Psiquiatria intervencionista personalizada: revisão narrativa sobre biomarcadores laboratoriais preditivos de resposta à ECT e TMS em depressão resistente
DOI:
https://doi.org/10.25118/2763-9037.2026.v16.1524Palavras-chave:
biomarcadores, Eletroconvulsoterapia, Estimulação Magnética Transcraniana, transtorno depressivo maior, previsão, ECTResumo
Introdução: O transtorno depressivo maior (TDM) é a principal causa de incapacidade global, com cerca de 30% dos pacientes evoluindo para o transtorno depressivo resistente ao tratamento (DRT). Diante da falha em múltiplos trials, a eletroconvulsoterapia (ECT) e a estimulação magnética transcraniana (TMS) são essenciais, mas carecem de biomarcadores para interromper a abordagem de tentativa e erro. Objetivo: Esta revisão narrativa de literatura tem como objetivo atualizar e sintetizar o conhecimento recente sobre os biomarcadores laboratoriais e moleculares com potencial preditivo de resposta clínica à ECT e à TMS no tratamento da DRT. Métodos: Foram consultadas as bases PubMed e Cochrane (2010-2025) para identificação de evidências recentes, selecionando-se 17 artigos para análise detalhada. O levantamento foi complementado por uma busca manual, totalizando 30 referências. Resultados e Discussão: A predição da resposta é específica à modalidade. A ECT é primariamente predita por marcadores de estresse crônico e Eixo HPA (cortisol pós-dexametasona e trajetória em cabelo). A TMS é mais sensível à integridade sistêmica (Índice de inflamação sistêmica - SII) e perfis epigenéticos (regiões diferencialmente metiladas - DMRs). O fator neurotrófico derivado do encéfalo (BDNF) sérico basal demonstrou utilidade preditiva nula. A tendência atual aponta para modelos de predição multimodais que integram dados moleculares à neuroimagem e aos marcadores metabólicos centrais. Conclusão: A psiquiatria de precisão na DRT é viável. O sucesso terapêutico será definido pela implementação de painéis de biomarcadores que avaliem o estresse periférico e o perfil epigenético para guiar a escolha entre ECT e TMS, otimizando o manejo do paciente.
Downloads
Métricas
Referências
1. Malhi GS, Mann JJ. Depression. Lancet. 2018;392(10161):2299-312. https://doi.org/10.1016/S0140-6736(18)31948-2 PMid:30396512
2. Lopes CS, Gomes NL, Junger WL, Menezes PR. Trend in the prevalence of depressive symptoms in Brazil: results from the Brazilian National Health Survey 2013 and 2019. Cad Saude Publica. 2022;38(Suppl 1):e00123421. https://doi.org/10.1590/0102-311x00123421 PMid:35544918
3. Hintz AM, Gomes-Filho IS, Loomer PM, de Sousa Pinho P, de Santana Passos-Soares J, Trindade SC, Cerqueira EMM, Alves CMC, Rios YSS, Batista JET, Figueiredo ACMG, Cruz SS. Depression and associated factors among Brazilian adults: the 2019 national healthcare population-based study. BMC Psychiatry. 2023;23(1):704. https://doi.org/10.1186/s12888-023-05133-9 PMid:37770824 PMCid:PMC10537974
4. McIntyre RS, Alsuwaidan M, Baune BT, Berk M, Demyttenaere K, Goldberg JF, et al. Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions. World Psychiatry. 2023;22(3):394-412. https://doi.org/10.1002/wps.21120 PMid:37713549 PMCid:PMC10503923
5. Al-Harbi KS. Treatment-resistant depression: therapeutic trends, challenges, and future directions. Patient Prefer Adherence. 2012;6:369-88. https://doi.org/10.2147/PPA.S29716 PMID: 22654508 PMCID: PMC3363299
6. Thase ME, Rush AJ. Treatment-resistant depression. In: Bloom FE, Kupfer DJ, editors. Psychopharmacology: The Fourth Generation of Progress. New York: Raven Press; 1995. p. 1081-1097.
