RENERIO FRAGUAS JUNIOR

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Lattes
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Departamento de Psiquiatria, Faculdade de Medicina - Docente
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Líder

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  • article 5 Citação(ões) na Scopus
    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, Eliane
    IntroductionDepression 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.
  • article 88 Citação(ões) na Scopus
    Stroke lesion in cortical neural circuits and post-stroke incidence of major depressive episode: A 4-month prospective study
    (2011) TERRONI, Luisa; AMARO JR., Edson; IOSIFESCU, Dan V.; TINONE, Gisela; SATO, Joao Ricardo; LEITE, Claudia Costa; SOBREIRO, Matildes F. M.; LUCIA, Mara Cristina Souza; SCAFF, Milberto; FRAGUAS, Renerio
    Objective. Little is known about the relevance of lesion in neural circuits reported to be associated with major depressive disorder. We investigated the association between lesion stroke size in the limbic-cortical-striatal-pallidal-thalamic (LCSPT) circuit and incidence of major depressive episode (MDE). Methods. We enrolled 68 patients with first-ever ischemic stroke and no history of major depressive disorder. Neurological and psychiatric examinations were performed at three time-points. We diagnosed major depressive episode, following DSM-IV criteria. Lesion location and volume were determined with magnetic resonance imaging, using a semi-automated method based on the Brodmann Cytoarchitectonic Atlas. Results. Twenty-one patients (31%) experienced major depressive episode. Larger lesions in the left cortical regions of the LCSPT circuit (3,760 vs. 660 mm(3); P = 0.004) were associated with higher incidence of MDE. Secondary analyses revealed that major depressive episode was associated with larger lesions in areas of the medial prefrontal cortex including the ventral (BA24) and dorsal anterior cingulate cortex (BA32) and subgenual cortex (BA25); and also the subiculum (BA28/36) and amygdala (BA34). Conclusions Our findings indicate that depression due to stroke is aetiologically related to the disruption of the left LCSPT circuit and support the relevance of the medial prefrontal cortex dysfunction in the pathophysiology of depression.
  • article 26 Citação(ões) na Scopus
    The association of major depressive episode and personality traits in patients with fibromyalgia
    (2011) SANTOS, Danyella de Melo; LAGE, Lais Verderame; JABUR, Eleonora Kehl; KAZIYAMA, Helena Hideko Seguchi; IOSIFESCU, Dan V.; LUCIA, Mara Cristina Souza de; FRAGUAS, Renerio
    INTRODUCTION: Personality traits have been associated with primary depression. However, it is not known whether this association takes place in the case of depression comorbid with fibromyalgia. OBJECTIVE: The authors investigated the association between a current major depressive episode and temperament traits (e. g., harm avoidance). METHOD: A sample of 69 adult female patients with fibromyalgia was assessed with the Temperament and Character Inventory. Psychiatric diagnoses were assessed with the Mini-International Neuropsychiatric Interview severity of depressive symptomatology with the Beck Depression Inventory, and anxiety symptomatology with the IDATE-state and pain intensity with a visual analog scale. RESULTS: A current major depressive episode was diagnosed in 28 (40.5%) of the patients. They presented higher levels of harm avoidance and lower levels of cooperativeness and self-directedness compared with non-depressed patients, which is consistent with the Temperament and Character Inventory profile of subjects with primary depression. However, in contrast to previous results in primary depression, no association between a major depressive episode and self-transcendence was found. CONCLUSIONS: The results highlight specific features of depression in fibromyalgia subjects and may prove important for enhancing the diagnosis and prognosis of depression in fibromyalgia patients.
  • article 17 Citação(ões) na Scopus
    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, Renerio
    Background: 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.
