HM Medical Clinic

 

040899 eating disorders

Current Concepts age of 40 years10 and are increasingly seen in youngchildren.11 Eating disorders are more prevalent inindustrialized societies than in nonindustrialized so-cieties and occur in all socioeconomic classes and major ethnic groups in the United States.12-14 Thedisorders appear to be caused by a combination of ANNE E. BECKER, M.D., PH.D., STEVEN K. GRINSPOON, M.D., ANNE KLIBANSKI, M.D., tal,19 and sociocultural20,21 factors. About half of those AND DAVID B. HERZOG, M.D.
who have anorexia nervosa or bulimia nervosa havea full recovery, approximately 30 percent have a par-tial recovery, and 20 percent have no substantial im- ATING disorders affect an estimated 5 mil- provement in symptoms.
lion Americans every year. These illnesses — anorexia nervosa, bulimia nervosa, binge-eat- ing disorder, and their variants — are characterized The assessment and management of eating disor- by a serious disturbance in eating, such as restriction ders address medical, nutritional, and psychological of intake or bingeing, as well as distress or excessive features of these illnesses and are ideally accomplished concern about body shape or body weight. In addi- by a multidisciplinary team working closely together.
tion to their effects on psychological well-being, they have a potentially devastating effect on health throughthe physiologic sequelae of altered nutritional status The medical assessment of an eating disorder fo- or purging. The mortality rate associated with ano- cuses on the complications of altered nutritional sta- rexia nervosa alone, at 0.56 percent per year, is more tus and purging, if present, and includes a careful than 12 times as high as the mortality rate among history of weight changes, dietary patterns, and the young women in the general population.
frequency and severity of any purging behavior and Although effective treatments are available for these of excessive exercise. Purging behavior may include disorders, substantial delays between the onset of emesis induced with ipecac or by other means or symptoms and treatment are common. Frequently, a abuse of laxatives, enemas, diuretics, anorexic drugs, person with an eating disorder does not disclose caffeine, or other stimulants. The differential diag- symptoms or may even conceal them because of a nosis of weight loss includes inflammatory bowel dis- lack of awareness of their effect on health, ignorance ease and diabetes mellitus — illnesses that may co- of available treatment, shame at the prospect of dis- exist with and complicate the management of eating cussing the symptoms, or unwillingness to consider disorders — as well as cancer and thyroid disease.
relinquishing them. Moreover, eating disorders may The patient's weight and height should be meas- go unrecognized in clinical settings in up to 50 per- ured and the appropriateness of weight for height, cent of cases.
age, and sex determined according to the percentage 2-4 When these disorders are detected, even dangerously ill patients can be averse to accept- of his or her expected body weight or the body-mass ing appropriate treatment.
index (the weight in kilograms divided by the squareof the height in meters) (Fig. 1). This information EPIDEMIOLOGY, CAUSE, AND OUTCOME
can guide decision making with respect to medical, Eating disorders typically occur in adolescent girls nutritional, pharmacologic, and psychotherapeutic or young women, although 5 to 15 percent of cases of anorexia nervosa and bulimia nervosa On physical examination, hypotension, bradycar- percent of cases of binge-eating disorder occur in dia, and hypothermia are often seen in association boys and men.
with extremely low weight. Other findings associat- 6 An estimated 3 percent of young women have these disorders, and probably twice ed with anorexia nervosa include dry skin, hyper- that number have clinically important variants.
carotenemia, lanugo, acrocyanosis, and atrophy of though eating disorders usually develop in adoles- the breasts. Swelling of the parotid and submandib- cence or young adulthood, they can occur after the ular glands, abnormal dentition, perimolysis (loss ofdentin on the lingual and occlusal surfaces of theteeth), and abrasions on the dorsum of the hand(caused by scraping against the incisors during at-tempts at vomiting) may be seen in association with From the Departments of Psychiatry (A.E.B., D.B.H.), Pediatrics chronic self-induced vomiting. The QT interval is (D.B.H.), and Medicine (S.K.G., A.K.), Massachusetts General Hospitaland Harvard Medical School; and the Harvard Eating Disorders Center, sometimes prolonged in patients with anorexia ner- Harvard Medical School (A.E.B., D.B.H.) — all in Boston. Address reprint vosa, even in the absence of abnormal serum elec- requests to Dr. Herzog at the Harvard Eating Disorders Center, 356 Boyl- trolyte levels. Left ventricular mass is often reduced ston St., Boston, MA 02116, or at [email protected].
