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
12 resultados
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- Temperament and character traits in major depressive disorder: a case control study(2017) NOGUEIRA, Barbara Schwair; FRAGUAS JUNIOR, Renerio; BENSENOR, Isabela Martins; LOTUFO, Paulo Andrade; BRUNONI, Andre RussowskyBACKGROUND: Patients with major depressive disorder (MDD) have distinct personality traits, compared with control subjects, although the role of anxiety and positive and negative affects in this finding is unclear. DESIGN AND SETTING: A case-control study enrolling 103 antidepressant-free depressed patients and 103 age and gender-matched controls was conducted at the University Hospital, University of Sao Paulo. METHODS: The self-reported scales of the Positive and Negative Affect Schedule (PANAS), State-Trait Anxiety Inventory (STAI) and Cloninger's Temperament and Character Inventory (TCI) were applied. Temperament and character traits were compared between groups using multivariate and bivariate analyses of variance (MANOVA and ANOVA). The influence of anxiety and affect was further investigated using ANOVA and mediation analyses. RESULTS: Depressed patients presented higher harm avoidance and lower self-directedness scores than controls. After adjustment for anxiety trait, harm avoidance was no longer significantly different between groups. Mediation analysis revealed that the anxiety trait, but not state-anxiety or affect, fully mediated the influence of group (depressed versus control subjects) on harm avoidance. CONCLUSIONS: Our findings confirm that depressed patients present personality traits distinct from those of controls and suggest that MDD is not directly associated with harm avoidance, but that this effect is fully mediated through the anxiety trait.
- Differential improvement in depressive symptoms for tDCS alone and combined with pharmacotherapy: an exploratory analysis from The Sertraline Vs. Electrical Current Therapy For Treating Depression Clinical Study(2014) BRUNONI, Andre R.; FRAGUAS JUNIOR, Renerio; KEMP, Andrew H.; LOTUFO, Paulo A.; BENSENOR, Isabela M.; FREGNI, FelipeTranscranial direct current stimulation (tDCS) is a promising therapy for major depression treatment, although little is known of its effects in ameliorating distinct symptoms of depression. Thus, it is important, not only to increase knowledge of its antidepressant mechanisms, but also to guide its potential use in clinical practice. Using data from a recent factorial, double-blinded, placebo-controlled trial applying tDCS-alone and combined with sertraline to treat 120 depressed outpatients over 6wk (Brunoni et al., 2013), we investigated the pattern of improvement in symptoms of depression from the Montgomery-Asberg depression scale (MADRS). First, we performed one multivariate analysis of variance with the score improvement of the 10 MADRS items as dependent variables. Significant (p<0.05) results were further explored with follow-up analyses of variance. TDCS (alone and combined with sertraline) improved concentration difficulties and pessimistic and suicidal thoughts. The combined treatment also improved apparent and reported sadness, lassitude and inability to feel. Indeed, tDCS/sertraline significantly ameliorated all but the vegetative' depression symptoms (inner tension, sleep and appetite items). We further discuss whether bifrontal tDCS over the dorsolateral prefrontal cortex could be associated with improvement in cognitive (concentration) and affective (pessimistic/suicidal thoughts) processing, while the combined treatment might have a more widespread antidepressant effect by simultaneously acting on different depression pathways. We also identified patterns of antidepressant improvement for tDCS that might aid in tailoring specific interventions for different subtypes of depressed patients, e.g. particularly those with suicidal ideation.
- 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 RussowskyIMPORTANCE 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.
- 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.
- 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 MartinsCONTEXT 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.
