Randomised controlled feasibility trial of real versus sham repetitive transcranial magnetic stimulation treatment in adults with severe and enduring anorexia nervosa: the TIARA study

Bethan Dalton, Savani Bartholdy, Jessica McClelland, Maria Kekic, Samantha J Rennalls, Jessica Werthmann, Ben Carter, Owen G O'Daly, Iain C Campbell, Anthony S David, Danielle Glennon, Nikola Kern, Ulrike Schmidt, Bethan Dalton, Savani Bartholdy, Jessica McClelland, Maria Kekic, Samantha J Rennalls, Jessica Werthmann, Ben Carter, Owen G O'Daly, Iain C Campbell, Anthony S David, Danielle Glennon, Nikola Kern, Ulrike Schmidt

Abstract

Objective: Treatment options for severe, enduring anorexia nervosa (SE-AN) are limited. Non-invasive neuromodulation is a promising emerging intervention. Our study is a feasibility randomised controlled trial of repetitive transcranial magnetic stimulation (rTMS) in individuals with SE-AN, which aims to inform the design of a future large-scale trial.

Design: Double-blind, parallel group, two-arm, sham-controlled trial.

Setting: Specialist eating disorders centre.

Participants: Community-dwelling people with anorexia nervosa, an illness duration of ≥3 years and at least one previous completed treatment.

Interventions: Participants received 20 sessions (administered over 4 weeks) of MRI-guided real or sham high-frequency rTMS to the left dorsolateral prefrontal cortex in addition to treatment-as-usual.

Outcomes: Primary outcomes were recruitment, attendance and retention rates. Secondary outcomes included body mass index (BMI), eating disorder symptoms, mood, quality of life and rTMS safety and tolerability. Assessments were conducted at baseline, post-treatment and follow-up (ie, at 0 month, 1 month and 4 months post-randomisation).

Results: Thirty-four participants (17 per group) were randomly allocated to real or sham rTMS. One participant per group was withdrawn prior to the intervention due to safety concerns. Two participants (both receiving sham) did not complete the treatment. rTMS was safe and well tolerated. Between-group effect sizes of change scores (baseline to follow-up) were small for BMI (d=0.2, 95% CI -0.49 to 0.90) and eating disorder symptoms (d=0.1, 95% CI -0.60 to 0.79), medium for quality of life and moderate to large (d=0.61 to 1.0) for mood outcomes, all favouring rTMS over sham.

Conclusions: The treatment protocol is feasible and acceptable to participants. Outcomes provide preliminary evidence for the therapeutic potential of rTMS in SE-AN. Largest effects were observed on variables assessing mood. This study supports the need for a larger confirmatory trial to evaluate the effectiveness of multi-session rTMS in SE-AN. Future studies should include a longer follow-up period and an assessment of cost-effectiveness.

Trial registration number: ISRCTN14329415; Pre-results.

Keywords: anorexia nervosa; eating disorders; neuromodulation; repetitive transcranial magnetic stimulation (rTMS).

Conflict of interest statement

Competing interests: OGO receives salary support from an NIHR Infrastructure grant for the Wellcome Trust/KCL Clinical Research Facility. Ulrike Schmidt is supported by an NIHR Senior Investigator Award. US, ASD and ICC receive salary support from the NIHR Mental Health BRC at SLaM NHS Foundation Trust and KCL.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
CONSORT diagram of participant involvement. CONSORT, Consolidated Standards of Reporting Trials; SLaM EDU, South London and Maudsley NHS Foundation Trust Eating Disorders Unit; NHS, National Health Service; rTMS, repetitive transcranial magnetic stimulation.

