Marcele Regine de Carvalho

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.

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.

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.

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.

The fear circuitry in panic disorder and its modulation by cognitive-behaviour therapy interventions

Panic disorder (PD) is a multidimensional anxiety disorder that involves the activation of a complex brain fear-network. The goals of this systematic review are to pinpoint some working functions of the most important neuroanatomical structures of fear and panic neurocircuitry and to raise hypotheses about how cognitive-behaviour therapy (CBT) may work on modulating the neurocircuitry of fear. The bibliographical search was carried out using mainly the PubMed database. Fifty-six articles were selected. A number of studies regarding several brain sites that participate in fear and anxiety circuitry were found and each region was described with its functionalities within the circuitry. Among the structures chosen were: the amygdala, the hippocampus and the prefrontal cortex, which play a special role. Study hypotheses showed that CBT may operate upstream from the amygdala and exert inhibitory effects on a variety of learned responses. It may work by strengthening the medial prefrontal cortex ability to inhibit firing of amygdala neurons, under the modulation of the hippocampus. Only two studies examined the modulation of fear neurocircuitry with CBT in PD. The results indicate that CBT has the potential to modify the dysfunctional neural circuitry associated with PD, but there is insufficient evidence to support the preliminary hypothesis.

Anxiogenic properties of a computer simulation for panic disorder with agoraphobia

BACKGROUND There are several useful methods to induce anxiety in patients with panic disorder with agoraphobia (PDA). Our aim was to ascertain if a computer simulation (CS) could induce anxiety and physiologic alterations in PDA patients. METHODS 10 healthy controls (HC) and 10 patients who fulfilled DSM-IV criteria for PDA were recruited for this study. The anxiety level was measured with the Subjective Units of Distress Scale (SUDS) and the Diagnostic Symptom Questionnaire (DSQ) was used to ascertain panic attack (PA) symptoms. The heart rate, skin conductance and respiration were monitored during exposure to the CS. The CS was a 3D computer animation of a short bus trip, from a first person perspective. RESULTS In PDA patients CS exposure increased anxiety levels, they also had higher scores in the DSQ and two of them had PA. Compared to the HC, the PDA patients had higher skin conductance level, electrodermal response magnitude, respiratory rate, tidal volume, and respiratory rate irregularities. The heart rate means were higher for PDA patients who had PA, followed by HC and PDA patients who did not have PA. There were no significant differences between the two groups regarding the sense of presence. LIMITATIONS The main limitations were the small sample size, and some PDA patients under medications. CONCLUSIONS This study indicated that CS exposure may induce anxiety, electrodermal and respiratory alterations in patients with PDA. CS exposure may be a useful tool in the research and treatment of PD patients.

Cognitive–behavioral therapy for bipolar disorder

Bipolar disorder is one of the most serious and prevalent psychiatric disorders. The aim of the present article is to review the efficiency of cognitive–behavioral therapy (CBT) for bipolar patients. Some studies show consistent evidence that cognitive therapy, concomitant to psycho-education and pharmacological treatment, offers efficacy in different phases of the disease. In most of the studies, patients undergoing CBT showed improvements in quality of life, with a reduction in both frequency and duration of mood episodes, as well as higher degrees of compliance and fewer hospitalizations. More studies are required to prove the effectiveness of CBT for bipolar disorder in the context of standardizing diagnostic criteria and measuring instruments to evaluate the disorder’s different phases and severity.

Exposição por realidade virtual no tratamento do medo de dirigir

A growing number of researches has appeared on virtual reality exposure therapy (VRET) to treat anxiety disorders. The purpose of this article was to review some evidences that support the VRET efficacy to treat driving phobia. The studies were identified through computerized search (PubMed/Medline, Web of Science, and Scielo databases) from 1984 to 2007. Some findings are promising. Anxiety/avoidance ratings declined from pre to post-treatment. VRET may be used as a first step in the treatment of driving phobia, as long as it may facilitate the in vivo exposure, thus reducing risks and high costs of such exposure. Notwithstanding, more randomized/controlled clinical trials are required to prove its efficacy.

Comparison between cognitive, behavioral and cognitive-behavioral approaches in the treatment of panic disorder

CONTEXTO: A terapia cognitivo-comportamental e a modalidade psicoterapeutica mais estudada no transtorno de pânico (TP) e demonstrou, nos mais diferentes estudos experimentais, ser bastante eficaz, inclusive quando comparada a grupos-controle, tratamentos psicofarmacologicos e outras formas de psicoterapias nao estruturadas. A literatura sobre o tratamento cognitivo-comportamental do TP contempla comparacoes entre as tecnicas mais utilizadas nesse tipo de psicoterapia. OBJETIVOS: Revisar a literatura que compara a eficacia dos enfoques cognitivo, comportamental e cognitivo-comportamental do TP e que destaca as limitacoes referentes a esses tratamentos psicologicos e as metodologias de pesquisa aplicadas. METODOS: Revisao sistematica da literatura, principalmente por meio da base de dados PubMed. RESULTADOS: Verificou-se que, na maioria dos estudos, a eficacia das intervencoes cognitiva, comportamental e de sua combinacao equiparou-se e hipoteses a esse respeito foram levantadas. CONCLUSOES: Deve-se atentar para o aprimoramento de importantes aspectos metodologicos, visando a resultados cada vez mais fidedignos que possam apontar direcionamentos que contribuam para o refinamento das tecnicas utilizadas.