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CNS Annual Meeting
Internally Produced & Endorsed
Sponsors: Congress of Neurological Surgeons (CNS) and the American Society of Stereotactic and Functional Neurosurgery
Endorsement: Reviewed for evidence-based integrity and endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons
Specialty: Stereotactic & Functional
Original text of the guideline was edited to reflect the update. Please click here for the original publication.
Michael D. Staudt, MD, MSc1,2, Nader Pouratian, MD, PhD3, Jonathan P. Miller, MD4, Clement Hamani, MD, PhD5, Nataly Raviv, MD6, Guy M. McKhann, MD7, Jorge A. Gonzalez-Martinez, MD, PhD8, Julie G. Pilitsis, MD, PhD6
1Department of Neurosurgery, Oakland University William Beaumont School of Medicine, Rochester, Michigan, USA
2Michigan Head and Spine Institute, Southfield, Michigan, USA
3Department of Neurosurgery, University of California, Los Angeles, CA, USA
4Department of Neurosurgery, Case Western Reserve University, Cleveland, OH, USA
5Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada
6Department of Neurosurgery, Albany Medical College, Albany, NY, USA
7Department of Neurological Surgery, Columbia University Irving Medical Center, New York, NY, USA
8Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA
Julie G. Pilitsis MD, PhD
Department of Neurosurgery
Albany Medical College
47 New Scotland Ave, MC-10
Albany, NY 12208
Keywords: bed nucleus of stria terminalis, deep brain stimulation, nucleus accumbens, obsessive-compulsive disorder, subthalamic nucleus
Abbreviations: AANS, American Association of Neurological Surgeons; ALIC, anterior limb of internal capsule ; BNST, bed nucleus of stria terminalis; CNS, Congress of Neurological Surgeons; DBS, deep brain stimulation; FDA, Food and Drug Administration; HDE, humanitarian device exemption; NAc, nucleus accumbens; OCD, obsessive-compulsive disorder; STN, subthalamic nucleus; VC/VS, ventral capsule/ventral striatum; Y-BOCS, Yale and Brown OCD Scale
Background: In 2020, the Guidelines Task Force conducted another systematic review of the relevant literature on deep brain stimulation for obsessive compulsive disorder to update the original 2014 guidelines to ensure timeliness and accuracy for clinical practice.
Objective: To conduct a systematic review of the literature and update the evidence-based guidelines on DBS for OCD.
Methods: The Guidelines Task Force conducted another systematic review of the relevant literature, using the same search terms and strategies used to search PubMed and Embase for relevant literature. The updated search included studies published between 1966 and December 2019. The same inclusion/exclusion criteria as the original guideline were also applied. Abstracts were reviewed and relevant full text articles were retrieved and graded. Of 864 articles, 10 were retrieved for full-text review and analysis. Recommendations were updated according to new evidence yielded by this update.
Results: Seven studies were included in the original guideline, reporting the use of bilateral DBS as more effective in improving OCD symptoms than sham treatment. An additional 10 studies were included in this update: 1 Class II and 9 Class III.
Conclusions: Based on the data published in the literature, the following recommendation can be made: 1) It is recommended that clinicians utilize bilateral subthalamic nucleus DBS over best medical management for the treatment of patients with medically refractory OCD (Level I). 2) Clinicians may use bilateral nucleus accumbens or bed nucleus of stria terminalis DBS for the treatment of patients with medically refractory OCD (Level II). There is insufficient evidence to make a recommendation for the identification of the most effective target.
In 2014, guidelines for the treatment of obsessive-compulsive disorder (OCD) with deep brain stimulation (DBS) were established by the American Society for Stereotactic and Functional Neurosurgery and the Congress of Neurological Surgeons.1 These guidelines were based on a literature review performed between 1966 and October 2012. The current article is a 5-year review of the medical literature in accordance with the standard operating procedures and methodology of the Congress of Neurological Surgeons for developing clinical practice guidelines.
In the original 2014 guidelines, 7 articles were included for analysis, with 3 studies having a double-blind phase in which active stimulation was compared with sham treatment. One of these studies fulfilled criteria for Class I evidence,2 whereas the other 2 were classified as Class II.3,4 Four additional studies were classified as Class III evidence,5-8 with the 2 studies by Greenberg et al. reporting the results of the same patient cohort at different follow-ups.6,7
The use of bilateral anterior limb of internal capsule (ALIC) DBS for OCD was approved by the US Food and Drug Administration (FDA) under a humanitarian device exemption (HDE) in 2009.9 Following this HDE approval and publication of the 2014 guidelines, there have been additional published studies reporting the use of DBS for OCD, although most do not meet criteria to be included in this guidelines update. The purpose of this update is to review the literature following publication of the original guidelines and to update the recommendations as appropriate. Based on the availability of new literature, the current article is a major update resulting in modification and update of prior recommendations (see Table 1) as well as an updated discussion.
