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Psychiatrists are called on to help patients with an array of stubborn mental health illnesses. Some of the most challenging to treat are also the deadliest: eating disorders. Characterized by a persistent disturbance of eating that impairs health and psychosocial functioning, these disorders include anorexia nervosa, avoidant/restrictive food intake disorder, binge eating disorder, bulimia nervosa, pica, and rumination disorder. Too often, their outcomes are tragic. Anorexia nervosa is associated with the highest mortality rate of all psychiatric disorders, with fatal outcomes observed in approximately 10% of cases, primarily from 

Recently I watched the 2017 Netflix film 

, a semi-autobiographical story about a 20-year-old named Ellen and her journey to recovery from anorexia nervosa. It is based on the experiences of Marti Noxon, the film’s director, and Lily Collins, the actress who plays Ellen. The film starts with a written warning of triggers, a warning that should be taken seriously by anyone likely to be upset or encouraged by the behavior.

In the film, Ellen is a cynical, artistic young woman whose anorexia has made her life unmanageable. Forced to see a new doctor by her nervous stepmother, she ends up in an inpatient rehab unlike any other she has been in before: A house with 7 young individuals supervised by a blunt house manager and an unconventional clinician—Dr Beckman, played by Keanu Reeves. The young patients are diverse, both demographically and in terms of their eating disorders. The housemates include a Black female with binge eating disorder, a White female with bulimia nervosa, a British white male with anorexia, and a pregnant White female with anorexia (who has a miscarriage). The movie’s diverse cast reflects the epidemiology of eating disorders, which affect individuals of various ages, sizes, socioeconomic statuses, gender identities, races, and cultural and ethnic backgrounds.

When we meet Ellen, her weight has fallen dangerously low; she exercises excessively, shows obsessive attention to counting calories, and hints at a preoccupation with thoughts of food, consistent with the diagnosis of anorexia nervosa. Another character with anorexia nervosa also feels distressed when she learns the number of calories that she has received through a feeding tube. Ellen wears loose clothing, which is a warning sign for anorexia, since loose outfits hide weight loss and can help the wearer 

 She reassures her sister and herself that she has it all under control, a common belief among patients with eating disorders.

Another character, Anna, has bulimia nervosa. She engages in the purging behavior of vomiting, uses laxatives, and exercises secretly. Anna’s experience of binge eating is not shown, despite binging being a core component of bulimia. Often, individuals with binge eating disorder are not given significant attention, even though this is the most common eating disorder in the 

The movie also shows the exasperation of the patients’ families. Ellen’s stepmother and stepsister exemplify the fallacies that so many individuals have about eating disorders. “Why don’t you just eat?” Ellen’s sister asks in exasperation, while her stepmom gibes: “Do you think this is beautiful?” The pathogenesis of eating disorders is complex and attributable to a combination of genetic, environmental, and biological factors, including dysregulation of homeostatic drive and the 

 Like most mental illnesses, childhood adversity plays an important role. Ellen’s mother came out as gay when Ellen was 13 years old and now lives in Phoenix, running a horse therapy farm with her partner. We do not see the father; he seems to be physically and emotionally absent. The child with the eating disorder is often expressing dysfunction within the family system through her behaviors and symptoms, as Ellen exemplifies.

Ellen and her peers are shown in a residential group home in which they have a lot of say in their treatment. This may not be a realistic portrayal. Treatment of eating disorders generally involves an interdisciplinary team; this team includes a mental health clinician, dietitian, and a general medical clinician. Although Beckham conducts individual and family sessions, the treatment approach overall does not match with commonly used, well-established therapy plans like cognitive behavioral therapy, psychodynamic psychotherapy, or the Maudsley model of 

Beckham has a tough tone: He calls Ellen’s attitude “childish and cowardly” and tells her, “You know how [to recover].” He makes statements such as, “Stop waiting for life to be easy. Stop hoping for somebody to save you....Face some hard facts and you could have an incredible life.” These ideas suggest that Ellen needs to simply use her willpower and decide to get better, which is not a realistic vision for recovery. For Ellen, it was not about eating, it was about deciding to choose life. To achieve long-term recovery, the focus needs to be redirected to the underlying emotional, cultural, psychological, and spiritual issues.

Several noteworthy scenes have stayed with me: The emotional scene when Ellen asks her mother to feed her like a baby; the thousands of emotions that trace across her face every time she steps on the scale to be weighed; and the way she constantly circles her upper arm with her middle finger and thumb (a practice known as body checking). At the end of her family therapy, Ellen states, “I’m sorry that I’m not a person anymore; that I’m a problem.” This is touching, because medical professionals and family can lose sight of the fact that their patients are individuals with feelings, not just diagnoses.

Noxon’s film does an incredible job of portraying the nuances of this complicated character living with an even more convoluted illness while also developing the world around her. 

 finds the humor in its material, the absurdity of real-life mixed in with real dangers. Collins, who has been honest about her own experiences with eating disorders, channels that struggle into a fine performance.

