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Sharma LP, Ganesh UM, Arumugham SS, Srinivas D, Venkatasubramanian G, Reddy YJ. Deep brain stimulation - A primer for psychiatrists. Asian J Psychiatr 2025; 104:104354. [PMID: 39787631 DOI: 10.1016/j.ajp.2024.104354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 12/13/2024] [Accepted: 12/24/2024] [Indexed: 01/12/2025]
Abstract
Deep Brain Stimulation is a form of neurostimulation where electrical stimulation is delivered via intracranial electrodes over specific subcortical targets. It has been increasingly used as an alternative to ablative procedures for psychiatric disorders refractory to standard treatments. This review describes the common psychiatric indications for DBS, the current evidence base, putative mechanisms, and future directions.
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Affiliation(s)
- Lavanya P Sharma
- OCD Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), India.
| | - Uma Maheswari Ganesh
- Department of Clinical Psychology, National Institute of Mental Health and Neurosciences (NIMHANS), India
| | - Shyam Sundar Arumugham
- OCD Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), India
| | - Dwarakanath Srinivas
- Department of Neurosurgery, National Institute of Mental Health and Neurosciences (NIMHANS), India
| | - Ganesan Venkatasubramanian
- OCD Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), India
| | - Yc Janardhan Reddy
- OCD Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), India
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2
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Sakai JT, Tanabe J, Battula S, Zipperly M, Mikulich-Gilbertson SK, Kern DS, Thompson JA, Raymond K, Gerecht PD, Foster K, Abosch A. Deep brain stimulation for the treatment of substance use disorders: a promising approach requiring caution. Front Psychiatry 2024; 15:1435109. [PMID: 39071229 PMCID: PMC11272460 DOI: 10.3389/fpsyt.2024.1435109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Accepted: 06/25/2024] [Indexed: 07/30/2024] Open
Abstract
Substance use disorders are prevalent, causing extensive morbidity and mortality worldwide. Evidence-based treatments are of low to moderate effect size. Growth in the neurobiological understanding of addiction (e.g., craving) along with technological advancements in neuromodulation have enabled an evaluation of neurosurgical treatments for substance use disorders. Deep brain stimulation (DBS) involves surgical implantation of leads into brain targets and subcutaneous tunneling to connect the leads to a programmable implanted pulse generator (IPG) under the skin of the chest. DBS allows direct testing of neurobiologically-guided hypotheses regarding the etiology of substance use disorders in service of developing more effective treatments. Early studies, although with multiple limitations, have been promising. Still the authors express caution regarding implementation of DBS studies in this population and emphasize the importance of safeguards to ensure patient safety and meaningful study results. In this perspectives article, we review lessons learned through the years of planning an ongoing trial of DBS for methamphetamine use disorder.
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Affiliation(s)
- Joseph T. Sakai
- Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, United States
| | - Jody Tanabe
- Department of Radiology, University of Colorado School of Medicine, Aurora, CO, United States
| | - Sharonya Battula
- Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, United States
| | - Morgan Zipperly
- Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, United States
| | | | - Drew S. Kern
- Department of Neurology, University of Colorado School of Medicine, Aurora, CO, United States
- Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO, United States
| | - John A. Thompson
- Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, United States
- Department of Neurology, University of Colorado School of Medicine, Aurora, CO, United States
- Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO, United States
| | - Kristen Raymond
- Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, United States
| | - Pamela David Gerecht
- Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO, United States
| | - Katrina Foster
- National Institute on Drug Abuse, Bethesda, MD, United States
| | - Aviva Abosch
- Department of Neurosurgery, University of Nebraska Medical Center, Omaha, NE, United States
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3
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Voineskos AN, Hawco C, Neufeld NH, Turner JA, Ameis SH, Anticevic A, Buchanan RW, Cadenhead K, Dazzan P, Dickie EW, Gallucci J, Lahti AC, Malhotra AK, Öngür D, Lencz T, Sarpal DK, Oliver LD. Functional magnetic resonance imaging in schizophrenia: current evidence, methodological advances, limitations and future directions. World Psychiatry 2024; 23:26-51. [PMID: 38214624 PMCID: PMC10786022 DOI: 10.1002/wps.21159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2024] Open
Abstract
Functional neuroimaging emerged with great promise and has provided fundamental insights into the neurobiology of schizophrenia. However, it has faced challenges and criticisms, most notably a lack of clinical translation. This paper provides a comprehensive review and critical summary of the literature on functional neuroimaging, in particular functional magnetic resonance imaging (fMRI), in schizophrenia. We begin by reviewing research on fMRI biomarkers in schizophrenia and the clinical high risk phase through a historical lens, moving from case-control regional brain activation to global connectivity and advanced analytical approaches, and more recent machine learning algorithms to identify predictive neuroimaging features. Findings from fMRI studies of negative symptoms as well as of neurocognitive and social cognitive deficits are then reviewed. Functional neural markers of these symptoms and deficits may represent promising treatment targets in schizophrenia. Next, we summarize fMRI research related to antipsychotic medication, psychotherapy and psychosocial interventions, and neurostimulation, including treatment response and resistance, therapeutic mechanisms, and treatment targeting. We also review the utility of fMRI and data-driven approaches to dissect the heterogeneity of schizophrenia, moving beyond case-control comparisons, as well as methodological considerations and advances, including consortia and precision fMRI. Lastly, limitations and future directions of research in the field are discussed. Our comprehensive review suggests that, in order for fMRI to be clinically useful in the care of patients with schizophrenia, research should address potentially actionable clinical decisions that are routine in schizophrenia treatment, such as which antipsychotic should be prescribed or whether a given patient is likely to have persistent functional impairment. The potential clinical utility of fMRI is influenced by and must be weighed against cost and accessibility factors. Future evaluations of the utility of fMRI in prognostic and treatment response studies may consider including a health economics analysis.
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Affiliation(s)
- Aristotle N Voineskos
- Campbell Family Mental Health Research Institute and Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Colin Hawco
- Campbell Family Mental Health Research Institute and Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Nicholas H Neufeld
- Campbell Family Mental Health Research Institute and Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Jessica A Turner
- Department of Psychiatry and Behavioral Health, Wexner Medical Center, Ohio State University, Columbus, OH, USA
| | - Stephanie H Ameis
- Campbell Family Mental Health Research Institute and Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Cundill Centre for Child and Youth Depression and McCain Centre for Child, Youth and Family Mental Health, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Alan Anticevic
- Interdepartmental Neuroscience Program, Yale University, New Haven, CT, USA
- Department of Psychiatry, Yale University, New Haven, CT, USA
| | - Robert W Buchanan
- Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Kristin Cadenhead
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
| | - Paola Dazzan
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Erin W Dickie
- Campbell Family Mental Health Research Institute and Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Julia Gallucci
- Campbell Family Mental Health Research Institute and Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
| | - Adrienne C Lahti
- Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Anil K Malhotra
- Institute for Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY, USA
- Department of Psychiatry, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
- Department of Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
- Department of Psychiatry, Zucker Hillside Hospital Division of Northwell Health, Glen Oaks, NY, USA
| | - Dost Öngür
- McLean Hospital/Harvard Medical School, Belmont, MA, USA
| | - Todd Lencz
- Institute for Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY, USA
- Department of Psychiatry, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
- Department of Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
- Department of Psychiatry, Zucker Hillside Hospital Division of Northwell Health, Glen Oaks, NY, USA
| | - Deepak K Sarpal
- Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Lindsay D Oliver
- Campbell Family Mental Health Research Institute and Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
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Kilian HM, Schiller B, Meyer-Doll DM, Heinrichs M, Schläpfer TE. Normalized affective responsiveness following deep brain stimulation of the medial forebrain bundle in depression. Transl Psychiatry 2024; 14:6. [PMID: 38191528 PMCID: PMC10774255 DOI: 10.1038/s41398-023-02712-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 12/06/2023] [Accepted: 12/12/2023] [Indexed: 01/10/2024] Open
Abstract
Deep brain stimulation (DBS) of the supero-lateral medial forebrain bundle (slMFB) is associated with rapid and sustained antidepressant effects in treatment-resistant depression (TRD). Beyond that, improvements in social functioning have been reported. However, it is unclear whether social skills, the basis of successful social functioning, are systematically altered following slMFB DBS. Therefore, the current study investigated specific social skills (affective empathy, compassion, and theory of mind) in patients with TRD undergoing slMFB DBS in comparison to healthy subjects. 12 patients with TRD and 12 age- and gender-matched healthy subjects (5 females) performed the EmpaToM, a video-based naturalistic paradigm differentiating between affective empathy, compassion, and theory of mind. Patients were assessed before and three months after DBS onset and compared to an age- and gender-matched sample of healthy controls. All data were analyzed using non-parametric Mann-Whitney U tests. DBS treatment significantly affected patients' affective responsiveness towards emotional versus neutral situations (i.e. affective empathy): While their affective responsiveness was reduced compared to healthy subjects at baseline, they showed normalized affective responsiveness three months after slMFB DBS onset. No effects occurred in other domains with persisting deficits in compassion and intact socio-cognitive skills. Active slMFB DBS resulted in a normalized affective responsiveness in patients with TRD. This specific effect might represent one factor supporting the resumption of social activities after recovery from chronic depression. Considering the small size of this unique sample as well as the explorative nature of this study, future studies are needed to investigate the robustness of these effects.
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Affiliation(s)
- Hannah Marlene Kilian
- Division of Interventional Biological Psychiatry, Department of Psychiatry and Psychotherapy Medical Center - University of Freiburg, Faculty of Medicine, DE-79104, Freiburg, Germany.
| | - Bastian Schiller
- Department of Psychology, Laboratory for Biological Psychology, Clinical Psychology and Psychotherapy, University of Freiburg, DE-79104, Freiburg, Germany
| | - Dora Margarete Meyer-Doll
- Division of Interventional Biological Psychiatry, Department of Psychiatry and Psychotherapy Medical Center - University of Freiburg, Faculty of Medicine, DE-79104, Freiburg, Germany
| | - Markus Heinrichs
- Department of Psychology, Laboratory for Biological Psychology, Clinical Psychology and Psychotherapy, University of Freiburg, DE-79104, Freiburg, Germany
| | - Thomas Eduard Schläpfer
- Division of Interventional Biological Psychiatry, Department of Psychiatry and Psychotherapy Medical Center - University of Freiburg, Faculty of Medicine, DE-79104, Freiburg, Germany
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Najera RA, Provenza N, Dang H, Katlowitz KA, Hertz A, Reddy S, Shofty B, Bellows ST, Storch EA, Goodman WK, Sheth SA. Dual-Target Deep Brain Stimulation for Obsessive-Compulsive Disorder and Tourette Syndrome. Biol Psychiatry 2023; 93:e53-e55. [PMID: 36863881 PMCID: PMC11166381 DOI: 10.1016/j.biopsych.2023.01.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 01/18/2023] [Indexed: 03/04/2023]
Affiliation(s)
- Ricardo A Najera
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas
| | - Nicole Provenza
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas
| | - Huy Dang
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas
| | | | - Alyssa Hertz
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas
| | - Sandesh Reddy
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas
| | - Ben Shofty
- Department of Neurosurgery, University of Utah, Salt Lake City, Utah
| | - Steven T Bellows
- Department of Neurology, Baylor College of Medicine, Houston, Texas
| | - Eric A Storch
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas
| | - Wayne K Goodman
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas
| | - Sameer A Sheth
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.
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Nagrale SS, Yousefi A, Netoff TI, Widge AS. In silicodevelopment and validation of Bayesian methods for optimizing deep brain stimulation to enhance cognitive control. J Neural Eng 2023; 20:036015. [PMID: 37105164 PMCID: PMC10193041 DOI: 10.1088/1741-2552/acd0d5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 03/18/2023] [Accepted: 04/27/2023] [Indexed: 04/29/2023]
Abstract
Objective.deep brain stimulation (DBS) of the ventral internal capsule/striatum (VCVS) is a potentially effective treatment for several mental health disorders when conventional therapeutics fail. Its effectiveness, however, depends on correct programming to engage VCVS sub-circuits. VCVS programming is currently an iterative, time-consuming process, with weeks between setting changes and reliance on noisy, subjective self-reports. An objective measure of circuit engagement might allow individual settings to be tested in seconds to minutes, reducing the time to response and increasing patient and clinician confidence in the chosen settings. Here, we present an approach to measuring and optimizing that circuit engagement.Approach.we leverage prior results showing that effective VCVS DBS engages cognitive control circuitry and improves performance on the multi-source interference task, that this engagement depends primarily on which contact(s) are activated, and that circuit engagement can be tracked through a state space modeling framework. We develop a simulation framework based on those empirical results, then combine this framework with an adaptive optimizer to simulate a principled exploration of electrode contacts and identify the contacts that maximally improve cognitive control. We explore multiple optimization options (algorithms, number of inputs, speed of stimulation parameter changes) and compare them on problems of varying difficulty.Main results.we show that an upper confidence bound algorithm outperforms other optimizers, with roughly 80% probability of convergence to a global optimum when used in a majority-vote ensemble.Significance.we show that the optimization can converge even with lag between stimulation and effect, and that a complete optimization can be done in a clinically feasible timespan (a few hours). Further, the approach requires no specialized recording or imaging hardware, and thus could be a scalable path to expand the use of DBS in psychiatric and other non-motor applications.
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Affiliation(s)
- Sumedh S Nagrale
- Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, United States of America
- Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, United States of America
| | - Ali Yousefi
- Department of Computer Science, Worcester Polytechnic Institute, Worcester, MA, United States of America
| | - Theoden I Netoff
- Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, United States of America
| | - Alik S Widge
- Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, United States of America
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7
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Cruz S, Gutiérrez-Rojas L, González-Domenech P, Díaz-Atienza F, Martínez-Ortega JM, Jiménez-Fernández S. Deep brain stimulation in obsessive-compulsive disorder: Results from meta-analysis. Psychiatry Res 2022; 317:114869. [PMID: 36240634 DOI: 10.1016/j.psychres.2022.114869] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 09/25/2022] [Accepted: 09/26/2022] [Indexed: 01/04/2023]
Abstract
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.
