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Brain-Directed Therapies as Adjuncts to Treatment of Eating Disorders

Brain-Directed Therapies as Adjuncts to Treatment of Eating Disorders. Ulrike Schmidt, MD PhD FRCPsych FAED Professor of Eating Disorders King’s College London Ulrike.schmidt@kcl.ac.uk. Productivity impacts of ED: Estimated as $15.1 billion in 2012, similar to anxiety & depression.  

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Brain-Directed Therapies as Adjuncts to Treatment of Eating Disorders

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  1. Brain-Directed Therapies as Adjuncts to Treatment of Eating Disorders Ulrike Schmidt, MD PhD FRCPsych FAED Professor of Eating Disorders King’s College London Ulrike.schmidt@kcl.ac.uk

  2. Productivity impacts of ED: Estimated as $15.1 billion in 2012, similar to anxiety & depression.   Includes: (a) Lost lifetime earnings for young people who die. (b) Productivity impacts of living with ED: e.g. lower employment participation and greater absenteeism & presenteeism. November 2012

  3. Anorexia Nervosa (AN) in Adults One of the most difficult psychiatric disorders to treat or study (Halmi et al., 2005; Fairburn et al., 2013) Especially those with severe and enduring AN Talking therapies are the treatment of choice, but only moderately effective New approaches to treatment are needed.

  4. Citation Classics (> 400 Citations) and Top Cited Papers in Major Depression & AN In AN, because there were few citation classics, the top 100 most cited papers were also examined. • Papers addressing psychosocial mechanisms were the most common category. • Very few were on Neurobiology or Treatment. Lipsman & Lozano (2011); Lipsman et al (2013)

  5. Neurobiology/Neurocircuitry in AN ‘Top-down’ vs ‘bottom-up’ dysregulation Lozano & Lipsman, 2013

  6. European Eating Disorders ReviewSpecial Edition: Brain-Directed Treatments e.g. Non-invasive Brain Stimulation Deep Brain Stimulation

  7. Growing Public Interest in Brain-Directed Treatments

  8. Repetitive Transcranial Magnetic Stimulation (rTMS) • Employs an electromagnetic field generated by a figure -eight coil to suppress (low-frequency) or enhance (high frequency) cortical neuronal activity in a localised area of the brain • Many different stimulation protocols • Clinical Applications: e.g. Depression (2nd line FDA approved treatment), Addictions, Psychosis For review see: McClelland, Bozhilova, Campbell & Schmidt, 2013; Medina & Tunez, 2013

  9. Repetitive Transcranial Magnetic Stimulation (rTMS) • Potential Mechanisms of Action: • Altered cortical excitability • Changes in regional cerebral blood flow • Effects on neuroendocrine & neurotransmitter systems • Increased neural plasticity • Growing interest in biomarkers and predictors of rTMS e.g. Medina & Tunez, 2013; Fidalgo et al.,2013; Downar et al., 2013

  10. Our Proof of Concept Studies: rTMS in Food Craving and BN One session of real high-frequency rTMS applied to the left DLPF cortex vs sham treatment in the context of a Food Challenge Task in: Women with high food craving People with bulimic disorders Results: Reduction in craving Reduction in binges over the following 24 hours Reduction in salivary cortisol Uher et al., 2005; Van den Eynde, et al., 2010; Claudino et al., 2011

  11. One-off High-Frequency DLPFC rTMS in AN:A Pilot Study (n=10) VAS ** ** * Van den Eynde et al.(2013) European Psychiatry

  12. Pilot Study of Therapeutic rTMS in Treatment-Resistant AN: Participants McClelland et al., 2013b, EEDR; McClelland et al., in preparation

  13. Within Session Measures: Urge to Restrict Food (Average) McClelland et al., 2013b, EEDR; McClelland et al., in preparation

  14. Patient 2: VAS-nonresponder Within Session Measures: Urge to RestrictExample of a Responder and a Non-Responder Patient 1: VAS-responder McClelland et al., 2013b, EEDR; McClelland et al., in preparation