In 1983, when Karen Carpenter died of anorexia, the general public expressed shock that someone could starve themselves to death. In the 1990s, unfortunately, skinny was the overwhelming female beauty standard. Now some websites glamorize anorexia, advising readers on how to avoid eating, and some show so-called 

 pictures on Instagram. The more we talk about eating disorders as a serious mental illness, the more we can break down the walls of stigma that keep individuals from seeking the early intervention that improves prognosis.

is chief resident physician of psychiatry at the University of Missouri–Columbia.

1. Arcelus J, Mitchell AJ, Wales J, Nielsen S. Mortality rates in patients with anorexia nervosa and other eating disorders. A meta-analysis of 36 studies. 

. National Eating Disorders Association. Accessed April 21, 2021. 

. National Eating Disorders Association. Accessed April 21, 2021. 

4. Treasure J, Claudino AM, Zucker N. Eating disorders. 

5. Zipfel S, Giel KE, Bulik CM, et al. Anorexia nervosa: aetiology, assessment, and treatment. 

A television drama looks at eating disorders from the patient, physician, and family perspectives. What does it get right—and wrong?

Breaking the Skinny Standard: Anorexia on Screen 

Obsessive-compulsive disorder and related conditions like 

, hording disorder, and trichotillomania are all common mental health issues. They all impair psychosocial functioning and quality of life, sometimes to a dangerous degree. Fortunately, well-known, first-line treatments are often effective. But for tough cases, clinicians may need other options.

In this Mental Health Minute, Katharine Phillips, MD, previews an upcoming panel at the American Psychiatric Association’s annual meeting: “

Treatment of Severe Obsessive-Compulsive and Related Disorders: What Do You Do If First-Line Treatments Don’t Work

?” Phillips and the panelists will discuss the latest research and treatment developments.

is currently professor of psychiatry, DeWitt Wallace Senior Scholar, and Residency Research Director for the Department of Psychiatry at Weill Cornell Medicine. She is also an attending psychiatrist at New York-Presbyterian Hospital and adjunct professor of Psychiatry and Human Behavior at the Alpert Medical School of Brown University.

Have your patients had unrealistic ideas about their bodies or appearances? 

Share comments with your colleagues by emailing 

. Comments may be shared online pending review and editing for style.

Obsessive-compulsive disorder and related conditions do not always respond to first-line treatments. Fortunately, new options are on the horizon. 

What To Do When First-Line Treatments Don’t Succeed

Stress is one of the biggest mental health issues facing Americans today. But what is stress, exactly, and how should it be treated? In this Mental Health Minute, Teralyn Sell, PhD, distinguishes between 3 kinds of stress and talks about what can (or cannot) be done about each of them.

 holds a doctorate in psychology and is the founder of Pro Recovery Rx, a supplement line dedicated to supporting brain health for individuals in addiction recovery. She also teaches a class called NeuroHealth Coach, which helps professionals integrate brain health into their daily lives.

How do you help patients understand and handle their stress? 

Not all stressors are alike—and different types require different treatments. 

What Are the 3 Kinds of Stress?

According to Susan J. Noonan, MD, MPH, high nutrient-dense foods, like colorful fruits and vegetables, whole grains, beans, fish, poultry, and a small amount of olive oil and dairy can improve your patient's mood and lower their risk for depressive episodes. 

Keeping glucose levels steady may also help prevent mood swings. 

 is a physician consultant and Certified Peer Specialist in the Department of Psychiatry at McLean Hospital and the Massachusetts General Hospital. She is the author of four books and a blog on managing depression, most recently 

Helping Others With Depression: Words to Say, Things to Do

 (December 2020). Dr Noonan offers peer counseling to fellow patients, including physicians and other professionals, and can be confidentially reached through her website at 

A healthy diet can improve mood and effectiveness of antidepressant medications. Here's why your patients should be eating healthier. 

Food Is the Fuel

 involving 2 million participants, people experiencing depression, anxiety disorder, or bulimia, are at heightened risk of excessive alcohol use.

Unhealthy alcohol use and psychiatric disorders frequently co‐occur, but understanding how the levels of alcohol consumption affect those with psychiatric disorders might provide valuable insight to health care providers. The study sought to learn more about these relationships.

Researchers used alcohol screenings from Kaiser Permanente Northern California (KPNC), an integrated healthcare delivery system, to collect data from a large, population‐based sample. More than 12 million alcohol screenings were conducted, which will help identify subgroups of patients with psychiatric disorders and co‐occurring unhealthy alcohol use.

Medical assistants asked 3 questions. One is a modified version of the National Institute on Alcohol Abuse and Alcoholism single‐item screening question used to determine whether the individual had drinking-heavy days: “How many times in the past 3 months have you had 5 or more drinks in a day?” The second and third are questions used to calculate average alcoholic drinks consumed per week: “On average, how many days per week do you have an alcoholic drink?” and “On a typical drinking day, how many drinks do you have?”

