Deep Brain Stimulation for Intractable Obsessive Compulsive Disorder: Pilot Study Using a Blinded, Staggered-Onset Design

doi:10.1016/j.biopsych.2009.11.028

Biological Psychiatry

Volume 67, Issue 6, 15 March 2010, Pages 535-542

https://doi.org/10.1016/j.biopsych.2009.11.028 Get rights and content

Background

Prior promising results have been reported with deep brain stimulation (DBS) of the anterior limb of the internal capsule in cases with severe obsessive compulsive disorder (OCD) who had exhausted conventional therapies.

Methods

In this pilot study, six adult patients (2 male; 4 female) meeting stringent criteria for severe (minimum Yale-Brown Obsessive Compulsive Scale [Y-BOCS] of 28) and treatment-refractory OCD had DBS electrode arrays placed bilaterally in an area spanning the ventral anterior limb of the internal capsule and adjacent ventral striatum referred to as the ventral capsule/ventral striatum. Using a randomized, staggered-onset design, patients were stimulated at either 30 or 60 days following surgery under blinded conditions.

Results

After 12 months of stimulation, four (66.7%) of six patients met a stringent criterion as “responders” (≥35% improvement in the Y-BOCS and end point Y-BOCS severity ≤16). Patients did not improve during sham stimulation. Depressive symptoms improved significantly in the group as a whole; global functioning improved in the four responders. Adverse events associated with chronic DBS were generally mild and modifiable with setting changes. Stimulation interruption led to rapid but reversible induction of depressive symptoms in two cases.

Conclusions

This pilot study suggests that DBS of the ventral capsule/ventral striatum region is a promising therapy of last resort for carefully selected cases of severe and intractable OCD. Future research should attend to subject selection, lead location, DBS programming, and mechanisms underpinning therapeutic benefits.

Section snippets

Patients

This study was conducted at the University of Florida as a collaboration of the departments of Psychiatry, Neurology, and Neurosurgery in consultation with Dr. Benjamin Greenberg of Brown University. Prior to recommending surgery, an independent internal multidisciplinary team (psychiatrist, neurologist, neurosurgeon, and medical ethicist) reviewed all past treatments, evaluations, and procedures to ensure appropriateness of the candidate. Psychiatric diagnoses were based upon administration of

DBS Lead Locations and Programming

A summary of the active DBS contacts used for chronic stimulation is provided in Table 1 along with lead locations. Three patients (patients 2, 3, and 5) had sham DBS programming for 1 month and then were subsequently activated at the next study visit under double-blind conditions. All patients were activated in a single contact monopolar setting for the first 6 months. Following the 6-month time point, trials of multiple monopolar stimulation resulted in salvage of one patient (patient 3) but

Discussion

Twelve months of bilateral stimulation of the VC/VS was associated with marked improvement in obsessive compulsive symptoms in four (66.7%) of six subjects with severe and intractable OCD. Even the two individuals who were classified as nonresponders requested that stimulation be continued because they experienced some subjective relief of anxiety, depressive, or tic symptoms. For the six subjects as a whole, both OCD and depressive symptoms improved significantly compared with baseline at the

References (35)

W.K. Goodman et al.
Deep brain stimulation in psychiatry: Concentrating on the road ahead
Biol Psychiatry
(2009)
B. Nuttin et al.
Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder
Lancet
(1999)
B.D. Greenberg et al.
Neurosurgery for intractable obsessive-compulsive disorder and depression: Critical issues
Neurosurg Clin North Am
(2003)
J.L. Abelson et al.
Deep brain stimulation for refractory obsessive-compulsive disorder
Biol Psychiatry
(2005)
D.A. Malone et al.
Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression
Biol Psychiatry
(2009)
Y.D. Van Der Werf et al.
The intralaminar and midline nuclei of the thalamusAnatomical and functional evidence for participation in processes of arousal and awareness
Brain Res Brain Res Rev
(2002)
W.K. Goodman et al.
Biological approaches to treatment-resistant obsessive compulsive disorder
L. Baer et al.
Cingulotomy for intractable obsessive-compulsive disorderProspective long-term follow-up of 18 patients
Arch Gen Psychiatry
(1995)
A.R. Rezai et al.
Surgery for movement disorders
Neurosurgery
(2008)
M.B. First et al.
Structured Clinical Interview for DSM IV Axis I Disorders—Clinician Version (SCID-CV)
(1997)

W.K. Goodman et al.