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Affiliation(s)
- Sheila Cruz
- Child and Adolescent Mental Health Service, Jaén University Hospital Complex, Jaén, Spain
| | - Luis Gutiérrez-Rojas
- Psychiatry and Neurosciences Research Group (CTS-549), Institute of Neurosciences, University of Granada, Granada, Spain; Department of Psychiatry, University of Granada, Granada, Spain; Psychiatry Service, Hospital San Cecilio, Granada, Spain.
| | | | - Francisco Díaz-Atienza
- Psychiatry and Neurosciences Research Group (CTS-549), Institute of Neurosciences, University of Granada, Granada, Spain; Department of Psychiatry, University of Granada, Granada, Spain; Child and Adolescent Mental Health Service, Granada Virgen de las Nieves University Hospital, Granada, Spain
| | - José M Martínez-Ortega
- Psychiatry and Neurosciences Research Group (CTS-549), Institute of Neurosciences, University of Granada, Granada, Spain; Department of Psychiatry, University of Granada, Granada, Spain
| | - Sara Jiménez-Fernández
- Child and Adolescent Mental Health Service, Jaén University Hospital Complex, Jaén, Spain; Psychiatry and Neurosciences Research Group (CTS-549), Institute of Neurosciences, University of Granada, Granada, Spain
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Gadot R, Najera R, Hirani S, Anand A, Storch E, Goodman WK, Shofty B, Sheth SA. Efficacy of deep brain stimulation for treatment-resistant obsessive-compulsive disorder: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2022; 93:jnnp-2021-328738. [PMID: 36127157 DOI: 10.1136/jnnp-2021-328738] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 05/22/2022] [Indexed: 11/03/2022]
Abstract
Deep brain stimulation (DBS) is an established and growing intervention for treatment-resistant obsessive-compulsive disorder (TROCD). We assessed current evidence on the efficacy of DBS in alleviating OCD and comorbid depressive symptoms including newly available evidence from recent trials and a deeper risk of bias analysis than previously available. PubMed and EMBASE databases were systematically queried using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We included studies reporting primary data on multiple patients who received DBS therapy with outcomes reported through the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Primary effect measures included Y-BOCS mean difference and per cent reduction as well as responder rate (≥35% Y-BOCS reduction) at last follow-up. Secondary effect measures included standardised depression scale reduction. Risk of bias assessments were performed on randomised controlled (RCTs) and non-randomised trials. Thirty-four studies from 2005 to 2021, 9 RCTs (n=97) and 25 non-RCTs (n=255), were included in systematic review and meta-analysis based on available outcome data. A random-effects model indicated a meta-analytical average 14.3 point or 47% reduction (p<0.01) in Y-BOCS scores without significant difference between RCTs and non-RCTs. At last follow-up, 66% of patients were full responders to DBS therapy. Sensitivity analyses indicated a low likelihood of small study effect bias in reported outcomes. Secondary analysis revealed a 1 standardised effect size (Hedges' g) reduction in depressive scale symptoms. Both RCTs and non-RCTs were determined to have a predominantly low risk of bias. A strong evidence base supports DBS for TROCD in relieving both OCD and comorbid depression symptoms in appropriately selected patients.
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Affiliation(s)
- Ron Gadot
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
| | - Ricardo Najera
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
| | - Samad Hirani
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
| | - Adrish Anand
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
| | - Eric Storch
- Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA
| | - Wayne K Goodman
- Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA
| | - Ben Shofty
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
| | - Sameer A Sheth
- Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
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9
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Long-term comparative effectiveness of deep brain stimulation in severe obsessive-compulsive disorder. Brain Stimul 2022; 15:1128-1138. [DOI: 10.1016/j.brs.2022.07.050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 07/09/2022] [Accepted: 07/25/2022] [Indexed: 11/21/2022] Open
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10
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Ruan H, Wang Y, Li Z, Tong G, Wang Z. A Systematic Review of Treatment Outcome Predictors in Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder. Brain Sci 2022; 12:brainsci12070936. [PMID: 35884742 PMCID: PMC9316868 DOI: 10.3390/brainsci12070936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 07/06/2022] [Accepted: 07/15/2022] [Indexed: 12/04/2022] Open
Abstract
Obsessive-compulsive disorder (OCD) is a chronic and debilitating mental disorder. Deep brain stimulation (DBS) is a promising approach for refractory OCD patients. Research aiming at treatment outcome prediction is vital to provide optimized treatments for different patients. The primary purpose of this systematic review was to collect and synthesize studies on outcome prediction of OCD patients with DBS implantations in recent years. This systematic review (PROSPERO registration number: CRD42022335585) followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-analysis) guidelines. The search was conducted using three different databases with the following search terms related to OCD and DBS. We identified a total of 3814 articles, and 17 studies were included in our review. A specific tract confirmed by magnetic resonance imaging (MRI) was predictable for DBS outcome regardless of implant targets, but inconsistencies still exist. Current studies showed various ways of successful treatment prediction. However, considering the heterogeneous results, we hope that future studies will use larger cohorts and more precise approaches for predictors and establish more personalized ways of DBS surgeries.
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Affiliation(s)
- Hanyang Ruan
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China; (H.R.); (Y.W.); (Z.L.); (G.T.)
| | - Yang Wang
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China; (H.R.); (Y.W.); (Z.L.); (G.T.)
| | - Zheqin Li
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China; (H.R.); (Y.W.); (Z.L.); (G.T.)
| | - Geya Tong
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China; (H.R.); (Y.W.); (Z.L.); (G.T.)
| | - Zhen Wang
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China; (H.R.); (Y.W.); (Z.L.); (G.T.)
- Institute of Psychological and Behavioral Science, Shanghai Jiao Tong University, Shanghai 200030, China
- Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500), Shanghai 200030, China
- Correspondence: ; Tel.: +86-180-1731-1286
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11
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Digital Addiction and Sleep. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19116910. [PMID: 35682491 PMCID: PMC9179985 DOI: 10.3390/ijerph19116910] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 06/02/2022] [Accepted: 06/03/2022] [Indexed: 12/25/2022]
Abstract
In 2020, the World Health Organization formally recognized addiction to digital technology (connected devices) as a worldwide problem, where excessive online activity and internet use lead to inability to manage time, energy, and attention during daytime and produce disturbed sleep patterns or insomnia during nighttime. Recent studies have shown that the problem has increased in magnitude worldwide during the COVID-19 pandemic. The extent to which dysfunctional sleep is a consequence of altered motivation, memory function, mood, diet, and other lifestyle variables or results from excess of blue-light exposure when looking at digital device screens for long hours at day and night is one of many still unresolved questions. This article offers a narrative overview of some of the most recent literature on this topic. The analysis provided offers a conceptual basis for understanding digital addiction as one of the major reasons why people, and adolescents in particular, sleep less and less well in the digital age. It discusses definitions as well as mechanistic model accounts in context. Digital addiction is identified as functionally equivalent to all addictions, characterized by the compulsive, habitual, and uncontrolled use of digital devices and an excessively repeated engagement in a particular online behavior. Once the urge to be online has become uncontrollable, it is always accompanied by severe sleep loss, emotional distress, depression, and memory dysfunction. In extreme cases, it may lead to suicide. The syndrome has been linked to the known chronic effects of all drugs, producing disturbances in cellular and molecular mechanisms of the GABAergic and glutamatergic neurotransmitter systems. Dopamine and serotonin synaptic plasticity, essential for impulse control, memory, and sleep function, are measurably altered. The full spectrum of behavioral symptoms in digital addicts include eating disorders and withdrawal from outdoor and social life. Evidence pointing towards dysfunctional melatonin and vitamin D metabolism in digital addicts should be taken into account for carving out perspectives for treatment. The conclusions offer a holistic account for digital addiction, where sleep deficit is one of the key factors.
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Mosley PE, Velakoulis D, Farrand S, Marsh R, Mohan A, Castle D, Sachdev PS. Deep brain stimulation for treatment-refractory obsessive-compulsive disorder should be an accepted therapy in Australia. Aust N Z J Psychiatry 2022; 56:430-436. [PMID: 34263654 DOI: 10.1177/00048674211031482] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Deep brain stimulation has shown promise for the treatment of severe, treatment-refractory obsessive-compulsive disorder. With the recent publication of the first Australian, randomised, sham-controlled trial of deep brain stimulation for obsessive-compulsive disorder, there are now four placebo-controlled trials demonstrating the efficacy of this therapy. Together with recent data identifying a biological substrate of effective stimulation that can predict response and that has been successfully reproduced, studies comparing and finding equivalent efficacy among different targets, as well as recent, large, open trials supporting the long-term effectiveness of deep brain stimulation, we argue that this should now be considered an accepted therapy for a select group of patients in the Australasian setting. We call on the Royal Australian and New Zealand College of Psychiatrists to revise their memorandum describing deep brain stimulation for obsessive-compulsive disorder as an 'experimental' treatment and recognise that it has proven efficacy. We stress that this should remain a therapy offered only to those with high treatment-refractory illnesses and only at specialised centres where there is an experienced multidisciplinary team involved in work-up, implantation and follow-up and also where frameworks are in place to provide careful clinical governance and ensure appropriate fully informed consent.
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Affiliation(s)
- Philip E Mosley
- Clinical Brain Networks Group, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.,Neurosciences Queensland, St Andrew's War Memorial Hospital, Spring Hill, QLD, Australia.,Queensland Brain Institute, The University of Queensland, St Lucia, QLD, Australia.,Faculty of Medicine, The University of Queensland, Herston, QLD, Australia.,Biomedical Informatics Group, CSIRO, Herston, QLD, Australia
| | - Dennis Velakoulis
- Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia.,Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Parkville, VIC, Australia
| | - Sarah Farrand
- Neuropsychiatry, Royal Melbourne Hospital, Parkville, VIC, Australia.,Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Parkville, VIC, Australia
| | - Rodney Marsh
- Neurosciences Queensland, St Andrew's War Memorial Hospital, Spring Hill, QLD, Australia.,Faculty of Medicine, The University of Queensland, Herston, QLD, Australia
| | - Adith Mohan
- Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.,Neuropsychiatric Institute, The Prince of Wales Hospital, Randwick, NSW, Australia
| | - David Castle
- Centre for Complex Interventions, Centre for Addiction and Mental Health, Toronto, ON, Canada.,Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Perminder S Sachdev
- Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.,Neuropsychiatric Institute, The Prince of Wales Hospital, Randwick, NSW, Australia
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Mahoney JJ, Koch-Gallup N, Scarisbrick DM, Berry JH, Rezai AR. Deep brain stimulation for psychiatric disorders and behavioral/cognitive-related indications: Review of the literature and implications for treatment. J Neurol Sci 2022; 437:120253. [DOI: 10.1016/j.jns.2022.120253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 02/23/2022] [Accepted: 04/03/2022] [Indexed: 11/15/2022]
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Müller S, van Oosterhout A, Bervoets C, Christen M, Martínez-Álvarez R, Bittlinger M. Concerns About Psychiatric Neurosurgery and How They Can Be Overcome: Recommendations for Responsible Research. NEUROETHICS-NETH 2022. [DOI: 10.1007/s12152-022-09485-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Abstract
Background
Psychiatric neurosurgery is experiencing a revival. Beside deep brain stimulation (DBS), several ablative neurosurgical procedures are currently in use. Each approach has a different profile of advantages and disadvantages. However, many psychiatrists, ethicists, and laypeople are sceptical about psychiatric neurosurgery.
Methods
We identify the main concerns against psychiatric neurosurgery, and discuss the extent to which they are justified and how they might be overcome. We review the evidence for the effectiveness, efficacy and safety of each approach, and discuss how this could be improved. We analyse whether and, if so, how randomised controlled trials (RCTs) can be used in the different approaches, and what alternatives are available if conducting RCTs is impossible for practical or ethical reasons. Specifically, we analyse the problem of failed RCTs after promising open-label studies.
Results
The main concerns are: (i) reservations based on historical psychosurgery, (ii) concerns about personality changes, (iii) concerns regarding localised interventions, and (iv) scepticism due to the lack of scientific evidence. Given the need for effective therapies for treatment-refractory psychiatric disorders and preliminary evidence for the effectiveness of psychiatric neurosurgery, further research is warranted and necessary. Since psychiatric neurosurgery has the potential to modify personality traits, it should be held to the highest ethical and scientific standards.
Conclusions
Psychiatric neurosurgery procedures with preliminary evidence for efficacy and an acceptable risk–benefit profile include DBS and micro- or radiosurgical anterior capsulotomy for intractable obsessive–compulsive disorder. These methods may be considered for individual treatment attempts, but multi-centre RCTs are necessary to provide reliable evidence.
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15
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Corripio I, Roldán A, McKenna P, Sarró S, Alonso-Solís A, Salgado L, Álvarez E, Molet J, Pomarol-Clotet E, Portella M. Target selection for deep brain stimulation in treatment resistant schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2022; 112:110436. [PMID: 34517055 DOI: 10.1016/j.pnpbp.2021.110436] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 08/28/2021] [Accepted: 09/07/2021] [Indexed: 11/19/2022]
Abstract
The use of deep brain stimulation (DBS) in treatment resistant patients with schizophrenia is of considerable current interest, but where to site the electrodes is challenging. This article reviews rationales for electrode placement in schizophrenia based on evidence for localized brain abnormality in the disorder and the targets that have been proposed and employed to date. The nucleus accumbens and the subgenual anterior cingulate cortex are of interest on the grounds that they are sites of potential pathologically increased brain activity in schizophrenia and so susceptible to the local inhibitory effects of DBS; both sites have been employed in trials of DBS in schizophrenia. Based on other lines of reasoning, the ventral tegmental area, the substantia nigra pars reticulata and the habenula have also been proposed and in some cases employed. The dorsolateral prefrontal cortex has not been suggested, probably reflecting evidence that it is underactive rather than overactive in schizophrenia. The hippocampus is also of theoretical interest but there is no clear functional imaging evidence that it shows overactivity in schizophrenia. On current evidence, the nucleus accumbens may represent the strongest candidate for DBS electrode placement in schizophrenia, with the substantia nigra pars reticulata also showing promise in a single case report; the ventral tegmental area is also of potential interest, though it remains untried.
