HELIO ELKIS

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Departamento de Psiquiatria, Faculdade de Medicina - Docente
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina

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  • article 11 Citação(ões) na Scopus
    Meta-analyses of cavum septum pellucidum in mood disorders in comparison with healthy controls or schizophrenia
    (2018) BERALDI, Gabriel H.; PRADO, Kelly S.; AMANN, Benedikt L.; RADUA, Joaquim; FRIEDMAN, Lee; ELKIS, Helio
    The cavum septum pellucidum (CSP) is a neurodevelopmental abnormality significantly more prevalent in subjects with schizophrenia (SCZ) than in healthy controls (HC). Using meta-analyses, we tested the hypotheses whether CSP would be more frequent in subjects with mood disorders when compared with HC or SCZ. We performed a search in MEDLINE and EMBASE followed by 10 meta-analyses of magnetic resonance imaging studies which examined the association of CSP in bipolar disorders (BD), major depressive disorder (MDD) or mood disorders (MD; considering MDD and BD combined) with either HC or SCZ. Nine studies were included, comprising 692 cases (363 with BD, 182 with MDD and 147 with MD), 463 with SCZ and 630 HC. CSP of any size was significantly associated with BD (OR = 2.07, 95% CI: 1.48-2.90) when compared with HC. Large CSP showed a trend to be associated with BD when compared with HC, but the association was not statistically significant (OR = 1.92, 95% CI 0.64-5.78). Large CSP was significantly associated with subjects with SCZ when compared with subjects with MD (OR = 0.57, 95% CI: 0.36-0.92). There was no association between CSP and MDD in comparison to HC or subjects with SCZ. Cortical structures are known to be altered in mood disorders. The present metanalysis found that certain midline brain abnormalities, such as CSP, are also associated with BD. (c) 2018 Published by Elsevier B.V.
  • 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 23 Citação(ões) na Scopus
    Time to rehospitalization in patients with schizophrenia discharged on first generation antipsychotics, non-clozapine second generation antipsychotics, or clozapine
    (2011) WERNECK, Ana Paula; HALLAK, Jaime Cecilio; NAKANO, Eduardo; ELKIS, Hello
    Rehospitalization is an important outcome of drug effectiveness in schizophrenia. In this study, the hypothesis that clozapine and some second generation antipsychotics (SGA) were superior to first generation antipsychotics (FGA) in preventing rehospitalization of patients with schizophrenia discharged from a university hospital in Brazil was tested. A retrospective observational study was conducted designed to evaluate time to rehospitalization of patients with schizophrenia discharged on a regimen of oral FGA, depot FGA, risperidone, olanzapine and amisulpride, other SGA, or clozapine, during a three-year follow-up period. Risk factors associated with rehospitalization were examined. Of the 464 patients with schizophrenia discharged from hospital, 242 met criteria for study entry. Higher rehospitalization rates were observed in patients treated with depot FGA (30%), risperidone (30%) and other SGA groups (28.5%), respectively. Clozapine was significantly associated with lower rehospitalization risk compared with risperidone. The risk of rehospitalization in patients on olanzapine and amisulpride, and oral FGA, was similar to that of patients in use of clozapine. These results however, are limited by the heterogeneity of illness severity across the groups.
  • article 95 Citação(ões) na Scopus
    Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness
    (2016) TORRES, Ulysses S.; DURAN, Fabio L. S.; SCHAUFELBERGER, Maristela S.; CRIPPA, Jose A. S.; LOUZA, Mario R.; SALLET, Paulo C.; KANEGUSUKU, Caroline Y. O.; ELKIS, Helio; GATTAZ, Wagner F.; BASSITT, Debora P.; ZUARDI, AntonioW.; HALLAK, Jaime Eduardo C.; LEITE, Claudia C.; CASTRO, Claudio C.; SANTOS, Antonio Carlos; MURRAY, Robin M.; BUSATTO, Geraldo F.
