For personal use. Only reproduce with permission from The Lancet Publishing Group.

SEMINAR
Eating disorders are of great interest to the public, of
perplexity to researchers, and a challenge to clinicians.
They feature prominently in the media, often attracting
sensational coverage. Their cause is elusive, with social,
psychological, and biological processes all seeming to play a
major part, and they are difficult to treat, with some
patients actively resisting attempts to help them.
Nevertheless, there is progress to report both in terms of
their understanding and treatment.
Classification and diagnosis
The classification of the eating disorders and their principal
diagnostic criteria are shown in panel 1.
16
Note that in
addition to anorexia nervosa and bulimia nervosa, there is a
third diagnostic category, atypical eating disorders,
3
the
equivalent American term being eating disorders not
otherwise specified.
1
A further eating disorder has also
been proposed, termed binge eating disorder.
1
Since this
condition is somewhat different in nature to the other three
diagnostic groups we will discuss it separately later.
General clinical features
Anorexia nervosa and bulimia nervosa are united by a
distinctive core psychopathology, which is essentially the
same in female and male individuals; patients overevaluate
their shape and weight. Whereas most of us assess ourselves
on the basis of our perceived performance in various
domainseg, relationships, work, parenting, sporting
prowesspatients with anorexia nervosa or bulimia nervosa
judge their self-worth largely, or even exclusively, in terms
of their shape and weight and their ability to control them.
Most of the other features of these disorders seem to be
secondary to this psychopathology and to its
consequencesfor example, self-starvation.
7
Thus, in
anorexia nervosa there is a sustained and determined
pursuit of weight loss and, to the extent that this pursuit is
successful, this behaviour is not seen as a problem. Indeed,
these patients tend to view their low weight as an
accomplishment rather than an affliction
8
and, as a
Lancet 2003; 361: 40716
Oxford University Department of Psychiatry, Warneford Hospital,
Oxford, UK (Prof C G Fairburn FRCPsych, Prof P J Harrison FRCPsych)
Correspondence to: Prof C G Fairburn, Oxford University Department
of Psychiatry, Warneford Hospital, Oxford OX3 7JX, UK
(e-mail: credo@medicine.ox.ac.uk)
consequence, they have limited motivation to change. In
bulimia nervosa, equivalent attempts to control shape and
weight are undermined by frequent episodes of
uncontrolled overeating (binge eating) with the result that
patients often describe themselves as failed anorexics. The
core psychopathology has other manifestations; for
example, many patients mislabel certain adverse physical
and emotional states as feeling fat, and some repeatedly
scrutinise aspects of their shape, which could contribute to
them overestimating their size.
Anorexia nervosa
In anorexia nervosa, the pursuit of weight loss is successful
in that a very low weight is achieved. This loss of weight is
primarily the result of a severe and selective restriction of
food intake, with foods viewed as fattening being excluded.
In most instances there is no true anorexia as such. In some
patients, the restriction over food intake is also motivated
by other psychological processes, including asceticism,
competitiveness, and a wish to punish themselves.
7
Many
patients engage in a driven type of over exercising, which
can contribute to their low weight. Self-induced vomiting
and other extreme forms of weight-control behaviour, such
as the misuse of laxatives or diuretics, are practised by a few
individuals. Some patients have times when they lose
control over eating, although the amounts eaten are often
not large. Symptoms of depression and anxiety disorders,
irritability, lability of mood, impaired concentration, loss of
sexual appetite, and obsessional features are frequent
accompaniments. Typically these features get worse as
weight is lost and improve with weight regain. Interest in
the outside world also declines as patients become
underweight, with the result that most become socially
withdrawn and isolated. This feature too is reversible.
Eating disorders
Christopher G Fairburn, Paul J Harrison
Eating disorders are an important cause of physical and psychosocial morbidity in adolescent girls and young adult
women. They are much less frequent in men. Eating disorders are divided into three diagnostic categories: anorexia
nervosa, bulimia nervosa, and the atypical eating disorders. However, the disorders have many features in common
and patients frequently move between them, so for the purposes of this Seminar we have adopted a transdiagnostic
perspective. The cause of eating disorders is complex and badly understood. There is a genetic predisposition, and
certain specific environmental risk factors have been implicated. Research into treatment has focused on bulimia
nervosa, and evidence-based management of this disorder is possible. A specific form of cognitive behaviour therapy is
the most effective treatment, although few patients seem to receive it in practice. Treatment of anorexia nervosa and
atypical eating disorders has received remarkably little research attention.
Seminar
THE LANCET Vol 361 February 1, 2003 www.thelancet.com 407
Search strategy
We searched the Medline and PsycINFO databases for articles
on eating disorders published since 1980. The key words used
were eating disorders, anorexia nervosa, bulimia nervosa,
bulimia, and binge eating. Only articles written in English were
reviewed. Additionally, we reviewed professional books (written
in English) on eating disorders published during this period.
The references listed at the end of this article were chosen on
the basis of their importance, accessibility, and usefulness as
sources of further information
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Bulimia nervosa
The main feature that distinguishes bulimia nervosa
from anorexia nervosa is that attempts to restrict food
intake are punctuated by repeated binges (episodes
of eating during which there is an aversive sense of loss of
control and an unusually large amount of food is eaten).
The amount consumed in these binges varies, but is
typically between 42 MJ (1000 kcals) and 84 MJ
(2000 kcals).
9,10
In most instances, binge eating is
followed by compensatory self-induced vomiting or
laxative misuse, but there is a subgroup who do not
purge. The combination of undereating and binge
eating results in bodyweight being generally
unremarkable, providing the other obvious difference
from anorexia nervosa. Most patients with bulimia
nervosa are distressed by their loss of control over eating
and ashamed of it, which makes them easier to engage
in treatment than those with anorexia nervosa, although
there is typically a delay of many years before they seek
help. Symptoms of depression and anxiety disorders
are often prominent and, as in the case of anorexia
nervosa, there is a subgroup who engage in substance
misuse or self-injury, or both.
1113
This subgroup is
probably over-represented in specialist treatment
centres.
14
Atypical eating disorders
Most atypical eating disorders closely resemble anorexia
nervosa and bulimia nervosa,
15,16
and many are as severe
and long lasting. Some are virtually identical to the two
prototypical disorders, but do not meet their precise
diagnostic criteria.
6
For example, the patients weight
might be just above the diagnostic threshold for anorexia
nervosa or she might still be menstruating. In others, the
picture is mixed. For instance, there could be extreme
dietary restraint, pronounced over exercising, occasional
binge eating, and a low-to-normal weight. Many such
patients have had anorexia nervosa or bulimia nervosa in
the past. Overevaluation of shape and weight is present in
most, although in some the focus is primarily on
maintaining strict control over eating.