The Yale-Brown Obsessive Compulsive Scale (Y-BOCS)Part II. Validity

Arch Gen Psychiatry

(1989)

W.K. Goodman et al.

The Yale-Brown obsessive Compulsive Scale (Y-BOCS)Part I. Development, use, and reliability

Arch Gen Psychiatry

(1989)

B.D. Greenberg et al.

Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: Worldwide experience

Mol Psychiatry

(2008)

M.S. Okun et al.

Deep brain stimulation in the internal capsule and nucleus accumbens region: Responses observed during active and sham programming

J Neurol Neurosurg Psychiatry

(2007)

M. Hamilton

A rating scale for depression

J Neurol Neurosurg Psychiatry

(1960)

W. Guy

ECDEU Assessment Manual for Psychopharmacology

(1976)

D.M. McNair et al.

Profile of Mood States

(1971)

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Stereo-EEG-guided network modulation for psychiatric disorders: Surgical considerations
2023, Brain Stimulation
Deep brain stimulation (DBS) and other neuromodulatory techniques are being increasingly utilized to treat refractory neurologic and psychiatric disorders.
/Hypothesis: To better understand the circuit-level pathophysiology of treatment-resistant depression (TRD) and treat the network-level dysfunction inherent to this challenging disorder, we adopted an approach of inpatient intracranial monitoring borrowed from the epilepsy surgery field.
We implanted 3 patients with 4 DBS leads (bilateral pair in both the ventral capsule/ventral striatum and subcallosal cingulate) and 10 stereo-electroencephalography (sEEG) electrodes targeting depression-relevant network regions. For surgical planning, we used an interactive, holographic visualization platform to appreciate the 3D anatomy and connectivity. In the initial surgery, we placed the DBS leads and sEEG electrodes using robotic stereotaxy. Subjects were then admitted to an inpatient monitoring unit for depression-specific neurophysiological assessments. Following these investigations, subjects returned to the OR to remove the sEEG electrodes and internalize the DBS leads to implanted pulse generators.
Intraoperative testing revealed positive valence responses in all 3 subjects that helped verify targeting. Given the importance of the network-based hypotheses we were testing, we required accurate adherence to the surgical plan (to engage DBS and sEEG targets) and stability of DBS lead rotational position (to ensure that stimulation field estimates of the directional leads used during inpatient monitoring were relevant chronically), both of which we confirmed (mean radial error 1.2±0.9 mm; mean rotation 3.6±2.6°).
This novel hybrid sEEG-DBS approach allows detailed study of the neurophysiological substrates of complex neuropsychiatric disorders.
Future directions in psychiatric neurosurgery: Proceedings of the 2022 American Society for Stereotactic and Functional Neurosurgery meeting on surgical neuromodulation for psychiatric disorders
2023, Brain Stimulation
Objective.
Despite advances in the treatment of psychiatric diseases, currently available therapies do not provide sufficient and durable relief for as many as 30–40% of patients. Neuromodulation, including deep brain stimulation (DBS), has emerged as a potential therapy for persistent disabling disease, however it has not yet gained widespread adoption. In 2016, the American Society for Stereotactic and Functional Neurosurgery (ASSFN) convened a meeting with leaders in the field to discuss a roadmap for the path forward. A follow-up meeting in 2022 aimed to review the current state of the field and to identify critical barriers and milestones for progress.
Design.
The ASSFN convened a meeting on June 3, 2022 in Atlanta, Georgia and included leaders from the fields of neurology, neurosurgery, and psychiatry along with colleagues from industry, government, ethics, and law. The goal was to review the current state of the field, assess for advances or setbacks in the interim six years, and suggest a future path forward. The participants focused on five areas of interest: interdisciplinary engagement, regulatory pathways and trial design, disease biomarkers, ethics of psychiatric surgery, and resource allocation/prioritization. The proceedings are summarized here.
Conclusion.
The field of surgical psychiatry has made significant progress since our last expert meeting. Although weakness and threats to the development of novel surgical therapies exist, the identified strengths and opportunities promise to move the field through methodically rigorous and biologically-based approaches. The experts agree that ethics, law, patient engagement, and multidisciplinary teams will be critical to any potential growth in this area.
Effectiveness of Deep Brain Stimulation in Treatment of Anorexia Nervosa and Obesity: A Systematic Review
2022, World Neurosurgery
Anorexia nervosa and obesity are common appetite disorders, which may be life threatening if not treated and often coincide with psychiatric disorders. We sought to investigate whether deep brain stimulation (DBS) of specific regions within the brain could aid in the treatment of these disorders. This review aims to organize the literature regarding the feasibility of DBS via clinical outcomes and synthesize the data on patient demographics and electrode parameters for future optimization.
PubMed, Scopus, and Web of Science databases were all queried on 7 June 2022 to identify studies reporting the effect of DBS in treatment of either anorexia nervosa or obesity. We included studies involving 1) DBS, 2) treatment of anorexia nervosa or obesity, and 3) body mass index (BMI) as the primary outcome variable. Case reports, retrospective cohort studies, and randomized controlled trials were all eligible for inclusion. Exclusion of articles was based on the following criteria: 1) meta-analyses or systematic reviews or 2) describes diseases other than only anorexia or obesity. Screening of the 999 articles returned by an initial search yielded 23 studies for inclusion and further data extraction. Qualitative assessment of included studies was subsequently conducted in accordance with Newcastle-Ottawa Scale criteria.
We included 23 articles (17 anorexia, 5 obesity) that met our inclusion and exclusion criteria, which included 8 case reports, 13 case series, and 1 case-control study. Our primary variables of interest were location of DBS, change in BMI after intervention, electrode parameters, and psychiatric comorbidities. A total of 131 patients were included and analyzed, 118 of those belonging in the anorexia cohort.
