RENERIO FRAGUAS JUNIOR
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Psiquiatria, Faculdade de Medicina - Docente
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Guidelines' recommendations for the treatment-resistant depression: A systematic review of their quality(2023) GABRIEL, Franciele Cordeiro; STEIN, Airton Tetelbom; MELO, Daniela de Oliveira; FONTES-MOTA, Gessica Caroline Henrique; SANTOS, Itamires Benicio dos; RODRIGUES, Camila da Silva; DOURADO, Andrea D.; RODRIGUES, Monica Cristiane; FRAGUAS, Renerio; FLOREZ, Ivan; CORREIA, Diogo Telles; RIBEIRO, ElianeIntroductionDepression is a serious and widespread mental health disorder. A significant proportion of patients with depression fail to remit after two antidepressant treatment trials, a condition named treatment-resistant depression (TRD). Clinical practice guidelines (CPGs) are instruments aimed to improve diagnosis and treatment. This study objective is to systematically appraise the quality and elaborate a comparison of high-quality CPGs with high-quality recommendations aimed at TRD. Methods and analysisWe searched several specialized databases and organizations that develop CPGs. Independent researchers assessed the quality of the CPGs and their recommendations using AGREE II and AGREE-REX instruments, respectively. We selected only high-quality CPGs that included definition and recommendations for TRD. We investigated their divergencies and convergencies as well as weak and strong points. ResultsAmong seven high-quality CPGs with high-quality recommendations only two (Germany's Nationale Versorgungs Leitlinie-NVL and US Department of Veterans Affairs and Department of Defense-VA/DoD) included specific TRD definition and were selected. We found no convergent therapeutic strategy among these two CPGs. Electroconvulsive therapy is recommended by the NVL but not by the VA/DoD, while repetitive transcranial magnetic stimulation is recommended by the VA/DoD but not by the NVL. While the NVL recommends the use of lithium, and a non-routine use of thyroid or other hormones, psychostimulants, and dopaminergic agents the VA/DoD does not even include these drugs among augmentation strategies. Instead, the VA/DoD recommends ketamine or esketamine as augmentation strategies, while the NVL does not mention these drugs. Other differences between these CPGs include antidepressant combination, psychotherapy as a therapeutic augmentation, and evaluation of the need for hospitalization all of which are only recommended by the NVL. ConclusionsHigh-quality CPGs for the treatment of depression diverge regarding the definition and use of the term TRD. There is also no convergent approach to TRD from currently high-quality CPGs.
- Association among depression, cognitive impairment and executive dysfunction after stroke(2012) TERRONI, Luisa; SOBREIRO, Matildes F.M.; CONFORTO, Adriana B.; ADDA, Carla C.; GUAJARDO, Valeri D.; LUCIA, Mara Cristina S. de; FRÁGUAS, RenérioABSTRACT The relationship between depression and cognitive impairment, frequent after stroke, is complex and has not been sufficiently elucidated. Objective: To review the relationship between post-stroke depression and cognitive impairment. Methods: We performed a PubMed database search spanning the last ten years, using the terms post-stroke depression, cognitive dysfunction, cognitive impairment and neuropsychological tests. Our target studies were original quantitative studies that investigated the relationship between post-stroke depression (PSD) and cognitive impairment in stroke patients. Articles published in English, Spanish, Italian and Portuguese were considered. Selection criteria were the use of neuropsychological tests to assess cognitive function, and of either instruments to diagnose major depression, or scales to assess depressive symptoms, within the first three months after stroke. Results: Six original quantitative studies fulfilled the criteria. The prevalence of PSD within the first three months after stroke ranged from 22% to 31%. Incidence ranged from 25% to 27% and was evaluated in only two studies. PSD was associated with increased cognitive impairment. Cognitive impairment was reported in 35.2% to 87% of the patients. Post-stroke cognitive deficits were reported mostly in executive function, memory, language, and speed of processing. Conclusion: Executive dysfunction and depression occur in stroke survivors, are frequently coexistent, and also associated with worse stroke prognosis. Healthcare professionals need to address and provide adequate treatment for depression and executive dysfunctions in stroke patients early in the first three months after stroke. Future studies should evaluate the efficacy of programs evaluating the early detection and treatment of PSD and executive dysfunction in stroke survivors.
