Aripiprazol no tratamento do transtorno de estresse pós-traumático: um ensaio clínico aberto

OBJECTIVE: Post traumatic stress disorder is frequent in the general population (7.8%-lifetime-USA). The selective serotonin reuptake inhibitors are the first choice of treatment but result in low remission rates. This study aims to evaluate the effect of aripiprazole monotherapy for the treatment of post traumatic stress disorder. METHOD: Thirty-two patients diagnosed with post traumatic stress disorder were included in a 16-week open label trial of aripiprazole. They were evaluated at baseline, week 8, and 16 with the Clinician-Administered PTSD Scale, Beck Depression Inventory, Beck Anxiety Inventory, Medical Outcome Study Short Form 36, and Social Adjustment Scale. Statistical analysis were performed with an intention-to-treat approach and last observation carried forward. A general linear model for repeated measures comparing the factor with 3 continuous measures from baseline, 8 and 16 weeks was used. A between-subject factor was included RESULTS: Nine patients discontinued the treatment. The mean aripiprazole dose was 9.6 (± 4.3) mg/day. The mean scores at baseline and endpoint for all measures were: Clinician-Administered PTSD Scale - 82.7 (± 23.1) and 51.4 (± 31.4) (F = 11.247, p = 0.001); Beck Anxiety Inventory - 31.7 (± 13.4) and 25.4 (± 18.2) (F = 8.931, p = 0.011); Social Adjustment Scale - 2.4 (± 0.45) and 2.27 (± 0.57) (F = 8.633, p = 0.012); Medical Outcome Study Short Form 36 - 76.6 (± 14.11) and 94.01 (± 25.06) (F = 10.127 p = 0.007); and Beck Depression Inventory - 26.06 (± 11.6) and 21.35 (± 12.6) (F = 1.580, p = 0.042). In all measurements, the differences were statistically significant. CONCLUSIONS: Patients achieved a good response to treatment with aripiprazole, but placebo-controlled studies are needed for more accurate results.OBJETIVO: O transtorno de estresse pós-traumático é um quadro prevalente (7,8%-lifetime-EUA) que provoca grande prejuízo aos pacientes. Os inibidores seletivos de recaptação de serotonina, medicação de primeira escolha para o tratamento, mostram baixos índices de remissão. Este estudo pretende apresentar uma diferente escolha de medicamento para tratar o transtorno de estresse pós-traumático. MÉTODO: Trinta e dois pacientes com transtorno de estresse pós-traumático receberam aripiprazol por 16 semanas. Foram submetidos na entrada, 8 e 16 semanas às escalas Clinician-Administered PTSD Scale, Beck Depression Inventory, Beck Anxiety Inventory, Medical Outcome Study Short Form 36 e Social Adjustment Scale. Foi usado o modelo linear generalizado para medidas repetidas comparando o fator com as três medidas contínuas nos três pontos de avaliação. Foi feita uma comparação entre sujeitos (grupo tratamento) usando modelo linear generalizado univariado. Usamos a intenção de tratamento e a estratégia da última observação com endpoint (Last Observation Carried Forward). RESULTADOS: Nove pacientes descontinuaram antes da segunda avaliação. A dose média foi 9,6 (± 4,3) mg/dia. As medidas na entrada e no final do tratamento foram: Clinician-Administered PTSD Scale - 82,7 (± 23,1) e 51,4 (± 31,4) (F = 11,247, p = 0,001); Beck Anxiety Inventory - 31,7 (± 13,4) e 25,4 (± 18,2) (F = 8,931, p = 0,011); Social Adjustment Scale - 2,4 (± 0,45) e 2,27 (± 0,57) (F = 8,633, p = 0,012); Medical Outcome Study Short Form 36 - 76,6 (± 14,11) e 94,01 (± 25,06) (F = 10,127 p = 0,007); e Beck Depression Inventory - 26,06 (± 11,6) e 21,35 (± 12,6) (F = 1,580, p = 0,042). Em todas as medidas, as diferenças foram estatisticamente significativas. CONCLUSÕES: O aripiprazol alcançou uma boa resposta em pacientes com transtorno de estresse pós-traumático, mas para resultados mais acurados ainda são necessários estudos controlados com placebo.Universidade Federal de São Paulo (UNIFESP) Department of Psychiatry Victims of Violence and Stress ProgramUNIFESP, Department of Psychiatry Victims of Violence and Stress ProgramSciEL

