LEANDRO DA COSTA LANE VALIENGO
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
16 resultados
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- Treatment of mixed depression with theta-burst stimulation (TBS): results from a double-blind, randomized, sham-controlled clinical trial(2021) TAVARES, Diego Freitas; SUEN, Paulo; SANTOS, Carla Garcia Rodrigues dos; MORENO, Doris Hupfeld; VALIENGO, Leandro Da Costa Lane; KLEIN, Izio; BORRIONE, Lucas; FORTE, Pamela Marques; BRUNONI, Andre R.; MORENO, Ricardo AlbertoMixed depression is probably different in terms of clinical course and response to treatment. Repetitive transcranial magnetic stimulation (rTMS) is well established in non-mixed depression, and theta-burst stimulation (TBS) protocol is replacing conventional protocols because of noninferiority and reduced delivery time. However, TBS has not been adequately studied in mixed states. This study was a double-blind, six-week, sham-controlled, and randomized clinical trial of bilateral TBS targeting the right and left dorsolateral prefrontal cortex, respectively. Adults with bipolar and major depressive disorder experiencing an acute mixed depression were eligible if they had not benefited from a first- or second-line treatment for acute unipolar or bipolar depression recommended by the Canadian Network for Mood and Anxiety Treatments. Out of 100 patients included, 90 composed modified intention-to-treat sample, which was patients that completed at least one week of the intervention. There were no significant differences in Montgomery-Asberg depression rating scale score changes (least squares mean difference between groups at week 3, -0.06 [95% CI, - 3.39 to 3.51; P = 0.97] in favor of sham TBS). Response and remission rates per MADRS were also not statistically different among active and sham groups (35.7% vs. 43.7%, and 28.5% vs. 37.5% respectively at week 6, ps > 0.51). No other analyses from baseline to weeks 3 or 6 revealed significant time x group interaction or mean differences among groups in the mITT sample. Bilateral TBS targeting the DLPFC is not efficacious as an add-on treatment of acute bipolar and unipolar mixed depression. ClinicalTrials.govIdentifier: NCT04123301
- Efficacy, Safety, and Tolerability of Theta-Burst Stimulation in Mixed Depression: Design, Rationale, and Objectives of a Randomized, Double-Blinded, Sham-Controlled Trial(2020) TAVARES, Diego Freitas; SANTOS, Carla Garcia Rodrigues dos; VALIENGO, Leandro Da Costa Lane; KLEIN, Izio; BORRIONE, Lucas; FORTE, Pamela Marques; BRUNONI, Andre R.; MORENO, Ricardo AlbertoIntroduction Mixed-specifier mood disorders are probably a different subgroup in terms of response to treatment, socio-demographic parameters, course, and family history. Here we describe the rationale and design of a clinical trial aimed to test the efficacy, safety, and tolerability of a non-pharmacological treatment known as theta-burst stimulation (TBS) for treating the mixed depressive episodes of both bipolar (I or II), and unipolar depression. Methods The study is designed as a randomized, sham-controlled, double-blinded clinical trial evaluating TBS for the treatment of moderate or severe major depressive episodes with mixed features of patients receiving at least one first or second-line pharmacological treatment for depressive episodes without adequate response. Ninety adult (18 to 65 years old) patients will be enrolled and submitted to 6-week (comprising 5 consecutive days a week sessions for the first 3 weeks and then 2 days a week for a further 3 week) of inhibitory followed by excitatory TBS in dorsolateral prefrontal cortex. Participants will be assessed using clinical and neuropsychological tests before and after the intervention. The primary outcome is change in Montgomery-angstrom sberg Depression Scale (MADRS) score over time and across groups. Cognitive parameters will also be assessed with neuropsychological tests. Results The clinical results will provide evidence about TBS as an adjunctive treatment for mixed depression treatment and neuropsychological parameters will contribute toward an improved understanding the effects of TBS in cognition. Conclusion Our results could introduce a novel therapeutic technique for mixed depressive episodes of both bipolar and unipolar disorders.