From these questions, patients were classified into 2 groups: low risk of alcohol abuse and unhealthy use. The unhealthy use class was further divided into subgroups: daily, where patients exceeded daily drinking limits; weekly, where patients exceeded weekly drinking limits; and both. Researchers then compared these answers to whether patients had a documented psychiatric disorder diagnosis, focusing on a list of 8 common psychiatric disorders: depression, bipolar disorder, anxiety disorder, obsessive compulsive disorder, schizophrenia, schizoaffective disorder, anorexia nervosa, and bulimia nervosa.

In the final sample of patients, it was found that the daily group was more likely to be male and aged 18 to 34 years old, while the weekly group was more likely to be female and aged 65 or older. The daily and weekly groups were more likely to have higher household incomes, greater than approximately $87,500. Those who reported no alcohol usage were more likely to be Asian, Native Hawaiian, or Pacific Islander. Those diagnosed with bipolar disorder or schizoaffective disorder were more likely to report no drinking, as well.

From this data pool, care management strategies for these patients can be formed, ideally for primary care settings. The findings support a need for screening for unhealthy alcohol use in primary care, which would help clinicians address alcohol problems early and help to prevent the onset of an alcohol use disorder.

1. Palzes VA, Parthasarathy S, Chi FW, Kline-Simon AH, et al. Associations Between Psychiatric Disorders and Alcohol Consumption Levels in an Adult Primary Care Population. 

Alcoholism: Clinical & Experimental Research.

https://onlinelibrary.wiley.com/doi/10.1111/acer.14477

2. Research Society on Alcoholism. Patients with Depression, Anxiety, and Bulimia at Heightened Risk of Unhealthy Drinking and Associated Health Issues. News release. November 2, 2020. 

https://www.newswise.com/articles/patients-with-depression-anxiety-and-bulimia-at-heightened-risk-of-unhealthy-drinking-and-associated-health-issues

A diagnosis of depression, anxiety disorders, or bulimia may also indicate a heightened risk of excessive drinking. 

The Intersection of Excessive Alcohol Use and Psychiatric Disorders 

Carlos M. Grilo, PhD, in his talk at the Annual Psychiatric Times® World CME Conference™, discussed the latest updates in diagnosing, understanding, and treatment options for patients with binge-eating disorder (BED).

“My biggest take home,” Grilo said, “is to avoid stigmatizing. Ask what language your patient would like used when discussing their weight.”

BED is a DSM-5 eating disorder, characterized by the consumption of large amounts of food while experiencing a loss of control. To classify as binge eating disorder, at least 3 of the 5 behavioral indicators must be met: 1) the patient must eat rapidly; 2) the patient must eat large amounts of food even when not hungry; 3) the patient must eat to the point of discomfort; 4) the patient will eat alone due to embarrassment; and 5) the patient will feel disgusted, depressed, or guilty about their eating.

Studies of adults with BED reveal that patients have both elevated psychiatric and medical comorbidity. The most common psychiatric comorbidities include mood disorders, anxiety, and substance use disorders. Medical comorbidities include obesity, chronic pain conditions, and cardiometabolic problems, like diabetes or hypertension.

When discussing pharmacotherapy treatment options for BED, Grilo noted that there is only 1 FDA-approved medication: lisdexamfetamine. Lisdexamfetamine is used for moderate to severe BED, taken once daily in the morning. Patients must be monitored carefully, as it has a black box warning that notes its high potential for abuse. 

Pharmacotherapy for treating BED is an emerging research topic. While several small clinical trials have found medications superior to placebos for reducing binge-eating, those studies only gauged the short-term, limited effects. Next to no data exists regarding long term effects.

A larger variety of psychological and behavioral treatments exist to treat BED. Specific focal psychological treatments, like cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT), are well-established, significantly reduce binge eating, and have approximately 50% remission rates. Behavioral weight loss (BWL), a generalist treatment, achieves comparable binge-eating reductions and produces some weight loss.

Grilo concluded his talk with a number of suggestions. First and foremost, be prepared to recognize BED. Once you have assessed the psychiatric and medical comorbidities, consider pharmacological, psychological, and combined therapy options. Let your patient know that treatments exist that may help, often quickly. Discuss options and alternatives, and above all, avoid stigmatizing.

The Annual Psychiatric Times® World CME Conference™ was held October 15 – 17. More information can be found 

. Next year’s conference is scheduled for September 30 – October 2, 2021, in San Diego.

Carlos M. Grilo, PhD, explained symptoms, causes, and treatment for binge-eating disorder in his talk at The Annual Psychiatric Times® World CME Conference™. 