Distribution
Panel 2
1721
gives a summary of what is known about the
distribution of eating disorders. The general belief is that
eating disorders have become more frequent over recent
decades. In the instance of bulimia nervosa, this notion
could well be true,
2225
but alternative explanations for the
apparent increase in anorexia nervosa
26,27
are plausible,
including greater help-seeking and better detection than
in the past, and changes in diagnostic practice.
18,28
The
SEMINAR
408 THE LANCET Vol 361 February 1, 2003 www.thelancet.com
Panel 1: Classification and diagnosis of eating disorders
Definition of an eating disorder
G There is a definite disturbance of eating habits or weight-control behaviour
G Either this disturbance, or associated core eating disorder features, results in a clinically significant impairment of physical
health or psychosocial functioning (core eating disorder features comprise the disturbance of eating and any associated
overevaluation of shape or weight)
G The behavioural disturbance should not be secondary to any general medical disorder or to any other psychiatric condition
Classification of eating disorders
G Anorexia nervosa
G Bulimia nervosa
G Atypical eating disorders (or eating disorder not otherwise specified)
1,3
Certain additional childhood-onset eating disorders are recognised,
4
though these are outside the scope of this Seminar
Principal diagnostic criteria
G Anorexia nervosa
Overevaluation of shape and weightie, judging self-worth largely, or exclusively, in terms of shape and weight
Active maintenance of an unduly low bodyweighteg, body-mass index 175 kg/m
2
Amenorrhoea in postmenarcheal females who are not taking an oral contraceptive. The value of the amenorrhoea criterion can
be questioned since most female patients who meet the other two diagnostic criteria are amenorrhoeic, and those who
menstruate seem to resemble closely those who do not
5,6
G Bulimia nervosa
Overevaluation of shape and weightie, judging self-worth largely, or exclusively, in terms of shape and weight
Recurrent binge eatingie, recurrent episodes of uncontrolled overeating
Extreme weight-control behavioureg, strict dietary restriction, frequent self-induced vomiting or laxative misuse
Diagnostic criteria for anorexia nervosa are not met
G Atypical eating disorders
Eating disorders of clinical severity that do not conform to the diagnostic criteria for anorexia nervosa or bulimia nervosa
Panel 2: Distribution of eating disorders
1721
Anorexia nervosa Bulimia nervosa
Worldwide distribution Predominantly Western societies Predominantly Western societies
Ethnic origin Mainly white people Mainly white people
Sex Most female (about 90%) Most female (uncertain proportion)
Age Adolescents (some young adults) Young adults (some adolescents)
Social class Possible excess in higher social classes Even distribution
Prevalence 07% (in teenage girls) 12% (in 1635-year old females)
Incidence (per 100 000 per year) 19 in females, 2 in males 29 in females, 1 in males
Secular change Possible increase Likely increase
For personal use. Only reproduce with permission from The Lancet Publishing Group.
fact that many instances do not come to medical attention
complicates research; for example, most individuals with
bulimia nervosa are not in treatment,
29,30
and the subgroup
who are is biassed in certain respects.
30
There has been little research done on the distribution
of the atypical eating disorders, although they are
frequently encountered in clinical practice. Figure 1, for
example, shows that atypical eating disorders were the
most common diagnostic category in three, well classified
case series.
15,16,31
To judge from clinical experience,
atypical eating disorders primarily affect adolescents and
young adult women.
Development and subsequent course
Anorexia nervosa typically starts in midteenage years with
the onset of dietary restriction, which proceeds to get out
of control. In some instances the disorder is short-lived
and self-limiting, or only requires a brief intervention.
These instances are most typical of young individuals
with a brief history. In others, the disorder becomes
entrenched and necessitates more intensive treatment. In
1020% of individuals, the disorder proves intractable
and unremitting.
32,33
This heterogeneity in course and
outcome is often neglected in accounts of the disorder.
The proportions with these outcomes vary in accord with
the age of the sample group and the treatment setting.
Some residual features are common, particularly
overconcern about shape, weight, and eating. A frequent
occurrence is the development of binge eating
34
and, in
about half the cases, full bulimia nervosa.
35
Most
prominent among the favourable prognostic factors are an
early age of onset and a short history, whereas
unfavourable prognostic factors include a long history,
severe weight loss, and binge eating and vomiting.
33
Anorexia nervosa is the one eating disorder to be
associated with a raised mortality rate, the standardised
mortality ratio over the first 10 years from presentation
being about 10.
19
Most deaths are either a direct result of
medical complications or due to suicide.
36
Bulimia nervosa has a slightly later age of onset than
anorexia nervosa.
37
It usually starts in much the same way
as anorexia nervosaindeed, in about a quarter of cases,
the diagnostic criteria for anorexia nervosa are met for a
time.
38
Eventually, however, episodes of binge eating
begin to interrupt the dietary restriction and, as a result,
bodyweight rises to normal or near normal levels. The
disorder tends to be self-perpetuating.
39
Thus the average
length of history at presentation is about 5 years,
37
and
even 510 years later on, between a third and a half of
individuals still have an eating disorder of clinical severity,
although in many it is atypical in form.
3942
No consistent
predictors of outcome have been identified, although
there is evidence that childhood obesity,
4345
low
selfesteem, and personality disturbance are associated
with a worse prognosis.
46
Little is known about the course of the atypical eating
disorders, although findings of a small, 3-year prospective
study
47
indicate that the eating disorder persisted in most
cases and that in almost half it evolved into anorexia
nervosa or bulimia nervosa.
Thus it seems that patients with eating disorders tend to
migrate between the diagnostic categories of anorexia
nervosa, bulimia nervosa, and the atypical eating
disorders. The main pathways are shown in figure 2. This
temporal movement, together with the fact that anorexia
nervosa, bulimia nervosa, and the atypical eating disorders
share the same distinctive psychopathology, suggest that
common mechanisms are involved in their persistence.
48
However, the fact that eating disorders do not evolve into
other conditions lends support to the distinctiveness of the
diagnostic category as a whole.
Pathogenesis
Research into the pathogenesis of the eating disorders
has focused almost exclusively on anorexia nervosa
and bulimia nervosa. There is undoubtedly a genetic
predisposition and a range of environmental risk factors,
and there is some information with respect to the identity
and relative importance of these contributions. However,
virtually nothing is known about the individual causal
processes involved, or about how they interact and vary
across the development and maintenance of the disorders.
Hence, rather than prematurely attempting to present a
unifying causal model, we indicate the main empirical
data available, and discuss briefly certain interpretational
issues.
Genetics
Eating disorders and certain associated traits run in
families.
49
There seems to be cross-transmission between
anorexia nervosa, bulimia nervosa, and the atypical eating
disorders, suggesting a shared familial liability.
50
The
prevalence of substance misuse is increased, especially in
the relatives of bulimic probands,
51,52
but there seems to
be no cross-transmission. There is also a raised prevalence
of depression,
51,53
the pattern of familial transmission
being unclear.
49
Additionally, there is evidence of familial
coaggregation of anorexia nervosa and obsessional and
perfectionist traits.