    Background: Structural brain abnormalities in schizophrenia have been repeatedly demonstrated in magnetic resonance imaging (MRI) studies, but it remains unclear whether these are static or progressive in nature. While longitudinalMRI studies have been traditionally used to assess the issue of progression of brain abnormalities in schizophrenia, information from cross-sectional neuroimaging studies directly comparing first-episode and chronic schizophrenia patients to healthy controls may also be useful to further clarify this issue. With the recent interest in multisite mega-analyses combining structural MRI data from multiple centers aiming at increased statistical power, the present multisite voxel-basedmorphometry (VBM) studywas carried out to examine patterns of brain structural changes according to the different stages of illness and to ascertainwhich (if any) of such structural abnormalities would be specifically correlated to potential clinical moderators, including cumulative exposure to antipsychotics, age of onset, illness duration and overall illness severity. Methods: Wegathered a large sample of schizophrenia patients (161, being 99 chronic and 62 first-episode) and controls (151) fromfour previousmorphometricMRI studies (1.5 T) carried out in the same geographical region of Brazil. Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8) software with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) algorithm. Group effects on regional gray matter (GM) volumes were investigated through whole-brain voxel-wise comparisons using General LinearModel Analysis of Co-variance (ANCOVA), always including total GMvolume, scan protocol, age and gender as nuisance variables. Finally, correlation analyseswere performed between the aforementioned clinical moderators and regional and global brain volumes. Results: First-episode schizophrenia subjects displayed subtle volumetric deficits relative to controls in a circumscribed brain regional network identified only in small volume-corrected (SVC) analyses (p < 0.05, FWE-corrected), including the insula, temporolimbic structures and striatum. Chronic schizophrenia patients, on the other hand, demonstrated an extensive pattern of regional GM volume decreases relative to controls, involving bilateral superior, inferior and orbital frontal cortices, right middle frontal cortex, bilateral anterior cingulate cortices, bilateral insulae and right superior and middle temporal cortices (p < 0.05, FWE-corrected over the whole brain). GM volumes in several of those brain regionswere directly correlated with age of disease onset on SVC analyses for conjoined (first-episode and chronic) schizophrenia groups. There were also widespread foci of significant negative correlation between duration of illness and relative GM volumes, but such findings remained significant only for the right dorsolateral prefrontal cortex after accounting for the influence of age of disease onset. Finally, significant negative correlations were detected between life-time cumulative exposure to antipsychotics and total GM and white matter volumes in schizophrenia patients, but no significant relationship was found between indices of antipsychotic usage and relative GM volume in any specific brain region. Conclusion: The above data indicate that brain changes associated with the diagnosis of schizophrenia are more widespread in chronic schizophrenia compared to first-episode patients. Our findings also suggest that relative GM volume deficits may be greater in (presumably more severe) cases with earlier age of onset, as well as varying as a function of illness duration in specific frontal brain regions. Finally, our results highlight the potentially complex effects of the continued use of antipsychotic drugs on structural brain abnormalities in schizophrenia, as we found that cumulative doses of antipsychotics affected brain volumes globally rather than selectively on frontal-temporal regions. (C) 2016 The Authors.
  • article 45 Citação(ões) na Scopus
    Efficacy of olanzapine in comparison with clozapine for treatment-resistant schizophrenia: evidence from a systematic review and meta-analyses
    (2013) SOUZA, Juliano S.; KAYO, Monica; TASSELL, Ivson; MARTINS, Camila Bertini; ELKIS, Helio
    Introduction. Clozapine is considered the gold standard for the treatment of patients with treatment-resistant schizophrenia (TRS); however, randomized controlled trials (RCT) of olanzapine showed efficacy similar to clozapine in patients with TRS. Methods. A systematic review was conducted comparing clozapine with olanzapine in patients with TRS. Meta-analyses were performed for single outcome measures. Response to treatment was measured by the percentage of responders, or mean change or endpoint values of psychotic symptoms scales. Effect sizes were shown as relative risks (RR), or standardized mean differences, with 95% confidence intervals. Findings. Seven RCT were included, comprising 648 patients. Five meta-analyses were performed. Olanzapine and clozapine had similar effects on dropout rates (RR=0.93, CI95% = 0.77-1.12), PANSS total endpoints (SMD=0.21, CI95% = -0.04-0.46), and PANSS total mean changes (SMD=0.08, CI95% = -0.01-0.027). Clozapine was superior to olanzapine for PANSS positive (SMD=0.51, CI95% = 0.17-0.86) and negative (SMD=0.50, CI95% = 0.16-0.85) subscales. There was a trend toward high doses of olanzapine producing higher effect sizes for this drug. Conclusions. The results of this study suggest that clozapine is significantly more efficacious than olanzapine in improving positive and negative symptoms in TRS patients.