Remove the Stigma Around Binge Eating Disorder 

Orthorexia nervosa (or pathologically “healthy” eating) is distinct from anorexia nervosa, bulimia, and avoidant/restrictive food intake disorder. There are high-risk populations for ON, such as athletes and others who are focused on being healthy However, most of those individuals will only experience social impairment. On the other hand, individuals who view food as medicine are at increased risk for life-threatening medical complications and even death.

In this video, we interview Thomas R. Dunn, PhD, author of a recent CME for 

. Dr Dunn is Professor, School of Psychological Sciences, University of Northern Colorado, Greeley, CO; and Staff Psychologist, Denver Health Medical Center; Dr Hawkins is Chief Executive Officer and Licensed Psychologist, Center for Change, Orem, UT.

Transcript edited for brevity and clarity. For the entire interview, please watch the video. -Ed

About 20 or 30 years ago there was a physician out here in Colorado who recognized that people were very passionate about the quality of food that they were eating, and they were going out of their way to try to find the freshest, most nutritious foods they could.

On the surface this sounds very reasonable, but we want to be careful about what kinds of foods we eat. One of the things he noticed was that there were people who were getting too carried away with this quest to be as healthy as possible. So he developed or coined this term called orthorexia, which is a sort of a straight or rigid diet. Over the years, European researchers especially have been studying this notion that there are people who seem to get pathological about their healthful eating.

So, most of us are aware of anorexia nervosa, a condition where people are worried about being fat; in the case of orthorexia, we are worried about being unhealthy. And so, there's a tipping point. There seem to be people who are overly thoughtful about their diet, when it gets to the point where they restrict to the point of not getting their nutrition. They may start off being vegetarian, then they're vegan, then they're raw, and then they restrict what they can eat. 

There are individuals that have rigid eating habits that have become problematic for them, in their social circles. For example, I dealt with a young woman who was flabbergasted that her fiance would break up with her. After they were engaged, her future mother and father-in-law were coming to celebrate, and they decided to go out to dinner. Sharing meals is a central way of celebrating. He told her, "Please don't be weird about the food," and she got into an argument with the waitress over the croutons. It was this pattern of interacting over diet, that was really disruptive in this case to her social life.

I've seen a couple of people in my practice, in the hospital for severe malnourishment because they believe their diet is going to cure some sort of malady. People who are engaging in food as medicine in that they have a condition, and they're fighting to try to treat that condition. By adopting an overly rigid diet, and they develop a blind spot. They don't see that not only is it not helping, but it's causing additional medical problems.

Sometimes there might be victim blaming for somebody with cancer who "has a terrible diet," eats too much sugar, and so on.

 People are willing to pass judgment on diets, about what people are eating at restaurants. And there has been some who have suggested that maybe orthorexia is really just a flavor of anorexia, and that is certainly a little bit more fashionable to say "I'm on a cleanse," or "I'm doing this diet." And we give people a pass for that. . . There is a lot of pressure out there. I recently evaluated a young man who I was very concerned with having a first break psychosis and his parent was very concerned that he was getting the right vitamins; she has done a lot of research and vitamins were going to help him though his substantial psychiatric emergency.

Although weight loss may be a favorable feature of healthful diets, "clean eating" can be taken to extremes. In this video, we interview Thomas R. Dunn, PhD, author of a recent CME for Psychiatric Times. Orthorexia Nervosa. 

Clean Eating to the Extreme

Scroll below the apple image for the quiz.

B. Complex psychosocial processes that relate to lack of early life deficits

C. Bio-psycho-social interactions that lead to dysregulation of brain circuitry

Based on our current understanding, what is the underlying etiology for anorexia nervosa? Take the quiz.

Mini Quiz: Etiology of Anorexia Nervosa

Anorexia nervosa is the third most common chronic illness among adolescent females. The mortality rate is 12-fold higher than with all other combined causes of death for females aged 15 to 24 years.

 The disorder is associated with severe emaciation from self-driven food refusal and a perception of being overweight despite very low body weight. Anorexia nervosa shows a complex interplay between neurobiological, psychological, and environmental factors, and it is a chronic disorder with frequent relapses, high treatment costs, and severe disease burden. Little is known about the pathophysiology or biomarkers that characterize anorexia nervosa brain function, treatment effectiveness is limited, and there are no FDA-approved medications.

What makes anorexia nervosa so difficult to treat is the seemingly willful food avoidance and self-driven relentless motivation to lose weight. While eating is a very normal behavior for most of us, overcoming the fear of eating and weight gain is extremely difficult for children or adults with anorexia nervosa. Humans have historically evolved to be biologically protected to survive times of food scarcity. The brain circuitry that drives food-seeking has been well defined in basic science models.

Developing neurobiological models for anorexia nervosa and existing mechanisms that disregard or override hunger signals has been much more difficult. Moreover, there are psychological and social factors involved in anorexia nervosa, including anxious traits and the tendency to worry, and their interaction combined with peer pressure and stress in general 

 This has made it difficult to tease apart environmental effects from brain biology that poses a vulnerability for developing or maintaining anorexia nervosa.

