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Discontinuation of deep brain stimulation to the medial forebrain bundle leads to depression relapse: considerations when reinstating stimulation

Molecular Psychiatry volume 28, pages 2174–2176 (2023)Cite this article

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Deep brain stimulation (DBS) of the superolateral medial forebrain bundle (MFB) for treatment-resistant depression has been seen to provide rapid and sustained antidepressant effects [1,2,3,4,5,6]. We report on four depression patient responders treated with MFB DBS experiencing either an unexpected discontinuation or decrease in applied stimulation, each part of our initial series [5, 6]. Each patient had depressive symptom relapse after discontinuation/decrease from previously applied stimulation and a different course of return to optimal anti-depressed state.

Case 1 (51 years, female, MFB DBS since 2016), pre-operative Montgomery-Asberg Depression Rating Scale (MADRS) score was 37. Two weeks after DBS onset, mood and anxiety were improved and by 12 weeks, she was classified as a responder with >50% reduction of MADRS scores; 1-year MADRS 11. She returned to clinic approximately 3 years after implantation with a few weeks of worsening anxiety much worse than mood. Upon interrogation, her implantable pulse generator (IPG) had expired approximately 2–3 weeks before, correlating to the time course of her clinical change. IPG replacement occurred the next day; parameters before depletion: (constant voltage) bilateral 4.0 V, 80 µs, 130 Hz. Stimulation was reinstated at 3 V bilaterally, cautiously to prevent diplopia (expected possible side effect at target, see below). One week later, she felt poor (MADRS 30); she also admitted that initially after replacement she experienced vertical diplopia which resolved over 12 h. We reprogrammed her back to 4.0 V but she immediately complained of painful diplopia, which was not present when she was at this setting previously. Slowly, this subsided with decreased stimulation; at 3.6 V bilaterally there was no diplopia. Over the next weeks, stimulation was increased by 0.1 V increments back to 4.0 V with no diplopia; MADRS 9.

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Fig. 1: Depiction of modulated fiber tracts seeded at cathodal contacts at specified parameters in an example patient.

References

  1. Schlaepfer TE, Bewernick BH, Kayser S, Mädler B, Coenen VA. Rapid effects of deep brain stimulation for treatment-resistant major depression. Biol Psychiatry. 2013;73:1204–12.

    Article  PubMed  Google Scholar 

  2. Bewernick BH, Kayser S, Gippert SM, Switala C, Coenen VA, Schlaepfer TE. Deep brain stimulation to the medial forebrain bundle for depression-long-term outcomes and a novel data analysis strategy. Brain Stimul. 2017;10:664–71.

    Article  PubMed  Google Scholar 

  3. Coenen VA, Bewernick BH, Kayser S, Kilian H, Boström J, Greschus S, et al. Superolateral medial forebrain bundle deep brain stimulation in major depression: a gateway trial. Neuropsychopharmacology. 2019;26:587.

    Google Scholar 

  4. Fenoy AJ, Schulz PE, Selvaraj S, Burrows CL, Zunta-Soares G, Durkin K, et al. A longitudinal study on deep brain stimulation of the medial forebrain bundle for treatment-resistant depression. Transl Psychiatry. 2018;8:111.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Fenoy AJ, Schulz PE, Sanches M, Selvaraj S, Burrows CL, Asir B, et al. Deep brain stimulation of the “medial forebrain bundle”: sustained efficacy of antidepressant effect over years. Mol Psychiatry 2022;27:2546–53. https://doi.org/10.1038/s41380-022-01504-y.

  6. Fenoy AJ, Quevedo J, Soares JC. Deep brain stimulation of the ‘medial forebrain bundle’: a strategy to modulate the reward system and manage treatment-resistant depression. Mol Psychiatry 2022;27:574–92. https://doi.org/10.1038/s41380-021-01100-6.

  7. Bergfeld IO, Mantione M, Hoogendoorn ML, Ruhé HG, Notten P, van Laarhoven J, et al. Deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2016;73:456–64.

    Article  PubMed  Google Scholar 

  8. Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, et al. Deep brain stimulation for treatment-resistant depression. Neuron. 2005;45:651–60.

    Article  CAS  PubMed  Google Scholar 

  9. Holtzheimer PE, Husain MM, Lisanby SH, Taylor SF, Whitworth LA, McClintock S, et al. Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial. Lancet Psychiatry. 2017;4:839–49.

    Article  PubMed  Google Scholar 

  10. Kilian HM, Meyer DM, Bewernick BH, Spanier S, Coenen VA, Schlaepfer TE. Discontinuation of superolateral medial forebrain bundle deep brain stimulation for treatment-resistant depression leads to critical relapse. Biol Psychiatry. 2019;85:e23–e24.

    Article  PubMed  Google Scholar 

  11. Evers J, Lowery M. The active electrode in the living brain: the response of the brain parenchyma to chronically implanted deep brain stimulation electrodes. Oper Neurosurg (Hagerstown). 2021;20:131–40. https://doi.org/10.1093/ons/opaa326.

  12. Vedam-Mai V, Rodgers C, Gureck A, Vincent M, Ippolito G, Elkouzi A, et al. Deep brain stimulation associated gliosis: a post-mortem study. Parkinsonism Relat Disord. 2018;54:51–5.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Fasano A, Helmich RC. Tremor habituation to deep brain stimulation: Underlying mechanisms and solutions. Mov Disord. 2019;34:1761–73.

    Article  PubMed  Google Scholar 

  14. Vora AK, Ward H, Foote KD, Goodman WK, Okun MS. Rebound symptoms following battery depletion in the NIH OCD DBS cohort: clinical and reimbursement issues. Brain Stimul. 2012;5:599–604.

    Article  CAS  PubMed  Google Scholar 

  15. Schaltenbrand G, Wahren W. Atlas for stereotaxy of the human brain. 2nd ed. New York: Thieme; 1977.

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Authors and Affiliations

  1. Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA

    Albert J. Fenoy

  2. Departments of Neurosurgery and Psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA

    Albert J. Fenoy

  3. Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, TX, USA

    Albert J. Fenoy

  4. Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UT Health), Houston, TX, USA

    Albert J. Fenoy, Joao Quevedo & Jair C. Soares

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Contributions

AJF was responsible for the preparation and editing of all drafts and the figure of this manuscript. JQ and JCS contributed to the editing of the final manuscript draft.

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Correspondence to Albert J. Fenoy.

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Competing interests

AJF serves as a consultant for Medtronic, Inc and receives grant support from the NIH/NINDS (1R01NS113893). JQ receives research support from the NIH/NIMH (1R21MH117636), the Faillace Department of Psychiatry and Behavioral Sciences, and LivaNova; has speaker bureau membership with Myriad Neuroscience, Janssen Pharmaceuticals, and Abbvie; is a consultant for Eurofarma; is stockholder at Instituto de Neurociencias Dr Joao Quevedo; and receives copyrights from Artmed Editora, Artmed Panamericana, and Elsevier/Academic Press. JCS receives grant/research support from Bristol-Meyers Squibb, Forest Laboratories, Merck and Elan Pharmaceuticals, and serves as a consultant for Pfizer, Abbot, and Astellas Pharma, Inc.

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Fenoy, A.J., Quevedo, J. & Soares, J.C. Discontinuation of deep brain stimulation to the medial forebrain bundle leads to depression relapse: considerations when reinstating stimulation. Mol Psychiatry 28, 2174–2176 (2023). https://doi.org/10.1038/s41380-023-01947-x

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