Download 040899 Eating Disorders - New England Journal of Medicine

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.