Table 1.

Articles for Assessment of Severe Enduring Anorexia Nervosa (SE-AN) criteria

Reference		Overview	Title	Mean BMI kg/m2 (SD)	Duration years	Previous treatment history	Other Measure of Severity
1.	[36] Ambwani et al., 2020	Retrospective study- Patients grouped into early stage and SE-AN	A multicenter audit of outpatient care for adult anorexia nervosa: Symptom trajectory, service use, and evidence in support of “early stage” versus “severe and enduring” classification.	Of SE-AN group:15.95 (1.27)	Defined for SE-AN Group ≥ 7	Patients in the SE-AN group had been hospitalized more often than those in the early-stage group	Defined for SE-AN group: Severity of psychological distress (DASS-total ≥ 60)
2.	[62] Bemer et al., 2021	Retrospective study-BMD in “extremely malnourished” “extremely severe” female inpatients with AN	Bone mineral density at extremely low weight in patients with anorexia nervosa	Excluded if BMI ≥ 16 Of participants: 12.60 ± 1.60	Of participants:11.10 ± 10.40	Not reported	Assessed BMD but did not use this to define severity of AN.
3.	[58] Bianchi et al., 2021	Position paper presenting “harm reduction” approach in SE-AN	The Ethical Defensibility of Harm Reduction and Eating Disorders	Refers to hypothetical patient with SE-AN as having a BMI of 14	Definition: ≥6	Not reported for defining SE-AN	Not reported for defining SE-AN. Emphasis on improving quality of life.
4.	[21] Broomfield et al., 2017	PRISMA literature review with the goal of better defining criteria for SE-AN.	Labeling and defining severe and enduring anorexia nervosa: A systematic review and critical analysis	Range in included studies:13.31–19.80	Range in included studies:2.88–20.4	Studies including criteria for previous failed treatment attempt(s)	Measures indicative of significant impairment of quality of life, psychological and/or social.
5.	[34] Broomfield et al., 2021	Expert panel study to better define “later stage AN”	Establishing consensus for labeling and defining the later stage of anorexia nervosa: A Delphi study	Participants consensus that duration of illness, quality of life and unsuccessful attempts at evidence-based treatment are important to include in a universal definition of illness
6.	[115] Calabrese et al., 2022	Clinical trial evaluating effectiveness of ketamine and a ketogenic diet on weight recovered participants with persistent eating disorder psychopathy.	Ketogenic diet and ketamine infusion treatment to target chronic persistent eating disorder psychopathology in anorexia nervosa: a pilot study	All considered “weight restored”	Inclusion criteria > 10	Not reported	All considered “weight restored” but with ongoing severe AN-related preoccupations
7.	[43] Calugi et al., 2017	Study evaluating outcomes of those with SE-AN and those with AN, but not SE-AN	Intensive enhanced cognitive behavioural therapy for severe and enduring anorexia nervosa: A longitudinal outcome study	Defined Severe (BMI 15-15.99) Defined Extreme (BMI < 15) For SE-AN group: 15.2 (2.0)	Definition for SE-AN group > 7 Participants in SE-AN group 12.3 (4.7)	84.4% of SEAN group noted recent treatment failure	EDE, EDE-12, GSI
8.	[45] Dalton et al., 2022	Clinical trial of rTMS effectiveness for SE-AN	My dad was like “it’s your brain, what are you doing?“’: Participant experiences of repetitive transcranial magnetic stimulation treatment in severe enduring anorexia nervosa.	Inclusion criteria > 14	Defining Inclusion criteria: ≥3 Participants: 15.05 ±11.33	Defining Inclusion criteria: ≥ 1 NICE-2017 recommended day or inpatient treatment. Participants: Number of previous hospitalizations 2.31±1.95 Mean duration of previous hospital stays in months 11.56 ±12.02	Various tools used though not to define SE-AN
9.	[46] Dalton et al., 2018	Clinical trial of rTMS effectiveness for SE-AN	Randomised controlled feasibility trial of real versus sham repetitive transcranial magnetic stimulation treatment in adults with severe and enduring anorexia nervosa: the TIARA study	Inclusion criteria > 14 Participants: 16 (1.44)	Defining Inclusion criteria: ≥3 Participants: 14.07 (10.75)	Defining Inclusion criteria: ≥ 1 NICE-2017 recommended day or inpatient treatment. Participants: Number of previous hospitalizations 2.18 (1.91) Mean duration of previous hospital stays in months 10.49 (11.66)	Various tools used though not to define SE-AN