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Affiliation(s)
- Iluminada Corripio
- Psychiatry Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
| | - Alexandra Roldán
- Psychiatry Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
| | - Peter McKenna
- FIDMAG Germanes Hospitalàries, Sant Boi de Llobregat, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
| | - Salvador Sarró
- FIDMAG Germanes Hospitalàries, Sant Boi de Llobregat, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
| | - Anna Alonso-Solís
- Psychiatry Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
| | - Laura Salgado
- Neurosurgery Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain
| | - Enric Álvarez
- Psychiatry Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
| | - Joan Molet
- Neurosurgery Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain
| | - Edith Pomarol-Clotet
- FIDMAG Germanes Hospitalàries, Sant Boi de Llobregat, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
| | - Maria Portella
- Psychiatry Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain
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16
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Welter ML, Alves Dos Santos JF, Clair AH, Lau B, Diallo HM, Fernandez-Vidal S, Belaid H, Pelissolo A, Domenech P, Karachi C, Mallet L. Deep Brain Stimulation of the Subthalamic, Accumbens, or Caudate Nuclei for Patients With Severe Obsessive-Compulsive Disorder: A Randomized Crossover Controlled Study. Biol Psychiatry 2021; 90:e45-e47. [PMID: 33012521 DOI: 10.1016/j.biopsych.2020.07.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 07/20/2020] [Accepted: 07/21/2020] [Indexed: 12/13/2022]
Affiliation(s)
- Marie-Laure Welter
- Institut du cerveau et de la moelle épinière, French Institute of Health and Medical Research U1127, French National Centre for Scientific Research Joint Research Unit 7225, Sorbonne Université, Paris, France; Neurophysiology Department, Clinical Research Center-Biological Resources Center 1404, Centre Hospitalier Universitaire de Rouen, University of Rouen, Rouen, France
| | | | - Anne-Helene Clair
- Institut du cerveau et de la moelle épinière, French Institute of Health and Medical Research U1127, French National Centre for Scientific Research Joint Research Unit 7225, Sorbonne Université, Paris, France
| | - Brian Lau
- Institut du cerveau et de la moelle épinière, French Institute of Health and Medical Research U1127, French National Centre for Scientific Research Joint Research Unit 7225, Sorbonne Université, Paris, France
| | - Hassimiou Mamadou Diallo
- Institut Pierre Louis d'Epidémiologie et de Santé Publique, French Institute of Health and Medical Research, Paris, France
| | - Sara Fernandez-Vidal
- Institut du cerveau et de la moelle épinière, French Institute of Health and Medical Research U1127, French National Centre for Scientific Research Joint Research Unit 7225, Sorbonne Université, Paris, France
| | - Hayat Belaid
- Neurosurgery Department, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Antoine Pelissolo
- French Institute of Health and Medical Research U955, Mondor Institute for Biomedical Research, Créteil, France; Neurosurgery Department, Département Médico-Universitaire de psychiatrie et d'addictologie, Hôpitaux Universitaires Henri Mondor - Albert Chenevier, Assistance Publique-Hôpitaux de Paris, Université Paris-Est Créteil, Créteil, France
| | - Philippe Domenech
- Institut du cerveau et de la moelle épinière, French Institute of Health and Medical Research U1127, French National Centre for Scientific Research Joint Research Unit 7225, Sorbonne Université, Paris, France; Neurosurgery Department, Département Médico-Universitaire de psychiatrie et d'addictologie, Hôpitaux Universitaires Henri Mondor - Albert Chenevier, Assistance Publique-Hôpitaux de Paris, Université Paris-Est Créteil, Créteil, France
| | - Carine Karachi
- Institut du cerveau et de la moelle épinière, French Institute of Health and Medical Research U1127, French National Centre for Scientific Research Joint Research Unit 7225, Sorbonne Université, Paris, France; Neurosurgery Department, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Luc Mallet
- Institut du cerveau et de la moelle épinière, French Institute of Health and Medical Research U1127, French National Centre for Scientific Research Joint Research Unit 7225, Sorbonne Université, Paris, France; Neurosurgery Department, Département Médico-Universitaire de psychiatrie et d'addictologie, Hôpitaux Universitaires Henri Mondor - Albert Chenevier, Assistance Publique-Hôpitaux de Paris, Université Paris-Est Créteil, Créteil, France; Department of Mental Health and Psychiatry, Global Health Institute, University of Geneva, Geneva, Switzerland.
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Mar-Barrutia L, Real E, Segalás C, Bertolín S, Menchón JM, Alonso P. Deep brain stimulation for obsessive-compulsive disorder: A systematic review of worldwide experience after 20 years. World J Psychiatry 2021; 11:659-680. [PMID: 34631467 PMCID: PMC8474989 DOI: 10.5498/wjp.v11.i9.659] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 05/02/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Twenty years after its first use in a patient with obsessive-compulsive disorder (OCD), the results confirm that deep brain stimulation (DBS) is a promising therapy for patients with severe and resistant forms of the disorder. Nevertheless, many unknowns remain, including the optimal anatomical targets, the best stimulation parameters, the long-term (LT) effects of the therapy, and the clinical or biological factors associated with response. This systematic review of the articles published to date on DBS for OCD assesses the short and LT efficacy of the therapy and seeks to identify predictors of response.
AIM To summarize the existing knowledge on the efficacy and tolerability of DBS in treatment-resistant OCD.
METHODS A comprehensive search was conducted in the PubMed, Cochrane, Scopus, and ClinicalTrials.gov databases from inception to December 31, 2020, using the following strategy: “(Obsessive-compulsive disorder OR OCD) AND (deep brain stimulation OR DBS).” Clinical trials and observational studies published in English and evaluating the effectiveness of DBS for OCD in humans were included and screened for relevant information using a standardized collection tool. The inclusion criteria were as follows: a main diagnosis of OCD, DBS conducted for therapeutic purposes and variation in symptoms of OCD measured by the Yale-Brown Obsessive-Compulsive scale (Y-BOCS) as primary outcome. Data were analyzed with descriptive statistics.
RESULTS Forty articles identified by the search strategy met the eligibility criteria. Applying a follow-up threshold of 36 mo, 29 studies (with 230 patients) provided information on short-term (ST) response to DBS in, while 11 (with 155 patients) reported results on LT response. Mean follow-up period was 18.5 ± 8.0 mo for the ST studies and 63.7 ± 20.7 mo for the LT studies. Overall, the percentage of reduction in Y-BOCS scores was similar in ST (47.4%) and LT responses (47.2%) to DBS, but more patients in the LT reports met the criteria for response (defined as a reduction in Y-BOCS scores > 35%: ST, 60.6% vs LT, 70.7%). According to the results, the response in the first year predicts the extent to which an OCD patient will benefit from DBS, since the maximum symptom reduction was achieved in most responders in the first 12-14 mo after implantation. Reports indicate a consistent tendency for this early improvement to be maintained to the mid-term for most patients; but it is still controversial whether this improvement persists, increases or decreases in the long term. Three different patterns of LT response emerged from the analysis: 49.5% of patients had good and sustained response to DBS, 26.6% were non responders, and 22.5% were partial responders, who might improve at some point but experience relapses during follow-up. A significant improvement in depressive symptoms and global functionality was observed in most studies, usually (although not always) in parallel with an improvement in obsessive symptoms. Most adverse effects of DBS were mild and transient and improved after adjusting stimulation parameters; however, some severe adverse events including intracranial hemorrhages and infections were also described. Hypomania was the most frequently reported psychiatric side effect. The relationship between DBS and suicide risk is still controversial and requires further study. Finally, to date, no clear clinical or biological predictors of response can be established, probably because of the differences between studies in terms of the neuroanatomical targets and stimulation protocols assessed.
CONCLUSION The present review confirms that DBS is a promising therapy for patients with severe resistant OCD, providing both ST and LT evidence of efficacy.
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Affiliation(s)
- Lorea Mar-Barrutia
- OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona 08907, Spain
| | - Eva Real
- OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona 08907, Spain
- Bellvitge Biomedical Research Institute-IDIBELL, Barcelona 08907, Spain
- CIBERSAM (Centro de Investigación en Red de Salud Mental), Carlos III Health Institute, Madrid 28029, Spain
| | - Cinto Segalás
- OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona 08907, Spain
- Bellvitge Biomedical Research Institute-IDIBELL, Barcelona 08907, Spain
- CIBERSAM (Centro de Investigación en Red de Salud Mental), Carlos III Health Institute, Madrid 28029, Spain
| | - Sara Bertolín
- OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona 08907, Spain
| | - José Manuel Menchón
- OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona 08907, Spain
- Bellvitge Biomedical Research Institute-IDIBELL, Barcelona 08907, Spain
- CIBERSAM (Centro de Investigación en Red de Salud Mental), Carlos III Health Institute, Madrid 28029, Spain
- Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona 08907, Spain
| | - Pino Alonso
- OCD Clinical and Research Unit, Department of Psychiatry, Hospital de Bellvitge, Barcelona 08907, Spain
- Bellvitge Biomedical Research Institute-IDIBELL, Barcelona 08907, Spain
- CIBERSAM (Centro de Investigación en Red de Salud Mental), Carlos III Health Institute, Madrid 28029, Spain
- Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona 08907, Spain
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18
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Polosan M, Figee M. Electrical deep neuromodulation in psychiatry. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2021; 159:89-110. [PMID: 34446252 DOI: 10.1016/bs.irn.2021.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Addressing treatment refractoriness in psychiatric diseases is an essential public health objective. The last two decades have seen an increasing interest for deep brain stimulation (DBS) of several brain targets. In this chapter, we have reviewed the main DBS clinical trials in psychiatric diseases, mainly obsessive compulsive disorders (OCD) and depression, but also emerging research in other psychiatric disorders. While its efficacy and safety are confirmed, DBS is still not considered as standard therapy in psychiatry. However, advances in neuroimaging research combined to behavioral and electrophysiological data uniquely provided by DBS studies improve knowledge on physiopathology in these brain diseases. This will help define the optimal brain targets according to specific phenotype dimensions. Revealing the mechanisms of action and effects of DBS will support that its impact goes beyond a loco-regional brain stimulation and confirms that electrical neuromodulation influences brain networks. Added to the progress in neuromodulation technology, these insights will hopefully facilitate a more widespread application of this promising treatment. Future development of a personalized multimodal assessment of underlying dysfunctional brain networks will open new circuit-specific treatment perspectives that may facilitate better patient outcomes.
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Affiliation(s)
- Mircea Polosan
- Univ. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neurosciences, Grenoble, France.
| | - Martijn Figee
- Center for Advanced Circuit Therapeutics, Mount Sinai West, Icahn School of Medicine at Mount Sinai, New York, United States
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19
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Hageman SB, van Rooijen G, Bergfeld IO, Schirmbeck F, de Koning P, Schuurman PR, Denys D. Deep brain stimulation versus ablative surgery for treatment-refractory obsessive-compulsive disorder: A meta-analysis. Acta Psychiatr Scand 2021; 143:307-318. [PMID: 33492682 DOI: 10.1111/acps.13276] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 11/05/2020] [Accepted: 01/10/2021] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Ablative surgery (ABL) and deep brain stimulation (DBS) are last-resort treatment options for patients suffering from treatment-refractory obsessive-compulsive disorder (OCD). The aim of this study was to conduct an updated meta-analysis comparing the clinical outcomes of the ablative procedures capsulotomy and cingulotomy and deep brain stimulation. METHODS We conducted a PubMed search to identify all clinical trials on capsulotomy, cingulotomy, and DBS. Random effects meta-analyses were performed on 38 articles with a primary focus on efficacy in reducing OCD symptoms as measured by a reduction in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score and the responder rate (≥35% reduction in Y-BOCS score). RESULTS With responder rates of 48% and 53% after 12-16 months and 56% and 57% at last follow-up for ABL and DBS, respectively, and large effect sizes in the reduction in Y-BOCS scores, both surgical modalities show effectiveness in treating refractory OCD. Meta-regression did not show a statistically significant difference between ABL and DBS regarding these outcomes. Regarding adverse events, a statistically significant higher rate of impulsivity is reported in studies on DBS. CONCLUSION This meta-analysis shows equal efficacy of ABL and DBS in the treatment of refractory OCD. For now, the choice of intervention should, therefore, rely on factors such as risk of developing impulsivity, patient preferences, and experiences of psychiatrist and neurosurgeon. Future research should provide more insight regarding differences between ABL and DBS and response prediction following direct comparisons between the surgical modalities, to enable personalized and legitimate choices between ABL and DBS.
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Affiliation(s)
- Sarah Babette Hageman
- Department of Psychiatry, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Geeske van Rooijen
- Department of Psychiatry, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Isidoor O Bergfeld
- Department of Psychiatry, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Frederike Schirmbeck
- Department of Psychiatry, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.,Arkin Institute for Mental Health, Amsterdam, the Netherlands
| | - Pelle de Koning
- Department of Psychiatry, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - P Rick Schuurman
- Department of Neurosurgery, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Damiaan Denys
- Department of Psychiatry, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.,Amsterdam Neuroscience, Amsterdam, The Netherlands.,Amsterdam Brain and Cognition, University of Amsterdam, Amsterdam, The Netherlands.,The Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands
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20
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Paulo DL, Bick SK. Advanced Imaging in Psychiatric Neurosurgery: Toward Personalized Treatment. Neuromodulation 2021; 25:195-201. [PMID: 33788971 DOI: 10.1111/ner.13392] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 02/22/2021] [Accepted: 03/08/2021] [Indexed: 11/30/2022]
Abstract
OBJECTIVES Our aim is to review several recent landmark studies discussing the application of advanced neuroimaging to guide target selection in deep brain stimulation (DBS) for psychiatric disorders. MATERIALS AND METHODS We performed a PubMed literature search of articles related to psychiatric neurosurgery, DBS, diffusion tensor imaging, probabilistic tractography, functional magnetic resonance imaging (MRI), and blood oxygen level-dependent activation. Relevant articles were included in the review. RESULTS Recent advances in neuroimaging, namely the use of diffusion tensor imaging, probabilistic tractography, functional MRI, and Positron emission tomography have provided higher resolution depictions of structural and functional connectivity between regions of interest. Applying these imaging modalities to DBS has increased understanding of the mechanism of action of DBS from the single structure to network level, allowed for new DBS targets to be discovered, and allowed for individualized DBS targeting for psychiatric indications. CONCLUSIONS Advanced neuroimaging techniques may be especially important to guide personalized DBS targeting in psychiatric disorders such as treatment-resistant depression and obsessive-compulsive disorder where symptom profiles and underlying disordered circuitry are more heterogeneous. These articles suggest that advanced imaging can help to further individualize and optimize DBS, a promising next step in improving its efficacy.
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Affiliation(s)
- Danika L Paulo
- Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Sarah K Bick
- Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
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21
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Menchón JM, Real E, Alonso P, Aparicio MA, Segalas C, Plans G, Luyten L, Brunfaut E, Matthijs L, Raymakers S, Bervoets C, Higueras A, Katati M, Guerrero J, Hurtado M, Prieto M, Stieglitz LH, Löffelholz G, Walther S, Pollo C, Zurowski B, Tronnier V, Kordon A, Gambini O, Ranieri R, Franzini A, Messina G, Radu-Djurfeldt D, Schechtmann G, Chen LL, Eitan R, Israel Z, Bergman H, Brelje T, Brionne TC, Conseil A, Gielen F, Schuepbach M, Nuttin B, Gabriëls L. A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder. Mol Psychiatry 2021; 26:1234-1247. [PMID: 31664175 PMCID: PMC7985042 DOI: 10.1038/s41380-019-0562-6] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Revised: 09/30/2019] [Accepted: 10/12/2019] [Indexed: 02/07/2023]
Abstract
Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS.
