A narrative review on invasive brain stimulation for treatment-resistant depression

Manoj P. Dandekar, Alexandre P. Diaz, Ziaur Rahman, Ritele H. Silva, Ziad Nahas, Scott Aaronson, Sudhakar Selvaraj, Albert J. Fenoy, Marsal Sanches, Jair C. Soares, Patricio Riva-Posse, Joao Quevedo

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations


While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic benefits, and the average response rate varies from 15.2-83%. Deep brain stimulation studies have shown encouraging results, including rapid response rates (> 30%), despite conflicting findings from randomized controlled trials. Several brain regions, such as the subcallosal-cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, anterior limb of the internal capsule, medial-forebrain bundle, lateral habenula, inferior-thalamic peduncle, and the bed-nucleus of the stria terminalis have been identified as key targets for TRD management. Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are needed to confirm its potential in patients with TRD.

Original languageEnglish (US)
Pages (from-to)317-330
Number of pages14
JournalRevista Brasileira de Psiquiatria
Issue number3
StatePublished - May 1 2022


  • Treatment-resistant depression
  • deep brain stimulation
  • epidural cortical stimulation subcallosal cingulate gyrus
  • medial forebrain bundle
  • vagus nerve stimulation
  • Brain
  • Humans
  • Psychotherapy
  • Depression
  • Deep Brain Stimulation/methods
  • Depressive Disorder, Treatment-Resistant/therapy

ASJC Scopus subject areas

  • Psychiatry and Mental health


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