Related content: Mini Quiz: Etiology of Anorexia Nervosa

Recent brain research in anorexia nervosa has focused on reward pathways, with the hypothesis that these pathways might disturb food approach mechanism in anorexia nervosa. Food is a salient stimulus or natural reward, and reward pathways similar to those of substance abuse are activated when we desire, approach, or eat food.

 Important regions in this circuitry include the ventral striatum, which receives midbrain dopaminergic input and drives motivation and the reward approach; the orbitofrontal cortex responsible for reward valuation; the insula, which processes our taste sensations and provides input to the striatum; and the hypothalamus, which integrates body homeostasis.

 The circuitry between those brain regions may adapt to weight loss and instead of driving eating may reinforce food restriction in individuals vulnerable to anorexia nervosa.

A variety of studies in the past applied tasks that either showed food pictures or delivered monetary or taste rewards to stimulate the reward system. The studies repeatedly showed that the insula, orbitofrontal cortex, or striatum activated differently in persons with anorexia nervosa during those tasks compared with healthy controls.

In our laboratory, the aim is to identify chemical targets to develop better treatments for anorexia nervosa. To accomplish this, we applied reward tasks that were closely associated with brain dopamine response to find evidence of dopaminergic involvement in the pathophysiology of anorexia nervosa.

The dopamine neurotransmitter system has been intensively studied and well characterized. Its neurons’ cell bodies lie in the brain stem in the ventral tegmental area and substantia nigra and from there distribute to the cortical and subcortical brain. The basal ganglia and especially the ventral striatum that includes the nucleus accumbens receive dopamine input and have been involved in the drive to reward stimuli. The reward stimuli can be unconditioned or conditioned (learned) stimuli.

A central feature of dopamine neuron response is that it is triggered by unexpectancy, ie, a discrepancy between what one expects versus what in fact happens. After receiving an unexpected reward such as food or money, a dopamine surge is elicited in the striatum and midbrain, which is called a 

. When receiving this reward becomes a regular occurrence, the dopamine signal is triggered by the conditioned stimulus that predicts the reward. However, the dopamine system does not respond when the actual reward is received (prediction matches the outcome). If the reward is predicted but not received (there is no food or money after expecting it), there is a dip in dopamine activity in the brain, which reflects the negative prediction error (unexpected omission).

This dynamic can be studied in the living human brain with functional brain imaging during the application of a Pavlovian conditioning paradigm: participants learn to associate sugar-taste or monetary stimuli with pictures of colored shapes that become the conditioned stimulus and appear on the screen before money or sweet solution are delivered (

). Sometimes when the participants expect to get the reward, they will not get it; at other times the reward is delivered unexpectedly.

During these studies, adults and adolescents with anorexia nervosa repeatedly showed elevated response to the unexpected conditions in the insula and striatum, which suggests altered dopamine function.

 Basic science found that in the process of food restriction, the dopamine system in the brain gets sensitized to stimulate food seeking. We interpreted this elevated activation as a normal response.

This brain activation does not drive eating as it would in heathy individuals. In fact, it can often be observed in individuals with anorexia nervosa that despite weight loss, fear of weight gain worsens and there is no limit as to how low the weight will drop. In our most recent study, we propose a model of how this drive to lose weight may be perpetuated and how the elevated prediction error response fits into this behavior.

 Our findings indicate that elevated brain response correlated positively with harm avoidance-a measure of trait anxiety-but negatively with weight gain during treatment.

Harm avoidance was positively correlated with drive for thinness and body dissatisfaction. We propose that when a person who develops anorexia nervosa starts to lose weight, the dopamine system quickly gets faster or more strongly involved, ie, sensitized. Weight loss leads to low blood sugar and changes in hormonal and neuropeptide levels, which signal to the hypothalamus that the organism should eat. However, this biological motivation and drive to eat disagrees with conscious motivation to not eat and lose weight, which leads to high levels of anxiety. To avoid weight gain and driven by extreme anxiety, the person with anorexia eats even less, which further reduces weight and triggers more biological drive to eat and further increases anxiety. Thus, setting off a vicious cycle that is difficult to break (

Clinically, this has been a useful model to discuss the neurobiology of anorexia nervosa with patients or families. I draw and develop this model in a monthly seminar with parents of children with anorexia nervosa, which helps them understand the typically very difficult to comprehend ongoing drive for food restriction.

Understanding a certain mechanism does not cure the illness, but it provides opportunities to support treatment. In psychotherapy it helps to go from something inexplicable to understanding the connection between an anxious temperament with a predisposition to worry and eating problems. This is also relevant for patients who have recovered but who may be at risk for relapse.

