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      Deep Brain Stimulation in Anorexia Nervosa: Hope for the Hopeless or Exploitation of the Vulnerable? The Oxford Neuroethics Gold Standard Framework

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          Abstract

          Neurosurgical interventions for psychiatric disorders have a long and troubled history ( 1, 2) but have become much more refined in the last few decades due to the rapid development of neuroimaging and robotic technologies ( 2). These advances have enabled the design of less invasive techniques, which are more focused, such as deep brain stimulation (DBS) ( 3). DBS involves electrode insertion into specific neural targets implicated in pathological behavior, which are then repeatedly stimulated at adjustable frequencies. DBS has been used for Parkinson’s disease and movement disorders since the 1960s ( 46) and over the last decade has been applied to treatment-refractory psychiatric disorders, with some evidence of benefit in obsessive–compulsive disorder (OCD), major depressive disorder, and addictions ( 7). Recent consensus guidelines on best practice in psychiatric neurosurgery ( 8) stress, however, that DBS for psychiatric disorders remains at an experimental and exploratory stage. The ethics of DBS—in particular for psychiatric conditions—is debated ( 1, 810). Much of this discourse surrounds the philosophical implications of competence, authenticity, personality, or identity change following neurosurgical interventions, but there is a paucity of applied guidance on neuroethical best practice in psychiatric DBS, and health-care professionals have expressed that they require more ( 11). This paper aims to redress this balance by providing a practical, applied neuroethical gold standard framework to guide research ethics committees, researchers, and institutional sponsors. We will describe this as applied to our protocol for a particular research trial of DBS in severe and enduring anorexia nervosa (SE-AN) ( https://clinicaltrials.gov/ct2/show/NCT01924598, unique identifier NCT01924598), but believe it may have wider application to DBS in other psychiatric disorders.

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          The outcome of anorexia nervosa in the 20th century.

          The present review addresses the outcome of anorexia nervosa and whether it changed over the second half of the 20th century. A total of 119 study series covering 5,590 patients suffering from anorexia nervosa that were published in the English and German literature were analyzed with regard to mortality, global outcome, and other psychiatric disorders at follow-up. There were large variations in the outcome parameters across studies. Mortality estimated on the basis of both crude and standardized rates was significantly high. Among the surviving patients, less than one-half recovered on average, whereas one-third improved, and 20% remained chronically ill. The normalization of the core symptoms, involving weight, menstruation, and eating behaviors, was slightly better when each symptom was analyzed in isolation. The presence of other psychiatric disorders at follow-up was very common. Longer duration of follow-up and, less strongly, younger age at onset of illness were associated with better outcome. There was no convincing evidence that the outcome of anorexia nervosa improved over the second half of the last century. Several prognostic features were isolated, but there is conflicting evidence. Most clearly, vomiting, bulimia, and purgative abuse, chronicity of illness, and obsessive-compulsive personality symptoms are unfavorable prognostic features. Anorexia nervosa did not lose its relatively poor prognosis in the 20th century. Advances in etiology and treatment may improve the course of patients with anorexia nervosa in the future.
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            Deep brain stimulation of the nucleus accumbens for treatment-refractory obsessive-compulsive disorder.

            Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder that affects 2% of the general population. Even when the best available treatments are applied, approximately 10% of patients remain severely afflicted and run a long-term deteriorating course of OCD. To determine whether bilateral deep brain stimulation of the nucleus accumbens is an effective and safe treatment for treatment-refractory OCD. The study consisted of an open 8-month treatment phase, followed by a double-blind crossover phase with randomly assigned 2-week periods of active or sham stimulation, ending with an open 12-month maintenance phase. Academic research. Patients Sixteen patients (age range, 18-65 years) with OCD according to DSM-IV criteria meeting stringent criteria for refractoriness to treatment were included in the study. Treatment with bilateral deep brain stimulation of the nucleus accumbens. Primary efficacy was assessed by score change from baseline on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Responders were defined by a score decrease of at least 35% on the Y-BOCS. In the open phase, the mean (SD) Y-BOCS score decreased by 46%, from 33.7 (3.6) at baseline to 18.0 (11.4) after 8 months (P < .001). Nine of 16 patients were responders, with a mean (SD) Y-BOCS score decrease of 23.7 (7.0), or 72%. In the double-blind, sham-controlled phase (n = 14), the mean (SD) Y-BOCS score difference between active and sham stimulation was 8.3 (2.3), or 25% (P = .004). Depression and anxiety decreased significantly. Except for mild forgetfulness and word-finding problems, no permanent adverse events were reported. Bilateral deep brain stimulation of the nucleus accumbens may be an effective and safe treatment for treatment-refractory OCD. isrctn.org Identifier: ISRCTN23255677.
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              Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus.

              The usefulness of high-frequency stimulation of the ventral intermediate nucleus (Vim) as the first neurosurgical procedure in disabling tremor was assessed in 26 patients with Parkinson's disease and 6 with essential tremor. 7 of these patients had already undergone thalamotomy contralateral to the stimulated side, and 11 others had bilateral Vim stimulation at the same time. Chronic stimulating electrodes connected to a pulse generator were implanted in the Vim. Tremor amplitude at rest, during posture holding, and during action and intention manoeuvres was assessed by means of accelerometry. Of the 43 thalami stimulated, 27 showed complete relief from tremor and 11 major improvement (88%). The improvement was maintained for up to 29 months (mean follow-up 13 [SD 9] months). Adverse effects were mild and could be eradicated by reduction or cessation of stimulation. This reversibility and adaptability, allowing control of side-effects, make thalamic stimulation preferable to thalamotomy, especially when treatment of both sides of the brain is needed.
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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                20 March 2017
                2017
                : 8
                : 44
                Affiliations
                [1] 1OxBREaD Research Group, Department of Psychiatry, University of Oxford , Oxford, UK
                [2] 2Neuroscience Ethics and Society Research Group, Department of Psychiatry, University of Oxford , Oxford, UK
                [3] 3Oxford Uehiro Centre for Practical Ethics, University of Oxford , Oxford, UK
                [4] 4Swansea University Medical School, Swansea University , Swansea, UK
                Author notes

                Edited by: Gregor Hasler, University of Bern, Switzerland

                Reviewed by: Damiaan Denys, Academic Medical Center (AMC), Netherlands; Thomas E. Schlaepfer, Albert Ludwig University of Freiburg, Germany

                *Correspondence: Rebecca J. Park, rebecca.park@ 123456psych.ox.ac.uk

                Specialty section: This article was submitted to Neuroimaging and Stimulation, a section of the journal Frontiers in Psychiatry

                Article
                10.3389/fpsyt.2017.00044
                5357647
                28373849
                b2557fbe-2fa7-4875-a17a-b85984b19c3a
                Copyright © 2017 Park, Singh, Pike and Tan.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 23 December 2016
                : 03 March 2017
                Page count
                Figures: 1, Tables: 3, Equations: 0, References: 82, Pages: 10, Words: 8941
                Funding
                Funded by: Medical Research Council 10.13039/501100000265
                Award ID: MC_PC_12020
                Categories
                Psychiatry
                Clinical Trial

                Clinical Psychology & Psychiatry
                anorexia nervosa,deep brain stimulation,capacity,patient advocacy,neuroethics,clinical trial,neuromodulation

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