1999, Massachusetts Medical Society.
in anorexia nervosa, although systolic function typi- 140 145 150 155 160 165 170 175 180 185 191 196 201 206 211 216 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 EatingDisorders Screening Program Body Weight Assessment Tool, with permission from the Harvard Eating Disor-ders Center, Boston.
cally is preserved. Mitral-valve prolapse may develop, a normal or moderately decreased level of thyroid- but it is usually only slight, and substantial mitral re- stimulating hormone28; these tests are indicated only gurgitation is uncommon.24 Intestinal dilatation from if true thyroid disease is likely. Hypercortisolemia chronic severe constipation and diminished intestin- and elevated urinary levels of free cortisol may be al motility as a result of chronic laxative abuse or present both in patients of low weight who have an- withdrawal may be associated with either anorexia orexia nervosa29 and in patients of normal weight nervosa or bulimia nervosa (Table 1).
who have bulimia nervosa.30 Routine laboratory tests include measurements of Despite the many signs of eating disorders, labora- serum electrolyte and serum glucose levels and a tory values and findings on physical examination may complete blood count. Although the pattern of elec- be normal, particularly in patients of normal weight trolyte abnormalities may provide evidence of vom- who have bulimia nervosa. Amenorrhea is a cardinal iting or abuse of laxatives or diuretics, the results of manifestation of anorexia nervosa, but oligomenor- these tests are often normal.25 Hypokalemia with an rhea or amenorrhea may also occur in patients of increase in the serum bicarbonate level may indicate normal weight who have bulimia nervosa.31 In ano- frequent vomiting or use of diuretics, whereas non– rexia nervosa, amenorrhea is most often the result of anion-gap acidosis is common in cases of laxative a decrease in the pulsatility of gonadotropin-releas- abuse. Hypokalemia is not typically seen in associa- ing hormone, resulting in hypogonadotropic hypo- tion with restrictive eating alone. Hyponatremia, gonadism and low or undetectable levels of serum es- however, is common in anorexia nervosa and may re- tradiol. Puberty, including the onset of menarche, flect excess water intake or inappropriate regulation may be delayed in adolescents with anorexia nervosa, of antidiuretic hormone.26 Hypoglycemia is com- leading to the arrest of linear growth. In men, low mon among patients of low weight but is usually weight is also associated with clinical hypogonadism asymptomatic. Leukopenia, neutropenia, anemia, and and decreased levels of serum testosterone.32 A thresh- thrombocytopenia have been well described in ano- old level of weight or body fat is thought to be nec- rexia nervosa.27 Thyroid-function tests often reflect essary for normal pulsatility of gonadotropin-releas- the euthyroid sick syndrome, characterized by de- ing hormone,33 but the underlying mechanism of creased levels of triiodothyronine and thyroxine but this association is unknown. Attention has focused on leptin, a product of the ob gene in adipocytes,34 TABLE 1. SIGNS, SYMPTOMS, AND MEDICAL
as a hormone that may regulate reproductive func- COMPLICATIONS OF ANOREXIA NERVOSA tion and signal the hypothalamus when fat mass is AND BULIMIA NERVOSA.
decreased. Leptin levels are decreased in patientswith 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 Enlargement of the parotid glandSubmandibular adenopathy of normal body weight and may be attributable to a low percentage of body fat, inadequate intake of di- Postural and nonpostural hypotension etary fats, excessive exercise, or depression or may be an adverse effect of a psychotropic medication.
Electrocardiographic abnormalities: low voltage, pro- Bone loss is a serious clinical problem that may longed QT interval, prominent U waves Sinus bradycardia accompany amenorrhea and undernutrition, and it Atrial and ventricular arrhythmias should be assessed by bone densitometry. In 50 per- Left ventricular changes: decreased mass, decreased cent of women with anorexia nervosa, bone-density Mitral-valve prolapse measurements are more than 2 SD below normal,29,36 Cardiomyopathy (due to ipecac poisoning) and both cortical and trabecular compartments are affected. Symptomatic compression fractures and ky- Esophagitis, hematemesis (including the Mallory– phosis have been reported. Bone loss can occur in Delayed gastric emptying young women after as short a period of illness as six Decreased intestinal motility months29,37 and may also occur in men.38 Since bone loss can persist even after the recovery of weight,39 Rectal prolapseGastric dilatation and rupture women with a history of anorexia nervosa may be at Abnormal results on liver-function tests increased long-term risk for fractures.40 Elevated serum amylase level Severe bone loss in anorexia nervosa probably has Endocrine and metabolic
a variety of causes, including estrogen deficiency, vi- Hypokalemia (including hypokalemic nephropathy)Hyponatremia, (rarely) hypernatremia tamin and micronutrient deficiencies, hypercortisol- emia, and a direct inhibitory effect of undernutrition on bone formation and osteoblast function.29,41 Fur- thermore, anorexia nervosa often occurs during ad- Euthyroid sick syndrome olescence, when accrual of bone mass is at its peak.