51
In the absence of adoption studies, twin designs have
been used to establish the genetic contribution to the
familiality of eating disorders. Clinic samples show
concordance for anorexia nervosa of around 55% in
SEMINAR
THE LANCET Vol 361 February 1, 2003 www.thelancet.com 409
Aberdeen, UK
(n=510)
Florence, Italy
(n=189)
Southampton, UK
(n=190)
Anorexia nervosa Bulimia nervosa Atypical eating
disorders
Figure 1: Diagnostic composition of three community-based
case series
15,16,31
Anorexia nervosa
Bulimia nervosa Atypical eating
disorders
Figure 2: Schematic representation of temporal movement
between the eating disorders
The size of the arrow indicates likelihood of movement in shown direction.
Arrows that point outside of the circle indicate recovery.
For personal use. Only reproduce with permission from The Lancet Publishing Group.
monozygotic twins and 5% in dizygotic twins, with the
corresponding figures for bulimia nervosa being 35% and
30%, respectively.
54
These findings suggest a significant
heritability of anorexia nervosa but not of bulimia nervosa.
Because clinic-based samples are potentially biassed,
population-based samples have also been studied.
Particular interest was generated by a report that indicated
that more than 80% of the variance in liability to bulimia
nervosa was genetic,
55
this estimate being much higher than
was expected from previous findings. Indeed, this finding
would make bulimia nervosa one of the most heritable of all
complex phenotypes. However, as table 1
5662
shows, there is
still uncertainty as to the size of the genetic contribution to
bulimia nervosa, and to anorexia nervosa, with there being
differing point estimates and wide confidence intervals. The
same applies to the contributions of individual-specific and
shared (common) environmental factors. Several issues
affect the interpretation of these data.
61,62
For example,
there has been insufficient power to detect shared
environmental effects, and established diagnostic criteria
have been broadened considerably to increase the number
of affected twins available for analysis.
Despite these caveats, there is a clear and possibly
substantial genetic contribution to both anorexia nervosa
and bulimia nervosa. Molecular genetic studies are being
undertaken to identify the underlying loci and genes.
Genetic association studies have focused on poly-
morphisms in serotonin (5-HT)-related genes, because
this neurotransmitter system is important in regulation of
eating and mood. Particular attention was drawn to the
5-HT2AR (HTR2A) gene after an association was
reported between allelic variation in the promoter region
(1438 AG) and anorexia nervosa.
63
However, three of
six studies, and a multicentre family-based study, have not
been able to confirm this observation.
64
A range of other
polymorphisms have been investigated, but no associations
with eating disorders have yet been clearly replicated, or
confirmed in a family study or by meta-analysis.
65
In the
first genome-wide linkage survey yet reported, only weak
evidence for linkage in anorexia nervosa was noted, the
highest non-parametric linkage score (180) being for a
marker on chromosome 4.
66
In families of probands with
the restricting subtype of anorexia nervosaie, those with
no binge eating or purgingthere was modest evidence of
linkage to chromosome 1p. A further analysis, which
covaried for related behavioural traits, came up with a
different locus on chromosome 1, as well as loci on
chromosomes 2 and 13.
67
All these findings must be
judged preliminary.
Other research into risk factors
Many other risk factors have been implicated,
68
and
their respective contributions have been assessed in an
integrated series of community-based, case-control studies
(panel 3).
6871
The various factors differ in nature and
specificity. Some are adverse premorbid experiences of the
type associated with many psychiatric disorderseg,
childhood sexual abuse. Others seem to predispose
especially to bulimia nervosaeg, childhood and parental
obesity, early menarche, parental alcoholismsome of
which could operate by sensitising the person to her or his
shape, thereby encouraging dieting. This effect is most
likely to be seen in women in view of the social pressure on
them to be slim. Yet other risk factors are character traits,
the two most prominent being low selfesteem and
perfectionism, the latter being a particularly common
antecedent of anorexia nervosa.
70
SEMINAR
410 THE LANCET Vol 361 February 1, 2003 www.thelancet.com
Panel 3: Main risk factors for anorexia nervosa and
bulimia nervosa
6871
General factors
Female
Adolescence and early adulthood
Living in a Western society
Individual-specific factors
Family history
G Eating disorder of any type
G Depression
G Substance misuse, especially alcoholism (bulimia nervosa)
G Obesity (bulimia nervosa)
Premorbid experiences
G Adverse parenting (especially low contact, high
expectations, parental discord)
G Sexual abuse
G Family dieting
G Critical comments about eating, shape, or weight from
family and others
G Occupational and recreational pressure to be slim
Premorbid characteristics
G Low selfesteem
G Perfectionism (anorexia nervosa and to a lesser extent
bulimia nervosa)
G Anxiety and anxiety disorders
G Obesity (bulimia nervosa)
G Early menarche (bulimia nervosa)
Origin of sample Heritability Shared environment Individual-specific environment
(%, 95% CI) (%, 95% CI) (%, 95% CI)
Anorexia nervosa
Wade et al, 2000
56
Virginia 58 (3384) 42 (1668)
Kortegaard et al, 2001
57
Denmark 48 (2765) 52 (NA)
Klump et al, 2001
58
Minnesota 76 (3595) 24 (565)
Bulimia nervosa*
Kendler et al, 1991
23
Virginia 54 (077) 1 (065) 46 (2377)
Bulik et al, 1998
55
Virginia 51 (086) 0 (068) 49 (14100)
Wade et al, 1999
59
Australia 32 (068) 0 (052) 68 (32100)
Kendler et al, 1995
60
Virginia 28 (762) 37 (1059) 35 (1949)
Bulik et al, 1998
55
Virginia 31 (054) 0 (035) 67 (4694)
Bulik et al, 1998
55
Virginia 83 (49100) 0 (030) 17 (036)
Wade et al, 1999
59
Australia 59 (3668) 0 (011) 41 (3348)
Kortegaard et al, 2001
57
Denmark 61 (4475) 24 (NA)
NA=not available. *Except for Kortegaard et al, the bulimia nervosa results are adapted from table 2 of the Bulik et al, review. Some of the point estimates differ from
those provided in the original reports because the review used a different statistical model. The diagnostic criteria (see panel 1) have been relaxed in all these studies,
often substantially. The Bulik et al study used two different definitions. The twins in the Virginia and Australia studies were interviewed on several occasions (waves).
Two of the studies
5559
used this information to improve diagnostic reliability. These important issues are discussed elsewhere.
61,62
Table 1: Eating disorders: estimates of heritability and environmental contributions in population-based twin studies
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Neurobiological findings
There has been extensive research into the neurobiology of
eating disorders.
