No Consistent Antidepressant Effects of Deep Brain Stimulation of the Bed Nucleus of the Stria Terminalis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Operative Procedures
2.3. Intra-Operative Stimulation
2.4. Post-Operative Stimulation Procedure
- Initial blinded stimulation: This entailed a twenty-week period where the patients were allocated to receive a randomised sequence of five stimulation conditions (listed below) for four weeks at a time. The randomisation was conducted according to a computer-generated random number sequence. The stimulation was programmed by one researcher who was aware of the stimulation type, but the patient and assessor of depressive symptoms were both blind to the treatment condition. The five conditions were:
- Sham stimulation (all electrodes inactive);
- Low-intensity “proximal” electrode DBS: This involved stimulation of the two most proximal electrodes on each side at 2 V;
- Low-intensity “distal” electrode DBS: This involved stimulation of the two distal electrodes on each side at 2 V;
- Moderate-intensity proximal electrode DBS: This involved stimulation of the two proximal electrodes on each side at 4 V;
- Moderate-intensity distal electrode DBS: This involved stimulation of the two distal electrodes on each side at 4 V;
- Blind follow-up phase: During this time, stimulation was recommenced using the stimulation parameters that achieved the maximum reduction in depressive symptoms in phase 1 (active or sham), and these parameters continued for three months. If no substantial anti-depressant response was achieved during phase 1, the patients proceeded to phase 3.
- Open programming phase: During this phase, stimulation was adjusted on an individualised basis to achieve the optimal clinical response for each patient.
2.5. Assessments
2.6. Analysis
3. Results
3.1. Participants
3.2. Clinical Outcome
3.2.1. Phase 1: Blinded Crossover
3.2.2. Phase 2: Blinded Follow-Up
Patient | Age | Sex | Years of Education | Family History of Mood Disorder | Age of Illness Onset | Prior Suicide Attempt/s | Duration of Current Episode (yrs) | Number of Prior Episodes | Number of Antidepressants Trialled | Number of Other Medications (Mood Stabilisers, Antipsychotics, Stimulants) | ECT | rTMS |
---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 53 | F | 12 | N | 45 | 0 | 6 | 1 | 14 | 13 | >150 across multiple courses | 2 courses |
2 | 31 | F | 13 | Y | 24 | 4 | 7 | 0 | 9 | 8 | 8 courses | 1 course |
3 | 45 | F | 17 | Y | 32 | 0 | 14 | 0 | 13 | 13 | 2 courses | 1 course |
4 | 45 | F | 16 | Y | 22 | 1 | 11 | 2 | 9 | 10 | Multiple acute and extended maintenance | 0 |
5 | 26 | F | 15 | Y | 10 | 2 | 15 | 0 | 13 | 7 | >85 across multiple courses | 1 course |
6 | 56 | F | 16 | Y | 48 | 0 | 8 | 0 | 10 | 10 | 5 courses | 1 course |
7 | 66 | F | 11 | N | 24 | 0 | 20 | 1 | 14 | 9 | 32 in one extended course of uni and bilateral | Multiple courses |
8 | 73 | M | 11 | Y | 3 | multiple | 15 | 2 | 17 | 17 | 3 courses | Multiple courses |