Hypercortisolism, elevated free cortisol level in urine Therefore, bone loss and inadequate bone formation Low serum estradiol levelDecreased serum testosterone level in adolescents with anorexia nervosa may result in severe osteopenia. Periodic assessment of the lumbar- Delay in pubertyArrested growth spine bone density by dual-energy x-ray absorptiom- etry is reasonable to determine the risk of compres- Lipid abnormalities sion fractures and the degree of ongoing bone loss.
The psychiatric assessment of patients with an eat- ing disorder focuses on establishing a diagnosis, iden- InfertilityInsufficient weight gain during pregnancy tifying any concurrent psychiatric illness, evaluating Low-birth-weight infant the risk of suicide, and exploring the psychosocial context of the symptoms. Although patients with an Dry skin and hair eating disorder may appear to be unwilling to par- ticipate in their treatment, clinicians can often elicit LanugoYellow skin due to hypercarotenemia information about symptoms by remaining aware of the characteristic signs of these disorders (Table 2) and by taking a straightforward, empathic, and non- Peripheral neuropathy Reversible cortical atrophyVentricular enlargement 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 overlapamong the features of eating disorders; for example,both anorexia nervosa and bulimia nervosa are markedby excessive concern about body shape or bodyweight, which contributes to efforts to control weight by restrictive eating or by inappropriate behavior to TABLE 2. ABNORMALITIES THAT MAY INDICATE
compensate for overeating. Binge eating characterizes AN UNDISCLOSED EATING DISORDER.
both binge-eating disorder and bulimia nervosa, andas many as half of patients with anorexia nervosa also binge and purge.42 The differential diagnosis of disor- Arrested growthMarked change or frequent fluctuation in weight dered eating includes depression and several organic Inability to gain weight brain syndromes (e.g., hypothalamic tumor).
Evaluation for concomitant psychiatric illness and Constipation or diarrheaSusceptibility to fractures assessment of the risk of suicide should be routine, because eating disorders are often accompanied by Hypokalemia, hyperphosphatemia, metabolic acido- sis or alkalosis, or high serum amylase levels mood, anxiety, and personality disorders. In addi-tion, anorexia nervosa is frequently accompanied by Behavioral
Change in eating habits
obsessive–compulsive disorder, and bulimia nervosa Difficulty eating in social settings and binge-eating disorder are often associated with Reluctance to be weighed substance abuse.42 Suicidal behavior often accompa- nies anorexia nervosa and bulimia nervosa and is a Absence from school or work chief contributor to the high mortality rate among Deceptive or secretive behavior patients with anorexia nervosa.1,43 Finally, evaluation Stealing (e.g., to obtain food)Substance abuse of the psychosocial context and precipitants of the Excessive exercise illness may guide the approach to psychotherapy.
The goals of treatment for all eating disorders in- clude stabilization of medical and nutritional status,identification and resolution of psychosocial precip-itants of the disorder, and reestablishment of health- TABLE 3. DIAGNOSTIC CRITERIA FOR EATING DISORDERS.*
ful patterns of eating. Although treatment in an out-patient setting is usually adequate, patients at medical or psychiatric risk may initially or periodically re- Body weight <85% of expected weight (or body-mass index «17.5)Intense fear of weight gain quire hospital-based day treatment or inpatient care.
Inaccurate perception of own body size, weight, or shape Indications for inpatient care include extremely low Amenorrhea (in girls and women after menarche) weight (generally defined as 75 percent or less of expected body weight) or rapid weight loss; severe Recurrent binge eating (at least two times per week for three months)† electrolyte imbalances, cardiac disturbances, or other Recurrent purging, excessive exercise, or fasting (at least two times per week for three months) acute medical disorders; severe or intractable purg- Excessive concern about body weight or shape ing; psychosis or a high risk of suicide; and symp- Absence of anorexia nervosa toms refractory to outpatient treatment.
