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The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne Current Concepts E ATING D ISORDERS ANNE E. BECKER, M.D., PH.D., STEVEN K. GRINSPOON, M.D., ANNE KLIBANSKI, M.D., AND DAVID B. HERZOG, M.D. E ATING disorders affect an estimated 5 million Americans every year. These illnesses — anorexia nervosa, bulimia nervosa, binge-eating disorder, and their variants — are characterized by a serious disturbance in eating, such as restriction of intake or bingeing, as well as distress or excessive concern about body shape or body weight. In addition to their effects on psychological well-being, they have a potentially devastating effect on health through the physiologic sequelae of altered nutritional status or purging. The mortality rate associated with anorexia nervosa alone, at 0.56 percent per year, is more than 12 times as high as the mortality rate among young women in the general population.1 Although effective treatments are available for these disorders, substantial delays between the onset of symptoms and treatment are common. Frequently, a person with an eating disorder does not disclose symptoms or may even conceal them because of a lack of awareness of their effect on health, ignorance of available treatment, shame at the prospect of discussing the symptoms, or unwillingness to consider relinquishing them. Moreover, eating disorders may go unrecognized in clinical settings in up to 50 percent of cases.2-4 When these disorders are detected, even dangerously ill patients can be averse to accepting appropriate treatment. EPIDEMIOLOGY, CAUSE, AND OUTCOME Eating disorders typically occur in adolescent girls or young women, although 5 to 15 percent of cases of anorexia nervosa and bulimia nervosa5 and 40 percent of cases of binge-eating disorder occur in boys and men.6 An estimated 3 percent of young women have these disorders, and probably twice that number have clinically important variants.7-9 Although eating disorders usually develop in adolescence or young adulthood, they can occur after the From the Departments of Psychiatry (A.E.B., D.B.H.), Pediatrics (D.B.H.), and Medicine (S.K.G., A.K.), Massachusetts General Hospital and Harvard Medical School; and the Harvard Eating Disorders Center, Harvard Medical School (A.E.B., D.B.H.) — all in Boston. Address reprint requests to Dr. Herzog at the Harvard Eating Disorders Center, 356 Boylston St., Boston, MA 02116, or at [email protected]. ©1999, Massachusetts Medical Society. 1092 · Apr il 8 , 19 9 9 age of 40 years10 and are increasingly seen in young children.11 Eating disorders are more prevalent in industrialized societies than in nonindustrialized societies and occur in all socioeconomic classes and major ethnic groups in the United States.12-14 The disorders appear to be caused by a combination of genetic,15,16 neurochemical,17,18 psychodevelopmental,19 and sociocultural 20,21 factors. About half of those who have anorexia nervosa or bulimia nervosa have a full recovery, approximately 30 percent have a partial recovery, and 20 percent have no substantial improvement in symptoms.22,23 ASSESSMENT The assessment and management of eating disorders address medical, nutritional, and psychological features of these illnesses and are ideally accomplished by a multidisciplinary team working closely together. Medical Assessment The medical assessment of an eating disorder focuses on the complications of altered nutritional status and purging, if present, and includes a careful history of weight changes, dietary patterns, and the frequency and severity of any purging behavior and of excessive exercise. Purging behavior may include emesis induced with ipecac or by other means or abuse of laxatives, enemas, diuretics, anorexic drugs, caffeine, or other stimulants. The differential diagnosis of weight loss includes inflammatory bowel disease and diabetes mellitus — illnesses that may coexist with and complicate the management of eating disorders — as well as cancer and thyroid disease. The patient’s weight and height should be measured and the appropriateness of weight for height, age, and sex determined according to the percentage of his or her expected body weight or the body-mass index (the weight in kilograms divided by the square of the height in meters) (Fig. 1). This information can guide decision making with respect to medical, nutritional, pharmacologic, and psychotherapeutic management. On physical examination, hypotension, bradycardia, and hypothermia are often seen in association with