Review Article

Deep Brain Stimulation for Treatment-Refractory Depression

Authors: Puneet Narang, MD, Amber Retzlaff, MD, Kanwarjeet Brar, MD, Steven Lippmann, MD


: Depression has a high lifetime prevalence and recurrence rate, with more than one-third of affected patients experiencing treatment-refractory depression. These individuals should benefit from additional treatment options such as deep brain stimulation (DBS), a research-grade intervention. DBS is being investigated for its efficacy in treatment-refractory cases. We reviewed the Englishlanguage literature published between the years 2010 and 2015 regarding the utility of DBS for patients with treatment-refractory depression. The literature review revealed that most DBS research is open label, with few large randomized, placebo-controlled trials to confirm results. Long-term response rates with DBS were between 40% and 70%, with clinical effects depending on location of electrode placement. Improvement was documented to last for months to years. Although DBS is potentially efficacious and a relatively safe option for patients with treatment resistance, it is invasive, costly, and still considered experimental. Understanding of the neurobiology of depression, the mechanism of DBS action, and biomarkers that may predict patient response remains obscure. Future research should contain careful design, including homogenous inclusion criteria and characterization of pretreatment patient mood, somatic complaints, and cognition; consistent outcome measures; monitoring of depressive symptoms at different brain-positioning targets across an adequate time course; and records of stimulus parameters.

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1. Berlim MT, McGirr A, Van den Eynde F, et al. Effectiveness and acceptability of deep brain stimulation (DBS) of the subgenual cingulate cortex for treatment-resistant depression: a systematic review and exploratory meta-analysis. J Affect Disord 2014;159:31-38.
2. Morishita T, Fayad SM, Higuchi MA, et al. Deep brain stimulation for treatment-resistant depression: systematic review of clinical outcomes. Neurotherapeutics 2014;11:475-484.
3. Lipsman N, Giacobbe P, Lozano AM. Deep brain stimulation for the management of treatment-refractory major depressive disorder. In: Sun B, De Salles A , eds. Neurosurgical Treatments for Psychiatric Disorders. New York: Springer; 2015:95-104.
4. Holtzheimer PE, Mayberg HS. Stuck in a rut: rethinking depression and its treatment. Trends Neurosci 2011;34:1-9.
5. Cook IA, Espinoza R, Leuchter AF. Neuromodulation for depression: invasive and noninvasive (deep brain stimulation, transcranial magnetic stimulation, trigeminal nerve stimulation). Neurosurg Clin N Am 2014;25:103-116.
6. Etié A, Oosterhof C, Bé C, et al. Astroglial control of the antidepressant-like effects of prefrontal cortex deep brain stimulation. EBioMedicine 2015;2:898-908.
7. Sun Y, Giacobbe P, Tang CW, et al. Deep brain stimulation modulates gamma oscillations and theta-gamma coupling in treatment resistant depression. Brain Stimul 2015;8:1033-1042.
8. Martín-Blanco A, Serra-Blasco M, Pérez-Egea R, et al. Immediate cerebral metabolic changes induced by discontinuation of deep brain stimulation of subcallosal cingulate gyrus in treatment-resistant depression. J Affect Disord 2015;173:159-162.
9. Altinay M, Estemalik E, Malone DA. A comprehensive review of the use of deep brain stimulation (DBS) in treatment of psychiatric and headache disorders. Headache 2015;55:345-350.
10. Serra-Blasco M, de Vita S, Rodrí MR, et al. Cognitive functioning after deep brain stimulation in subcallosal cingulate gyrus for treatment-resistant depression: an exploratory study. Psychiatry Res 2015;225:341-346.
11. Schlaepfer TE, Bewernick BH, Kayser S, et al. Deep brain stimulation of the human reward system for major depression--rationale, outcomes and outlook. Neuropsychopharmacology 2014;39:1303-1314.
12. Crowell AL, Riva-Posse P, Garlow SJ, et al. Toward an understanding of the neural circuitry of major depressive disorder through the clinical response to deep brain stimulation of different anatomical targets. Curr Behav Neurosci Rep 2014;1:55.
13. Gálvez JF, Keser Z, Mwangi B, et al. The medial forebrain bundle as a deep brain stimulation target for treatment resistant depression: a review of published data. Prog Neuropsychopharmacol Biol Psychiatry 2015;58:59-70.
14. Moreines JL, McClintock SM, Kelley ME, et al. Neuropsychological function before and after subcallosal cingulate deep brain stimulation in patients with treatment-resistant depression. Depress Anxiety 2014;31:690-698.
15. Livingston R, Anandan S, Moukaddam N. Electroconvulsive therapy, transcranial magnetic stimulation, and deep brain stimulation in treatment-resistant depression. Psychiatr Ann 2016;46:240-246.
16. Jiménez-Sánchez L, Castañé A, Pérez-Caballero L, et al. Activation of AMPA receptors mediates the antidepressant action of deep brain stimulation of the infralimbic prefrontal cortex. Cereb Cortex 2016;26:2778-2789.
17. Veerakumar A, Challis C, Gupta P, et al. Antidepressant-like effects of cortical deep brain stimulation coincide with pro-neuroplastic adaptations of serotonin systems. Biol Psychiatry 2014;76:203-212.
18. Perez-Caballero L, Perez-Egea R, Romero-Grimaldi C, et al. Early responses to deep brain stimulation in depression are modulated by anti-inflammatory drugs. Mol Psychiatry 2014;19:607-614.
19. Malone DA, Jr. Use of deep brain stimulation in treatment-resistant depression. Cleve Clin J Med 2010;77(Suppl 3):S77-S80.
20. Bewernick BH, Kayser S, Sturm V, et al. Long-term effects of nucleus accumbens deep brain stimulation in treatment-resistant depression: evidence for sustained efficacy. Neuropsychopharmacology 2012;37:1975-1985.
21. Dougherty DD, Rezai AR, Carpenter LL, et al. A randomized sham-controlled trial of deep brain stimulation of the ventral capsule/ventral striatum for chronic treatment-resistant depression. Biol Psychiatry 2015;78:240-248.
22. National Institutes of Health. Deep brain stimulation for treatment resistant depression. Accessed April 21, 2016.