Valfrido L. de-Melo-Neto

Current findings of fMRI in panic disorder: contributions for the fear neurocircuitry and CBT effects

Thanks to brain imaging great advances have been made concerning the comprehension of neural substrates related to panic disorder (PD). This article aims to: review the recent functional MRI (fMRI) studies concerning PD; correlate the PD fMRI neurobiological findings with the fear neurocircuitry hypothesis; discuss the fear neurocircuitry hypothesis and link it to cognitive–behavior therapy findings; and comment on fMRI study limitations and suggest methodological changes for future research. As a whole, there is increasing evidence that brain structures such as the prefrontal cortex, the anterior cingulate cortex and limbic areas (hippocampus and amygdala) might play a major role in the panic response.

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 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.

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.

Double-blind comparison of 30 and 60 mg tranylcypromine daily in patients with panic disorder comorbid with social anxiety disorder

Our objective was to explore the dose-response relationship in patients with panic disorder and social anxiety disorder comorbidity (DSM-IV). After 1 week of no-drug washout, 36 such patients were assigned to a double-blind controlled comparison of the effects of 30 mg and 60 mg of tranylcypromine, and were followed up for 12 weeks. The main instrument used to measure the number of panic attacks was the Sheehan Panic and Anticipatory Anxiety Scale. The primary outcome measure for social anxiety disorder symptoms was the mean change from baseline in the Liebowitz Social Anxiety Scale (LSAS). After 12 weeks of treatment, panic attacks were reduced 69.6% from baseline in the 30-mg group (n=19) compared with a 74.8% reduction in the 60-mg group (n=17). Twelve patients (70.6%) of the higher dose group and 14 patients (68.4%) of the lower dose were completely free of panic attacks. There was no difference in efficacy between the tranylcypromine groups in the panic disorder symptoms. The 60-mg dose was more efficacious as measured by the LSAS scores, showing a significant difference in relation to the lower group. Mean change from baseline in LSAS total score (mean+/-SD) for 30-mg group was 17.9+/-14.7 and for the 60-mg group was 35.0+/-14.8. The social anxiety symptom scale showed a two-fold greater change with the 60-mg dose, and the 30-mg dose group could be considered the equivalent of a placebo control group. Tranylcypromine--60 mg daily--was found effective in the treatment of panic disorder and social anxiety disorder comorbidity.

Subtipos respiratório e não respiratório do transtorno de pânico: Comparações clínicas e de qualidade de vida

Resumo Objectivo: comparar os scores dos diversos dominios de qualidade de vida e quadro clinico entre os doentes com subtipos respiratorio e nao respiratorio de transtorno de pânico (TP) em tratamento no Laboratorio de Pânico e Respiracao da UFRJ. Metodo: estudo transversal com 32 doentes com TP com ou sem comorbidades em tratamento ambulatorial, selecionados consecutivamente e diagnostica-dos atraves do MINI v.4.4. Destes, 12 (37,5%) apresentam o subtipo respiratorio (SR) e 20 (62,5%) o subtipo nao respiratorio (SN), de acordo com Briggs et al. Resultados: Em relacao aos indices de qualidade de vida, houve apenas diferenca no dominio psicologico, sendo que os doentes do subgrupo SN apresentaram piores scores. Os diferentes subtipos de TP (SR e SN) nao apresentaram diferencas significativas quanto a distribuicao por genero, idade, escolaridade, ocupa-cao, estado civil, tabagismo e comorbidades. Clinica-mente tambem nao foram encontradas diferencas significativas nos scores de ansiedade, nem de gravidade do TP (BAI, STAI-T, STAI-S, PAS), bem como nao se observaram diferencas quanto a idade de inicio do transtorno ou tempo de evolucao da doenca. Conclusao: Doentes do subtipo nao respiratorio, que apresentam indices semelhantes de ansiedade e gravidade do TP, quando em tratamento, apresentam piores scores de qualidade de vida psicologica do que os do subtipo respiratorio. Rev Port Pneumol 2009; XV (5): 859-874

Phobic postural vertigo: a cognitive-behavior approach

VERTIGEM POSTURAL FóbICA: UMA AbORdAGEM COGnITIVA-COMPORTAMEnTAL Clinical Psychologist, Graduate Student and Researcher of the Institute of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro RJ, Brazil (UFRJ); MD, Msc. Graduate Student and Researcher of the Institute of Psychiatry, UFRJ; Ph.D., Associate Professor of Institute of Psychology, State University of Rio de Janeiro, Rio de Janeiro RJ, Brazil (UERJ); MD, PhD, Associate Professor of Medical School/Institute of Psychiatry, UFRJ. This research project is supported by the Brazilian Council for Scientific and Technological Development (CNPq), grant 554411/2005-9.

Respiratory and non-respiratory panic disorder subtypes: Clinical and quality of life comparisons

AIM to compare the scores of the WHOQOL quality of life domains with the clinical features of patients with respiratory and non-respiratory panic disorders (PD) treated at the UFRJ Panic and Respiration Laboratory. METHOD cross sectional study. Thirty-two PD outpatients under treatment were consecutively selected and evaluated by the MINI v.4.4. They were divided into two different groups according to Briggs et al. classification of respiratory and non-respiratory PD subtypes. Twelve (37.5%) patients had the respiratory subtype (SR) and 20 (62.5%) the non-respiratory subtype (SN). RESULTS the SN patients presented worse scores in the psychological domain of the WHOQOL. There were no differences between groups in gender, age, level of schooling, occupational status, marital status, smoking and comorbidities. There were no differences in the anxiety questionnaires and PD questionnaire (BAI, STAI-T, STAI-S, PAS) scores and in the age at the beginning of the disorder and the disorders duration. CONCLUSION non-respiratory subtype patients presented worse scores in the psychological domain of WHOQOL than the respiratory subtype group, when they had similar anxiety and PD scores.

O tabagismo e o transtorno do pânico: gravidade e comorbidades

INTRODUCAO: Estudos indicam que ha uma associacao entre tabagismo e transtorno do pânico, e alguns autores sugerem que o tabagismo aumenta o risco de ataques de pânico e transtorno do pânico. Este estudo analisa a hipotese de que pacientes fumantes com esse transtorno apresentam um quadro clinico mais grave. METODO: Sessenta e quatro pacientes em tratamento no Laboratorio do Pânico e Respiracao (Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro), com transtorno do pânico, segundo criterios do Manual de Diagnostico e Estatistica das Perturbacoes Mentais (DSM, 4a edicao), foram divididos em grupos de tabagistas e nao-tabagistas. Os grupos foram avaliados quanto a caracteristicas sociodemograficas, comorbidades e gravidade do quadro clinico. RESULTADOS: Nao houve diferenca significativa em relacao a gravidade do transtorno do pânico; no entanto, tabagistas tiveram prevalencia de depressao significativamente maior (p = 0,014) do que nao-tabagistas. CONCLUSAO: Este estudo nao evidenciou que o transtorno do pânico em tabagistas e mais grave, porem indicou que esses pacientes tem mais comorbidade com depressao.