  • article 29 Citação(ões) na Scopus
    Understanding the impact of persistent symptoms in schizophrenia: Cross-sectional findings from the Pattern study
    (2015) HARO, Josep Maria; ALTAMURA, Carlo; CORRAL, Ricardo; ELKIS, Helio; EVANS, Jonathan; MALLA, Ashok; KREBS, Marie-Odile; ZINK, Mathias; BERNASCONI, Corrado; LALONDE, Justine; NORDSTROEM, Anna-Lena
    Background: The high societal burden of schizophrenia is largely caused by the persistence of symptoms and accompanying functional impairment. To date, no studies have specifically assessed the course of persistent symptoms or the individual contributions of positive and negative symptoms to patient functioning. The cross-sectional analysis of the Pattern study provides an international perspective of the burden of schizophrenia. Methods: Clinically stable outpatients from 140 study centers across eight countries (Argentina, Brazil, Canada, France, Germany, Italy, Spain and the United Kingdom) were assessed using clinical rating scales: Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Schizophrenia (CGI-SCH) Scale and the Personal and Social Performance (PSP) Scale. Additional measures included patient-reported outcomes, patient sociodemographic variables, living situation, employment and resource use. Results: Overall, 1379 patients were assessed and analyzed and had similar sociodemographic characteristics across countries, with 61.6% having persistent positive and/or negative symptoms. Positive and negative symptoms had been persistent for a mean of 9.6 and 8.9 years (SD: 8.8 and 9.6), respectively. Approximately 86% of patients had a functional disability classified as greater than mild. Patients with a higher PANSS Negative Symptom Factor Score were more likely to have a poorer level of functioning. Conclusions: This analysis examines individual contributions of persistent positive and negative symptoms on patient functioning in different countries. A high prevalence of patients with persistent symptoms and functional impairment was a consistent finding across countries. Longitudinal observations are necessary to assess how to improve persistent symptoms of schizophrenia and overall patient functioning.
  • article 8 Citação(ões) na Scopus
    Cortical surface abnormalities are different depending on the stage of schizophrenia: A cross-sectional vertexwise mega-analysis of thickness, area and gyrification
    (2021) ROSA, Pedro Gomes Penteado; ZUGMAN, Andre; CERQUEIRA, Carlos Toledo; SERPA, Mauricio Henriques; DURAN, Fabio Luis de Souza; ZANETTI, Marcus Vinicius; BASSITT, Debora Pastore; ELKIS, Helio; CRIPPA, Jose Alexandre S.; SALLET, Paulo Clemente; GATTAZ, Wagner Farid; HALLAK, Jaime Eduardo Cecilio; LOUZA, Mario Rodrigues; GADELHA, Ary; JACKOWSKI, Andrea Parolin; BRESSAN, Rodrigo Affonseca; BUSATTO FILHO, Geraldo
    Background: Brain magnetic resonance imaging studies have not investigated the cortical surface comprehensively in schizophrenia subjects by assessing thickness, surface area and gyrification separately during the first episode of psychosis (FEP) or chronic schizophrenia (ChSch). Methods: We investigated cortical surface abnormalities in 137 FEP patients and 240 ChSch subjects compared to 297 Healthy Controls (HC) contributed by five cohorts. Maps showing results of vertexwise between-group comparisons of cortical thickness, area, and gyrification were produced using T1-weighted datasets processed using FreeSurfer 5.3, followed by validated quality control protocols. Results: FEP subjects showed large clusters of increased area and gyrification relative to HC in prefrontal and insuli cortices (Cohen's d: 0.049 to 0.28). These between-group differences occurred partially beyond the effect of sample. ChSch subjects displayed reduced cortical thickness relative to HC in smaller fronto-temporal foci (d:-0.73 to-0.35), but not beyond the effect of sample. Differences between FEP and HC subjects were associated with male gender, younger age, and earlier illness onset, while differences between ChSch and HC were associated with treatment-resistance and first-generation antipsychotic (FGA) intake independently of sample effect. Conclusions: Separate assessments of FEP and ChSch revealed abnormalities that differed in regional distribution, phenotypes affected and effect size. In FEP, associations of greater cortical area and gyrification abnormalities with earlier age of onset suggest an origin on anomalous neurodevelopment, while thickness reductions in ChSch are at least partially explained by treatment-resistance and FGA intake. Associations of between-group differences with clinical variables retained statistical significance beyond the effect of sample.