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Affiliation(s)
- José M. Menchón
- grid.5841.80000 0004 1937 0247Bellvitge University Hospital-IDIBELL, University of Barcelona, CIBERSAM, Barcelona, Spain
| | - Eva Real
- grid.5841.80000 0004 1937 0247Bellvitge University Hospital-IDIBELL, University of Barcelona, CIBERSAM, Barcelona, Spain
| | - Pino Alonso
- grid.5841.80000 0004 1937 0247Bellvitge University Hospital-IDIBELL, University of Barcelona, CIBERSAM, Barcelona, Spain
| | - Marco Alberto Aparicio
- grid.5841.80000 0004 1937 0247Bellvitge University Hospital-IDIBELL, University of Barcelona, CIBERSAM, Barcelona, Spain
| | - Cinto Segalas
- grid.5841.80000 0004 1937 0247Bellvitge University Hospital-IDIBELL, University of Barcelona, CIBERSAM, Barcelona, Spain
| | - Gerard Plans
- grid.5841.80000 0004 1937 0247Bellvitge University Hospital-IDIBELL, University of Barcelona, CIBERSAM, Barcelona, Spain
| | - Laura Luyten
- grid.5596.f0000 0001 0668 7884KU Leuven and/or UZ Leuven and/or UPC KU Leuven, Leuven, Belgium
| | - Els Brunfaut
- grid.5596.f0000 0001 0668 7884KU Leuven and/or UZ Leuven and/or UPC KU Leuven, Leuven, Belgium
| | - Laurean Matthijs
- grid.5596.f0000 0001 0668 7884KU Leuven and/or UZ Leuven and/or UPC KU Leuven, Leuven, Belgium
| | - Simon Raymakers
- grid.5596.f0000 0001 0668 7884KU Leuven and/or UZ Leuven and/or UPC KU Leuven, Leuven, Belgium
| | - Chris Bervoets
- grid.5596.f0000 0001 0668 7884KU Leuven and/or UZ Leuven and/or UPC KU Leuven, Leuven, Belgium
| | - Antonio Higueras
- grid.411380.f0000 0000 8771 3783Hospital Virgen de las Nieves, Granada, Spain
| | - Majed Katati
- grid.411380.f0000 0000 8771 3783Hospital Virgen de las Nieves, Granada, Spain
| | - José Guerrero
- grid.411380.f0000 0000 8771 3783Hospital Virgen de las Nieves, Granada, Spain
| | - Mariena Hurtado
- grid.411380.f0000 0000 8771 3783Hospital Virgen de las Nieves, Granada, Spain
| | - Mercedes Prieto
- grid.411380.f0000 0000 8771 3783Hospital Virgen de las Nieves, Granada, Spain
| | | | - Georg Löffelholz
- grid.411656.10000 0004 0479 0855Inselspital Bern, Bern, Switzerland
| | - Sebastian Walther
- grid.411656.10000 0004 0479 0855Inselspital Bern, Bern, Switzerland ,grid.412559.e0000 0001 0694 3235Translational Research Center, University Hospital of Psychiatry, Bern, Switzerland
| | - Claudio Pollo
- grid.411656.10000 0004 0479 0855Inselspital Bern, Bern, Switzerland
| | - Bartosz Zurowski
- grid.412468.d0000 0004 0646 2097Universitätsklinik Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Volker Tronnier
- grid.412468.d0000 0004 0646 2097Universitätsklinik Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Andreas Kordon
- grid.5963.9Oberbergklinik Schwarzwald, Hornberg, and Universitätsklinikum Freiburg, Klinik für Psychiatrie und Psychotherapie, Freiburg, Germany
| | - Orsola Gambini
- grid.415093.aDepartment of Health Sciences, University of Milano, San Paolo Hospital Milano, Milano, Italy
| | - Rebecca Ranieri
- grid.415093.aDepartment of Health Sciences, University of Milano, San Paolo Hospital Milano, Milano, Italy
| | - Angelo Franzini
- Fondazione IRCCS Istituto Naz Neurologico C.Besta, Milano, Italy
| | - Giuseppe Messina
- Fondazione IRCCS Istituto Naz Neurologico C.Besta, Milano, Italy
| | - Diana Radu-Djurfeldt
- grid.24381.3c0000 0000 9241 5705Psykiatri Sydvast, OCD-departement, Karolinska University Hospital-region in Huddinge, Stockholm, Sweden
| | - Gaston Schechtmann
- grid.24381.3c0000 0000 9241 5705Department of Neurosurgery, Karolinska Institutet and University Hospital, Stockholm, Sweden
| | - Long-Long Chen
- grid.24381.3c0000 0000 9241 5705Department of Neurosurgery, Karolinska Institutet and University Hospital, Stockholm, Sweden
| | - Renana Eitan
- grid.17788.310000 0001 2221 2926Psychiatry Department, Hadassah-University Hospital, Jerusalem, Israel
| | - Zvi Israel
- grid.17788.310000 0001 2221 2926Psychiatry Department, Hadassah-University Hospital, Jerusalem, Israel
| | - Hagai Bergman
- grid.17788.310000 0001 2221 2926Psychiatry Department, Hadassah-University Hospital, Jerusalem, Israel
| | - Tim Brelje
- grid.419673.e0000 0000 9545 2456Medtronic, Minneapolis, USA
| | - Thomas C. Brionne
- grid.471158.e0000 0004 0384 6386Medtronic International Trading Sàrl, Tolochenaz, Switzerland
| | - Aurélie Conseil
- grid.471158.e0000 0004 0384 6386Medtronic International Trading Sàrl, Tolochenaz, Switzerland
| | - Frans Gielen
- grid.419671.c0000 0004 1771 1765Medtronic Bakken Research Center, Maastricht, The Netherlands
| | | | - Bart Nuttin
- grid.5596.f0000 0001 0668 7884KU Leuven and/or UZ Leuven and/or UPC KU Leuven, Leuven, Belgium
| | - Loes Gabriëls
- grid.5596.f0000 0001 0668 7884KU Leuven and/or UZ Leuven and/or UPC KU Leuven, Leuven, Belgium
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22
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Szechtman H, Harvey BH, Woody EZ, Hoffman KL. The Psychopharmacology of Obsessive-Compulsive Disorder: A Preclinical Roadmap. Pharmacol Rev 2020; 72:80-151. [PMID: 31826934 DOI: 10.1124/pr.119.017772] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
This review evaluates current knowledge about obsessive-compulsive disorder (OCD), with the goal of providing a roadmap for future directions in research on the psychopharmacology of the disorder. It first addresses issues in the description and diagnosis of OCD, including the structure, measurement, and appropriate description of the disorder and issues of differential diagnosis. Current pharmacotherapies for OCD are then reviewed, including monotherapy with serotonin reuptake inhibitors and augmentation with antipsychotic medication and with psychologic treatment. Neuromodulatory therapies for OCD are also described, including psychosurgery, deep brain stimulation, and noninvasive brain stimulation. Psychotherapies for OCD are then reviewed, focusing on behavior therapy, including exposure and response prevention and cognitive therapy, and the efficacy of these interventions is discussed, touching on issues such as the timing of sessions, the adjunctive role of pharmacotherapy, and the underlying mechanisms. Next, current research on the neurobiology of OCD is examined, including work probing the role of various neurotransmitters and other endogenous processes and etiology as clues to the neurobiological fault that may underlie OCD. A new perspective on preclinical research is advanced, using the Research Domain Criteria to propose an adaptationist viewpoint that regards OCD as the dysfunction of a normal motivational system. A systems-design approach introduces the security motivation system (SMS) theory of OCD as a framework for research. Finally, a new perspective on psychopharmacological research for OCD is advanced, exploring three approaches: boosting infrastructure facilities of the brain, facilitating psychotherapeutic relearning, and targeting specific pathways of the SMS network to fix deficient SMS shut-down processes. SIGNIFICANCE STATEMENT: A significant proportion of patients with obsessive-compulsive disorder (OCD) do not achieve remission with current treatments, indicating the need for innovations in psychopharmacology for the disorder. OCD may be conceptualized as the dysfunction of a normal, special motivation system that evolved to manage the prospect of potential danger. This perspective, together with a wide-ranging review of the literature, suggests novel directions for psychopharmacological research, including boosting support systems of the brain, facilitating relearning that occurs in psychotherapy, and targeting specific pathways in the brain that provide deficient stopping processes in OCD.
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Affiliation(s)
- Henry Szechtman
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada (H.S.); SAMRC Unit on Risk Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, and Center of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University (Potchefstroom Campus), Potchefstroom, South Africa (B.H.H.); Department of Psychology, University of Waterloo, Waterloo, Ontario, Canada (E.Z.W.); and Centro de Investigación en Reproducción Animal, CINVESTAV-Universidad Autónoma de Tlaxcala, Tlaxcala, Mexico (K.L.H.)
| | - Brian H Harvey
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada (H.S.); SAMRC Unit on Risk Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, and Center of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University (Potchefstroom Campus), Potchefstroom, South Africa (B.H.H.); Department of Psychology, University of Waterloo, Waterloo, Ontario, Canada (E.Z.W.); and Centro de Investigación en Reproducción Animal, CINVESTAV-Universidad Autónoma de Tlaxcala, Tlaxcala, Mexico (K.L.H.)
| | - Erik Z Woody
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada (H.S.); SAMRC Unit on Risk Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, and Center of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University (Potchefstroom Campus), Potchefstroom, South Africa (B.H.H.); Department of Psychology, University of Waterloo, Waterloo, Ontario, Canada (E.Z.W.); and Centro de Investigación en Reproducción Animal, CINVESTAV-Universidad Autónoma de Tlaxcala, Tlaxcala, Mexico (K.L.H.)
| | - Kurt Leroy Hoffman
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada (H.S.); SAMRC Unit on Risk Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, and Center of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University (Potchefstroom Campus), Potchefstroom, South Africa (B.H.H.); Department of Psychology, University of Waterloo, Waterloo, Ontario, Canada (E.Z.W.); and Centro de Investigación en Reproducción Animal, CINVESTAV-Universidad Autónoma de Tlaxcala, Tlaxcala, Mexico (K.L.H.)
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23
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Deep Brain Stimulation for Major Depression and Obsessive-Compulsive Disorder—Discontinuation of Ongoing Stimulation. PSYCH 2020. [DOI: 10.3390/psych2030015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Deep brain stimulation (DBS) is currently under research for the treatment of psychiatric disorders, e.g., obsessive-compulsive disorder (OCD) and treatment-resistant depression (TRD). Since the application of DBS in psychiatry has been in use for about 20 years, it is necessary to evaluate its long-term use now. A main issue in the long-term treatment of DBS concerns the effects of a discontinuation of stimulation due to intended as well as unintended reasons. In this contribution, the literature describing discontinuation effects following DBS in OCD and TRD is reviewed. Furthermore, a patient is reported in depth who experienced an unintended discontinuation of supero-lateral medial forebrain bundle (slMFB) DBS for TRD. In this case, the battery was fully depleted without the patient noticing. DBS had led to a sustained response for seven years before discontinuation of stimulation for just several weeks caused a progressive worsening of depression. Altogether, the rapid occurrence of symptom worsening, the absence of a notification about the stimulation status and the difficulties to recapture antidepressant response represent important safety aspects. For a further understanding of the described effects, time courses until worsening of depression as well as biological mechanisms need to be investigated in double-blind controlled trials.
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24
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Emotions Modulate Subthalamic Nucleus Activity: New Evidence in Obsessive-Compulsive Disorder and Parkinson's Disease Patients. BIOLOGICAL PSYCHIATRY: COGNITIVE NEUROSCIENCE AND NEUROIMAGING 2020; 6:556-567. [PMID: 33060034 DOI: 10.1016/j.bpsc.2020.08.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 08/05/2020] [Accepted: 08/06/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Subthalamic nucleus (STN) deep brain stimulation alleviates obsessive-compulsive disorder (OCD) symptoms, suggesting that this basal ganglia structure may play a key role in integrating limbic and motor information. We explored the modulation of STN neural activity by visual emotional information under different motor demands. METHODS We compared STN local field potentials acquired in 7 patients with OCD and 15 patients with Parkinson's disease off and on levodopa while patients categorized pictures as unpleasant, pleasant, or neutral and pressed a button for 1 of these 3 categories depending on the instruction. RESULTS During image presentation, theta power increased for unpleasant compared with neutral images in both patients with OCD and patients with Parkinson's disease. Only in patients with OCD was theta power also increased in pleasant compared with neutral trials. During the button press in patients with OCD, no modification of STN activity was seen on average, but theta power increased when the image triggering the motor response was unpleasant. Conversely, in patients with Parkinson's disease, a beta decrease was observed during the button press unrelated to the valence of the stimulus. Finally, in patients with OCD, a significant positive relationship was observed between the amplitude of the emotionally related theta response and symptom severity (measured using the Yale-Brown Obsessive Compulsive Scale). CONCLUSIONS We highlighted modulations of STN theta band activity related to emotions that were specific to OCD and correlated with OCD symptom severity. STN theta-induced activity might therefore underlie dysfunction of the limbic STN and its related network leading to OCD pathophysiology.
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25
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Görmezoğlu M, Bouwens van der Vlis T, Schruers K, Ackermans L, Polosan M, Leentjens AF. Effectiveness, Timing and Procedural Aspects of Cognitive Behavioral Therapy after Deep Brain Stimulation for Therapy-Resistant Obsessive Compulsive Disorder: A Systematic Review. J Clin Med 2020; 9:jcm9082383. [PMID: 32722565 PMCID: PMC7464329 DOI: 10.3390/jcm9082383] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 07/21/2020] [Accepted: 07/22/2020] [Indexed: 02/07/2023] Open
Abstract
Background and aim: Deep brain stimulation (DBS) is an effective treatment for patients with severe therapy-resistant obsessive-compulsive disorder (OCD). After initiating DBS many patients still require medication and/or behavioral therapy to deal with persisting symptoms and habitual behaviors. The clinical practice of administering postoperative cognitive behavioral therapy (CBT) varies widely, and there are no clinical guidelines for this add-on therapy. The aim of this review is to assess the efficacy, timing and procedural aspects of postoperative CBT in OCD patients treated with DBS. Method: Systematic review of literature. Results: The search yielded 5 original studies, one case series and three reviews. Only two clinical trials have explicitly focused on the effectiveness of CBT added to DBS in patients with therapy-resistant OCD. These two studies both showed effectiveness of CBT. However, they had a distinctly different design, very small sample sizes and different ways of administering the therapy. Therefore, no firm conclusions can be drawn or recommendations made for administering CBT after DBS for therapy-resistant OCD. Conclusion: The effectiveness, timing and procedural aspects of CBT added to DBS in therapy-resistant OCD have hardly been studied. Preliminary evidence indicates that CBT has an added effect in OCD patients being treated with DBS. Since the overall treatment effect is the combined result of DBS, medication and CBT, future trials should be designed in such a way that they allow quantification of the effects of these add-on therapies in OCD patients treated with DBS. Only in this way information can be gathered that contributes to the development of an algorithm and clinical guidelines for concomittant therapies to optimize treatment effects in OCD patients being treated with DBS.
