Eating Disorders

Joel Yager, M.D. Michael J. Devlin, M.D. Katherine A. Halmi, M.D. David B. Herzog, M.D. James E. Mitchell, M.D. Pauline S. Powers, M.D. Kathryn J. Zerbe, M.D.
CLINICAL SYNTHESIS

Abstract: The diagnostic category of eating disorders encompasses anorexia nervosa, bulimia nervosa, and the heterogeneous group of eating disorders not otherwise specified, most prominent among which is binge-eating disorder, currently detailed in research criteria in DSM-IV-TR and under consideration for inclusion as a separate diagnosis. In recent decades researchers have increasingly appreciated the multifaceted contributions to the etiology and pathogenesis of eating disorders, including genetic, familial, developmental, and psychosocial influences. Comorbidity with other axis I and axis II disorders is common, and medical comorbidity is of particular significance because of marked nutritional impairments that often accompany these disorders. Although the evidence-based treatment literature is sparse, particularly for anorexia nervosa, progress has been made with respect to nutritional, psychosocial, and psychopharmacological interventions for these disorders, and a growing consensus among clinicians has resulted in practice guidelines that attend to each of these dimensions. CLINICAL
CONTEXT CME Financial Disclosure Joel Yager, M.D., Department of Psychiatry, University of New Mexico School of Medicine. No significant financial conflict of interest or affiliation to report. Michael J. Devlin, M.D., New York State Psychiatric Institute, Department of Psychiatry, College of Physicians and Surgeons, Columbia University. No significant financial conflict of interest or affiliation to report. Katherine A. Halmi, M.D., Department of Psychiatry, Weill-Cornell Medical College. No significant financial conflict of interest or affiliation to report. David B. Herzog, M.D., Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School. No significant financial conflict of interest or affiliation to report. James E. Mitchell, M.D., Neuropsychiatric Research Institute and Department of Neuroscience, University of North Dakota School of Medicine and Health Science. No significant financial conflict of interest or affiliation to report. Pauline S. Powers, M.D., Department of Psychiatry and Behavioral Medicine, University of South Florida College of Medicine. No significant financial conflict of interest or affiliation to report. Kathryn J. Zerbe, M.D., Departments of Psychiatry and Obstetrics and Gynecology, Oregon Health Sciences Center. No significant financial conflict of interest or affiliation to report. Address correspondence to Joel Yager, M.D., Department of Psychiatry/MSC09 5030, University of New Mexico School of Medicine, 1 University of New Mexico, Albuquerque, New Mexico 871310001; e-mail, jyager@unm.edu.

Eating disorders primarily affect women, although in clinical settings males constitute some 5%10% of cases of anorexia nervosa and bulimia nervosa and about 30% of cases of binge-eating disorder (13). Significantly impaired patients with mixed signs and symptoms of anorexia nervosa, bulimia nervosa, and/or binge-eating disorder comprise a large percentage of patients seen in treatment centers. Currently, binge-eating disorder is classified under the category of eating disorders not otherwise specified, but it may attain separate diagnostic status in future editions of DSM. The diagnostic criteria for anorexia nervosa, bulimia nervosa, and binge-eating disorder are listed in Tables 1, 2, and 3. For these disorders, developmental vulnerabilities such as shyness and childhood anxiety disorders (4), perfectionism (5), obsessive-compulsive traits (6), early mood disorders (7), familial transmission (8, 9), physical impairments (10, 11), and high psychiatric comorbidity (1214) inform treatment. In the bulimia and binge-eating subgroups in particular, co-occurring substance use disorders (14) and a propensity toward obesity (2) are also relevant. Treatment and

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DSM-IV-TR Diagnostic Criteria for Anorexia Nervosa

Table 1. A. Refusal to maintain body weight at or above a minimally normal weight for age and height (e.g., weight loss leading to maintenance of body weight less than 85% of that expected; or failure to make expected weight gain during period of growth, leading to body weight less than 85% of that expected) B. Intense fear of gaining weight or becoming fat, even though underweight C. Disturbance in the way in which ones body weight or shape is experienced, undue influence of body weight or shape on self-evaluation, or denial of the seriousness of the current low body weight D. In postmenarcheal females, amenorrhea, i.e., the absence of at least three consecutive menstrual cycles. (A woman is considered to have amenorrhea if her periods occur only following hormone, e.g., estrogen, administration.)