Writing Group and question Establishment
The Guidelines Task Force initiated an update of the original systematic review of the literature and evidence-based guideline relevant to the use of deep brain stimulation for the treatment of patients with obsessive compulsive disorder. This guideline update was developed for educational purposes to assist practitioners in their clinical decision-making processes. Additional information about the methods utilized in this systematic review is provided via the Congress of Neurological Surgeons Methodology.
The PubMed and Embase databases were searched using the terms “deep brain stimulation” and “obsessive compulsive disorder”, or “electrical stimulation” and “obsessive compulsive disorder”. Articles published between 1966 and December 2019 were screened via the inclusion and exclusion criteria established in the previous guidelines publication (Table 2).1 A total of 748 and 175 articles were identified through the PubMed and Embase database searches, respectively. As the original guidelines did not include an Embase database search, the search was repeated for both databases from 1966. After removal of 59 duplicate entries, 864 articles underwent title and abstract review by 2 independent investigators (Figure 1). A total of 93 articles underwent full review and 17 met inclusion criteria. Seven of these 17 articles were analyzed in the original guidelines, and 10 new articles were selected for inclusion in this update. A total of 76 articles were excluded for the following reasons: the DBS target was ambiguous in 7 studies, 4 reported on non-DBS interventions, 27 had less than 6 patients, 4 had a follow-up period of less than 6 months, 13 reported a non-clinical outcome of interest, and 21 reported on the same patient population that was detailed in a separate article (i.e. clinical results in one article, and imaging studies in another).
Study Selection and Eligibility Criteria
A total of 93 citations underwent a full text, double blind review by the task force using the same inclusion and exclusion criteria as the original guideline.1 The authors did not include systematic reviews, guidelines, or meta-analyses conducted by others. Those documents were developed using different inclusion criteria than those specified in this guideline. Therefore, those documents may include studies that do not meet the inclusion criteria specified above. See PRISMA Article Flow Chart (Figure 1).
Data Collection Process
The abstracts that met the selection criteria mentioned above were retrieved in full-text form. Each article’s adherence to the selection criteria was assessed. To determine how the data could be classified, the information in the full-text articles was then evaluated to determine whether they were providing results of therapy or were more centered on diagnostic or prognostic information. Agreement on these assessments and on the salient points regarding the type of study design and objectives, and the conclusions and data classification was then reached by exchanging drafts and comments among authors. The information was then used for construction of the evidence tables.
Rating Quality of Evidence
The quality of evidence was rated using an evidence hierarchy for therapeutic studies. Demonstrating the highest degree of clinical certainty, Class I evidence is used to support recommendations of the strongest type, defined as Level I recommendations. Level II recommendations reflect a moderate degree of clinical certainty and are supported by Class II evidence. Level III recommendations denote clinical uncertainty supported by Class III evidence. This hierarchy is shown in Table 3. Additional information regarding the hierarchy classification of evidence is found on the CNS Guidelines Procedures and Policies page.
In accordance with the National Academy of Medicine’s standards for developing clinical practice guidelines the task force will monitor related publications following the release of this document and will revise the entire document and/or specific sections “if new evidence shows that a recommended intervention causes previously unknown substantial harm; that a new intervention is significantly superior to a previously recommended intervention from an efficacy or harms perspective; or that a recommendation can be applied to new populations.”10 In addition, the task force will confirm within 5 years from the date of publication that the content reflects current clinical practice and the available technologies regarding DBS for OCD.
Of the 10 studies evaluated to update the guidelines, no study fulfilled criteria to be classified as a Class I study. One study was classified as Class II, which was a trial of ALIC or bed nucleus of stria terminalis (BNST) DBS.11 Nine additional studies were classified as Class III.12-20 Table 4 outlines those studies included for consideration in the updated guidelines.
The first recommendation from the 2014 guidelines indicated that there is Level I evidence, based on a single Class I study,2 for the use of bilateral subthalamic nucleus (STN) DBS for the treatment of medically refractory OCD. In the interim, the STN was the DBS target in two additional Class III studies.15,16 No additional Class I studies have been performed in the interim to justify additional recommendations. The verbiage of the recommendation was updated with respect to formatting only. The recommendation now reads: It is recommended that clinicians utilize bilateral STN DBS over best medical management for the treatment of patients with medically refractory OCD.