Early Trauma Inventory (ETI): cross-cultural adaptation and internal consistency

Early life stress is a strong predictor of future psychopathology during adulthood. The Early Trauma Inventory (ETI) was developed to detect the presence and impact of traumatic experiences that occurred up to 18 years of age. The ETI was translated and cross-culturally adapted and had its consistency evaluated. Victims of violence that met the inclusion and exclusion criteria were submitted to SCID-I and ETI. Ninety-one patients with post-traumatic stress disorder (PTSD) were included. Cronbach's alpha in the different domains varied from 0.595 to 0.793, and the total score was 0.878. Except for emotional abuse, most of the various domains displayed inter-item correlation rates of 0.51 to 0.99. The adapted version was useful for clinical and research purposes and showed good internal consistency and inter-item correlation. The ETI is a valid instrument with good consistency for evaluating history of childhood and adolescent trauma in adults.As experiências traumáticas precoces são um fator de risco preditivo de problemas psicopatológicos futuros. O Early Trauma Inventory (ETI) é um instrumento que avalia em indivíduos adultos experiências traumáticas ocorridas antes dos 18 anos de idade. Tal instrumento foi traduzido, transculturalmente adaptado e sua consistência interna foi avaliada. Vítimas de violência que preencheram os critérios de inclusão e exclusão foram submetidas a uma entrevista diagnóstica (SCID-I) e ao ETI. Foram incluídos 91 pacientes com o transtorno do estresse pós-traumático (TEPT). O alfa de Cronbach nos diferentes domínios variou de 0,595-0,793, e o escore total foi de 0,878. A maior parte dos itens nos vários domínios, com exceção do abuso emocional, apresentou índices de correlação interitem entre 0,51-0,99. A versão adaptada foi útil tanto na clínica quanto na pesquisa. Apresentou boa consistência interna e na correlação interitem. O ETI é um instrumento válido, com boa consistência para se avaliar a presença de história de traumas precoces em indivíduos adultos.Universidade Federal de São Paulo (UNIFESP)Universidade de São Paulo Instituto de PsicologiaUNIFESPSciEL

The posttraumatic stress disorder project in Brazil: neuropsychological, structural and molecular neuroimaging studies in victims of urban violence

<p>Abstract</p> <p>Background</p> <p>Life trauma is highly prevalent in the general population and posttraumatic stress disorder is among the most prevalent psychiatric consequences of trauma exposure. Brazil has a unique environment to conduct translational research about psychological trauma and posttraumatic stress disorder, since urban violence became a Brazilian phenomenon, being particularly related to the rapid population growth of its cities. This research involves three case-control studies: a neuropsychological, a structural neuroimaging and a molecular neuroimaging study, each focusing on different objectives but providing complementary information. First, it aims to examine cognitive functioning of PTSD subjects and its relationships with symptomatology. The second objective is to evaluate neurostructural integrity of orbitofrontal cortex and hippocampus in PTSD subjects. The third aim is to evaluate if patients with PTSD have decreased dopamine transporter density in the basal ganglia as compared to resilient controls subjects. This paper shows the research rationale and design for these three case-control studies.</p> <p>Methods and design</p> <p>Cases and controls will be identified through an epidemiologic survey conducted in the city of São Paulo. Subjects exposed to traumatic life experiences resulting in posttraumatic stress disorder (cases) will be compared to resilient victims of traumatic life experiences without PTSD (controls) aiming to identify biological variables that might protect or predispose to PTSD. In the neuropsychological case-control study, 100 patients with PTSD, will be compared with 100 victims of trauma without posttraumatic stress disorder, age- and sex-matched controls. Similarly, 50 cases and 50 controls will be enrolled for the structural study and 25 cases and 25 controls in the functional neuroimaging study. All individuals from the three studies will complete psychometrics and a structured clinical interview (the Structured Clinical Interview for DSM-IV and the Clinician-Administered PTSD Scale, Beck Anxiety Inventory, Beck Depression Inventory, Global Assessment of Function, The Social Adjustment Scale, Medical Outcomes Study 36-Item Short-Form Health Survey, Early Trauma Inventory, Clinical global Impressions, and Peritraumatic Dissociative Experiences Questionnaire). A broad neuropsychological battery will be administered for all participants of the neuropsychological study. Magnetic resonance scans will be performed to acquire structural neuroimaging data. Single photon emission computerized tomography with [(99m)Tc]-TRODAT-1 brain scans will be performed to evaluate dopamine transporters.</p> <p>Discussion</p> <p>This study protocol will be informative for researchers and clinicians interested in considering, designing and/or conducting translational research in the field of trauma and posttraumatic stress disorder.</p

The accuracy of the Clinician-Administered PTSD Scale (CAPS) to identify PTSD cases in victims of urban violence

