LEANDRO DA COSTA LANE VALIENGO

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Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina

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  • article 6 Citação(ões) na Scopus
    Efficacy of Transcranial Direct Current Stimulation to Improve Insight in Patients With Schizophrenia: A Systematic Review and Meta-analysis of Randomized Controlled Trials
    (2022) ADAM, Ondine; BLAY, Martin; BRUNONI, Andre R.; CHANG, Hsin-An; GOMES, July S.; JAVITT, Daniel C.; JUNG, Do-Un; KANTROWITZ, Joshua T.; KOOPS, Sanne; LINDENMAYER, Jean-Pierre; PALM, Ulrich; SMITH, Robert C.; SOMMER, Iris E.; VALIENGO, Leandro do Costa Lane; WEICKERT, Thomas W.; BRUNELIN, Jerome; MONDINO, Marine
    Background and Hypothesis Impaired insight into the illness and its consequences is associated with poor outcomes in schizophrenia. While transcranial direct current stimulation (tDCS) may represent a potentially effective treatment strategy to relieve various symptoms of schizophrenia, its impact on insight remains unclear. To investigate whether tDCS would modulate insight in patients with schizophrenia, we undertook a meta-analysis based on results from previous RCTs that investigated the clinical efficacy of tDCS. We hypothesize that repeated sessions of tDCS will be associated with insight improvement among patients. Study Design PubMed and ScienceDirect databases were systematically searched to identify RCTs that delivered at least 10 tDCS sessions in patients with schizophrenia. The primary outcome was the change in insight score, assessed by the Positive and Negative Syndrome Scale (PANSS) item G12 following active tDCS sessions as opposed to sham stimulation. Effect sizes were calculated for all studies and pooled using a random-effects model. Meta-regression and subgroup analyses were conducted. Study Results Thirteen studies (587 patients with schizophrenia) were included. A significant pooled effect size (g) of -0.46 (95% CI [-0.78; -0.14]) in favor of active tDCS was observed. Age and G12 score at baseline were identified as significant moderators, while change in total PANSS score was not significant. Conclusions Ten sessions of active tDCS with either frontotemporoparietal or bifrontal montage may improve insight into the illness in patients with schizophrenia. The effect of this treatment could contribute to the beneficial outcomes observed in patients following stimulation.
  • article 6 Citação(ões) na Scopus
    Cognitive outcomes after tDCS in schizophrenia patients with prominent negative symptoms: Results from the placebo-controlled STARTS trial
    (2021) BULUBAS, Lucia; GOERIGK, Stephan; GOMES, July S.; BREM, Anna-Katharine; CARVALHO, Juliana B.; PINTO, Bianca S.; ELKIS, Helio; GATTAZ, Wagner F.; PADBERG, Frank; BRUNONI, Andre R.; VALIENGO, Leandro
    Cognitive deficits and negative symptoms in schizophrenia are associated with poor functional outcomes and limited in terms of treatment. The Schizophrenia Treatment With Electric Transcranial Stimulation (STARTS) trial has shown efficacy of transcranial direct current stimulation (tDCS) for improving negative symptoms. In this secondary analysis, we investigate its effects on cognitive performance. In STARTS, a double-blinded, sham controlled, randomized clinical trial, patients were treated with twice-daily, 20-min, 2-mA fronto-temporal tDCS over 5 days or sham-tDCS. In 90 patients, we evaluated the cognitive performance up to 12 weeks post-treatment. We found that active-tDCS showed no beneficial effects over sham-tDCS in any of the tests. Based on a 5-factor cognitive model, improvements of executive functions and delayed memory were observed in favor of shamtDCS. Overall, the applied active-tDCS protocol, primarily designed to improve negative symptoms, did not promote cognitive improvement. We discuss possible protocol modification potentially required to increase tDCS effects on cognition. ClinicalTrials.gov identifier: NCT02535676
  • article 9 Citação(ões) na Scopus
    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 Alberto
    Mixed 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
  • article 2 Citação(ões) na Scopus
    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 Alberto
    Introduction 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.