10.	[47] Dalton, Foerde, et al., 2020	Clinical trial of rTMS effectiveness for SE-AN	The effect of repetitive transcranial magnetic stimulation on food choice-related self-control in patients with severe, enduring anorexia nervosa.	Inclusion criteria > 14 Participants: 15.90 ± 1.40	Defining Inclusion criteria: ≥3	Defining Inclusion criteria: ≥ 1 NICE-2017 recommended day or inpatient treatment.	Various tools used, though not to define SE-AN
11.	[48] Dalton, Lewis, et al., 2020	Clinical trial of rTMS effectiveness for SE-AN (follow-up)	Repetitive transcranial magnetic stimulation treatment in severe, enduring anorexia nervosa: An open longer-term follow-up	See Dalton 2018	See Dalton 2018	See Dalton 2018	See Dalton 2018
12.	[37] Fernandes Arroteia et al., 2020	Case report “severe” “chronic” AN response to Deep brain stimulation	Impressive weight gain after deep brain stimulation of nucleus accumbens in treatment-resistant bulimic anorexia nervosa	Participant: 12.8	Participant:26	“The patient has participated in various psychiatric therapies, including behavioural therapy”	Various tools used, though not to define SE-AN
13.	[116] Forbes, 2020	Opinion piece on withdrawal of care for adolescents with “severe anorexia”	Futility in adolescent anorexia nervosa and the question of withdrawal of care	Not included	Refers to > 7, though points out this cannot be applied for adolescents.	Not included	Not included
14.	[54] González Macías et al., 2021	Case report of intervention for SE-AN.	Group family psychotherapy during relapse. Case report of a novel intervention for severe and enduring anorexia nervosa	Participant: 16.0 No defining criteria for SEAN used	Participant:11 No defining criteria for SEAN used though “chronicity” noted as defining	Participant: None specifically for eating disorders No defining criteria for SEAN used though “treatment failure” noted as defining	Participant: Vomiting of 70 a week, compulsive exercise, self-injuries, risk behaviors
15.	[117] Guinhut et al., 2021	Study evaluating mortality for patient admitted to a specialized clinical nutrition unit for “extremely severe malnutrition”	Five-year mortality of severely malnourished patients with chronic anorexia nervosa admitted to a medical unit	Defining: <13 Participants: 12.7 (± 2.2)	Participants:9.8 ± 9.3	Participants: 2.9 ± 3.4	Various tools used though not to define SE-AN
16.	[22] Hay & Touyz, 2018	Editorial on defining SEAN	Classification challenges in the field of eating disorders: can severe and enduring anorexia nervosa be better defined?	Defining criteria: “underweight”	Notes that long duration is one criterion for SE-AN Agreed lower limit 3	Defining criteria: “Exposure to at least two evidence-based treatments appropriately delivered together with (an appropriate) diagnostic assessment”	Defining criteria: “A persistent state of dietary restriction, and overvaluation of weight/shape with functional impairment”
17.	[55] Hemmingsen et al., 2020	Case report of cognitive performance patient with “chronic” AN and “extremely low BMI”	Case report: cognitive performance in an extreme case of anorexia nervosa with a body mass index of 7.7	Participant: 7.2	Patient: 25	Patient: Repeated hospitalizations in treatment facilities specializing in eating disorders.	Various tools used though not to define SE-AN
18.	[57] Herpertz-Dahlmann, 2020	Commentary on detecting risk of developing “serious and enduring” AN	Serious and enduring anorexia nervosa from a developmental point of view: How to detect potential risks at an early stage and prevent chronic illness?	Not reported	Refers to Hay & Touyz, 2018: >3	Refers to Hay & Touyz et al., 2018: Exposure to at least two evidence-based treatments	Not reported
19.	[118] Israely et al., 2017	Clinical trial evaluating effectiveness of tyrosine in “severe hospitalized” AN patients	A Double-Blind, Randomized Cross-Over Trial of Tyrosine Treatment on Cognitive Function and Psychological Parameters in Severe Hospitalized Anorexia Nervosa Patients	Participants: 15.5 (1.6)	Participants: 6.3 (4.9)	Participants: Number of prior hospitalizations 1.4 (0.7)	Various tools used, though not to define SE-AN