Every year in August, around the time when school starts, I see several patients with symptom relapse in my outpatient clinic. This is due to heightened stress over grades that triggers eating problems and food restrictions. The subsequent weight loss may then set in motion the vicious biological cycle as previously described.

As do other biological studies including genetic research, such a model serves another important purpose. Psychiatric diseases are often associated with stigma and personal guilt. The more we understand the underlying neurobiology of psychiatric disorders such as eating disorders, the more we will be able to develop medical models, find more effective treatments, and reduce stigma.

Our research has helped to pose new hypotheses for potential treatment directions. In animal models, fear extinction was aided by dopamine receptor stimulation.

 A main focus of psychotherapy for anorexia nervosa is weight restoration, such as family-based therapy in youth, which requires overcoming the fears of eating. We hypothesized that dopamine receptor stimulation could be helpful in the treatment process for anorexia nervosa. We compared youth treated with the partial dopamine D2 receptor agonist aripiprazole with those who did not receive aripiprazole. The patients who received aripiprazole had better weight outcomes at the end of treatment.

 However, a controlled study is missing, and no firm conclusions can be drawn from these results. Although such a medication alone would probably not cure anorexia nervosa, it could, however, act as a catalyst in concert with psychotherapy.

The conceptualization of the neurobiology of anorexia nervosa in our model poses a dichotomy of frontal cortex cognitive-emotional and subcortical basal ganglia involving circuits. What has been very difficult to model from a biological perspective are the severe eating disorder core behaviors such as body dissatisfaction and drive for thinness. Those thoughts and drives can persist life-long in a person despite having recovered weight-wise from anorexia nervosa. It is possible that the anxious traits commonly found in anorexia nervosa-even before the onset of the disorder-come into play and perpetuate those behaviors, making “letting go” extremely difficult.

Models to test how to target the behaviors pharmacologically still need to be developed. Serotonin reuptake inhibitors can help with anxiety and depression but do not improve the core behaviors of anorexia nervosa.

 A more complex biochemical model may be needed for anorexia nervosa. Such a model would take into account the interaction between neurotransmitter systems such as dopamine and serotonin and signals from the body periphery such as gut hormones and their adaptation to food intake.

Recent data lend themselves to applying a neurobiological model when talking with patients, parents, or families about anorexia nervosa. This can reduce personal burden, shame, or guilt. Weight restoration continues to be a key aspect of treatment, and there is the possibility that this is supported by dopamine receptor agonists, although this is yet uncertain as controlled studies are lacking.

Dr Frank is Professor in Residence, University of California, San Diego, Eating Disorder Program for Treatment and Research, and Rady Children’s Hospital, San Diego, CA. He reports that he has received research funding from the NIMH, is on the Scientific Advisory Board of EDCare, and has provided expect testimony for Senter Goldfarb, & Rice.

1. Golden NH. Eating disorders in adolescence and their sequelae. 

2. Attia E. Anorexia nervosa: current status and future directions. 

3. Kessler RM, Hutson PH, Herman BK, Potenza MN. The neurobiological basis of binge-eating disorder. 

4. Kaye WH, Wierenga CE, Bailer UF, et al. 

Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa

5. Kelley AE, Berridge KC. The neuroscience of natural rewards: relevance to addictive drugs. J Neurosci. 2002;22:3306-3311.

6. Haber SN, Behrens TE. The neural network underlying incentive-based learning: implications for interpreting circuit disruptions in psychiatric disorders. 

7. DeGuzman M, Shott ME, Yang TT, et al. Association of elevated reward prediction error response with weight gain in adolescent anorexia nervosa. 

8. Frank GK, Reynolds JR, Shott ME, et al. Anorexia nervosa and obesity are associated with opposite brain reward response. 

9. Frank GKW, DeGuzman MC, Shott ME, et al. Association of brain reward learning response with harm avoidance, weight gain, and hypothalamic effective connectivity in adolescent anorexia nervosa. 

10. Abraham AD, Neve KA, Lattal KM. Dopamine and extinction: a convergence of theory with fear and reward circuitry. 

11. Frank GK, Shott ME, Hagman JO, et al. The partial dopamine D2 receptor agonist aripiprazole is associated with weight gain in adolescent anorexia nervosa. 

12. Lock J, La Via MC, and the AACAP Committee on Quality I. Practice parameter for the assessment and treatment of children and adolescents with eating disorders. 

13. Frank GKW, DeGuzman MD, Shott ME. Motivation to eat and not to eat: the psychobiological conflict in anorexia nervosa. 

This article describes a model for anorexia nervosa that is useful when working with patients or families to help them understand the complexity of the illness.

Dysregulation of Brain Processing in Anorexia Nervosa

Eating disorders (ED) are associated with significant comorbid psychopathology and the most extensive medical complications of any psychiatric disorder. Disordered behaviors that present across diagnoses (eg, restriction, binge eating, compensatory behaviors) are linked with acute medical risks that often require careful medical monitoring and clinical intervention. Yet, individuals with EDs frequently express hesitancy towards recovery and have great difficulty controlling their ED symptoms.

