HELIO ELKIS
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Psiquiatria, Faculdade de Medicina - Docente
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
44 resultados
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- 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, HelioThe 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.
- ECT versus Sham for clozapine-resistant schizophrenia: A secondary analysis of a pilot study based on PANSS-30 individual items(2020) MELZER-RIBEIRO, Debora Luciana; GRILLI-TISSOT, Maria Cristina Ribeiro; ELKIS, Helio
- Efficacy and Moderators of Cognitive Behavioural Therapy for Psychosis Versus Other Psychological Interventions: An Individual-Participant Data Meta-Analysis(2020) TURNER, David T.; REIJNDERS, Mirjam; GAAG, Mark van der; KARYOTAKI, Eirini; VALMAGGIA, Lucia R.; MORITZ, Steffen; LECOMTE, Tania; TURKINGTON, Douglas; PENADES, Rafael; ELKIS, Helio; CATHER, Corinne; SHAWYER, Frances; O'CONNOR, Kieron; LI, Zhan-Jiang; BARRETTO, Eliza Martha de Paiva; CUIJPERS, PimBackground Study-level meta-analyses have demonstrated the efficacy of cognitive-behavioural therapy for psychosis (CBTp). Limitations of conventional meta-analysis may be addressed using individual-participant-data (IPD). We aimed to determine a) whether results from IPD were consistent with study-level meta-analyses and b) whether demographic and clinical characteristics moderate treatment outcome. Methods We systematically searched PubMed, Embase, PsychInfo and CENTRAL. Authors of RCTs comparing CBTp with other psychological interventions were contacted to obtain original databases. Hierarchical mixed effects models were used to examine efficacy for psychotic symptoms. Patient characteristics were investigated as moderators of symptoms at post-treatment. Sensitivity analyses were conducted for risk of bias, treatment format and study characteristics. Results We included 14 of 23 eligible RCTs in IPD meta-analyses including 898 patients. Ten RCTs minimised risk of bias. There was no significant difference in efficacy between RCTs providing IPD and those not (p >0.05). CBTp was superior vs. other interventions for total psychotic symptoms and PANSS general symptoms. No demographic or clinical characteristics were robustly demonstrated as moderators of positive, negative, general or total psychotic symptoms at post-treatment. Sensitivity analyses demonstrated that number of sessions moderated the impact of treatment assignment (CBTp or other therapies) on total psychotic symptoms (p = 0.02). Conclusions IPD suggest that patient characteristics, including severity of psychotic symptoms, do not significantly influence treatment outcome in psychological interventions for psychosis while investing in sufficient dosage of CBTp is important. IPD provide roughly equivalent efficacy estimates to study-level data although significant benefit was not replicated for positive symptoms. We encourage authors to ensure IPD is accessible for future research.
- 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, LeandroCognitive 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
- Which are the best evidence-based therapeutic options for clozapine and ECT resistant schizophrenia? A case-report(2021) DAMIANO, Rodolfo Furlan; AVRICHIR, Belquiz S.; MELZER-RIBEIRO, Debora L.; SALLET, Paulo Clemente; ELKIS, HelioThis is a case description of a patient with clozapine and ECT resistance schizophrenia with several suicide attempts. We discussed evidence-based clinical decisions to deal with such conditions.
- Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology(2017) HOWES, Oliver D.; MCCUTCHEON, Rob; AGID, Ofer; BARTOLOMEIS, Andrea de; BEVEREN, Nico J. M. van; BIRNBAUM, Michael L.; BLOOMFIELD, Michael A. P.; BRESSAN, Rodrigo A.; BUCHANAN, Robert W.; CARPENTER, William T.; CASTLE, David J.; CITROME, Leslie; DASKALAKIS, Zafiris J.; DAVIDSON, Michael; DRAKE, Richard J.; DURSUN, Serdar; EBDRUP, Bjorn H.; ELKIS, Helio; FALKAI, Peter; FLEISCHACKER, W. Wolfgang; GADELHA, Ary; GAUGHRAN, Fiona; GLENTHOJ, Birte Y.; GRAFF-GUERRERO, Ariel; HALLAK, Jaime E. C.; HONER, William G.; KENNEDY, James; KINON, Bruce J.; LAWRIE, Stephen M.; LEE, Jimmy; LEWEKE, F. Markus; MACCABE, James H.; MCNABB, Carolyn B.; MELTZER, Herbert; MOELLER, Hans-Juergen; NAKAJIMA, Shinchiro; PANTELIS, Christos; MARQUES, Tiago Reis; REMINGTON, Gary; ROSSELL, Susan L.; RUSSELL, Bruce R.; SIU, Cynthia O.; SUZUKI, Takefumi; SOMMER, Iris E.; TAYLOR, David; THOMAS, Neil; UCOK, Alp; UMBRICHT, Daniel; WALTERS, James T. R.; KANE, John; CORRELL, Christoph U.Objective: Research and clinical translation in schizophrenia is limited by inconsistent definitions of treatment resistance and response. To address this issue, the authors evaluated current approaches and then developed consensus criteria and guidelines. Method: A systematic review of randomized antipsychotic clinical trials in treatment-resistant schizophrenia was performed, and definitions of treatment resistance were extracted. Subsequently, consensus operationalized criteria were developed through 1) a multiphase, mixed methods approach, 2) identification of key criteria via an online survey, and 3) meetings to achieve consensus. Results: Of 2,808 studies identified, 42 met inclusion criteria. Of these, 21 studies (50%) did not provide operationalized criteria. In the remaining studies, criteria varied considerably, particularly regarding symptom severity, prior treatment duration, and antipsychotic dosage thresholds; only two studies (5%) utilized the same criteria. The consensus group identified minimum and optimal criteria, employing the following principles: 1) current symptoms of a minimum duration and severity determined by a standardized rating scale; 2) moderate or worse functional impairment; 3) prior treatment consisting of at least two different antipsychotic trials, each for a minimum duration and dosage; 4) systematic monitoring of adherence and meeting ofminimumadherence criteria; 5) ideally at least one prospective treatment trial; and 6) criteria that clearly separate responsive from treatment-resistant patients. Conclusions: There is considerable variation in current approaches to defining treatment resistance in schizophrenia. The authors present consensus guidelines that operationalize criteria for determining and reporting treatment resistance, adequate treatment, and treatment response, providing a benchmark for research and clinical translation.
