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Braz J Psychiatry. 2020 Mar 16. pii: S1516-44462020005006202. doi: 10.1590/1516-4446-2019-0741. [Epub ahead of print]

Precision non-implantable neuromodulation therapies: a perspective for the depressed brain.

Author information

1
Serviço Interdisciplinar de Neuromodulação, Laboratório de Neurociências (LIM-27), Departamento e Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brazil.
2
Centro de Neuropsicologia e Intervenção Cognitivo-Comportamental, Faculdade de Psicologia e Ciências da Educação, Universidade de Coimbra, Coimbra, Portugal.
3
Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
4
Department of Psychiatry, University Hospital (UZ Brussel), Brussels, Belgium.
5
Ghent Experimental Psychiatry (GHEP) Lab, Ghent University, Ghent, Belgium.
6
Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
7
Max Planck Institute of Psychiatry, Munich, Germany.
8
Division of Interventional Cognitive Neurology, Department of Neurology, Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
9
Laboratório de Neuroimagem em Psiquiatria (LIM-21), Departamento e Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina, USP, São Paulo, SP, Brazil.
10
Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
11
Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada.
12
Spring Health, New York, NY, USA.
13
Department of Psychiatry, Yale University, New Haven, CT, USA.
14
Noninvasive Neuromodulation Unit, Experimental Therapeutic & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
15
Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University, Durham, NC, USA.
16
Department of Psychiatry and Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
17
Centre for Mental Health and Krembil Research Institute, University Health Network, Toronto, ON, Canada.
18
Laboratório de Neurociências (LIM-27), Departamento e Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina, USP, São Paulo, SP, Brazil.
19
Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBioN), Departamento e Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina, USP, São Paulo, SP, Brazil.
20
School of Psychiatry and Black Dog Institute, University of New South Wales, Sydney, Australia.
21
Estudo Longitudinal de Saúde do Adulto (ELSA), Centro de Pesquisa Clínica e Epidemiológica, Hospital Universitário, USP, São Paulo, SP, Brazil.
22
Laboratório de Ressonância Magnética em Neurorradiologia (LIM-44) and Instituto de Radiologia, Hospital das Clínicas, Faculdade de Medicina, USP, São Paulo, SP, Brazil.
23
Neurocognitive Research Laboratory, Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, USA.
24
Wellcome Centre for Integrative Neuroimaging, Oxford Centre for Human Brain Activity, Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, United Kingdom.
25
Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
26
Laboratório de Psiquiatria Molecular e Programa de Transtorno Bipolar, Hospital de Clínicas de Porto Alegre (HCPA), Programa de Pós-Graduação em Psiquiatria e Ciências do Comportamento, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
27
Departamento de Psiquiatria, Seção de Afeto Negativo e Processos Sociais (SANPS), HCPA, UFRGS, Porto Alegre, RS, Brazil.
28
Department of Experimental Clinical and Health Psychology, Psychopathology and Affective Neuroscience Lab, Ghent University, Ghent, Belgium.
29
Hospital Universitário, USP, São Paulo, SP, Brazil.

Abstract

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.

PMID:
32187319
DOI:
10.1590/1516-4446-2019-0741
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