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• Published: 26 November 2015

Anorexia nervosa

• Janet Treasure 1 ,
• Stephan Zipfel 2 ,
• Nadia Micali 3 , 4 ,
• Tracey Wade 5 ,
• Eric Stice 6 ,
• Angélica Claudino 7 ,
• Ulrike Schmidt 1 ,
• Guido K. Frank 8 ,
• Cynthia M. Bulik 9 , 10 &
• Elisabet Wentz 11  

Nature Reviews Disease Primers volume  1 , Article number:  15074 ( 2015 ) Cite this article

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• Feeding behaviour
• Nutrition disorders
• Psychiatric disorders

Anorexia nervosa (AN) is a psychiatric condition characterized by severe weight loss and secondary problems associated with malnutrition. AN predominantly develops in adolescence in the peripubertal period. Without early effective treatment, the course is protracted with physical, psychological and social morbidity and high mortality. Despite these effects, patients are noted to value the beliefs and behaviours that contribute to their illness rather than regarding them as problematic, which interferes with screening, prevention and early intervention. Involving the family to support interventions early in the course of the illness can produce sustained changes; however, those with a severe and/or protracted illness might require inpatient nursing support and/or outpatient psychotherapy. Prevention programmes aim to moderate the overvaluation of ‘thinness’ and body dissatisfaction as one of the proximal risk factors. The low prevalence of AN limits the ability to identify risk factors and to study the timing and sex distribution of the condition. However, genetic profiles, premorbid features, and brain structures and functions of patients with AN show similarities with other psychiatric disorders and contrast with obesity and metabolic disorders. Such studies are informing approaches to address the neuroadaptation to starvation and the other various physical and psychosocial deficits associated with AN. This Primer describes the epidemiology, diagnosis, screening and prevention, aetiology, treatment and quality of life of patients with AN.

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Introduction (J.T.); Epidemiology (N.M.); Mechanisms/pathophysiology (C.M.B. and G.K.F.); Diagnosis, screening and prevention (T.W. and E.S.); Management (J.T., S.Z. and A.C.); Quality of Life (E.W.); Outlook (U.S.); Overview of the Primer (J.T.).

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J.T. has received royalties from authored books, and an honorarium from Lilly for a presentation at the Diabetes Meeting 2015. She has received research grants from the National Institute for Health Research (NIHR) under the Research for Patient Benefit (RfPB) programme, Mental Health Biomedical Research Centre at South London, the Maudsley NHS Foundation Trust, King's College London, the Swiss Anorexia Nervosa Foundation, Guy's and St Thomas' Charity and the Psychiatry Research Trust. E.S. has received research grants funding from the World Association of Girl Guides and Girl Scouts. A.C. has received a travel grant from Eli Lilly in the past 5 years and won a prize for her work in 2010 at the VI Congresso Brasileiro de Cérebro, Comportamento e Emoções, RS, Brazil, which included support for attending an international conference (registration and travel expenses) by Lundbeck. C.M.B. has received a research grant from Shire Pharmaceuticals and royalties from Walker and Pearson, and acknowledges funding from the Swedish Research Council (VR Dnr: 538-2013-8864). All other authors declare no competing interests.

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Treasure, J., Zipfel, S., Micali, N. et al. Anorexia nervosa. Nat Rev Dis Primers 1 , 15074 (2015). https://doi.org/10.1038/nrdp.2015.74

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At its April 2021 meeting, the American Psychiatric Association (APA) Board of Trustees approved “The American Psychiatric Association Practice Guideline for the Treatment of Patients With Eating Disorders.” The full guideline is available at APA’s Practice Guidelines website.

The goal of this guideline is to improve the quality of care and treatment outcomes for patients with eating disorders, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR; American Psychiatric Association 2022 ). Since publication of the last American Psychiatric Association (APA) practice guideline on eating disorders ( American Psychiatric Association 2006 ), there have been many studies on psychotherapies for individuals with these diagnoses as well as some studies on pharmacotherapies. Despite this, there are still substantial gaps in the availability and use of evidence-based treatments for individuals with an eating disorder ( Kazdin et al. 2017 ). This practice guideline aims to help clinicians enhance care for their patients by reviewing current evidence and providing evidence-based statements ( Box 1 ) that are intended to increase knowledge, improve assessment, and optimize treatment of eating disorders.

Box 1. Guideline Statements a

Assessment and determination of treatment plan.

APA recommends (1C) screening for the presence of an eating disorder as part of an initial psychiatric evaluation.

APA recommends (1C) that the initial evaluation of a patient with a possible eating disorder include assessment of

the patient’s height and weight history (e.g., maximum and minimum weight, recent weight changes);

presence of, patterns in, and changes in restrictive eating, food avoidance, binge eating, and other eating-related behaviors (e.g., rumination, regurgitation, chewing and spitting);

patterns and changes in food repertoire (e.g., breadth of food variety, narrowing or elimination of food groups);

presence of, patterns in, and changes in compensatory and other weight control behaviors, including dietary restriction, compulsive or driven exercise, purging behaviors (e.g., laxative use, self-induced vomiting), and use of medication to manipulate weight;

percentage of time preoccupied with food, weight, and body shape;

prior treatment and response to treatment for an eating disorder;

psychosocial impairment secondary to eating or body image concerns or behaviors; and

family history of eating disorders, other psychiatric illnesses, and other medical conditions (e.g., obesity, inflammatory bowel disease, diabetes mellitus).

APA recommends (1C) that the initial psychiatric evaluation of a patient with a possible eating disorder include weighing the patient and quantifying eating and weight control behaviors (e.g., frequency, intensity, or time spent on dietary restriction, binge eating, purging, exercise, and other compensatory behaviors).

APA recommends (1C) that the initial psychiatric evaluation of a patient with a possible eating disorder identify co-occurring health conditions, including co-occurring psychiatric disorders.

APA recommends (1C) that the initial psychiatric evaluation of a patient with a possible eating disorder include a comprehensive review of systems.

APA recommends (1C) that the initial physical examination of a patient with a possible eating disorder include assessment of vital signs, including temperature, resting heart rate, blood pressure, orthostatic pulse, and orthostatic blood pressure; height, weight, and BMI (or percent median BMI, BMI percentile, or BMI Z-score for children and adolescents); and physical appearance, including signs of malnutrition or purging behaviors.

APA recommends (1C) that the laboratory assessment of a patient with a possible eating disorder include a complete blood count and a comprehensive metabolic panel, including electrolytes, liver enzymes, and renal function tests.

APA recommends (1C) that an electrocardiogram be done in patients with a restrictive eating disorder, patients with severe purging behavior, and patients who are taking medications that are known to prolong QTc intervals.

APA recommends (1C) that patients with an eating disorder have a documented, comprehensive, culturally appropriate, and person-centered treatment plan that incorporates medical, psychiatric, psychological, and nutritional expertise, commonly via a coordinated multidisciplinary team.

Anorexia Nervosa

10. APA recommends (1C) that patients with anorexia nervosa who require nutritional rehabilitation and weight restoration have individualized goals set for weekly weight gain and target weight.

11. APA recommends (1B) that adults with anorexia nervosa be treated with an eating disorder-focused psychotherapy, which should include normalizing eating and weight control behaviors, restoring weight, and addressing psychological aspects of the disorder (e.g., fear of weight gain, body image disturbance).

12. APA recommends (1B) that adolescents and emerging adults with anorexia nervosa who have an involved caregiver be treated with eating disorder-focused family based treatment, which should include caregiver education aimed at normalizing eating and weight control behaviors and restoring weight.

Bulimia Nervosa

13. APA recommends (1C) that adults with bulimia nervosa be treated with eating disorder-focused cognitive-behavioral therapy and that a serotonin reuptake inhibitor (e.g., 60 mg fluoxetine daily) also be prescribed, either initially or if there is minimal or no response to psychotherapy alone by 6 weeks of treatment.

14. APA suggests (2C) that adolescents and emerging adults with bulimia nervosa who have an involved caregiver be treated with eating disorder-focused family based treatment.

Binge-Eating Disorder

15. APA recommends (1C) that patients with binge-eating disorder be treated with eating disorder-focused cognitive-behavioral therapy or interpersonal therapy, in either individual or group formats.

16. APA suggests (2C) that adults with binge-eating disorder who prefer medication or have not responded to psychotherapy alone be treated with either an antidepressant medication or lisdexamfetamine.

a The authors of the guideline determined each final rating, as described in the section “Guideline Development Process” (see Table 1 in the full guideline ). A recommendation (denoted by the numeral 1 after the guideline statement) indicates confidence that the benefits of the intervention clearly outweigh harms. A suggestion (denoted by the numeral 2 after the guideline statement) indicates greater uncertainty. Although the benefits of the statement are still viewed as outweighing the harms, the balance of benefits and harms is more difficult to judge, or either the benefits or the harms may be less clear. With a suggestion, patient values and preferences may be more variable, and this can influence the clinical decision that is ultimately made. Each guideline statement also has an associated rating for the strength of supporting research evidence. Three ratings are used: high, moderate, and low (denoted by the letters A, B, and C, respectively) and reflect the level of confidence that the evidence for a guideline statement reflects a true effect based on consistency of findings across studies, directness of the effect on a specific health outcome, precision of the estimate of effect, and risk of bias in available studies ( Agency for Healthcare Research and Quality 2014 ; Balshem et al. 2011 ; Guyatt et al. 2006 ).

The lifetime prevalence of eating disorders in the United States is approximately 0.80% for anorexia nervosa (AN), 0.28% for bulimia nervosa (BN), and 0.85% for binge-eating disorder (BED) ( Udo and Grilo 2018 ), although estimates can vary depending on the study location, sample demographic characteristics, case finding, and diagnostic approaches ( Galmiche et al. 2019 ; Santomauro et al. 2021 ; Wu et al. 2020 ). Furthermore, data suggest an increasing incidence of eating disorders and inpatient care for eating disorders, particularly AN, during the COVID-19 pandemic ( Agostino et al. 2021 ; Asch et al. 2021 ; Otto et al. 2021 ; Taquet et al. 2021 ). Importantly, the lifetime burdens and psychosocial impairments associated with an eating disorder can be substantial because these illnesses can persist for decades, and they typically have an onset in adolescence or early adulthood ( Udo and Grilo 2018 ).

In the United States, for the 2018–2019 fiscal year, the total economic costs of eating disorders were estimated to be $64.7 billion, with an additional $326.5 billion attributable to reductions in well-being associated with eating disorders ( Streatfeild et al. 2021 ).