extremely low weight. Other findings associated with anorexia nervosa include dry skin, hypercarotenemia, lanugo, acrocyanosis, and atrophy of the breasts. Swelling of the parotid and submandibular glands, abnormal dentition, perimolysis (loss of dentin on the lingual and occlusal surfaces of the teeth), and abrasions on the dorsum of the hand (caused by scraping against the incisors during attempts at vomiting) may be seen in association with chronic self-induced vomiting. The QT interval is sometimes prolonged in patients with anorexia nervosa, even in the absence of abnormal serum electrolyte levels. Left ventricular mass is often reduced in anorexia nervosa, although systolic function typi- CURR ENT C ONC EP TS Height (cm) 140 145 150 155 160 165 170 175 180 185 191 196 201 206 211 216 290 132 BMI=30 270 123 250 114 230 105 BMI=25 210 95 190 86 BMI=20 Overweight 170 77 BMI=17.5 Normal weight 150 130 68 59 Underweight 110 Weight (kg) Weight (lb) Obese 50 Very underweight 90 41 70 32 55 57 59 61 63 65 67 69 71 73 75 77 79 81 83 85 Height (in.) Figure 1. Weight Ranges for Adults According to the Body-Mass Index. Anorexia nervosa is characterized by a body-mass index of 17.5 or lower. Adapted from the National Eating Disorders Screening Program Body Weight Assessment Tool, with permission from the Harvard Eating Disorders Center, Boston. cally is preserved. Mitral-valve prolapse may develop, but it is usually only slight, and substantial mitral regurgitation is uncommon.24 Intestinal dilatation from chronic severe constipation and diminished intestinal motility as a result of chronic laxative abuse or withdrawal may be associated with either anorexia nervosa or bulimia nervosa (Table 1). Routine laboratory tests include measurements of serum electrolyte and serum glucose levels and a complete blood count. Although the pattern of electrolyte abnormalities may provide evidence of vomiting or abuse of laxatives or diuretics, the results of these tests are often normal.25 Hypokalemia with an increase in the serum bicarbonate level may indicate frequent vomiting or use of diuretics, whereas non– anion-gap acidosis is common in cases of laxative abuse. Hypokalemia is not typically seen in association with restrictive eating alone. Hyponatremia, however, is common in anorexia nervosa and may reflect excess water intake or inappropriate regulation of antidiuretic hormone.26 Hypoglycemia is common among patients of low weight but is usually asymptomatic. Leukopenia, neutropenia, anemia, and thrombocytopenia have been well described in anorexia nervosa.27 Thyroid-function tests often reflect the euthyroid sick syndrome, characterized by decreased levels of triiodothyronine and thyroxine but a normal or moderately decreased level of thyroidstimulating hormone 28; these tests are indicated only if true thyroid disease is likely. Hypercortisolemia and elevated urinary levels of free cortisol may be present both in patients of low weight who have anorexia nervosa29 and in patients of normal weight who have bulimia nervosa.30 Despite the many signs of eating disorders, laboratory values and findings on physical examination may be normal, particularly in patients of normal weight who have bulimia nervosa. Amenorrhea is a cardinal manifestation of anorexia nervosa, but oligomenorrhea or amenorrhea may also occur in patients of normal weight who have bulimia nervosa.31 In anorexia nervosa, amenorrhea is most often the result of a decrease in the pulsatility of gonadotropin-releasing hormone, resulting in hypogonadotropic hypogonadism and low or undetectable levels of serum estradiol. Puberty, including the onset of menarche, may be delayed in adolescents with anorexia nervosa, leading to the arrest of linear growth. In men, low weight is also associated with clinical hypogonadism and decreased levels of serum testosterone.32 A threshold level of weight or body fat is thought to be necessary for normal pulsatility of gonadotropin-releasing hormone,33 but the underlying mechanism of this association is unknown. Attention has focused Vol ume 340 Numb e r 14 · 1093 The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne TABLE 1. SIGNS, SYMPTOMS, AND MEDICAL COMPLICATIONS OF ANOREXIA NERVOSA AND BULIMIA NERVOSA. Orofacial Perimolysis Dental caries Cheilosis Enlargement of the parotid gland Submandibular adenopathy Cardiovascular Postural and nonpostural hypotension Acrocyanosis Electrocardiographic abnormalities: low voltage, prolonged QT interval, prominent U waves Sinus bradycardia Atrial and ventricular