Patient | Sham | Proximal 2 mV | Proximal 4 mV | Distal 2 mV | Distal 4 mV |
---|---|---|---|---|---|
1 | completed | completed | stopped | completed | stopped |
2 | completed | completed | completed | stopped | not attempted |
3 | completed | completed | completed | completed | completed |
4 | completed | completed | completed | completed | completed |
5 | completed | completed | withdrew | completed | stopped |
6 | completed | Stopped | not attempted | completed | completed |
7 | completed | completed | completed | completed | completed |
8 | Withdrew | completed | completed | completed | stopped |
3.2.3. Phase 3: Open-Label Treatment
MADRS | HAMD | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Patient | Pre-Op | Post-Op | Sham | Proximal | Distal | 3 Months | Pre-Op | Post-Op | Sham | Proximal | Distal | 3 Months | ||||
2 mV | 4 mV | 2 mV | 4 mV | 2 mV | 4 mV | 2 mV | 4 mV | |||||||||
1 | 43 | 44 | 50 | 51 | 55 | 27 | 24 | 32 | 37 | 34 | ||||||
2 | 50 | 51 | 52 | 27 | 53 | 29 | 33 | 34 | 35 | 24 | 34 | 25 | ||||
3 | 45 | 47 | 46 | 45 | 50 | 46 | 48 | 29 | 29 | 28 | 25 | 29 | 28 | 27 | ||
4 | 31 | 38 | 44 | 44 | 25 | 37 | 34 | 27 | 25 | 30 | 27 | 26 | 19 | 25 | 26 | 22 |
5 | 43 | 45 | 38 | 41 | 44 | 38 | 29 | 26 | 29 | 25 | 26 | 29 | ||||
6 | 28 | 27 | 42 | 27 | 25 | 28 | 24 | 21 | 33 | 19 | 19 | 20 | ||||
7 | 34 | 42 | 41 | 40 | 40 | 31 | 37 | 38 | 23 | 27 | 28 | 28 | 24 | 22 | 23 | 26 |
8 | 40 | 34 | 42 | 42 | 48 | 27 | 21 | 30 | 30 | 30 | 15 | |||||
Mean | 39.3 | 41.0 | 44.7 | 41.4 | 42.0 | 41.1 | 36.0 | 32.0 | 27.1 | 26.5 | 30.3 | 27.9 | 27.2 | 26.3 | 23.8 | 24.4 |
SD | 7.1 | 7.2 | 4.6 | 6.8 | 9.8 | 9.2 | 8.2 | 4.9 | 3.0 | 4.2 | 2.8 | 4.2 | 5.2 | 4.6 | 3.1 | 3.1 |
3.3. Safety and Side Effects
3.4. Cognitive Outcome
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Baseline | Post Op | Follow Up | |||||||
---|---|---|---|---|---|---|---|---|---|
n | Mean | SD | n | Mean | SD | n | Mean | SD | |
Logical memory story total immediate recall | 8 | 14.4 | 7.4 | 8 | 18.4 | 12.2 | 5 | 23.0 | 10.3 |
Logical memory story total delay recall | 8 | 12.3 | 9.3 | 8 | 12.4 | 12.5 | 5 | 22.0 | 12.8 |
Logical memory story total recognition | 8 | 23.1 | 5.4 | 8 | 146.8 | 344.4 | 5 | 25.8 | 4.7 |
COWAT score letters | 8 | 33.0 | 17.7 | 8 | 30.5 | 20.0 | 6 | 39.5 | 14.0 |
COWAT score animals | 8 | 15.8 | 8.9 | 8 | 15.0 | 8.1 | 6 | 15.7 | 7.8 |
RAVLT score trial A1 | 8 | 5.3 | 3.4 | 8 | 4.6 | 2.8 | 5 | 6.4 | 2.2 |
RAVLT score trial A2 | 8 | 8.1 | 3.5 | 8 | 7.4 | 4.6 | 5 | 8.8 | 2.9 |
RAVLT score trial A3 | 8 | 9.6 | 3.9 | 8 | 133.4 | 349.8 | 5 | 10.6 | 2.3 |
RAVLT score trial A4 | 8 | 9.1 | 3.9 | 8 | 133.8 | 349.6 | 5 | 11.2 | 4.0 |
RAVLT score trial A5 | 8 | 10.3 | 4.3 | 8 | 133.8 | 349.6 | 5 | 12.0 | 3.2 |
RAVLT score trial B | 8 | 4.5 | 2.4 | 8 | 128.8 | 351.6 | 5 | 5.2 | 2.2 |
RAVLT score trial A6 | 8 | 8.0 | 5.2 | 8 | 132.3 | 350.3 | 5 | 9.8 | 5.1 |
RAVLT score item 7 baseline | 8 | 7.3 | 5.8 | 7 | 8.1 | 6.2 | 5 | 9.8 | 4.9 |
RAVLT recognition score | 8 | 12.1 | 4.1 | 7 | 13.4 | 3.9 | 5 | 12.8 | 3.5 |