7. Bergfeld IO, Mantione M, Figee M, Schuurman PR, Lok A, Denys D. Treatment-resistant depression and suicidality. J Affect Disord. 2018;235:362-7. https://doi.org/10.1016/j.jad.2018.04.016 PMid:29665520
8. Ruiz AC, Haseeb A, Baumgartner W, Leung E, Scaini G, Quevedo J. New insights into the mechanisms of electroconvulsive therapy in treatment-resistant depression. Front Psychiatry. 2025;16:1614076. https://doi.org/10.3389/fpsyt.2025.1614076 PMid:40896230 PMCid:PMC12391056
9. Mickey BJ, Ginsburg Y, Sitzmann AF, Grayhack C, Sen S, Kirschbaum C, Maixner DF, Abelson JL. Cortisol trajectory, melancholia, and response to electroconvulsive therapy. J Psychiatr Res. 2018;103:46-53. https://doi.org/10.1016/j.jpsychires.2018.05.007 PMid:29775916 PMCid:PMC6457450
10. Longpré-Poirier C, Miron JP, Garel N, Samson-Daoust E, Rizkallah E, Desbeaumes Jodoin V, Juster R-P, Lespérance P. Elevated allostatic load is associated with poorer response to repetitive transcranial magnetic stimulation in treatment-resistant depression. Psychiatry Res. 2024;340:116122. https://doi.org/10.1016/j.psychres.2024.116122 PMid:39137557
11. Wang Q, Li L, Zhao H, Cheng W, Cui G, Fan L, Dong X, Xu T, Geng Z. Predictors of response to accelerated rTMS in the treatment of treatment-resistant depression. Eur Arch Psychiatry Clin Neurosci. 2025;275(6):1725-36. https://doi.org/10.1007/s00406-024-01903-y PMid:39292262
12. Kruse JL, Congdon E, Olmstead R, Njau S, Breen EC, Narr KL, Espinoza R. Inflammation and Improvement of Depression Following Electroconvulsive Therapy in Treatment-Resistant Depression. J Clin Psychiatry. 2018;79(2):17m11597. https://doi.org/10.4088/JCP.17m11597 PMid:29489077 PMCid:PMC6013272
13. Zincir S, Ozturk PK, Bilgen AE, Izci F, Yukselir C. Levels of serum Immunomodulators and its alteration with electroconvulsive therapy in treatment resistant depression. Neuropsychiatr Dis Treat. 2016;12:1389-96. https://doi.org/10.2147/NDT.S106652 PMid:27366071 PMCid:PMC4913984
14. Kranaster L, Hoyer C, Mindt S, Neumaier M, Müller N, Zill P, Schwarz MJ,Moll N, Lutz B, Bindila L,Zerr I, Schmitz M, Blennow K, Zetterberg H, Haffner D, Leifheit-Nestler M, Ozbalci C, Sartorius A. The novel seizure quality index for the antidepressant outcome prediction in electroconvulsive therapy: association with biomarkers in the cerebrospinal fluid. Eur Arch Psychiatry Clin Neurosci. 2020;270(7):911-19. https://doi.org/10.1007/s00406-019-01086-x PMid:31760473
15. Bilgen AE, Bozkurt Zincir S, Zincir S, Ozdemir B, Ak M, Aydemir E, Sener I. Effects of electroconvulsive therapy on serum levels of brain-derived neurotrophic factor and nerve growth factor in treatment resistant major depression. Brain Res Bull. 2014104:82-7. https://doi.org/10.1016/j.brainresbull.2014.04.005 PMid:24747833
16. Brunoni AR, Baeken C, Machado-Vieira R, Gattaz WF, Vanderhasselt MA. BDNF blood levels after non-invasive brain stimulation interventions in major depressive disorder: a systematic review and meta-analysis. World J Biol Psychiatry. 2015;16(2):114-22. https://doi.org/10.3109/15622975.2014.958101 PMid:25264290
17. Santos LA. Avaliação do BDNF plasmático em pacientes com depressão resistente ao tratamento submetidos à Eletroconvulsoterapia (ECT) e Magnetoconvulsoterapia (MST) [dissertação]. São Paulo: Universidade de São Paulo, Faculdade de Medicina; 2024. https://doi.org/10.11606/D.5.2024.tde-29082024-150417
18. Minelli A, Maffioletti E, Bortolomasi M, Conca A, Zanardini R, Rillosi L, Abate M, Giacopuzzi M, Maina G, Gennarelli M, Bocchio-Chiavetto L. Association between baseline serum vascular endothelial growth factor levels and response to electroconvulsive therapy. Acta Psychiatr Scand. 2014;129(6):461-6. https://doi.org/10.1111/acps.12187 PMid:23957507
19. Fukuda AM, Hindley LE, Kang JWD, Tirrell E, Tyrka AR, Ayala A, Carpenter LL. Peripheral vascular endothelial growth factor changes after transcranial magnetic stimulation in treatment-resistant depression. Neuroreport. 2020;31(16):1121-27. https://doi.org/10.1097/WNR.0000000000001523 PMid:32956213 PMCid:PMC7541741