- Differential Associations of Specific Selective Serotonin Reuptake Inhibitors With Resting-State Heart Rate and Heart Rate Variability: Implications for Health and Well-Being(2016) KEMP, Andrew H.; FRAGUAS, Renerio; BRUNONI, Andre R.; BITTENCOURT, Marcio S.; NUNES, Maria A.; DANTAS, Eduardo M.; ANDREAO, Rodrigo V.; MILL, Jose G.; RIBEIRO, Antonio L. P.; KOENIG, Julian; THAYER, Julian F.; BENSENOR, Isabela M.; LOTUFO, Paulo A.Objective Debate has focused on the effects of the selective serotonin reuptake inhibitor (SSRI) antidepressants on heart rate (HR) and HR variability (HRV), both of which are predictors of adverse cardiovascular events. Here, we examine the associations between specific SSRI antidepressants and resting state HR (and HRV) after accounting for a host of potential confounding factors using propensity score techniques. Methods Participants included 10,466 not taking antidepressants, 46 participants taking escitalopram, 86 taking citalopram, 66 taking fluoxetine, 103 taking paroxetine, and 139 taking sertraline. HR and HRV (root mean square of successive squared differences, high frequency) were extracted from 10-minute resting-state ECGs. Analyses including propensity score weighting and matching were conducted using R-statistics to control for potentially confounding variables. Results Major findings indicated that users of all SSRI medicationsexcept fluoxetinedisplayed lower HRV relative to nonusers. Users of paroxetine also displayed significantly lower HRV relative to users of citalopram (Cohen's d = 0.42), fluoxetine (Cohen's d = 0.54), and sertraline (Cohen's d = 0.35), but not escitalopram. Although associations were also observed for HR, these were less robust than those for HRV. Conclusions Although paroxetine is associated with decreases in HRV relative to nonusers, as well as users of other SSRI medications, fluoxetine was the only medication not to display significant alterations in HR or HRV. These conclusions are limited by the cross-sectional design and nonrandomized nature of medication prescriptions. Findings highlight the importance of focusing on specific medications, rather than more heterogeneous groupings according to antidepressant action, and may have implications for health and well-being for the longer term.
- Precision non-implantable neuromodulation therapies: a perspective for the depressed brain(2020) BORRIONE, Lucas; BELLINI, Helena; RAZZA, Lais Boralli; AVILA, Ana G.; BAEKEN, Chris; BREM, Anna-Katharine; BUSATTO, Geraldo; CARVALHO, Andre F.; CHEKROUD, Adam; DASKALAKIS, Zafiris J.; DENG, Zhi-De; DOWNAR, Jonathan; GATTAZ, Wagner; LOO, Colleen; LOTUFO, Paulo A.; MARTIN, Maria da Graca M.; MCCLINTOCK, Shawn M.; O'SHEA, Jacinta; PADBERG, Frank; PASSOS, Ives C.; SALUM, Giovanni A.; VANDERHASSELT, Marie-Anne; FRAGUAS, Renerio; BENSENOR, Isabela; VALIENGO, Leandro; BRUNONI, Andre R.Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although non-implantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more ""precision-oriented"" practice.
- Associations between symptoms of depression and heart rate variability: An exploratory study(2018) BORRIONE, Lucas; BRUNONI, Andre R.; SAMPAIO-JUNIOR, Bernardo; APARICIO, Luana M.; KEMP, Andrew H.; BENSENOR, Isabela; LOTUFO, Paulo A.; FRAGUAS, RenerioMajor depressive disorder (MDD) is associated with decreased heart rate variability (HRV), a predictor of cardiovascular morbidity by many, but not all studies. This inconsistency could be due to the association of HRV with specific depressive symptoms. Here, we investigated the association of HRV parameters with components of depressive symptoms from 120 MDD patients, at baseline of a published trial comparing the effect of sertraline to transcranial direct current stimulation. We used Principal Component Analysis to extract components of the Hamilton Rating Scale for Depression (HAM-D-17), the Montgomery Asberg Depression Rating Scale (MADRS) and the Beck Inventory for Depressive Symptomatology (BDI). We constructed one equation of multiple linear regression for each HRV parameter as the dependent variable, and the components of depressive symptoms of the three scales as the independent ones, adjusted for age and gender. A component of HAM-D-17 predicted LF/HF (low frequency/high frequency) and a component of MADRS predicted LF (low frequency). ""Guilt"" and ""loss of interest/pleasure in activities"" were present in the components of both scales, and the MADRS component also included ""psychomotor retardation"". These results suggest that melancholic features might be relevant for the association between MDD and HRV. Considering multiple comparisons, these results are preliminary.