arrhythmias Left ventricular changes: decreased mass, decreased cavity size Mitral-valve prolapse Cardiomyopathy (due to ipecac poisoning) Gastrointestinal Esophagitis, hematemesis (including the Mallory– Weiss syndrome) Delayed gastric emptying Decreased intestinal motility Constipation Rectal prolapse Gastric dilatation and rupture Abnormal results on liver-function tests Elevated serum amylase level Endocrine and metabolic Hypokalemia (including hypokalemic nephropathy) Hyponatremia, (rarely) hypernatremia Hypomagnesemia Hyperphosphatemia Hypoglycemia Hypothermia Euthyroid sick syndrome Hypercortisolism, elevated free cortisol level in urine Low serum estradiol level Decreased serum testosterone level Amenorrhea, oligomenorrhea Delay in puberty Arrested growth Osteoporosis Lipid abnormalities Obesity Renal Renal calculi Reproductive Infertility Insufficient weight gain during pregnancy Low-birth-weight infant Integumentary Dry skin and hair Hair loss Lanugo Yellow skin due to hypercarotenemia Hand abrasions Neurologic Peripheral neuropathy Reversible cortical atrophy Ventricular enlargement Hematologic Anemia, leukopenia, neutropenia, thrombocytopenia 1094 · Apr il 8 , 19 9 9 on leptin, a product of the ob gene in adipocytes,34 as a hormone that may regulate reproductive function and signal the hypothalamus when fat mass is decreased. Leptin levels are decreased in patients with anorexia nervosa, and this abnormality is closely correlated with fat mass.35 Although resumption of menses typically accompanies weight gain, in some cases amenorrhea persists even after the attainment of normal body weight and may be attributable to a low percentage of body fat, inadequate intake of dietary fats, excessive exercise, or depression or may be an adverse effect of a psychotropic medication. Bone loss is a serious clinical problem that may accompany amenorrhea and undernutrition, and it should be assessed by bone densitometry. In 50 percent of women with anorexia nervosa, bone-density measurements are more than 2 SD below normal,29,36 and both cortical and trabecular compartments are affected. Symptomatic compression fractures and kyphosis have been reported. Bone loss can occur in young women after as short a period of illness as six months 29,37 and may also occur in men.38 Since bone loss can persist even after the recovery of weight,39 women with a history of anorexia nervosa may be at increased long-term risk for fractures.40 Severe bone loss in anorexia nervosa probably has a variety of causes, including estrogen deficiency, vitamin and micronutrient deficiencies, hypercortisolemia, and a direct inhibitory effect of undernutrition on bone formation and osteoblast function.29,41 Furthermore, anorexia nervosa often occurs during adolescence, when accrual of bone mass is at its peak. Therefore, bone loss and inadequate bone formation in adolescents with anorexia nervosa may result in severe osteopenia. Periodic assessment of the lumbarspine bone density by dual-energy x-ray absorptiometry is reasonable to determine the risk of compression fractures and the degree of ongoing bone loss. Psychiatric Assessment The psychiatric assessment of patients with an eating disorder focuses on establishing a diagnosis, identifying any concurrent psychiatric illness, evaluating the risk of suicide, and exploring the psychosocial context of the symptoms. Although patients with an eating disorder may appear to be unwilling to participate in their treatment, clinicians can often elicit information about symptoms by remaining aware of the characteristic signs of these disorders (Table 2) and by taking a straightforward, empathic, and nonjudgmental approach. To establish a diagnosis of anorexia nervosa, bulimia nervosa, or binge-eating disorder, all the criteria listed in Table 3 must be met. There is considerable overlap among the features of eating disorders; for example, both anorexia nervosa and bulimia nervosa are marked by excessive concern about body shape or body weight, which contributes to efforts to control weight C URR ENT C ONC EP TS TABLE 2. ABNORMALITIES THAT MAY INDICATE AN UNDISCLOSED EATING DISORDER. Somatic Arrested growth Marked change or frequent fluctuation in weight Inability to gain weight Fatigue Constipation or diarrhea Susceptibility to fractures Delayed menarche Hypokalemia, hyperphosphatemia, metabolic acidosis or alkalosis, or high serum amylase levels Behavioral Change in eating habits Difficulty eating in social settings Reluctance to be weighed Depression Social withdrawal Absence from