The second original recommendation indicated that there is Level II evidence, based on a single Class II study,3 for the use of bilateral nucleus accumbens (NAc) DBS for the treatment of medically refractory OCD. In the interim, the DBS of NAc was studied in 5 additional Class III studies.12-14,18,19 An additional Class II study was reported by Luyten et al.,11 with implantation of bilateral DBS electrodes into the BNST and/or ALIC; overall improved therapeutic effects were seen with BNST stimulation compared to ALIC stimulation. As such, this recommendation has been expanded: Clinicians may use bilateral NAc or BNST DBS for the treatment of patients with medically refractory OCD (Level II).
The third original recommendation indicated that there is insufficient evidence to make a recommendation for the use of unilateral DBS for the treatment of medically refractory OCD. At the time of initial guideline publication, only 1 Class II study performed unilateral NAc DBS for the treatment of medically refractory OCD.4 No additional studies of unilateral DBS have been performed in the interim. As such, this recommendation has been removed.
Since the publication of the original DBS for OCD guidelines in 2014, multiple new studies have been published. Although it is encouraging that additional studies have been performed, there continues to be a lack of high-quality randomized controlled trials to support Level I recommendations. Whereas 1 Class II study was performed in the interim, the additional published trials were lower quality Class III studies. The majority of published studies continue to have low recruitment and short length of follow-up that preclude inclusion in these updated guidelines. However, based on the availability of new literature, a major update is required resulting in modification of the original recommendations (Table 4).
The trial reported by Luyten et al.11 was well-designed, however was not classified as Class I due to certain limitations. This study included a randomized sham-controlled 3-month blinded crossover trial followed by open-label observation of up to 14 years, and was classified as Class II because only a subset of enrolled subjects (17 of 24) participated in the randomized phase. The trial reported by Tyagi et al.16 was downgraded primarily due to the indirectness of the evidence. In this study, 6 patients were implanted with bilateral electrodes separately targeting the STN and ventral capsule/ventral striatum (VC/VS), with the latter leads traversing the ALIC and NAc. Patients then underwent a randomized 3-month blinded stimulation phase of one target, followed by an additional 3-month cross-over phase stimulating the other target. This was followed by 3 subsequent open phases with combined stimulation of both targets, stimulation with optimized settings, and finally stimulation with concurrent cognitive-behavioral therapy. Although this study had a novel design, there was no comparison of active stimulation vs. sham treatment and no washout period. Furthermore, interpretation of the data is limited by the use of combined stimulation of two separate targets. The remainder of studies classified as Class III were case or case-control series, and did not include a blinded phase in which active stimulation was compared to sham treatment.12-15,17-20
Key Issues for Future Investigation
The use of bilateral ALIC DBS for OCD was approved by the US FDA under a HDE in 2009.9 This approval was based on data generated from the multicenter study of 26 patients reported by Greenberg et al.7 As such, the ALIC continues to be the most commonly implanted target, and is also necessary for insurance coverage. Despite the publication of additional high quality studies since the initial HDE approval, clinical practice is largely unchanged. Indeed, it has been suggested that approval of the HDE would create challenges regarding patient recruitment for larger clinical trials or different targets.21,22
In the original guidelines, an important focus of discussion was the clarification of the most effective DBS target. No recommendation was made due to the lack of data. As the literature has expanded, the most commonly targeted regions include the VC/VS and NAc; however, it is important to recognize that the VC/VS is a region, not a defined structure, with the NAc as its most ventral extension. In the literature, the description of DBS targets for OCD can be inconsistent or ambiguous when comparing results between studies or even within the same study. Overlap has been observed with the reporting of coordinates for striatal region targets, which includes the VC/VS, NAc, ALIC and BNST.23 For example, some of the studies included in the updated guidelines describe targeting both the ALIC and NAc along the same electrode trajectory.12,16,18,19 Furthermore, in the study which led to HDE approval, improved results were seen with refinement of the implantation target more posteriorly, with distal contacts in the caudal NAc or traversing the BNST;7 however, bilateral ALIC DBS continues to be the only FDA approved target. Future guideline updates may consider the recommendation of a “striatal target” based on pooled evidence from these striatal subregions.
It is possible that DBS results in stimulation of multiple targets, or that an optimal target can be stimulated with different electrode trajectories. As such, it is not possible to conclusively propose a single “most effective” target, and improving DBS outcomes may depend on identifying patient- or disease-specific commonalities. An additional area in need of further study is identification of patient- or disease-specific phenotypes in order to determine which candidates will respond best to DBS. OCD is a markedly heterogeneous disorder, and the variations in treatment response observed in the literature may be explained by diversity in phenotype. Therefore, there remains insufficient evidence to make a recommendation for the identification of the most effective target. Furthermore, the analysis performed in this guideline does not compare the efficacy or quality of data for DBS compared to other established or novel surgical therapies for OCD, including stereotactic radiosurgery, radiofrequency thermocoagulation, or focused ultrasound.
