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Deep Brain Stimulation in Treatment-Resistant Major Depressive Disorder

Table Summarizing Clinical Research Studies

Studies used in this table were either double-blinded crossover trials and/or prospective trials; 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: Subcallosal Cingulate Gyrus (SCG)

Holtzheimer
(2012)
Subcallosal
cingulate
deep brain
stimulation
for treatment-
resistant
unipolar
and bipolar
depression
United States
---
• National Institutes of Health
• Dana Foundation
• Emory Healthcare
• Stanley Medical Research Institute
• Woodruff Foundation
• St. Jude Medical
Condition after Bilateral SCG
vs
Condition before Implantation
17 • Adults (ages 18 - 70)
• Disabling Major Depressive Disorder (10/17)
• Bipolar Disorder (7/17)
• Current depressive episode lasting at least 12 months
• No response to at least 4 anti-depressive drug regimens
• Failure of or inability to receive electroconvulsive therapy
• No recent suicidal ideation, substance abuse, or personality disorder

Length:
24 months
Prospective
Cohort Study


Performed with FDA Investigational Device
Exemption Approvals and Approved by the Institutional Review Board
• Significant improvement seen at 24 months (average of 72.4% improvement)
• Discontinuation of stimulation resulted in recurrence of depression
• 92% of patients had at least a 50% improvement in their depression score
• 58% of patients achieved remission

• Improvement in overall daily function (average of 132.2% improvement)

Major Adverse Events:
   • Suicidality (3/17)
   • Worsening depression (2/17)
   • Anxiety (5/17)
   • Infection (5/17)
   • System malfunction (3/17) 
Lozano
(2012)
A multicenter
pilot study of
subcallosal
cingulate area
deep brain
stimulation for
treatment-
resistant
depression
United States
Canada
---
• St. Jude Medical
Condition after Bilateral SCG
vs
Condition before Implantation
21 • Adults (ages 30 - 60)
• Disabling Major Depressive Disorder diagnosed before 35 years of age
No Bipolar Disorder
• Current depressive episode lasting at least 24 months
• No response to at least 4 anti-depressive drug regimens
• Failure of or inability to receive electroconvulsive therapy
• No recent suicidal ideation, substance abuse, or personality disorder
• No neurologic disorder
• No cardiac pacemaker
• Not pregnant

Length:
12 months
Prospective
Cohort Study


Approved by
each
Institutional Review Board
• Significant improvement seen at 12 months (average of 41.4% improvement)
• 29% of patients had at least a 50% improvement in their depression score
• 62% of patients had at least a 40% improvement in their depression score

Major Adverse Events:
   • Suicidality (2/21)
   • Infection (1/21)
   • System malfunction (1/21)
   • Nausea/Vomiting (7/21)
Kennedy
(2011)
Deep brain
stimulation
for treatment-
resistant
depression:
follow-up
after 3 to
6 years
United States
Canada
---
• University Health Network, Toronto
Condition after Bilateral SCG
vs
Condition before Implantation
20 • Adults (ages 30 - 60)
• Disabling Major Depressive Disorder diagnosed before 35 years of age
No Bipolar Disorder
• Current depressive episode lasting at least 1 year
• No response to at least 4 anti-depressive drug regimens
• Failure of or inability to receive electroconvulsive therapy
• No recent suicidal ideation, substance abuse, or personality disorder
• No neurologic disorder
• No cardiac pacemaker
• Not pregnant

Length:
3-6 years
(average 42 months)

Prospective
Cohort Study


Approved by Institutional Research
Ethics Board
• At 3 years, 75% of patients had at least a 50% improvement in their depression score
• 42.9% of patients achieved remission
• At last follow-up, 64.3% of patients had at least a 50% improvement in their depression score

• Significant improvement in overall daily function seen over time

Major Adverse Events:
   • Suicidality (3/20)
   • Worsening depression (3/20)
   • Perioperative seizure (1/20)
   • Infection (3/20)
McNeely
(2008)
Neuro-
psychological
impact of
Cg25 deep
brain
stimulation
for treatment-
resistant
depression:
preliminary
results over
12 months
Canada
---
• Brain & Behavior Research Foundation
Condition after Bilateral SCG
vs
Condition before Implantation
6 • Adults (ages 37 - 59)
• Severe Major Depressive Disorder
• Current depressive episode lasting at least 1 year
• No response to at least 4 anti-depressive drug regimens
• Failure of electroconvulsive therapy (5/6)

