Deep brain stimulation of the medial forebrain bundle: Distinctive responses in resistant depression
Abstract
Background Treatment resistant depression (TRD) is a serious, disabling disease. Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB), as proposed by Schlaepfer et al. (2013), has led to rapid anti-depressant response but has not been replicated.Methods In this interim analysis of an ongoing pilot study of ten subjects, we assessed the efficacy of MFB-DBS in a cohort of four TRD patients over a 52-week period using the Montgomery-Åsberg Depression Rating Scale (MADRS) as the primary assessment tool. Implanted patients entered a 4-week single-blinded sham stimulation period prior to stimulation initiation. Deterministic fiber tracking analysis was performed to compare modulated fiber tracts between patients.Results Intraoperatively, responder patients displayed immediate increased signs of energy and motivation upon stimulation at target. There was no significant mean change in mood during sham stimulation phase. Three of 4 patients had >50% decrease in MADRS scores at 7 days post-stimulation initiation relative to baseline. One patient withdrew from study participation. At 26 weeks, two of 3 remaining patients continue to have >80% decrease in MADRS scores. One patient failed to have response; evaluation of modulated fiber tracts revealed reduced frontal connectivity to the target region.Limitations This is an interim report, with limited conclusions.Conclusion This study of MFB-DBS shows similar rapid anti-depressant effects within the first week of stimulation as initially reported by Schlaepfer et al. (2013). Implementation of anhedonia measurements would greatly augment characterization of the striking motivational effects observed. We urge others to pursue this target to further prove efficacy. ClinicalTrials.gov (identifier: NCT02046330) https://clinicaltrials.gov/ct2/show/NCT02046330.
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In the open-label phase of the Fenoy et al. study, at 1 year the response rate was 66% and the remission rate was 50%.
“at 1 year (RS: 66%, RM: 50%)”
From Deep brain stimulation for depression. (2022) · cites this paper as [70]
In the Fenoy et al. single-blind phase, no significant difference was found between blinded on and off conditions.
“Results do not indicate any significant difference between blinded on/off conditions”
From Deep brain stimulation for depression. (2022) · cites this paper as [70]
In the open-label phase of the Fenoy et al. study, the response rate at 1 week of MFB DBS was 50%.
“promising response and remission rates were observed at 1 week of MFB DBS (RS: 50%)”
From Deep brain stimulation for depression. (2022) · cites this paper as [70]
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Deep Brain Stimulation for Depression
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Alternatives to Pharmacological and Psychotherapeutic Treatments in Psychiatric Disorders
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- Authors
- Fenoy, A. J., Schulz, P., Selvaraj, S., Burrows, C., Spiker, D., Cao, B., Zunta-Soares, G., Gajwani, P., Quevedo, J., & Soares, J.
- Affiliations
- The University of Texas Health Science Center at Houston (US)
- Corresponding author
- Fenoy, Albert J.
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 203
- Pages
- 143-151
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W2409297594
- Cited by
- 125
- References
- 44
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 13 · 2023: 13 · 2022: 17 · 2021: 22 · 2020: 11 · 2019: 9 · 2018: 19 · 2017: 12
- FWCI
- 10.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Meyers Squibb
- Forest Laboratories
- Merck
- Elan Pharmaceuticals
- Dunn Foundation
- Topics
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- deep brain stimulation, medial forebrain bundle, treatment-resistant depression, deterministic fiber tracking, anhedonia, motivation, sham stimulation
- MeSH terms
- Adult, Affect, Female, Humans, Male, Medial Forebrain Bundle, Middle Aged, Motivation, Pilot Projects, Treatment Outcome, Deep Brain Stimulation, Diffusion Tensor Imaging, Neuroimaging, Depressive Disorder, Treatment-Resistant
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