  • article 96 Citação(ões) na Scopus
    Efficacy and Safety of Transcranial Direct Current Stimulation as an Add-on Treatment for Bipolar Depression A Randomized Clinical Trial
    (2018) SAMPAIO-JUNIOR, Bernardo; TORTELLA, Gabriel; BORRIONE, Lucas; MOFFA, Adriano H.; MACHADO-VIEIRA, Rodrigo; CRETAZ, Eric; SILVA, Adriano Fernandes da; FRAGUAS, Renerio; APARICIO, Luana V.; KLEIN, Izio; LAFER, Beny; GOERIGK, Stephan; BENSENOR, Isabela Martins; LOTUFO, Paulo Andrade; GATTAZ, Wagner F.; BRUNONI, Andre Russowsky
    IMPORTANCE More effective, tolerable interventions for bipolar depression treatment are needed. Transcranial direct current stimulation (tDCS) is a novel therapeutic modality with few severe adverse events that showed promising results for unipolar depression. OBJECTIVE To determine the efficacy and safety of tDCS as an add-on treatment for bipolar depression. DESIGN, SETTING, AND PARTICIPANTS A randomized, sham-controlled, double-blind trial (the Bipolar Depression Electrical Treatment Trial [BETTER]) was conducted from July 1, 2014, to March 30, 2016, at an outpatient, single-center academic setting. Participants included 59 adults with type I or II bipolar disorder in a major depressive episode and receiving a stable pharmacologic regimen with 17-item Hamilton Depression Rating Scale (HDRS-17) scores higher than 17. Data were analyzed in the intention-to-treat sample. INTERVENTIONS Ten daily 30-minute, 2-mA, anodal-left and cathodal-right prefrontal sessions of active or sham tDCS on weekdays and then 1 session every fortnight until week 6. MAIN OUTCOMES AND MEASURES Change in HDRS-17 scores at week 6. RESULTS Fifty-nine patients (40 [68%] women), with a mean (SD) age of 45.9 (12) years participated; 36 (61%) with bipolar I and 23 (39%) with bipolar II disorder were randomized and 52 finished the trial. In the intention-to-treat analysis, patients in the active tDCS condition showed significantly superior improvement compared with those receiving sham (beta(int) = -1.68; number needed to treat, 5.8; 95% CI, 3.3-25.8; P = .01). Cumulative response rates were higher in the active vs sham groups (67.6% vs 30.4%; number needed to treat, 2.69; 95% CI, 1.84-4.99; P = .01), but not remission rates (37.4% vs 19.1%; number needed to treat, 5.46; 95% CI, 3.38-14.2; P = .18). Adverse events, including treatment-emergent affective switches, were similar between groups, except for localized skin redness that was higher in the active group (54% vs 19%; P = .01). CONCLUSIONS AND RELEVANCE In this trial, tDCS was an effective, safe, and tolerable add-on intervention for this small bipolar depression sample. Further trials should examine tDCS efficacy in a larger sample.
  • article 16 Citação(ões) na Scopus
    Cognitive changes after tDCS and escitalopram treatment in major depressive disorder: Results from the placebo-controlled ELECT-TDCS trial
    (2020) MORENO, Marina L.; GOERIGK, Stephan A.; BERTOLA, Laiss; SUEMOTO, Claudia K.; RAZZA, Lais B.; MOFFA, Adriano H.; VERONEZI, Beatriz P.; TORT, Luara; NOGUEIRA, Barbara S.; GATTAZ, Wagner F.; FRAGUAS, Renerio; PADBERG, Frank; LOTUFO, Paulo A.; BENSENOR, Isabela M.; BRUNONI, Andre R.
    Background: Cognitive deficits in major depressive disorder (MDD) are associated with low quality of life and higher suicide risk. Antidepressant drugs have modest to null effects in improving such deficits. Therefore, we investigated the cognitive effects of transcranial direct current stimulation (tDCS), which is a promising antidepressant non-pharmacological intervention, in MDD. Methods: An exploratory analysis on cognitive performance was conducted in 243 depressed patients from the Escitalopram vs. Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS), a sham-controlled study comparing the efficacy of tDCS vs. escitalopram. A neuropsychological battery was applied at baseline and endpoint (10 weeks of treatment) to create composite cognitive scores (processing speed, working memory, and verbal fluency). Linear mixed regression models were used to evaluate changes according to intervention groups, adjusted for confounding variables (age, years of schooling, gender, and benzodiazepine use) and depression improvement. Results: No cognitive deterioration was observed in any group. Patients receiving tDCS presented reduced practice gains compared to placebo in processing speed. In patients receiving escitalopram vs. placebo and in the subgroup of clinical responders ( > 50% depression improvement from baseline), those receiving tDCS vs. placebo presented increased performance in verbal fluency. No significant differences between tDCS and escitalopram groups were detected. Limitations: Absence of healthy controls. Conclusion: Prefrontal tDCS did not lead to cognitive deficits in depressed patients, although it reduced practice effects in processing speed. tDCS responders presented increased performance in verbal fluency. Further investigation of tDCS cognitive effects in depression is warranted.