72
This work has focused on neuropeptide
and monoamine (especially 5-HT) systems thought to be
central to the physiology of eating and weight regulation. Of
the various central and peripheral abnormalities reported,
many are likely to be secondary to the aberrant eating and
associated weight loss. However, some aspects of 5-HT
function remain abnormal after recovery,
7274
leading to
speculation that there is a trait monoamine abnormality
that might predispose to the development of eating
disorders or to associated characteristics such as
perfectionism. Furthermore, normal dieting in healthy
women alters central 5-HT function, providing a potential
mechanism by which eating disorders might be precipitated
in women vulnerable for other reasons.
75,76
Psychological processes
Specific psychological theories have been proposed to
account for the development and maintenance of eating
disorders. Most influential in terms of treatment have been
cognitive behavioural theories.
48,7780
In brief, these theories
propose that the restriction of food intake that characterises
the onset of many eating disorders has two main origins,
both of which may operate. The first is a need to feel in
control of life, which gets displaced onto controlling
eating.
80
The second is overevaluation of shape and weight
in those who have been sensitised to their appearance. In
both instances, the resulting dietary restriction is highly
reinforcing. Subsequently, other processes begin to operate
and serve to maintain the eating disorder. They include
social withdrawal, the fact that extreme and rigid dietary
restraint promotes binge eating in certain individuals, and
the negative effect of binge eating on concerns about shape
and the sense of being in control. There is increasing
evidence that correction of these processes is necessary for
recovery, especially in those with bulimia nervosa.
48
Binge eating disorder
By comparison with anorexia nervosa and bulimia
nervosa, little is known about binge eating disorder.
Although it shares with bulimia nervosa the symptom of
binge eating, its overlap with the other eating disorders is
limited. For example, the condition seems to primarily
affect an older age group, its sex ratio is less uneven, the
binge eating occurs against the background of a general
tendency to overeat rather than dietary restraint (which
probably accounts for its strong association with obesity),
and the fact that findings from natural history studies
39,81
and drug trials
82,83
both suggest that there is a high spon-
taneous remission rate at least in the short-term. Panel
4
8290
summarises current knowledge about the disorder.
Medical complications and their management
The physical abnormalities seen in anorexia nervosa seem
to be largely secondary to these patients disturbed eating
habits and their compromised nutritional state. Hence
most are reversed by restoration of healthy eating habits
and sound nutrition, with the possible exception of
reduced bone density. The main physical features are
listed in panel 5.
91,92
The physical abnormalities seen in
bulimia nervosa are usually minor unless vomiting, or
laxative or diuretic misuse are frequent, in which case
there is risk of electrolyte disturbance.
9395
Patients who
vomit frequently are also at risk of dental damage.
96
Equivalent physical abnormalities are noted in individuals
with those atypical eating disorders in which bodyweight
is very low or there is a high frequency of purging. There
are no established medical complications of binge eating
disorder per se (other than those secondary to comorbid
obesity).
The panoply of physical abnormalities seen in the
eating disorders can cloud thinking about diagnosis and
management. The diagnosis of an eating disorder is made
on positive grounds, using the history and mental state
examination to detect the characteristic behavioural and
attitudinal features; not by simply ruling out possible
physical causes. No laboratory tests are required to make
the diagnosis and, unless there are positive reasons to
suspect the presence of physical disease, no tests are
required to exclude other medical disorders. In general,
the management of any physical abnormalities should
focus on the correction of the eating disorder. Starvation-
induced hypothyroidism should not, for example, be
treated with thyroxine. Nevertheless, life-threatening
complications must be addressed and the patients
nutritional state needs to be optimised.
Two clinical problems deserve particular mention. The
first, osteopenia and osteoporosis, is especially common in
longstanding and severe cases of anorexia nervosa
97
and is
SEMINAR
THE LANCET Vol 361 February 1, 2003 www.thelancet.com 411
Panel 4: Current knowledge about binge eating disorder
8290
Definition Recurrent episodes of binge eating in the absence of extreme weight-control behaviour
1
Clinical features Frequent binge eating, much as in bulimia nervosa, but against the background of a general tendency to
overeat.
85,86
Strong association with obesity.
82
By definition, self-induced vomiting and laxative misuse are not
present or only occasional. Depressive features and dissatisfaction with shape common, although these
features tend to be less severe than in bulimia nervosa
Distribution Patients typically present in their 40s and as many as a quarter are male.
87
Prevalence in the community
has not been satisfactorily established. Present in 510% of those seeking treatment for obesity
Pathogenesis Barely studied. Lower exposure to "eating disorder risk factors" than in anorexia nervosa and bulimia
nervosa.
71
Nature of relation with obesity unclear
Course Little known. Patients typically give long histories of being prone to binge eat, particularly at times of stress,
but many also report extended periods free from binge eating. Spontaneous remission rate seems high
39,81
Medical complications None established, other than those secondary to any comorbid obesity
Response to treatment In the short-term seems more treatment-responsive than anorexia nervosa and bulimia nervosa. Notable
placebo response rate.
82,83
Frequency of binge eating declines in response to various pharmacological and
psychological treatments, including cognitive behaviour therapy,
88
interpersonal psychotherapy,
88
behavioural
weight loss programmes,
83
and self-help,
89,90
but with little accompanying weight change. No studies of long-
term course or outcome
For personal use. Only reproduce with permission from The Lancet Publishing Group.
associated with a substantially increased risk of fractures.
98
The pathophysiology is not well understood and there is
uncertainty over management.
99,100
Restoration of a healthy
weight and an adequate diet, and with them the resumption
of spontaneous menstruation, are of central importance.
The benefits of calcium supplementation and oestrogen
replacement are unclear.
101,102
Preliminary evidence in adult
patients suggests that the strategy of combining anabolic
(recombinant human insulin-like growth factor I) and
antiresorptive (oral contraceptive) therapy could be of
help.
102
The second problem concerns pregnancy and
childrearing. Generally, eating disorders improve during
pregnancy, but birthweight can be abnormal and there is a
higher rate of caesarean section in individuals with eating
disorders than in those without.
103,104
In a small proportion
of cases, childrearing is impaired, with secondary effects on
the childs feeding and growth.
105
Whether or not there are
more general effects on child development is not known.