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 Medical treatment of eating disorders is directed Eating until uncomfortably full at correcting and preventing the complications of ab- Eating when not hungryEating alone normal weight and purging. Treatment routinely in- Feeling disgusted or guilty after a binge cludes educating the patient about the importance No recurrent purging, excessive exercise, or fasting of addressing symptoms, as well as monitoring weight, Absence of anorexia nervosa vital signs (heart rate, blood pressure, and temper- Other (atypical) eating disorders
ature) and, if purging or excessive water intake is Clinically important disordered eating, inappropriate weight control, or ex- cessive concern about body weight or shape that does not meet all the ongoing, serum electrolyte levels. Weight gain is a criteria for anorexia nervosa, bulimia nervosa, or binge-eating disorder primary goal of treatment of anorexia nervosa andrequires active management. Education about nutri- *Adapted from the Diagnostic and Statistical Manual of Mental Disor- ders, 4th ed.,6 with the permission of the publisher.
tion, adjustment of caloric and nutritional intake, †A binge is characterized by the consumption of an unusually large and limitations on exercise and other modifications quantity of food during a discrete period of time, with lack of control over of behavior are the preferred methods of effecting weight gain and usually require collaboration with anutritionist. Enteral or parenteral nutrition is reservedfor patients with severe undernutrition that has beenrefractory to treatment by these methods.44,45 Weight gain by any method for patients with se- vere anorexia nervosa warrants close medical super- vision, since rapid refeeding and weight gain may nutrition is prolonged, even if estrogen replacement lead to gastric bloating, edema, and in rare cases, is begun, the primary goal of treatment in patients congestive heart failure.46 Weight loss is often a pri- with anorexia nervosa should be to increase weight.
mary goal of treatment for obese patients with binge- Vitamin supplementation should be provided, in- eating disorder. For some patients, however — par- cluding calcium at a dose of 1000 to 1500 mg per ticularly those with a history of repeated weight loss day and a multivitamin to ensure that vitamin D in- and weight gain or with an early onset of binge eat- take is adequate (400 IU per day). The role of bis- ing — it may be advantageous to provide specific phosphonates and other antiresorptive agents in the treatment for binge eating before proceeding with management of osteopenia in anorexia nervosa has weight management.47 not been established.
Because of the complications associated with an- orexia nervosa and bulimia nervosa, an electrocar- diogram is essential for determining whether hypo- Eating disorders respond to a variety of psycho- kalemia or palpitations are present and for assessing therapeutic approaches, and a combination of indi- the safety of any planned psychopharmacologic man- vidual, group, and family treatment is often benefi- agement. Prolongation of the QT interval contrain- cial. Anorexia nervosa may respond best to family dicates the use of tricyclic antidepressants for the therapy among those with early-onset, nonchronic treatment of an eating disorder and requires imme- disease,52 but because of cognitive deficits associated diate medical intervention and correction of any ab- with undernutrition in this disorder, the efficacy of normal electrolyte levels, since a prolonged QT in- psychotherapy may be limited until weight gain oc- terval may increase the risk of ventricular tachycardia curs.53 For bulimia nervosa, the best-established ap- and sudden death. Although gastric-motility agents proach is cognitive–behavioral therapy — a struc- have limited value in relieving the bloating associat- tured, time-limited therapy that addresses the relations ed with refeeding,48 alleviation of the severe consti- among thoughts, affect, and behavior. Interpersonal pation associated with long-term use of laxatives or psychotherapy, also focused and time-limited, ad- their withdrawal may require stool softeners and bulk- dresses interpersonal sources of stress that are pre- forming laxatives.46 Specific medical treatment is not sumed antecedents to disordered eating, and this ap- indicated when laboratory analysis reveals the pres- proach has been found to be as effective as the ence of the euthyroid sick syndrome; the results of cognitive–behavioral approach in the treatment of thyroid tests return to normal with weight gain.