- The association of post-stroke anhedonia with salivary cortisol levels and stroke lesion in hippocampal/parahippocampal region(2015) TERRONI, Luisa; AMARO JR., Edson; IOSIFESCU, Dan V.; MATTOS, Patricia; YAMAMOTO, Fabio I.; TINONE, Gisela; CONFORTO, Adriana B.; SOBREIRO, Matildes F. M.; GUAJARDO, Valeri D.; LUCIA, Mara Cristina S. De; MOREIRA, Ayrton C.; SCAFF, Milberto; LEITE, Claudia C.; FRAGUAS, RenerioBackground: Anhedonia constitutes a coherent construct, with neural correlates and negative clinical impact, independent of depression. However, little is known about the neural correlates of anhedonia in stroke patients. In this study, we investigated the association of post-stroke anhedonia with salivary cortisol levels and stroke location and volume. Patients and methods: A psychiatrist administered the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition to identify anhedonia in 36 inpatients, without previous depression, consecutively admitted in a neurology clinic in the first month after a first-ever ischemic stroke. Salivary cortisol levels were assessed in the morning, evening, and after a dexamethasone suppression test. We used magnetic resonance imaging and a semi-automated brain morphometry method to assess stroke location, and the MRIcro program according to the Brodmann Map to calculate the lesion volume. Results: Patients with anhedonia had significantly larger diurnal variation (P-value =0.017) and higher morning levels of salivary cortisol (1,671.9 +/- 604.0 ng/dL versus 1,103.9 +/- 821.9 ng/dL; P-value =0.022), and greater stroke lesions in the parahippocampal gyrus (Brodmann area 36) compared to those without anhedonia (10.14 voxels; standard deviation +/- 17.72 versus 0.86 voxels; standard deviation +/- 4.64; P-value =0.027). The volume of lesion in the parahippocampal gyrus (Brodmann area 36) was associated with diurnal variation of salivary cortisol levels (rho=0.845; P-value =0.034) only in anhedonic patients. Conclusion: Our findings suggest that anhedonia in stroke patients is associated with the volume of stroke lesion in the parahippocampal gyrus and with dysfunction of the hypothalamic-pituitary-adrenal axis.
- The relationship of major depressive disorder with Crohn?s disease activity(2023) FACANALI, Carolina Bortolozzo Graciolli; SOBRADO JUNIOR, Carlos Walter; FRAGUAS JUNIOR, Renerio; FACANALI JUNIOR, Marcio Roberto; BOARINI, Lucas Rodrigues; SOBRADO, Lucas Faraco; CECCONELLO, IvanIntroduction: Crohn's disease (CD) has been related to an increased prevalence of psychiatric disorders and suicide risk (SR). However, the nature of their relationship still deserves clarification. The aim of this study is to assess the prevalence of major depressive disorder (MDD) in patients with CD, and to investigate the relationship between MDD and CD outcomes.Methods: A cross-sectional study involving CD patients was performed. CD activity was evaluated by the Harvey -Bradshaw index and CD phenotype by the Montreal classification. The presence of MDD was assessed by the Patient Health Questionnaire score-9 (PHQ-9). Sociodemographic data and other characteristics were retrieved from electronic medical records.Results: 283 patients with CD were included. The prevalence of MDD was 41.7%. Females had a risk of MDD 5.3 times greater than males. CD disease duration was inversely correlated with MDD severity. Individuals with active CD were more likely to have MDD (OR = 796.0; 95% CI 133.7-4738.8) than individuals with CD remis-sion. MDD was more prevalent in inflammatory behavior (45.5%) and there were no statistical differences regard-ing the disease location. 19.8% of the sample scored positive for SR.Conclusion: The present results support data showing an increased prevalence of MDD in individuals with CD. Additionally, it indicates that MDD in CD might be related to the activity of CD. Prospective studies are warranted to confirm these results and to address whether MDD leads to CD activity, CD activity leads to MDD or both ways are existent.