EDs are typically chronic and follow a treatment-refractory trajectory. Existing research indicates that even the most effective evidence-based outpatient treatment yields recovery for only around one-half of patients.

 In our clinic, we often encounter patients like “Hayley,” “Georgia,” and “Michael” (see Case Vignettes) for whom outpatient treatment has been unsuccessful. Like many other eating disorder treatment programs, our program seeks to optimize recovery by providing more intensive treatment with stepped levels of care.

Hayley is a 24-year-old graduate student and a competitive runner who competes regularly. She has a diagnosis of anorexia nervosa, restricting type (AN-R), which developed when she was 20 after a period of binging. Two years ago, Hayley began working with a multidisciplinary outpatient team, but she has continued to lose weight. She attributes the weight loss to her unwillingness to eat the large amount of food it would take to offset the calories she burns while running and training. She initially presented to her primary care physician feeling weak then was admitted to an inpatient eating disorders unit for bradycardia. Upon discharge from the hospital she was referred to a partial hospitalization treatment program.

Most research explores the efficacy of treatment at the outpatient level; little is known about the comparative value of the higher levels of care for patients with EDs.

 However, these approaches are important alternatives for treatment-refractory EDs because they provide the more intensive treatment and meal support that many severely ill patients need.

 Common reasons for needing higher levels of care include substantial weight loss that might be life threatening; difficulty eating enough food to gain weight; severe binge/purge behaviors; incapacitating ED symptoms; comorbid substance abuse; and anxiety, depression, obsessive compulsive disorder, or suicidal intent.

It is not unusual that such behaviors result in medical instability with symptoms of cardiovascular compromise, electrolyte disturbances, or hypoglycemia. It is important to note that some individuals have a lack of insight about their behaviors or are not motivated to engage in treatment. Because of these factors, the mortality rate for anorexia nervosa and bulimia nervosa can be 5% or higher.

 Higher levels of care provide a structured and protective environment that can be essential for these serious, life-threatening disorders.

Georgia, aged 17 years, has bulimia nervosa (BN) with comorbid major depressive disorder, panic attacks, and a history of sexual trauma. She has been engaging in polysubstance abuse, including alcohol, marijuana, prescription painkillers, and cocaine, since the age of 12. She has been hospitalized several times for suicide attempts and accidental drug overdoses. She binges and purges daily and states that she is only able to reduce these behaviors when using substances. Her outpatient therapist feels overwhelmed by all of Georgia’s comorbidities and is not sure how to help her reduce these self-destructive behaviors, so she refers Georgia to a PHP program.

Higher levels of care for EDs include various types of programs, with different levels of intensity.

The treatment goals for EDs are similar and include:

• Interrupting binge, purge, and restrictive behaviors;

• Providing psychoeducation regarding regular eating;

Psychotherapy approaches among higher levels of care are typically informed by cognitive behavioral and dialectical behavioral therapies. Family-based treatment is often incorporated for children and adolescents. Patients might transition between levels of care due to variables such as symptom severity, medical status, motivational status, treatment history, and financial limitations.

There are several different levels of care from which to choose:

 is the highest level of care available. This setting can be in a medical hospital and is intended for patients with acute medical instability. Alternatively, this may be in a psychiatric hospital if there are severe behavioral symptoms. In either event, subspecialty medical and behavioral consultation are readily available, meals are supervised, and one-to-one monitoring is available.

 offer full-time treatment in a non-hospital setting. Patients receive multidisciplinary care that includes nutritional support, medication management, and individual and group therapy.

(PHP), or daytreatment, offer treatment in an outpatient setting approximately six to 10 hours a day, between three and seven days per week. Patients typically spend nights and sometimes weekends on their own, allowing them to practice the skills they are learning in social, occupational, and leisure settings outside of treatment.

 (IOPs) offer treatment approximately three hours a day, from three to five days per week. At both the PHP and IOP levels, patients receive meal support, group therapy, individual therapy, dietary sessions, and medication management.

Treatment efficacy for higher levels of care. 

Randomized controlled trials (RCTs) are necessary to avoid the confounding effects of psychopathology severity and evaluate the comparative efficacy of different levels of care. Since patients with more severe symptoms and greater functional impairment are more likely to present to higher levels of care than those with mild ED pathology (and milder ED pathology is associated with better outcomes), reliable findings are dependent on patients matched with controls based on symptom severity or random assignment to level of care.

Unfortunately, RCTs that compare different levels of care are limited given significant costs and ethical considerations related to randomizing acutely ill patients. As such, literature on higher levels of care treatment efficacy is scarce and consists largely of open trials assessing outcome at discharge. A 2015 review of PHP and residential programs identified that duration of treatment was similar between these levels of care, and all but one study reported improvements in outcomes (ie, body mass index [BMI], number of binge/purge episodes) at discharge.