  • article 7 Citação(ões) na Scopus
    Emotional reactivity to valence-loaded stimuli are related to treatment response of neurocognitive therapy
    (2016) VANDERHASSELT, Marie-Anne; RAEDT, Rudi De; NAMUR, Victoria; VALIENGO, Leandro C. L.; LOTUFO, Paulo A.; BENSENOR, Isabela M.; BAEKEN, Chris; BOGGIO, Paulo S.; BRUNONI, Andre R.
    Emotional Context Insensitivity (ECI) is a psychological feature observed in depressed patients characterized by a decreased emotional reactivity when presented to positive- and negative valence-loaded stimuli. Given that fronto-cingulate-limbic circuits are implicated in abnormal reactivity to valence-loaded stimuli, neurocognitive treatments engaging the prefrontal cortex may be able to modulate this emotional blunting observed in MDD. Therefore, our goal was to evaluate emotional reactivity in depressed patients before and after a combination of neurocognitive interventions that engage the prefrontal cortex (cognitive control training and/or transcranial direct current stimulation). In line with the premises of the ECI framework, before the start of the antidepressant intervention, patients showed blunted emotional reactivity after exposure to negative valence-loaded stimuli. This emotional reactivity pattern changed after 9 sessions of the intervention: positive affect decreased and negative affect increased after watching a series of negative valence-loaded stimuli (i.e. images). Interestingly, higher emotional reactivity (as indexed by a larger increase in negative affect after watching the valence-loaded stimuli) at baseline predicted reductions in depression symptoms after the intervention. On the other hand, higher emotional reactivity (as indexed by a decrease in positive affect) after the intervention was marginally associated with reductions in depression symptoms. To conclude, emotional reactivity increased after the neurocognitive antidepressant intervention and it was directly associated to the degree of depression improvement.
  • article 49 Citação(ões) na Scopus
    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.
  • article 0 Citação(ões) na Scopus
    Interventional psychiatry: 13 reasons why
    (2022) BRUNONI, Andre R.; VALIENGO, Leandro; GALLUCCI-NETO, Jose
  • article 4 Citação(ões) na Scopus
    A study protocol for an ongoing multi-arm, randomized, double-blind, sham-controlled clinical trial with digital features, using portable transcranial electrical stimulation and internet-based behavioral therapy for major depression disorders: The PSYLECT study
    (2022) BORRIONE, Lucas; CIRILLO, Patricia C.; APARICIO, Luana V. M.; CAVENDISH, Beatriz A.; VALIENGO, Leandro; MOURA, Darin O.; SOUZA, Juliana P. de; LUETHI, Matthias S.; KLEIN, Izio; BARIANI, Bruna; GALLUCCI-NETO, Jose; SUEN, Paulo; PADBERG, Frank; GOERIGK, Stephan; VANDERHASSELT, Marie-Anne; DENG, Zhi De; O'SHEA, Jacinta; LOTUFO, Paulo A.; BENSENOR, Isabela M.; BRUNONI, Andre R.
    Background Transcranial electrical stimulation (tES) is considered effective and safe for depression, albeit modestly, and prone to logistical burdens when performed in external facilities. Investigation of portable tES (ptES), and potentiation of ptES with remote psychological interventions have shown positive, but preliminary, results. Research design We report the rationale and design of an ongoing multi-arm, randomized, double-blind, sham-controlled clinical trial with digital features, using ptES and internet-based behavioral therapy (iBT) for major depressive disorder (MDD) (NCT04889976). Methods We will evaluate the efficacy, safety, tolerability and usability of (1) active ptES + active iBT ('double-active'), (2) active ptES + sham iBT ('ptES-only'), and (3) sham ptES + sham iBT ('double-sham'), in adults with MDD, with a Hamilton Depression Rating Scale - 17 item version (HDRS-17) score >= 17 at baseline, during 6 weeks. Antidepressants are allowed in stable doses during the trial. Results We primarily co-hypothesize changes in HDRS-17 will be greater in (1) 'double-active' compared to 'ptES-only,' (2) 'double-active' compared to 'double-sham,' and (3) 'ptES-only' compared to 'double-sham.' We aim to enroll 210 patients (70 per arm). Conclusions Our results should offer new insights regarding the efficacy and scalability of combined ptES and iBT for MDD, in digital mental health.