Eating disorders are also associated with increases in all-cause mortality and deaths due to suicide ( Auger et al. 2021 ; Nielsen and Vilmar 2021 ; Tith et al. 2020 ; van Hoeken and Hoek 2020 ). In addition, rates of suicide attempts are increased in individuals who have an eating disorder ( Keski-Rahkonen 2021 ; Smith et al. 2018 ; Udo et al. 2019 ). Morbidity and mortality among individuals with an eating disorder are heightened by the common co-occurrence of health conditions such as diabetes and other psychiatric disorders, particularly depression, anxiety, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), ADHD, and substance use disorders ( Ahn et al. 2019 ; Cliffe et al. 2020 ; Gibbings et al. 2021 ; Keski-Rahkonen 2021 ; Udo and Grilo 2019 ).

Accordingly, the overall goal of this guideline is to enhance the assessment and treatment of eating disorders, thereby reducing the mortality, morbidity, and significant psychosocial and health consequences of these important psychiatric conditions.

Overview of the Development Process

Since the publication of Clinical Practice Guidelines We Can Trust ( Institute of Medicine 2011 ), a report of the Institute of Medicine (now known as National Academy of Medicine), there has been an increasing focus on using clearly defined, transparent processes for rating the quality of evidence and the strength of the overall body of evidence in systematic reviews of the scientific literature. This guideline was developed using a process intended to be consistent with the recommendations of the Institute of Medicine ( Institute of Medicine 2011 ) and the Principles for the Development of Specialty Society Clinical Guidelines of the Council of Medical Specialty Societies (2012). Parameters used for the guideline’s systematic review are included with the full text of the guideline. The APA website features a full description of the guideline development process.

Rating the Strength of Research Evidence and Recommendations

Development of guideline statements entails weighing the potential benefits and harms of the statement and then identifying the level of confidence in that determination. (See Appendix G in the supplemental information accompanying the full guideline online for detailed descriptions of the potential benefits and harms for each statement.) This concept of balancing benefits and harms to determine guideline recommendations and strength of recommendations is a hallmark of GRADE (Grading of Recommendations Assessment, Development and Evaluation), which is used by multiple professional organizations around the world to develop practice guideline recommendations ( Guyatt et al. 2013 ). With the GRADE approach, recommendations are rated by assessing the confidence that the benefits of the statement outweigh the harms and burdens of the statement, determining the confidence in estimates of effect as reflected by the quality of evidence, estimating patient values and preferences (including whether they are similar across the patient population), and identifying whether resource expenditures are worth the expected net benefit of following the recommendation ( Andrews et al. 2013 ).

In weighing the balance of benefits and harms for each statement in this guideline, our level of confidence is informed by available evidence (see Appendix C in the supplemental information accompanying the full guideline online), which includes evidence from clinical trials as well as expert opinion and patient values and preferences. Evidence for the benefit of a particular intervention within a specific clinical context is identified through systematic review and is then balanced against the evidence for harms. In this regard, harms are broadly defined and may include serious adverse events, less serious adverse events that affect tolerability, minor adverse events, negative effects of the intervention on quality of life, barriers and inconveniences associated with treatment, direct and indirect costs of the intervention (including opportunity costs), and other negative aspects of the treatment that may influence decision making by the patient, the clinician, or both.

Many topics covered in this guideline have relied on forms of evidence such as consensus opinions of experienced clinicians or indirect findings from observational studies rather than research from randomized trials. It is well recognized that there are guideline topics and clinical circumstances for which high-quality evidence from clinical trials is not possible or is unethical to obtain ( Council of Medical Specialty Societies 2012 ). For example, many questions need to be asked as part of an assessment and inquiring about a particular symptom or element of the history cannot be separated out for study as a discrete intervention. It would also be impossible to separate changes in outcomes due to assessment from changes in outcomes due to ensuing treatment. Research on psychiatric assessments and some psychiatric interventions can also be complicated by multiple confounding factors such as the interaction between the clinician and the patient or the patient’s unique circumstances and experiences. The GRADE working group and guidelines developed by other professional organizations have noted that a strong recommendation or “good practice statement” may be appropriate even in the absence of research evidence when sensible alternatives do not exist ( Andrews et al. 2013 ; Brito et al. 2013 ; Djulbegovic et al. 2009 ; Hazlehurst et al. 2013 ). For each guideline statement, we have described the type and strength of the available evidence as well as the factors, including patient preferences, that were used in determining the balance of benefits and harms.

Guideline Scope

The scope of this document is shaped by the diagnostic criteria for eating disorders and by the available evidence as obtained by a systematic review of the literature through September 2021, particularly focusing on AN, BN, and BED as defined by DSM-III, DSM-III-R, DSM-IV, DSM-IV-TR, DSM-5, or ICD-10. This practice guideline addresses evidence-based pharmacological, psychotherapeutic, and other nonpharmacological treatments for eating disorders in adolescents, emerging adults, and adults. In addition, it includes statements related to assessment and treatment planning, which are an integral part of patient-centered care.

Our systematic review attempted to include literature on avoidant/restrictive food intake disorder (ARFID); however, rigorous clinical trial data were not available due to the relative recency of the introduction of this diagnosis. We have included some discussion of ARFID in the implementation sections of this document, particularly as it relates to assessment and treatment planning. We specifically excluded rumination disorder and pica from our search of the literature due to their typical age of onset in infancy or childhood and the limited evidence on their treatment. We also excluded treatment of obesity from the scope of this guideline because obesity is not categorized as an eating disorder.

Data are also limited on individuals with eating disorders and significant physical health conditions or co-occurring psychiatric conditions, including substance use disorders. Many of the available studies of eating disorders did not analyze data separately for these patient subgroups or excluded individuals with these comorbidities. Nevertheless, in the absence of more robust evidence, the statements in this guideline should generally be applicable to individuals with co-occurring conditions. Additionally, although treatment-related costs are often barriers to receiving treatment and cost-effectiveness considerations are relevant to health care policy, cost-effectiveness considerations are outside the scope of this guideline.

The full text of the practice guideline describes aspects of guideline implementation that are relevant to individual patients' circumstances and preferences. A detailed description of research evidence related to the effects of pharmacological and nonpharmacological treatments in individuals with eating disorders can be found in the appendices accompanying the full guideline at psychiatryonline.org/guidelines .

From the APA Practice Guideline Writing Group (Catherine Crone, M.D., Chair).

Practice Guidelines are assessments of scientific and clinical information that are current as of the date of authorship but are not continually updated and may not reflect the most recent evidence. They are provided as an educational service and should not be considered as a statement of the standard of care or inclusive of all proper treatments or methods of care. They are not intended to substitute for the independent professional judgment of the treating clinician. The ultimate recommendation regarding a particular assessment, clinical procedure, or treatment plan must be made by the clinician in light of the psychiatric evaluation, other clinical data, and the diagnostic and treatment options available. The guidelines are available on an “as is” basis, and APA makes no warranty, expressed or implied, regarding them. APA assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the guidelines.

APA and the Guideline Writing Group especially thank Laura J. Fochtmann, M.D., M.B.I., Blair Uniacke, M.D., Seung-Hee Hong, and Jennifer Medicus for their outstanding work and effort in developing this guideline. APA also wishes to acknowledge the contributions of other APA staff including Michelle Dirst, Andrew Lyzenga, and Kristin Kroeger Ptakowski. APA wishes to give special recognition to Joel Yager, M.D. for his decades of contributions to APA and its practice guidelines, including his work on the Systematic Review Group and serving as Chair of the Eating Disorders Writing Group for three prior versions of this guideline. APA also thanks the APA Committee on Practice Guidelines (Daniel J. Anzia, M.D., Chair), liaisons from the APA Assembly for their input and assistance, and APA Councils and others for providing feedback during the comment period.

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• Cited by None

• DOI: 10.14814/phy2.16092
• Corpus ID: 270665875

A refined rodent model of anorexia nervosa: Simulating state‐specific effects of caloric restriction and weight restoration

• Megan E. Rosa‐Caldwell , Lauren Breithaupt , +5 authors S. Rutkove
• Published in Physiological Reports 1 June 2024
• Medicine, Biology

53 References

Effects of rodent thermoregulation on animal models in the research environment..

• Highly Influential

Body Mass Index Specifiers in Anorexia Nervosa: Anything below the “Extreme”?

The oestrous cycle and skeletal muscle atrophy: investigations in rodent models of muscle loss, establishment of a chronic activity-based anorexia rat model, memory impairment is associated with the loss of regular oestrous cycle and plasma oestradiol levels in an activity-based anorexia animal model, weight restoration on a high carbohydrate refeeding diet promotes rapid weight regain and hepatic lipid accumulation in female anorexic rats, exposure to activity-based anorexia impairs contextual learning in weight-restored rats without affecting spatial learning, taste, anxiety, or dietary-fat preference., dsm-iv-tr and dsm-5 eating disorders in adolescents: prevalence, stability, and psychosocial correlates in a population-based sample of male and female adolescents., comparing rat's to human's age: how old is my rat in people years, animal models of eating disorders., related papers.

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• Case report
• Open access
• Published: 15 February 2022

Terminal anorexia nervosa: three cases and proposed clinical characteristics

• Jennifer L. Gaudiani   ORCID: orcid.org/0000-0002-2035-9390 1 ,
• Alyssa Bogetz 2 &
• Joel Yager 2  

Journal of Eating Disorders volume  10 , Article number:  23 ( 2022 ) Cite this article

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Most individuals with eating disorders will either recover, settle into an unrecovered but self-defined acceptable quality of life, or continue to cycle from crisis to relative stability over time. However, a minority of those with severe and enduring eating disorders recognize after years of trying that recovery remains elusive, and further treatment seems both futile and harmful. No level of harm reduction proves achievable or adequately ameliorates their suffering. In this subgroup, many of those with anorexia nervosa will experience the medical consequences of malnutrition as their future cause of death. Whereas anyone who wishes to keep striving for recovery despite exhaustion and depletion should wholeheartedly be supported in doing so, some patients simply cannot continue to fight. They recognize that death from anorexia nervosa, while perhaps not welcome, will be inevitable. Unfortunately, these patients and their carers often receive minimal support from eating disorders health professionals who are conflicted about terminal care, and who are hampered and limited by the paucity of literature on end-of-life care for those with anorexia nervosa.

• Case presentation

Three case studies elucidate this condition. One patient was so passionate about this topic that she asked to be a posthumous co-author of this paper.