Specify type:
Restricting type: during the current episode of anorexia nervosa, the person has not regularly engaged in binge-eating or purging behavior (i.e., self-induced vomiting or the misuse of laxatives, diuretics, or enemas). Binge-eating/purging type: during the current episode of anorexia nervosa, the person has regularly engaged in binge-eating or purging behavior (i.e., self-induced vomiting or the misuse of laxatives, diuretics, or enemas.

DSM-IV-TR Diagnostic Criteria for Bulimia Nervosa

Table 2. A. Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following: (1) Eating, in a discrete period of time (e.g., within any 2-hour period), an amount of food that is definitely larger than most people would eat during a similar period of time and under similar circumstances (2) A sense of lack of control over eating during the episode (e.g., a feeling that one cannot stop eating or control what or how much one is eating) B. Recurrent inappropriate compensatory behavior in order to prevent weight gain, such as self-induced vomiting; misuse of laxatives, diuretics, enemas, or other medications; fasting; or excessive exercise C. The binge eating and inappropriate compensatory behaviors both occur, on average, at least twice a week for 3 months. D. Self-evaluation is unduly influenced by body shape and weight. E. The disturbance does not occur exclusively during episodes of anorexia nervosa.

prognosis also vary with coexisting personality traits and disorders. The prognosis is most promising for patients who are otherwise high functioning and worse for those who are highly disturbed, constricted, and avoidant and those who are highly disturbed, impulsive, and emotionally dysregulated (15). For patients with long-term cases, chronic medical problems, among them osteoporosis and cardiovascular problems, become especially important. Obesity and its complications are prevalent among patients with binge-eating disorders (2). Treatment often requires interdisciplinary care, with primary care physicians, nurses, registered dieticians, psychologists, social workers, and a variety of ancillary therapists working with the psychiatrist. Inpatient treatment facilities that specialize in the treatment of eating disorders are not abundant, and many areas lack treatment programs for eating disorders. Geographic and/or financial constraints often limit access to treatment options for patients and their families and clinicians. Since most cases of anorexia nervosa and many cases of bulimia nervosa begin in the early to midteens, families are vitally concerned; they must always be considered and involved, and they are sometimes deputized to serve as members of the treatment team (16). Families are understandably distressed by the potential lethality of these conditions; death from suicide and malnutrition are potential outcomes in young women with eating disorders (1719). Given the demographics of patients with eating disorders, issues of concern to adolescents in particular and women of all ages are also of prime importance in treatment. In vulnerable adolescents facing anorexia nervosa and bulimia nervosa, these pressures produce negative self-evaluations regarding appearance, fat phobias, and a drive toward self-starvation, purging, and excessive exercise. For those with binge-eating disorders, satisfying food cravings to salve states of emotional dysregulation may lead to significant obesity and self-disparagement.

TREATMENT

STRATEGIES AND EVIDENCE

Specify type:
Purging type: during the current episode of bulimia nervosa, the person has regularly engaged in self-induced vomiting or the misuse of laxatives, diuretics, or enemas. Nonpurging type: during the current episode of bulimia nervosa, the person has used other inappropriate compensatory behaviors, such as fasting or excessive exercise, but has not regularly engaged in selfinduced vomiting or the misuse of laxatives, diuretics, or enemas.