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Affiliation(s)
- Meltem Görmezoğlu
- Department of Psychiatry, Ondokuz Mayıs University, 55270 Samsun, Turkey;
- Department of Neurosurgery, Maastricht University Medical Centre, 6229 Maastricht, The Netherlands; (T.B.v.d.V.); (L.A.)
| | - Tim Bouwens van der Vlis
- Department of Neurosurgery, Maastricht University Medical Centre, 6229 Maastricht, The Netherlands; (T.B.v.d.V.); (L.A.)
| | - Koen Schruers
- Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, 6229 Maastricht, The Netherlands;
- School of Mental Health and Neuroscience, Maastricht University, 6229 Maastricht, The Netherlands
| | - Linda Ackermans
- Department of Neurosurgery, Maastricht University Medical Centre, 6229 Maastricht, The Netherlands; (T.B.v.d.V.); (L.A.)
- School of Mental Health and Neuroscience, Maastricht University, 6229 Maastricht, The Netherlands
| | - Mircea Polosan
- Grenoble Institute of Neurosciences, University of Grenoble Alpes, 38058 Grenoble, France;
| | - Albert F.G. Leentjens
- Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, 6229 Maastricht, The Netherlands;
- School of Mental Health and Neuroscience, Maastricht University, 6229 Maastricht, The Netherlands
- Correspondence:
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26
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Lehto LJ, Canna A, Wu L, Sierra A, Zhurakovskaya E, Ma J, Pearce C, Shaio M, Filip P, Johnson MD, Low WC, Gröhn O, Tanila H, Mangia S, Michaeli S. Orientation selective deep brain stimulation of the subthalamic nucleus in rats. Neuroimage 2020; 213:116750. [PMID: 32198048 DOI: 10.1016/j.neuroimage.2020.116750] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Revised: 02/22/2020] [Accepted: 03/13/2020] [Indexed: 11/28/2022] Open
Abstract
Deep brain stimulation (DBS) has become an important tool in the management of a wide spectrum of diseases in neurology and psychiatry. Target selection is a vital aspect of DBS so that only the desired areas are stimulated. Segmented leads and current steering have been shown to be promising additions to DBS technology enabling better control of the stimulating electric field. Recently introduced orientation selective DBS (OS-DBS) is a related development permitting sensitization of the stimulus to axonal pathways with different orientations by freely controlling the primary direction of the electric field using multiple contacts. Here, we used OS-DBS to stimulate the subthalamic nucleus (STN) in healthy rats while simultaneously monitoring the induced brain activity with fMRI. Maximal activation of the sensorimotor and basal ganglia-thalamocortical networks was observed when the electric field was aligned mediolaterally in the STN pointing in the lateral direction, while no cortical activation was observed with the electric field pointing medially to the opposite direction. Such findings are consistent with mediolateral main direction of the STN fibers, as seen with high resolution diffusion imaging and histology. The asymmetry of the OS-DBS dipolar field distribution using three contacts along with the potential stimulation of the internal capsule, are also discussed. We conclude that OS-DBS offers an additional degree of flexibility for optimization of DBS of the STN which may enable a better treatment response.
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Affiliation(s)
- Lauri J Lehto
- Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA
| | - Antonietta Canna
- Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA; Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, Salerno, Italy
| | - Lin Wu
- Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA
| | - Alejandra Sierra
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
| | - Ekaterina Zhurakovskaya
- Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
| | - Jun Ma
- Department of Neurosurgery, University of Minnesota, Minneapolis, USA
| | - Clairice Pearce
- Department of Neurosurgery, University of Minnesota, Minneapolis, USA
| | - Maple Shaio
- Department of Neurosurgery, University of Minnesota, Minneapolis, USA
| | - Pavel Filip
- Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA; First Department of Neurology, Faculty of Medicine, Masaryk University and University Hospital of St. Anne, Brno, Czech Republic
| | - Matthew D Johnson
- Department of Biomedical Engineering, University of Minnesota, Minneapolis, USA
| | - Walter C Low
- Department of Neurosurgery, University of Minnesota, Minneapolis, USA
| | - Olli Gröhn
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
| | - Heikki Tanila
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
| | - Silvia Mangia
- Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA
| | - Shalom Michaeli
- Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA.
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27
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Corripio I, Roldán A, Sarró S, McKenna PJ, Alonso-Solís A, Rabella M, Díaz A, Puigdemont D, Pérez-Solà V, Álvarez E, Arévalo A, Padilla PP, Ruiz-Idiago JM, Rodríguez R, Molet J, Pomarol-Clotet E, Portella MJ. Deep brain stimulation in treatment resistant schizophrenia: A pilot randomized cross-over clinical trial. EBioMedicine 2020; 51:102568. [PMID: 31927311 PMCID: PMC6953640 DOI: 10.1016/j.ebiom.2019.11.029] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Accepted: 11/18/2019] [Indexed: 01/11/2023] Open
Abstract
Background Up to 30% of patients with schizophrenia are resistant to antipsychotic drug treatment, with 60% of such cases also failing to respond to clozapine. Deep brain stimulation (DBS) has been used in treatment resistant patients with other psychiatric disorders, but there is a lack of trials in schizophrenia, partly due to uncertainties over where to site the electrodes. This trial aimed to examine the effectiveness of nucleus accumbens (NAcc) and subgenual anterior cingulate cortex (subgenual ACC) targeted DBS; the primary outcome measure was PANSS total score, as assessed fortnightly. Methods Eight patients with schizophrenia, who met criteria for treatment resistance and were also resistant to/intolerant of clozapine, were randomly assigned using central allocation to receive DBS in the NAcc or subgenual ACC. An open stabilization phase lasting at least six months was followed by a randomized double-blind crossover phase lasting 24 weeks in those who met symptomatic improvement criteria. The primary end-point was a 25% improvement in PANSS total score. (ClinicalTrials.gov Identifier: NCT02377505; trial completed). Findings One implanted patient did not receive DBS due to complications of surgery. Of the remaining 7 patients, 2/3 with NAcc and 2/4 with subgenual ACC electrode placements met the symptomatic improvement criteria (58% and 86%, and 37% and 68% improvement in PANSS total score, respectively). Three of these patients entered the crossover phase and all showed worsening when the stimulation was discontinued. The fourth patient worsened after the current was switched off accidentally without her or the investigators’ knowledge. Physical adverse events were uncommon, but two patients developed persistent psychiatric adverse effects (negative symptoms/apathy and mood instability, respectively). Interpretation These preliminary findings point to the possibility of DBS having therapeutic effects in patients with schizophrenia who do not respond to any other treatment. Larger trials with careful attention to blinding will be necessary to establish the extent of the benefits and whether these can be achieved without psychiatric side-effects.
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Affiliation(s)
- Iluminada Corripio
- Psychiatry Department, Institut d'Investigació Biomèdica-Sant Pau (IIB-SANT PAU), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
| | - Alexandra Roldán
- Psychiatry Department, Institut d'Investigació Biomèdica-Sant Pau (IIB-SANT PAU), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - Salvador Sarró
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, C/. Dr. Antoni Pujadas 38, 08830 Sant Boi de Llobregat, Barcelona, Spain; Psychiatry Department, Benito Menni CASM Hermanas Hospitalarias, Sant Boi de Llobregat, Spain
| | - Peter J McKenna
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, C/. Dr. Antoni Pujadas 38, 08830 Sant Boi de Llobregat, Barcelona, Spain.
| | - Anna Alonso-Solís
- Psychiatry Department, Institut d'Investigació Biomèdica-Sant Pau (IIB-SANT PAU), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
| | - Mireia Rabella
- Psychiatry Department, Institut d'Investigació Biomèdica-Sant Pau (IIB-SANT PAU), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
| | - Anna Díaz
- Psychiatry Department, Institut d'Investigació Biomèdica-Sant Pau (IIB-SANT PAU), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - Dolors Puigdemont
- Psychiatry Department, Institut d'Investigació Biomèdica-Sant Pau (IIB-SANT PAU), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
| | - Víctor Pérez-Solà
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Psychiatry Department, Institut de Neuropsiquiatria i Addicions, Hospital del Mar, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - Enric Álvarez
- Psychiatry Department, Institut d'Investigació Biomèdica-Sant Pau (IIB-SANT PAU), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
| | - Antonio Arévalo
- FIDMAG Germanes Hospitalàries Research Foundation, C/. Dr. Antoni Pujadas 38, 08830 Sant Boi de Llobregat, Barcelona, Spain; Psychiatry Department, Hospital Sagrat Cor Hermanas Hospitalarias, Barcelona, Spain
| | - Pedro P Padilla
- FIDMAG Germanes Hospitalàries Research Foundation, C/. Dr. Antoni Pujadas 38, 08830 Sant Boi de Llobregat, Barcelona, Spain; Psychiatry Department, Centro Neuropsiquiátrico Nuestra Señora del Carmen Hermanas Hospitalarias, Zaragoza, Spain
| | - Jesus M Ruiz-Idiago
- FIDMAG Germanes Hospitalàries Research Foundation, C/. Dr. Antoni Pujadas 38, 08830 Sant Boi de Llobregat, Barcelona, Spain; Unitat Polivalent Barcelona Nord Hospital, Hospital Mare de Déu de la Mercè Hermanas Hospitalarias, Barcelona, Spain
| | - Rodrigo Rodríguez
- Neurosurgery Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - Joan Molet
- Neurosurgery Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - Edith Pomarol-Clotet
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, C/. Dr. Antoni Pujadas 38, 08830 Sant Boi de Llobregat, Barcelona, Spain
| | - Maria J Portella
- Psychiatry Department, Institut d'Investigació Biomèdica-Sant Pau (IIB-SANT PAU), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
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Vicheva P, Butler M, Shotbolt P. Deep brain stimulation for obsessive-compulsive disorder: A systematic review of randomised controlled trials. Neurosci Biobehav Rev 2020; 109:129-138. [PMID: 31923474 DOI: 10.1016/j.neubiorev.2020.01.007] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 12/22/2019] [Accepted: 01/06/2020] [Indexed: 12/26/2022]
Abstract
Deep brain stimulation (DBS) is considered a promising intervention for treatment-resistant obsessive-compulsive disorder (trOCD). We conducted a systematic search to investigate the efficacy and safety of DBS for OCD. Primary outcomes included the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), adverse events (AE), and quality of life. We assessed affective state, global functioning, cognition, and tolerability as secondary outcomes. Eight studies comprising 80 patients with trOCD were analysed both individually and collectively. We found a pooled mean reduction in Y-BOCS of 38.68 %, indicating DBS could be considered an effective therapy for trOCD. Most AE were mild and transient, however there were five severe surgery-related AE: intracerebral haemorrhage in three patients and infection in two. Mood-related serious AE were one completed suicide, three suicide attempts in two patients, and suicidal thoughts and depression in four. Despite this, affective state improved following stimulation. Despite being limited by significant heterogeneity across studies, our review has shown DBS to be an effective treatment in otherwise trOCD. There is a need to standardise study methodology in future research.
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Affiliation(s)
- Petya Vicheva
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
| | - Matthew Butler
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Psychiatry, South London and Maudsley NHS Foundation Trust, London, UK
| | - Paul Shotbolt
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Psychiatry, South London and Maudsley NHS Foundation Trust, London, UK
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29
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Dell'Osso B, Cremaschi L, Oldani L, Altamura AC. New Directions in the Use of Brain Stimulation Interventions in Patients with Obsessive-Compulsive Disorder. Curr Med Chem 2019; 25:5712-5721. [PMID: 28474552 DOI: 10.2174/0929867324666170505113631] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2016] [Revised: 03/20/2017] [Accepted: 04/23/2017] [Indexed: 01/03/2023]
Abstract
Obsessive-Compulsive Disorder (OCD) is a highly disabling condition with early onset and chronic course in most of the affected patients. In addition, OCD may show high comorbidity and suicide attempt rates, which worsen the overall burden of the disease for patients and their caregivers. First-line treatments for OCD consist of pro-serotonergic compounds and cognitive-behavioral therapy. Nonetheless, many patients show only limited benefit from such interventions and require additional "next-step" interventions, including augmentative antipsychotics and glutamate-modulating agents. Based on the knowledge about altered neurocircuitry in OCD, brain stimulation techniques, including transcranial magnetic and electrical stimulations (TMS and tDCS) and deep brain stimulation (DBS), have been increasingly investigated over the last decade, revealing positive results for otherwise intractable and treatment-refractory patients. Available evidence in the field is in continuous evolution and professionals actively involved in the management of OCD patients, psychiatrists in particular, need to be updated about latest developments. Through the analysis of controlled studies, meta-analyses, and International treatment guidelines, the present article is aimed at providing the state of the art on the use of brain stimulation techniques for the treatment of OCD.
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Affiliation(s)
- Bernardo Dell'Osso
- Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.,Department of Psychiatry and Behavioral Sciences, Bipolar Disorders Clinic, Stanford University, CA, United States
| | - Laura Cremaschi
- Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Lucio Oldani
- Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - A Carlo Altamura
- Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
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30
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Albert U, Marazziti D, Di Salvo G, Solia F, Rosso G, Maina G. A Systematic Review of Evidence-based Treatment Strategies for Obsessive- compulsive Disorder Resistant to first-line Pharmacotherapy. Curr Med Chem 2019; 25:5647-5661. [PMID: 29278206 DOI: 10.2174/0929867325666171222163645] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 10/19/2017] [Accepted: 11/22/2017] [Indexed: 01/04/2023]
Abstract
BACKGROUND Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). However, a significant proportion of patients do not respond satisfactorily to first-choice treatments. Several options have been investigated for the management of resistant patients. OBJECTIVE The aim of the present paper is to systematically review the available literature concerning the strategies for the treatment of resistant adult patients with OCD. METHOD We first reviewed studies concerning the definition of treatment-resistant OCD; we then analyzed results of studies evaluating several different strategies in resistant patients. We limited our review to double-blind, placebo-controlled studies performed in adult patients with OCD whose resistance to a first adequate (in terms of duration and dosage) SRI trial was documented and where outcome was clearly defined in terms of decrease in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores and/or response/ remission rates (according to the YBOCS). RESULTS We identified five strategies supported by positive results in placebo-controlled randomized studies: 1) antipsychotic addition to SRIs (16 RCTs, of them 10 positive; 4 head-to-head RCTs); among antipsychotics, available RCTs examined the addition of haloperidol (butyrophenone), pimozide (diphenyl-butylpiperidine), risperidone (SDA: serotonin- dopamine antagonist), paliperidone (SDA), olanzapine (MARTA: multi-acting receptor targeted antipsychotic), quetiapine (MARTA) and aripiprazole (partial dopamine agonist); 2) CBT addition to medication (2 positive RCTs); 3) switch to intravenous clomipramine (SRI) administration (2 positive RCTs); 4) switch to paroxetine (SSRI: selective serotonin reuptake inhibitor) or venlafaxine (SNRI: serotonin-norepinephrine reuptake inhibitor) when the first trial was negative (1 positive RCT); and 5) the addition of medications other than an antipsychotic to SRIs (18 RCTs performed with several different compounds, with only 4 positive studies). CONCLUSION Treatment-resistant OCD remains a significant challenge to psychiatrists. To date, the most effective strategy is the addition of antipsychotics (aripiprazole and risperidone) to SRIs; another effective strategy is CBT addition to medications. Other strategies, such as the switch to another first-line treatment or the switch to intravenous administration are promising but need further confirmation in double-blind studies. The addition of medications other than antipsychotics remains to be studied, as several negative studies exist and positive ones need confirmation (only 1 positive study).