Management of eating disorders
Over the past 20 years the treatment of bulimia nervosa has
attracted considerable research attention, and evidence-
based management is now possible. There have been few
randomised controlled studies into the treatment of
anorexia nervosa or the atypical eating disorders, with the
result that in their instance treatment recommendations
have to be tentative. In the absence of satisfactory
SEMINAR
412 THE LANCET Vol 361 February 1, 2003 www.thelancet.com
Panel 5: Main physical features of anorexia nervosa
9193
Physical symptoms
G Heightened sensitivity to cold
G Gastrointestinal symptomseg, constipation, fullness after eating, bloatedness
G Dizziness and syncope
G Amenorrhoea (in females not taking an oral contraceptive), low sexual appetite, infertility
G Poor sleep with early morning wakening
Physical signs
G Emaciation; stunted growth and failure of breast development (if prepubertal onset)
G Dry skin; fine downy hair (lanugo) on the back, forearms, and side of the face; in patients with hypercarotenaemia, orange
discolouration of the skin of the palms and soles
G Swelling of parotid and submandibular glands (especially in bulimic patients)
G Erosion of inner surface of front teeth (perimylolysis) in those who vomit frequently
G Cold hands and feet; hypothermia
G Bradycardia; orthostatic hypotension; cardiac arrhythmias (especially in underweight patients and those with electrolyte abnormalities)
G Dependent oedema (complicating assessment of bodyweight)
G Weak proximal muscles (elicited as difficulty rising from a squatting position)
Abnormalities on physical investigation
G Endocrine
Low concentrations of leutenising hormone, follicle stimulating hormone, and oestradiol
Low T
3
, T
4
in low normal range, normal concentrations of thyroid stimulating hormone (low T
3
syndrome)
Mild increase in plasma cortisol
Raised growth hormone concentration
Severe hypoglycaemia (rare)
Low leptin (but possibly higher than would be expected for bodyweight)
G Cardiovascular
ECG abnormalities (especially in those with electrolyte disturbance): conduction defects, especially prolongation of the Q-T interval,
of major concern
G Gastrointestinal
Delayed gastric emptying
Decreased colonic motility (secondary to chronic laxative misuse)
Acute gastric dilatation (rare, secondary to binge eating or excessive re-feeding)
G Haematological
Moderate normocytic normochromic anaemia
Mild leucopenia with relative lymphocytosis
Thrombocytopenia
G Other metabolic abnormalities
Hypercholesterolaemia
Raised serum carotene
Hypophosphataemia (exaggerated during refeeding)
Dehydration
Electrolyte disturbance (varied in form; present in those who vomit frequently or misuse large quantities of laxatives or diuretics):
vomiting results in metabolic alkalosis and hypokalaemia; laxative misuse results in metabolic acidosis, hyponatraemia,
hypokalaemia
G Other abnormalities
Osteopenia and osteoporosis (with heightened fracture risk)
Enlarged cerebral ventricles and external cerebrospinal fluid spaces (pseudoatrophy)
For personal use. Only reproduce with permission from The Lancet Publishing Group.
systematic reviews of the full range of the research that has
been done, table 2 is intended to convey the empirical
standing of the main treatments advocated and
implemented. Note that many of these treatments have little
or no evidence to support them. The treatment of male
patients follows the same principles as that of female
patients.
Bulimia nervosa
There have been more than 50 randomised controlled trials
done to assess treatments for bulimia nervosa, and their
main findings are reasonably consistent.
106108
Although
almost all the trials have been efficacy rather than
effectiveness studies, there are good reasons to think that
their findings are relevant to management in most
psychiatric settings.
109,110
The research has generated three robust findings. First,
the most effective treatment is a specific type of cognitive
behaviour therapy that focuses on modifying the specific
behaviours and ways of thinking that maintain these
patients eating disorder.
111,112
It typically involves about 20
individual treatment sessions over 5 months and results in
substantial improvement with (on intent-to-treat analyses) a
third to a half of the patients making a complete and lasting
recovery.
106
The remainder range in outcome from greatly
improved to not improved at all. The second finding is that
antidepressant drugs have an antibulimic effect. They result
in a rapid decline in the frequency of binge eating and
purging, and an improvement in mood, but the effect is not
as great as that obtained with cognitive behaviour therapy
and, more importantly, the limited evidence available
suggests it is often not sustained. The third research finding
is a negative one: no consistent predictors of outcome have
been identified.
Three less robust findings have also emerged from the
trials. First, combining cognitive behaviour therapy with
antidepressant drugs results in few consistent benefits over
cognitive behaviour therapy alone.
113,114
Second, findings
from two trials suggest that a short-term focal
psychotherapy termed interpersonal psychotherapy
115,116
could be as effective as cognitive behaviour therapy, but it
takes considerably longer to work.
117,118
Third, simple largely
behavioural treatments (including forms of self-help) that
include elements of cognitive behaviour therapy could help
a subset of patients,
119-123
although they are unlikely to be
sufficient for the majority.
In summary, cognitive behaviour therapy is the clear
treatment of choice for bulimia nervosa. It is not a panacea,
but it has the potential to benefit many patients. Having said
that, clinical experience and research evidence
124,125
suggest
that few patients receive such therapy. Arguably, the main
role for antidepressant drugs is as a readily-delivered initial
intervention (possibly provided in primary care), the second
step being full cognitive behaviour therapy (delivered by a
trained therapist). Evidence-based guidelines cannot be
formulated for the treatment of those patients who do not
respond to cognitive behaviour therapy.
48,126
Anorexia nervosa
In view of the paucity of research on the treatment of
anorexia nervosa, the following comments simply
summarise mainstream opinion. In principle, there are four
aspects to management. The first is to help patients see that
they need help and to maintain their motivation thereafter.
This aim is crucial given their reluctance to change. The
second is weight restoration. This goal is needed to reverse
the malnutrition and of itself usually leads to substantial
improvement in the patients overall state. Weight
restoration can be achieved on an outpatient, daypatient, or
inpatient basis, their relative merits being the subject of
debate.
127130
Indications for admission to hospital include
risk of suicide, severe interpersonal problems at home, and
failure of less intensive methods. Physical indications
include a very low weight, rapid weight loss, and the
presence of medical complications, such as pronounced
oedema, severe electrolyte disturbance, hypoglycaemia, or
great intercurrent infection. Under such circumstances,
admission should be to a general medical ward or a
psychiatric unit with good access to general medical help.
In either instance, staff experienced in the management of
the disorder are a great advantage. Admission should
always be viewed as a preliminary to subsequent outpatient
treatment.
The third aspect of management is addressing patients
overevaluation of shape and weight, their eating habits, and
their general psychosocial functioning. There is no single
way to achieve this aim. One approach that has some
research support is a family-based treatment,
131
which
seems to be of most help to younger patients
132
and is thus
mainly used with adolescents. There are various forms of
family therapy and which is best is unclear.
133
Cognitive
behaviour therapy is a logical alternative for older patients,
SEMINAR
THE LANCET Vol 361 February 1, 2003 www.thelancet.com 413
Anorexia nervosa Bulimia nervosa Atypical eating disorders Binge eating disorder
Evidence Effect Evidence Effect Evidence Effect Evidence Effect
Drug treatment
Antidepressants (acute treatment) Modest 0 Considerable ** None Modest **
Antidepressants (relapse prevention) Modest * Modest * None None
Antipsychotics Modest 0 None None None
Appetite suppressants None Modest 0 None Modest **
Psychological treatment
Cognitive analytic therapy (CAT) Modest * None None None
Cognitive behaviour therapy (CBT) Modest * Strong *** None Moderate ***
"Dialectical behaviour therapy"-based treatment None Modest ** None Modest **
Exposure with response prevention (ERP) None Moderate ** None None
Family-based therapy for adolescents Moderate *** None None None
Interpersonal psychotherapy (IPT) None Moderate ** None Modest ***
Nutritional counselling Modest 0 Modest * None None
Psychodynamic psychotherapy Modest * Modest * None None
Psychoeducational self-help None Moderate * None Moderate **
Schema-based cognitive therapy None None None None
12-step approaches None None None- None
Weight of evidence: none=no studies done, modest=fewer than four trials (none of superior quality), moderate=at least four trials or two trials of superior quality,
considerable=rating between moderate and strong, strong=at least ten trials and at least five trials of superior quality. Magnitude of effect:=treatment not studied, 0=no
beneficial effect, *=slight beneficial effect, **=some beneficial effect, ***=moderate beneficial effect, ****=pronounced beneficial effectie, substantial and persistent
effect.