- Cognitive outcomes of TMS treatment in bipolar depression: Safety data from a randomized controlled trial(2018) MYCZKOWSKI, Martin L.; FERNANDES, Adriano; MORENO, Marina; VALIENGO, Leandro; LAFER, Beny; MORENO, Ricardo A.; PADBERG, Frank; GATTAZ, Wagner; BRUNONI, Andre R.Background: Bipolar depression (BD) is a highly prevalent condition associated with marked cognitive deficits that persist even in the euthymic phase of the illness. Pharmacological treatments for BD might further aggravate cognitive impairment, highlighting the need of developing interventions that present cognitive safety. In this study, we evaluated the cognitive effects of H1-coil (deep) transcranial magnetic stimulation (TMS) in patients with treatment-resistant bipolar depression. Methods: Fourty-three patients were randomized to receive 20 sessions of active (55 trains, 18 Hz, 120% resting motor threshold intensity) or sham rTMS within a double-blind, sham-controlled trial. A battery of 20 neuropsychological assessments, grouped in 6 domains (attention and processing speed, working memory and executive function, inhibitory control, language, immediate verbal memory, and long-term verbal memory) was performed at baseline and after 4 and 8 weeks of trial onset. Depressive symptoms were assessed with the 17 item Hamilton Rating Scale for Depression. Results: Cognitive improvement was shown for all cognitive domains. It occurred regardless of intervention group and depression improvement. For the language domain, greater improvement was observed in the sham group over time. No correlations between depression (at baseline or during treatment) and cognitive improvement were found. Limitations: Absence of healthy control group. Conclusion: The results of this exploratory study provide evidence on the cognitive safety of H1-coil TMS for BD patients. Putative pro-cognitive effects of rTMS in BD were not observed and thus should be further investigated.
- Impact of 5-HTTLPR and BDNF polymorphisms on response to sertraline versus transcranial direct current stimulation: Implications for the serotonergic system(2013) BRUNONI, A. R.; KEMP, A. H.; SHIOZAWA, P.; CORDEIRO, Q.; VALIENGO, L. C. L.; GOULART, A. C.; COPRERSKI, B.; LOTUFO, P. A.; BRUNONI, D.; PEREZ, A. B. A.; FREGNI, F.; BENSENOR, I. M.Transcranial direct current stimulation (tDCS) has been intensively investigated as a non-pharmacological treatment for major depressive disorder (MDD). While many studies have examined the genetic predictors of antidepressant medications, this issue remains to be investigated for tDCS. In the current study, we evaluated whether the BDNF Val66Met and the 5-HTT (5-HTTLPR) polymorphisms were associated with tDCS antidepressant response. We used data from a factorial trial that evaluated the efficacy of tDCS and sertraline and enrolled 120 moderate-to-severe, antidepressant-free participants. In the present study, we used analyses of variance to evaluate whether the BDNF (Val/Val vs. Met-carries) and 5-HTTLPR alleles (long/long vs short-carriers) were predictors of tDCS (active/sham) and sertraline (sertraline/placebo) response. Analyses were conducted on the polymorphisms separately and also on their interaction. Genotype frequencies were in Hardy-Weinberg equilibrium. BDNF polymorphism was not associated with treatment response. We found that 5-HTTLPR predicted tDCS effects as long/long homozygotes displayed a larger improvement comparing active vs. sham tDCS, while short-allele carriers did not. A dose-response relationship between active-sham differences with the long allele was also suggested. These results strengthen the role of the serotonergic system in the tDCS antidepressant effects and expand previous findings that reported that tDCS mechanisms of action partially involve serotonergic receptors. Therefore, we hypothesize that tDCS is a neuromodulation technique that acts over depression through the modulation of serotonergic system and that tDCS ""top-down"" antidepressant effects might not be optimal in brain networks with a hyperactive amygdala inducing bottom-up effects, such as occurs in short-carriers.
- Treatment of Bipolar Depression with Deep TMS: Results from a Double-Blind, Randomized, Parallel Group, Sham-Controlled Clinical Trial(2017) TAVARES, Diego F.; MYCZKOWSKI, Martin L.; ALBERTO, Rodrigo L.; VALIENGO, Leandro; RIOS, Rosa M.; GORDON, Pedro; SAMPAIO-JUNIOR, Bernardo de; KLEIN, Izio; MANSUR, Carlos G.; MARCOLIN, Marco Antonio; LAFER, Beny; MORENO, Ricardo A.; GATTAZ, Wagner; DASKALAKIS, Zafiris J.; BRUNONI, Andre R.Bipolar depression (BD) is a highly prevalent condition with limited therapeutic options. Deep (H1-coil) transcranial magnetic stimulation (dTMS) is a novel TMS modality with established efficacy for unipolar depression. We conducted a randomized sham-controlled trial to evaluate the efficacy and safety of dTMS in treatment-resistant BD patients. Patients received 20 sessions of active or sham dTMS over the left dorsolateral prefrontal cortex (H1-coil, 55 18 Hz 2 s 120% MT trains). The primary outcome was changes in the 17-item Hamilton Depression Rating Scale (HDRS-17) from baseline to endpoint (week 4). Secondary outcomes were changes from baseline to the end of the follow-up phase (week 8), and response and remission rates. Safety was assessed using a dTMS adverse effects questionnaire and the Young Mania Rating Scale to assess treatment-emergent mania switch (TEMS). Out of 50 patients, 43 finished the trial. There were 2 and 5 dropouts in the sham and active groups, respectively. Active dTMS was superior to sham at end point (difference favoring dTMS = 4.88; 95% CI 0.43 to 9.32, p = 0.03) but not at follow-up. There was also a trend for greater response rates in the active (48%) vs sham (24%) groups (OR = 2.92; 95% CI = 0.87 to 9.78, p = 0.08). Remission rates were not statistically different. No TEMS episodes were observed. Deep TMS is a potentially effective and well-tolerated add-on therapy in resistant bipolar depressed patients receiving adequate pharmacotherapy.