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Affiliation(s)
- Umberto Albert
- Rita Levi Montalcini Department of Neuroscience, University of Turin, Italy; A.O.U. San Luigi Gonzaga of Orbassano, Turin, Italy
| | - Donatella Marazziti
- Dipartimento di Medicina Clinica e Sperimentale, Section of Psychiatry, University of Pisa, Pisa, Italy
| | - Gabriele Di Salvo
- Rita Levi Montalcini Department of Neuroscience, University of Turin, Italy; A.O.U. San Luigi Gonzaga of Orbassano, Turin, Italy
| | - Francesca Solia
- Rita Levi Montalcini Department of Neuroscience, University of Turin, Italy; A.O.U. San Luigi Gonzaga of Orbassano, Turin, Italy
| | - Gianluca Rosso
- Rita Levi Montalcini Department of Neuroscience, University of Turin, Italy; A.O.U. San Luigi Gonzaga of Orbassano, Turin, Italy
| | - Giuseppe Maina
- Rita Levi Montalcini Department of Neuroscience, University of Turin, Italy; A.O.U. San Luigi Gonzaga of Orbassano, Turin, Italy
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31
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Neural circuits in goal-directed and habitual behavior: Implications for circuit dysfunction in obsessive-compulsive disorder. Neurochem Int 2019; 129:104464. [DOI: 10.1016/j.neuint.2019.104464] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Revised: 04/11/2019] [Accepted: 05/09/2019] [Indexed: 01/04/2023]
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32
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The effects of deep-brain non-stimulation in severe obsessive-compulsive disorder: an individual patient data meta-analysis. Transl Psychiatry 2019; 9:183. [PMID: 31383848 PMCID: PMC6683131 DOI: 10.1038/s41398-019-0522-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 05/28/2019] [Accepted: 06/20/2019] [Indexed: 01/13/2023] Open
Abstract
Non-intervention-related effects have long been recognized in an array of medical interventions, to which surgical procedures like deep-brain stimulation are no exception. While the existence of placebo and micro-lesion effects has been convincingly demonstrated in DBS for major depression and Parkinson's disease, systematic investigations for obsessive-compulsive disorder (OCD) are currently lacking. We therefore undertook an individual patient data meta-analysis with the aim of quantifying the effect of DBS for severe, treatment-resistant OCD that is not due to the electrical stimulation of brain tissue. The MEDLINE/PubMed database was searched for double-blind, sham-controlled randomized clinical trials published in English between 1998 and 2018. Individual patient data was obtained from the original authors and combined in a meta-analysis. We assessed differences from baseline in obsessive-compulsive symptoms following sham treatment, as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Four studies met the inclusion criteria, randomizing 49 patients to two periods of active or sham stimulation. To preclude confounding by period effects, our estimate was based only on data from those patients who underwent sham stimulation first (n = 24). We found that sham stimulation induced a significant change in the Y-BOCS score (t = -3.15, P < 0.005), lowering it by 4.9 ± 1.6 points [95% CI = (-8.0, -1.8)]. We conclude that non-stimulation-related effects of DBS exist also in OCD. The identification of the factors determining the magnitude and occurrence of these effects will help to design strategies that will ultimately lead to a betterment of future randomized clinical trials.
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Niemann M, Schneider GH, Kühn A, Vajkoczy P, Faust K. Clinical Efficacy of Bilateral Deep Brain Stimulation Does Not Change After Implantable Pulse Generator Replacement but the Impedances Do: A Prospective Study. Neuromodulation 2019; 23:530-536. [PMID: 31323173 DOI: 10.1111/ner.13022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Revised: 05/13/2019] [Accepted: 06/12/2019] [Indexed: 01/01/2023]
Abstract
BACKGROUND Deep brain stimulation (DBS) is an approved therapy option for movement disorders such as Parkinson's disease (PD), essential Tremor (ET), and dystonia. While current research focuses on rechargeable implantable pulse generators (IPGs), little is known about changes of the motor functions after IPG replacement and the consequences of additionally implanted hardware. OBJECTIVE To assess changes of the motor functions, the therapy impedances, and the total electric energy delivered (TEED) after elective IPG replacement. METHODS We prospectively acquired the data of 47 patients with PD, ET, and dystonia treated with bilateral DBS. Motor functions were rated prior to and after surgery using the revised Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III), the Fahn-Tolosa-Marin Tremor-Rating-Scale (FTM-TRS), and the Unified Dystonia Rating Scale (UDRS). Furthermore, the therapy impedances and TEED were assessed at the aforementioned times. RESULTS While preoperative motor scores were 48.32 ± 17.16 in PD, 39.71 ± 12.28 in ET, and 18.48 ± 16.30 in dystonia patients, postoperative scores were 47.84 ± 24.33, 32.86 ± 15.82, and 15.02 ± 15.17, respectively. Only in dystonia patients, motor scores significantly differed. Perioperative therapy impedance changes were 142.66 ± 105.35 Ω (Kinetra® to Activa® PC), -68.75 ± 43.05 Ω (Activa® PC to Activa® PC), and - 51.38 ± 38.75 Ω (Activa® PC to Activa® RC). Perioperative TEED changes were - 37.15 ± 38.87 μJ, 2.03 ± 35.91 μJ, and 12.39 ± 6.31 μJ in that first, second, and third group, respectively. Both the therapy impedances and TEED significantly differed between groups. CONCLUSION Although there were no statistically significant changes in the motor functions of all patients after elective IPG replacement, the therapy impedances were significantly higher and TEED was significantly lower after IPG replacement with concurrent Pocket Adapter implantation.
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Affiliation(s)
- Marcel Niemann
- Department of Neurosurgery, Charité University Medicine Berlin, Berlin, Germany
| | | | - Andrea Kühn
- Department of Neurology, Charité University Medicine Berlin, Berlin, Germany
| | - Peter Vajkoczy
- Department of Neurosurgery, Charité University Medicine Berlin, Berlin, Germany
| | - Katharina Faust
- Department of Neurosurgery, Charité University Medicine Berlin, Berlin, Germany
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Provenza NR, Matteson ER, Allawala AB, Barrios-Anderson A, Sheth SA, Viswanathan A, McIngvale E, Storch EA, Frank MJ, McLaughlin NCR, Cohn JF, Goodman WK, Borton DA. The Case for Adaptive Neuromodulation to Treat Severe Intractable Mental Disorders. Front Neurosci 2019; 13:152. [PMID: 30890909 PMCID: PMC6412779 DOI: 10.3389/fnins.2019.00152] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Accepted: 02/11/2019] [Indexed: 12/20/2022] Open
Abstract
Mental disorders are a leading cause of disability worldwide, and available treatments have limited efficacy for severe cases unresponsive to conventional therapies. Neurosurgical interventions, such as lesioning procedures, have shown success in treating refractory cases of mental illness, but may have irreversible side effects. Neuromodulation therapies, specifically Deep Brain Stimulation (DBS), may offer similar therapeutic benefits using a reversible (explantable) and adjustable platform. Early DBS trials have been promising, however, pivotal clinical trials have failed to date. These failures may be attributed to targeting, patient selection, or the “open-loop” nature of DBS, where stimulation parameters are chosen ad hoc during infrequent visits to the clinician’s office that take place weeks to months apart. Further, the tonic continuous stimulation fails to address the dynamic nature of mental illness; symptoms often fluctuate over minutes to days. Additionally, stimulation-based interventions can cause undesirable effects if applied when not needed. A responsive, adaptive DBS (aDBS) system may improve efficacy by titrating stimulation parameters in response to neural signatures (i.e., biomarkers) related to symptoms and side effects. Here, we present rationale for the development of a responsive DBS system for treatment of refractory mental illness, detail a strategic approach for identification of electrophysiological and behavioral biomarkers of mental illness, and discuss opportunities for future technological developments that may harness aDBS to deliver improved therapy.
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Affiliation(s)
- Nicole R Provenza
- Brown University School of Engineering, Providence, RI, United States.,Charles Stark Draper Laboratory, Cambridge, MA, United States
| | - Evan R Matteson
- Brown University School of Engineering, Providence, RI, United States
| | - Anusha B Allawala
- Brown University School of Engineering, Providence, RI, United States
| | - Adriel Barrios-Anderson
- Psychiatric Neurosurgery Program at Butler Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, United States
| | - Sameer A Sheth
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | - Ashwin Viswanathan
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
| | - Elizabeth McIngvale
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, United States
| | - Eric A Storch
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, United States
| | - Michael J Frank
- Department of Cognitive, Linguistic, and Psychological Sciences, Brown University, Providence, RI, United States.,Department of Psychology, University of Pittsburgh, Pittsburgh, PA, United States
| | - Nicole C R McLaughlin
- Psychiatric Neurosurgery Program at Butler Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, United States
| | - Jeffrey F Cohn
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA, United States
| | - Wayne K Goodman
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, United States
| | - David A Borton
- Brown University School of Engineering, Providence, RI, United States.,Carney Institute for Brain Science, Brown University, Providence, RI, United States.,Department of Veterans Affairs, Providence Medical Center, Center for Neurorestoration and Neurotechnology, Providence, RI, United States
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35
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Senova S, Clair AH, Palfi S, Yelnik J, Domenech P, Mallet L. Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder: Towards an Individualized Approach. Front Psychiatry 2019; 10:905. [PMID: 31920754 PMCID: PMC6923766 DOI: 10.3389/fpsyt.2019.00905] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2019] [Accepted: 11/15/2019] [Indexed: 12/19/2022] Open
Abstract
Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder featuring repetitive intrusive thoughts and behaviors associated with a significant handicap. Of patients, 20% are refractory to medication and cognitive behavioral therapy. Refractory OCD is associated with suicidal behavior and significant degradation of social and professional functioning, with high health costs. Deep brain stimulation (DBS) has been proposed as a reversible and controllable method to treat refractory patients, with meta-analyses showing 60% response rate following DBS, whatever the target: anterior limb of the internal capsule (ALIC), ventral capsule/ventral striatum (VC/VS), nucleus accumbens (NAcc), anteromedial subthalamic nucleus (amSTN), or inferior thalamic peduncle (ITP). But how do we choose the "best" target? Functional neuroimaging studies have shown that ALIC-DBS requires the modulation of the fiber tract within the ventral ALIC via the ventral striatum, bordering the bed nucleus of the stria terminalis and connecting the medial prefrontal cortex with the thalamus to be successful. VC/VS effective sites of stimulation were found within the VC and primarily connected to the medial orbitofrontal cortex (OFC) dorsomedial thalamus, amygdala, and the habenula. NAcc-DBS has been found to reduce OCD symptoms by decreasing excessive fronto-striatal connectivity between NAcc and the lateral and medial prefrontal cortex. The amSTN effective stimulation sites are located at the inferior medial border of the STN, primarily connected to lateral OFC, dorsal anterior cingulate, and dorsolateral prefrontal cortex. Finally, ITP-DBS recruits a bidirectional fiber pathway between the OFC and the thalamus. Thus, these functional connectivity studies show that the various DBS targets lie within the same diseased neural network. They share similar efficacy profiles on OCD symptoms as estimated on the Y-BOCS, the amSTN being the target supported by the strongest evidence in the literature. VC/VS-DBS, amSTN-DBS, and ALIC-DBS were also found to improve mood, behavioral adaptability and potentially both, respectively. Because OCD is such a heterogeneous disease with many different symptom dimensions, the ultimate aim should be to find the most appropriate DBS target for a given refractory patient. This quest will benefit from further investigation and understanding of the individual functional connectivity of OCD patients.
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Affiliation(s)
- Suhan Senova
- AP-HP, Groupe Hospitalier Henri-Mondor, DHU PePsy, Neurosurgery, Psychiatry and Addictology departments, Créteil, France.,Université Paris Est Creteil, Faculté de Médecine, Créteil, France.,IMRB UPEC/INSERM U 955 Team 14, Créteil, France
| | - Anne-Hélène Clair
- Sorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, Institut du Cerveau et de la Moelle épinière, Paris, France
| | - Stéphane Palfi
- AP-HP, Groupe Hospitalier Henri-Mondor, DHU PePsy, Neurosurgery, Psychiatry and Addictology departments, Créteil, France.,Université Paris Est Creteil, Faculté de Médecine, Créteil, France.,IMRB UPEC/INSERM U 955 Team 14, Créteil, France
| | - Jérôme Yelnik
- Sorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, Institut du Cerveau et de la Moelle épinière, Paris, France
| | - Philippe Domenech
- AP-HP, Groupe Hospitalier Henri-Mondor, DHU PePsy, Neurosurgery, Psychiatry and Addictology departments, Créteil, France.,Université Paris Est Creteil, Faculté de Médecine, Créteil, France.,Sorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, Institut du Cerveau et de la Moelle épinière, Paris, France
| | - Luc Mallet
- AP-HP, Groupe Hospitalier Henri-Mondor, DHU PePsy, Neurosurgery, Psychiatry and Addictology departments, Créteil, France.,Université Paris Est Creteil, Faculté de Médecine, Créteil, France.,Sorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, Institut du Cerveau et de la Moelle épinière, Paris, France.,Department of Mental Health and Psychiatry, Global Health Institute, University of Geneva, Geneva, Switzerland
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36
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Fontenelle LF, Yücel M. A Clinical Staging Model for Obsessive-Compulsive Disorder: Is It Ready for Prime Time? EClinicalMedicine 2019; 7:65-72. [PMID: 31193644 PMCID: PMC6537549 DOI: 10.1016/j.eclinm.2019.01.014] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 01/30/2019] [Accepted: 01/30/2019] [Indexed: 01/02/2023] Open
Abstract
Recent changes to the diagnostic classification of obsessive-compulsive disorder (OCD), including its removal from the anxiety/neurotic, stress-related and somatoform disorders chapters of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and International Classification of Diseases 11th Revision (ICD-11), are based on growing evidence of unique pathogenic signatures and linked diagnostic and treatment approaches. In this review, we build on these recent developments and propose a 'clinical staging model' of OCD that integrates the severity of symptoms and phase of illness for personalised case management. A clinical staging model is especially relevant for the early identification and management of subthreshold OCD - a substantial and largely neglected portion of the population who, despite having milder symptoms, experience harms that may impact personal relationships, work-related functioning and productivity. Research on the pathogenesis, classification and management of such cases is needed, including the development of new outcomes measures that prove sensitive to changes in future clinical trials. Early intervention strategies in OCD are likely to yield better long-term outcomes.
