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Deep Brain Stimulation in Obsessive Compulsive Disorder

Table Summarizing Clinical Research Studies

Studies used in this table were either double-blinded crossover trials and/or prospective trials with at least 10 participants; no retrospective case series or reviews are included.

First Author (Year) Study Title Country
Funder(s)
Intervention Tested Study Size Inclusion Criteria,
Patient Demographics
Trial Type Findings

Investigational Brain Stimulation Target: Junction of Ventral Capsule and Ventral Striatum (VC/VS)

Greenberg
(2010)
Deep brain
stimulation
of the
ventral internal
capsule/ventral
striatum
for obsessive-
compulsive
disorder:
worldwide
experience
United States
Belgium
---
• Brain & Behavior Research Foundation
• National Institute of Mental Health
• Medtronic Inc.
Condition after Bilateral VC/VS Stimulation
vs
Condition before Implantation
26 • Adults (ages 22 - 59)
• Severe OCD for at least 5 years
• Failure of
at least 3
months of traditional pharmacological and behavioral therapy

• No previous
or current psychotic, personality, or neurologic disorders

• Not pregnant

Co-Morbid Conditions:
Major Depressive Disorder (22/26)

Prospective Cohort Study

Performed
with FDA Investigational Device Exemption Approvals

Length:
31.4 ± 4.1 months
(17 with
>24
months)

• Significant improvement over first 3 months of stimulation with continued effect seen at 36 months (average of 38.5% improvement
• Over time, there is an increase in the percentage of patients receiving benefit (61.5% with at least a 35% improvement of their OCD score at 36 months)
• Improvement in concurrent depression (average of 43.2% improvement)
• Improvement in concurrent anxiety (average of 52.6% improvement)
• Improvement in overall daily function (average of 69.5% improvement)

Major Adverse Events:
• Intracranial hemorrhage (2/26)
• Worsening of depression (3/26

Investigational Brain Stimulation Target: Nucleus Accumbens (NAcc)

Huff
(2010)
Unilateral
deep brain
stimulation
of the nucleus
accumbens
in patients
with treatment-
resistant
obsessive-
compulsive
disorder:
Outcomes
after one year
Germany
---
• Cologne Fortune Program Grant
• Medtronic Inc.
Condition with Right-sided NAcc Stimulation
vs
Condition without Stimulation
vs
Condition before Implantation
10 • Adults
(ages 21 - 65)

• Severe OCD for at least 5 years
• Failure of 4 pharmaceutical and behavioral therapy treatment regimens, each lasting at least 10 weeks
• No previous
or current psychotic, personality, or neurologic disorders

• No substance abuse
• Not pregnant

Co-Morbid Conditions:
Major Depressive Disorder (6/10)
Double
Blinded

Crossover Study
followed
by a

Prospective Cohort
Study


Approved
by the Institutional Ethics Committee
and in accordance with the Helsinki Declaration

Length:
15 months
(6 months blinded)

• Significant improvement seen at 12 months (average of 21.4%)
• Slightly greater improvement with active stimulation (average OCD score 10.3% better)
• 50% patients had at least a 25% improvement in their OCD score
• Improvement in concurrent depression (average of 30.0% improvement)
• Improvement in overall daily function (average of 45.1% improvement)
• No significant improvement in
anxiety or cognitive function

Major Adverse Events:
• Dysesthesia (1/10)
Denys
(2010)
Deep brain
stimulation
of the nucleus
accumbens for
treatment-
refractory
obsessive-
compulsive
disorder
The Netherlands
---
• Netherlands Organization for
Scientific Research
• Medtronic Inc.
Condition with Bilateral NAcc Stimulation
vs
Condition without Stimulation
vs
Condition before Implantation
16 • Adults (ages 18 - 65)
• Disabling
OCD for
at least
5 years

• Failure of 4 pharmaceutical and behavioral therapy treatment regimens, each lasting at least 12 weeks
• No previous
or current psychotic, personality,
or neurologic disorders

• No substance abuse

Co-Morbid Conditions:
Major Depressive Disorder (6/16)
Prospective Cohort Study
with a
Double
Blinded

Crossover Segment

Registered
in the International Control Trial Registry and approved by the Institutional Medical
Ethics Review Committee

Length:
21 months
(1 month blinded
)
• Significant improvement seen at 8 months (average of 46% improvement)
• Persistent improvement seen at 21 months (average of 52% improvement)
• Greater improvement with active stimulation (average OCD score 25% better)
• 56.3% of patients had at least a 35% improvement in their OCD score
• Improvement in concurrent depression (average of 45.1% improvement)
• Improvement in concurrent anxiety (average of 42.6% improvement)

Major Adverse Events:
• Increased libido (7/16)
• Mild forgetfulness (5/16)
• Word-finding problems (3/16)