- 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, HelloRehospitalization 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.
- 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.
- Efficacy of electroconvulsive therapy augmentation for partial response to clozapine: a pilot randomized ECT - sham controlled trial(2017) MELZER-RIBEIRO, Debora Luciana; RIGONATTI, Sergio Paulo; KAYO, Monica; AVRICHIR, Belquiz S.; RIBEIRO, Rafael Bernardon; SANTOS, Bernardo dos; FORTES, Marisa; ELKIS, HelioBackground: Thirty percent of schizophrenia patients are treatment-resistant. Objective: This is a single-blinded sham-controlled trial to assess the efficacy of electroconvulsive therapy (ECT) as augmentation strategy in patients with clozapine-resistant schizophrenia. Methods: Twenty three subjects were randomly assigned to 12 sessions of ECT (N = 13) or placebo (Sham ECT) (N = 10). The primary outcome was improvement on psychotic symptoms as measured by the mean reduction of the PANSS positive subscale. The assessments were performed by blind raters. Results: At baseline both groups were similar, except for negative and total symptoms of the PANSS, which were higher in the Sham group. At the endpoint both groups had a significant decrease from basal score. In the ECT group the PANSS total score decreased 8.78%, from 81.23 to 74.75 (p - 0.042), while the positive subscale had a mean reduction of 19% (19.31 to 16.17, p = 0.006). In the Sham group, the mean reduction of PANSS total score was 15.27% (96.80 to 87.43; p = 0.036), and the PANSS positive subscale decreased 27.81% (22.90 to 19.14, p = 0.008). The CGI score in ECT group decreased 23.0% (5.23 to 4.17; p = 0.001) and decreased 24.31% in the Sham ECT group (5.80 to 4.86; p = 0.004). Discussion: In this pilot study, we found no difference between the groups.
- Early Improvement As a Predictor of Later Response to Antipsychotics in Schizophrenia: A Diagnostic Test Review(2015) SAMARA, Myrto T.; LEUCHT, Claudia; LEEFLANG, Mariska M.; ANGHELESCU, Ion-George; CHUNG, Young-Chul; CRESPO-FACORRO, Benedicto; ELKIS, Helio; HATTA, Kotaro; GIEGLING, Ina; KANE, John M.; KAYO, Monica; LAMBERT, Martin; LIN, Ching-Hua; MOELLER, Hans-Juergen; PELAYO-TERAN, Jose Maria; RIEDEL, Michael; RUJESCU, Dan; SCHIMMELMANN, Benno G.; SERRETTI, Alessandro; CORRELL, Christoph U.; LEUCHT, StefanObjective: How long clinicians should wait before considering an antipsychotic ineffective and changing treatment in schizophrenia is an unresolved clinical question. Guidelines differ substantially in this regard. The authors conducted a diagnostic test meta-analysis using mostly individual patient data to assess whether lack of improvement at week 2 predicts later nonresponse. Method: The search included EMBASE, MEDLINE, BIOSIS, PsycINFO, Cochrane Library, CINAHL, and reference lists of relevant articles, supplemented by requests to authors of all relevant studies. The main outcome was prediction of nonresponse, defined as <50% reduction in total score on either the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) (corresponding to at least much improved) from baseline to endpoint (4-12 weeks), by <20% PANSS or BPRS improvement (corresponding to less than minimally improved) at week 2. Secondary outcomes were absent cross-sectional symptomatic remission and <20% PANSS or BPRS reduction at endpoint. Potential moderator variables were examined by meta regression. Results: In 34 studies (N=9,460) a <20% PANSS or BPRS reduction at week 2 predicted nonresponse at endpoint with a specificity of 86% and a positive predictive value (PPV) of 90%. Using data for observed cases (specificity=86%, PPV=85%) or lack of remission (specificity=77%, PPV=88%) yielded similar results. Conversely, using the definition of <20% reduction at endpoint yielded worse results (specificity=70%, PPV=55%). The test specificity was significantly moderated by a trial duration of <6 weeks, higher baseline illness severity, and shorter illness duration. Conclusions: Patients not even minimally improved by week 2 of antipsychotic treatment are unlikely to respond later and may benefit from a treatment change.