Length:
12 months

Prospective
Cohort Study


Approved
by each Institutional Ethical Review Committee
• Significant improvement seen at 12 months (average of 60% improvement)

• No negative effects on cognition with chronic stimulation

Major Adverse Events: 
   None

Investigational Brain Stimulation Target: Nucleus Accumbens (NAcc)

Bewernick
(2012)
Long-term
effects of
nucleus
accumbens
deep brain
stimulation
in treatment-
resistant
depression:
evidence for
sustained
efficacy

United States
Germany
---
• Medtronic Inc.
• Volkswagen Foundation
Condition after Bilateral N Ac
vs
Condition before Implantation
11 • Adults (ages 32 - 65)
• Disabling Major Depressive Disorder diagnosed at least 5 years ago
• Current depressive episode lasting at least 2 years
• No response to at least 4 anti-depressive drug regimens
• Failure of electroconvulsive therapy
• Failure of psychotherapy
• No psychotic or personality disorder
• No neurologic disorder

Length:
24 months

Prospective
Cohort Study


Approved
by each Institutional Review Board
• Significant improvement seen at 12 months (average of 37.3% improvement)
• Significant improvement seen at 24 months (average of 39.4% improvement)
• 45.5% of patients had at least a 50% improvement in their depression score

• Improvement in concurrent anxiety (average of 37% improvement)
• No negative effects on cognition with chronic stimulation

Major Adverse Events:
   • Suicidality (1/11)
   • Seizure (2/11)
   • Trouble with swallowing (3/11)
Schlaepfer
(2008)
Deep brain
stimulation
to reward
circuitry
alleviates
anhedonia in
refractory
major
depression
Germany
---
• Medtronic Inc.
Condition with Bilateral N Ac Stimulation
vs
Condition without Stimulation
vs
Condition before Implantation
3 • Adults (ages 37 - 66)
• Severe Major Depressive Disorder
• No response to anti-depressive drugs
• Failure of electroconvulsive therapy
• Failure of psychotherapy

Length:
12.3 ± 9.3
months

(4 week
crossover)

Double Blinded
Crossover Study
followed by a
Prospective
Cohort Study


Approved
by the Institutional Review Board
• Improvement seen after one week of stimulation (average of 27.2% improvement)
• Effect was significantly diminished when stimulation was turned off for one week (average of only 6.7% improvement from baseline)
• Significant improvement seen at last follow-up (average of 80% improvement)

Major Adverse Events:
   None

Investigational Brain Stimulation Target: Ventral Capsule/Ventral Striatum

Malone
(2009)
Deep brain
stimulation
of the ventral
capsule
/ventral
striatum for
treatment-
resistant
depression
United States
---
• Medtronic Inc.
Condition after Bilateral VC/VS Stimulation
vs
Condition before Implantation
15 • Adults (ages 18 - 55)
• Severe Major Depressive Disorder (14/15) diagnosed at least 5 years ago
• Current depressive episode lasting at least 2 years
• Severe Bipolar Disorder (1/15)
• No response to at least 5 anti-depressive drug regimens after at least 4 weeks
• Failure of electroconvulsive therapy
• Failure of psychotherapy
• No psychotic or neurologic disorder
• No recent suicidal ideation, substance abuse, or personality disorder
• Not pregnant

Length:
23.5 ±
14.9
months

Prospective
Cohort Study


Performed with FDA Investigational Device
Exemption Approvals and Approved
by the Institutional Review Board
• Significant improvement seen at 12 months (average of 45.5% improvement)
• Significant improvement seen at last follow-up (average of 55.8% improvement)
• At last follow-up, 53.3% of patients had at least a 50% improvement in their depression score and 40% of patients were considered to be in remission

• Improvement in overall daily function (average of 61.8% improvement)

Major Adverse Events:
   • Suicidality (2/15)
   • Worsening depression (1/15)
   • Lead Fracture (1/15)


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


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 Friday, June 16, 2017 08:19 AM