Non-implantable neuromodulation therapies: a perspective for the depressed brain

• Grant number: 19/06009-6
• Support type: Research Projects - Thematic Grants
• Duration: March 01, 2021 - February 28, 2026
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal researcher: Andre Russowsky Brunoni
• Grantee: Andre Russowsky Brunoni
• Home Institution: Hospital Universitário (HU). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Assoc. researchers: Geraldo Busatto Filho ; Giovanni Abrahão Salum Júnior ; Isabela Judith Martins Bensenor ; Ives Cavalcante Passos ; Laiss Bertola de Moura Ricardo ; Leandro da Costa Lane Valiengo ; Maria da Graça Morais Martin ; Maurício Henriques Serpa ; Paulo Andrade Lotufo ; Renério Fráguas Junior ; Vanessa de Jesus Rodrigues de Paula ; Wagner Farid Gattaz
• Associated scholarship(s): 21/10827-6 - Evaluation of left dorsolateral prefrontal cortex volume as a predictor of clinical response to the use of theta-burst stimulation in the treatment of unipolar depression, BP.DR; 22/03266-0 - Investigation of neuroimaging assessments and current flow modeling as target engagement and predictor biomarkers of convulsive therapies, BP.PD; 22/01197-1 - Non-implantable Neuromodulation Therapies: A perspective for the depressed brain, BP.TT; + associated scholarships 21/10574-0 - Prognostic enhancement in depressed patients on different non-implantable neuromodulation interventions, BP.PD; 21/09730-8 - Management of clinical trial data in the Precision Non-Implantable Neuromodulation project using REDcap, BP.TT; 21/05237-5 - Using machine-learning approaches in non-invasive brain stimulation trials to identify clusters of symptoms associated with clinical response, BP.IC; 21/04294-5 - Structural and functional neuroimaging predictor and state biomarkers in depression after non-invasive brain stimulation and ECT: systematic review and meta-analysis, BP.IC; 21/02845-4 - Project manager of RCT1: home-use tDCS plus internet behavioral therapy (iBT) in unipolar depression, BP.TT - associated scholarships

Abstract

Major Depressive Disorder (MDD) is a condition with high prevalence and morbidity worldwide. Treatments have limited efficacy and are curbed by adverse effects (Pharmacotherapy) or availability and costs (psychotherapy). Thus, developing novel interventions is tremendously relevant and can bring major gains in psychiatric care. Non-Implantable Neuromodulatory (NIN) approaches such as transcranial Direct Current Stimulation (tDCS) and Magnetic Seizure Therapy (MST) represent a third therapeutic principle, i.e. neuronal network modulation, which can benefit from making full use of the large body of data in MDD derived from neuroimaging and neurophysiology research. Moreover, the development of NIN addresses the need for innovative interventions in MDD. This project focuses on MDD at different stages of therapy-resistance and investigates tDCS and MST for gaining a deeper understanding of their mechanisms of action and developing both interventions towards a wider clinical application. Two Randomized Clinical Trials (RCTs) were designed to investigate the efficacy of state-of-the-art NIN techniques, which represent novel developments from previous NIN approaches that are only moderately effective or associated with cognitive side effects. RCT1 uses a 3-arm, double-blind design to compare the efficacy of 24 sessions (6 times per week in 3 weeks, then twice a week until week 6) home-use tDCS combined with internet-Based behavioral Therapy (iBT) modules versus tDCS-only and versus sham in 210 adult patients with unipolar depression. RCT2 uses a non-inferiority design to compare 8-16 sessions over 6 weeks of Magnetic Seizure Therapy (MST) versus ECT in treatment-resistant depressed, adult patients, considering both clinical efficacy and cognitive changes as co-primary outcomes. In addition, we will investigate cognition (module 1) and neuroimaging (module 2, only for RCT2) as putative clinical and biological endophenotypes that predict treatment response and change according to treatment. Predictors will be examined using statistical approaches and machine learning algorithms in the Prognostic Enhancement module (module 3). This thematic project will take place at two Institutions (University Hospital and Institute of Psychiatry at USP) with experience in trials using devices and includes an advisory board of international researchers from 12 universities in the US, Canada, UK, Australia, Germany, Switzerland, and Belgium that will leverage collaborations and dissemination of results. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

RAZZA, LAIS B.; DE SMET, STEFANIE; MOFFA, ADRIANO; SUDBRACK-OLIVEIRA, PEDRO; VANDERHASSELT, MARIE-ANNE; BRUNONI, ANDRE R.. Follow-up effects of transcranial direct current stimulation (tDCS) for the major depressive episode: A systematic review and meta-analysis. PSYCHIATRY RESEARCH, v. 302, AUG 2021. (19/06009-6, 19/10760-9, 19/07256-7, 18/10861-7)

BORRIONE, LUCAS; KLEIN, IZIO; RAZZA, LAIS B.; SUEN, PAULO; BRUNONI, ANDRE R.. Use of app-based psychological interventions in combination with home-use transcranial direct current stimulation for the treatment of major depressive disorder: A case series. Journal of Affective Disorders, v. 288, p. 189-190, JUN 1 2021. (18/10861-7, 19/06009-6)