- Factors associated with higher quality of clinical practice guidelines and their recommendations for the pharmacological treatment of depression: a systematic review(2023) GABRIEL, Franciele Cordeiro; MELO, Daniela Oliveira de; STEIN, Airton Tetelbom; FONTES-MOTA, Gessica Caroline Henrique; SANTOS, Itamires Benicio dos; RODRIGUES, Camila da Silva; RODRIGUES, Monica Cristiane; RIBEIRO, Tatiane Bomfim; FRAGUAS, Renerio; FLOREZ, Ivan D.; TELLES-CORREIA, Diogo; RIBEIRO, ElianeObjective The objective of this study was to assess the quality of clinical practice guidelines (CPGs) for the pharmacological treatment of depression along with their recommendations and factors associated with higher quality. Design We conducted a systematic review that included CPGs for the pharmacological treatment of depression in adults. Data sources We searched for publications from 1 January 2011 to 31 December 2021, in MEDLINE, Cochrane Library, Embase, PsycINFO, BVS and 12 other databases and guideline repositories. Eligibility criteria for selecting studies We included CPGs containing recommendations for the pharmacological treatment of depression in adults at outpatient care setting, regardless of whether it met the U.S. National Academy of Medicine criteria, or not. If a CPG included recommendations for both children and adults, they were considered. No language restriction was applied. Data extraction and synthesis Data extraction was also conducted independently and in duplicate, a process that was validated in a previous project. The quality of the CPGs and their recommendations were assessed by three independent reviewers using Appraisal of Guidelines for Research and Evaluation (AGREE II) and Appraisal of Guidelines for Research and Evaluation-Recommendations Excellence (AGREE-REX). A CPG was considered to be of high quality if AGREE II Domain 3 was >= 60%; while their recommendations were considered high if AGREE-REX Domain 1 was >= 60%. Results Seventeen out of 63 (27%) CPGs were classified as high quality, while 7 (11.1%) had high-quality recommendations. The factors associated with higher-scoring CPGs and recommendations in the multiple linear regression analyses were 'Handling of conflicts of interest', 'Multiprofessional team' and 'Type of institution'. 'Inclusion of patient representative in the team' was also associated with higher-quality recommendations. Conclusions The involvement of professionals from diverse backgrounds, the handling of conflicts of interest, and the inclusion of patients' perspectives should be prioritised by developers aiming for high-quality CPGs for the treatment of depression.
- Subcutaneous Ketamine in Depression: A Systematic Review(2021) CAVENAGHI, Vitor Breseghello; COSTA, Leandro Paulino da; LACERDA, Acioly Luiz Tavares; HIRATA, Edson Shiguemi; MIGUEL, Euripedes Constantino; FRAGUAS, RenerioBackground: Ketamine has been shown to produce a rapid and robust antidepressant effect. Though numerous routes of administration have been studied, subcutaneous (SC) has proven to be a convenient and cost-effective route making its use particularly relevant in developing countries. Here we provide a systematic review covering the use of SC racemic ketamine and esketamine in depression, including its efficacy, safety and tolerability. Methods: A systematic literature search was carried out, from inception through March, 2021, using PubMed/MEDLINE, EMBASE and Web of Science, with no limits of language. After identifying 159 potentially relevant articles, 12 articles were selected after applying our inclusion/exclusion criteria. These comprised two randomized clinical trials, five case-reports and five retrospective studies. Given the small number of studies found and their heterogeneous nature, a meta-analysis was not considered appropriate. Here we provide a synthesis of these data including participant characteristics, dose range, efficacy, safety/ tolerability. Risk of bias was accessed using the Cochrane risk of bias tool. Results: SC Ketamine was administered to unipolar and bipolar patients a single or multiple doses, weekly or twice-weekly, a dose-titration approach was made in major studies, dose ranged from 0.1 to 0.5 mg/Kg of racemic ketamine and 0.5-1 mg/Kg of esketamine. Across all studies, SC ketamine showed a rapid and robust antidepressant effect, with response/ remission rates from 50 to 100% following both single or multiple doses, with transitory side effects. Conclusion: SC racemic ketamine and esketamine in depression is a promising strategy showing beneficial efficacy and tolerability. Future studies exploring the SC route, its cost-effectiveness, and a direct comparison with IV and intranasal (IN) protocols are warranted. Systematic Review Registration: CRD42019137434
