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

Lucas Borrione, Helena Bellini, Lais Boralli Razza, Ana G. Avila, Chris Baeken, Anna Katharine Brem, Geraldo Busatto, Andre F. Carvalho, Adam Chekroud, Zafiris J. Daskalakis, Zhi De Deng, Jonathan Downar, Wagner Gattaz, Colleen Loo, Paulo A. Lotufo, Maria da Graça M. Martin, Shawn M. McClintock, Jacinta O’shea, Frank Padberg, Ives C. PassosGiovanni A. Salum, Marie Anne Vanderhasselt, Renerio Fraguas, Isabela Benseñor, Leandro Valiengo, Andre R. Brunoni

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)403-419
Number of pages17
JournalRevista Brasileira de Psiquiatria
Issue number4
StatePublished - Jul 1 2020


  • Electroconvulsive therapy
  • Major depressive disorder
  • Precision medicine
  • Transcranial direct current stimulation
  • Transcranial magnetic stimulation

ASJC Scopus subject areas

  • Psychiatry and Mental health


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