bulimia nervosa.54,55 Both cognitive–behavioral ther- Persons who have induced vomiting benefit from den- apy and interpersonal therapy are also effective in patients with binge-eating disorder.56 Primary therapy for amenorrhea in patients with Psychodynamic psychotherapy is useful in the treat- anorexia nervosa is directed toward improvement in ment of all these disorders, and the concomitant use overall nutritional status. The decision to treat amen- of behavioral strategies early in treatment to control orrhea with a combination of estrogen and proges- symptoms is often indispensable.57 Whether or not tin must be individualized for each patient. For ex- family therapy is initiated, education of the patient's ample, in patients who have symptoms of estrogen parents or partner concerning the illness is often deficiency, such as atrophy of the breasts or dry skin, helpful in enlisting the family's support of the treat- estrogen replacement may be warranted. However, ment. Parents of adolescent patients should be in- estrogen has no established effect on bone density in formed that clinician–patient discussions are confi- women with anorexia nervosa and cannot be recom- dential unless there is concern about the patient's mended for use in all cases.49 Periodic administration of progestin (e.g., medroxyprogesterone acetate) is Psychopharmacologic therapy is generally not ef- not likely to be useful, because of decreased serum fective in treating the primary symptoms of anorexia estrogen levels and endometrial atrophy. Although nervosa, but fluoxetine may stabilize recovery in pa- fertility is usually impaired in patients who currently tients with anorexia who have attained 85 percent have or who have a history of amenorrhea, concep- of their expected body weight.48 Zinc and cypro- tion can occur. A variety of obstetrical complica- heptadine have not been therapeutically useful, and tions, including insufficient weight gain during preg- antidepressant and neuroleptic agents, though com- nancy and low birth weight in infants, have been monly used in treating anorexia nervosa, have not reported in patients with active anorexia nervosa or been shown to improve symptoms in controlled tri- bulimia nervosa. Bulimia nervosa may increase the als.48 A variety of other pharmacologic agents have risk of miscarriage, and anorexia nervosa may increase some role in treating mood changes, anxiety, or psy- the risk of premature birth and prenatal death.50 Post- chotic symptoms associated with anorexia nervosa ponement of conception until remission is therefore but have limited efficacy in patients with inadequate Because bone loss may continue if severe under- In contrast with its limited value in treating ano- rexia nervosa, psychopharmacologic therapy is mod- 3. Stewart DE, Robinson E, Goldbloom DS, Wright C. Infertility and eat-
erately effective in treating bulimia nervosa in adults.
ing disorders. Am J Obstet Gynecol 1990;163:1196-9.
4. Whitehouse AM, Cooper PJ, Vize CV, Hill C, Vogel L. Prevalence of
Of the several classes of antidepressant medication eating disorders in three Cambridge general practices: hidden and conspic- with demonstrated efficacy in the treatment of this uous morbidity. Br J Gen Pract 1992;42:57-60.
5. Andersen AE. Eating disorders in males. In: Brownell KD, Fairburn
disorder, the best studied and most easily tolerated CG, eds. Eating disorders and obesity: a comprehensive handbook. New are fluoxetine (60 mg per day) — the only drug cur- York: Guilford Press, 1995:177-87.
rently approved by the Food and Drug Administra- 6. Diagnostic and statistical manual of mental disorders, 4th ed.: DSM-IV.
Washington, D.C.: American Psychiatric Association, 1994:539-50, 729-
tion for the treatment of bulimia, desipramine (up to 300 mg per day), and imipramine (up to 300 mg 7. Hoek HW. The distribution of eating disorders. In: Brownell KD, Fair-
per day). A number of other agents with proven burn CG, eds. Eating disorders and obesity: a comprehensive handbook. New York: Guilford Press, 1995:207-11.
efficacy in reducing bulimic symptoms are not rec- 8. Spitzer RL, Yanovski S, Wadden T, et al. Binge eating disorder: its fur-
ommended as first-line agents (e.g., trazodone or ther 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.
phenelzine) or may be contraindicated because of Int J Eat Disord 1995;18:209-19.
associated risks (e.g., bupropion).48 Other serotonin- 10. Beck D, Casper R , Andersen A. Truly late onset of eating disorders: a
reuptake inhibitors are used routinely for the treat- study of 11 cases averaging 60 years of age at presentation. Int J Eat Disord 1996;20:389-95.
ment of bulimia nervosa but have not been studied 11. Bostic JQ, Muriel AC, Hack S, Weinstein S, Herzog D. Anorexia ner-
in controlled trials.
vosa in a 7-year-old girl. J Dev Behav Pediatr 1997;18:331-3.
The initial selection of a psychopharmacologic 12. Crago M, Shisslak CM, Estes LS. Eating disturbances among Ameri-
can minority groups: a review. Int J Eat Disord 1996;19:239-48.
agent should rest on minimization of adverse effects.