For patients with anorexia, we found that the most common place for DBS was the subcallosal cingulate followed by the nucleus accumbens, resulting in an overall increase in BMI by 24.82% over the span of a mean 17.1 months. Psychiatric comorbidities (major depressive disorder, obsessive-compulsive disorder, and anxiety) were common in the anorexia cohort. For patients with obesity, DBS was most common in the lateral hypothalamus followed by the nucleus accumbens, resulting in a small decrease in BMI by 3.97% over a mean 17.2 months. Data were insufficient for this cohort to report on additional psychiatric comorbidities or calculate the duration from diagnosis to treatment.
DBS seems to be a promising solution in addressing treatment-refractory anorexia, but additional prospective studies are still needed to confirm this same usefulness for the treatment of obesity. Primary limitations included the apparent lack of data on DBS for obesity as well as the dearth of cohort studies assessing efficacy of DBS compared with control treatments. Although these limitations could not be addressed in the current review, this study may incentivize future trials to assess DBS in patients with appetite disorders in a more controlled fashion.
Deep brain stimulation in obsessive-compulsive disorder: Results from meta-analysis
2022, Psychiatry Research
The aim of this work is to investigate the effectiveness of Deep Brain Stimulation (DBS) in patients with severe Obsessive Compulsive Disorder (OCD) who are resistant to pharmacological treatments, focusing on obsessive compulsive, depressive and anxiety symptoms as well as global function. A systematic review and meta-analysis including 25 studies (without language restrictions) from between 2003 and 2020 was performed. A total of 303 patients were evaluated twice (before and after DBS). After DBS treatment OCD patients with resistance to pharmacological treatments showed a significant improvement of obsessive-compulsive symptoms (25 studies; SMD=2.39; 95% CI, 1.91 to 2.87; P<0.0001), depression (9 studies; SMD= 1.19; 95%CI, 0.84 to 1.54; P<0.0001), anxiety (5 studies; SMD=1.00; 95%CI, 0.32 to 1.69; P=0.004) and functionality (7 studies; SMD=-3.51; 95%CI, -5.00 to -2.02; P=0.005) measured by the standardized scales: Yale Brown Obsessive Compulsive Scale (YBOCS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) and Global Assessment of Function (GAF). Publication bias were discarded by using funnel plot. The main conclusions of this meta-analysis highlight the statistically significant effectiveness of DBS in patients with severe OCD who are resistant to conventional pharmacological treatments, underlying its role in global functioning apart from obsessive-compulsive symptoms.
Psychopathological and neuropsychological outcomes of deep brain stimulation for severe- treatment-resistant obsessive-compulsive disorder: An open-label case series
2022, Journal of Clinical Neuroscience
Deep brain stimulation (DBS) is considered a promising intervention for treatment-resistant obsessive–compulsive disorder (OCD). The present study describes the outcomes of the first DBS procedures for OCD in Iran.
Four women patients (age range, 25–35 years) with severe OCD meeting stringent criteria for refractoriness to treatment were selected by Psychosurgery Review Board. DBS electrodes were bilaterally implanted in the internal capsule and nucleus accumbens (NAc). Clinical and neuropsychological assessments were undertaken before and after implantation. The outcomes included Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Hamilton Anxiety Rating Scale (HAM-A), neuropsychological assessments including the Wisconsin Card Sorting Test, Wechsler Memory Scale, and adverse events.
The baseline mean score of the Y-BOCS and HAM-A was 32 ± 6 and 23 ± 14 respectively and decreased to 26 ± 8 and 17 ± 9 after one-year implantation, showing a 19% improvement. Two patients were responders and showed a notable improvement. One patient's score declined 28%, who was not satisfied with DBS results, and one patient worsened under-stimulation. Improvements in the severity of anxiety and cognitive performance were consistent with OCD improvement, and the successfully treated patients showed improvement in anxiety and cognitive performance. No significant cognitive declines were seen. Two patients' suicidal ideation appeared after DBS as an important adverse event.
Bilateral DBS of the internal capsule/NAc may be an effective and safe treatment for treatment-refractory OCD. However, there is a need to consider accessibility, high cost, cost-effectiveness, and standardized methodology in future research.
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Noninvasive brain stimulation using transcranial focused ultrasound (FUS) has many potential applications as a research and clinical tool, including incorporation into neural prosthetics for cognitive rehabilitation. To develop this technology, it is necessary to evaluate the safety and efficacy of FUS neuromodulation for specific brain targets and cognitive functions. It is also important to test whether repeated long-term application of FUS to deep brain targets improves or degrades behavioral and cognitive function. To this end, we investigated the effects of FUS in the dorsal striatum of nonhuman primates (NHP) performing a visual-motor decision-making task for small or large rewards. Over the course of 2 years, we performed 129 and 147 FUS applications, respectively, in two NHP. FUS (0.5 MHz @ 0.2–0.8 MPa) was applied to the putamen and caudate in both hemispheres to evaluate the effects on movement accuracy, motivation, decision accuracy, and response time. Sonicating the caudate or the putamen unilaterally resulted in modest but statistically significant improvements in motivation and decision accuracy, but at the cost of slower reaction times. The effects were dose (i.e., FUS pressure) and reward dependent. There was no effect on reaching accuracy, nor was there long-term behavioral impairment or neurological trauma evident on T1-weighted, T2-weighted, or susceptibility-weighted MRI scans. Sonication also resulted in significant changes in resting state functional connectivity between the caudate and multiple cortical regions. The results indicate that applying FUS to the dorsal striatum can positively impact the motivational and cognitive aspects of decision making. The capability of FUS to improve motivation and cognition in NHPs points to its therapeutic potential in treating a wide variety of human neural diseases, and warrants further development as a novel technique for non-invasive deep brain stimulation.