  15. Eating Disorder Examination Questionnaire McClelland et al, 2013b; McClelland et al., in preparation

  16. Depression, Anxiety & Stress Scale McClelland et al., 2013b, EEDR; McClelland et al., in preparation

  17. Body Mass Index McClelland et al., 2013b, EEDR; McClelland et al., in preparation

  18. Eating Behaviours Most patients want to have more rTMS sessions Feedback from Patients Affect & Cognition “No change” “Better equipped to cope with things” “More relaxed around food… want to stretch boundaries” “Helps reinforce positive feelings” “Less anxious” “No low mood after vomiting” “More open to trying different foods” “Calmer, more positive” “Binge/purge behaviours are less rewarding” McClelland et al., 2013b, EEDR; McClelland et al., in preparation

  19. Eating Behaviours Feedback from Carers Affect & Cognition Better able to cope with non-routine activities, more flexible & accepting of change She noticed improvements in mood, but less so with eating so a felt a sense of disappointment More determined to change Considers ‘trying new foods’ Some periods of normal eating Clearer thinking… Purges less often Improved & more consistent mood, much ‘brighter’, more relaxed & positive, energised outlook on life, more confident… Little changed in what she eats McClelland et al., 2013b, EEDR; McClelland et al., in preparation

  20. Transcranial Direct Current Stimulation (tDCS) • Delivery of a weak electrical current between two surface electrodes; anodal and cathodal tDCS cause excitatory & inhibitory effects respectively on underlying cortical neurons • Clinical Applications: e.g. Depression, Addictions, Alzheimer’s & Parkinson’s Disease • In MDD: tDCS superior to sham (medium effect size) For review see Shiozawa et al., 2014, Int J Neuropsychopharmacology

  21. Effects of Prefrontal Cortex tDCS onFood Craving and Temporal Discounting in Women with Frequent Food Craving Participants: 17 women with frequent food cravings Aims: (a) Assess effects of tDCS on food craving; (b) Assess whether tDCS effects on food craving are moderated by Temporal Discounting (Assessed on a Monetary Task; Rubia et al., 2009) Design: Randomised sham-controlled within subjects cross-over design Method: 1 session of bilateral tDCS applied to the DLPFC (anode right/cathode left) Participants were exposed to real food and to a film of people eating. Food craving and Temporal Discounting (TD) were assessed before and after real and sham tDCS

  22. Mean Percentage Change in Food Challenge Task (FCT) Scores Kekic et al. (2014) Appetite, in press.

  23. Mean Pre- and Post-tDCS Global FCT Scores for Participants with High and Low Temporal Discounting • No difference in TD in real vs sham tDCS • Those with Low TD (i.e. more reflective choice behaviour) were more responsive to anti-craving effects of real tDCS than those with high TD (i.e. more impulsive choice behaviour) Kekic et al. (2014) Appetite, in press.

  24. Effects of non-invasive neurostimulation on craving (Jansen et al., 2013)

  25. Figure 1 DBS: Yearly Growth in the Number of Publications from 1980 to 2011 Lozano & Lipsman, Neuron 77, 406-24

  26. Positioning of DBS Electrodes in the Sub-Callosal Cortex Lipsman et al. (2013) The Lancet

  27. Changes in BMI of Each Patient Lipsman et al. (2013) The Lancet

  28. Yale-Brown-Cornell Eating Disorders Scale Lipsman et al., (2013) The Lancet

  29. Summary • Neural models of eating disorders support investigations into therapeutic potential of neuromodulation (NIBS; DBS) • Existing research has demonstrated effects on ED symptoms following rTMS, tDCS & DBS in clinical and analogue populations. • Neuromodulation treatments may be useful as adjuncts to psychotherapy in those patients with severe and enduring AN. • Many questions remain regarding patient selection, efficacy and mechanisms of action (mediators, moderators, predictors) • We need RCTs – but these are difficult to do (Brunoni & Fregni, 2011) • We need studies of neural predictors and correlates of these treatments

  30. Ongoing Work • Sham-controlled RCT assessing effects of 1 session neuronavigated rTMS on ED symptoms and choice behaviour in patients with AN (n=60) • Neural (structural MRI, fMRI, DTI) predictors and correlates of therapeutic rTMS in AN • Effects of tDCS on eating disorder symptoms and choice behaviour in AN and BN

  31. Acknowledgements: The ED-NIBS team: J Mcclelland, M Kekic, S Bartholdi & I Campbell Collaborators: A David, K Rubia & S Nestler

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