20. Dahrendorff J, Pages K, Currier G, Sarker MH, Graham Z, Louis-Jacques AF, Dagne G, Uddin M. Epigenetic profiles of response to transcranial magnetic stimulation in treatment resistant depression. BMC Med Genomics. 2025;18(1):181. https://doi.org/10.1186/s12920-025-02240-2 PMid:41225566 PMCid:PMC12613596
21. Carvalho Silva R, Martini P, Hohoff C, Mattevi S, Bortolomasi M, Abate M, Menesello V, Gennarelli M, Baune BT, Minelli A. Unraveling epigenomic signatures and effectiveness of electroconvulsive therapy in treatment-resistant depression patients: a prospective longitudinal study. Clin Epigenetics. 2024;16(1):93. https://doi.org/10.1186/s13148-024-01704-z PMid:39020437 PMCid:PMC11256624
22. Maffioletti E, Gennarelli M, Gainelli G, Bocchio-Chiavetto L, Bortolomasi M, Minelli A. BDNF Genotype and Baseline Serum Levels in Relation to Electroconvulsive Therapy Effectiveness in Treatment-Resistant Depressed Patients. J ECT. 2019;35(3):189-94. https://doi.org/10.1097/YCT.0000000000000583 PMid:30994478
23. Maffioletti E, Carvalho Silva R, Bortolomasi M, Baune BT, Gennarelli M, Minelli A. Molecular Biomarkers of Electroconvulsive Therapy Effects and Clinical Response: Understanding the Present to Shape the Future. Brain Sci. 2021;11(9):1120. https://doi.org/10.3390/brainsci11091120 PMid:34573142 PMCid:PMC8471796
24. Viikki M, Anttila S, Kampman O, Illi A, Huuhka M, Setälä-Soikkeli E, Mononen N, Lehtimäki T, Leinonen E. Vascular endothelial growth factor (VEGF) polymorphism is associated with treatment resistant depression. Neurosci Lett. 2010;477(3):105-8. https://doi.org/10.1016/j.neulet.2010.04.039 PMid:20417690
25. Allen AP, Naughton M, Dowling J, Walsh A, O'Shea R, Shorten G, Scott L, McLoughlin DM, Cryan JF, Clarke G, Dinan TG. Kynurenine pathway metabolism and the neurobiology of treatment-resistant depression: Comparison of multiple ketamine infusions and electroconvulsive therapy. J Psychiatr Res. 2018;100:24-32. https://doi.org/10.1016/j.jpsychires.2018.02.011 PMid:29475018
26. Dexmedetomidine Adjuvant Treatment for Depressed Patients Undergoing ECT. ClinicalTrials.gov Identifier: NCT04661475 [internet]. 2021. [citado 2025 Dez 03]. Disponível em: https://clinicaltrials.gov/study/NCT04661475
27. Dunlop K, Dua A, Liston C. A comparison of symptom-specific resting state functional connectivity biomarkers of 10 HZ and ITBS-RTMS in treatment-resistant depression. Brain Stimul. 2021;14(6):1712. (Abstract FS3E.07). https://doi.org/10.1016/j.brs.2021.10.406
28. A Pilot Study of Creatine monohydrate as an augmenting agent for ECT in persons with major depressive disorder. ClinicalTrials.gov Identifier: NCT04504253 [Internet]. 2024. [citado 2025 Dez 03]. Disponível em: https://clinicaltrials.gov/study/NCT04504253?cond=NCT04504253&rank=1&tab=results
29. Duprat R, Baeken C, Wu GR, De Raedt R, van Heeringen K. Subgenual Anterior Cingulate-Medial Orbitofrontal Functional Connectivity in Medication-Resistant Major Depression: A Neurobiological Marker for Accelerated Intermittent Theta Burst Stimulation Treatment? Biol Psychiatry Cogn Neurosci Neuroimaging. 2017;2(7):556-65. https://doi.org/10.1016/j.bpsc.2017.01.001 PMid:29560909
30. Matsui H, Tamura T, Kameyama M, Furuta K, Omori Y, Takeuchi T, Takahashi H, Sugihara G. Indicative biomarkers of Lewy body disease as predictors of treatment resistance in late-onset depression. Int Psychogeriatr. 2025;37(5):100043. https://doi.org/10.1016/j.inpsyc.2025.100043 PMid:39893132
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Copyright (c) 2026 Lara Vitoria Haubert , Luiza Martins Barbosa, Tauãna Machado Otaran Savian
Este trabalho está licenciado sob uma licença Creative Commons Attribution-NonCommercial 4.0 International License.
Debates em Psiquiatria permite que o (s) autor (es) mantenha(m) seus direitos autorais sem restrições. Atribuição-NãoComercial 4.0 Internacional (CC BY-NC 4.0) - Debates em Psiquiatria é regida pela licença CC-BY-NC
