Rafael C. Freire

Panic disorder and control of breathing

Anxiety disorders, particularly panic disorder (PD), are associated with respiratory abnormalities. PD consists of unexpected panic attacks (PA) with anxiety, fear and many autonomic and respiratory symptoms. There is a substantial body of literature demonstrating that stimulation of respiration is a common event in panic disorder patients during PA. A number of abnormalities in respiration, such as enhanced CO(2) sensitivity, have been detected in PD patients. As a result, some investigators advanced that there is a fundamental abnormality in the physiological mechanisms that control breathing in PD. Studies indicate that PD patients with dominant respiratory symptoms are particularly sensitive to respiratory tests compared with those who do not manifest dominant respiratory symptoms, possibly representing a distinct subtype. Accumulated evidence suggests that respiratory physiology remains normal in PD patients and that their tendency to hyperventilate and to react with panic to respiratory stimulants like CO(2) represents the triggering of a hypersensitive fear network. However, some recent evidences support the presence of subclinical abnormalities in respiration and other functions related to body homeostasis. The fear network, composed by the hippocampus, the medial prefrontal cortex, the amygdala and its brainstem projections, may be abnormally sensitive in PD patients. This theory might explain why both medication and psychosocial therapies are clearly effective. The evidence of abnormalities in several neurochemical systems might be just the expression of the complex interactions among brain circuits. Our aim was to review the relationship between respiration and panic disorder, addressing the respiratory subtype of panic disorder, the hyperventilation syndrome, the respiratory challenge tests, the current mechanistic concepts and the pharmacological implications.

Panic disorder respiratory subtype: psychopathology, laboratory challenge tests, and response to treatment.

Objective: Our objective is to summarize the new findings concerning the respiratory subtype (RS) of panic disorder (PD) since its first description. Methods: Two searches were made in the Institute for Scientific Information Web of Science: with the keywords “panic disorder” and “respiratory symptoms,” and all articles that cited Briggs and colleagues’ 1993 article “Subtyping of Panic Disorder by Symptom Profile” (Br J Psychiatry 1993;163:201–9). Altogether, 133 articles were reviewed. Results: We describe and discuss RS epidemiology, genetics, psychopathology, demographic features, clinical features, correlations with the respiratory system, traumatic suffocation history, provocative tests, and nocturnal panic. Compared to patients with the nonrespiratory subtype (non‐RS), the RS patients had higher familial history of PD, lower comorbidity with depression, longer duration of illness, lower neuroticism scores, and higher scores in severity scales, such as the Panic and Agoraphobia Scale, Panic‐Agoraphobia Spectrum scale and the Clinical Global Impression scale. Tests to induce panic attacks, such as those with CO2, hyperventilation, and caffeine, produce panic attacks in a higher proportion of RS patients than non‐RS patients. Differences in the subtypes’ improvement with the pharmacologic treatment were found. There are also some controversial findings regarding the RS, including the age of onset of PD, and alcohol and tobacco use in RS patients. Conclusions: Some characteristics, such as the increased sensitivity to CO2 and the higher familial history of PD, clearly distinguish the RS from the non‐RS. Nevertheless, there are also controversial findings. More studies are needed to determine the validity of the RS subtype.

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.

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.

Use of the Hospital Anxiety and Depression Scale (HADS) in a Cardiac Emergency Room – Chest Pain Unit

OBJECTIVE To determine the prevalence of anxiety and depression in patients complaining of chest pain who seek a chest pain unit attendance. INTRODUCTION Patients arriving at a Chest Pain Unit may present psychiatric disorders not identified, isolated or co-morbid to the main illness, which may interfere in the patient prognosis. METHODOLOGY Patients were assessed by the “Hospital Anxiety and Depression Scale” as a screening instrument wile following a systematized protocol to rule out the diagnosis of acute coronary syndrome and other potentially fatal diseases. Patients with 8 or more points in the scale were considered “probable case” of anxiety or depression. RESULTS According to the protocol, 59 (45.4%) of 130 patients studied presented Chest Pain of Determined Cause, and 71 (54.6%) presented Chest Pain of Indefinite Cause. In the former group, in which 43 (33.1%) had acute coronary syndrome, 33.9% were probable anxiety cases and 30.5% depression cases. In the second group, formed by patients without acute coronary syndrome or any clinical conditions involving greater morbidity and mortality risk, 53.5% were probable anxiety cases and 25.4% depression. CONCLUSION The high anxiety and depression prevalence observed may indicate the need for early and specialized approach to these disorders. When coronary arterial disease is present, this may decrease complications and shorten hospital stay. When psychiatric disorder appears isolated, is possible to reduce unnecessary repeated visits to emergency room and increase patient’s quality of life.

A randomized, naturalistic, parallel-group study for the long-term treatment of panic disorder with clonazepam or paroxetine.

Abstract This long-term extension of an 8-week randomized, naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam (n = 47) and paroxetine (n = 37) over a 3-year total treatment duration. Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine (both taken at bedtime). This study reports data from the long-term period (34 months), following the initial 8-week treatment phase. Thus, total treatment duration was 36 months. Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine, but patients with partial primary treatment success were switched to the combination therapy. At initiation of the long-term study, the mean doses of clonazepam and paroxetine were 1.9 (SD, 0.30) and 38.4 (SD, 3.74) mg/d, respectively. These doses were maintained until month 36 (clonazepam 1.9 [SD, 0.29] mg/d and paroxetine 38.2 [SD, 3.87] mg/d). Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)–Improvement rating than treatment with paroxetine (mean difference: CGI-Severity scale −3.48 vs −3.24, respectively, P = 0.02; CGI-Improvement scale 1.06 vs 1.11, respectively, P = 0.04). Both treatments similarly reduced the number of panic attacks and severity of anxiety. Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine (28.9% vs 70.6%, P < 0.001). The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course. There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events.