13. Gard MCE, Freeman CP. The dismantling of a myth: a review of eat-
Consecutive trials of other agents may enhance the ing disorders and socioeconomic status. Int J Eat Disord 1996;20:1-12.
14. Pike KM, Walsh BT. Ethnicity and eating disorders: implications for
response in patients in whom the initial medication incidence and treatment. Psychopharmacol Bull 1996;32:265-74.
is not effective.58,59 Concomitant psychiatric illness 15. Strober M. Family-genetic studies of eating disorders. J Clin Psychiatry
should also be treated. For bulimia nervosa, the ef- 1991;52:Suppl:9-12.
16. Kendler KS, MacLean C, Neale M, Kessler R , Heath A, Eaves L. The
ficacy of cognitive–behavioral therapy is reported to genetic epidemiology of bulimia nervosa. Am J Psychiatry 1991;148:1627- be greater than that of medication,60-62 but adjunc- tive medication, especially if chosen by consecutive 17. Brewerton TD. Toward a unified theory of serotonin dysregulation
in eating and related disorders. Psychoneuroendocrinology 1995;20:561-
trial, may enhance the efficacy of this type of psy- chotherapy.63-65 Pharmacologic management of binge- 18. Kaye WH, Weltzin TE. Serotonin activity in anorexia and bulimia ner-
vosa: relationship to the modulation of feeding and mood. J Clin Psychia-
eating disorder has not been well studied, but desip- ramine and fluvoxamine appear to have some efficacy 19. Bruch H. Eating disorders: obesity, anorexia nervosa, and the person
in reducing the frequency of bingeing.48,66 within. New York: Basic Books, 1973.
20. Garner DM, Garfinkel PE, Schwartz D, Thompson M. Cultural ex-
pectations of thinness in women. Psychol Rep 1980;47:483-91.
21. Becker AE, Hamburg P. Culture, the media, and eating disorders.
Eating disorders are common among adolescent Harv Rev Psychiatry 1996;4:163-7.
22. Steinhausen H-C. Treatment and outcome of adolescent anorexia ner-
girls and young women and are associated with po- vosa. Horm Res 1995;43:168-70.
tentially serious medical complications, yet they of- 23. Keel PK, Mitchell JE. Outcome in bulimia nervosa. Am J Psychiatry
1997;154:313-21.
ten go undetected and untreated.67-69 All patients 24. Cooke RA, Chambers JB. Anorexia nervosa and the heart. Br J Hosp
with eating disorders should be evaluated and treat- Med 1995;54:313-7.
ed for medical complications of the disease at the 25. Greenfeld D, Mickley D, Quinlan DM, Roloff P. Hypokalemia in out-
patients with eating disorders. Am J Psychiatry 1995;152:60-3.
same time that psychotherapy and nutritional coun- 26. Gold PW, Kaye W, Robertson GL, Ebert M. Abnormalities in plasma
seling are undertaken. Pharmacologic agents are of- and cerebrospinal-fluid arginine vasopressin in patients with anorexia ner- ten useful as adjuncts to psychotherapy for bulimia vosa. N Engl J Med 1983;308:1117-23.
27. Devuyst O, Lambert M, Rodhain J, Lefebvre C, Coche E. Haemato-
nervosa or binge-eating disorder; in the case of an- logical changes and infectious complications in anorexia nervosa: a case- orexia nervosa, psychotropic medication is generally control study. QJM 1993;86:791-9.
28. Moshang T Jr, Parks JS, Baker L, et al. Low serum triiodothyronine
reserved for patients with a concurrent psychiatric in patients with anorexia nervosa. J Clin Endocrinol Metab 1975;40:470-3.
illness or those who have recovered some weight.
29. Biller BMK, Saxe V, Herzog DB, Rosenthal DI, Holzman S, Klibanski
A. Mechanisms of osteoporosis in adult and adolescent women with ano-
rexia nervosa. J Clin Endocrinol Metab 1989;68:548-54.
30. Mortola JF, Rasmussen DD, Yen SSC. Alterations of the adrenocorti-
Supported in part by grants from the National Institutes of Health cotropin-cortisol axis in normal weight bulimic women: evidence for a cen- (5R01 MH38333, R01 DK5265, and 5M01 RR01066) and by the tral mechanism. J Clin Endocrinol Metab 1989;68:517-22.