  • article 17 Citação(ões) na Scopus
    Loss of interest, depressed mood and impact on the quality of life: Cross-sectional survey
    (2011) GUAJARDO, Valeri D.; SOUZA, Bruno P. F.; HENRIQUES, Sergio G.; LUCIA, Mara C. S.; MENEZES, Paulo R.; MARTINS, Milton A.; TARDIVO, Leila S. L. P. C.; GATTAZ, Wagner F.; FRAGUAS, Renerio
    Background: Depressive symptoms and chronic disease have adverse effects on patients' health-related quality of life (H-RQOL). However, little is known about this effect on H-RQOL when only the two core depressive symptoms - loss of interest and depressed mood - are considered. The objective of this study is to investigate H-RQOL in the presence of loss of interest and depressed mood at a general medical outpatient unit. Methods: We evaluated 553 patients at their first attendance at a general medical outpatient unit of a teaching hospital. H-RQOL was assessed with the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). Depressed mood and loss of interest were assessed by the Primary Care Evaluation of Mental Disorders (PRIME-MD)Patient Questionnaire. A physician performed the diagnosis of chronic diseases by clinical judgment and classified them in 13 possible pre-defined categories. We used multiple linear regression to investigate associations between each domain of H-RQOL and our two core depression symptoms. The presence of chronic diseases and demographic variables were included in the models as covariates. Results: Among the 553 patients, 70.5% were women with a mean age of 41.0 years (range 18-85, SD +/- 15.4). Loss of interest was reported by 54.6%, and depressed mood by 59.7% of the patients. At least one chronic disease was diagnosed in 59.5% of patients; cardiovascular disease was the most prevalent, affecting 20.6% of our patients. Loss of interest and depressed mood was significantly associated with decreased scores in all domains of H-RQOL after adjustment for possible confounders. The presence of any chronic disease was associated with a decrease in the domain of vitality. The analysis of each individual chronic disease category revealed that no category was associated with a decrease in more than one domain of H-RQOL. Conclusion: Loss of interest and depressed mood were associated with significant decreases in H-RQOL. We recommend these simple tests for screening in general practice.
  • article 27 Citação(ões) na Scopus
    Development of the Ketamine Side Effect Tool (KSET)
    (2020) SHORT, Brooke; DONG, Vanessa; GALVEZ, Veronica; VULOVIC, Vedran; MARTIN, Donel; BAYES, Adam J.; ZARATE, Carlos A.; MURROUGH, James W.; MCLOUGHLIN, Declan M.; RIVA-POSSE, Patricio; SCHOEVERS, Robert; FRAGUAS, Renerio; GLUE, Paul; FAM, Johnson; MCSHANE, Rupert; LOO, Colleen K.