Table 2: Empirical standing of treatments advocated for patients with eating disorders: weight of supporting evidence from
randomised controlled trials (published and in press) and magnitude of treatment effects observed
For personal use. Only reproduce with permission from The Lancet Publishing Group.
not least in view of its effectiveness in bulimia nervosa.
However, its use in anorexia nervosa has not been well
described and there is little evidence to support this method
of care. Both forms of treatment require training to
implement them, and both are best offered on an outpatient
basis.
The fourth aspect of management, use of compulsory
treatment, is only relevant to a few cases. Reconciling
respect for patients wishes and their right to receive good
treatment can be difficult, and compulsory treatment,
though legally permissible, should never be undertaken
lightly.
134,135
Drug treatment does not have an established place in the
management of anorexia nervosa. No drug has been shown
to be of clinical value in promoting weight regain,
136,137
although preliminary findings suggest that fluoxetine might
reduce the risk of relapse in those patients whose weight has
recently been restored.
138
This observation needs to be
substantiated.
Atypical eating disorders
Since the treatment of the atypical eating disorders has
received almost no research attention, the only advice that
can be given is for clinicians to follow the guidelines for
treatment of bulimia nervosa in instances in which there is
binge eating, and those for the treatment of anorexia
nervosa in instances in which weight is low.
Clinical and research priorities
Several research themes and priorities emerge from this
Seminar. First, the existing scheme for classifying eating
disorders is unsatisfactory and anomalous, in that about half
the cases seen in clinical practice are relegated to an atypical
or not otherwise specified group (figure 1). This system is a
historical accident that needs to be rectified, since far more
unites the three categories of eating disorder than separates
them.
48
A classificatory scheme that reflects clinical reality
would greatly facilitate research and clinical practice.
Second, to clarify the pathogenesis of eating disorders
requires larger and more sophisticated twin studies than
those used to date, as well as continuing genome-wide
linkage and association studies. The search for genes might
also benefit from studies of related phenotypes, such as
obesity,
139
thinness,
140
and weight lability. Most importantly,
the research must be targeted on the interaction of genetic
and environmental processes, and this should be from a
developmental perspective. Third, there is a pressing need
for more treatment research, both in terms of developing
more effective treatments and focusing on the full range of
eating disorders. This research, and perhaps clinical
practice, would be improved by ignoring professional and
administrative boundaries that exist between adolescent and
adult eating disorder services, given the age distribution of
these disorders. Last, the gulf between research evidence
and service provision needs to be investigated and bridged;
too few patients receive evidence-based treatment and too
many receive suboptimal or inappropriate therapy.
Conflict of interest statement
None declared.
Acknowledgments
We thank Zafra Cooper, Robert Palmer, Deborah Waller,
B Timothy Walsh, and G Terence Wilson for their most helpful comments.
CGF is supported by a Principal Research Fellowship (046386) from the
Wellcome Trust. The sponsor had no role in the writing of this Seminar.
References
1 American Psychiatric Association. Diagnostic and statistical manual of
mental disorders, 4th edn (DSM-IV). Washington: American
Psychiatric Association, 1994.
2 Walsh BT, Garner DM. Diagnostic issues. In: Garner DM,
Garfinkel PE, eds. Handbook of treatment for eating disorders,
2nd edn. New York: Guilford Press, 1997: 2533.
3 Fairburn CG, Walsh BT. Atypical eating disorders (eating disorder not
otherwise specified). In: Fairburn CG, Brownell KD, eds. Eating
disorders and obesity: a comprehensive handbook, 2nd edn. New York:
Guilford Press, 2002: 17177.
4 Bryant-Waugh R, Lask B. Childhood-onset eating disorders. In:
Fairburn CG, Brownell KD, eds. Eating disorders and obesity: a
comprehensive handbook. 2nd edn. New York: Guilford Press, 2002:
21014.
5 Garfinkel PE, Lin E, Goering P, et al. Should amenorrhoea be
necessary for the diagnosis of anorexia nervosa? Evidence from a
Canadian community sample. Br J Psychiatry 1996; 168: 50006.
6 Andersen AE, Bowers WA, Watson T. A slimming program for eating
disorders not otherwise specified: reconceptualizing a confusing,
residual diagnostic category. Psychiatr Clin North Am 2001; 24: 27180.
7 Beumont PJV. Clinical presentation of anorexia nervosa and bulimia
nervosa. In: Fairburn CG, Brownell KD, eds. Eating disorders and
obesity: a comprehensive handbook, 2nd edn. New York: Guildford
Press, 2002: 16270.
8 Vitousek K, Watson S, Wilson GT. Enhancing motivation for change
in treatment-resistant eating disorders. Clin Psychol Rev 1998; 18:
391420.
9 Rosen JC, Leitenberg H, Fisher C, Khazam C. Binge-eating episodes in
bulimia nervosa: the amount and type of food consumed.
Int J Eat Disord 1986; 5: 25567.
10 Rossiter EM, Agras WS. An empirical test of the DSM-III-R definition
of binge. Int J Eat Disord 1990; 9: 51318.
11 Paul T, Schroeter K, Dahme B, Nutzinger DO. Self-injurious behavior
in women with eating disorders. Am J Psychiatry 2002; 159: 40811.
12 Dansky BS, Brewerton TD, Kilpatrick DG. Comorbidity of bulimia
nervosa and alcohol use disorders: results from the national womens
study. Int J Eat Disord 2000; 27: 18090.
13 Holderness HC, Brooks-Gunn J, Warren MP. Co-morbidity of eating
disorders and substance abuse: review of the literature.
Int J Eat Disord 1994; 16: 134.
14 Welch SL, Fairburn CG. Impulsivity or comorbidity in bulimia
nervosa: a controlled study of deliberate self-harm and alcohol and drug
misuse in a community sample. Br J Psychiatry 1996; 169: 45158.
15 Turner H, Bryant-Waugh R. Eating disorder not otherwise specified
(EDNOS) profiles of clients presenting at a community eating disorder
service. Eur Eat Disord Rev (in press).
16 Ricca V, Mannucci E, Mezzani B, et al. Psychopathological and clinical
features of outpatients with an eating disorder not otherwise specified.