References

    1. Zipfel S, Giel KE, Bulik CM, et al. . Anorexia nervosa: aetiology, assessment, and treatment. Lancet Psychiatry 2015;2:1099–111. 10.1016/S2215-0366(15)00356-9
    1. Treasure J, Zipfel S, Micali N, et al. . Anorexia nervosa. Nat Rev Dis Primers 2015;1:15074 10.1038/nrdp.2015.74
    1. Steinhausen HC. The outcome of anorexia nervosa in the 20th century. Am J Psychiatry 2002;159:1284–93. 10.1176/appi.ajp.159.8.1284
    1. Arkell J, Robinson P. A pilot case series using qualitative and quantitative methods: biological, psychological and social outcome in severe and enduring eating disorder (anorexia nervosa). Int J Eat Disord 2008;41:650–6. 10.1002/eat.20546
    1. Brockmeyer T, Friederich HC, Schmidt U. Advances in the treatment of anorexia nervosa: a review of established and emerging interventions. Psychol Med 2018;48:1–37. 10.1017/S0033291717002604
    1. Touyz S, Le Grange D, Lacey H, et al. . Treating severe and enduring anorexia nervosa: a randomized controlled trial. Psychol Med 2013;43:2501–11. 10.1017/S0033291713000949
    1. Andries A, Frystyk J, Flyvbjerg A, et al. . Dronabinol in severe, enduring anorexia nervosa: a randomized controlled trial. Int J Eat Disord 2014;47:18–23. 10.1002/eat.22173
    1. Hay PJ, Touyz S, Sud R. Treatment for severe and enduring anorexia nervosa: a review. Aust N Z J Psychiatry 2012;46:1136–44. 10.1177/0004867412450469
    1. Dalton B, Campbell IC, Schmidt U. Neuromodulation and neurofeedback treatments in eating disorders and obesity. Curr Opin Psychiatry 2017;30:458–73. 10.1097/YCO.0000000000000361
    1. Choudhary P, Roy P, Kumar Kar S. Improvement of weight and attitude towards eating behaviour with high frequency rTMS augmentation in anorexia nervosa. Asian J Psychiatr 2017;28:160 10.1016/j.ajp.2017.05.010
    1. McClelland J, Kekic M, Campbell IC, et al. . Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment in Enduring Anorexia Nervosa: A Case Series. Eur Eat Disord Rev 2016;24:157–63. 10.1002/erv.2414
    1. Dunlop KA, Woodside B, Downar J. Targeting Neural Endophenotypes of Eating Disorders with Non-invasive Brain Stimulation. Front Neurosci 2016;10:30 10.3389/fnins.2016.00030
    1. McClelland J, Kekic M, Bozhilova N, et al. . A Randomised Controlled Trial of Neuronavigated Repetitive Transcranial Magnetic Stimulation (rTMS) in Anorexia Nervosa. PLoS One 2016;11:e0148606 10.1371/journal.pone.0148606
    1. Van den Eynde F, Guillaume S, Broadbent H, et al. . Repetitive transcranial magnetic stimulation in anorexia nervosa: a pilot study. Eur Psychiatry 2013;28:98–101. 10.1016/j.eurpsy.2011.06.002
    1. McClelland J, Bozhilova N, Nestler S, et al. . Improvements in symptoms following neuronavigated repetitive transcranial magnetic stimulation (rTMS) in severe and enduring anorexia nervosa: findings from two case studies. Eur Eat Disord Rev 2013;21:500–6. 10.1002/erv.2266
    1. Bartholdy S, McClelland J, Kekic M, et al. . Clinical outcomes and neural correlates of 20 sessions of repetitive transcranial magnetic stimulation in severe and enduring anorexia nervosa (the TIARA study): study protocol for a randomised controlled feasibility trial. Trials 2015;16:548 10.1186/s13063-015-1069-3
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th edn Arlington, VA: American Psychiatric Publishing, 2013.
    1. National Institute for Health and Care Excellence. Eating disorders: recognition and treatment. NICE Clinical Guideline NG69. 2017. (accessed 27th November 2017).
    1. Broomfield C, Stedal K, Touyz S, et al. . Labeling and defining severe and enduring anorexia nervosa: a systematic review and critical analysis. Int J Eat Disord 2017;50:611–23. 10.1002/eat.22715
    1. Fitzgerald PB, Hoy K, McQueen S, et al. . A randomized trial of rTMS targeted with MRI based neuro-navigation in treatment-resistant depression. Neuropsychopharmacology 2009;34:1255–62. 10.1038/npp.2008.233
    1. Fairburn C. Appendix: Eating Disorder Examination Questionnaire (EDE-Q Version 6.0) Cognitive Behaviour Therapy and Eating Disorders. New York: Guilford Press, 2008.
    1. Levinson CA, Byrne M. The fear of food measure: a novel measure for use in exposure therapy for eating disorders. Int J Eat Disord 2015;48:271–83. 10.1002/eat.22344
    1. Godier LR, Park RJ. A novel measure of compulsive food restriction in anorexia nervosa: validation of the Self-Starvation Scale (SS). Eat Behav 2015;17:10–13. 10.1016/j.eatbeh.2014.12.004
    1. Marinilli Pinto A, Guarda AS, Heinberg LJ, et al. . Development of the eating disorder recovery self-efficacy questionnaire. Int J Eat Disord 2006;39:376–84. 10.1002/eat.20256
    1. Lovibond S, Lovibond P. Manual for the Depression Anxiety Stress Scales. 2nd ed Sydney: Psychology Foundation, 1995.