school or work Deceptive or secretive behavior Stealing (e.g., to obtain food) Substance abuse Excessive exercise by restrictive eating or by inappropriate behavior to compensate for overeating. Binge eating characterizes both binge-eating disorder and bulimia nervosa, and as many as half of patients with anorexia nervosa also binge and purge.42 The differential diagnosis of disordered eating includes depression and several organic brain syndromes (e.g., hypothalamic tumor). Evaluation for concomitant psychiatric illness and assessment of the risk of suicide should be routine, because eating disorders are often accompanied by mood, anxiety, and personality disorders. In addition, anorexia nervosa is frequently accompanied by obsessive–compulsive disorder, and bulimia nervosa and binge-eating disorder are often associated with substance abuse.42 Suicidal behavior often accompanies anorexia nervosa and bulimia nervosa and is a chief contributor to the high mortality rate among patients with anorexia nervosa.1,43 Finally, evaluation of the psychosocial context and precipitants of the illness may guide the approach to psychotherapy. OUTPATIENT MANAGEMENT TABLE 3. DIAGNOSTIC CRITERIA FOR EATING DISORDERS.* Anorexia nervosa Body weight <85% of expected weight (or body-mass index «17.5) Intense fear of weight gain Inaccurate perception of own body size, weight, or shape Amenorrhea (in girls and women after menarche) Bulimia nervosa Recurrent binge eating (at least two times per week for three months)† Recurrent purging, excessive exercise, or fasting (at least two times per week for three months) Excessive concern about body weight or shape Absence of anorexia nervosa Binge-eating disorder Recurrent binge eating (at least two days per week for six months)† Marked distress with at least three of the following: Eating very rapidly Eating until uncomfortably full Eating when not hungry Eating alone Feeling disgusted or guilty after a binge No recurrent purging, excessive exercise, or fasting Absence of anorexia nervosa Other (atypical) eating disorders Clinically important disordered eating, inappropriate weight control, or excessive concern about body weight or shape that does not meet all the criteria for anorexia nervosa, bulimia nervosa, or binge-eating disorder *Adapted from the Diagnostic and Statistical Manual of Mental Disorders, 4th ed.,6 with the permission of the publisher. †A binge is characterized by the consumption of an unusually large quantity of food during a discrete period of time, with lack of control over eating. The goals of treatment for all eating disorders include stabilization of medical and nutritional status, identification and resolution of psychosocial precipitants of the disorder, and reestablishment of healthful patterns of eating. Although treatment in an outpatient setting is usually adequate, patients at medical or psychiatric risk may initially or periodically require hospital-based day treatment or inpatient care. Indications for inpatient care include extremely low weight (generally defined as 75 percent or less of expected body weight) or rapid weight loss; severe electrolyte imbalances, cardiac disturbances, or other acute medical disorders; severe or intractable purging; psychosis or a high risk of suicide; and symptoms refractory to outpatient treatment. Medical Treatment Medical treatment of eating disorders is directed at correcting and preventing the complications of abnormal weight and purging. Treatment routinely includes educating the patient about the importance of addressing symptoms, as well as monitoring weight, vital signs (heart rate, blood pressure, and temperature) and, if purging or excessive water intake is ongoing, serum electrolyte levels. Weight gain is a primary goal of treatment of anorexia nervosa and requires active management. Education about nutrition, adjustment of caloric and nutritional intake, and limitations on exercise and other modifications of behavior are the preferred methods of effecting weight gain and usually require collaboration with a nutritionist. Enteral or parenteral nutrition is reserved for patients with severe undernutrition that has been refractory to treatment by these methods.44,45 Weight gain by any method for patients with severe anorexia nervosa warrants close medical superVol ume 340 Numb e r 14 · 1095 The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne vision, since rapid refeeding and weight gain may lead to gastric bloating, edema, and in rare cases, congestive heart failure.46 Weight loss is