Conclusions

Consistent with literature on managing terminal illness, this article proposes clinical characteristics of patients who may be considered to have a terminal eating disorder: diagnosis of anorexia nervosa, older age (e.g. age over 30), previous participation in high quality care, and clear and consistent determination by a patient who possesses decision-making capacity that additional treatment would be futile, knowing their actions will result in death. By proposing the clinical characteristics of terminal anorexia nervosa, we hope to educate, inspire compassion, and help providers properly assess these patients and provide appropriate care. We hope that this proposal stimulates further expert consensus definitions and clinical guidelines for management of this population. In our view, these patients deserve the same attendant care and rights as all other patients with terminal illness, up to and including medical aid in dying in jurisdictions where such care is legal.

As a patient with severe and enduring anorexia nervosa advocating for my legal right to MAID (medical aid in dying), I confronted numerous obstacles and challenges from the medical profession, related not just to the question of whether I should have access to MAID generally, but more so, how my anorexia, a psychiatric condition frequently misunderstood by the medical community, interacted with my decision making capacity and desire to pursue MAID as one potential option knowing that my illness was indeed terminal. –Alyssa

The vast majority of potentially terminal illnesses carry with them thoughtfully considered and evidence-based staging criteria. These criteria allow patients and clinicians to distinguish mild and likely curable presentations of the disease from irreversible, pre-terminal and terminal stages. Medical specialties treating cancer, organ failure, or various infectious diseases have dedicated considerable attention and resources to delineating levels of severity. While preliminary suggestions for labeling severe and enduring anorexia nervosa (SE-AN) [ 1 ] and for staging the disorder have been proposed [ 2 ], generally accepted staging criteria for anorexia nervosa (AN) have not yet been developed. Remarkably, the same diagnostic label (“AN”) and treatment criteria that apply to teenagers only a few months into their disorder are also used for patients who are decades older, who have lived through innumerable admissions to inpatient and residential care facilities, and whose quality of life has been irrevocably damaged by persistent, severe mental and physical illness. The field acknowledges SE-AN as a somewhat distinct clinical condition, but despite thoughtful clinical and research efforts [ 3 , 4 ] the designation has not been formalized as a diagnosis, and consensus regarding criteria for SE-AN remains elusive [ 5 ].

AN carries the second highest mortality rate in the DSM-5 after opioid use disorder, with a death rate estimated at 5–16 times that of the general population. [ 6 , 7 ] Several important recent studies confirm and expand upon these data. A specialized medical inpatient unit in France for those with severe anorexia nervosa evaluated 384 patients admitted over 17 years, with a mean age at admission of 29.4 years old. The standardized mortality ratio (SMR) was 15.9 for women and 22.4 for men, where older age was determined to be a major predictor of mortality. The mean age at death was 41.3 (± 15.3) years, on average two years after hospital admission. The SMR was maximally increased for patients whose first admission to the unit took place while they were between 25 and 35 years old. Specifically, those admitted between 30–34 years old had the highest SMR of 26. Somatic (medical) causes accounted for 43% of deaths, while 11.5% of deaths were caused by suicide. [ 6 ] In a registry-based observational epidemiological study encompassing the entire population of Denmark over 44 years, the SMR for all-cause mortality reached a maximum of about 6 in the age group 20–34 years, and the SMR for suicide in those with AN was 11. Natural causes accounted for two-thirds of death in those with AN. [ 8 ] Finally, a retrospective cohort study evaluated 19,041 individuals with an eating disorder in Ontario, Canada, using administrative healthcare data. The entire cohort, not comprised only of those with AN, had an SMR of 5; they found that potential years of life lost were 6 times higher than expected compared with the Ontario population. Similar to the other studies, peak values for SMRs were observed among adults between 30 and 44 years old, and again the SMRs observed in males were almost two-fold higher than in females. [ 9 ] Importantly, the profound suffering inherent in AN drives the high suicide rate noted in multiple studies, where up to 20% of patients who die prematurely do so by suicide [ 10 ]. Compared with gender- and age-matched groups, patients with AN are 18 times more likely to die by suicide [ 11 ].

Based on these data, AN can unquestionably prove fatal. Despite this fact, the field lacks clinical roadmaps for compassionate, appropriate care for those who will not be able to survive. This does great disservice to patients and their families. By comparison, we do not expect individuals with metastatic lung cancer who have disease progression despite past treatments, which often come with negative sequelae, to keep presenting for those same ineffective treatments. Rather, they are more likely to receive the psychological preparation, connection, and medical and emotional support offered to patients with terminal conditions. Although current laboratory measures and imaging studies by themselves are unable to help us stage patients with AN, based primarily on clinical histories and patients’ narratives we can better understand the clinical course of this illness and the subset of patients with AN who may seek palliative care [ 12 , 13 , 14 ].

There is growing recognition that palliative care may be appropriate for some patients, but the clinical characteristics for terminal anorexia nervosa have not been proposed. Delineating and validating this stage would greatly assist patients, families, and clinicians across disciplines, especially those in palliative and hospice care. Designating terminal AN may more readily enable patients to receive palliative care, hospice care, and emotional and practical resources for loved ones, as well as access to medical aid in dying (MAID) where legal. Therapeutic goals in these situations are to ameliorate suffering and honor the life lived. Of note, MAID is offered to individuals whose death is inevitable within six months from an underlying disease process; it provides patients a choice in how they die, not whether they die. It is not a means of suicide.

In this paper, we describe three cases of exceptional people whose AN was terminal, and who died peacefully with family around them. All three were patients of a private practice outpatient medical clinic specializing in eating disorders in Denver, Colorado. One patient, who had been a medical researcher herself, was so passionate about the topic that she asked to join as a posthumous author on this paper so her voice could be heard. The other two patients’ parents consented to share their son’s/daughter’s stories and reviewed, and all three families edited the relevant story prior to manuscript submission. All families agreed that first names should be used instead of a pseudonym or initials in order to emphasize the truly personal, real-life origin of these stories. Based on these experiences and others [ 12 , 14 ], we conclude by proposing a set of clinical characteristics of those who can be identified as having terminal AN.

Case presentations

Case 1: aaron.

Aaron was a 33-year-old man with a long history of restrictive AN, severe obsessive compulsive disorder (OCD), recurrent major depression, and chronic suicidality. He had been a sensitive child with low self-esteem and perfectionism from a young age. His parents noticed OCD traits from early childhood, but he did not receive this formal diagnosis until years later.

During his freshman year in high school, a health class warned about the risks of “eating junk food.” Aaron began to run regularly and played hours of basketball daily. One by one, he eliminated dietary fats and created food rules. His parents thought this was just a stage, an assessment they came to understand very differently over time, but they eventually recognized his serious problems and established a treatment team. Later in high school, Aaron was hospitalized several times for AN, participated in family therapy, and required his mother’s presence, even at school, to complete meals. Despite graduating as valedictorian of his high school class, he was initially too ill to start college. Later, his attempt to begin college was thwarted by his need for constant supervision of food intake. Aaron’s perfectionism and self-criticism ultimately ended his college career.

Over the next two decades, Aaron spent countless months in medical hospitals and in inpatient and residential eating disorder settings. He repeatedly gained the weight required for discharge so that he could return home, only to inevitably relapse. He felt mortified and guilty about the amount of money his family spent on his treatment, and he was acutely aware of life passing him by.

In his early 30 s, following a long and serious downward spiral during which he refused a higher level of care, his family finally threatened to call 911 if he did not enter treatment. Consequently, he was admitted to an inpatient eating disorder program. After first spending time in a hospital setting for stabilization where he refused to eat, a feeding tube was placed. A court mandate to ensure ongoing treatment was requested and granted on grounds of grave disability from his mental illness, and he spent the next 10 months against his will in inpatient and residential eating disorder care. He cut off communication with his parents but allowed the treatment team to talk with them. Eventually his therapist convinced him to have family sessions over the phone; it was the only time his parents could talk to him.

Aaron’s persistent resistance to treatment throughout his stay at the eating disorder program caused difficulty in maintaining his nutritional stability. He underwent in-depth exposure and response prevention therapy around food as he continued to be tube fed, and he was finally able to sustain his weight with oral food. At that time, he only agreed to eat to avoid the prospect of being administered olanzapine against his will, as he feared this medication would cause him to gain weight.

After Aaron had been fully weight restored for several months, he was stepped down to a partial hospital program (PHP). He immediately restricted intake and proceeded to lose nearly a pound a day, resulting in readmission to residential treatment where, after intensive efforts, he once again achieved his target weight. Aaron struggled with basic activities of daily living due to his OCD. For instance, he resisted using lotion or lip balm as he feared they might be absorbed into his skin as calories. He completed a course of intranasal ketamine in hopes of alleviating his OCD, depression, and suicidality, but ketamine treatments had no meaningful impact.

Author JG (hereafter referred to as “Dr. G”) first met Aaron for an outpatient medical consultation after he had completed this most recent residential treatment and was once again about to step down to PHP. This consultation constituted one component of an organized, comprehensive future discharge plan. In this initial medical visit, after a year of residential treatment, Aaron was medically stable. He desperately missed his eating disorder behaviors, fantasized about eating less and losing weight, and wished his AN would have already taken his life. Aaron mused that his all-or-nothing, perfectionistic temperament made the unknown terrifying, but he felt proud of how rigidly he had previously adhered to his eating disorder rituals, as he believed that few others could achieve a similar degree of calorie restriction. Despite his long history of treatments, including his year of suffering through the long court-mandated treatment, Aaron had never meaningfully changed his eating related attitudes, thoughts, or behaviors. He had absolutely no motivation for recovery.

During the initial consultation, Dr. G informed both Aaron and his emotionally supportive and highly invested parents that she could offer ongoing outpatient medical care along one of two pathways. In one, Aaron would complete PHP, be discharged to home (where he lived with his parents), see a therapist and dietitian regularly, and work on whatever degree of recovery he could bear, aiming toward a quality of life that he called “living productively.” Should he decide that he required a higher level of care, the team would promptly support that choice. On the second pathway, if Aaron relapsed and declined readmission, the outpatient team would no longer battle with him to seek a higher level of care, given the futility of his most recent, autonomy-depriving treatment course. Rather, the family and team would support and comfort him until such time as he required home palliative care and eventually hospice support. Aaron initially felt that these two choices were needlessly stark and binary, and he settled back into PHP.