There have been several, more recent naturalistic studies of higher levels of care treatment that also offer support for the effectiveness of care in most patients.

 However, less than half of the open trials identified in the review reported follow-up data after discharge.

 Moreover, follow-up completion rates tend to be low; the average rate of follow-up completion was 66% for PHP and 37% for residential. Although most of the studies reported that positive treatment outcomes at discharge were maintained or improved at follow-up, the missing data at follow-up make long-term results difficult to interpret.

As previously mentioned, the literature on treatment efficacy at higher levels of care is preliminary and consists largely of open trials. Within the context of these trials, researchers have begun to study the predictors of long-term recovery. However, more is known about predictors of recovery from EDs in general, regardless of type of treatment, and no study has looked at how predictors of successful outcome might differ depending on level of care received.

 conducted a metaanalysis of predictors of treatment outcome that included a large number of patients treated at a higher level of care. Their findings indicate that patients with higher BMI, fewer binge/purge behaviors, greater motivation to recover, lower depression, lower shape/weight concern, fewer comorbidities, better interpersonal functioning, and fewer familial problems at baseline had better outcomes both at end-of-treatment and follow-up. The most robust predictor of outcome at both end-of-treatment and follow-up was the meditational mechanism of greater early symptom change.

The literature consistently corroborates that early behavioral change predicts later symptom remission.

 Given that higher levels of care treatment settings typically involve meal supervision and more opportunities to quickly learn skills, these settings may be uniquely well-suited to facilitating early symptom change.

When determining the appropriate level of care, practitioners should consider practice guidelines published by reputable organizations as well as individual variables important in predicting treatment response. The American Psychiatric Association (APA), Royal Australian and New Zealand College of Psychiatrists (RANZCP), and National Institute of Clinical Excellence (NICE) published guidelines for ED treatment that outline factors to consider in making decisions regarding level of care.

Michael is a 12-year-old boy who has avoidant/restrictive food intake disorder (ARFID), generalized anxiety disorder, and panic attacks. He endorses fear of food contamination and reports eating the same foods at the same time every day to avoid illness and/or vomiting. Michael has seen outpatient providers over the past few years for low weight, stunted growth, and gastrointestinal complaints. He was recently admitted to an inpatient eating disorders unit for low weight. Following discharge, he was unable to maintain weight at the outpatient level due to food-related fears resulting in restricted intake. As such, he was readmitted to the inpatient unit; he was later referred to PHP for continued care.

The NICE and RANZCP guidelines recommend first seeking outpatient care and suggest transfering to higher levels of care if there is no improvement of symptoms. Alternatively, the APA advises consideration of various factors when making initial treatment recommendations (

). All guidelines clearly outline criteria for determining medical stability and recommend that patients who do meet these requirements be considered for admission to inpatient hospitalization (

). A recent update on the medical management of EDs offers a list of criteria that indicate medical instability in adolescents that deviates slightly from the APA recommendations.

The RANZCP and APA guidelines suggest that inpatient treatment may be needed if ED symptoms are uncontrolled and require 24-hour supervision. Inpatient care and partial hospitalization also are appropriate when there is significant risk of suicide or self-harm. The NICE and APA guidelines advise considering logistical issues concerning the geographic location of treatment; they recommend that patients first receive care at facilities close to their home. Research indicates that PHPs are more cost-effective than residential or inpatient treatment; therefore, financial factors are important considerations.

 Clinicians might also consider recent scientific developments related to variables that account for significant variance in treatment response.

As any clinician who works with patients who have EDs knows, there are, unfortunately, many patients who are treatment resistant in outpatient care. For patients like Hayley, Georgia, and Michael, specialized higher levels of care facilities can be a relief for the clinician and life-changing for the patient.

Hayley was able to achieve her ideal body weight with PHP and stepped down to IOP. She decided not to return to competitive sports before returning to her outpatient team. Georgia stopped using drugs and alcohol within the structure of PHP, participated in weekly family therapy, and learned skills for coping with emotional dysregulation. Michael restored his weight in PHP through repeated food exposures that helped him increase his food volume and variety and decrease his fears surrounding contamination.

For many of the complex, severely ill patients who present to treatment, intensive treatment with stepped levels of care can offer a cost-effective structure that promotes positive behavioral change.

Dr Anderson is Associate Clinical Professor Director of Training, Ms Simpson is Milieu Therapist, and
	Dr Kaye is Professor and Founder and Executive Director, Eating Disorders Program, Department of Psychiatry, University of California, San Diego, CA. The authors report no conflicts of interest concerning the subject matter of this article.

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Eating disorders (ED) are associated with significant comorbid psychopathology and the most extensive medical complications of any psychiatric disorder.

Eating Disorders