often a primary goal of treatment for obese patients with bingeeating disorder. For some patients, however — particularly those with a history of repeated weight loss and weight gain or with an early onset of binge eating — it may be advantageous to provide specific treatment for binge eating before proceeding with weight management.47 Because of the complications associated with anorexia nervosa and bulimia nervosa, an electrocardiogram is essential for determining whether hypokalemia or palpitations are present and for assessing the safety of any planned psychopharmacologic management. Prolongation of the QT interval contraindicates the use of tricyclic antidepressants for the treatment of an eating disorder and requires immediate medical intervention and correction of any abnormal electrolyte levels, since a prolonged QT interval may increase the risk of ventricular tachycardia and sudden death. Although gastric-motility agents have limited value in relieving the bloating associated with refeeding,48 alleviation of the severe constipation associated with long-term use of laxatives or their withdrawal may require stool softeners and bulkforming laxatives.46 Specific medical treatment is not indicated when laboratory analysis reveals the presence of the euthyroid sick syndrome; the results of thyroid tests return to normal with weight gain. Persons who have induced vomiting benefit from dental care. Primary therapy for amenorrhea in patients with anorexia nervosa is directed toward improvement in overall nutritional status. The decision to treat amenorrhea with a combination of estrogen and progestin must be individualized for each patient. For example, in patients who have symptoms of estrogen deficiency, such as atrophy of the breasts or dry skin, estrogen replacement may be warranted. However, estrogen has no established effect on bone density in women with anorexia nervosa and cannot be recommended for use in all cases.49 Periodic administration of progestin (e.g., medroxyprogesterone acetate) is not likely to be useful, because of decreased serum estrogen levels and endometrial atrophy. Although fertility is usually impaired in patients who currently have or who have a history of amenorrhea, conception can occur. A variety of obstetrical complications, including insufficient weight gain during pregnancy and low birth weight in infants, have been reported in patients with active anorexia nervosa or bulimia nervosa. Bulimia nervosa may increase the risk of miscarriage, and anorexia nervosa may increase the risk of premature birth and prenatal death.50 Postponement of conception until remission is therefore recommended.51 Because bone loss may continue if severe under1096 · Apr il 8 , 19 9 9 nutrition is prolonged, even if estrogen replacement is begun, the primary goal of treatment in patients with anorexia nervosa should be to increase weight. Vitamin supplementation should be provided, including calcium at a dose of 1000 to 1500 mg per day and a multivitamin to ensure that vitamin D intake is adequate (400 IU per day). The role of bisphosphonates and other antiresorptive agents in the management of osteopenia in anorexia nervosa has not been established. Psychiatric Treatment Eating disorders respond to a variety of psychotherapeutic approaches, and a combination of individual, group, and family treatment is often beneficial. Anorexia nervosa may respond best to family therapy among those with early-onset, nonchronic disease,52 but because of cognitive deficits associated with undernutrition in this disorder, the efficacy of psychotherapy may be limited until weight gain occurs.53 For bulimia nervosa, the best-established approach is cognitive–behavioral therapy — a structured, time-limited therapy that addresses the relations among thoughts, affect, and behavior. Interpersonal psychotherapy, also focused and time-limited, addresses interpersonal sources of stress that are presumed antecedents to disordered eating, and this approach has been found to be as effective as the cognitive–behavioral approach in the treatment of bulimia nervosa.54,55 Both cognitive–behavioral therapy and interpersonal therapy are also effective in patients with binge-eating disorder.56 Psychodynamic psychotherapy is useful in the treatment of all these disorders, and the concomitant use of behavioral strategies early in treatment to control symptoms is often indispensable.57 Whether or not family therapy is initiated, education of the patient’s parents or partner concerning the illness is often helpful in