20.	[50] Johansson et al., 2022	Study evaluating polygenic risk association with severity and outcome for “severe and enduring eating disorders”	Polygenic association with severity and long-term outcome in eating disorder cases	Participants: 15.91 (1.39) AN-R Participants: 16.52 (1.49) AN-BP	Follow-up time (difference in years between year at first registration and year when recontacted for recruitment) ≥ 5 years	Treatment resistance noted as important and as such all participants had undergone at least one treatment attempt	SEED definition: CIA score ≥ 18 and a follow-up time ≥ 5 years (i.e., years between initial registration and ANGI recruitment)
21.	[49] Knyahnytska et al., 2019	Study evaluating feasibility and safety of insula dTMS in those with SE-AN	Insula H-coil deep transcranial magnetic stimulation in severe and enduring anorexia nervosa (SEAN): A pilot study	Participants: 16.6 ± 0.9	Definition of treatment resistance: >5	Definition of treatment resistance: Failure to respond to at least 2 trials of intensive treatment interventions	Various tools used, though not to define SE-AN
22.	[59] Marzola et al., 2021	Study attempting to determine profiles for those with AN of varying duration. Those with LD-AN, have more previous unsuccessful treatment attempts, and lower lifetime BMI. Did not impact treatment response.	Inpatients with severe- enduring anorexia nervosa: Understanding the “enduringness” specifier	Participant in long duration group: At baseline 14.3 (2.1) Lowest lifetime 12.8 (1.9)	Long duration defined as ≥ 7	Participant in long duration group: Number of previous hospitalizations 2.6 (3.2) SD	Numerous assessments were conducted but none allowing for a clear definition of SEAN from non-SEAN AN
23.	[119] Mishima et al., 2021	Study using MRI to evaluate structural brain changes in those with SE-AN.	Structural brain changes in severe and enduring anorexia nervosa: A multimodal magnetic resonance imaging study of gray matter volume, cortical thickness, and white matter integrity.	Participants: 14.2 (2.5)	Participants: 15.7 (9.0)	Not reported	Various tools used, though not to define SE-AN
24.	[51] Oudijn et al., 2021	Study evaluating DBS in those with “treatment-refractory anorexia nervosa”	Deep brain stimulation of the ventral anterior limb of the capsula interna in patients with treatment-refractory anorexia nervosa.	Inclusion criteria: <15	Inclusion criteria: ≥10	Inclusion criteria: “Lack of response to ≥2 typical modes of treatment including ≥1 inpatient treatment of hospitalization”	Inclusion criteria: GAF score ≤45 for ≥2 years
25.	[64] Park et al., 2018	Study evaluating feasibility and efficacy of DBS in those with SE-AN	Study Protocol: Using Deep- Brain Stimulation, Multimodal Neuroimaging and Neuroethics to Understand and Treat Severe Enduring Anorexia Nervosa	Inclusion criteria: >13, < 16	Inclusion criteria: >7	Inclusion criteria: “lack of response to two or more typical modes of treatment, such as inpatient weight restoration, psychotherapy and psychopharmacology”	Inclusion criteria: Disabling severity with substantial functional impairment1
26.	[52] Pérez et al., 2022	Study evaluating efficacy of DBS in those with SE-AN.	Cognitive and quality-of-life related factors of body mass index (BMI) improvement after deep brain stimulation in the subcallosal cingulate and nucleus accumbens in treatment-refractory chronic anorexia nervosa	Inclusion criteria: >13, < 15.99 (participants outside this range could participate if meeting other criteria)	Inclusion criteria: ≥10	Inclusion criteria: Lack of response to ≥3 voluntary intensive treatments or clinical worsening and unwillingness to receive further treatment, including hospital admissions for involuntary feeding.	Various tools used, though not to define SE-AN
27.	[35] Raykos et al., 2018	Study examining whether AN duration or severity impacts response to cognitive behavioral therapy. Study found that they did not.	Severe and enduring anorexia nervosa? Illness severity and duration are unrelated to outcomes from cognitive behaviour therapy.	Participants: 16.8 (1.5)	Participants:5 [3 low, 12 high] Grouped into 3-, 7- and 11-year illness duration for assessment.	Participants: 91.8% and 55.2% had a history of psychological treatment and psychiatric hospitalizations, respectively.	Noted “the severity of problematic eating disorder attitudes and cognitions at pretreatment (had) no impact on the amount of change in BMI during the early phase of treatment.”