Two months after the initial consultation, Aaron continued to endure PHP, primarily to honor his commitment to his residential treatment team that he would see through his course of treatment. But he felt no better. He received a course of intravenous ketamine to supplement the intranasal ketamine treatment initiated in the residential program, but he experienced no improvements in mood, hopelessness, or OCD. Just before discharge to his parents’ home, he still hadn’t decided which treatment pathway to choose. He would not accept psychiatric medications, and a team consisting of a physician, therapist, and dietitian was established to care for him at home.

However, starting on the day of his discharge from PHP, Aaron stopped eating altogether, a course of behavior that is rare even in those with severe AN. He drank only water, stating, “I don’t want to die, but my eating disorder is in charge.” A week later, he met with his longstanding outpatient therapist. She was very apprehensive about his ability to remain in the community, and she felt ambivalent concerning what her role might be if he insisted on remaining at home. Aaron told her, “I wish I could eat, but I won't eat; I don't want to die, but I feel hopeless that there's any other pathway.” The therapist worried that she would be forced to have Aaron detained against his will in his home state. A formal decision-making evaluation was performed by a local psychiatrist, and Aaron was found to possess decisional capacity. Consulting with his home therapist, Dr. G proposed that Aaron’s refusal to eat was less about “wanting to die” than simply accepting that he could not live—he was not “attracted to life” [ 17 ]. Dr. G suggested that the proper course at this point would be to proceed with a home palliative care consultation and shift treatment goals to supporting comfort and dignity, as Aaron clearly declined a return to treatment.

During a telemedicine meeting with Dr. G a week later, Aaron asserted, “I don't want to do this for anybody else anymore. It's time to do things only if I want them.” At about this time, Aaron also sought comfort from his therapist and his religious leader, as the prospect of death frightened him, and he was unsure what dying would mean. But he described that being given the choice of what would happen next was empowering – “different, scary, relieving, and right” – in great contrast to repeatedly feeling powerless and demeaned by his many prior chaotic relapses followed by intense pressures to return to treatment. Aaron signed a Do Not Resuscitate (DNR) order and within the next few days was referred to a home palliative and hospice care organization. Dr. G spoke with the organization’s medical director to explain why this brilliant 33-year-old man who was refusing to eat was being referred for palliative care. Aaron hoped that the home palliative care service would help him and his family “process this sorrow and fear.”

Two weeks later, after more than a month of eating nothing and drinking only water, Aaron’s OCD and insomnia were heightened; he worried that by simply smelling his mother’s cooking he might be ingesting those calories. He believed that he might absorb calories from the grocery cart of the person ahead of him at the store. Always reluctant to take medications, he began to consider accepting anxiolytics from the hospice staff, whom he thought were extremely kind.

Aaron noted that by spending no energy forcing himself to eat, he was able to direct energy toward engaging in his faith. His siblings came to visit, and as they talked and laughed, he realized it had been years since they had connected positively. Throughout the course of his eating disorder, every family connection had felt fraught. He summarized his collective family’s response to this pre-terminal phase as, “They were very supportive. They recognize the gravity of this situation. They aren't angry, sad but not fearful.” As he chose to spend his days talking with his parents and sleeping, he noted that he was thinking about others "rather than being so self-absorbed." Imagining his parents’ distress made him sad, and he wanted his parents to keep getting support after his death. "This is one of the hardest things they've had to deal with in their lives."

Even as he rapidly lost weight, Aaron’s body distortions grew worse, and he kept wishing his weight would fall even faster. After almost six weeks without food, Aaron began accepting anxiolytics and antiemetics. He obsessed that someone might have injected his water bottles with calories. When Dr. G asked if he had any words to share for posterity, he expressed words of warning for those who might find themselves in his situation: “OCD will amplify,” “Be prepared for an annoying obsessive brain that might drive you crazy,” and “Just because you aren’t eating doesn’t mean it’s all good now.” He expressed how vital it was to “have people in your life [doctor, parents, family, close friends] whom you trust and can seek reassurance from, who love you unconditionally,” whose comforting words can be “life-saving in terms of giving you peace.” He connected deeply with a feeling that peace comes from God.

After about eight and a half weeks without any food, Aaron was spontaneously vomiting daily and feeling much weaker. Beautifully cared for by home hospice, he began to take low dose morphine for pain and distress. When Aaron’s parents wondered what his death certificate would say about cause of death, Dr. G reassured them that the cause would be anorexia nervosa and malnutrition, not suicide. Often speaking through tears, Aaron’s parents described how they were enjoying a deep loving sweetness with their son that they hadn’t experienced in years, and how they would miss him when he died. They felt compassion for those who lose a loved one abruptly without having time for love, connection, and closure. Often, they saw glimpses of the boy they hadn’t seen in years, as when he looked at photos that made him laugh.

Two weeks later, Aaron passed away with his family surrounding him. Even as they were exhausted and grieving deeply, his parents expressed enormous gratitude for the care he received and for the way they had been able to reconnect with him.

Case 2: Jessica

Jessica was a 36-year-old woman with a history of OCD and AN, purging subtype (laxatives) that began during her junior year of high school, when she tried to lose weight prior to a vacation. This started a pattern of restricting, binge eating, and then overexercising that persisted into college. When her weight, which had remained normal for some time, did eventually drop, she left college for intensive outpatient eating disorder treatment. It was such a difficult experience that from this time on, she mistrusted eating disorders providers. She lamented that she lost most of the fun of college to her eating disorder.

Due to progressive constipation, Jessica began using laxatives, which led to laxative abuse. She soon found that every time she stopped taking laxatives, her weight skyrocketed (due to rehydration and rebound edema). Ultimately, her AN caused her to drop out of nursing school. Jessica experienced her first hip fracture from severe osteoporosis when she was critically emaciated at age 27, requiring her to move home with her parents; the following month she incurred a stress fracture of her shoulder from using crutches. Her parents pursued guardianship as Jessica was refusing a higher level of care, but her medical team refused to release records to the family’s attorney due to HIPAA. Without the option to pursue guardianship with mandated longer-term residential treatment, her parents came to believe this was the critical juncture where recovery might have been possible, but instead her disease became more entrenched. Over the next 7 months, working with her outpatient primary care provider, dietitian, and therapist, she slowly gained a meaningful amount of weight, although she remained very underweight. Following this, she got an excellent job and once again lived independently from her parents, working productively for three years. However, at age 29, her increased anxiety, the side effects of laxative abuse, and the shame of her anorexia caused her to separate herself from her family and to work from home, increasing her isolation. She checked herself into an expert inpatient medical center to stop using laxatives and then spent a week in inpatient eating disorder treatment before leaving against medical advice. Jessica did manage to stay off laxatives for a year but was plagued by edema. Repeatedly, restriction and overexercise would recur, usually accompanied by laxative abuse, which at its worst consisted of taking 100 tablets a day.

During her initial consultation with Dr. G, Jessica memorably stated, “The eating disorder keeps me out of integrity with my values. It doesn't feel good. You believe something but aren't living it. This is the biggest motivation for wanting to change. I really want to live in alignment with my values, honoring my body, feeling things, stopping being unkind to my body.” Although very kind and compassionate towards others, she struggled to show herself the same grace.

Jessica met criteria for immediate admission back to the inpatient medical service, but given her prior negative experiences with treatment, she wanted to attempt to keep working and live near her parents. She agreed to outpatient care with a multidisciplinary team, focusing on harm-reduction goals. Initially, Jessica was able to follow medical and nutritional recommendations faithfully. Then, within three months of initiating outpatient medical care she fell and sustained a pelvic fracture. This was frightening, disabling, and prevented her from taking her calming (and to her, calorie-burning) nature walks. Overcome by managing the challenges of a rapidly changing body on her own and worried about her fracture and bone health, Jessica readmitted herself to specialized inpatient medical care for medical stabilization. Following stabilization, she agreed to transfer to residential care to attempt a full course of eating disorder treatment. However, after two weeks in the residential care program she left against clinical advice, unable to follow the meal plan consistently and feeling extremely distressed by her bodily changes (even though her weight had barely changed).

At home, Jessica again tried hard to follow treatment recommendations at a harm-reduction level (no laxatives, low caloric intake, gentle movement in the outdoors), but once more the distress of bodily changes was too much for her to bear. About a month after leaving the residential program, Jessica first talked about the possibility of palliative care and began talking with her mom about suicidal thoughts. Most nights she would say she hoped she didn’t wake up the next morning. In order to help Jessica resist the laxatives that gave her such severe abdominal pain and nausea, and still hoping to support her in finding an acceptable degree of harm reduction, Dr. G worked with Jessica to use diuretics to manage fluid weight changes. (Notably, this approach would rarely if ever be offered in a more typical eating disorders treatment plan.) Jessica operated within these guidelines and constraints for the next five months, at times thinking she might be able to persist, but more often lamenting that this strategy was still too difficult and painful. By this point, she had been granted indefinite leave from work and moved in with her parents.

About nine months after initial consultation, Jessica acknowledged that it was time for a palliative approach, confessing, “I’m just ready. It's been a long fight. I'm eating so little, and I'm back on the laxatives every couple of days.” She declined intranasal or intravenous ketamine which might have ameliorated her depression, OCD symptoms, and hopelessness. As she felt progressively miserable physically and psychologically, her suicidality increased. She purchased a gun, and one night she drove to a bridge with thoughts of jumping off, but then decided to return home. She had difficulty finding a therapist who understood terminal AN and who could accept her treatment trajectory, but she found and worked with a kind naturopathic doctor who specialized in mental health, and she did experience some benefit from psychiatric medications.

At this point, fearful of suffering a long, drawn-out death from starvation and unwilling to put her parents through the agony of witnessing this decline, Jessica requested referral to a palliative care specialist who assessed patients for medical aid in dying (MAID). Dr. G spoke with Jessica’s parents repeatedly, assuring them that guardianship and forced treatment were likely now to be futile. The parents had done everything possible to help their daughter find an acceptable quality of life. Jessica signed a DNR order. After speaking with the palliative care physician by phone to discuss the case and advocate for Jessica, Dr. G completed the MAID forms as consulting physician, given that Jessica’s prognosis was presumed to be 6 months or less. The palliative care physician prescribed the MAID medications.

About a year after the initial consultation, and about three months after the MAID consultation, Dr. G saw Jessica for the last time via telemedicine. Jessica wrote to Dr. G in an e-mail, “I’ve been back in a place the last several weeks where the emotional pain and the physical and emotional exhaustion of living like this are just too much for me. I’m trying to make it to the end of May, maybe through June to meet my brother’s upcoming baby before I go.” Jessica described her life as filled with unbearable pain and anxiety. Watching people walking around the neighborhood making future plans felt devastating, because she’d “give anything to be in anybody else’s shoes.” Yet when she thought about stopping diuretics, eating enough food, and gaining weight so she could physically live that life, she said, “it feels impossible.”