enlisting the family’s support of the treatment. Parents of adolescent patients should be informed that clinician–patient discussions are confidential unless there is concern about the patient’s safety. Psychopharmacologic therapy is generally not effective in treating the primary symptoms of anorexia nervosa, but fluoxetine may stabilize recovery in patients with anorexia who have attained 85 percent of their expected body weight.48 Zinc and cyproheptadine have not been therapeutically useful, and antidepressant and neuroleptic agents, though commonly used in treating anorexia nervosa, have not been shown to improve symptoms in controlled trials.48 A variety of other pharmacologic agents have some role in treating mood changes, anxiety, or psychotic symptoms associated with anorexia nervosa but have limited efficacy in patients with inadequate nutrition. In contrast with its limited value in treating ano- C URR ENT C ONC EP TS rexia nervosa, psychopharmacologic therapy is moderately effective in treating bulimia nervosa in adults. Of the several classes of antidepressant medication with demonstrated efficacy in the treatment of this disorder, the best studied and most easily tolerated are fluoxetine (60 mg per day) — the only drug currently approved by the Food and Drug Administration for the treatment of bulimia, desipramine (up to 300 mg per day), and imipramine (up to 300 mg per day). A number of other agents with proven efficacy in reducing bulimic symptoms are not recommended as first-line agents (e.g., trazodone or phenelzine) or may be contraindicated because of associated risks (e.g., bupropion).48 Other serotoninreuptake inhibitors are used routinely for the treatment of bulimia nervosa but have not been studied in controlled trials. The initial selection of a psychopharmacologic agent should rest on minimization of adverse effects. Consecutive trials of other agents may enhance the response in patients in whom the initial medication is not effective.58,59 Concomitant psychiatric illness should also be treated. For bulimia nervosa, the efficacy of cognitive–behavioral therapy is reported to be greater than that of medication,60-62 but adjunctive medication, especially if chosen by consecutive trial, may enhance the efficacy of this type of psychotherapy.63-65 Pharmacologic management of bingeeating disorder has not been well studied, but desipramine and fluvoxamine appear to have some efficacy in reducing the frequency of bingeing.48,66 SUMMARY Eating disorders are common among adolescent girls and young women and are associated with potentially serious medical complications, yet they often go undetected and untreated.67-69 All patients with eating disorders should be evaluated and treated for medical complications of the disease at the same time that psychotherapy and nutritional counseling are undertaken. Pharmacologic agents are often useful as adjuncts to psychotherapy for bulimia nervosa or binge-eating disorder; in the case of anorexia nervosa, psychotropic medication is generally reserved for patients with a concurrent psychiatric illness or those who have recovered some weight. Supported in part by grants from the National Institutes of Health (5R01 MH38333, R01 DK5265, and 5M01 RR01066) and by the Rubenstein Foundation. We are indebted to Dr. Jennifer Rathbun for helpful comments on previous drafts of the manuscript. REFERENCES 1. Sullivan PF. Mortality in anorexia nervosa. Am J Psychiatry 1995;152: 1073-4. 2. King MB. Eating disorders in a general practice population: prevalence, characteristics and follow-up at 12 to 18 months. Psychol Med Monogr Suppl 1989;14:1-34. 3. Stewart DE, Robinson E, Goldbloom DS, Wright C. Infertility and eating disorders. Am J Obstet Gynecol 1990;163:1196-9. 4. Whitehouse AM, Cooper PJ, Vize CV, Hill C, Vogel L. Prevalence of eating disorders in three Cambridge general practices: hidden and conspicuous morbidity. Br J Gen Pract 1992;42:57-60. 5. Andersen AE. Eating disorders in males. In: Brownell KD, Fairburn CG, eds. Eating disorders and obesity: a comprehensive handbook. New York: Guilford Press, 1995:177-87. 6. Diagnostic and statistical manual of mental disorders, 4th ed.: DSM-IV. Washington, D.C.: American Psychiatric Association, 1994:539-50, 72931. 7. Hoek HW. The distribution of eating disorders. In: Brownell KD, Fairburn CG, eds. Eating disorders and obesity: a comprehensive handbook. New York: Guilford Press, 1995:207-11. 8. Spitzer RL, Yanovski S, Wadden T, et al. Binge eating disorder: its further validation in a multisite study. Int J Eat Disord 1993;13:137-53. 