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Updated: Apr 5, 2026

Author Spotlight: Therapeutic Benefit of Closed-Loop Deep Brain Stimulation in Depression Treatment
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Deep brain stimulation for depression: Scientific issues and future directions.

Philip E Mosley1, Rodney Marsh2, Adrian Carter3

  • 1The Asia-Pacific Centre for Neuromodulation, UQ Centre for Clinical Research, The University of Queensland, Herston, QLD, Australia Department of Psychiatry, Royal Brisbane & Women's Hospital, Herston, QLD, Australia Neurosciences Queensland, St Andrew's War Memorial Hospital, Spring Hill, QLD, Australia Systems Neuroscience Group, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia p.mosley@uq.edu.au.

The Australian and New Zealand Journal of Psychiatry
|August 16, 2015
PubMed
Summary

Deep brain stimulation (DBS) shows promise for treatment-resistant depression in open trials, but recent placebo-controlled studies yielded conflicting results. Further research is needed to understand these discrepancies and optimize patient selection for DBS therapy.

Keywords:
Deep brain stimulationdepressionmelancholiarandomised controlled trialsuicidetractography

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Neurosurgery

Background:

  • Deep brain stimulation (DBS) is an experimental treatment for treatment-resistant depression (TRD).
  • Previous open-label studies indicated sustained positive responses to chronic DBS in many TRD patients.
  • Recent randomized, double-blind, placebo-controlled trials (RCTs) failed to replicate these positive findings, creating a discrepancy in the literature.

Purpose of the Study:

  • To conceptually examine potential explanations for the discrepant findings between open-label and RCTs of DBS for TRD.
  • To review existing literature and compare findings from open-label studies with data from RCTs.
  • To identify factors that may influence the efficacy and interpretation of DBS for intractable depression.

Main Methods:

  • Systematic review of published studies on DBS for depressive symptoms from PubMed and PsycINFO.
  • Exclusion of case reports and redundant cohort descriptions.
  • Comparison with data from RCTs (ClinicalTrials.gov, conference abstracts) and publications from leading research groups.

Main Results:

  • Ten open-label studies involving eight patient cohorts and four operative targets reported positive outcomes.
  • These positive results were not replicated in the available data from RCTs.
  • Several studies reported instances of suicide or suicide attempts during the postoperative period.

Conclusions:

  • Potential explanations for discrepant findings include the placebo effect, network activation patterns, surgical candidacy criteria, and trial design (e.g., crossover duration).
  • A greater focus on patient selection, particularly for individuals with melancholic depression, is suggested.
  • Methodological refinements and careful consideration of psychiatric adverse events are crucial for future DBS trials in depression.