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Deep brain stimulation for refractory major depressive disorder: a comprehensive review

Abstract

Deep brain stimulation (DBS) has emerged as a promising treatment for select patients with refractory major depressive disorder (MDD). The clinical effectiveness of DBS for MDD has been demonstrated in meta-analyses, open-label studies, and a few controlled studies. However, randomized controlled trials have yielded mixed outcomes, highlighting challenges that must be addressed prior to widespread adoption of DBS for MDD. These challenges include tracking MDD symptoms objectively to evaluate the clinical effectiveness of DBS with sensitivity and specificity, identifying the patient population that is most likely to benefit from DBS, selecting the optimal patient-specific surgical target and stimulation parameters, and understanding the mechanisms underpinning the therapeutic benefits of DBS in the context of MDD pathophysiology. In this review, we provide an overview of the latest clinical evidence of MDD DBS effectiveness and the recent technological advancements that could transform our understanding of MDD pathophysiology, improve the clinical outcomes for MDD DBS, and establish a path forward to develop more effective neuromodulation therapies to alleviate depressive symptoms.

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Fig. 1: Symptoms of MDD.
Fig. 2: DBS targets to modulate pathophysiological networks implicated in MDD.
Fig. 3: Symptom markers, neuroimaging, and electrophysiology to advance DBS for MDD.

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Acknowledgements

We would like to acknowledge the Norman Fixel Institute for Neurological Diseases and the DBS Think Tank for providing important insights into MDD DBS discussed in this review. Parts of Fig. 1 and Fig. 3 were drawn by using pictures from Servier Medical Art, which is licensed under a Creative Commons Attribution 3.0 Unported License.

Funding

CDH received funding from the Parkinson’s Foundation and the NIH UH3 NS115631.

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Conceptualization (KAJ, MSO, KWS, HSM, CDH), Writing – original draft (KAJ), Writing – review and editing (MSO, KWS, HSM, CDH), Supervision (CDH).

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Correspondence to Coralie de Hemptinne.

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COMPETING INTERESTS

KAJ and CDH reported no conflicts of interest. KWS receives salary and equity options from Neumora Inc. and is supported by 1K23NS110962, 1UH3NS115631-01, R21 MH124759, P0546993. HSM receives consulting and IP licensing fees from Abbott Labs and is supported by NIH BRAIN UH3NS103550, R01MH102238, R01MH132789. MSO serves as Medical Advisor the Parkinson’s Foundation, and has received research grants from NIH, Parkinson’s Foundation, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. MSO’s research is supported by NIH R01 NR014852, R01NS096008, UH3NS119844, U01NS119562. MSO is PI of the NIH R25NS108939 Training Grant. MSO has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, Perseus, Robert Rose, Oxford and Cambridge (movement disorders books). MSO is an associate editor for New England Journal of Medicine Journal, Watch Neurology, and JAMA Neurology. MSO has participated in CME and educational activities (past 12–24 months) on movement disorders sponsored by WebMD/Medscape, RMEI Medical Education, American Academy of Neurology, Movement Disorders Society, Mediflix and by Vanderbilt University. The institution and not MSO receives grants from industry. MSO has participated as a site PI and/or co-I for several NIH-, foundation-, and industry-sponsored trials over the years but has not received honoraria. Research projects at the University of Florida receive device and drug donations.

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Johnson, K.A., Okun, M.S., Scangos, K.W. et al. Deep brain stimulation for refractory major depressive disorder: a comprehensive review. Mol Psychiatry 29, 1075–1087 (2024). https://doi.org/10.1038/s41380-023-02394-4

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