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.

The relationship between the severity of asthma and comorbidites with anxiety and depressive disorders

OBJETIVO: Existem evidencias de que a asma esta associada a um aumento da presenca de sintomas psiquiatricos e de transtornos mentais. O objetivo do presente estudo e o de averiguar a frequencia de transtornos de ansiedade e depressao em uma amostra de pacientes asmaticos ambulatoriais e observar se ha relacao deste tipo de comorbidade com a gravidade da asma. METODO: Sessenta e dois pacientes consecutivos de dois ambulatorios universitarios especializados em asma foram examinados. Os diagnosticos psiquiatricos foram obtidos em entrevista com a utilizacao do Mini-International Neuropsychiatric Interview 4.4 Version. RESULTADOS: Vinte e sete (43,5%) pacientes preencheram os criterios para ao menos um diagnostico psiquiatrico. Os diagnosticos mais frequentes foram depressao maior (24,0%), transtorno de ansiedade generalizada (20,9%) e transtornos do espectro pânico/agorafobia (17,7%). Nao encontramos diferencas significativas na prevalencia de transtornos de ansiedade e depressao entre os grupos com asma leve/moderada e com asma grave. Apesar da alta frequencia de depressao e transtornos de ansiedade, apenas 4 (6,5%) pacientes estavam em tratamento psiquiatrico e 13 (20,9%) estavam usando benzodiazepinicos. Doze dos 15 (80,0%) pacientes em uso de medicacao psicotropica nao estavam em tratamento psiquiatrico no momento do estudo. CONCLUSAO: Nossos resultados demonstram a elevada comorbidade de transtornos de ansiedade e depressao em pacientes asmaticos, independente da gravidade da asma.

The effectiveness of cognitive behavioral group therapy in treating bipolar disorder: a randomized controlled study

OBJETIVO: Estudos recentes sugerem que uma psicoterapia estruturada aplicada junto com a farmacoterapia pode alterar o curso do transtorno afetivo bipolar. Entretanto, poucos estudos investigam os resultados da terapia cognitivo-comportamental em grupo sobre este transtorno psiquiatrico. O objetivo desta pesquisa foi avaliar a eficacia de 14 sessoes de terapia cognitivo-comportamental em grupo concomitante a farmacoterapia para bipolares e comparar com a farmacoterapia sozinha. METODO: Quarenta e um pacientes com transtorno bipolar I e II participaram do estudo e foram alocados aleatoriamente para um dos dois grupos; trinta e sete preencheram todas as escalas. Os sintomas de humor e ansiedade de todos os participantes foram acessados. A analise estatistica foi utilizada para investigar se os grupos diferiam com relacao aos dados demograficos e entre os escores pre-, durante e pos-tratamento (intra/intergrupos). RESULTADOS: Os participantes dos dois grupos mostraram-se similares nas caracteristicas demograficas. A adicao da terapia cognitivo-comportamental em grupo ao tratamento farmacologico foi efetiva. O grupo da terapia cognitivo-comportamental em grupo apresentou menos sintomas de mania, depressao e ansiedade, bem como uma reducao na frequencia e duracao dos episodios de humor. CONCLUSAO: As sessoes de terapia cognitivo-comportamental em grupo foram especialmente importantes na melhora dos sintomas depressivos.OBJECTIVE Recent studies suggest that, when combined with pharmacotherapy, structured psychotherapy may modify the course of bipolar disorder. However, there are few studies that have examined the effects of cognitive behavioral group therapy on the course of this disorder. The aim of the present study was to evaluate the effectiveness of 14 sessions of cognitive behavioral group therapy, combined with pharmacotherapy, on the treatment of patients with bipolar disorder, and to compare our results against those from the use of pharmacotherapy alone. METHOD Forty-one patients with bipolar I and II disorder participated in the study and were randomly allocated to one of two treatment groups; thirty-seven patients remained in the study until its completion. Mood and anxiety symptoms were measured in all subjects. Statistical analysis was used to investigate if the groups differed with respect to demographic characteristics and the scores recorded in the pre- and post-treatment stages, as well as during treatment (intra/inter groups). RESULTS Patients showed statistically similar population characteristics. The association of cognitive behavioral group therapy and pharmacological treatment proved to be effective. Patients who had undergone cognitive behavioral group therapy presented fewer symptoms of mania, depression and anxiety, as well as fewer and shorter mood change episodes. CONCLUSION Cognitive behavioral group therapy sessions substantially contributed to the improvement of depression symptoms.

Virtual reality as a mechanism for exposure therapy

Virtual reality (VR) is as effective in inducing emotional responses as reality and its application is extremely valuable in exposure treatment. In virtual environments, the patients experience similar physiological symptoms and fear as they do in real life situations, thereby facilitating the habituation process. Our goal is to offer an overview of the current panorama of VR and psychotherapy, underlining the (virtual) exposure technique and the studies that focus on panic disorder treatment through the use of VR. The literature was revised through consultation to the ISI and PubMed databases. Virtual exposure treatment offers good results and great patient acceptability. However, despite the importance of this data for the evaluation of treatment efficacy, only a few studies measure physiological responses during exposure. Lack of controlled studies and standardized treatment protocols were observed. Despite the great advance of VR use in psychotherapy, a great deal of its potential is still unknown, therefore requiring the creation of new virtual environments so that controlled studies regarding its clinical application can be conducted. Throughout the process of elaboration and investigation, clinical experiences in virtual environments must be related to real experiences in a flexible context that combines relevant cultural, physical and cognitive aspects.