9. Shisslak CM, Crago M, Estes LS. The spectrum of eating disturbances. Int J Eat Disord 1995;18:209-19. 10. Beck D, Casper R, Andersen A. Truly late onset of eating disorders: a study of 11 cases averaging 60 years of age at presentation. Int J Eat Disord 1996;20:389-95. 11. Bostic JQ, Muriel AC, Hack S, Weinstein S, Herzog D. Anorexia nervosa in a 7-year-old girl. J Dev Behav Pediatr 1997;18:331-3. 12. Crago M, Shisslak CM, Estes LS. Eating disturbances among American minority groups: a review. Int J Eat Disord 1996;19:239-48. 13. Gard MCE, Freeman CP. The dismantling of a myth: a review of eating disorders and socioeconomic status. Int J Eat Disord 1996;20:1-12. 14. Pike KM, Walsh BT. Ethnicity and eating disorders: implications for incidence and treatment. Psychopharmacol Bull 1996;32:265-74. 15. Strober M. Family-genetic studies of eating disorders. J Clin Psychiatry 1991;52:Suppl:9-12. 16. Kendler KS, MacLean C, Neale M, Kessler R, Heath A, Eaves L. The genetic epidemiology of bulimia nervosa. Am J Psychiatry 1991;148:162737. 17. Brewerton TD. Toward a unified theory of serotonin dysregulation in eating and related disorders. Psychoneuroendocrinology 1995;20:56190. 18. Kaye WH, Weltzin TE. Serotonin activity in anorexia and bulimia nervosa: relationship to the modulation of feeding and mood. J Clin Psychiatry 1991;52:Suppl:41-8. 19. Bruch H. Eating disorders: obesity, anorexia nervosa, and the person within. New York: Basic Books, 1973. 20. Garner DM, Garfinkel PE, Schwartz D, Thompson M. Cultural expectations of thinness in women. Psychol Rep 1980;47:483-91. 21. Becker AE, Hamburg P. Culture, the media, and eating disorders. Harv Rev Psychiatry 1996;4:163-7. 22. Steinhausen H-C. Treatment and outcome of adolescent anorexia nervosa. Horm Res 1995;43:168-70. 23. Keel PK, Mitchell JE. Outcome in bulimia nervosa. Am J Psychiatry 1997;154:313-21. 24. Cooke RA, Chambers JB. Anorexia nervosa and the heart. Br J Hosp Med 1995;54:313-7. 25. Greenfeld D, Mickley D, Quinlan DM, Roloff P. Hypokalemia in outpatients with eating disorders. Am J Psychiatry 1995;152:60-3. 26. Gold PW, Kaye W, Robertson GL, Ebert M. Abnormalities in plasma and cerebrospinal-fluid arginine vasopressin in patients with anorexia nervosa. N Engl J Med 1983;308:1117-23. 27. Devuyst O, Lambert M, Rodhain J, Lefebvre C, Coche E. Haematological changes and infectious complications in anorexia nervosa: a casecontrol study. QJM 1993;86:791-9. 28. Moshang T Jr, Parks JS, Baker L, et al. Low serum triiodothyronine in patients with anorexia nervosa. J Clin Endocrinol Metab 1975;40:470-3. 29. Biller BMK, Saxe V, Herzog DB, Rosenthal DI, Holzman S, Klibanski A. Mechanisms of osteoporosis in adult and adolescent women with anorexia nervosa. J Clin Endocrinol Metab 1989;68:548-54. 30. Mortola JF, Rasmussen DD, Yen SSC. Alterations of the adrenocorticotropin-cortisol axis in normal weight bulimic women: evidence for a central mechanism. J Clin Endocrinol Metab 1989;68:517-22. 31. Pirke KM, Dogs M, Fichter MM, Tuschl RJ. Gonadotrophins, oestradiol and progesterone during the menstrual cycle in bulimia nervosa. Clin Endocrinol (Oxf ) 1988;29:265-70. 32. Andersen AE, Wirth JB, Strahlman ER. Reversible weight-related increase in plasma testosterone during treatment of male and female patients with anorexia nervosa. Int J Eat Disord 1982;1(2):74-83. 33. Frisch RE, Revelle R, Cook S. Components of weight at menarche and the initiation of the adolescent growth spurt in girls: estimated total water, lean body weight and fat. Hum Biol 1973;45:469-83. 34. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-32. [Erratum, Nature 1995;374:479.] Vol ume 340 Numb e r 14 · 1097 The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne 35. Grinspoon S, Gulick T, Askari H, et al. Serum leptin levels in women with anorexia nervosa. J Clin Endocrinol Metab 1996;81:3861-3. 36. Rigotti NA, Nussbaum SR, Herzog DB, Neer RM. Osteoporosis in women with anorexia nervosa. N Engl J Med 1984;311:1601-6. 37. Bachrach LK, Guido D, Katzman D, Litt IF, Marcus R. Decreased bone density in adolescent girls with anorexia nervosa. Pediatrics 1990;86: 440-7. 38. Rigotti NA, Neer RM, Jameson L. Osteopenia and bone fractures in a man with anorexia and hypogonadism. JAMA 1986;256:385-8. 39. Herzog W, Minne H, Deter C, et al. Outcome of bone mineral density in anorexia nervosa patients 11.7 years after first admission. J Bone Miner Res 1993;8:597-605. 40. Rigotti NA, Neer RM, Skates SJ, Herzog DB, Nussbaum SR. The clinical course of osteoporosis in anorexia nervosa: a longitudinal study of cortical bone mass. JAMA 1991;265:1133-8. 