Jessica waited several weeks to fill the MAID prescription. She then set multiple dates to use it over a couple of months and changed her mind as that date got closer. A month before her death, she started to receive home hospice services. During this time period, she had long conversations with her parents, brother, and friends, noting that she had many happy memories over her life, apologizing for what she had put them all through over the years, and stating that she hated her eating disorder. She told them she realized that, while her eating disorder behaviors made it seem like she hadn’t loved or trusted them at times, she loved them all very much. She repeatedly told her family that she didn’t want to die, that she didn’t want to miss out on future time with her family, friends, and niece and nephew, but she just couldn’t continue to exist this way. The emotional pain and anxiety were unbearable. She couldn’t live a normal life, and she felt her body was too destroyed to recover. Her parents believe that in her last month she was trying to die naturally by barely eating, reducing her fluid intake, and walking for hours daily, even when she had to sit down often to catch her breath. She stopped driving and carried identification in case she collapsed on a walk. She fainted at home several times in the week before her death, including the night before she died. On the day she took the MAID prescription, she stayed in bed, was at peace, and spent time talking with each parent and her brother. Together as a family, they reminisced, laughed, cried, had their “hug circle” as they had called it since her childhood, and felt surrounded by love. Her parents each held a hand, and her brother sat right next to her. During the three doses of the medicine taken over an hour, she was comfortable and conscious. Within ten minutes of taking the final dose, Jessica closed her eyes, and her breathing slowed.

Jessica didn’t choose to live with anorexia. For all the years she endured living within its prison and myriad complications, her parents ultimately felt strongly that she deserved to choose the time, place, and way of her release. They felt that an unexpected blessing of MAID was that it allowed Jessica to live several months longer than she otherwise would have. Knowing she didn’t have to die a violent death by suicide, that she would have a peaceful way out when the pain and anxiety became unbearable, and that she would be able to die with dignity surrounded by loving family, allowed her to hold on longer. As a dying wish to her mother, she shared, “Mom, I'd like you to do something that will help others not go through what I went through."

Case 3: Alyssa

Alyssa, the posthumous author on this paper, was a 36-year-old woman with OCD, depression, and restrictive AN who described herself as having “a type A, neurotic personality: a sensitive, compassionate, loving person who's incredibly self-critical and has wanted to do things 0% or 110% with no gray area.” She first felt suicidal at age 13, when she realized that her body was too large to fit into standard dress sizes for her upcoming Bat Mitzvah. She started therapy at that time and was continually in therapy thereafter. After going through high school at a higher weight, the summer before college she vowed to change her body and began exercising in earnest. In college it was easy to restrict. By the time she returned home for Thanksgiving she had lost a substantial amount of weight. Everyone praised her, and she experienced “a deluge of external validation that was irresistible,” firmly establishing her eating disorder by age 18. Alyssa wrestled with AN throughout the rest of her education and career. A brilliant academic, she became the only non-physician Assistant Director of a major academic medical center residency department, mentoring residents and students, doing research, and publishing in major journals.

After struggling with AN for 15 years, during which she received intermittent outpatient support, Alyssa moved in with her parents and reduced her workload. She was extremely helpful in her mother’s struggle with a cancer diagnosis and often underplayed the significance of her own illness. At age 33, to correct severe hypercalcemia she was admitted to the teaching hospital in which she had previously worked. The family felt that her AN was hardly addressed during that hospitalization, in part due to the fact that institutional expertise for AN was confined to a pediatric program. To them, this felt like a vital missed opportunity to attempt changing her disease trajectory, in particular as the only recommendation on discharge was to seek residential eating disorder care.

Alyssa worked for 7 months to obtain insurance authorization for care in a residential eating disorders program, and to gain enough weight to meet their admission criteria. However, upon admission to that program she was deemed still too underweight (by one pound) and was referred to a specialized inpatient medical program. Being rejected for care after so much work also felt like a missed therapeutic opportunity. After a delay, Alyssa spent several weeks in the specialized hospital program and met the minimal criteria for discharge, departing with the understanding that she would immediately enroll in another residential program. However, after discharge from the hospital she refused to do so and could never accept going to an eating disorders program thereafter.

In the years prior to initial consultation with Dr. G, Alyssa’s outpatient treatment team included a local primary care physician with whom she was very close, a therapist she had been seeing regularly in recent years, and an expert eating disorders therapist who had worked with her and the family over the years. Over a period of three years, Alyssa had intermittently thought about and even phoned Dr. G’s outpatient medical clinic, but she never booked an appointment, indicating that she felt very ambivalent about recovery and was considering a palliative care approach. When she finally presented for an initial consultation, Alyssa identified her goals as follows: “I really want a life, to use my Masters in Social Work degree to help others heal, to find a partner, and to experience pleasure, laughter, joy, and freedom, including from my own brain.” As her main barrier she cited the chronic, longstanding shame and body disgust that persistently kept her from meeting her own needs.

At the time of initial consultation, Alyssa met criteria for inpatient medical hospitalization, although she experienced remarkably few physical symptoms, which reinforced her view that she must be “fine.” She declined a higher level of care. Nonetheless, she saw herself as shamefully thin, more keenly felt given her extended family’s experience of the Holocaust. She wanted to be able to walk down the street without turning heads due to being so emaciated, but concurrently struggled to balance this desire against her strong resistance to gaining weight.

Alyssa agreed to ongoing care with the clinic and accepted referral to an expert registered dietitian. She committed to at least attempt a harm reduction approach in which she would slowly restore weight to a point where she could be more physically, mentally, and professionally functional, and where she could resume her yoga practice. However, she stipulated that she would halt weight restoration if and when her AN thinking could no longer bear it. Over the course of the next year or so, she valiantly succeeded in increasing her caloric intake considerably above her previous severely restrictive baseline. But due to the hypermetabolic state often seen in malnourished patients who increase their caloric intake, she experienced no meaningful weight gain.

Nine months after initial consultation, Alyssa emphatically reflected that her goals had not changed, but she had grave doubts about her ability to achieve them. She described feeling “utterly exhausted” and could no longer muster the strength to keep fighting. She vividly described her daily internal battles, struggling every minute of the day to eat enough of her meal plan and constantly fighting against the extreme headwinds of her AN’s resistance. Once she had eaten, she would bitterly berate and punish herself for having done so. At this point she was not certain that her AN was terminal, but she was moving strongly in that direction and wanted to understand her options.

Dr. G clarified that at any time, Alyssa could choose to pursue full recovery and a higher level of care, could continue fighting as she was, or could consider two options that did not focus on recovery. The first option would be choosing palliative care. This would acknowledge that she would likely not survive and also allow her to consider a "bucket list" of experiences for the time she had left. Palliative care would mean that she could eat what appealed to her, with no pressure applied by the team. The treatment focus would be on finding joy and comfort as much as possible. Dr. G emphasized the value of signing a DNR document to protect Alyssa from the mandates of the healthcare system in the event that she experienced an abrupt decline and/or cardiac arrest. Alyssa was also advised that a home palliative care/hospice evaluation would be useful to oversee her treatment as desired during this stage, for emotional and practical support if needed and to protect her parents from any potential legal repercussions should she pass away at home as an emaciated adult. Dr. G noted that for some patients, this stage can last a long time, and that some can “reset” when pressures to gain weight and threats of mandated treatment are removed. In some cases, this state of reduced external pressure might even lead to renewed ability to engage in meaningful harm reduction and even recovery work.

The second option would be to seek hospice care. Hospice care would be suitable if the torments of her AN and the extraordinary difficulties of moving about the world in a skeletal body were beyond being helped by a palliative care approach. Given her faster metabolism, if Alyssa abandoned her attempts to consume a higher meal plan, she would clearly have a less than six-month prognosis and qualify for hospice care. With this option, Dr. G would refer Alyssa to a home hospice service, anticipating that she would become increasingly frail. The home hospice staff would establish warm relationships with Alyssa and her parents, make sure that anxiety, insomnia, nausea, and/or pain were managed, and provide them all access to psychological and spiritual support as desired. During this time, Alyssa could live her life as she chose. As she became less independent, hospice would provide assistive aids such as a shower chair, bedside commode, and hospital bed. The overall goals would be to maximize Alyssa’s comfort, dignity, and time to connect with family.

During this conversation, Dr. G also noted that Alyssa lived in a location where MAID was legal. If she chose the hospice route—and had interest—a referral for the option of MAID was also possible. Alyssa was informed that she herself would have to administer the MAID medications if she chose to use them; no one else could administer them to her. After completing the required regulatory processes and filling the prescription, MAID medications could be used or not as desired. But, as the human body can be exceptionally resilient even with terminal malnutrition, having the medications at hand would give Alyssa the opportunity, while still having an intact brain, to choose not to suffer through additional weeks of extreme physical discomfort and weakness.

A week after these options were reviewed, Alyssa wrote Dr. G:

After deep reflection and discussion with my parents, I’ve decided it makes sense to initiate the Hospice process (Ie evaluation, etc.) now so my family and I are prepared for what may come. I would value your guidance and help with this….I do not know if they have ever worked with patients like myself… I would love for you to be the PCP overseeing this process regardless of the Hospice we select if, and only if, you are comfortable with this. I want to be clear that my priority is to obtain access to the medications that would support my legal right to die should I wind up choosing this path in the future. I feel strongly that based on our thorough discussion, I am aware of my options and their risks and benefits in light of the trajectory of my illness. Please do let me know what I can do to help facilitate initiation of this process. I am available and happy to help.

In a family meeting the following week, Alyssa’s father, a physician, tearfully shared the principles he and Alyssa’s mother had come to accept during intense conversations with their daughter: She had the right to choose care or no care after having been ill for 18 years. There would be no ultimatums. This disease would probably be the reason that "we lose you." They knew how much she had suffered and continued to suffer, and they understood that at some point the psychological anguish would become unbearable for her. They respected that this could be as bad as physical pain. They accepted that when the anguish became unbearable, Alyssa would have the right to end her life by taking medical aid in dying medications. They agreed that financial planning and end of life planning were worthy tasks. To Dr. G and to Alyssa, these words conveyed deeply reassuring love, compassion, and support.