- Transcranial direct current stimulation for the treatment of post-stroke depression: results from a randomised, sham-controlled, double-blinded trial(2017) VALIENGO, Leandro C. L.; GOULART, Alessandra C.; OLIVEIRA, Janaina F. de; BENSENOR, Isabela M.; LOTUFO, Paulo A.; BRUNONI, Andre R.Background Post-stroke depression is a disabling condition occurring in about one-third of patients with stroke. Pharmacological treatments have limited efficacy and important side effects. Recently, transcranial direct current stimulation (tDCS) has shown efficacy in treating depression. This study aimed to assess the efficacy and safety of tDCS for post-stroke depression. Methods 48 antidepressant-free patients with post-stroke depression were randomised into two groups (active and sham tDCS). 12 30 min sessions of 2 mA anodal left/cathodal right dorsolateral prefrontal tDCS were administered over 6 weeks (once daily on weekdays for 2 weeks, then 1 session every other week). The primary outcome was the change in the Hamilton Depression Rating Scale (17-items) at 6 weeks. We employed a repeated-measures analysis of variance; the depression score was the dependent variable, and time and group were independent variables. In this intention-to-treat analysis, missing data were addressed according to the last observation carried forward and the mixed-model repeated-measures analysis methods. Results 5 patients dropped out (two in the active group). Active tDCS was significantly superior to sham at end point (mean difference, 4.7 points; SD=9.21; p<0.001). Response and remission rates were significantly higher in the active (37.5% and 20.8%, respectively) versus the sham (4.1% and 0%, respectively) group, with a number-needed-to-treat of 3 and 5, respectively. Conclusions This was the first controlled study to demonstrate that tDCS was safe and effective for post-stroke depression. Therefore, tDCS might be a favourable option for treating these patients.
- 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.
- Cognitive control therapy and transcranial direct current stimulation for depression: A randomized, double-blinded, controlled trial(2014) BRUNONI, A. R.; BOGGIO, P. S.; RAEDT, R. De; BENSENOR, I. M.; LOTUFO, P. A.; NAMUR, V.; VALIENGO, L. C. L.; VANDERHASSELT, M. A.Background: Based on findings that major depressive disorder (MDD) is associated to decreased dorsolateral prefrontal cortical (DLPFC) activity; interventions that increase DLPFC activity might theoretically present antidepressant effects. Two of them are cognitive control therapy (CCT), a neurocognitive intervention that uses computer-based working memory exercises, and transcranial direct current stimulation (tDCS), which delivers weak, electric direct currents over the scalp. Methods: We investigated whether tDCS enhanced the effects of CCT in a double-blind trial, in which participants were randomized to sham tDCS and CCT (n=17) vs. active tDCS and CCT (n=20). CCT and tDCS were applied for 10 consecutive workdays. Clinicaltrials.gov identifier: NCT01434836. Results: Both CCT alone and combined with tDCS ameliorated depressive symptoms after the acute treatment period and at follow-up, with a response rate of approximately 25%. Older patients and those who presented better performance in the task throughout the trial (possibly indicating greater engagement and activation of the DLPFC) had greater depression improvement in the combined treatment group. Limitations: Our exploratory findings should be further confirmed in prospective controlled trials. Discussion: CCT and tDCS combined might be beneficial for older depressed patients, particularly for those who have cognitive resources to adequately learn and improve task performance over time This combined therapy might be specifically relevant in this subgroup that is more prone to present cognitive decline and prefrontal cortical atrophy.
