Ketogenic diet and ketamine infusion treatment to target chronic persistent eating disorder psychopathology in anorexia nervosa: a pilot study
In an open‑label pilot of five weight‑restored adults with chronic anorexia nervosa psychopathology, a therapeutic ketogenic diet followed by six ketamine infusions was safe, maintained weight for most participants and produced significant improvements on multiple eating‑disorder measures. The findings suggest this combined TKD‑ketamine approach may ameliorate persistent shape/weight preoccupations by normalising underlying neurobiology, warranting further controlled trials.
Authors
- Calabrese, L.
- Scolnick, B.
- Zupec-Kania, B.
Published
Abstract
Purpose
Anorexia nervosa (AN) is a severe psychiatric disorder, and shape and weight concerns are often chronic despite weight normalization. No specific treatments exist for those preoccupations that interfere with recovery and trigger relapse. A case study using a ketogenic diet followed by ketamine infusions led to sustained remission in one patient with chronic AN. Here we conducted an open-label trial to test whether this response could be replicated.
Methods
Five adults weight recovered from AN but with persistent eating disorder thoughts and behaviors adopted a therapeutic ketogenic diet (TKD) aimed at maintaining weight. After sustaining nutritional ketosis, participants received six ketamine infusions and were followed over 6 months.
Results
All participants completed the study protocol without significant adverse effects. Two participants maintained TKD for 8 weeks prior to ketamine infusions due to good behavioral response and remained on TKD. Three participants received TKD for 4 weeks prior to and during ketamine, then tapered off after the final infusion. The group showed significant improvements on the Clinical Impairment Assessment (p = 0.008), Eating Disorder Examination Questionnaire (EDEQ) Global score (p = 0.006), EDEQ-Eating Concerns (p = 0.005), EDEQ-Shape Concerns (p = 0.016), EDEQ-Weight Concerns (p = 0.032), Eating Disorders Recovery Questionnaire (EDRQ) Acceptance of Self and Body (0.027) and EDRQ-Social and Emotional Connection (p = 0.001). Weight remained stable, except for one participant who relapsed 4 months after treatment and off TKD.
Conclusion
This novel treatment appears to be safe and effective for adults with chronic AN-related psychopathology. The results from this open trial support that there are specific neurobiological underpinnings of AN that can be normalized using TKD and ketamine. Level of evidence Level IV, multiple time series with intervention
Research Summary of 'Ketogenic diet and ketamine infusion treatment to target chronic persistent eating disorder psychopathology in anorexia nervosa: a pilot study'
Introduction
Anorexia nervosa (AN) is a severe, often chronic psychiatric disorder characterised by self-starvation, intense fear of weight gain, distorted body image and entrenched food- and exercise-related compulsions. Existing treatments, including psychotherapies and available medications, have limited effectiveness for severe and enduring forms of AN, and there is no FDA‑approved pharmacotherapy. Recent preclinical and clinical observations implicate biological mechanisms in AN's pathophysiology: in activity‑based anorexia (ABA) animal models, high‑fat low‑carbohydrate diets prevented self‑starvation and promoted recovery, and ketamine (an NMDA receptor antagonist) improved obsessional symptoms in prior human reports. Both ketogenic diet and ketamine modulate dopaminergic systems, which have been proposed as centrally involved in AN, suggesting a mechanistic rationale for combining metabolic (therapeutic ketogenic diet, TKD) and pharmacological (ketamine) interventions. Calabrese and colleagues designed an open‑label pilot trial to test whether the therapeutic sequence observed in a prior case report—TKD to induce nutritional ketosis followed by a course of ketamine infusions—could be replicated in a small group of adults with long‑standing AN who were weight recovered but continued to experience severe eating‑disorder psychopathology. The primary aim was to assess safety, feasibility and change in AN‑related symptoms (shape/weight concerns, eating‑related preoccupations and functional impairment) over a 6‑month follow‑up period; the TKD was deliberately aimed at maintaining, not reducing, body weight.
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