Eat Weight Disord 2001; 6: 15765.
17 Hoek HW. Review of the epidemiological studies of eating disorders.
Int Rev Psychiatry 1993; 5: 6174.
18 van Hoeken D, Lucas AR. Epidemiology. In: Hoek HW, Treasure JL,
Katzman MA, eds. Neurobiology in the treatment of eating disorders.
Chichester: Wiley, 1998: 97126.
19 Nielsen S. Epidemiology and mortality of eating disorders.
Psychiatr Clin North Am 2001; 24: 20114.
20 Pawluck DE, Gorey KM. Secular trends in the incidence of anorexia
nervosa: integrative review of population-based studies. Int J Eat Disord
1998; 23: 34752.
21 Rastam M, Gillberg C, Garton M. Anorexia nervosa in a Swedish
urban region: a population-based study. Br J Psychiatry 1989; 155:
64246.
22 Bushnell JA, Wells JE, Hornblow AR, Oakley-Browne MA, Joyce P.
Prevalence of 3 bulimia syndromes in the general population.
Psychol Med 1990; 20: 67180.
23 Kendler KS, MacLean C, Neale M, et al. The genetic epidemiology of
bulimia nervosa. Am J Psychiatry 1991; 148: 162737.
24 Soundy TJ, Lucas AR, Suman VJ, Melton LJ. Bulimia nervosa in
Rochester, Minnesota from 1980 to 1990. Psychol Med 1995; 25:
106571.
25 Turnbull S, Ward A, Treasure J, Jick H, Derby L. The demand for
eating disorder care: an epidemiological study using the general practice
research database. Br J Psychiatry 1996; 169: 70512.
26 Lucas AR, Beard CM, OFallon WM, Kurland LT. 50-year trends in
the incidence of anorexia nervosa in Rochester, MN: a population-
based study. Am J Psychiatry 1991; 148: 91722.
27 Lucas AR, Crowson CS, OFallon WM, Melton LJ. The ups and
downs of anorexia nervosa. Int J Eat Disord 1999; 26: 397405.
28 Fombonne E. Anorexia nervosa: no evidence for an increase.
Br J Psychiatry 1995; 166: 46271.
29 Fairburn CG, Cooper PJ. Self-induced vomiting and bulimia nervosa:
an undetected problem. BMJ 1982; 284: 115355.
30 Fairburn CG, Welch SL, Norman PA, OConnor ME, Doll HA.
Bias and bulimia nervosa: how typical are clinic cases?
Am J Psychiatry 1996; 153: 38691.
SEMINAR
414 THE LANCET Vol 361 February 1, 2003 www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
31 Millar HR. New eating disorder service. Psychiatr Bull 1998; 22:
75154.
32 Sullivan PF, Bulik CM, Fear JL, Pickering A. Outcome of anorexia
nervosa: a case-control study. Am J Psychiatry 1998; 155: 93946.
33 Steinhausen H-C. The outcome of anorexia nervosa in the 20th
century. Am J Psychiatry 2002; 159: 128493.
34 Eddy KT, Keel PK, Dorer DJ, et al. Longitudinal comparison of
anorexia nervosa subtypes. Int J Eat Disord 2002; 31: 191201.
35 Bulik C, Sullivan PF, Fear J, Pickering A. Predictors of the
development of bulimia nervosa in women with anorexia nervosa.
J Nerv Ment Dis 1997; 185: 70407.
36 Nielsen S, Moller-Madsen S, Isager T, et al. Standardized mortality in
eating disorders: a quantitative summary of previously published and
new evidence. J Psychosom Res 1998; 44: 41334.
37 Mitchell JE, Hatsukami D, Eckert ED, Pyle RL. Characteristics of
275 patients with bulimia. Am J Psychiatry 1985; 142: 48285.
38 Sullivan PF, Bulik CM, Carter FA, Gendall KA, Joyce PR. The
significance of a prior history of anorexia in bulimia nervosa.
Int J Eat Disord 1996; 20: 25361.
39 Fairburn CG, Cooper Z, Doll HA, Norman P, OConnor M. The
natural course of bulimia nervosa and binge eating disorder in young
women. Arch Gen Psychiatry 2000; 57: 65965.
40 Collings S, King M. 10-year follow-up of 50 patients with bulimia
nervosa. Br J Psychiatry 1994; 164: 8087.
41 Fichter MM, Quadflieg N. Six-year course of bulimia nervosa.
Int J Eat Disord 1997; 22: 36184.
42 Herzog DB, Dorer DJ, Keel PK, et al. Recovery and relapse in
anorexia and bulimia nervosa: A 7.5-year follow-up study.
J Am Acad Child Adolesc Psychiatry 1999; 38: 82937.
43 Fairburn CG, Norman PA, Welch SL, OConnor ME, Doll HA,
Peveler RC. A prospective study of outcome in bulimia nervosa and
the long-term effects of three psychological treatments.
Arch Gen Psychiatry 1995; 52: 30412.
44 Bulik CM, Sullivan PF, Joyce PR, Carter FA, McIntosh VV.
Predictors of 1-year treatment outcome in bulimia nervosa.
Compr Psychiatry 1998; 39: 20614.
45 Fairburn CG, Stice E, Cooper Z, et al. Understanding persistence in
bulimia nervosa: a five-year naturalistic study. J Consult Clin Psychol
(in press).
46 Bell L. Does concurrent psychopathology at presentation influence
response to treatment for bulimia nervosa? Eat Weight Disord 2002; 7:
16881.
47 Herzog DB, Hopkins JD, Burns CD. A follow-up study of 33
subdiagnostic eating disordered women. Int J Eat Disord 1993; 14:
26167.
48 Fairburn CG, Cooper Z, Shafran R. Cognitive behaviour therapy for
eating disorders: a transdiagnostic theory and treatment.
Behav Res Ther (in press).
49 Lilenfeld LR, Kaye WH. Genetic studies of anorexia and bulimia
nervosa. In: Hoek HW, Treasure JL, Katzman MA, eds.
Neurobiology in the treatment of eating disorders. Chichester: Wiley,
1998: 16994.
50 Strober M, Freeman R, Lampert C, Diamond J, Kaye W. Controlled
family study of anorexia nervosa and bulimia nervosa: evidence of
shared liability and transmission of partial syndromes.
Am J Psychiatry 2000; 157: 393401.
51 Lilenfeld LR, Kaye WH, Greeno CG, et al. A controlled family study
of anorexia nervosa and bulimia nervosa - Psychiatric disorders in
first-degree relatives and effects of proband comorbidity.
Arch Gen Psychiatry 1998; 55: 60310.
52 Kaye WH, Lilenfeld LR, Plotnicov K, et al. Bulimia nervosa and
substance dependence: association and family transmission.
Alcohol Clin Exp Res 1996; 20: 87881.