BVMT score trial 1 | 8 | 4.6 | 3.0 | 8 | 4.8 | 4.1 | 6 | 5.2 | 3.9 |
BVMT score trial 2 | 8 | 6.6 | 3.1 | 8 | 7.1 | 2.9 | 6 | 7.5 | 3.7 |
BVMT score trial 3 | 8 | 7.4 | 3.2 | 8 | 8.5 | 3.1 | 6 | 8.7 | 3.4 |
BVMT score delay | 8 | 6.8 | 3.8 | 8 | 8.1 | 4.1 | 6 | 9.0 | 3.5 |
BVMT score recognition | 8 | 11.0 | 0.9 | 8 | 11.3 | 1.0 | 6 | 11.2 | 1.0 |
Stroop word score | 8 | 75.5 | 29.2 | 6 | 74.5 | 15.9 | 5 | 77.2 | 22.8 |
Stroop colour score | 8 | 51.8 | 17.4 | 6 | 56.8 | 12.6 | 5 | 60.8 | 13.0 |
Stroop word-colour score | 8 | 23.5 | 12.6 | 6 | 32.2 | 14.4 | 5 | 37.6 | 8.7 |
Stroop interference | 4 | −5.2 | 5.4 | 3 | −5.5 | 8.5 | 0 | ||
Trail-making A time | 8 | 41.9 | 22.5 | 8 | 44.0 | 33.2 | 6 | 43.3 | 30.7 |
Trail-making B time | 6 | 111.0 | 39.6 | 6 | 91.3 | 41.5 | 6 | 111.8 | 60.0 |
Digit span forward score | 8 | 7.8 | 3.3 | 8 | 8.4 | 4.0 | 5 | 8.2 | 3.2 |
Digit span forward longest number score | 8 | 5.3 | 1.6 | 8 | 5.1 | 1.8 | 5 | 5.6 | 1.8 |
Digit span back score | 8 | 7.4 | 2.4 | 8 | 6.9 | 3.3 | 5 | 7.2 | 3.4 |
Digit span back longest number score | 8 | 4.0 | 1.2 | 8 | 3.8 | 1.6 | 5 | 4.0 | 1.9 |
Digit span sequence score | 8 | 7.0 | 1.8 | 8 | 6.3 | 2.4 | 5 | 7.4 | 2.8 |
Digit span sequence longest number score | 8 | 7.9 | 7.2 | 8 | 4.5 | 1.3 | 5 | 5.2 | 1.1 |
Digit span total | 8 | 21.8 | 7.2 | 8 | 20.6 | 9.8 | 5 | 22.8 | 8.6 |
RCFT copy score | 8 | 32.3 | 5.6 | 6 | 30.8 | 6.2 | 5 | 32.4 | 5.0 |
RCFT delay recall score | 8 | 12.3 | 8.5 | 6 | 178.9 | 401.9 | 5 | 16.5 | 10.0 |
Verbal paired associates—immediate | 6 | 34.7 | 14.2 | 5 | 229.2 | 430.6 | 5 | 41.4 | 15.1 |
Verbal paired associates—delay | 6 | 9.2 | 4.2 | 5 | 207.6 | 442.4 | 5 | 11.0 | 3.7 |
Verbal paired associates—recognition | 6 | 32.8 | 9.7 | 5 | 229.8 | 430.0 | 5 | 37.6 | 2.9 |
Coding at baseline | 8 | 50.0 | 13.4 | 6 | 49.5 | 17.3 | 4 | 53.8 | 19.7 |
Tower of London—total correct | 5 | 7.0 | 3.4 | 6 | 170.5 | 405.9 | 4 | 6.0 | 3.2 |
Tower of London—total move score | 7 | 38.1 | 18.5 | 6 | 204.3 | 389.6 | 4 | 41.3 | 14.9 |
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Fitzgerald, P.B.; Hoy, K.; Richardson, K.E.; Gainsford, K.; Segrave, R.; Herring, S.E.; Daskalakis, Z.J.; Bittar, R.G. No Consistent Antidepressant Effects of Deep Brain Stimulation of the Bed Nucleus of the Stria Terminalis. Brain Sci. 2024, 14, 499. https://doi.org/10.3390/brainsci14050499
Fitzgerald PB, Hoy K, Richardson KE, Gainsford K, Segrave R, Herring SE, Daskalakis ZJ, Bittar RG. No Consistent Antidepressant Effects of Deep Brain Stimulation of the Bed Nucleus of the Stria Terminalis. Brain Sciences. 2024; 14(5):499. https://doi.org/10.3390/brainsci14050499
Chicago/Turabian StyleFitzgerald, Paul B., Kate Hoy, Karyn E. Richardson, Kirsten Gainsford, Rebecca Segrave, Sally E. Herring, Zafiris J. Daskalakis, and Richard G. Bittar. 2024. "No Consistent Antidepressant Effects of Deep Brain Stimulation of the Bed Nucleus of the Stria Terminalis" Brain Sciences 14, no. 5: 499. https://doi.org/10.3390/brainsci14050499