- Transcranial direct current stimulation (tDCS) for preventing major depressive disorder relapse: Results of a 6-month follow-up(2019) APARICIO, Luana V. M.; ROSA, Vivianne; RAZZA, Lais M.; SAMPAIO-JUNIOR, Bernardo; BORRIONE, Lucas; VALIENGO, Leandro; LOTUFO, Paulo A.; BENSENOR, Isabela M.; FRAGUAS, Renerio; MOFFA, Adriano H.; GATTAZ, Wagner F.; BRUNONI, Andre RussowskyBackgroundThe efficacy of transcranial direct current stimulation (tDCS) as a continuation therapy for the maintenance phase of the depressive episode is low and insufficiently investigated in literature. We investigated whether it could be enhanced by using a more intensive treatment regimen compared to previous reports. MethodsTwenty-four patients (16 with unipolar depression and eight with bipolar depression) who presented acute tDCS response (50% depression improvement in the Hamilton Depression Rating Scale [HDRS]) after receiving 15 tDCS sessions were followed for up to 6 months or until relapse, defined as clinical worsening and/or HDRS>15. Sessions were performed twice a week (maximum of 48 sessions) over 24weeks. The anode and the cathode were positioned over the left and right dorsolateral prefrontal cortex (2mA current, 30 min sessions were delivered). We performed Kaplan-Meier survival analysis and Cox proportional hazards ratios to evaluate predictors of relapse. ResultsOut of 24 patients, 18 completed the follow-up period. tDCS treatment was well tolerated. The mean survival duration was 17.5weeks (122 days). The survival rate at the end of follow-up was 73.5% (95% confidence interval, 50-87). A trend (P=0.09) was observed for lower relapse rates in nontreatment- vs. antidepressant treatment-resistant patients (7.7%vs. 45.5%, respectively). No differences in efficacy between unipolar and bipolar depression were observed. ConclusionAn intensive tDCS treatment regimen consisting of sessions twice a week achieved relatively low relapse rates after a 6-month follow up of tDCS responders, particularly for nontreatment-resistant patients.
- Trial of Electrical Direct-Current Therapy versus Escitalopram for Depression(2017) BRUNONI, A. R.; MOFFA, A. H.; SAMPAIO-JUNIOR, B.; BORRIONE, L.; MORENO, M. L.; FERNANDES, R. A.; VERONEZI, B. P.; NOGUEIRA, B. S.; APARICIO, L. V. M.; RAZZA, L. B.; CHAMORRO, R.; TORT, L. C.; FRAGUAS, R.; LOTUFO, P. A.; GATTAZ, W. F.; FREGNI, F.; BENSENOR, I. M.BACKGROUND We compared transcranial direct-current stimulation (tDCS) with a selective serotonin-reuptake inhibitor for the treatment of depression. METHODS In a single-center, double-blind, noninferiority trial involving adults with unipolar depression, we randomly assigned patients to receive tDCS plus oral placebo, sham tDCS plus escitalopram, or sham tDCS plus oral placebo. The tDCS was administered in 30-minute, 2-mA prefrontal stimulation sessions for 15 consecutive weekdays, followed by 7 weekly treatments. Escitalopram was given at a dose of 10 mg per day for 3 weeks and 20 mg per day thereafter. The primary outcome measure was the change in the 17-item Hamilton Depression Rating Scale (HDRS-17) score (range, 0 to 52, with higher scores indicating more depression). Noninferiority of tDCS versus escitalopram was defined by a lower boundary of the confidence interval for the difference in the decreased score that was at least 50% of the difference in the scores with placebo versus escitalopram. RESULTS A total of 245 patients underwent randomization, with 91 being assigned to escitalopram, 94 to tDCS, and 60 to placebo. In the intention-to-treat analysis, the mean (+/- SD) decrease in the score from baseline was 11.3 +/- 6.5 points in the escitalopram group, 9.0 +/- 7.1 points in the tDCS group, and 5.8 +/- 7.9 points in the placebo group. The lower boundary of the confidence interval for the difference in the decrease for tDCS versus escitalopram (difference, -2.3 points; 95% confidence interval [CI], -4.3 to -0.4; P = 0.69) was lower than the noninferiority margin of -2.75 (50% of placebo minus escitalopram), so noninferiority could not be claimed. Escitalopram and tDCS were both superior to placebo (difference vs. placebo, 5.5 points [95% CI, 3.1 to 7.8; P<0.001] and 3.2 points [95% CI, 0.7 to 5.5; P = 0.01], respectively). Patients receiving tDCS had higher rates of skin redness, tinnitus, and nervousness than did those in the other two groups, and new-onset mania developed in 2 patients in the tDCS group. Patients receiving escitalopram had more frequent sleepiness and obstipation than did those in the other two groups. CONCLUSIONS In a single-center trial, tDCS for the treatment of depression did not show noninferiority to escitalopram over a 10-week period and was associated with more adverse events. (Funded by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo and others; ELECT-TDCS ClinicalTrials.gov number, NCT01894815.)