Ketamine as a Novel Psychopharmacotherapy for Eating Disorders: Evidence and Future Directions

Eating disorders (EDs) are common, disabling psychiatric conditions with complex aetiology, high morbidity and mortality, and substantial personal and economic burden. Existing treatments rely primarily on psychotherapies and nutritional management, with pharmacological options showing only modest benefits for bulimia nervosa (BN) and binge eating disorder (BED) and effectively no approved agents for anorexia nervosa (AN). Given frequent chronicity, low remission rates and a subgroup of severe and enduring illness that is treatment‑refractory, there is a pressing need for novel therapeutic approaches that can address both core ED psychopathology and common comorbidities such as depression and suicidality. This review examines contemporary evidence on ketamine, a noncompetitive N‑methyl‑D‑aspartate receptor (NMDAr) antagonist with rapid antidepressant effects, as a potential treatment for EDs. The authors set out to summarise published clinical reports in which ketamine was used as a primary, adjunctive, or combined pharmacotherapy for EDs, to identify patterns in dosing and outcomes, and to outline directions for future empirical work. The paper emphasises the transdiagnostic rationale for ketamine in EDs while noting that existing studies are preliminary and concentrated mainly on AN.

The clinical evidence base for ketamine in eating disorders is limited and is composed largely of case series and single‑case reports, with most publications focused on anorexia nervosa. Study designs, routes of administration, dosing schedules, and concomitant treatments varied substantially across reports, which complicates direct comparison. An early uncontrolled series by Mills and colleagues treated 15 patients with chronic, atypical refractory AN (mean illness duration 11.3 years ± 5.0) with intermittent ketamine infusions combined with oral nalmefene. Infusions ranged from 2–15 sessions given at 5–21 day intervals and were delivered at 20 mg/hour over 10 hours. Clinical response, defined as ≥ 50% reduction in symptom severity, occurred in nine patients (responders) while six were non‑responders. Responders showed marked and sustained remission with little-to-no disease activity at 7–24 months follow‑up, significant reductions in obsessive‑compulsive neurosis (p < .001), increased weight acceptance and partial-to-complete weight restoration; non‑responders did not show significant improvements. Response was associated with AN subtype (restricting or binge/purge) in this series. A longitudinal case series described four patients with severe and enduring pathology (two with AN‑R, two with EDNOS‑BP) and comorbid treatment‑resistant depression. Ketamine was administered intramuscularly and/or intravenously, typically starting at 0.5 mg/kg over 30–90 minutes and titrated to 0.8–0.9 mg/kg as tolerated, with repeat dosing every 4–6 weeks across at least 12 months. The series reported clinically meaningful reductions in depressive symptoms and more modest improvements in anxiety and disordered eating; patients with AN‑R had more robust and sustained responses than those with EDNOS‑BP, along with improved psychosocial functioning. Several single‑case reports provide heterogeneous but clinically notable outcomes. Scolnick and colleagues described a 29‑year‑old woman with severe enduring AN‑R who, after adopting a ketogenic diet, received four ketamine infusions starting at 0.75 mg/kg and titrated up to 1.2 mg/kg; following treatment she experienced marked reductions in ED‑related obsessive‑compulsive tendencies, depression and weight restoration, with cognitive and behavioural recovery sustained for six months. Another case of a 29‑year‑old woman with chronic refractory AN‑R and major depression received nine infusions of 0.5 mg/kg over 40 minutes (twice weekly for four weeks). She progressed from active to passive suicidal ideation and achieved remission by the eighth infusion, but relapsed rapidly after the ninth, illustrating a short duration of effect in at least one instance. Ragnhildstveit and colleagues reported the first use of ketamine‑assisted psychotherapy (KAP) in an extreme, enduring case of bulimia nervosa‑binge/purge (BN‑BP) in a 21‑year‑old. Treatment comprised three courses of six sessions (18 sessions total) with each session including 30 minutes preparatory psychotherapy, 40 minutes intravenous ketamine at 0.5 mg/kg combined with guided psychotherapy, and 30 minutes integration psychotherapy. The patient progressively reduced binging and purging, achieved complete cessation at three months, and maintained remission for over one year. Across reports, adverse effects reported are consistent with known ketamine effects and include transient psychotomimetic phenomena such as depersonalisation and derealisation. Several studies noted rapid but sometimes short‑lived improvements, with relapse intervals reported in other literature at approximately 2–6 weeks for antidepressant effects. The heterogeneity of dosing, adjunctive treatments (for example nalmefene, ketogenic diet, or psychotherapy), and small sample sizes limit firm conclusions about efficacy or safety. The paper also cites patient‑attitude research and qualitative studies indicating interest in psychedelic‑assisted treatments for EDs. A mixed‑methods survey (N = 200) found general support for psychedelics including ketamine but raised concerns about safety, therapeutic setting and trust that patients felt could be mitigated by education and controlled monitoring. Small qualitative studies of ayahuasca and broader psychedelic experiences reported reductions in ED cognitions and improved processing of painful memories; an acute effects study (N = 28) reported improvements in depression and wellbeing among participants with lifetime EDs.

The authors interpret the assembled case reports and series as signalling therapeutic potential for ketamine in eating disorders, particularly for clinical non‑responders and those with severe, enduring illness. They highlight that ketamine's rapid modulation of glutamatergic systems, promotion of synaptogenesis and neuroplasticity, and the presence of a putative critical window after administration provide a plausible biological rationale for its transdiagnostic utility across mood and compulsive disorders often comorbid with EDs. Ragnhildstveit and colleagues position these findings against the wider ketamine literature, noting parallels with rapid antidepressant effects and emerging evidence that combining ketamine with psychotherapy can enhance and prolong clinical benefit. The paper emphasises KAP as a promising framework and describes a three‑step model of preparatory psychotherapy, ketamine dosing, and integration psychotherapy; the reported BN‑BP KAP case is presented as illustrative of potential synergy between pharmacology and psychotherapy. Key limitations acknowledged include the very small and heterogeneous evidence base, reliance on uncontrolled case series and single‑case reports, variability in dosing and concurrent interventions, limited focus on AN to the exclusion of BN, BED and ARFID, and absence of randomised controlled data. Generalisability is further constrained by selective reporting and lack of standardised outcome measures and long‑term follow‑up across studies. The authors also note patient concerns regarding safety and therapeutic setting that must be addressed in clinical trials. In terms of implications, the paper calls for methodologically rigorous next steps: open‑pilot studies, adequately powered feasibility and randomised trials, and implementation research that includes standardised, empirically derived treatment regimens and outcome measures. Longitudinal assessments are recommended to characterise response durability, especially in severe and enduring cases. The authors urge investigation of optimal dose, frequency and duration of ketamine for EDs, systematic evaluation of KAP and other strategies to prolong effect, and comprehensive safety profiling across diagnostic subgroups and the lifespan. Ensuring appropriate "set and setting", informed consent, and follow‑up monitoring are listed as practical considerations for future clinical work.

Ragnhildstveit and colleagues conclude that while the literature on ketamine for eating disorders is small and preliminary, existing case reports and series point to potential therapeutic value, especially for treatment‑resistant patients. They recommend further empirical study across ED subtypes and severities, standardisation of treatment protocols and outcome measures, and investigation of adjunctive approaches such as ketamine‑assisted psychotherapy to define safety, efficacy and clinical contexts in which ketamine may be most useful.