Treatment plans should include assessment and treatment of several problem sets: physiological impairments; behaviors that maintain eating disorders, such as restrictive eating, excessive exercise, binge eating, and purging; self-endangering attitudes, thoughts, and emotions that sustain the disorders; and co-occurring psychiatric disorders (20). In treating anorexia nervosa especially, key initial tasks may include enhancing the patients motivation, involving the patient in treatment despite his

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or her ambivalence, and engaging the familys assistance in conducting treatment. Although motivational interviewing techniques used in substance use disorders are being examined for their potential utility in increasing readiness for change among patients with eating disorders, the effectiveness of such techniques remains to be demonstrated (21). The extent of the initial medical workup depends on the patients degree of nutritional impairment. Along with the usual metabolic measures, such as CBC, electrolytes, magnesium, calcium, liver function tests, blood urea nitrogen, creatinine, and thyroid-stimulating hormone, current recommendations sometimes include complement factor 3, a sensitive measure known to indicate malnutrition even when other parameters are normal (22). For thin patients, an electrocardiogram is recommended, and for those showing any cardiovascular signs or symptoms, a cardiac ultrasound may be considered (23). A bone density scan is recommended because osteopenia may occur within a year after onset of amenorrhea (24). Demonstrating early osteopenia may help motivate wavering patients. Psychological assessment should include family members whenever feasible.

DSM-IV-TR Research Criteria for Binge-Eating Disorder

Table 3. A. Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following: (1) Eating, in a discrete period of time (e.g., within any 2-hour period), an amount of food that is definitely larger than most people would eat in a similar period of time under similar circumstances (2) A sense of lack of control over eating during the episode (e.g., a feeling that one cannot stop eating or control what or how much one is eating) B. The binge-eating episodes are associated with three (or more) of the following: (1) Eating much more rapidly than normal (2) Eating until feeling uncomfortably full (3) Eating large amounts of food when not feeling physically hungry (4) Eating alone because of being embarrassed by how much one is eating (5) Feeling disgusted with oneself, depressed, or very guilty after overeating C. Marked distress regarding binge eating is present. D. The binge eating occurs, on average, at least 2 days a week for 6 months.
CLINICAL SYNTHESIS

TREATING

ANOREXIA NERVOSA

Although few controlled clinical trials have been conducted (20, 25), numerous observational studies suggest that initial treatment should focus on refeeding (20, 26, 27). Ambulatory treatment usually requires an interdisciplinary team that includes a general physician and a registered dietician who will monitor weight and laboratory indicators if the psychiatrist does not routinely perform these functions. Initial caloric intake should be tolerable to the patient but increased every few days to ensure a weight gain of 12 pounds per week (20). Controlled studies show that family involvement in treatment improves outcomes for younger patients, except when highly dysfunctional family patterns preclude such involvement (28, 29). The decision about when to hospitalize a patient with anorexia nervosa depends on specific physiological and psychiatric status, patient and family motivation and ability to adhere to weight-gain programs, and personal and local resources. Indications for hospitalization and other settings of care are detailed in APAs Practice Guideline for the Treatment of Patients With Eating Disorders (20). Especially for patients whose initial weight is 25% or more below expected weight but also for patients at higher weight levels, depending on a comprehensive assessment of psychiatric and medical circumstances, hospitalization is often necessary to ensure adequate intake and to limit

Note: The method of determining frequency differs from that used for bulimia nervosa; future research should address whether the preferred method of setting a frequency threshold is counting the number of days on which binges occur or counting the number of episodes of binge eating.
E. The binge eating is not associated with the regular use of inappropriate compensatory behaviors (e.g., purging, fasting, excessive exercise) and does not occur exclusively during the course of anorexia nervosa or bulimia nervosa.

physical activity. In younger children and adolescents, hospitalization should be considered even earlier if the patient is losing weight rapidly, before too much weight is lost, since early intervention may avert rapid physiological decline and loss of cortical white and gray matter (20). Generally, specialized eating disorders units yield better outcomes than general psychiatric units because of nursing expertise and effectively conducted protocols (30). One study suggested that short-term outcomes for involuntarily hospitalized patients are similar to those for voluntarily admitted patients (31). Higher rates of relapse and rehospitalization have been shown to occur when patients are prematurely discharged from inpatient care (32). Since weight gains of more than 24 pounds per week may be physiologically unsafe, patients who need to gain 2030 pounds to restore health may require 23 months of hospital treatment. Partial hospitalization programs have been