- The Impact of Post-Stroke Depressive Symptoms on Cognitive Performance in Women and in Men: A 4 Month Prospective Study(2023) SOBREIRO, Matildes F. M.; TERRONI, Luisa; GUAJARDO, Valeri Delgado; MATTOS, Patricia Ferreira; LEITE, Claudia da Costa; JR, Edson Amaro; TINONE, Gisela; IOSIFESCU, Dan V.; FRAGUAS, RenerioBackground: Depressive symptoms have been associated with cognitive impairment after stroke, and women may be specifically affected. Objective: The aim of this study was to investigate gender-specific characteristics in the relationship between changes in depression severity and changes in cognitive performance after stroke. Methods: We prospectively evaluated 73 patients without a previous history of depression in the first and fourth months after a first ischemic stroke. The severity of depressive symptoms was assessed using the 31-item version of the Hamilton Rating Scale for Depression, and executive function, attention, working memory, and verbal fluency were assessed using a neuropsychological battery. Results: We included 46 (63.0%) men and 27 (36.9%) women, with mean ages of 55.2 (SD & PLUSMN; 15.1) and 46.8 (SD & PLUSMN; 14.7) years, respectively. We found significant improvement in the digit span forward and Stroop dots from month 1 to month 4 post stroke for both men and women. Women, but not men, presented a correlation between changes in phonemic verbal fluency and changes in the 31-item version of the Hamilton Rating Scale for Depression scores. Improvement in depression was correlated with improvement in verbal fluency, and worsening in depression was correlated with worsening in verbal fluency. Conclusions: Our results suggest that women might be more vulnerable to the relationship between depressive symptoms and cognitive performance, and improvement of depression may be necessary for women's improvement in phonemic verbal fluency from the first to the fourth month after a stroke. We did not adjust the results for multiple comparisons. Thus, our findings might be considered preliminary, and confirmatory studies, also focusing on specific characteristics of women that could explain these differences, are warranted.
- The Influence of Depression on the Psychometric Properties of the Maslach Burnout Inventory-Human Services Survey: A Cross-Sectional Study With Nursing Assistants(2018) TRIGO, Telma R.; FREITAS, Camila C. S. de; WANG, Yuan-Pang; RIBEIRO, Floracy G.; LUCIA, Mara Cristina S. de; SIQUEIRA, Jose O.; IOSIFESCU, Dan V.; HALLAK, Jaime Eduardo C.; FRAGUAS, RenerioBackground: The Maslach Burnout Inventory-Human Services Survey (MBI-HSS) is the most commonly used instrument to assess burnout. Although various factors have been reported to influence its validity, the influence of major depressive disorder (MDD) has not been previously considered. We developed this study to investigate the influence of MDD on the psychometric properties of the MBI-HSS in nursing assistants. Results: From a sample of 521 nursing assistants, we found in those with MDD (n = 138, 24.56%) a degree of data mis fit into the model, revealed by non-acceptable values for the root mean square error of approximation (RMSEA; 0.073; p = 0.004) and for the comparative fit index (CFI; 0.912), while in the non-MDD group these indices were acceptable and good, respectively, for RMSEA (0.048; p = 0.639) and for CFI (0.951). Also, we found higher coefficients of correlation among MBI-HSS factors and less items loading properly in their respective factors in the MDD subset, when compared to the non-MDD subset. For the total sample, while original 3-factor solution was an acceptable model, the bifactor model fitted data better. Conclusions: MDD may impair the construct validity of MBI-HSS subscales, by increasing measurement error and decreasing model fitness. Therefore, researchers and health professionals should be aware of potential changes in the psychometric properties of the MBI-HSS when applied in subjects with depression.