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Archival ReportDeep Brain Stimulation for Intractable Obsessive Compulsive Disorder: Pilot Study Using a Blinded, Staggered-Onset Design

Background

Methods

Results

Conclusions

Section snippets

Patients

DBS Lead Locations and Programming

Discussion

Biol Psychiatry

Lancet

Neurosurg Clin North Am

Biol Psychiatry

Biol Psychiatry

Brain Res Brain Res Rev

Biological approaches to treatment-resistant obsessive compulsive disorder

Cingulotomy for intractable obsessive-compulsive disorderProspective long-term follow-up of 18 patients

Arch Gen Psychiatry

Surgery for movement disorders

Neurosurgery

Structured Clinical Interview for DSM IV Axis I Disorders—Clinician Version (SCID-CV)

The Yale-Brown Obsessive Compulsive Scale (Y-BOCS)Part II. Validity

Arch Gen Psychiatry

The Yale-Brown obsessive Compulsive Scale (Y-BOCS)Part I. Development, use, and reliability

Arch Gen Psychiatry

Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: Worldwide experience

Mol Psychiatry

Deep brain stimulation in the internal capsule and nucleus accumbens region: Responses observed during active and sham programming

J Neurol Neurosurg Psychiatry

A rating scale for depression

J Neurol Neurosurg Psychiatry

ECDEU Assessment Manual for Psychopharmacology

Profile of Mood States

Archival Report
Deep Brain Stimulation for Intractable Obsessive Compulsive Disorder: Pilot Study Using a Blinded, Staggered-Onset Design