Deep brain stimulation for anorexia nervosa

The Lancet (Impact Factor: 45.22). 07/2013; 382(9889):305-306. DOI: 10.1016/S0140-6736(13)61630-X
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    ABSTRACT: BACKGROUND: Anorexia nervosa is characterised by a chronic course that is refractory to treatment in many patients and has one of the highest mortality rates of any psychiatric disorder. Deep brain stimulation (DBS) has been applied to circuit-based neuropsychiatric diseases, such as Parkinson's disease and major depression, with promising results. We aimed to assess the safety of DBS to modulate the activity of limbic circuits and to examine how this might affect the clinical features of anorexia nervosa. METHODS: We did a phase 1, prospective trial of subcallosal cingulate DBS in six patients with chronic, severe, and treatment-refractory anorexia nervosa. Eligible patients were aged 20-60 years, had been diagnosed with restricting or binge-purging anorexia nervosa, and showed evidence of chronicity or treatment resistance. Patients underwent medical optimisation preoperatively and had baseline body-mass index (BMI), psychometric, and neuroimaging investigations, followed by implantation of electrodes and pulse generators for continuous delivery of electrical stimulation. Patients were followed up for 9 months after DBS activation, and the primary outcome of adverse events associated with surgery or stimulation was monitored at every follow-up visit. Repeat psychometric assessments, BMI measurements, and neuroimaging investigations were also done at various intervals. This trial is registered with, number NCT01476540. FINDINGS: DBS was associated with several adverse events, only one of which (seizure during programming, roughly 2 weeks after surgery) was serious. Other related adverse events were panic attack during surgery, nausea, air embolus, and pain. After 9 months, three of the six patients had achieved and maintained a BMI greater than their historical baselines. DBS was associated with improvements in mood, anxiety, affective regulation, and anorexia nervosa-related obsessions and compulsions in four patients and with improvements in quality of life in three patients after 6 months of stimulation. These clinical benefits were accompanied by changes in cerebral glucose metabolism (seen in a comparison of composite PET scans at baseline and 6 months) that were consistent with a reversal of the abnormalities seen in the anterior cingulate, insula, and parietal lobe in the disorder. INTERPRETATION: Subcallosal cingulate DBS seems to be generally safe in this sample of patients with chronic and treatment-refractory anorexia nervosa. FUNDING: Klarman Family Foundation Grants Program in Eating Disorders Research and Canadian Institutes of Health Research.
    The Lancet 03/2013; 381(9875). DOI:10.1016/S0140-6736(12)62188-6 · 45.22 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate preservation of cognitive function after deep brain stimulation (DBS) of the subgenual cingulate (Cg25) for treatment-resistant depression (TRD). We have previously reported on the treatment methods, safety, and 6-month clinical outcome (Mayberg et al., Neuron. 2005;45:651-660). Comprehensive neuropsychological assessments tapping 4 domains of frontal lobe function, and general cognitive abilities, were completed before implantation and at 3, 6, and 12 months postonset of continuous DBS in 6 TRD patients. No adverse neuropsychological effects were noted following surgery, onset and maintenance of DBS with the exception of transient motor slowing noted at 3 and 6 months that improved to normative levels by 12 months. Several areas of cognition that were below average or impaired at baseline improved over follow-up, and these changes were not correlated with improvements in mood. Though the sample size is small, these results support cognitive safety of Cg25 DBS for TRD.
    The Journal of nervous and mental disease 06/2008; 196(5):405-10. DOI:10.1097/NMD.0b013e3181710927 · 1.69 Impact Factor
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    ABSTRACT: Deep brain stimulation (DBS) may be an effective intervention for treatment-resistant depression (TRD), but available data are limited. To assess the efficacy and safety of subcallosal cingulate DBS in patients with TRD with either major depressive disorder (MDD) or bipolar II disorder (BP). Open-label trial with a sham lead-in phase. Academic medical center. Patients Men and women aged 18 to 70 years with a moderate-to-severe major depressive episode after at least 4 adequate antidepressant treatments. Ten patients with MDD and 7 with BP were enrolled from a total of 323 patients screened. Intervention Deep brain stimulation electrodes were implanted bilaterally in the subcallosal cingulate white matter. Patients received single-blind sham stimulation for 4 weeks followed by active stimulation for 24 weeks. Patients then entered a single-blind discontinuation phase; this phase was stopped after the first 3 patients because of ethical concerns. Patients were evaluated for up to 2 years after the onset of active stimulation. Change in depression severity and functioning over time, and response and remission rates after 24 weeks were the primary efficacy end points; secondary efficacy end points were 1 year and 2 years of active stimulation. A significant decrease in depression and increase in function were associated with chronic stimulation. Remission and response were seen in 3 patients (18%) and 7 (41%) after 24 weeks (n = 17), 5 (36%) and 5 (36%) after 1 year (n = 14), and 7 (58%) and 11 (92%) after 2 years (n = 12) of active stimulation. No patient achieving remission experienced a spontaneous relapse. Efficacy was similar for patients with MDD and those with BP. Chronic DBS was safe and well tolerated, and no hypomanic or manic episodes occurred. A modest sham stimulation effect was found, likely due to a decrease in depression after the surgical intervention but prior to entering the sham phase. The findings of this study support the long-term safety and antidepressant efficacy of subcallosal cingulate DBS for TRD and suggest equivalent safety and efficacy for TRD in patients with BP. Trial Registration Identifier: NCT00367003.
    Archives of general psychiatry 01/2012; 69(2):150-8. DOI:10.1001/archgenpsychiatry.2011.1456 · 14.48 Impact Factor