Deep brain stimulation for depression: Scientific issues and future directions.
OBJECTIVE
Deep brain stimulation is an experimental intervention for treatment-resistant depression. Open trials have shown a sustained response to chronic stimulation in many subjects. However, two recent randomised, double-blind, placebo-controlled trials failed to replicate these results. This article is a conceptual paper examining potential explanations for these discrepant findings.


METHODS
We conducted a systematic review of the published studies obtained from PubMed and PsycINFO. Studies were selected if they directly examined the impact of deep brain stimulation on depressive symptoms. We excluded case reports and papers re-describing the same cohort of patients. We compared them with data from the placebo-controlled trials, available from Clinicaltrials.gov and abstracts of the American Society for Stereotactic and Functional Neurosurgery. We supplemented our investigation by reviewing additional publications by the major groups undertaking deep brain stimulation for mood disorders.


RESULTS
We selected 10 open studies reporting on eight cohorts of patients using four different operative targets. All published studies reported positive results. This was not replicated in data available from the randomised, placebo-controlled trials. Many studies reported suicide or suicide attempts in the postoperative period.


CONCLUSIONS
We consider the placebo effect, the pattern of network activation, surgical candidacy and design of a blinded trial including the length of a crossover period. We suggest a greater focus on selecting patients with melancholia. We anticipate that methodological refinements may facilitate further investigation of this technology for intractable depression. We conclude by noting the psychiatric adverse events that have been reported in the literature to date, as these will also influence the design of future trials of deep brain stimulation for depression.
The 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.
Philip E
PE
Mosley
The 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.
Rodney
R
Marsh
School of Psychological Sciences, Monash University, Melbourne, VIC, Australia.
Adrian
A
Carter
D046690:Deep Brain Stimulation / Q000523:psychology*; D061218:Depressive Disorder, Treatment-Resistant / Q000628:therapy*; D006801:Humans; D015990:Placebo Effect; D011184:Postoperative Period; D016032:Randomized Controlled Trials as Topic; D013406:Suicide, Attempted
Deep brain stimulation; depression; melancholia; randomised controlled trial; suicide; tractography