Anorexia Nervosa (AN) is a life-threatening eating disorder characterised by an intense fear of weight gain and disturbed body image, which motivates severe dietary restriction or other weight loss behaviours (e.g. purging). Treatment efficacy in adults with AN remains low: only a small percentage of individuals fully recover, and dropout rates are high. For adolescents with a relatively short term illness duration (under 3 years), family-based therapy has been associated with more favourable outcomes. However, for those adolescents with a longer illness duration (over 3 years), there are no specific treatments associated with positive long-term outcomes and these individuals are at risk of developing a severe and enduring form of the illness (SE-AN).

In part, treatment can be problematic due to ambivalence, which is reflected in poor take-up of certain treatments (e.g. pharmacological treatments that lead to weight gain) and high drop-out rates. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy for treatment of AN in adults and improving treatment adherence. However, this has yet to be investigated in adolescents with AN.

This study will use a novel type of rTMS, theta burst stimulation (TBS), including intermittent TBS (iTBS) and continuous TBS (cTBS). TBS takes as little as a few minutes duration compared to the classical rTMS protocol which takes approximately 37.5 minutes. In addition, TBS has been found to produce longer after-effects of the induced plastic changes and has a lower stimulation intensity, which may therefore be more practical and potentially safer to administer in people with AN. Thus, the aim of this proof-of-concept trial is to obtain preliminary data on the safety and short-term (i.e. up to 24 hours) effects of a single session of iTBS and cTBS, compared to sham TBS, on reducing core symptoms of AN.

Inclusion Criteria:

• Male and female participants over the age of 13
• BMI over 14 (for participants over the age of 18) or over 66% of the median BMI for age and gender (for participants under the age of 18)
• Right-handed
• Current Diagnostic and Statistical Manual-5 (DSM-5) diagnosis of AN-restricting type (AN-R) or AN-binge/purge type (AN-BP) and an illness duration of 3 years or more
• Must have completed at least one adequate previous course of eating disorder treatment (e.g. one 6-month course of specialist outpatient therapy, specialist day-care or in-patient treatment for re-feeding)
• Participants under the age of 18 must have informed consent from parent(s)/carer(s)
• Must have approval from treating eating disorders clinician or general practitioner (GP) to participate

Exclusion Criteria:

• Having a history of head or eye injury
• Having a history of a neurological disease including previous seizures of any kind
• Having metallic implants anywhere in the head or body
• Being on a dose of any psychotropic medication that has not been stable for at least 14 days prior to participation in the study
• Taking antipsychotic medication
• Taking anti-convulsive medication
• Pregnancy or suspected pregnancy in female participants
• Having a current other major psychiatric disorder (e.g. major depressive disorder, substance dependence, schizophrenia or bipolar) needing treatment in its own right
• Excessive alcohol (>3 units per day, 5 days of the week) and/or cigarette consumption (>15 cigarettes per day)
• Severe abnormalities in the screening clinical blood sample
• An rTMS safety questionnaire and an MRI safety questionnaire will also be administered and if deemed not safe to deliver rTMS or undergo MRI scanning, people will be excluded on this basis.

Researcher unable to be blinded as stimulation site is dependent on the participants allocation to intermittent or continuous TBS.