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found to be effective in direct relation to their intensity: 8-hour, 5-day-a-week programs may approach inpatient programs in effectiveness, whereas programs that involve fewer hours and/or fewer days per week are much less effective (33, 34). In fact, however, few partial hospitalization programs specialized for treatment of eating disorders exist. For acutely thin patients with anorexia nervosa, there have been few controlled medication studies to guide treatment. For patients treated in wellimplemented inpatient programs, adding a selective serotonin reuptake inhibitor (SSRI) provides no advantage for weight gain or reduction of hospital stay (35, 36). Several small open-label studies (3739), the largest of which involved 20 patients, and one small controlled trial comparing olanzapine and low-dose chlorpromazine (40) suggest that low doses of atypical antipsychotic medications such as olanzapine (2.5 to 15 mg/day) may improve weight gain and psychological indicators, but good controlled studies are lacking. With regard to psychotherapy, a recent small controlled study suggests that although dropout rates were substantial for all treatments, for acutely ill patients neither cognitive behavior therapy (CBT) nor interpersonal psychotherapy was superior to a wellconducted manualized nonspecific supportive clinical management based on empathic care, nutritional education, and advice (41). In dealing with the osteopenia and osteoporosis resulting from anorexia nervosa, the only intervention shown to potentially reverse bone loss is nutritional rehabilitation during the period of bone growth, ensuring sufficient dietary protein, carbohydrates, fats, calcium, and vitamin D (42). Supplemental estrogen-progestins (43), calcium, and/or vitamin D have not been shown to meaningfully reverse skeletal deterioration but are often prescribed in routine practice. Interventions for bone revitalization using recombinant human insulin-like growth factors (IGF) (44) and biphosphonates (24, 45) are being investigated but cannot be recommended for routine clinical use. Comorbid psychiatric disorders, such as obsessivecompulsive disorder, severe mood disorders, and/or substance dependence, require modifications of psychiatric medications and psychotherapies. A controlled trial has shown that after sufficient weight restoration has occurred to permit return to ambulatory aftercare, fluoxetine, averaging 40 mg/day, may help avert subsequent weight loss, depression, and rehospitalization (46). Another controlled study demonstrated that although dropout rates were high, CBT after weight gain may reduce relapse (47). In controlled trials with adult patients, other psychotherapies, including focal psychoana-

lytic and family therapy, have proved better than low-contact treatment (48). For younger patients, family involvement is always required, and family therapy clearly shows advantage for patients 18 years of age or younger (49). Recovery is often prolonged even in the best of situations. Full psychosocial recovery may take 57 years, with treatment continuing long after weight is restored (50, 51).

TREATING

BULIMIA NERVOSA

Both psychotherapeutic and medication treatments are available for treating bulimia nervosa, and some studies suggest that combining CBT and an SSRI yields the best results (52). Available evidence supports CBT-based treatments as the most effective single approach (53, 54), but many psychiatrists are not well trained in this area. Controlled studies show that both individual and group CBT and interpersonal psychotherapy are effective in treating bulimia nervosa (55), and dialectical behavior therapy focusing on emotion regulation skills has been shown to result in significant improvement in binging and purging behavior compared with waiting-list control subjects (56). CBT either alone or in combination with nutritional therapy was more effective than nutritional therapy alone or a control support group (57). In cases where clinical complexity does not immediately mandate more intensive interventions, self-management strategies employing written, Web-based, or CD-ROM-based CBT-oriented manuals (5863) may effectively help some patients with bulimia nervosa and bingeeating disorder. However, limitations are evident; many patients do not complete these trials (64), and many who do complete them ultimately seek professional treatment (58). Adding fluoxetine to selfhelp manual-based interventions may yield better outcomes than either treatment alone (65). Among patients who failed an initial course of CBT, a small controlled study showed that those who were subsequently assigned to a fluoxetine group did better than those who received placebo (66). However, high dropout and low abstinence rates have been seen among patients who underwent a trial of interpersonal psychotherapy or medication management after failing CBT (67). For relapse prevention, scheduling regular visits is recommended, since simply telling successfully treated patients with bulimia nervosa to come back if they have additional problems appears ineffective as a relapse prevention technique (68). Various medications have been used in treating bulimia nervosa. SSRIs have long been considered the gold standard, particularly fluoxetine, for which the largest controlled studies have been conducted

