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

Deep Brain Stimulation in Treatment-Resistant Major Depressive Disorder

Table Summarizing Clinical Research Studies

Investigational Brain Stimulation Target: Subcallosal Cingulate Gyrus (SCG)

Investigational Brain Stimulation Target: Nucleus Accumbens (NAcc)

Investigational Brain Stimulation Target: Ventral Capsule/Ventral Striatum