  • article 75 Citação(ões) na Scopus
    Efficacy and Safety of Transcranial Direct Current Stimulation for Treating Negative Symptoms in Schizophrenia A Randomized Clinical Trial
    (2020) VALIENGO, Leandro da Costa Lane; GOERIGK, Stephan; GORDON, Pedro Caldana; PADBERG, Frank; SERPA, Mauricio Henriques; KOEBE, Stephanie; SANTOS, Leonardo Afonso dos; LOVERA, Roger Alberto Marcos; CARVALHO, Juliana Barbosa de; BILT, Martinus van de; LACERDA, Acioly L. T.; ELKIS, Helio; GATTAZ, Wagner Farid; BRUNONI, Andre R.
    This randomized clinical trial studies the efficacy and safety of transcranial direct current stimulation compared with sham as an add-on treatment for patients with schizophrenia with predominant negative symptoms. Importance Negative symptoms represent a substantial burden in schizophrenia. Although preliminary studies have suggested that transcranial direct current stimulation (tDCS) is effective for some clusters of symptoms, the clinical benefits for negative symptoms are unclear. Objective To determine the efficacy and safety of tDCS vs sham as an add-on treatment for patients with schizophrenia and predominant negative symptoms. Design, Setting, and Participants The double-blind Schizophrenia Treatment With Electric Transcranial Stimulation (STARTS) randomized clinical trial was conducted from September 2014 to March 2018 in 2 outpatient clinics in the state of Sao Paulo, Brazil. Patients with schizophrenia with stable negative and positive symptoms and a minimum score of 20 points in the negative symptoms subscale of the Positive and Negative Syndrome Scale (PANSS) were included. Interventions Ten sessions of tDCS performed twice a day for 5 days or a sham procedure. The anode and the cathode were positioned over the left prefrontal cortex and the left temporoparietal junction, respectively. Main Outcomes and Measures Change in the PANSS negative symptoms subscale score at week 6 was the primary outcome. Patients were followed-up for an additional 6 weeks. Results Of the 100 included patients, 20 (20.0%) were female, and the mean (SD) age was 35.3 (9.3) years. A total of 95 patients (95.0%) finished the trial. In the intention-to-treat analysis, patients receiving active tDCS showed a significantly greater improvement in PANSS score compared with those receiving the sham procedure (difference, 2.65; 95% CI, 1.51-3.79; number needed to treat, 3.18; 95% CI, 2.12-6.99; P < .001). Response rates for negative symptoms (20% improvement or greater) were also higher in the active group (20 of 50 [40%]) vs the sham group (2 of 50 [4%]) (P < .001). These effects persisted at follow-up. Transcranial direct current stimulation was well tolerated, and adverse effects did not differ between groups, except for burning sensation over the scalp in the active group (43.8%) vs the sham group (14.3%) (P = .003). Conclusions and Relevance Transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia. Question Is transcranial direct current stimulation (tDCS) a safe and effective add-on therapy for negative symptoms in schizophrenia? Findings In this randomized clinical trial of 100 patients with schizophrenia with predominant negative symptoms, active tDCS was superior to sham in ameliorating negative symptoms, with superior response rates (20% improvement) for negative symptoms. These effects were sustained at follow-up, and tDCS was not associated with significant adverse effects. Meaning Transcranial direct current stimulation is an affordable, safe, and effective add-on treatment for negative symptoms in schizophrenia.
  • article 68 Citação(ões) na Scopus
    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.