41. Grinspoon S, Baum H, Lee K, Anderson E, Herzog D, Klibanski A. Effects of short-term recombinant human insulin-like growth factor I administration on bone turnover in osteopenic women with anorexia nervosa. J Clin Endocrinol Metab 1996;81:3864-70. 42. Herzog DB, Nussbaum KM, Marmor AK. Comorbidity and outcome in eating disorders. Psychiatr Clin North Am 1996;19:843-59. 43. Harris EC, Barraclough B. Suicide as an outcome for mental disorders: a meta-analysis. Br J Psychiatry 1997;170:205-28. 44. Practice guideline for eating disorders. Am J Psychiatry 1993;150:21228. 45. Mehler PS, Weiner KL. Anorexia nervosa and total parenteral nutrition. Int J Eat Disord 1993;14:297-304. 46. Rigotti NA. Eating disorders. In: Carlson KJ, Eisenstat SA, eds. Primary care of women. St. Louis: Mosby–Year Book, 1995:443-9. 47. Marcus MD. Treatment of obese patients with binge eating disorder. In: Goldstein DJ, ed. The management of eating disorders. Totowa, N.J.: Humana Press (in press). 48. Becker AE, Hamburg P, Herzog DB. The role of psychopharmacologic management in the treatment of eating disorders. In: Dunner DL, Rosenbaum JF, eds. Annual of drug therapy. Philadelphia: W.B. Saunders, 1998:17-51. 49. Klibanski A, Biller BMK, Schoenfeld DA, Herzog DB, Saxe VC. The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa. J Clin Endocrinol Metab 1995;80:898-904. 50. Franko DL, Walton BE. Pregnancy and eating disorders: a review and clinical implications. Int J Eat Disord 1993;13:41-7. 51. Stewart DE, Raskin J, Garfinkel PE, MacDonald OL, Robinson GE. Anorexia nervosa, bulimia, and pregnancy. Am J Obstet Gynecol 1987; 157:1194-8. 52. Russell GF, Szmukler GI, Dare C, Eisler I. An evaluation of family therapy in anorexia nervosa and bulimia nervosa. Arch Gen Psychiatry 1987;44:1047-56. 1098 · Ap r il 8 , 19 9 9 53. Bruch H. Anorexia nervosa: therapy and theory. Am J Psychiatry 1982;139:1531-8. 54. Agras WS. Nonpharmacologic treatments of bulimia nervosa. J Clin Psychiatry 1991;52:Suppl:29-33. 55. Fairburn CG, Jones R, Peveler RC, Hope RA, O’Connor M. Psychotherapy and bulimia nervosa: longer-term effects of interpersonal psychotherapy, behavior therapy, and cognitive behavior therapy. Arch Gen Psychiatry 1993;50:419-28. 56. Bruce B, Wilfley D. Binge eating among the overweight population: a serious and prevalent problem. J Am Diet Assoc 1996;96:58-61. 57. Tobin DL. Psychodynamic psychotherapy and binge eating. In: Fairburn CG, Wilson GT, eds. Binge eating: nature, assessment, and treatment. New York: Guilford Press, 1993:287-313. 58. Mitchell JE, Pyle RL, Eckert ED, Hatsukami D, Pomeroy C, Zimmerman R. Response to alternative antidepressants in imipramine nonresponders with bulimia nervosa. J Clin Psychopharmacol 1989;9:2913. 59. Pope HG Jr, Hudson JI, Jonas JM, Yurgelun-Todd D. Antidepressant treatment of bulimia: a two-year follow-up study. J Clin Psychopharmacol 1985;5:320-7. 60. Wilson GT, Fairburn CG. Cognitive treatments for eating disorders. J Consult Clin Psychol 1993;61:261-9. 61. Jimerson DC, Herzog DB, Brotman AW. Pharmacologic approaches in the treatment of eating disorders. Harv Rev Psychiatry 1993;1:82-93. 62. Mitchell JE, Pyle RL, Eckert ED, Hatsukami D, Pomeroy C, Zimmerman R. A comparison study of antidepressants and structured intensive group psychotherapy in the treatment of bulimia nervosa. Arch Gen Psychiatry 1990;47:149-57. 63. Beumont PJ, Russell JD, Touyz SW, et al. Intensive nutritional counselling in bulimia nervosa: a role for supplementation with fluoxetine? Aust N Z J Psychiatry 1997;31:514-24. 64. Agras WS, Rossiter EM, Arnow B, et al. One-year follow-up of psychosocial and pharmacologic treatments for bulimia nervosa. J Clin Psychiatry 1994;55:179-83. 65. Walsh BT, Wilson GT, Loeb KL, et al. Medication and psychotherapy in the treatment of bulimia nervosa. Am J Psychiatry 1997;154:52331. 66. Hudson JI, McElroy SL, Raymond NC, et al. Fluvoxamine in the treatment of binge-eating disorder: a multicenter placebo-controlled, double-blind trial. Am J Psychiatry 1998;155:1756-62. 67. Gillberg C, Rastam M, Gillberg IC. Anorexia nervosa: who sees the patients and who do the patients see? Acta Paediatr 1994;83:967-71. 68. Bryant-Waugh RJ, Lask BD, Shafran RL, Fosson AR. Do doctors recognise eating disorders in children? Arch Dis Child 1992;67:103-5. 69. Ogg EC, Millar HR, Pusztai EE, Thom AS. General practice consultation patterns preceding diagnosis of eating disorders. Int J Eat Disord 1997;22:89-93.