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; 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)
Greenberg (2006)	Three-year outcomes in deep brain stimulation for highly resistant obsessive- compulsive disorder	United States --- • Brain & Behavior Research Foundation • National Institute of Mental Health • Medtronic Inc.	Condition after Bilateral VC/VS Stimulation  vs Condition before Implantation	8	• Adults (ages 22 - 59) • Severe OCD for at least 11 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 (7/8)	Prospective Cohort Study Performed with FDA Investigational Device Exemption Approvals Length: ≥ 36 months	• Significant improvement seen at 36 months (average of 35.5% improvement) • 50% patients had at least a 35% improvement in their OCD score • Improvement in concurrent depression (average of 27.0% improvement) • Improvement in concurrent anxiety (average of 56.0% improvement) • Improvement in overall daily function (average of 32.0% improvement) Major Adverse Events:    • Intracranial hemorrhage (1/8)    • Discontinued stimulation due to lack of adequate therapeutic effects (2/8)
Nuttin (2003)	Long-term electrical capsular stimulation in patients with obsessive- compulsive disorder	Belgium --- • Fonds voor Wetenschappelijk Onderzoek-Vlaanderen • Research Council of the Katholieke Universiteit Leuven • Verkennende Internationale Samenwerking • Medtronic Inc.	Condition with Bilateral VC/VS Stimulation  vs Condition without Stimulation	4	• Adults (ages 18 - 60) • Disabling OCD for at least 5 years • Failure of at least 2 traditional pharmacological agents and behavioral therapy • No previous or current psychotic, personality, or neurologic disorders Co-Morbid Conditions:    Major Depressive Disorder (2/4)    Somatoform Disorder (1/4)	Double Blinded Crossover Study followed by a Prospective Cohort Study (no mention of ethical review) Length: 21 months (6 months blinded)	• Greater improvement with active stimulation   (average OCD score 38.7% better) • Condition similar to baseline when stimulation turned off • 75% patients had at least a 35% improvement in their OCD score • Greater improvement in depression with active stimulation   (average score 41.8% better) • Increased suicidal ideation noted when stimulator turned off • Imaging demonstated a decrease in frontal lobe activity with stimulation Major Adverse Events:    • Device removal due to ineffectiveness (1/4)
Tsai (2002)	Pilot study of deep brain stimulation in refractory obsessive- compulsive disorder ethnic Chinese patients	Taiwan --- • Buddhist Tzu-Chi Hospital	Condition with Bilateral VC/VS Stimulation  vs Condition before Implantation	4	• Adult males (ages 21 - 30) • Severe OCD for at least 3 years • Failure of multiple pharmacological trials and behavioral therapy • No previous or current psychotic, personality, or neurologic disorders • No substance abuse Co-Morbid Conditions:    Major Depressive Disorder (3/4)	Prospective Cohort Study Approved by the Taiwan Department of Health Length: 15 months	• Significant improvement seen at 15 months (average of 33.06% improvement) • 100% patients had at least a 30% improvement in their OCD score • Improvement in concurrent depression (average of 32.51% improvement) • Improvement in overall daily function (average of 31.03% improvement) Major Adverse Events:    • Allergic reaction (1/4)    • Brief hypomania (2/4)
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)
Franzini (2010)	Deep-brain stimulation of the nucleus accumbens in obsessive compulsive disorder: clinical, surgical and electrophysiological considerations in two consecutive patients	Italy --- none mentioned	Condition with Bilateral NAcc Stimulation  vs Condition before Implantation	2	• Adult males (ages 33 - 41) • 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 (1/2)    Bipolar Disorder (1/2)	Prospective Cohort Study (no mention of ethical review) Length: 25.5 ± 2.12 months	•Significant improvement seen at last-follow-up (average of 38.2%) •Improvement in concurrent depression (average of 57.7% improvement) •Improvement in overall daily function (average of 50% improvement) Major Adverse Events:    None
Investigational Brain Stimulation Target: Subthalamic Nucleus (STN)
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: Inferior Thalamic Peduncle (ITP)
Jimenez- Ponce (2009)	Preliminary study in patients with obsessive- compulsive disorder treated with electrical stimulation in the inferior thalamic peduncle	Mexico --- none	Condition after Bilateral ITP Stimulation  vs Condition before Implantation	5	• Adults (ages 21-65) • Severe OCD for at least 5 years • Failure of 3 pharmaceutical and behavioral therapy treatment regimens, each lasting at least 6 months • No previous or current psychotic, personality, or neurologic disorders • No substance abuse Co-Morbid Conditions:    Past Substance Abuse (3/5)    Schizoid Personality (1/5)	Prospective Cohort Study Approved by the Institutional Ethics Committee and in accordance with the Helsinki Declaration Length: 12 months	• Significant improvement seen at 12 months (average of 49.1% improvement) • All patients had at least a 44% improvement in their OCD score • Improvement in overall daily function (average of 300% improvement) Major Adverse Events:    None

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 reference:

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, Clement Hamani, et al., Neurosurgery, doi: 10.1227/NEU.0000000000000499, published online 22 September 2014.

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.