Alyssa’s parents asked whether any treatments remained that might yet change the outcome of her course, specifically noting that Alyssa had not completed a full residential eating disorder program, never fully restored weight, never tried newer psychedelic options such as ketamine, psilocybin, or MDMA, and hadn’t had a feeding tube. Dr. G acknowledged that all but the feeding tube might ordinarily be undertaken prior to someone’s seeking end of life care for AN. Yet, she had been suffering for so long, and despite many conversations about all these treatment possibilities, Alyssa would not consent to any of them. Therefore, given her clarity of understanding around these issues and her sense that she could not fight anymore, everyone had to accept that they weren’t meaningful options. With regards to a surgical feeding tube in the context of AN rather than due an anatomical impediment, Dr. G noted that if someone restricts the “tube God gave them,” i.e. their esophagus, they would also be very likely to restrict through a surgical feeding tube, so that would not be a long term solution.

An excellent home hospice agency agreed to work with Alyssa and her family, and Dr. G placed a referral for a MAID consultation. The palliative care physician met with Alyssa about MAID. Since the idea of requesting MAID for a patient with AN was so foreign and unnerving to him, he asked Alyssa to be assessed formally for decision-making capacity. After a local psychiatrist confirmed that Alyssa clearly possessed decision-making capacity, the palliative care doctor fully accepted Alyssa’s right to enter home hospice care and could understand the rationale for MAID provision. However, even as he and his team provided empathetic support, he ultimately felt personally unable to write the MAID medication prescription due to his discomfort with the unique presentation. Clarification with the state’s Medical Board and other regulatory entities determined that Dr. G, licensed in this state although based in another state, could serve as prescribing physician, and that Alyssa’s longstanding primary care physician could serve as consulting physician. Dr. G prescribed the MAID medications about six weeks after Alyssa entered hospice care. Four days before her death, eager to contribute to this article, Alyssa sent Dr. G the following (unedited) notes about her thoughts on this complicated topic:

Below I share the considerations I made as I weighed the potential benefits and risks of pursing MAID. I share my experience in hopes of offering a first-hand perspective that may help other patients and physicians as they consider and weigh the option of utilizing MAID, rather than offering a prescriptive decision-making tool or recommending that all patients with terminal SEAN have access to such medication.

Personal considerations:

MAID not pursued in isolation, but rather in the context of being in Hospice care following a terminal dx of anorexia (i.e., estimated 6 months or left to live). I would not have qualified for Hospice care unless my illness was terminal (i.e., not reversible for me in light of physical, mental, emotional damage to my body).

In my individual case, death was inevitable. I clearly understood my prognosis and accepted this. I saw MAID as an opportunity to select a specified time and circumstances for my death. Death itself is fraught with fear, ambiguity, a sense of powerlessness and tremendous anguish, not just for the patient who is dying, but for that patient’s family. Upon deep reflection, I came to see MAID as an opportunity to relieve my suffering and minimize at least some of my family’s suffering related to my death by choosing the when and how of my death, rather than “wait” for sudden death from cardiac arrest or other outcome of my illness or experience a slow and protracted death as my family and I watch my body and mind degrade over days and maybe even weeks of time

I had to ask important questions about my quality of life and whether for me, the quality of my life was more important than the quantity of days I remained alive. I was experiencing extreme physical pain, was unable to walk, could not sit without discomfort, I couldn’t swallow my food, my breath was labored, and I had frequent chest pain. I was not living. I felt like “dead girl barely walking.” For me personally, a longer life spent in bed feeling ill and suffering and dependent on others to provide most of my care was not how I wanted to live. My concerns about this suffering trumped any fear of selecting the route of my death (again, knowing that death was inevitable). Knowing that I could utilize MAID if the suffering became so severe offered me a sense of ease and peace of mind in my final stage of life that I would not have had otherwise

One question that I needed to answer for myself honestly was whether I understood the impact use of MAID would have on my family. I had to confront that my use of MAID would be difficult for them, not just the idea of my using it but how their presence at the end of my death, watching me administer my own medications to die, would be ingrained in their memories of me as their daughter and their sister, and how this story of my passing would affect my family throughout the generations to come (i.e., what stories would they tell about my life and death, how could this be traumatizing or perhaps seen as healing?). Such questions could only be answered through ongoing involvement and discussion with my family members, which we had with my physicians and amongst ourselves

Another important question I asked was how would I want a family member to die if I knew their illness was terminal and death was imminent. Would I see their use of MAID as a compassionate act towards themselves? How would I tell their story? Would I extend the compassion I was asking for from them to them if the situation were reversed? I also asked them individually how they would want to die if they could have the option of choosing?

All in all, a voluntary decision, not made in haste, thoughtful, careful, meticulous. Decision made as arrangements were made for my passing including burial arrangements, financial and family orders.

Decision also heavily considered with spiritual advisors (chaplain, Rabbi, etc.)

Challenges faced:

MAID in general is highly controversial and its use is RARE – even for patients who do receive it, many do not end up using it. Only a handful of physicians who support using it. Makes it unknown and scary for physicians and patients alike; limited research

Makes acceptance of its use more difficult for family members, too

Prescribing MAID (for some physicians) may feel counter to physician identity as healer & fixer; may spark deep internal/ethical/moral debate for individual physicians as they weigh the option of whether to prescribe

Do they see this as an act of compassion for patients who wish to relieve their suffering?

Do they see this as prescribing a means of suicide?

Anorexia specific – for me, a big issue that caused most ethical debate was whether my case of anorexia nervosa was “reversible.” Many physicians misunderstand SEAN (not even an official DSM diagnosis) and that while anorexia nervosa is a psychiatric illness, it comes with severe medical complications that ultimately are the reason for death. Some of the physicians I worked with could not believe my illness was indeed terminal, but rather felt that there would be something that could be done to reverse the physical damage done to my body that would somehow lengthen my life (even if not for very long – i.e., 1 year).

Yes, perhaps I could stay alive for a few months while in the hospital, but I would have to live in the hospital (MDs might see the benefit of this, but could I? NO! This is where my own reflection around quality of life came in)

My personal belief that this is what makes having such an extreme form of AN so agonizing – mental and emotional suffering is compounded by painful physical complications

Gross misunderstanding about anorexia nervosa in general.

Just over a day before she died, Alyssa wrote to Dr. G, “Thank you with all of my heart for helping to make this possible. I view it as a tremendous act of love.” With family and spiritual support surrounding her, Alyssa became unresponsive in the natural course of her malnutrition. Shortly thereafter, she passed away peacefully. She never actually ingested the MAID medication she had at her disposal.

By presenting these three cases, we have intended to convey some of the emotional, moral, and ethical challenges and dilemmas that patients with SE-AN, their families, and their professional caregivers may face at the end of life. Suffering from unrelenting and irredeemable disorders, these patients made difficult choices, ultimately deciding “enough is enough” [ 18 ]. The anguish endured by these patients and their families resulted in part from lack of professional understanding and consensus regarding terminal care for patients with AN. Neither the fields of palliative and hospice care nor eating disorders have provided definitions or guidance regarding what constitutes a terminal condition in AN or proper ways to address patients and their families grappling with this condition.

Accordingly, we present the following proposed clinical characteristics of those with terminal AN for consideration by both fields (Table 1 ). As illustrated by our cases, no set of criteria will apply perfectly to every patient who identifies with having a terminal case of AN. However, based on prior literature on criteria for clinical terminality [ 15 ], high SMR in those who have previously received inpatient care, are older, and have a history of more severely medically compromised presentations [ 6 , 7 , 8 , 9 , 10 , 11 ], and clinical expertise, the authors propose these clinical characteristics. Some deviation within the second and third characteristics is to be expected and must be individualized to the patient situation. However, the first and fourth must be met in full.

Proposed clinical characteristics of patients with terminal anorexia nervosa

A diagnosis of anorexia nervosa . Anorexia nervosa is the only eating disorder that carries a guaranteed medical cause of death from malnutrition should weight loss continue unabated. As a result, consistent with literature on duration of life during hunger strikes resulting in death [ 16 ], a prognosis of less than 6 months can fairly be established when the patient acknowledges further treatment to be futile and stops engaging in active recovery work. A less than six-month prognosis is congruent with current practice around determination of terminal diagnoses. We fully recognize that patients with SE-AN are likely to have other psychiatric conditions as well.

Age of 30 or older . This criterion accommodates for what is clinically seen as a potential “late maturation phase” in which even those who have been sick for a long time may discover a shift in values and desires that motivates recovery as they enter their late 20 s. Every effort should be made to promote full recovery and continuation of life in those younger than 30. However, the SMR data of multiple recent studies showing the highest death rates in those with a history of inpatient admissions, longer duration of AN, and age over 30 years old [ 6 , 7 , 8 , 9 ], taken alongside what functionally has often been a decade or two of exhaustive, ultimately unsuccessful eating disorder treatment, indicates that the age of around 30 as a minimum for terminal AN is reasonable.

Prior persistent engagement in high-quality, multidisciplinary eating disorder care. Worldwide access to expert eating disorder care varies widely, as does the availability of access to expert inpatient, residential, and full day treatment programs for those with eating disorders. Thus, the definition of care identified here must remain somewhat broad. Before someone can decide they cannot recover, they must have participated in high-quality, expert care to the maximum extent that this is available. This provision should motivate policies that allow for transfers of patients out of designated “networks” that lack expertise, with funding coverage provided at a center of excellence. Ideally, at least some of this treatment will have been undertaken at a sufficiently high level of care to provide extensive structure and support, preferably to the point of full weight restoration at least once in the relatively recent past. Congruent with receipt of such care, qualified health care professionals on the team must support the patient in their decision to stop fighting. We acknowledge that many factors may impact patients’ ability to participate in such care, including lack of access to eating disorders expertise, limitations of the healthcare system, and a personal sense—often based on prior treatment experiences—that admission to certain care settings would cause more harm than good.

Consistent, clear expression by an individual who possesses decision-making capacity that they understand further treatment to be futile, they choose to stop trying to prolong their lives, and they accept that death will be the natural outcome. Careful determination of decisional capacity is required in each case [ 19 ]. An individual who wavers in their conviction or expresses different goals to different people is not yet ready to receive the appellation of terminal AN.

Most eating disorders providers have cared for patients with AN who, despite suffering for decades, continue to show extraordinary determination and resilience. These patients still want help, at least with a harm-avoidance strategy if not with outright full recovery. In these cases, every effort must be made to support the patient’s wishes and provide appropriate resources for recovery. There must be no “giving up” on those who still seek to get better. Indeed, the drive to live and ability to find aspects of life worth fighting for can be seen vividly in the majority of those with AN, even in the face of years or decades of illness and suffering. The psychological imperatives of AN that often lead patients to resist or refuse clinically appropriate care, hazarding medical and psychological risk and deterioration, may seem to conflict with a stated desire to keep trying for recovery. However, in honoring patient autonomy, responsive care must always be offered as long as an individual states that this is their wish.

