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Deep brain stimulation of the “medial forebrain bundle”: sustained efficacy of antidepressant effect over years

Molecular Psychiatry volume 27, pages 2546–2553 (2022)Cite this article

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Abstract

Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB) has emerged as a quite efficacious therapy for treatment resistant depression (TRD), leading to rapid antidepressant effects. In this study, we complete our assessment of our first 10 enrolled patients throughout one year post-implantation, showing sustained antidepressant effect up to 5 years. The primary outcome measure was a 50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score, which was interpreted as a response. Deterministic fiber tracking was used to individually map the target area. An insertional effect was seen during the 4-week sham stimulation phase (29% mean MADRS reduction, p = 0.02). However, after 2 weeks of initiating stimulation, five patients met response criteria (47% mean MADRS reduction, p < 0.001). One patient withdrew from study participation at 6 weeks. Twelve weeks after initiating stimulation, six of nine remaining patients had a >50% decrease in MADRS scores relative to baseline (52% mean MADRS reduction, p = 0.001); these same six patients continued to meet response criteria at 52 weeks (63% overall mean MADRS reduction, p < 0.001). Four of five patients who achieved the 5-year time point analysis continued to be responders (81% mean MADRS reduction, p < 0.001). Evaluation of modulated fiber tracts reveals significant common prefrontal/orbitofrontal connectivity to the target region in all responders. Key points learned from this study that we can incorporate in future protocols to better elucidate the effect of this therapy are a longer blinded sham stimulation phase and use of scheduled discontinuation concomitant with functional imaging.

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Fig. 1: MADRS scores recorded over 52 weeks, expressed as % change (Δ) from baseline. Initiation = bilateral DBS ON at t = 4w OFF (End Sham).
Fig. 2: Representation of active cathodal contacts in two planes for each of the ten patients presented in this series, superimposed upon the deterministic tractographic-defined target medial forebrain bundle (red/orange).
Fig. 3: MADRS scores recorded over 5 years, reported for 1, 2, and 5 years.
Fig. 4: Structural connectivity of the supero-lateral medial forebrain bundle.

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Acknowledgements

The Center of Excellence on Mood Disorders is funded by the Pat Rutherford Jr. Chair in Psychiatry, John S. Dunn Foundation, and Anne and Don Fizer Foundation Endowment for Depression Research.

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Authors and Affiliations

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

    Albert J. Fenoy & Christopher R. Conner

  2. 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, Marsal Sanches, Sudhakar Selvaraj, Bashar Asir, Joao Quevedo & Jair C. Soares

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

    Paul E. Schulz & Christina L. Burrows

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Contributions

AJF was responsible for preparation and editing of all drafts and figures of this manuscript; PES, MS, SS, CLB, BA, JQ, JCS contributed to editing of final manuscript draft; CRC contributed to final figure production.

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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 (1R01NS113893-01A1). PES is a consultant for Lilly, Acadia, and Biogen, has grant support from the Weston Brain Foundation, the Frontotemporal Disease association, and the Kleberg Foundation, and has NIH support on unrelated projects. SS has received grants/research support from NIH/NIMH (1R21MH119441-01A1) and SAMHSA (6H79FG000470-01M003); research support from Compass Pathways, LivaNova, Janssen; speaking honoraria from the British Medical Journal Publishing Group and copyright with Cambridge University Press. JQ receives research support from the NIH/NIMH (1R21MH117636-01A1), the Faillace Department of Psychiatry and Behavioral Sciences, and LivaNova; has speaker bureau membership with Myriad Neuroscience, Janssen Pharmaceuticals, and Abbvie; is 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. MS, CRC, and CLB reported no biomedical financial interests or potential conflicts of interest.

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Fenoy, A.J., Schulz, P.E., Sanches, M. et al. Deep brain stimulation of the “medial forebrain bundle”: sustained efficacy of antidepressant effect over years. Mol Psychiatry 27, 2546–2553 (2022). https://doi.org/10.1038/s41380-022-01504-y

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