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(69). With fluoxetine, the higher dose levels usually used to treat obsessive-compulsive disorders (typically 60 mg) are more effective than the lower doses usually effective for depression (typically 20 mg). Early smaller series showed effectiveness for tricyclic antidepressants and monoamine oxidase inhibitors, which are now rarely used. These medications are no longer recommended as first-line treatments. Other classes of agents have been investigated, largely in relatively small industry-sponsored studies. In double-blind studies, inositol (which has also been effective in treating depression and obsessive-compulsive disorder) (70), ondansetron (71), and topiramate (72, 73), and, in open trials, the selective noradrenergic receptor inhibitor (SNRI) reboxetine (not available in the United States) (74, 75) have all been reported to be effective in treating bulimia nervosa.

promise for binge-eating disorder in recent trials, but about 25% of patients in these studies discontinued the anticonvulsant because of adverse events. Overall, the available evidence seems to favor psychotherapy alone over medications alone for treatment of binge-eating disorder. In a recent randomized double-blind placebo-controlled trial, the addition of 60 mg/day of fluoxetine to CBT did not appear to alter rates of remission or produce substantial advantage on dimensional measures of binge eating or psychological distress (84). In some other instances, adding medications to CBT-based psychotherapy has appeared to enhance the effects of CBT on eating behavior or at least on symptoms of depression (85).

CLINICAL SYNTHESIS

QUESTIONS

AND CONTROVERSIES

TREATING
SPECIFIED

EATING DISORDER NOT OTHERWISE

Within this heterogeneous category, binge-eating disorder merits particular attention. Interpreting treatment studies of binge-eating disorder requires caution, since the symptoms of this disorder are often labile, and high placebo response rates are frequently seen. CBT and interpersonal psychotherapy have been studied most extensively in binge-eating disorder, and both appear to do reasonably well at keeping patients in treatment. Results of psychosocial treatments resemble those for bulimia nervosa (76). Treatment of binge-eating disorder often entails concurrent interventions to address comorbid obesity, usually involving behaviors, exercise, and diet. Some research shows that patients with binge-eating disorder who receive CBT do better if they also receive exercise instruction monitored by and subsequently maintained with biweekly booster sessions conducted by exercise staff (77). Results of medication studies for binge-eating disorder also parallel those for bulimia nervosa. More recent studies, most of them industry funded, have shown several SSRIs to be somewhat effective. In 6week double-blind placebo-controlled trials, fluoxetine (78) and citalopram (79) have each been shown to be more effective than placebo in reducing bingeeating behavior and promoting weight loss. In another small study, fluvoxamine was not more effective than placebo, although improvement was seen with both (80). In a 12-week randomized doubleblind placebo-controlled trial, the SNRI sibutramine was superior to placebo in reducing binge eating, with differential results evident by the third week (81). Several novel anticonvulsants, including topiramate (82) and zonisamide (83), have also shown

