TY - JOUR
T1 - No Consistent Antidepressant Effects of Deep Brain Stimulation of the Bed Nucleus of the Stria Terminalis
AU - Fitzgerald, Paul B.
AU - Hoy, Kate
AU - Richardson, Karyn E.
AU - Gainsford, Kirsten
AU - Segrave, Rebecca
AU - Herring, Sally E.
AU - Daskalakis, Zafiris J.
AU - Bittar, Richard G.
N1 - Funding Information:
The DBS devices used in this study were supplied by Medtronic Ltd. Medtronic played no role in the study design, the analysis or the preparation of this manuscript. The study was supported by an NHMRC grant (APP1077859). P.B.F. is supported by an NHMRC Investigator Grant (1193596). In the last 3 years, P.B.F. has received equipment for research from Nexstim and BrainsWay Ltd. He is a founder of TMS Clinics Australia and Resonance Therapeutics. K.E.H. is a founder of Resonance Therapeutics. In the last 10 years, Z.J.D. has received research and equipment in-kind support for an investigator-initiated study through BrainsWay Inc. and Magventure Inc. He also currently serves on the scientific advisory board for BrainsWay Inc. His work has been supported by the National Institutes of Mental Health (NIMH), the Canadian Institutes of Health Research (CIHR), Brain Canada and the Temerty Family, Grant and Kreutzkamp Family Foundations. This study was prospectively registered with the Australian New Zealand Clinical Trials Registry on 15 April 2013, registration number: ACTRN12613000412730.
Funding Information:
This study was supported by a National Health and Medical Research Council (NHMRC) Project Grant (1077859). P.B.F. is supported by an Investigator Grant from NHMRC (1193596). K.H. was supported by NHMRC Fellowships (1082894 and 1135558). Z.J.D. is supported by a Canadian Institutes of Health Research (CIHR) Clinician Scientist Award and by Constance and Stephen Lieber through a National Alliance for Research on Schizophrenia and Depression (NARSAD) Lieber Young Investigator Award.
Publisher Copyright:
© 2024 by the authors.
PY - 2024/5
Y1 - 2024/5
N2 - Background: Applying deep brain stimulation (DBS) to several brain regions has been investigated in attempts to treat highly treatment-resistant depression, with variable results. Our initial pilot data suggested that the bed nucleus of the stria terminalis (BNST) could be a promising therapeutic target. Objective: The aim of this study was to gather blinded data exploring the efficacy of applying DBS to the BNST in patients with highly refractory depression. Method: Eight patients with chronic severe treatment-resistant depression underwent DBS to the BNST. A randomised, double-blind crossover study design with fixed stimulation parameters was followed and followed by a period of open-label stimulation. Results: During the double-blind crossover phase, no consistent antidepressant effects were seen with any of the four stimulation parameters applied, and no patients achieved response or remission criteria during the blinded crossover phase or during a subsequent period of three months of blinded stimulation. Stimulation-related side effects, especially agitation, were reported by a number of patients and were reversible with adjustment of the stimulation parameters. Conclusions: The results of this study do not support the application of DBS to the BNST in patients with highly resistant depression or ongoing research utilising stimulation at this brain site. The blocked randomised study design utilising fixed stimulation parameters was poorly tolerated by the participants and does not appear suitable for assessing the efficacy of DBS at this location.
AB - Background: Applying deep brain stimulation (DBS) to several brain regions has been investigated in attempts to treat highly treatment-resistant depression, with variable results. Our initial pilot data suggested that the bed nucleus of the stria terminalis (BNST) could be a promising therapeutic target. Objective: The aim of this study was to gather blinded data exploring the efficacy of applying DBS to the BNST in patients with highly refractory depression. Method: Eight patients with chronic severe treatment-resistant depression underwent DBS to the BNST. A randomised, double-blind crossover study design with fixed stimulation parameters was followed and followed by a period of open-label stimulation. Results: During the double-blind crossover phase, no consistent antidepressant effects were seen with any of the four stimulation parameters applied, and no patients achieved response or remission criteria during the blinded crossover phase or during a subsequent period of three months of blinded stimulation. Stimulation-related side effects, especially agitation, were reported by a number of patients and were reversible with adjustment of the stimulation parameters. Conclusions: The results of this study do not support the application of DBS to the BNST in patients with highly resistant depression or ongoing research utilising stimulation at this brain site. The blocked randomised study design utilising fixed stimulation parameters was poorly tolerated by the participants and does not appear suitable for assessing the efficacy of DBS at this location.
KW - bed nucleus of the stria terminalis
KW - clinical response
KW - deep brain stimulation
KW - major depression
KW - treatment resistance
UR - http://www.scopus.com/inward/record.url?scp=85194398044&partnerID=8YFLogxK
U2 - 10.3390/brainsci14050499
DO - 10.3390/brainsci14050499
M3 - Article
C2 - 38790480
AN - SCOPUS:85194398044
SN - 2076-3425
VL - 14
JO - Brain Sciences
JF - Brain Sciences
IS - 5
M1 - 499
ER -