Investigational Brain Stimulation Target: Subthalamic Nucleus (STN)

Mallet (2019) Long-term effects of subthalamic stimulation in obsessive-compulsive disorder: Follow-up of a randomized controlled trial France
---
• Programme Hospitalier de la Recherche Clinique Assistance Publique–Hôpitaux de Paris
• Agence Nationale de la Recherche Program for Young Researchers
Condition at Condition at Inclusion in Bilateral STN Stimulation Randomized Controlled Trial vs. Condition after 46 months of Bilateral STN Stimulation
14
(12 at final assessment)
• Adults (ages 18-60)
• Severe OCD for at least 5 years
• Failure of 4 pharmaceutical and behavioral therapy treatment regimens
• No previous or current psychotic, personality, or neurologic disorders
• No substance abuse

Co-Morbid Conditions:
• Major Depressive Disorder (4/12)
Prospective Follow-up to Randomized Controlled Trial

Approved by the Institutional Ethics Committee
and in accordance with the Helsinki Declaration

Study Length:
46 months
• Significant improvement at 46 months (45% median decrease in Y-BOCS scores) in responders at final assessment (11/12)
• Significant and progressive improvement with time, concomitant with increased DBS voltage (scores at 46 mos. vs. 16 mos.)
• Significant improvement in global functioning and social/family life
• Significant positive relationship between symptoms at 46 months and age of onset

Major Adverse Events
• Hypomania and impulsivity (4/12)
• Suicide attempt (3/12)
Mallet
(2008)
Subthalamic
nucleus
stimulation in severe
obsessive-compulsive
disorder
France
---
• Programme Hospitalier de la Recherche Clinique Assistance Publique–Hôpitaux de Paris
• Agence Nationale de la Recherche Program for Young Researchers
Condition after Bilateral STN Stimulation
vs
Condition before Implantation
17 • Adults (ages 18-60)
• Severe OCD for at least 5 years
• Failure of 4 pharmaceutical and behavioral therapy treatment regimens
• No previous
or current psychotic, personality,
or neurologic disorders

• No substance abuse

Co-Morbid Conditions:
Major Depressive Disorder (6/17)
Double
Blinded

Crossover Study

Approved by the Institutional Ethics Committee
and in accordance with the Helsinki Declaration

Length:
10 months
(6 months blinded)

• Significant improvement seen with 3 months of stimulation (average of 36.7%)
• Greater improvement with active stimulation
(average OCD score 32.1% better)
• Improvement in overall daily function (average of 33.3% improvement)
• Greater improvement in function with active stimulation
(average score 30.2% better)
• No significant change in concurrent anxiety

Major Adverse Events:
Intracranial hemorrhage (1/17)
• Infection resulting in device removal (2/17)
Investigational Brain Stimulation Target: Bed Nucleus of the Stria Terminalis / Anterior Limbs of the Internal Capsule (BST/ALIC)
Luyten
(2016)
Electrical stimulation in the bed nucleus of the stria terminalis alleviates severe obsessive-compulsive disorder Belgium
--
Research Foundation- Flanders (FWO)
Agency for Innovation by Science and Technology
Medtronic Inc.

Condition with BST/ALIC Stimulation at Last Follow-up (> 4 Years)
vs.
at 4 Years Post-Implantation vs. Condition Before Implantation

24 Adults (ages 18-60)
Severe OCD of at least 5 years
Failure of at least 3 pharmaceutical and behavioral therapy treatment regimens
• OCD (Y-BOCS) score at least 30/40; Global Assessment of Functioning score 45 or less
No previous or current psychotic, personality, or neurologic disorders
No substance abuse
Co-Morbid Conditions:
Major Depressive Disorder
Anxiety Disorder

Double-blind, randomized crossover design with 4 year unblinded follow-up

Approved by the Ethics Committees of the University Hospitals of Leuven and Antwerp

Length: up to 16 years (24 with >14 years)
(6 months blinded)

Significant improvement in OCD symptoms during blinded “on” phase of stimulation compared to before implantation (average of 42%); improvement in concurrent anxiety (average of 71%); depression (average of 54%), and global functions (30 points)
After 4 years, significant improvement in OCD symptoms (66%), concurrent anxiety (58%) and depression (67%), and global functioning (30 points)
Significant improvement at last follow-up (up to 14 years) in OCD symptoms (45%); concurrent anxiety (45%); concurrent depression (49%); and global functioning (30 points)
First clinical evidence for BST involvement with OCD; observations suggest BST may be better stimulation target compared to ALIC to reduce obsessions and compulsions
Chronic stimulation in BST/ALIC induced metabolic decreases in anterior cingulate, prefrontal, and orbitofrontal cortices
No stimulation-induced cognitive and memory impairment