Patients in their earlier and younger years of AN may say they would rather die than gain weight or nourish themselves properly, a characteristic indicating that AN may present as an ego-syntonic mental illness. Nonetheless, the majority of patients with AN ultimately recover, and such expressions of anguish can be met with compassion and appropriate multidisciplinary care. We would not condone accepting a terminal diagnosis in younger patients. Of note, there are no explicit physiologic markers or measurables (weight, degree of weight loss, presence of or degree of organ failure, vital signs) which delineate someone with terminal AN. Even individuals with extreme medical malnutrition may recover fully if they so choose and have access to expert care. By contrast, if all criteria for terminal AN are met, as in the case of Aaron, individuals should not be obliged to demonstrate extreme medical instability before having the right to choose to stop fighting. Furthermore, while the obsessional ruminations of individuals with AN can be perplexing, clinicians should not regard the presence of body distortions and food fears as proof that these patients are unable to understand personal options and make reasoned health care decisions.

How can we determine that patients with severe anorexia nervosa possess the clinical decision-making capacity necessary to permit them to withdraw from treatment? With respect to decision-making capacity, four traditional criteria are usually applied: understanding, appreciation, ability to reason, and communication of decision [ 20 ]. In Dr. G’s estimation, confirmed in the two cases where formal independent assessment by a psychiatrist was performed, each of the patients met these criteria and was therefore capable of deciding to withdraw from conventional treatment. Alyssa’s clear, incisive writing just days before her death beautifully illustrates the insight and cognitive capacity that many patients with AN possess right up to the end of their life.

Clinical, legal, and ethical commentators in the field concur that withdrawal from treatment may be appropriate when further treatment, whether voluntary of involuntary, will provide only brief improvement, and is unlikely to offer sustained quality of life [ 21 , 22 ]. A formal assessment of decision-making capacity may help ameliorate family member fears that such an important decision is being made in an appropriate and ethical manner, especially when AN fears and distortions can seem so irrational. In addition, a formal bioethics evaluation might be valuable, but consideration of this must be balanced against most bioethicists’ lack of experience with patients who have AN, with the risk that their own innate and misguided reaction that “this patient just has to eat” could undermine a qualified patient’s decisions that are supported by their longstanding care team and family. Even medical ethicists must be wary about how their own cognitive and affective biases might influence their recommendations. [ 23 ]

Family members and carers play an immensely important role in the lives of those with AN. They bear witness to the suffering and challenges experienced by those with AN and are usually directly involved in the recovery process in multiple ways (financial/material support/behavioral support/engagement in the therapeutic work, among others). Many dread the day their child legally becomes an adult and can choose to exclude them from the details of recovery work, such that they become the financial supporters of care they are no longer privy to. The exhaustion, fear, love, and hope experienced by family members cannot be overstated. In any case where a patient meets the criteria for terminal AN, it is always preferable to include family members in the discussions and ideally come to a consensus. There may be dissent within a family about whether their loved one should be allowed to make the decision to stop fighting. These three cases illustrated how each family was meaningfully involved in the clinical discussions in the months before each patient’s death. Each family’s ultimate acceptance (through deep grief) of their son or daughter’s prognosis and choice contributed to a heightened sense of connection and love prior to death.

Acknowledging the considerable controversies surrounding MAID for patients with mental disorders [ 24 , 25 , 26 ], we also submit that patients with terminal AN who are severely physiologically compromised, and whose end-of life suffering results from both psychological and physical pain, should be afforded access to medical aid in dying in locations where such assistance has been legalized—just like other patients with terminal conditions.

AN confers an exceptionally high death rate. The lack of acceptance of terminality in AN and the absence of professionally condoned protocols and standard procedures for supporting patients and families through these phases further complicates end-of-life stages for the adults with AN who cannot keep fighting. These represent a small fraction even of the population of those with SE-AN. Per our proposed clinical characteristics, patients must not only decline further recovery-oriented treatment (which is not uncommon at times for those with AN), but also must explicitly and consistently choose to stop trying to prolong their lives, accepting that death will be the natural outcome. When a patient begins talking about the possibility of not being able to survive, every effort should be made to validate such a serious perspective and to offer an individualized and thoughtful series of harm reduction strategies and treatment options that might make life bearable. However, the process of seeking alternatives to death must not be so exhaustive as to disrespect limits the patient sets; while a family might be desperate for their loved one to try an experimental treatment or “just try going to treatment one more time,” they must ultimately accept the patient’s lack of consent for these.

Our proposed clinical characteristics of patients with terminal AN have no bearing on those who wish to keep fighting despite very long-standing and severe disease, even when their eating disorder behaviors seem incongruent with survival. Very specifically, to move toward a designation of terminal AN, an individual must express consistently that they can no longer live with their disease and will no longer maintain a minimum nutritional intake needed to support life. To be clear, each patient is unique and requires careful individual assessment and consideration as to the best approach going forward. Consistent with calls from others regarding the need for better definition and agreement regarding labeling and staging for SE-AN in general [1,2,3,4 5], the authors hope that these cases and characteristics of those with terminal AN will provide a starting point for identification, care, and further discussion. We would strongly encourage the development of expert consensus criteria and clinical guidelines endorsed by both the fields of palliative and hospice care and eating disorders. These brave, suffering individuals deserve no less.

Availability of data and materials

All narrative data and record of e-mails exchanged with patients and families throughout and after their care with the clinic are available.

Abbreviations

• Anorexia nervosa

Dr. Jennifer Gaudiani

Medical Aid in Dying

Obsessive Compulsive Disorder

• Severe and enduring anorexia nervosa

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Acknowledgements

Dr. Gaudiani would like to acknowledge the Gaudiani Clinic’s nurse, Abby Brockman, RN, for her excellent clinical care of these patients and their families.

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Dr. Gaudiani was the internist for the three patients, drafted the article, and reviewed and approved revisions. Ms. Bogetz (deceased patient) contributed to the text and proposed criteria. Dr. Yager consulted with Alyssa and her family, contributed to the text, and provided extensive editing.

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Gaudiani, J.L., Bogetz, A. & Yager, J. Terminal anorexia nervosa: three cases and proposed clinical characteristics. J Eat Disord 10 , 23 (2022). https://doi.org/10.1186/s40337-022-00548-3

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No evidence for cross-sectional or longitudinal associations between cognitive flexibility performances and nutritional status in a cohort of inpatients with anorexia nervosa.

1. Introduction

2. materials and methods, 2.1. study population, 2.2. measures, 2.2.1. self-report questionnaires, 2.2.2. neuropsychological assessment.

• The alertness subtest was used to adjust for potential psychomotor retardation. Participants were asked to press the answer key as quickly as possible as soon as a cross appeared in the center of the screen. The cross appeared at random intervals and no feedback was provided. The variable of interest was the median reaction time (RT).
• The flexibility subtest is a set-shifting task with low learning sensitivity. The complex non-verbal condition with 100 trials was chosen to control for the potential bias of age-related differences in verbal ability. A series of angular and rounded figures appeared simultaneously on the screen ( Supplementary Figure S1 ) and participants were required to press the right or left response key as quickly as possible depending on whether the target stimulus appeared to the right or left of the screen’s center. The instruction was to respond alternately to angular and rounded targets, starting with the angular shape. No feedback was provided. The variable of interest was the median reaction time (RT) for correct answers.

2.2.3. Nutritional Status

2.3. statistical analyses, 3.1. sample characteristics, 3.2. identification of potentially confounding variables, 3.3. cross-sectional associations, 3.4. longitudinal associations, 3.5. post hoc analyses, 4. discussion, 5. conclusions, supplementary materials, author contributions, institutional review board statement, informed consent statement, data availability statement, acknowledgments, conflicts of interest.

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Share and Cite

Castaño, L.; Fatseas, M.; Cuzacq, M.; Mattar, L.; Godart, N.; Berthoz, S. No Evidence for Cross-Sectional or Longitudinal Associations between Cognitive Flexibility Performances and Nutritional Status in a Cohort of Inpatients with Anorexia Nervosa. Nutrients 2024 , 16 , 1982. https://doi.org/10.3390/nu16131982

Castaño L, Fatseas M, Cuzacq M, Mattar L, Godart N, Berthoz S. No Evidence for Cross-Sectional or Longitudinal Associations between Cognitive Flexibility Performances and Nutritional Status in a Cohort of Inpatients with Anorexia Nervosa. Nutrients . 2024; 16(13):1982. https://doi.org/10.3390/nu16131982

Castaño, Lutzi, Melina Fatseas, Maylis Cuzacq, Lama Mattar, Nathalie Godart, and Sylvie Berthoz. 2024. "No Evidence for Cross-Sectional or Longitudinal Associations between Cognitive Flexibility Performances and Nutritional Status in a Cohort of Inpatients with Anorexia Nervosa" Nutrients 16, no. 13: 1982. https://doi.org/10.3390/nu16131982

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Schmidt U, Sharpe H, Bartholdy S, et al. Treatment of anorexia nervosa: a multimethod investigation translating experimental neuroscience into clinical practice. Southampton (UK): NIHR Journals Library; 2017 Aug. (Programme Grants for Applied Research, No. 5.16.)

Treatment of anorexia nervosa: a multimethod investigation translating experimental neuroscience into clinical practice.

Chapter 1 background and structure of the report.

