¹LVR University Hospital Essen, Clinic for Paediatric and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Essen, Germany, ²King's College London, Psychological Medicine, London, United Kingdom, ³King's College London, Department of Health Service & Population Research, London, United Kingdom, ⁴Imperial College London, Department of Brain Sciences, London, United Kingdom, ⁵King's College London, Department of Neuroimaging, London, United Kingdom, ⁶King's College London, Department of Biostatistics & Health Informatics, London, United Kingdom, ⁷Central and North West London NHS Foundation Trust, Vincent Square Eating Disorders Service, London, United Kingdom

Background: Approximately a third of people with anorexia nervosa (AN) develop a severe and enduring form of the illness, which is often accompanied by depression. This can be a key barrier to recovery. Anti-depressant medications are less effective in treating depression in patients with acute AN, thus new pharmacological treatment options are needed. Ketamine is currently used for treatment-resistant depression in the UK and may be effective in patients with both AN and depression.

Aims & Objectives: The primary objective of the EDEN study is to investigate the feasibility of using oral ketamine in this population, as indicated by participant recruitment, assessment response rate and drop-out rate. Secondary objectives include acceptability of the intervention, changes in key outcomes (depression, eating disorder symptoms, and quality of life) at 28 days, 3- and 6-months post-randomisation, and to collect data on the safety and tolerability of oral ketamine in this population.

Method: The EDEN study is a randomised, double-blinded (participant, researchers, assessors and analyst), single-centre, placebo-controlled feasibility study of 60 adults (≥18 years old) with a diagnosis of depression that has not responded to one or more treatments and AN with a duration of ≥3 years. Participants will be randomised (1:1) to receive oral ketamine 60-180mg, or placebo, twice per week for four weeks. Study participation consists of three phases; (i) Pre-dose Assessments (Screening and Baseline), (ii) Dosing period (8 dosing visits, twice weekly for 4 weeks), and (iii) Follow-up (at 28 days end of intervention, 3- and 6-months post-randomisation).

Results: Recruitment for the study commenced in August 2025. Quantitative feasibility results of the study will be available in 2028. However, individual experiences of participants in the study so far will be presented.

Discussion & Conclusions: Treating depressive symptoms in individuals with AN currently remains a clinical challenge, given that typical anti-depressants show little efficacy in this population. An adequately powered Phase II RCT comparing low-dose oral ketamine with a placebo is needed to definitively determine its effectiveness and safety in treating depression in people with AN. Given that there are challenges in recruiting and retaining this patient group for treatment RCTs, particularly where a pharmacological intervention may be involved, we hope that the results from this feasibility study will inform the development of a successful RCT protocol.