TY - JOUR
T1 - Deep brain stimulation of the “medial forebrain bundle”
T2 - sustained efficacy of antidepressant effect over years
AU - Fenoy, Albert J.
AU - Schulz, Paul E.
AU - Sanches, Marsal
AU - Selvaraj, Sudhakar
AU - Burrows, Christina L.
AU - Asir, Bashar
AU - Conner, Christopher R.
AU - Quevedo, Joao
AU - Soares, Jair C.
N1 - Funding Information:
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.
Funding Information:
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.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
KW - Antidepressive Agents/therapeutic use
KW - Deep Brain Stimulation/methods
KW - Depressive Disorder, Treatment-Resistant/therapy
KW - Humans
KW - Medial Forebrain Bundle/physiology
KW - Treatment Outcome
UR - http://www.scopus.com/inward/record.url?scp=85126227540&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85126227540&partnerID=8YFLogxK
U2 - 10.1038/s41380-022-01504-y
DO - 10.1038/s41380-022-01504-y
M3 - Article
C2 - 35288633
AN - SCOPUS:85126227540
SN - 1359-4184
VL - 27
SP - 2546
EP - 2553
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 5
ER -