DBS is being increasingly used in the treatment of medically refractory OCD with overall good results, resulting in the publication of multiple new reports since the original guidelines were introduced in 2014. Although the overall level of evidence remains low, a major update to the original recommendations can be made due to the availability of new evidence. Additional research is necessary to identify which patient-specific characteristics and surgical target(s) are most likely to benefit patients with OCD.
Conflicts of Interest
All Guideline Task Force members were required to disclose all potential COIs prior to beginning work on the guideline, using the COI disclosure form of the AANS/CNS Joint Guidelines Review Committee. The CNS Guidelines Committee and Guideline Task Force Chair reviewed the disclosures and either approved or disapproved the nomination and participation on the task force. The CNS Guidelines Committee and Guideline Task Force Chair may approve nominations of task force members with possible conflicts and restrict the writing, reviewing, and/or voting privileges of that person to topics that are unrelated to the possible COIs. See Table 5 for a complete list of disclosures.
This evidence-based clinical practice guidelines were funded exclusively by the Congress of Neurological Surgeons, which received no funding from outside commercial sources to support the development of this document.
Disclaimer of Liability
This clinical, systematic, evidence-based clinical practice guideline was developed by a multi-disciplinary physician volunteer taskforce and is provided as an educational tool based on an assessment of the current scientific and clinical information regarding deep brain stimulation for the treatment of patients with obsessive-compulsive disorder. These guidelines are disseminated with the understanding that the recommendations by the authors and consultants who have collaborated in their development are not meant to replace the individualized care and treatment advice from a patient's physician(s). If medical advice or assistance is required, the services of a physician should be sought. The proposals contained in these guidelines may not be suitable for use in all circumstances. The choice to implement any particular recommendation contained in these guidelines must be made by a managing physician in light of the situation in each particular patient and on the basis of existing resources.
The guidelines task force would like to acknowledge the Congress of Neurological Surgeons Guidelines Committee for their contributions throughout the development of the guideline, the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Guidelines Review Committee for their review, comments, and suggestions throughout peer review, as well as the contributions of Trish Rehring, MPH, CHES, Associate Director of Evidence-Based Practice Initiatives for the CNS. Throughout the review process, the reviewers and authors were blinded from one another. At this time the guidelines task force would like to acknowledge the following individual peer reviewers for their contributions: Jennifer Sweet, MD, Kimon Bekelis, MD, Jeffrey Olson, MD, Jon T. Willie, MD, Sharona Ben-Haim, MD.
Figure 1. Flowchart showing the process involved in identifying relevant literature for the 2020 Update.
Table 1: Recommendations
Table 2. Study Selection Criteria
Table 3. Rating Evidence Quality
Classification of Evidence on Therapeutic Effectiveness
Class I Evidence
Class II Evidence
Class III Evidence
Evidence from case series, comparative studies with
Table 4. Evidence Tables for the 2020 Update
Bilateral BNST/ALIC DBS. 24 patients, 17 whom completed a double-blind randomized crossover trial (consisting of ON and OFF phases lasting 3 months each), 18 followed for >4 years. 48-171 month follow-up.
16/24 patients (67%) were responders. At last follow-up, median improvements in scores were as follows: 45% on Y-BOCS, 45% on HARS, 49% on HDRS, and 30 points on GAF. Y-BOCS score was highly correlated with the ON score during the crossover trial (R=0.83, p<0.001). Data interpreted as suggesting that BNST might be a better target for reducing obsessions and compulsions than ALIC.
Bilateral NAc/ALIC DBS. Case series of six patients undergoing DBS. Computational models were created for each patient in order to assess fiber tract activation. 24-month follow-up.
Bilateral NAc/ALIC DBS. Case series with open-label design, involving 20 patients undergoing stimulation for one year. 12-month follow-up.
Bilateral NAc/ALIC DBS. Case series involving 22 patients undergoing DBS and the development of patient-specific models of connectivity. 12-month follow-up.
Abbreviations: Randomized controlled trial (RCT); Yale-Brown Obsessive Compulsive Scale (Y-BOCS); Responders (≥35% Y-BOCS reduction); Partial responders (25-35% Y-BOCS reduction); EuroQol group-5 Dimensional (EQ-5D); Hamilton Depression Rating Scale (HDRS); Hamilton Anxiety Rating Scale (HARS); Global Assessment of Functioning (GAF) Scale.
Table 5. Conflict of Interest
Consultant: Koh Young Inc.
Consultant: Boston Scientific, Nevro, TerSera, Medtronic, Saluda and Abbott
Grant Support: Medtronic, Boston Scientific, Abbott, Nevro, TerSera, NIH 2R01CA166379-06 and NIH U44NS115111
Medical Advisor: Aim Medical Robotics and Karuna
*conflict not related to guideline topic
Abbreviations: NIH- National Institutes of Health