Questions and controversies abound on the treatment of eating disorders, and many of them may yield to future research. For anorexia nervosa, few controlled trials have been conducted because of substantial difficulties in implementing and sustaining controlled trials with this patient group, and many trials suffer from high dropout rates. Consequently, debates remain on optimal nutritional, pharmacological, and psychotherapeutic strategies. For example, the use of supplemental overnight nasogastric feedings for hospitalized patients who are willing to tolerate this intervention deserves more study (86). Similarly, the use of atypical antipsychotics with or without SSRIs for underweight patients merits further investigation. SSRIs may prove to be particularly important for patients who are unable to access specialty inpatient programs. The use of biphosphonates and other currently experimental interventions using bone growth factors to retard or reverse osteopenia and osteoporosis demands more investigation. The value of incorporating psychotherapeutic elements derived from various schools transtheoretically, where different approaches are tailored to different stages of these disorders to yield optimum benefits, is unclear. Although motivational enhancement for unmotivated, resistant patients with eating disorders sounds good in theory, its value has yet to be demonstrated in practice. For younger patients and their families, the so-called Maudsley approach of actively enlisting parents to take charge of their childrens eating is receiving considerable attention, but empirical studies are needed to delineate which patients and under what circumstances this approach is most useful. For bulimia nervosa, current questions to be addressed concern the best mix and staging of transtheoretical psychotherapy treatment elements

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in relation to severity and concurrent psychiatric comorbidities, the combination of such treatments with medications and other somatic treatments, and management of the difficult syndromes that remain unresponsive to current treatments. For binge-eating disorder, treatment of the psychological and behavioral problems in the context of obesitywhich itself is still difficult to treat remains challenging. In particular, questions regarding the potential value and hazards of gastric surgery in treating seriously obese binge eaters are unresolved.

REFERENCES
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RECOMMENDATIONS
AUTHORS

FROM THE

Clinicians treating patients with eating disorders should be familiar with APAs current practice guidelines (20) and Guideline Watch updates, the most recent of which was published in February 2005 (87). Additional guidelines, many of which also address the role of nonpsychiatric practitioners, are also available, such as those from the National Institute for Clinical Excellence in Great Britain (27, 88), the Royal Australian and New Zealand College of Psychiatrists (26), pediatric groups (89, 90), and the American Dietetic Association (91). Interventions have been evaluated in Cochrane reviews (25). The guidelines all point to the importance of early intervention, interdisciplinary treatment, initial refeeding, careful medical monitoring, involving the family in the treatment of younger patients, flexible psychotherapeutic interventions at various points, judicious use of medications, and individualizing treatments on the basis of specific clinical features. All bemoan the fact that limited evidence has resulted in very broadly written guidelines. Clinicians searching for resources for patients may find suitable consultants and psychotherapists through the Academy for Eating Disorders (www. aedweb.org). Patients and families may be directed to resources through the National Eating Disorders Association (www.nationaleatingdisorders.org) and the National Association of Anorexia Nervosa and Associated Disorders (www.anad.org).
DISCLOSURE OF UNAPPROVED, OFF-LABEL, INVESTIGATIONAL USE OF A PRODUCT
OR

APA policy requires disclosure by CME authors of unapproved or investigational use of products discussed in CME programs. Off-label use of medications by individual physicians is permitted and common. Decisions about off-label use can be guided by the scientific literature and clinical experience. This article contains discussion of unlabeled use of a commercial product or investigational use of a product not yet approved for this purpose.

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27. Dix A: Clinical management special: mental health: one to chew over. Health Serv J 2004; 114(5899):2829 28. Eisler I, Dare C, Hodes M, Russell G, Dodge E, Le Grange D: Family therapy for adolescent anorexia nervosa: the results of a controlled comparison of two family interventions. J Child Psychol Psychiatry 2000; 41:727736 29. Robin AL, Siegel PT, Moye AW, Gilroy M, Dennis AB, Sikand A: A controlled comparison of family versus individual therapy for adolescents with anorexia nervosa. J Am Acad Child Adolesc Psychiatry 1999; 38:14821489 30. Wolfe BE, Gimby LB: Caring for the hospitalized patient with an eating disorder. Nurs Clin North Am 2003; 38:7599 31. Watson TL, Bowers WA, Andersen AE: Involuntary treatment of eating disorders. Am J Psychiatry 2000; 157:18061810 32. Howard WT, Evans KK, Quintero-Howard CV, Bowers WA, Andersen AE: Predictors of success or failure of transition to day hospital treatment for inpatients with anorexia nervosa. 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