    1. Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol 1988;54:1063–70. 10.1037/0022-3514.54.6.1063
    1. McNair D, Lorr M, Droppleman L. Profile of Mood States Manual. San Diego: Educational and Industrial Testing Services, 1992.
    1. Foa EB, Huppert JD, Leiberg S, et al. . The Obsessive-Compulsive Inventory: development and validation of a short version. Psychol Assess 2002;14:485–96. 10.1037/1040-3590.14.4.485
    1. Herdman M, Gudex C, Lloyd A, et al. . Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res 2011;20:1727–36. 10.1007/s11136-011-9903-x
    1. Bohn K, Doll HA, Cooper Z, et al. . The measurement of impairment due to eating disorder psychopathology. Behav Res Ther 2008;46:1105–10. 10.1016/j.brat.2008.06.012
    1. Bohn K, Fairburn CG. The Clinical Impairment Assessment questionnaire (CIA). Cognitive Behavioral Therapy for Eating Disorders. New York: Guilford Press, 2008.
    1. Beecham J, Knapp M. Costing psychiatric interventions Thornicroft G, Measuring Mental Health Needs. London: Gaskell, 2001:200–24.
    1. Rossi S, Hallett M, Rossini PM, et al. . Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 2009;120:2008–39. 10.1016/j.clinph.2009.08.016
    1. Lancaster GA, Dodd S, Williamson PR. Design and analysis of pilot studies: recommendations for good practice. J Eval Clin Pract 2004;10:307–12. 10.1111/j.2002.384.doc.x
    1. Van den Eynde F, Claudino AM, Mogg A, et al. . Repetitive transcranial magnetic stimulation reduces cue-induced food craving in bulimic disorders. Biol Psychiatry 2010;67:793–5. 10.1016/j.biopsych.2009.11.023
    1. Wonderlich S, Mitchell JE, Crosby RD, et al. . Minimizing and treating chronicity in the eating disorders: a clinical overview. Int J Eat Disord 2012;45:467–75. 10.1002/eat.20978
    1. Schmidt U, Magill N, Renwick B, et al. . The Maudsley Outpatient Study of Treatments for Anorexia Nervosa and Related Conditions (MOSAIC): Comparison of the Maudsley Model of Anorexia Nervosa Treatment for Adults (MANTRA) with specialist supportive clinical management (SSCM) in outpatients with broadly defined anorexia nervosa: A randomized controlled trial. J Consult Clin Psychol 2015;83:796–807. 10.1037/ccp0000019
    1. Byrne S, Wade T, Hay P, et al. . A randomised controlled trial of three psychological treatments for anorexia nervosa. Psychol Med 2017:2823–33. 10.1017/S0033291717001349
    1. Gaynes BN, Lloyd SW, Lux L, et al. . Repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis. J Clin Psychiatry 2014;75:477–89. quiz 89 10.4088/JCP.13r08815
    1. Hallett M. Transcranial magnetic stimulation and the human brain. Nature 2000;406:147–50. 10.1038/35018000
    1. Lipsman N, Lam E, Volpini M, et al. . Deep brain stimulation of the subcallosal cingulate for treatment-refractory anorexia nervosa: 1 year follow-up of an open-label trial. Lancet Psychiatry 2017;4:285–94. 10.1016/S2215-0366(17)30076-7
    1. Leggett LE, Soril LJ, Coward S, et al. . Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression in Adult and Youth Populations: A Systematic Literature Review and Meta-Analysis. Prim Care Companion CNS Disord 2015;17:17 10.4088/PCC.15r01807
    1. Brunelin J, Jalenques I, Trojak B, et al. . The efficacy and safety of low frequency repetitive transcranial magnetic stimulation for treatment-resistant depression: the results from a large multicenter French RCT. Brain Stimul 2014;7:855–63. 10.1016/j.brs.2014.07.040
    1. Fitzgerald PB, Brown TL, Marston NA, et al. . Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial. Arch Gen Psychiatry 2003;60:1002–8. 10.1001/archpsyc.60.9.1002
    1. Bakker N, Shahab S, Giacobbe P, et al. . rTMS of the dorsomedial prefrontal cortex for major depression: safety, tolerability, effectiveness, and outcome predictors for 10 Hz versus intermittent theta-burst stimulation. Brain Stimul 2015;8:208–15. 10.1016/j.brs.2014.11.002
    1. Dunlop K, Gaprielian P, Blumberger D, et al. . MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder. J Vis Exp 2015:e53129 10.3791/53129
    1. Bajbouj M, Padberg F. A perfect match: noninvasive brain stimulation and psychotherapy. Eur Arch Psychiatry Clin Neurosci 2014;264(Suppl 1):27–33. 10.1007/s00406-014-0540-6
    1. De Raedt R, Vanderhasselt MA, Baeken C. Neurostimulation as an intervention for treatment resistant depression: from research on mechanisms towards targeted neurocognitive strategies. Clin Psychol Rev 2015;41:61–9. 10.1016/j.cpr.2014.10.006
    1. Elmasry J, Loo C, Martin D. A systematic review of transcranial electrical stimulation combined with cognitive training. Restor Neurol Neurosci 2015;33:263–78. 10.3233/RNN-140473

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren