RESUMO
OBJECTIVE: Decades of research have highlighted the involvement of the prefrontal cortex, anterior cingulated cortex, and limbic areas (amygdala) in panic disorder (PD). However, little attention has been given specifically to the inferior frontal gyrus. The current study aimed to investigate the neural substrates, including the inferior frontal gyrus, of both panic-related and negative conditions among individuals with PD and healthy controls. METHODS: We examined 13 medication-free PD patients and 14 healthy controls with functional magnetic resonance imaging (fMRI) during exposure to negative and neutral pictures and a set of specific panic-related pictures. RESULTS: Subtraction between the conditions indicated activation of the left amygdala region and the right inferior frontal gyrus in PD patients during the specific panic-related condition, whereas the left amygdalar region and left inferior frontal gyrus were activated during the negative condition in controls. CONCLUSION: These results suggest that in patients with PD, a prominent bottom-up process is involved in specific panic-related conditions, which might be associated with weak modulation of the left frontal area. These data add to our current understanding of the neural correlates of PD and can contribute to future clinical interventions targeting the functional reestablishment of these regions.
Assuntos
Transtorno de Pânico , Encéfalo/diagnóstico por imagem , Emoções , Humanos , Imageamento por Ressonância Magnética , Transtorno de Pânico/diagnóstico por imagem , Córtex Pré-FrontalRESUMO
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.
Assuntos
Anticonvulsivantes/administração & dosagem , Clonazepam/administração & dosagem , Transtorno de Pânico/tratamento farmacológico , Paroxetina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Adolescente , Adulto , Anticonvulsivantes/efeitos adversos , Brasil , Clonazepam/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Entrevista Psicológica , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/diagnóstico , Transtorno de Pânico/psicologia , Paroxetina/efeitos adversos , Inventário de Personalidade , Estudos Prospectivos , Retratamento , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Adulto JovemRESUMO
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.
Assuntos
Clonazepam/administração & dosagem , Transtorno de Pânico/tratamento farmacológico , Transtorno de Pânico/psicologia , Síndrome de Abstinência a Substâncias/prevenção & controle , Síndrome de Abstinência a Substâncias/psicologia , Adolescente , Adulto , Idoso , Clonazepam/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Escalas de Graduação Psiquiátrica/normas , Síndrome de Abstinência a Substâncias/etiologia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
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.
Assuntos
Inibidores da Monoaminoxidase/uso terapêutico , Transtorno de Pânico/tratamento farmacológico , Transtornos Fóbicos/tratamento farmacológico , Tranilcipromina/uso terapêutico , Adulto , Análise de Variância , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/complicações , Transtornos Fóbicos/complicações , Escalas de Graduação Psiquiátrica , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Mood disorders are considered related to anxiety disorders and their association may determine clinical course and prognosis. We aimed to describe with retrospective methodology the demographic, clinical, and treatment features in a group of panic disorder comorbid with bipolar I disorder (PD-BI) patients who were been treated for at least 3 year-period and compare them with bipolar I (BI) patients who were treated during the same period. METHOD: We compared the demographic and clinical data of 26 PD-BI, 28 BI, and 25 panic disorder (PD) outpatients without history of comorbidity with mood disorder were diagnosed and treated for at least 3 years in the Federal University of Rio de Janeiro. RESULTS: PD group have a higher educational level, are more married, and are more economically active. In the PD-BI and BI patients the disorders started earlier. They also turn out to have an equivalent pattern in the presence of drug abuse episodes, moderate or severe depressive episodes, psychotic episodes, suicide attempts, maniac episodes, mixed episodes, use of fewer days of antidepressants and benzodiazepines, and use of more days of antipsychotics and mood stabilizers. The PD-BI and the BI groups had a higher frequency of depressive episodes and psychotic episodes. LIMITATIONS: It is a retrospective data description based on a naturalistic treatment. The sample has a small size and the some data could be different in a large sample. CONCLUSION: PD-BI patients have demographic, clinical and therapeutic features similar to BI and the data support its validation as a special severe bipolar I disorder subgroup.
Assuntos
Transtorno Bipolar/epidemiologia , Transtorno de Pânico/epidemiologia , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Brasil , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/diagnóstico , Transtorno de Pânico/tratamento farmacológico , Estudos Retrospectivos , Fatores SocioeconômicosRESUMO
Our aim was to observe the induction of anxiety symptoms and panic attacks by a caffeine challenge test in panic disorder (PD) patients (DSM-IV) and their healthy first-degree relatives. We randomly selected 25 PD patients, 27 healthy first-degree relatives of probands with PD, and 22 healthy volunteers with no family history of PD. In a randomized double-blind experiment performed over two occasions 7 days apart, 480 mg caffeine and a caffeine-free solution were administered in a coffee form. Using specific panic attack criteria, 52.0% (n=13) PD patients, 40.7% (n=11) first-degree relatives (chi2=1.81, df=1, P=0.179), and none of the control subjects had a panic attack after the test (chi2=51.7, df=2, P<0.001). In this caffeine challenge test, PD patients and their first-degree relatives were more sensitive than healthy volunteers to the panic attack symptoms but less sensitive to headache, increase in blood pressure, and insomnia. Our data suggest that there is an association between panic attacks after the intake of 480 mg of caffeine in PD patients and their first-degree relatives. There is a clear differentiation of PD patients and their first-degree relatives by a caffeine test from the healthy group.
Assuntos
Cafeína , Estimulantes do Sistema Nervoso Central , Citratos , Transtorno de Pânico/genética , Adulto , Nível de Alerta/efeitos dos fármacos , Nível de Alerta/genética , Método Duplo-Cego , Feminino , Predisposição Genética para Doença/genética , Predisposição Genética para Doença/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/diagnóstico , Transtorno de Pânico/psicologia , Inventário de Personalidade , Fenótipo , Adulto JovemRESUMO
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.
Assuntos
Dióxido de Carbono/efeitos adversos , Hiperventilação/induzido quimicamente , Hiperventilação/epidemiologia , Transtorno de Pânico/epidemiologia , Transtorno de Pânico/etiologia , Administração por Inalação , Adulto , Dióxido de Carbono/administração & dosagem , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , MasculinoRESUMO
Our aim was to compare the demographic and clinical features of panic disorder (PD) patients with agoraphobia-DSM-IV-who had a panic attack after both an oral caffeine and the 35% carbon dioxide (CO2) challenge tests (responsive group) and compare them with PD patients who did not have a panic attack after both tests (non-responsive group). We examined 83 PD patients submitted to a 35% CO2 test and to an oral caffeine (480 mg) intake within 1 week interval. A panic attack was induced in 51 (61.4%) patients during the CO2 test (chi2=31.67, df=1, p<0.001) and in 38 (45.8%) patients during the caffeine test (chi2=18.28, df=1, p=0.023). All patients who had a panic attack during the caffeine test also had a panic attack during the CO2 test (n=38)-responsive group. The responsive had more (chi2=24.55, df=1, p=0.008) respiratory PD subtype, disorder started earlier (Mann-Whitney, p<0.001) had a higher familial prevalence of PD (chi2=20.34, df=1, p=0.019), less previous alcohol abuse (chi2=23.42, df=1, p<0.001), and had more previous depressive episodes (chi2=27.35, df=1, p<0.001). Our data suggest that there is an association between respiratory PD subtype and hyperreactivity to challenge tests: CO2 and oral caffeine.