As a consequence of the increasing urban violence in Brazil, many cases of posttraumatic stress disorder (PTSD) are now seen in the community and clinical settings. the main aim of this article is to assess the psychometric properties of the Clinician-Administered PTSD Scale (CAPS) to study factors related to the etiology, prognosis, and efficacy of interventions of PTSD in civilian populations. PTSID outpatients from a program of victims of violence and subjects identified in an epidemiological survey conducted in the city of São Paulo completed a battery of validated instruments and the CAPS. Instrument reliability and validity were measured. the comparison between the CAPS scores and the Structured Clinical Interview for DSM IV (SCID) interview resulted in the following validity coefficients: sensitivity = 90%, specificity = 95%, and misclassification rate = 7.1%. the area under the receiver operating characteristic (ROC) curve was 0.97. There was a positive correlation between CAPS scores with Beck Depression Inventory (BDI; 0.70) and Beck Anxiety Inventory (BAI; 0.76) scores. the Kappa coefficients were all higher than 0.63 for all CAPS items. the internal consistency for all CAPS items resulted in a Cronbach's alpha coefficient of 0.97. the CAPS showed to be both an accurate and a reliable research instrument to identify PTSD cases in a civilian population. (C) 2009 Elsevier Ireland Ltd. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Psiquiatria, BR-04026001 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psiquiatria, BR-04026001 São Paulo, BrazilFAPESP: 2004/15039-0CNPq: 420122/2005-2CAPES: 27909024886Web of Scienc

Reduced cerebellar left hemisphere and vermal volume in adults with PTSD from a community sample

Background: Traumatic events exposure is a necessary condition for developing posttraumatic stress disorder (PTSD), but not all individuals exposed to the same trauma will develop PTSD. Human studies have suggested that the cerebellum is involved in human fear perception, anticipation, and recollection. in this context, the current study evaluated whether cerebellar volume is associated with PTSD.Methods: Eighty-four victims of violence, 42 who fulfilled the DSM-IV-TR criteria for PTSD and 42 resilient controls, were identified through an epidemiologic survey conducted in the city of 530 Paulo. Subjects were evaluated using the Clinician-Administered PTSD Scale (CAPS), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Early Trauma Inventory (ETI). All subjects underwent a magnetic resonance imaging (MRI) scan to evaluate their cerebellar hemispheres and vermis.Results: PTSD subjects had relative smaller left hemisphere (p = 0.04) and vermis (p < 0.01) volumes persisted after controlling for gender, age, and brain volume. in PTSD group, left cerebellar hemisphere volume correlated negatively with PTSD (p = 0.01) and depressive symptoms (p = 0.04). Vermal volume correlated negatively with PTSD symptoms (p < 0.01), early traumatic life events (p < 0.01), depressive symptoms (p = 0.04) and anxiety (p = 0.01).Conclusion: the cerebellum is involved in emotion modulation, and our results suggest that cerebellar volumetric reduction is associated with mood, anxiety and PTSD symptoms. Early traumatic life experiences are related to vermal volume reduction and may be a risk factor for future PTSD development. (C) 2011 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo UNIFESP, LiNC, Edificio Pesquisas UNIFESP 2, BR-04039032 São Paulo, BrazilUFT, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Programa Atendimento & Pesquisa Violencia PROVE, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Nucleo Estat & Metodol Aplicadas NEMAP, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, LiNC, Edificio Pesquisas UNIFESP 2, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Programa Atendimento & Pesquisa Violencia PROVE, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Nucleo Estat & Metodol Aplicadas NEMAP, BR-04039032 São Paulo, BrazilFAPESP: 2004/15039-0CNPq: 420122/2005-2Web of Scienc

Reduction of anterior cingulate in adults with urban violence- related PTSD

Background: To evaluate differences in limbic structure volume of subjects exposed to urban violence during adulthood, between those who developed posttraumatic stress disorder (with PTSD) and resilient matched controls (without PTSD).Methods: Limbic volumetric measures of 32 subjects with PTSD and 32 subjects without PTSD who underwent brain MRI were analyzed in an epidemiological study in the city of São Paulo. the hippocampus, amygdala, cingulate, and parahipocampal gyri volumes were estimated using FreeSurfer software. We also investigated the association between limbic volumetric measurements, symptom's severity, and early life stress history (measure by Early Trauma Inventory - ETI).Results: Subjects with PTSD presented reduced volume of the right rostral part of the anterior cingulate, compared to subjects without PTSD, after controlling for iraracranial volume, Eft and depressive symptoms. Subjects with PTSD presented larger bilateral hippocampus and right amygdala, but secondary to the higher EU in PTSD group there was a positive correlation between with bilateral hippocampus, bilateral amygclala, and left parahippocampus.Limitations.: First, the cross-sectional study design precludes causal interpretation of limbic structure reduction in PTSD, consequence of PTSD, or other life events. Finally, since the sample size was not sufficiently large, we could not observe whether or not limbic structure volume could be related to the type of trauma.Conclusions: the present study provides evidence of a reduced anterior cingulate volume in subjects with PTSD than in resilient subjects exposed to urban violence. Enlargement of hippocampus and amygdala volume was observed in subjects with PTSD, however secondary to early trauma experience. (C) 2014 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, LiNC, BR-04039032 São Paulo, BrazilUniv Fed Tocantins, Palmas, TO, BrazilUniversidade Federal de São Paulo, LiNC, BR-04039032 São Paulo, BrazilFAPESP: 2004/15039-0CNPq: 420122/2005-2Web of Scienc