    Background: Currently, no specific, systematic assessment tool for the monitoring and reporting of ketamine-related side effects exists. Our aim was to develop a comprehensive Ketamine Side Effect Tool (KSET) to capture acute and longer-term side effects associated with repeated ketamine treatments. Methods: Informed by systematic review data and clinical research, we drafted a list of the most commonly reported side effects. Face and content validation were obtained via feedback from collaborators with expertise in psychiatry and anaesthetics, clinical trial piloting and a modified Delphi Technique involving ten international experts. Results: The final version consisted of four forms that collect information at time points: screening, baseline, immediately after a single treatment, and longer-term follow-up. Instructions were developed to guide users and promote consistent utilisation. Limitations: Further evaluation of feasibility, construct validity and reliability is required, and is planned across multiple international sites. Conclusions: The structured Ketamine Side Effect Tool (KSET) was developed, with confirmation of content and face validity via a Delphi consensus process. This tool is timely, given the paucity of data regarding ketamine's safety, tolerability and abuse potential over the longer term, and its recent adoption internationally as a clinical treatment for depression. Although based on data from depression studies, the KSET has potential applicability for ketamine (or derivatives) used in other medical disorders, including chronic pain. We recommend its utilisation for both research and clinical scenarios, including data registries.
  • article 50 Citação(ões) na Scopus
    The Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS): rationale and study design of a non-inferiority, triple-arm, placebo-controlled clinical trial
    (2015) BRUNONI, Andre Russowsky; SAMPAIO-JUNIOR, Bernardo; MOFFA, Adriano Henrique; BORRIONE, Lucas; NOGUEIRA, Barbara Schwair; APARICIO, Luana Vanessa Marotti; VERONEZI, Beatriz; MORENO, Marina; FERNANDES, Raquel Albano; TAVARES, Diego; BUENO, Priscila Vilela Silveira; SEIBT, Ole; BIKSON, Marom; FRAGUAS, Renerio; BENSENOR, Isabela Martins
    CONTEXT AND OBJECTIVE: Major depressive disorder (MDD) is a common psychiatric condition, mostly treated with antidepressant drugs, which are limited due to refractoriness and adverse effects. We describe the study rationale and design of ELECT-TDCS (Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study), which is investigating a non-pharmacological treatment known as transcranial direct current stimulation (tDCS). DESIGN AND SETTING: Phase-III, randomized, non-inferiority, triple-arm, placebo-controlled study, ongoing in Sao Paulo, Brazil. METHODS: ELECT-TDCS compares the efficacy of active tDCS/placebo pill, sham tDCS/escitalopram 20 mg/day and sham tDCS/placebo pill, for ten weeks, randomizing 240 patients in a 3: 3: 2 ratio, respectively. Our primary aim is to show that tDCS is not inferior to escitalopram with a non-inferiority margin of at least 50% of the escitalopram effect, in relation to placebo. As secondary aims, we investigate several biomarkers such as genetic polymorphisms, neurotrophin serum markers, motor cortical excitability, heart rate variability and neuroimaging. RESULTS: Proving that tDCS is similarly effective to antidepressants would have a tremendous impact on clinical psychiatry, since tDCS is virtually devoid of adverse effects. Its ease of use, portability and low price are further compelling characteristics for its use in primary and secondary healthcare. Multimodal investigation of biomarkers will also contribute towards understanding the antidepressant mechanisms of action of tDCS. CONCLUSION: Our results have the potential to introduce a novel technique to the therapeutic arsenal of treatments for depression.
  • article 5 Citação(ões) na Scopus
    Executive function and depressive symptoms of retardation in nonelderly stroke patients
    (2014) SOBREIRO, Matildes F. M.; MIOTTO, Eliane Correa; TERRONI, Luisa; TINONE, Gisela; IOSIFESCU, Dan V.; LUCIA, Mara C. S. de; SCAFF, Milberto; LEITE, Claudia da Costa; AMARO JR., Edson; FRAGUAS, Renerio
    The depression-executive dysfunction syndrome, a late-onset depression of vascular origin with executive dysfunction and psychomotor retardation, has also been described after stroke. We verified whether this syndrome also occurs in nonelderly stroke patients by investigating the association between domains of depressive symptoms with executive functions in 87 first-ever ischemic stroke patients. The retardation domain of the 31-item Hamilton Rating Scale for Depression was associated with decreased performance on verbal fluency (assessed with FAS). The association was maintained for younger patients (aged <60 years) after adjusting for confounders. This result supports the clinical presentation of depression-executive dysfunction syndrome in younger stroke patients. Confirmation of this finding, its neural correlates, and clinical implication deserve further investigation.