- THE SERTRALINE VERSUS ELECTRICAL CURRENT THERAPY FOR TREATING DEPRESSION CLINICAL STUDY (SELECT-TDCS): RESULTS OF THE CROSSOVER AND FOLLOW-UP PHASES(2013) VALIENGO, Leandro; BENSENOR, Isabela Martins; GOULART, Alessandra C.; OLIVEIRA, Janaina Farias de; ZANAO, Tamires Araujo; BOGGIO, Paulo Sergio; LOTUFO, Paulo Andrade; FREGNI, Felipe; BRUNONI, Andre RussowskyBackgroundTranscranial direct current stimulation (tDCS) is a promising nonpharmacological therapy for major depression. In the Sertraline versus Electrical Current Therapy for Treating Depression Clinical Trial (SELECT-TDCS) trial, phase-I (Brunoni et al., JAMA Psychiatry, 2013) we found that tDCS is effective for the acute episode. Here, we describe tDCS effects during phases II (crossover) and III (follow-up) of this trial (NCTs: 01149889 and 01149213). MethodsPhase II (n = 25) was the open-label, crossover phase in which phase-I nonresponders who had received sham-tDCS received a 10-day course of active-tDCS. In phase-III (n = 42), all active-tDCS responders (>50% Montgomery-Asberg Depression Rating Scale (MADRS) improvement or MADRS 12) were enrolled to a 24-week, follow-up phase in which a maximum of nine tDCS sessions were performedevery other week for 3 months and, thereafter, once a month for the subsequent 3 monthssessions would be interrupted earlier whether the subject relapsed. TDCS was applied at 2 mA/30 min, with the anode over the left and the cathode over the right dorsolateral prefrontal cortex. Relapse was the outcome measure. ResultsIn phase-II, 52% of completers responded to tDCS. In phase-III, the mean response duration was 11.7 weeks. The survival rate per Kaplan-Meier analysis was 47%. Patients with treatment-resistant depression presented a much lower 24-week survival rate as compared to nonrefractory patients (10% vs. 77%, OR = 5.52; P < .01). Antidepressant use (sertraline 50 mg/day, eight patients) was not a predictor of relapse. TDCS was well tolerated and with few side effects. ConclusionContinuation tDCS protocols should be optimized as to prevent relapse among tDCS responders, particularly for patients with baseline treatment-resistant depression. Depression and Anxiety 30: 646-653, 2013. (C) 2013 Wiley Periodicals, Inc.
- Assessment of non-BDNF neurotrophins and GDNF levels after depression treatment with sertraline and transcranial direct current stimulation in a factorial, randomized, sham-controlled trial (SELECT-TDCS): An exploratory analysis(2015) BRUNONI, Andre R.; MACHADO-VIEIRA, Rodrigo; ZARATE JR., Carlos A.; VIEIRA, Erica L. M.; VALIENGO, Leandro; BENSENOR, Isabela M.; LOTUFO, Paulo A.; GATTAZ, Wagner F.; TEIXEIRA, Antonio L.The neurotrophic hypothesis of depression states that the major depressive episode is associated with lower neurotrophic factors levels, which increase with amelioration of depressive symptoms. However, this hypothesis has not been extended to investigate neurotrophic factors other than the brain-derived neurotrophic factor (BDNF). We therefore explored whether plasma levels of neurotrophins 3 (NT-3) and 4 (NT-4), nerve growth factor (NGF) and glial cell line derived neurotrophic factor (GDNF) changed after antidepressant treatment and correlated with treatment response. Seventy-three patients with moderate-to-severe, antidepressant-free unipolar depression were assigned to a pharmacological (sertraline) and a non-pharmacological (transcranial direct current stimulation, tDCS) intervention in a randomized, 2 x 2, placebo-controlled design. The plasma levels of NT-3, NT-4, NGF and GDNF were determined by enzyme-linked immunosorbent assay before and after a 6-week treatment course and analyzed according to clinical response and allocation group. We found that tDCS and sertraline (separately and combined) produced significant improvement in depressive symptoms. Plasma levels of all neurotrophic factors were similar across groups at baseline and remained significantly unchanged regardless of the intervention and of clinical response. Also, baseline plasma levels were not associated with clinical response. To conclude, in this 6-week placebo-controlled trial, NT-3, NT-4, NGF and GDNF plasma levels did not significantly change with sertraline or tDCS. These data suggest that these neurotrophic factors are not surrogate biomarkers of treatment response or involved in the antidepressant mechanisms of tDCS.