Major Adverse Events
Intracerebral hemorrhage (2/24)
Suicide attempts (4/24)
Seizures (tonic-clonic 2/24; absence/partial 3/24)


Updated in 2020 by Alicia Brown, first year medical student at Augusta University / University of Georgia Medical Partnership, under the supervision of International Neuromodulation Society (INS) member Marshall Bedder, MD, FRCPC, DABAPM, DABAM, FASAM, Clinical Associate Professor of Psychiatry & Health Behavior, Medical College of Georgia, Augusta University and INS Public Education and Website Manager Nancy Garcia. (Originally compiled during 2012-2013 by International Neuromodulation Society member Chengyuan Wu, MD, MSBmE, Thomas Jefferson University Hospital, Department of Neurosurgery and second-year medical student Lekhaj Daggubati, Drexel University School of Medicine.)

Additional references:

  1. Alonso P, CuadrasD, Gabriëls L, Denys D, Goodman W, Greenberg BD, Jimenez-Ponce F, Kuhn J, Lenartz D, Mallet L, Nuttin B, Real E, Segalas C, Schuurman R, du Montcel ST, Menchon JM. Deep Brain Stimulation for Obsessive-Compulsive Disorder: A Meta-Analysis of Treatment Outcome and Predictors of Response. PLoS One. 2015;10(7):e0133591. Epub 2015 Jul 24. doi:10.1371/journal.pone.0133591.
  2. Borders C, Hsu F, Sweidan AJ, Matei ES, Bota RG. Deep brain stimulation for obsessive compulsive disorder: A review of results by anatomical target. Ment Illn. 2018;10(2):7900. Published 2018 Nov 6. doi:10.4081/mi.2018.7900.
  3. Douglas Y. Deep Brain Stimulation Successfully Treats Refractory OCD Although Targets Vary. Psychiatry Advisor. Feb. 10, 2020; https://www.psychiatryadvisor.com/home/topics/anxiety/deep-brain-stimulation-successfully-treats-refractory-ocd-although-targets-vary/. Accessed Aug. 6, 2020.
  4. Greenberg BD, Gabriels LA, Malone DA Jr, Rezai AR, Friehs GM, Okun MS, Shapira NA, Foote KD, Cosyns PR, Kubu CS, Malloy PF, Salloway SP, Giftakis JE, Rise MT, Machado AG, Baker KB, Stypulkowski PH, Goodman WK, Rasmussen SA, Nuttin BJ. Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience. Mol Psychiatry. 2010 Jan;15(1):64-79. Epub 2008 May 20. doi:10.3389/fnins.2018.00998.
  5. Guzick A, Hunt PJ, Bijanki KR, et al. Improving long term patient outcomes from deep brain stimulation for treatment-refractory obsessive-compulsive disorder. Expert Rev Neurother. 2020;20(1):95-107. doi:10.1080/14737175.2020.1694409.
  6. Hamani C, Pilitsis J, Rughani AI, et al. Deep brain stimulation for obsessive-compulsive disorder: systematic review and evidence-based guideline sponsored by the American Society for Stereotactic and Functional Neurosurgery and the Congress of Neurological Surgeons (CNS) and endorsed by the CNS and American Association of Neurological Surgeons. Neurosurgery. 2014;75(4):327-333. doi:10.1227/NEU.0000000000000499
  7. Li, Ningfei & Baldermann, Juan Carlos & Kibleur, Astrid & Treu, Svenja & Akram, Harith & Elias, Gavin & Boutet, Alexandre & Lozano, Andres & Al-Fatly, Bassam & Strange, Bryan & Barcia, Juan & Zrinzo, Ludvic & Joyce, Eileen & Chabardes, Stephan & Visser-Vandewalle, Veerle & Polosan, Mircea & Kuhn, Jens & Kühn, Andrea & Horn, Andreas. (2020). A unified connectomic target for deep brain stimulation in obsessive-compulsive disorder. Nature Communications. 11. 1234567890. doi:10.1038/s41467-020-16734-3.
  8. van Westen, M., Rietveld, E., Bergfeld, I.O., de Koning, P., Vullink, N., Ooms, P., Graat, I., Liebrand, L., van den Munckhof, P., Schuurman, R. and Denys, D. (2020), Optimizing Deep Brain Stimulation Parameters in Obsessive–Compulsive Disorder. Neuromodulation: Technology at the Neural Interface. doi:10.1111/ner.13243.
  9. Vicheva P, Butler M, Shotbolt P. Deep brain stimulation for obsessive-compulsive disorder: A systematic review of randomised controlled trials. Neurosci Biobehav Rev. 2020;109:129-138. doi:10.1016/j.neubiorev.2020.01.007.

Please note: This information should not be used as a substitute for medical treatment and advice. Always consult a medical professional about any health-related questions or concerns.

 

 

Last Updated on Monday, October 12, 2020 07:57 PM