No Consistent Antidepressant Effects of Deep Brain Stimulation of the Bed Nucleus of the Stria Terminalis

Author:

Fitzgerald Paul B.1ORCID,Hoy Kate2,Richardson Karyn E.3,Gainsford Kirsten1,Segrave Rebecca34,Herring Sally E.2ORCID,Daskalakis Zafiris J.5,Bittar Richard G.67

Affiliation:

1. School of Medicine and Psychology, Australian National University, Canberra, ACT 2601, Australia

2. Bionics Institute of Australia, East Melbourne, Melbourne, VIC 3002, Australia

3. BrainPark, Turner Institute for Brain and Mental Health, Monash University, Clayton, VIC 3168, Australia

4. Monash Biomedical Imaging, Monash University, Clayton, VIC 3168, Australia

5. Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA

6. Precision Brain Spine and Pain Centre, Melbourne, VIC 3109, Australia

7. Faculty of Health, Deakin University, Melbourne, VIC 3000, Australia

Abstract

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.

Funder

National Health and Medical Research Council

Investigator Grant from NHMRC

NHMRC Fellowships

Canadian Institutes of Health Research (CIHR) Clinician Scientist Award

National Alliance for Research on Schizophrenia and Depression (NARSAD) Lieber Young Investigator Award

Publisher

MDPI AG

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