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Affiliation(s)
- Leonardo F. Fontenelle
- Obsessive, Compulsive, and Anxiety Spectrum Research Program, Institute of Psychiatry, Federal University of Rio de Janeiro, Brazil
- D'Or Institute for Research and Education, Rio de Janeiro, Brazil
- Brain & Mental Health Research Hub, Turner Institute for Brain and Mental Health, Monash University, Victoria, Australia
- Corresponding author at: Rua Visconde de Pirajá, 547, 617, Ipanema, Rio de Janeiro-RJ, CEP: 22410-003, Brazil.
| | - Murat Yücel
- Brain & Mental Health Research Hub, Turner Institute for Brain and Mental Health, Monash University, Victoria, Australia
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Sugiyama K, Nozaki T, Asakawa T, Sameshima T, Koizumi S, Hiramatsu H, Namba H. Deep Brain Stimulation for Intractable Obsessive-compulsive Disorder: The International and Japanese Situation/Scenario. Neurol Med Chir (Tokyo) 2018; 58:369-376. [PMID: 30089754 PMCID: PMC6156130 DOI: 10.2176/nmc.st.2018-0115] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Deep brain stimulation (DBS) is used to treat symptoms by modulating the cortico-striato-thalamo-cortical (CSTC) loop in the central nervous system (CNS), and attempts to research loop circuit disorders have been globally initiated among the intractable neurological and psychiatric disorders. DBS treatment has been evaluated for all these newly found CNS loop circuit disorders. In 2011, neurosurgical treatments for psychiatric disorders were renamed from “psychosurgery” to “neurosurgery for psychiatric disorders (NPD)” by the World Society for Stereotactic and Functional Neurosurgery (WSSFN). Moreover, in 2014, “Consensus on guidelines for stereotactic neurosurgery for psychiatric disorders” was published by the WSSFN to address the differences in correspondence of stereotactic NPD. Globally, two multicenter prospective randomized control trials regarding DBS of the subcallosal cingulated gyrus and ventral anterior internal capsule/ventral striatum for intractable depression have been terminated after futility analysis. However, DBS for intractable obsessive-compulsive disorder (OCD), unlike for intractable depression, is showing steady development. In Japan, NPDs have not been performed since 1975 following the adoption of “Resolution of total denial for psychosurgery” by the Japanese Society of Psychiatry and Neurology. Nevertheless, a trend to adopt new neuro-modulation techniques for psychiatric disorders, including DBS, are emerging. We have created a clinical research protocol for the use of DBS in intractable OCD, which has been approved by the ethical committee of Hamamatsu University School of Medicine, with the hope of commencing DBS treatment for intractable OCD patients in the near future.
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Affiliation(s)
- Kenji Sugiyama
- Department of Neurosurgery, Hamamatsu University School of Medicine
| | - Takao Nozaki
- Department of Neurosurgery, Hamamatsu University School of Medicine
| | - Tetsuya Asakawa
- Department of Neurosurgery, Hamamatsu University School of Medicine
| | | | | | - Hisaya Hiramatsu
- Department of Neurosurgery, Hamamatsu University School of Medicine
| | - Hiroki Namba
- Department of Neurosurgery, Hamamatsu University School of Medicine
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Lamothe H, Baleyte JM, Smith P, Pelissolo A, Mallet L. Individualized Immunological Data for Precise Classification of OCD Patients. Brain Sci 2018; 8:E149. [PMID: 30096863 PMCID: PMC6119917 DOI: 10.3390/brainsci8080149] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 08/01/2018] [Accepted: 08/03/2018] [Indexed: 12/11/2022] Open
Abstract
Obsessive⁻compulsive disorder (OCD) affects about 2% of the general population, for which several etiological factors were identified. Important among these is immunological dysfunction. This review aims to show how immunology can inform specific etiological factors, and how distinguishing between these etiologies is important from a personalized treatment perspective. We found discrepancies concerning cytokines, raising the hypothesis of specific immunological etiological factors. Antibody studies support the existence of a potential autoimmune etiological factor. Infections may also provoke OCD symptoms, and therefore, could be considered as specific etiological factors with specific immunological impairments. Finally, we underline the importance of distinguishing between different etiological factors since some specific treatments already exist in the context of immunological factors for the improvement of classic treatments.
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Affiliation(s)
- Hugues Lamothe
- Centre Hospitalier Intercommunal de Créteil, 94000 Créteil, France.
- Institut du Cerveau et de la Moelle Epinière, Sorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, 75013 Paris, France.
- Fondation FondaMental, 94000 Créteil, France.
| | - Jean-Marc Baleyte
- Centre Hospitalier Intercommunal de Créteil, 94000 Créteil, France.
- Fondation FondaMental, 94000 Créteil, France.
| | - Pauline Smith
- Institut du Cerveau et de la Moelle Epinière, Sorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, 75013 Paris, France.
| | - Antoine Pelissolo
- Fondation FondaMental, 94000 Créteil, France.
- Assistance Publique-Hôpitaux de Paris, Pôle de Psychiatrie, Hôpitaux Universitaires Henri Mondor-Albert Chenevier, Université Paris-Est Créteil, 94000 Créteil, France.
- INSERM, U955, Team 15, 94000 Créteil, France.
| | - Luc Mallet
- Institut du Cerveau et de la Moelle Epinière, Sorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, 75013 Paris, France.
- Fondation FondaMental, 94000 Créteil, France.
- Assistance Publique-Hôpitaux de Paris, Pôle de Psychiatrie, Hôpitaux Universitaires Henri Mondor-Albert Chenevier, Université Paris-Est Créteil, 94000 Créteil, France.
- Department of Mental Health and Psychiatry, Global Health Institute, University of Geneva, 1202 Geneva, Switzerland.
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Bosanac P, Hamilton BE, Lucak J, Castle D. Identity challenges and 'burden of normality' after DBS for severe OCD: a narrative case study. BMC Psychiatry 2018; 18:186. [PMID: 29895269 PMCID: PMC5998583 DOI: 10.1186/s12888-018-1771-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Accepted: 05/31/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Deep Brain Stimulation (DBS) is an emerging and potentially powerful biological treatment for severe Obsessive-Compulsive Disorder (OCD), but the wider impact of the intervention and the sometimes dramatic reduction in symptoms need greater attention in research and practice. The aim of this case study is to explore the subjective experience of preparing for and undergoing DBS as a treatment for severe and treatment-refractory OCD and the experience of the impact of the treatment. METHODS This study of subjective experience before and after DBS is based on narrative analysis of two in-depth interviews conducted in November 2014 (1 year after DBS surgery) with a 30-year-old man and his father, utilizing Consolidated Criteria for Reporting Qualitative Studies (COREQ) criteria. RESULTS The parallel stories show how OCD posed severe challenges to identity and social milestones, with profound positive and negative impact on the person and family. Yet symptom remission was accompanied by expanded horizons, but also by uncertainty and intense distress associated with the changed identity. DISCUSSION The concept of 'burden of normality' is discussed, in light of a treatment experience with DBS for OCD that gives rise to a new array of life challenges and opportunities, with implications for clinical care. CONCLUSIONS The concept of burden of normality has, thus far, not extended to evaluations of people who have had DBS for severe OCD and that of their lived experience and recovery trajectory thereafter. This concept highlights that there is work to be done on expectations of normal living and on the transitioning self-concept, in the post-surgical period.
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Affiliation(s)
- Peter Bosanac
- St. Vincent's Hospital, Melbourne and Department of Psychiatry, University of Melbourne, Melbourne, Australia.
| | | | - James Lucak
- 0000 0000 8606 2560grid.413105.2St Vincent’s Hospital, Melbourne, Australia
| | - David Castle
- 0000 0001 2179 088Xgrid.1008.9St. Vincent’s Hospital, Melbourne and Department of Psychiatry, University of Melbourne, Melbourne, Australia
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Abstract
Deep brain stimulation (DBS) has been offered to patients suffering of severe and resistant neuropsychiatric disorders like Obsessive Compulsive Disorder (OCD), Gilles de la Tourette Syndrome (TS) and Major Depression (MDD). Modulation of several targets within the cortico-striato-thalamo-cortical circuits can lead to a decrease of symptom severity in those patients. This review focuses on the recent clinical outcomes in DBS in psychiatric disorders. Studies on OCD and TS are now focusing on the long-term effects of DBS, with encouraging results regarding not only the decrease of symptoms, but also quality of life. They also highlighted efficient adjuvant techniques, like cognitive and behavioural therapy and support programs, to enhance an often-partial response to DBS. The application of DBS for MDD is more recent and, despite encouraging initial open-label studies, two large randomised studies have failed to demonstrate an efficacy of DBS in MDD according to evidence-based medicine criteria. Last years, DBS was also tested in other resistant psychiatric disorders, as anorexia nervosa and addiction, with encouraging preliminary results. However, today, no target – whatever the disease – can meet the criteria for clinical efficacy as recently defined by an international committee for neurosurgery for psychiatric disorders. Consequently, DBS in psychiatric disorders still needs to proceed within the frame of clinical trials.
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Affiliation(s)
- Anne-Hélène Clair
- Sorbonne University, UPMC Paris 06 University, INSERM, CNRS, Institut du Cerveau et de la Moelle épinière, Paris, France
| | - William Haynes
- Sorbonne University, UPMC Paris 06 University, INSERM, CNRS, Institut du Cerveau et de la Moelle épinière, Paris, France.,Neurosurgery department, University Hospital of Montpellier, Montpellier, France
| | - Luc Mallet
- Sorbonne University, UPMC Paris 06 University, INSERM, CNRS, Institut du Cerveau et de la Moelle épinière, Paris, France.,Psychiatry and Addictology Department - Neurosurgery Department, Personalized Neurology & Psychiatry University Department, University Hospitals Henri Mondor - Albert Chenevier, Créteil, France
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Kisely S, Li A, Warren N, Siskind D. A systematic review and meta-analysis of deep brain stimulation for depression. Depress Anxiety 2018; 35:468-480. [PMID: 29697875 DOI: 10.1002/da.22746] [Citation(s) in RCA: 85] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 02/09/2018] [Accepted: 02/10/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Deep brain stimulation is increasingly being used for treatment-resistant depression. Blinded, randomized controlled trials of active versus sham treatment have been limited to small numbers. METHOD We performed a systematic review and meta-analysis on the effectiveness of deep brain stimulation (DBS) in depression. Cochrane Central Register of Controlled Trials, PubMed/Medline, Embase and PsycINFO, Chinese Biomedical Literature Service System, and China Knowledge Resource Integrated Database were searched for single- or double placebo-controlled, crossover, and parallel-group trials in which DBS was compared with sham treatment using validated scales. RESULTS Ten papers from nine studies met inclusion criteria, all but two of which were double-blinded RCTs. The main outcome was a reduction in depressive symptoms. It was possible to combine data for 190 participants. Patients on active, as opposed to sham, treatment had a significantly higher response (OR = 5.50; 95% CI = 2.79, 10.85; p < .0001) and reductions in mean depression score (SMD = -0.42; 95% CI = -0.72, -0.12; p = .006). However, the effect was attenuated on some of the subgroup and sensitivity analyses, and there were no differences for most other outcomes. In addition, 84 participants experienced a total of 131 serious adverse effects, although not all could be directly associated with the device or surgery. Finally, publication bias was possible. CONCLUSIONS DBS may show promise for treatment-resistant depression but remains an experimental treatment until further data are available.
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Affiliation(s)
- Steve Kisely
- The University of Queensland Southern Clinical School, Queensland, Australia.,Metro South Health Service, Woolloongabba, Australia.,Griffith Institute of Health, Griffith University, Queensland, Australia.,Departments of Psychiatry, Community Health and Epidemiology, Dalhousie University, Nova Scotia, Canada
| | - Amy Li
- The University of Queensland Southern Clinical School, Queensland, Australia
| | - Nicola Warren
- The University of Queensland Southern Clinical School, Queensland, Australia.,Metro South Health Service, Woolloongabba, Australia
| | - Dan Siskind
- The University of Queensland Southern Clinical School, Queensland, Australia.,Metro South Health Service, Woolloongabba, Australia
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Fontenelle LF, Frydman I, Hoefle S, Oliveira-Souza R, Vigne P, Bortolini TS, Suo C, Yücel M, Mattos P, Moll J. Decoding moral emotions in obsessive-compulsive disorder. Neuroimage Clin 2018; 19:82-89. [PMID: 30035005 PMCID: PMC6051311 DOI: 10.1016/j.nicl.2018.04.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Revised: 03/07/2018] [Accepted: 04/01/2018] [Indexed: 11/20/2022]
Abstract
Background Patients with obsessive-compulsive disorder (OCD) exhibit abnormal neural responses when they experience particular emotions or when they evaluate stimuli with emotional value. Whether these brain responses are sufficiently distinctive to discriminate between OCD patients and healthy controls is unknown. The present study is the first to investigate the discriminative power of multivariate pattern analysis of regional fMRI responses to moral and non-moral emotions. Method To accomplish this goal, we performed a searchlight-based multivariate pattern analysis to unveil brain regions that could discriminate 18 OCD patients from 18 matched healthy controls during provoked guilt, disgust, compassion, and anger. We also investigated the existence of distinctive neural patterns while combining those four emotions (herein termed multiemotion analysis). Results We found that different frontostriatal regions discriminated OCD patients from controls based on individual emotional experiences. Most notably, the left nucleus accumbens (NAcc) discriminated OCD patients from controls during both disgust and the multiemotion analysis. Among other regions, the angular gyrus responses to anger and the lingual and the middle temporal gyri in the multi-emotion analysis were highly discriminant between samples. Additional BOLD analyses supported the directionality of these findings. Conclusions In line with previous studies, differential activity in regions beyond the frontostriatal circuitry differentiates OCD from healthy volunteers. The finding that the response of the left NAcc to different basic and moral emotions is highly discriminative for a diagnosis of OCD confirms current pathophysiological models and points to new venues of research.