31. Pirke KM, Dogs M, Fichter MM, Tuschl RJ. Gonadotrophins, oestra-
diol and progesterone during the menstrual cycle in bulimia nervosa. Clin
We are indebted to Dr. Jennifer Rathbun for helpful comments on Endocrinol (Oxf ) 1988;29:265-70.
previous drafts of the manuscript. 32. Andersen AE, Wirth JB, Strahlman ER. Reversible weight-related in-
crease 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
1. Sullivan PF. Mortality in anorexia nervosa. Am J Psychiatry 1995;152:
and the initiation of the adolescent growth spurt in girls: estimated total water, lean body weight and fat. Hum Biol 1973;45:469-83.
2. King MB. Eating disorders in a general practice population: prevalence,
34. Zhang Y, Proenca R , Maffei M, Barone M, Leopold L, Friedman JM.
characteristics and follow-up at 12 to 18 months. Psychol Med Monogr Positional cloning of the mouse obese gene and its human homologue. Na- Suppl 1989;14:1-34.
ture 1994;372:425-32. [Erratum, Nature 1995;374:479.] 35. Grinspoon S, Gulick T, Askari H, et al. Serum leptin levels in women
53. Bruch H. Anorexia nervosa: therapy and theory. Am J Psychiatry
with anorexia nervosa. J Clin Endocrinol Metab 1996;81:3861-3.
36. Rigotti NA, Nussbaum SR , Herzog DB, Neer RM. Osteoporosis in
54. Agras WS. Nonpharmacologic treatments of bulimia nervosa. J Clin
women with anorexia nervosa. N Engl J Med 1984;311:1601-6.
37. Bachrach LK, Guido D, Katzman D, Litt IF, Marcus R. Decreased
55. Fairburn CG, Jones R , Peveler RC, Hope RA, O'Connor M. Psycho-
bone density in adolescent girls with anorexia nervosa. Pediatrics 1990;86: therapy and bulimia nervosa: longer-term effects of interpersonal psycho- therapy, behavior therapy, and cognitive behavior therapy. Arch Gen Psy- 38. Rigotti NA, Neer RM, Jameson L. Osteopenia and bone fractures in
a man with anorexia and hypogonadism. JAMA 1986;256:385-8.
56. Bruce B, Wilfley D. Binge eating among the overweight population: a
39. Herzog W, Minne H, Deter C, et al. Outcome of bone mineral density
serious and prevalent problem. J Am Diet Assoc 1996;96:58-61.
in anorexia nervosa patients 11.7 years after first admission. J Bone Miner 57. Tobin DL. Psychodynamic psychotherapy and binge eating. In: Fair-
Res 1993;8:597-605.
burn CG, Wilson GT, eds. Binge eating: nature, assessment, and treatment. 40. Rigotti NA, Neer RM, Skates SJ, Herzog DB, Nussbaum SR. The
New York: Guilford Press, 1993:287-313.
clinical course of osteoporosis in anorexia nervosa: a longitudinal study of 58. Mitchell JE, Pyle RL, Eckert ED, Hatsukami D, Pomeroy C, Zim-
cortical bone mass. JAMA 1991;265:1133-8.
merman R. Response to alternative antidepressants in imipramine non- 41. Grinspoon S, Baum H, Lee K, Anderson E, Herzog D, Klibanski A.
responders with bulimia nervosa. J Clin Psychopharmacol 1989;9:291- Effects of short-term recombinant human insulin-like growth factor I ad- ministration on bone turnover in osteopenic women with anorexia nervosa. 59. Pope HG Jr, Hudson JI, Jonas JM, Yurgelun-Todd D. Antidepressant
J Clin Endocrinol Metab 1996;81:3864-70.
treatment of bulimia: a two-year follow-up study. J Clin Psychopharmacol 42. Herzog DB, Nussbaum KM, Marmor AK. Comorbidity and outcome
in eating disorders. Psychiatr Clin North Am 1996;19:843-59.
60. Wilson GT, Fairburn CG. Cognitive treatments for eating disorders.
43. Harris EC, Barraclough B. Suicide as an outcome for mental disorders:
J Consult Clin Psychol 1993;61:261-9.
a meta-analysis. Br J Psychiatry 1997;170:205-28.
61. Jimerson DC, Herzog DB, Brotman AW. Pharmacologic approaches
44. Practice guideline for eating disorders. Am J Psychiatry 1993;150:212-
in the treatment of eating disorders. Harv Rev Psychiatry 1993;1:82-93.
