in PD and general well-being was maintained during both the taper and follow-up phases. Clonazepam can be successfully discontinued without any major withdrawal symptoms if the dose is reduced gradually. We recommend reducing the dosage of clonazepam after intermediate-term use by 0.25 mg/wk.

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 (chi(2) = 1.28, d.f. = 1, P = 0.672) respiratory symptoms (fear of dying, chest/pain discomfort, 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%, chi(2) = 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.