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Affiliation(s)
- Leonardo F Fontenelle
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Brain & Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Victoria, Australia; Obsessive, Compulsive, and Anxiety Spectrum Research Program, Institute of Psychiatry, Federal University of Rio de Janeiro, Brazil.
| | - Ilana Frydman
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Obsessive, Compulsive, and Anxiety Spectrum Research Program, Institute of Psychiatry, Federal University of Rio de Janeiro, Brazil
| | - Sebastian Hoefle
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
| | | | - Paula Vigne
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Obsessive, Compulsive, and Anxiety Spectrum Research Program, Institute of Psychiatry, Federal University of Rio de Janeiro, Brazil
| | - Tiago S Bortolini
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
| | - Chao Suo
- Brain & Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Victoria, Australia
| | - Murat Yücel
- Brain & Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Victoria, Australia
| | - Paulo Mattos
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
| | - Jorge Moll
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
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Fox KCR, Foster BL, Kucyi A, Daitch AL, Parvizi J. Intracranial Electrophysiology of the Human Default Network. Trends Cogn Sci 2018; 22:307-324. [PMID: 29525387 PMCID: PMC5957519 DOI: 10.1016/j.tics.2018.02.002] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Revised: 02/01/2018] [Accepted: 02/03/2018] [Indexed: 02/07/2023]
Abstract
The human default network (DN) plays a critical role in internally directed cognition, behavior, and neuropsychiatric disease. Despite much progress with functional neuroimaging, persistent questions still linger concerning the electrophysiological underpinnings, fast temporal dynamics, and causal importance of the DN. Here, we review how direct intracranial recording and stimulation of the DN provides a unique combination of high spatiotemporal resolution and causal information that speaks directly to many of these outstanding questions. Our synthesis highlights the electrophysiological basis of activation, suppression, and connectivity of the DN, each key areas of debate in the literature. Integrating these unique electrophysiological data with extant neuroimaging findings will help lay the foundation for a mechanistic account of DN function in human behavior and cognition.
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Affiliation(s)
- Kieran C R Fox
- Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Stanford Human Intracranial Cognitive Electrophysiology Program (SHICEP), Stanford, CA, USA.
| | - Brett L Foster
- Departments of Neurosurgery and Neuroscience, Baylor College of Medicine, Houston, TX, USA
| | - Aaron Kucyi
- Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Stanford Human Intracranial Cognitive Electrophysiology Program (SHICEP), Stanford, CA, USA
| | - Amy L Daitch
- Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Stanford Human Intracranial Cognitive Electrophysiology Program (SHICEP), Stanford, CA, USA
| | - Josef Parvizi
- Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Stanford Human Intracranial Cognitive Electrophysiology Program (SHICEP), Stanford, CA, USA; Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
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Acute Effects of Electrical Stimulation of the Bed Nucleus of the Stria Terminalis/Internal Capsule in Obsessive-Compulsive Disorder. World Neurosurg 2018; 111:e471-e477. [DOI: 10.1016/j.wneu.2017.12.084] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Revised: 12/13/2017] [Accepted: 12/14/2017] [Indexed: 01/16/2023]
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Deep brain stimulation and treatment-resistant obsessive-compulsive disorder: A systematic review. REVISTA DE PSIQUIATRIA Y SALUD MENTAL 2017; 12:37-51. [PMID: 28676437 DOI: 10.1016/j.rpsm.2017.05.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Revised: 04/05/2017] [Accepted: 05/15/2017] [Indexed: 12/13/2022]
Abstract
INTRODUCTION At least 10% of patients with Obsessive-compulsive Disorder (OCD) are refractory to psychopharmacological treatment. The emergence of new technologies for the modulation of altered neuronal activity in Neurosurgery, deep brain stimulation (DBS), has enabled its use in severe and refractory OCD cases. The objective of this article is to review the current scientific evidence on the effectiveness and applicability of this technique to refractory OCD. METHOD We systematically reviewed the literature to identify the main characteristics of deep brain stimulation, its use and applicability as treatment for obsessive-compulsive disorder. Therefore, we reviewed PubMed/Medline, Embase and PsycINFO databases, combining the key-words 'Deep brain stimulation', 'DBS' and 'Obsessive-compulsive disorder' 'OCS'. The articles were selected by two of the authors independently, based on the abstracts, and if they described any of the main characteristics of the therapy referring to OCD: applicability; mechanism of action; brain therapeutic targets; efficacy; side-effects; co-therapies. All the information was subsequently extracted and analysed. RESULTS The critical analysis of the evidence shows that the use of DBS in treatment-resistant OCD is providing satisfactory results regarding efficacy, with assumable side-effects. However, there is insufficient evidence to support the use of any single brain target over another. Patient selection has to be done following analyses of risks/benefits, being advisable to individualize the decision of continuing with concomitant psychopharmacological and psychological treatments. CONCLUSIONS The use of DBS is still considered to be in the field of research, although it is increasingly used in refractory-OCD, producing in the majority of studies significant improvements in symptomatology, and in functionality and quality of life. It is essential to implement random and controlled studies regarding its long-term efficacy, cost-risk analyses and cost/benefit.
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Abstract
Eating disorders (EDs), including anorexia nervosa, bulimia nervosa, and binge-eating disorder, constitute a class of common and deadly psychiatric disorders. While numerous studies in humans highlight the important role of neurobiological alterations in the development of ED-related behaviors, the precise neural substrate that mediates this risk is unknown. Historically, pharmacological interventions have played a limited role in the treatment of eating disorders, typically providing symptomatic relief of comorbid psychiatric issues, like depression and anxiety, in support of the standard nutritional and psychological treatments. To date there are no Food and Drug Administration-approved medications or procedures for anorexia nervosa, and only one Food and Drug Administration-approved medication each for bulimia nervosa (fluoxetine) and binge-eating disorder (lisdexamfetamine). While there is little primary interest in drug development for eating disorders, postmarket monitoring of medications and procedures approved for other indications has identified several novel treatment options for patients with eating disorders. In this review, I utilize searches of the PubMed and ClinicalTrials.gov databases to highlight emerging treatments in eating disorders.
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Affiliation(s)
- Michael Lutter
- Eating Recovery Center of Dallas, 4716 Alliance Blvd. #400, Plano, TX, 75093, USA.
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Abstract
Deep brain stimulation (DBS) is a promising putative modality for the treatment of refractory psychiatric disorders such as major depression and obsessive-compulsive disorder (OCD). Several targets have been posited; however, a clear consensus on differential efficacy and possible modes of action remain unclear. DBS to the supero-lateral branch of the medial forebrain bundle (slMFB) has recently been introduced for major depression (MD). Due to our experience with slMFB stimulation for MD, and because OCD might be related to similar dysfunctions of the reward system, treatment with slMFB DBS seams meaningful. Here we describe our first 2 cases together with a hypothetical mode of action. We describe diffusion tensor imaging (DTI) fiber tractographically (FT)-assisted implantation of the bilateral DBS systems in 2 male patients. In a selected literature overview, we discuss the possible mode of action. Both patients were successfully implanted and stimulated. The follow-up time was 12 months. One patient showed a significant response (Yale-Brown Obsessive-Compulsive Scale [YBOCS] reduction by 35%); the other patient reached remission criteria 3 months after surgery (YBOCS<14) and showed mild OCD just above the remission criterion at 12 months follow-up. While the hypermetabolism theory for OCD involves the cortico-striato-thalamo-cortical (CSTC) network, we think that there is clinical evidence that the reward system plays a crucial role. Our findings suggest an important role of this network in mechanisms of disease development and recovery. In this uncontrolled case series, continuous bilateral DBS to the slMFB led to clinically significant improvements of ratings of OCD severity. Ongoing research focuses on the role of the reward system in OCD, and its yet-underestimated role in this underlying neurobiology of the disease.
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Mulders AEP, Plantinga BR, Schruers K, Duits A, Janssen MLF, Ackermans L, Leentjens AFG, Jahanshahi A, Temel Y. Deep brain stimulation of the subthalamic nucleus in obsessive-compulsive disorder: Neuroanatomical and pathophysiological considerations. Eur Neuropsychopharmacol 2016; 26:1909-1919. [PMID: 27838106 DOI: 10.1016/j.euroneuro.2016.10.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Revised: 07/04/2016] [Accepted: 10/29/2016] [Indexed: 11/17/2022]
Abstract
Obsessive-compulsive disorder (OCD) is among the most disabling chronic psychiatric disorders and has a significant negative impact on multiple domains of quality of life. For patients suffering from severe refractory OCD, deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been applied. Reviewing the literature of the last years we believe that through its central position within the cortico-basal ganglia-thalamocortical circuits, the STN has a coordinating role in decision-making and action-selection mechanisms. Dysfunctional information-processing at the level of the STN is responsible for some of the core symptoms of OCD. Research confirms an electrophysiological dysfunction in the associative and limbic (non-motor) parts of the STN. Compared to Parkinson׳s disease patients, STN neurons in OCD exhibit a lower firing rate, less frequent but longer bursts, increased burst activity in the anterior ventromedial area, an asymmetrical left-sided burst distribution, and a predominant oscillatory activity in the δ-band. Moreover, there is direct evidence for the involvement of the STN in both checking behavior and OCD symptoms, which are both related to changes in electrophysiological activity in the non-motor STN. Through a combination of mechanisms, DBS of the STN seems to interrupt the disturbed information-processing, leading to a normalization of connectivity within the cortico-basal ganglia-thalamocortical circuits and consequently to a reduction in symptoms. In conclusion, based on the STN׳s strategic position within cortico-basal ganglia-thalamocortical circuits and its involvement in action-selection mechanisms that are responsible for some of the core symptoms of OCD, the STN is a mechanism-based target for DBS in OCD.
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Affiliation(s)
- A E P Mulders
- Department of Neurosurgery, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Translational Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
| | - B R Plantinga
- Department of Neurosurgery, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Translational Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Biomedical Image Analysis, Eindhoven University of Technology, Eindhoven, The Netherlands
| | - K Schruers
- Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - A Duits
- Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - M L F Janssen
- Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Translational Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands
| | - L Ackermans
- Department of Neurosurgery, Maastricht University Medical Center, Maastricht, The Netherlands
| | - A F G Leentjens
- Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - A Jahanshahi
- Department of Neurosurgery, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Translational Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Y Temel
- Department of Neurosurgery, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Translational Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
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van den Heuvel OA, van Wingen G, Soriano-Mas C, Alonso P, Chamberlain SR, Nakamae T, Denys D, Goudriaan AE, Veltman DJ. Brain circuitry of compulsivity. Eur Neuropsychopharmacol 2016; 26:810-27. [PMID: 26711687 DOI: 10.1016/j.euroneuro.2015.12.005] [Citation(s) in RCA: 195] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Revised: 08/28/2015] [Accepted: 12/01/2015] [Indexed: 01/27/2023]
Abstract
Compulsivity is associated with alterations in the structure and the function of parallel and interacting brain circuits involved in emotional processing (involving both the reward and the fear circuits), cognitive control, and motor functioning. These brain circuits develop during the pre-natal period and early childhood under strong genetic and environmental influences. In this review we bring together literature on cognitive, emotional, and behavioral processes in compulsivity, based mainly on studies in patients with obsessive-compulsive disorder and addiction. Disease symptoms normally change over time. Goal-directed behaviors, in response to reward or anxiety, often become more habitual over time. During the course of compulsive disorders the mental processes and repetitive behaviors themselves contribute to the neuroplastic changes in the involved circuits, mainly in case of chronicity. On the other hand, successful treatment is able to normalize altered circuit functioning or to induce compensatory mechanisms. We conclude that insight in the neurobiological characteristics of the individual symptom profile and disease course, including the potential targets for neuroplasticity is an unmet need to advance the field.
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Affiliation(s)
- Odile A van den Heuvel
- Department of Psychiatry, VU University Medical Center (VUmc), Amsterdam, The Netherlands; Department of Anatomy & Neurosciences, VUmc, Amsterdam, The Netherlands; The Obsessive-Compulsive Disorder Team, Haukeland University Hospital, Bergen, Norway.
| | - Guido van Wingen
- Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Carles Soriano-Mas
- OCD Clinical and Research Unit, Department of Psychiatry, Bellvitge University Hospital; Bellvitge Biomedical Research Institute (IDIBELL), and CIBERSAM (Centro de Investigación en Red de Salud Mental), Carlos III Health Institute, Barcelona, Spain; Department of Psychobiology and Methodology in Health Sciences, Universitat Autònoma de Barcelona, Spain
| | - Pino Alonso
- OCD Clinical and Research Unit, Department of Psychiatry, Bellvitge University Hospital; Bellvitge Biomedical Research Institute (IDIBELL), and CIBERSAM (Centro de Investigación en Red de Salud Mental), Carlos III Health Institute, Barcelona, Spain; Department of Clinical Sciences, Bellvitge Campus, University of Barcelona, Spain
| | - Samuel R Chamberlain
- Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Cambridge and Peterborough NHS Foundation Trust (CPFT), Cambridge, United Kingdom
| | - Takashi Nakamae
- Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Damiaan Denys
- Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Anna E Goudriaan
- Academic Medical Center, Department of Psychiatry, Amsterdam Institute for Addiction Research, University of Amsterdam, Amsterdam, The Netherlands; Arkin Mental Health and Jellinek Addiction Treatment, Amsterdam, The Netherlands
| | - Dick J Veltman
- Department of Psychiatry, VU University Medical Center (VUmc), Amsterdam, The Netherlands
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Girgis F, Pace J, Sweet J, Miller JP. Hippocampal Neurophysiologic Changes after Mild Traumatic Brain Injury and Potential Neuromodulation Treatment Approaches. Front Syst Neurosci 2016; 10:8. [PMID: 26903824 PMCID: PMC4746250 DOI: 10.3389/fnsys.2016.00008] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Accepted: 01/25/2016] [Indexed: 12/22/2022] Open
Abstract
Traumatic brain injury (TBI) is the leading cause of death and disability in individuals below age 45, and five million Americans live with chronic disability as a result. Mild TBI (mTBI), defined as TBI in the absence of major imaging or histopathological defects, is responsible for a majority of cases. Despite the lack of overt morphological defects, victims of mTBI frequently suffer lasting cognitive deficits, memory difficulties, and behavioral disturbances. There is increasing evidence that cognitive and memory dysfunction is related to subtle physiological changes that occur in the hippocampus, and these impact both the phenotype of deficits observed and subsequent recovery. Therapeutic modulation of physiological activity by means of medications commonly used for other indications or brain stimulation may represent novel treatment approaches. This review summarizes the present body of knowledge regarding neurophysiologic changes that occur in the hippocampus after mTBI, as well as potential targets for therapeutic modulation of neurologic activity.
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Affiliation(s)
- Fady Girgis
- Department of Neurosurgery, University Hospitals Case Medical Center, Case Western Reserve University Cleveland, OH, USA
| | - Jonathan Pace
- Department of Neurosurgery, University Hospitals Case Medical Center, Case Western Reserve University Cleveland, OH, USA
| | - Jennifer Sweet
- Department of Neurosurgery, University Hospitals Case Medical Center, Case Western Reserve University Cleveland, OH, USA
| | - Jonathan P Miller
- Department of Neurosurgery, University Hospitals Case Medical Center, Case Western Reserve University Cleveland, OH, USA
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