62. Mitchell JE, Pyle RL, Eckert ED, Hatsukami D, Pomeroy C, Zimmer-
45. Mehler PS, Weiner KL. Anorexia nervosa and total parenteral nutri-
man R. A comparison study of antidepressants and structured intensive tion. Int J Eat Disord 1993;14:297-304.
group psychotherapy in the treatment of bulimia nervosa. Arch Gen Psy- 46. Rigotti NA. Eating disorders. In: Carlson KJ, Eisenstat SA, eds. Pri-
mary care of women. St. Louis: Mosby–Year Book, 1995:443-9.
63. Beumont PJ, Russell JD, Touyz SW, et al. Intensive nutritional coun-
47. Marcus MD. Treatment of obese patients with binge eating disorder.
selling in bulimia nervosa: a role for supplementation with fluoxetine? Aust In: Goldstein DJ, ed. The management of eating disorders. Totowa, N.J.: N Z J Psychiatry 1997;31:514-24.
Humana Press (in press).
64. Agras WS, Rossiter EM, Arnow B, et al. One-year follow-up of psy-
48. Becker AE, Hamburg P, Herzog DB. The role of psychopharmacolog-
chosocial and pharmacologic treatments for bulimia nervosa. J Clin Psychi- ic management in the treatment of eating disorders. In: Dunner DL, Rosenbaum JF, eds. Annual of drug therapy. Philadelphia: W.B. Saunders, 65. Walsh BT, Wilson GT, Loeb KL, et al. Medication and psychother-
apy in the treatment of bulimia nervosa. Am J Psychiatry 1997;154:523- 49. Klibanski A, Biller BMK, Schoenfeld DA, Herzog DB, Saxe VC. The
effects of estrogen administration on trabecular bone loss in young women 66. Hudson JI, McElroy SL, Raymond NC, et al. Fluvoxamine in the
with anorexia nervosa. J Clin Endocrinol Metab 1995;80:898-904.
treatment of binge-eating disorder: a multicenter placebo-controlled, dou- 50. Franko DL, Walton BE. Pregnancy and eating disorders: a review and
ble-blind trial. Am J Psychiatry 1998;155:1756-62.
clinical implications. Int J Eat Disord 1993;13:41-7.
67. Gillberg C, Rastam M, Gillberg IC. Anorexia nervosa: who sees the
51. Stewart DE, Raskin J, Garfinkel PE, MacDonald OL, Robinson GE.
patients and who do the patients see? Acta Paediatr 1994;83:967-71.
Anorexia nervosa, bulimia, and pregnancy. Am J Obstet Gynecol 1987; 68. Bryant-Waugh RJ, Lask BD, Shafran RL, Fosson AR. Do doctors rec-
ognise eating disorders in children? Arch Dis Child 1992;67:103-5.
52. Russell GF, Szmukler GI, Dare C, Eisler I. An evaluation of family
69. Ogg EC, Millar HR , Pusztai EE, Thom AS. General practice consul-
therapy in anorexia nervosa and bulimia nervosa. Arch Gen Psychiatry tation patterns preceding diagnosis of eating disorders. Int J Eat Disord

Source: http://img.tapuz.co.il/forums/6549253.pdf

Mary meeker web 2.0 final

Technology / Internet Trends November 5, 2008 Web 2.0 Summit – San Francisco Morgan Stanley does and seeks to do business with companies covered in Morgan Stanley Research. As a result, investors should be aware that the firm may have a conflict of interest that could affect the objectivity of Morgan Stanley Research. Investors should consider Morgan Stanley Research as only a single factor in making their investment decision. Customers of Morgan Stanley inthe US can receive independent, third-party research on companies covered in Morgan Stanley Research, at no cost to them, where such research is available. Customers can access this independent research at www.morganstanley.com/equityresearch or can call 1-800-624-2063 to request a copy of this research.For analyst certification and other important disclosures, refer to the Disclosure Section, located at the end of this report.

Microsoft word - kai 1_2015 final_en _kh-a he mrh tita2.docx

SERIAL PUBLICATION 1/2015 NATIONAL OTC MEDICINES PROGRAMME NATIONAL OTC MEDICINES Serial Publication Fimea Develops, Assesses and Informs 1/2015 © Finnish Medicines Agency Fimea 2015 Publisher Finnish Medicines Agency Fimea Postal address: P.O. Box 55, FI-00034 FIMEA Telephone: +358 29 522 3341 www.fimea.fi ISBN 978-952-5624-51-9 ISSN-L 1799-7135 ISSN 1799-7135 (printed) ISSN 1799-7143 (web)