  • article 1 Citação(ões) na Scopus
    Clozapine prescription trends in Brazil in the last decade
    (2022) MASSUDA, Raffael; GAMA, Clarissa S.; BELMONTE-DE-ABREU, Paulo; ELKIS, Helio; LUCENA, David Freitas de; BRESSAN, Rodrigo; NOTO, Cristiano; GADELHA, Ary
    Objective: Clozapine is a second-generation antipsychotic indicated for treatment-resistant schizophrenia. Studies in several countries have shown a low rate of clozapine use despite the fact that approximately 30% of schizophrenia cases are treatment-resistant. In Brazil, few studies have addressed the frequency and variety of antipsychotic use in individuals diagnosed with schizophrenia (ICD F20). The objective of this study was to measure the rates of clozapine use in this population in the last decade using Brazilian Ministry of Health data. Methods: Prescriptions made between 2010 and 2020 in all 26 states and the Federal District registered at the Outpatient Information System Database from the Brazilian Health System (SIASUS) were evaluated. Results: A total of 25,143,524 prescriptions were recorded in this period, with clozapine representing 8.86% of all antipsychotics. The most frequently prescribed antipsychotic for patients with schizophrenia was olanzapine (35.8%), followed by quetiapine (27.5%). From 2010 to 2020, the rate of clozapine prescriptions in Brazil increased from 7.2% to 10.9%. Conclusions: Despite a slight increase in prescriptions in the last decade, clozapine is still underutilized in Brazil.
  • 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 41 Citação(ões) na Scopus
    A cross-national factor analytic comparison of three models of PANSS symptoms in schizophrenia
    (2014) STEFANOVICS, Elina A.; ELKIS, Helio; Liu Zhening; ZHANG, Xiang Y.; ROSENHECK, Robert A.
    The 30-item Positive and Negative Syndrome Scale (PANSS) is used worldwide in the assessment of symptom severity in schizophrenia. The present study uses confirmatory factor analysis (CFA) to compare three different factorial models and to evaluate the best-fitting representation of schizophrenia symptom structure on the PANSS across four samples of patients diagnosed with schizophrenia from the US (the CATIE schizophrenia trial), Sao Paulo, Brazil, and from Beijing and Changsha, China. We examine the goodness of fit of several previously proposed models. The traditional trifactorial model for the PANSS and two five-factor models were evaluated using absolute and incremental indices. Single group CFA found that the five-factor model proposed by NIMH researchers based on an extensive literature review demonstrates the best fit in each of the four samples. This model used 20 of the 30 PANSS items grouped into five factors: positive, negative, disorganized, excited, and depressed symptoms. Subgroups defined by age, gender, nationality, hospitalization status, and severity of illness also did not differ in overall symptom structure as assessed by several standard indices. Our findings suggest that the five factor NIMH model showed the best representation among all four samples from different countries and potentially contrasting cultures.