• Introduction

Anorexia nervosa (AN) has existed throughout different epochs and cultures. 1 Key symptoms are restricted food intake, weight loss, hyperactivity, and in some cases bingeing and purging. Psychological features include morbid fear of fatness and body image disturbance. AN typically affects young females, although it also affects some men. 2 AN usually starts in adolescence, when brain development is incomplete. 3 Starvation can impair brain function in a lasting way. 4 Early intervention is essential in producing good outcomes. 5 Treatments in the later stages of illness are much less successful. AN is highly heritable but environmental factors are aetiologically important. 6 , 7 Progress has been made in identifying risk factors for AN (e.g. premorbid feeding problems, obsessive compulsive and anxious traits, high levels of exercising and overinvolved parenting). 6 , 7 Research on the genetic, epigenetic and neurobiological underpinnings of eating disorder (ED) psychopathology 8 – 13 has identified neurocognitive and social cognitive biomarkers, such as impaired set-shifting, poor central coherence or emotion processing impairments, including poor theory of mind, 14 – 18 which have the potential to inform predictions of treatment outcome and prognosis. A key challenge is to utilise all this knowledge to develop targeted treatments. To this end, we have developed a model of how AN arises and is maintained, informed by these and other clinical neuroscience findings and with the aim of guiding treatment. 19 , 20

People with AN consult their general practitioner (GP) significantly more than others in the 5 years prior to diagnosis. 21 A single consultation about eating or weight/shape concerns strongly predicts the subsequent emergence of AN. 22 Although GPs exclusively treat 20% of cases with AN, 23 they are often not confident at managing AN, 24 and there is usually a considerable delay between a diagnosis being made in primary care and the point when more specialist help becomes available. 25

Many parts of the UK lack NHS provision of specialist services for AN. 26 , 27 Treatment by non-specialists is problematic as many patients are admitted unnecessarily and for lengthy periods, 28 with extra costs to the NHS. 29 For example, 35% of people with AN seen in non-specialist Child and Adolescent Mental Health Services (CAMHS) are admitted to hospital, contrasting with only 10% of those seen in specialist ED services. 30 More child and adolescent psychiatric beds (20%) are occupied by young people with AN than any other diagnostic group. 31 Weight gain 32 and longer-term outcomes 33 are poor in non-specialist units and the mortality is higher. 34 , 35 Thus, there is a need to disseminate specialist knowledge of this illness. Transitions between services (e.g. from child to adult services, home to university health services, inpatient to follow-up care) are common and can result in fragmented care, thus putting patients at risk. 36 , 37

Lifetime prevalence rates for AN are 1.6% in women and 0.3% in men. 7 The median duration of illness is 6 years. 38 Physical complications affect all organs 39 and the risk of death is the highest of any psychiatric disorder. 40 If they become pregnant the pregnancy is considered high risk and they experience difficulties feeding and playing with their children. 41 Severe psychiatric comorbidity is common. 42 Quality of life is severely impaired, 43 more so than in depression. 44 The cost per case of AN is at least that of schizophrenia. 45 , 46 AN accounts for the highest proportion of admissions of duration > 90 days (26.8%) and the longest median length of stay (36 days). 28 Eating disorders are one of the leading causes of disease burden in terms of years of life lost through death or disability in young women. 47 The family are usually the main carers. They report similar difficulties to carers of people with psychosis, but are more distressed. 25 , 48 The burden of caregiving and other societal costs have never been examined in economic terms.

This report presents the results of seven independent but integrated work packages (WPs), which form the Applied Research into Anorexia Nervosa and Not Otherwise Specified Eating Disorders (ARIADNE) programme. These WPs focus on optimal disease management for people with AN at all stages of illness, from prevention and detection through to treatment and preventing relapse. The studies focus on a range of populations, including samples from the community, those drawn from inpatient and outpatient settings, as well as specialist groups, such as mothers with an ED and carers of those with an ED. The majority of our WPs focus on building evidence on the efficacy and effectiveness of interventions for these populations, grounded in our clinical neuroscience model of AN. We report on findings from six independent interventions that have been developed and tested by the ARIADNE group during this programme. In addition, we present analyses of the economic and clinical implications of existing care pathways and patterns of service use.

• Aims and objectives of the ARIADNE programme

Responding to the need for high-quality research into the management of AN, the overarching aims of the ARIADNE programme were to:

• produce, validate and disseminate improved evidence-based interventions for AN
• collaborate with patients and carers throughout the project
• improve clinical outcomes in AN, by early detection and intervention, by reducing chronicity and relapse, and by improving carer outcomes
• improve acceptability and cost-effectiveness of AN treatments
• deliver standardised, trainable and disseminable AN treatments
• assess service utilisation and NHS costs of AN and implications of changes in clinical practice for patient care and resources.

Our objectives were: WP1a, to develop a training programme for school staff to enable them to detect and manage EDs; WP1b, to develop and test a school-based prevention programme for risk factors for EDs; WP2a, to develop an improved treatment for adults with AN that targets disease-maintaining factors, is matched to symptoms, personality and neuropsychological profile and which can be used as a first-line treatment in outpatient settings, and to evaluate the efficacy and cost-effectiveness of this treatment; WP2b, to test and validate components of this treatment, designed as intensive modules for inpatients with AN (i.e. those with severe, chronic or treatment-resistant AN); WP3, to evaluate the efficacy and cost-effectiveness of a carer skills training intervention, and to assess its impact on carer outcomes (e.g. distress, caregiving efficacy) and patient outcomes; WP4, to improve understanding of the nature of a debilitating core symptom of AN (i.e. hyperactivity); WP5, to develop and test a relapse prevention programme for inpatients with AN; WP6, to obtain information on the needs of mothers of children with an ED and the risks of the maternal ED for their offspring and to use this information to inform the development of an intervention for mothers with an ED to minimise the impact of their ED on their children; WP7a, to study existing care pathways for AN, with a focus on the impact of having access to specialist ED services; and WP7b, to study service utilisation and cost of illness in EDs.

• Patient and public involvement in the ARIADNE programme

Patient, carer and public involvement has been central to the research in the ARIADNE programme. Mrs Susan Ringwood, the Chief Executive Officer of Beat (the main UK patient carer organisation for EDs) was a co-applicant on the programme. As such, she was involved in the development of the overall programme aims, ensuring that the research questions were aligned with patients’ and carers’ needs. Patients and carers were also part of the Programme Steering Group.

Examples of patient and public involvement (PPI) in specific WPs are as follows.

Example 1: early intervention in schools

Wok package 1a involved the development and pilot testing of a teacher training programme for EDs (see Chapter 2 ). This research was devised and led by a former ED service user. It involved an extensive period of public consultation, which was used to assess the needs of both school staff and school students in this area. Thorough consultation was achieved through online surveys reaching over 800 school staff and over 500 students. Intervention materials for the training programme were then developed using an iterative process in which two panels of school staff (six members per panel) reviewed draft materials and their feedback was incorporated. PPI ensured that the training materials being developed were responding to a genuine need and were aligned with the needs of the school staff that would be using them.

Example 2: prevention

The intervention development in WP1b for the prevention programme (see Chapter 3 ) was informed by focus groups with 22 adolescent girls, who provided their experiences of body dissatisfaction, disordered eating and their recommendations for a preventative intervention. The intervention materials were then developed in conjunction with a panel of key stakeholders, which included a young person with a history of an ED, two young people without a history of an ED, and three secondary school teachers. Feedback provided by this panel was incorporated into the materials in an iterative process.

Example 3: carers interventions

Work package 3 evaluated an intervention for carers of people with AN, which was used as an adjunct to inpatient treatment (see Chapter 6 ). It included extensive PPI, with several members of the research team having personal experiences of an ED. The self-help materials (Experienced Carers Helping Others; ECHO) were developed in collaboration with patients and carers. 49 In addition, the majority of telephone coaching sessions offered during the intervention were provided by trained individuals with personal experience of an ED (either having recovered from the disorder themselves or as a carer). The findings from this trial are being disseminated to the public through a website dedicated to carers of those with an ED [URL: www.thenewmaudsleyapproach.co.uk (accessed 3 July 2017)], a newsletter, the database of ED volunteers and the annual carer’s conference which we run with Beat – the main national organisation for people with EDs and their families.

From the above, it is clear that patients and carers were involved in designing the programme, implementing the WPs and disseminating findings. Such collaboration between researchers and service user representatives has been highlighted as exemplifying good practice in service user involvement by the Mental Health Research Network (MHRN). 50

• Report structure

The overarching aims of the ARIADNE programme were realised through seven independent, but integrated, WPs which are presented in detail in this report. An outline of the chapters is as follows:

Work package 1: prevention and early intervention

Chapters 2 and 3 focus on prevention, detection and early intervention of EDs. In Chapter 2 , we present the development and evaluation of a learning package for school staff on how to recognise symptoms of EDs, how to communicate about EDs sensitively and how to assess risk. Chapter 3 outlines the development of a teacher-delivered prevention programme for EDs, and the results of a cluster randomised controlled trial (RCT) evaluating its efficacy.

Work package 2: treatment

Chapters 4 and 5 focus on treatment of AN. In Chapter 4 we present the evaluation of the Maudsley Model of Anorexia Nervosa Treatment for Adults (MANTRA) using a large RCT with individuals in an outpatient setting. Chapter 5 explores the use of components of this treatment in an inpatient setting, designed as intensive modules for severe, chronic or treatment-resistant AN. Here, we evaluate this approach through case report, qualitative evaluation and a pilot trial comparing it to treatment as usual (TAU).

Work package 3: carers interventions

Chapter 6 presents an intervention for those caring for individuals with AN. We present findings from a large RCT assessing the impact of a guided self-help intervention for carers of individuals with AN (ECHO), in addition to standard inpatient care. We report on outcomes for both carers and for patients up to 12 months post discharge from inpatient care.

Work package 4: physical activity in anorexia nervosa

Chapter 7 focuses on the assessment of activity levels and endocrine changes in individuals with AN. We present data from an observational study. Individuals with AN (inpatients and outpatients) are compared with individuals with anxiety and healthy controls (HCs) using a range of methods, including body composition, endocrine measurements, self-report and actimetry.

Work package 5: relapse prevention

Chapter 8 focuses on relapse prevention. Here, we present a feasibility RCT on a novel e-mail-guided manual-based intervention to be used in the post-hospitalisation aftercare of patients with AN.

Work package 6: mothers with an eating disorder

In Chapter 9 , we present research on mothers with an ED, a special population that may need tailored services. We report findings regarding fertility difficulties in women with an ED, and associations between maternal EDs and their children’s diet and growth trajectories.

Work package 7: care pathways and economic evaluations

Chapter 10 presents results regarding service use, focusing on how access to specialist services affects rates of referrals, admissions for inpatient treatment, continuity of care and service user experiences. Chapter 11 uses data from ARIADNE WPs (WPs 2, 3, 5 and 7a), plus the British Cohort Study (1970) (BCS-70), to identify the costs of services and treatments used by people with AN and to estimate its annual costs for England.

General discussion

Chapter 12 draws together the findings from the seven WPs and highlights clinical implications and recommendations for future research based on this programme.

Included under terms of UK Non-commercial Government License .

• Cite this Page Schmidt U, Sharpe H, Bartholdy S, et al. Treatment of anorexia nervosa: a multimethod investigation translating experimental neuroscience into clinical practice. Southampton (UK): NIHR Journals Library; 2017 Aug. (Programme Grants for Applied Research, No. 5.16.) Chapter 1, Background and structure of the report.
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