28.	[120] Russell et al., 2019	Literature review on “harm reduction” approach in SE-AN	Harm minimization in severe and enduring anorexia nervosa.	Does not propose criteria	Does not propose criteria	Does not propose criteria	Does not propose criteria
29.	[53] Scaife et al., 2022	Study evaluating efficacy of DBS in those with SE-AN	Deep brain stimulation of the nucleus accumbens in severe enduring anorexia nervosa: A pilot study.	Inclusion criteria:>13, < 16	Inclusion criteria:>7	Inclusion criteria: ≥3 voluntary intensive treatments (partial or full hospitalization) and ≥2 trials of psychological treatment	Various tools used though not to define SE-AN
30.	[70] Smith & Woodside, 2020	Retrospective study of data from inpatient eating disorder treatment facility to compare characteristics of patients with multiple admissions to those with good outcomes	Characterizing Treatment-Resistant Anorexia Nervosa	Participants in treatment- resistant group: 14.36 [13.56 low, 15.60 high]	Participants in treatment-resistant group: 6.84 [low 2.62, 12.32 high]	Treatment-resistant defined as two or more incomplete inpatient admissions and no complete admissions	Participants in treatment- resistant group: EDEQ 5.29 [low 4.76, high 5.59] and BDI: 46.00 [low 34.00, high 53.00]
31.	[121] Strand et al., 2020	Review paper providing background on palliative care for SE-AN.	A palliative care approach in psychiatry: Clinical implications	“More or less permanent low BMI”	“Longstanding Illness”	“Numerous treatment episodes have not resulted in any lasting remission”	“Patient who has ‘tried everything’ without success”
32.	[33] Sun et al., 2015	Chapter reviewing neurosurgical treatments for psychiatric conditions, including SEAN	Surgical treatments for anorexia nervosa	Participants weight must be < 85% of ideal body weight (and/or BMI < 17.5)	DSM-IV criterion C, and GAF ≤45 or less for at least 2 years	Participants must have been treated with an appropriate therapy for more than 3 years. At least two types of therapy must have been applied with no response.	“Must have experienced a rapid decrease in body weight over a short time period, which could be life-threatening without effective intervention”
33.	[122] Tumba et al., 2023	Perspective paper presenting the difficulties of SEAN cases, the harm reduction approach and physician-assisted suicide.	Clinical and Ethical Dilemmas in the Involuntary Treatment of Anorexia Nervosa	Definition: 13–14	Definition: 6–12	Not included	Definition: “Have decreased likelihood of remission, have acquired various physical consequences of prolonged disordered eating, potassium (3.0 mmol/L); persistent risk of acute medical decompensation and need for hospitalization.”
34.	[44] Voderholzer et al., 2018	Case study of “chronically ill” participant with “extreme” AN	3-year course after successful therapy of extreme anorexia nervosa	Participant: 8.5	Participant: 7	Participant: 3 prior inpatient stays in eating disorder specialty clinics	Participant: Extreme urge to move
35.	[56] Westermair et al., 2020	Perspective paper presenting palliative care for SE-AN	A palliative approach for severest anorexia nervosa?	Criteria for palliative care: Extremely low BMI (e.g. <13 kg/m2	Criteria for palliative care long duration of illness (e.g. 10 years)	Criteria for palliative care: High number of inpatient admissions and coercive measures without sustained symptom reduction (e.g.,>3)	Criteria for palliative care: Pronounced purging behavior. Psychiatric comorbidities Somatic comorbidities Unwillingness to change, identification with/pride in the disease
36.	[60] Wildes et al., 2017	Study on developing an empirically based definition of SE-AN	Characterizing severe and enduring anorexia nervosa: An empirical approach	Noted: “patients with AN could be grouped into higher and lower severity profiles that differed with respect to eating disorder behaviors and quality-of-life, as well as several external validators including age, weight concerns, and lifetime mood and anxiety comorbidity. Moreover, within each severity profile, there was dimensional variability in eating disorder behavior, quality-of-life, and indicators of chronicity (i.e., illness duration, repeated bouts of hospital treatment, and low BMI)”.
37.	[20] (Wonderlich et al., 2020	Review of historical issues in diagnosing SE-AN as well as novel treatments and clinical perspectives	Severe and enduring anorexia nervosa: Update and observations about the current clinical reality.	Refers to Hays 2018 proposed criteria: “underweight”	Refers to Hay 2018 proposed criteria: >3	Refers to Hay & Touyz, 2018 proposed criteria: “Exposure to at least two evidence-based treatments appropriately delivered together with (an appropriate) diagnostic assessment”	Refers to Hay & Touyz, 2018 proposed criteria: “A persistent state of dietary restriction, and overvaluation of weight/shape with functional impairment”
38.	[69] Zhu et al., 2020	Review of psychological treatments for those with SE-AN	Psychological treatments for people with severe and enduring anorexia nervosa: A mini review	Refers to Hay 2018 proposed criteria: “underweight”	Refers to Hay & Touyz, 2018 proposed criteria: >3	Refers to Hay & Touyz, 2018 proposed criteria: “Exposure to at least two evidence-based treatments appropriately delivered together with (an appropriate) diagnostic assessment”	Refers to Hay & Touyz, 2018 proposed criteria: “A persistent state of dietary restriction, and overvaluation of weight/shape with functional impairment”

AN-R- Anorexia Nervosa-Restricting type; AN-BP- Anorexia Nervosa Binge Purge type; BDI-Beck Depression Inventory; BMD-Bone Mineral density; BMI-Body Mass Index; CIA- Clinical Impairment Scale; DASS-Depression, Anxiety, and Stress Scales; EDE- Eating Disorder Examination; GAF-Global Assessment of Function; GSI- Global Severity Index; MRI: Magnetic resonance imaging; NA-Not Applicable (and/or provided); NICE-National Institute for Health and Care Excellence; rTMS- Repetitive Transcranial Magnetic Stimulation; SE-AN- Severe and Enduring Anorexia Nervosa; SD-Standard Deviation