53 Strober M, Lampert C, Morrell W, Burroughs J, Jacobs C.
A controlled family study of anorexia nervosa: evidence of familial
aggregation and lack of shared transmission with affective disorders.
Int J Eat Disord 1990; 9: 23953.
54 Treasure J, Holland A. Genetic vulnerability to eating disorders:
evidence from twin and family studies. In: Remschmidt H,
Schmidt MH, eds. Child and youth psychiatry: European
perspectives. New York: Hogrefe and Huber, 1989: 5968.
55 Bulik CM, Sullivan PF, Kendler KS. Heritability of binge-eating and
broadly defined bulimia nervosa. Biol Psychiatry 1998; 44: 121018.
56 Wade TD, Bulik CM, Neale M, Kendler KS. Anorexia nervosa and
major depression: shared genetic and environmental risk factors.
Am J Psychiatry 2000; 157: 46971.
57 Kortegaard LS, Hoerder K, Joergensen J, Gillberg C, Kyvik KO.
A preliminary population-based twin study of self-reported eating
disorder. Psychol Med 2001; 31: 36165.
58 Klump KL, Miller KB, Keel PK, McGue M, Iacono WG. Genetic
and environmental influences on anorexia nervosa syndromes in a
population-based twin sample. Psychol Med 2001; 31: 73740.
59 Wade T, Martin NG, Neale MC, et al. The structure of genetic and
environmental risk factors for three measures of disordered eating.
Psychol Med 1999; 29: 92534.
60 Kendler KS, Walters EE, Neale MC, et al. The structure of the
genetic and environmental risk factors for 6 major psychiatric
disorders in women: phobia, generalized anxiety disorder, panic
disorder, bulimia, major depression, and alcoholism.
Arch Gen Psychiatry 1995; 52: 37483.
61 Fairburn CG, Cowen PJ, Harrison PJ. Twin studies and the etiology
of eating disorders. Int J Eat Disord 1999; 26: 34958.
62 Bulik CM, Sullivan PF, Wade TD, Kendler KS. Twin studies of
eating disorders: a review. Int J Eating Disord 2000; 27: 120.
63 Collier DA, Arranz MJ, Li T, et al. Association between 5-HT2A
gene promoter polymorphism and anorexia nervosa. Lancet 1997; 350:
412.
64 Gorwood PA, Ades J, Bellodi L, et al. The 5-HT2A-1438G/A
polymorphism in anorexia nervosa: a combined analysis of 316 trios
from six European centres. Mol Psychiatry 2002; 7: 9094.
65 Hinney A, Remschmidt H, Hebebrand J. Candidate gene
polymorphisms in eating disorders. Eur J Pharmacol 2000; 410:
14759.
66 Grice DE, Halmi KA, Fichter MM, et al. Evidence for a susceptibility
gene for anorexia nervosa on chromosome 1. Am J Hum Genet 2002;
70: 78792.
67 Devlin B, Bacanu SA, Klump KL, et al. Linkage analysis of anorexia
nervosa incorporating behavioral covariates. Hum Mol Genet 2002; 11:
68996.
68 Connors ME. Developmental vulnerabilities for eating disorders. In:
Smolak L, Levine MP, Striegel-Moore R, eds. The developmental
psychopathology of eating disorders: implications for research,
prevention and treatment. New Jersey: Lawrence Erlbaum, 1996:
285310.
69 Fairburn CG, Welch SL, Doll HA, Davies BA, OConnor ME. Risk
factors for bulimia nervosa: a community-based case-control study.
Arch Gen Psychiatry 1997; 54: 50917.
70 Fairburn CG, Cooper Z, Doll HA, Welch SL. Risk factors for
anorexia nervosa: three integrated case-control comparisons.
Arch Gen Psychiatry 1999; 56: 46876.
71 Fairburn CG, Doll HA, Welch SL, et al. Risk factors for binge eating
disorder: a community-based case-control study. Arch Gen Psychiatry
1998; 55: 42532.
72 Kaye W, Strober M. The neurobiology of eating disorders. In:
Charney DS, Nestler EJ, Bunney BS, eds. Neurobiology of mental
illness. New York: Oxford University Press, 1999: 891906.
73 Kaye WH, Frank GK, Meltzer CC, et al. Altered serotonin 2A
receptor activity in women who have recovered from bulimia nervosa.
Am J Psychiatry 2001; 158: 115255.
74 Frank GK, Kaye WH, Meltzer CC, et al. Reduced 5-HT2A receptor
binding after recovery from anorexia nervosa. Biol Psychiatry 2002; 52:
896906.
75 Goodwin GM, Fairburn CG, Cowen PJ. Dieting changes serotonergic
function in women, not men: implications for the etiology of anorexia
nervosa. Psychol Med 1987; 17: 83942.
76 Cowen PJ, Clifford EM, Walsh AES, Williams C, Fairburn CG.
Moderate dieting causes 5-HT2C receptor supersensitivity.
Psychol Med 1996; 26: 115559.
77 Garner DM, Bemis KM. A cognitive-behavioral approach to anorexia
nervosa. Cognitive Ther Res 1982; 6: 12350.
78 Slade PD. Towards a functional analysis of anorexia nervosa and
bulimia nervosa. Br J Clin Psychol 1982; 21: 16779.
79 Fairburn CG. Eating disorders. In: Clark DM, Fairburn CG, eds.
Science and practice of cognitive behaviour therapy. Oxford: Oxford
University Press, 1997: 20941.
80 Fairburn CG, Shafran R, Cooper Z. A cognitive behavioural theory of
anorexia nervosa. Behav Res Ther 1999; 37: 113.
81 Cachelin FM, Striegel-Moore RH, Elder KA, et al. Natural course of
a community sample of women with binge eating disorder.
Int J Eat Disord 1999; 25: 4554.
82 Dingemans AE, Bruna MJ, Furth EF van. Binge eating disorder: a
review. Int J Obes 2002; 26: 299307.
83 Stunkard AJ. Binge-eating disorder and the night-eating syndrome. In:
Wadden TA, Stunkard AJ, eds. Handbook of obesity treatment.
New York: Guilford Press, 2002: 10721.
84 Grilo CM. Binge eating disorder. In: Fairburn CG, Brownell KD, eds.
Eating disorders and obesity: a comprehensive handbook, 2nd edn.
New York: Guilford Press, 2002: 17882.
85 Yanovski SZ, Leet M, Yanovski JA, et al. Food selection and intake of
obese women with binge eating disorder. Am J Clin Nutrition 1992;
56: 97580.
86 Goldfein JA, Walsh BT, LaChaussee JL, Kissileff HR, Devlin MJ.
Eating behavior in binge eating disorder. Int J Eat Disord 1993; 14:
42731.
SEMINAR
THE LANCET Vol 361 February 1, 2003 www.thelancet.com 415
For personal use. Only reproduce with permission from The Lancet Publishing Group.
87 Barry DT, Grilo CM, Masheb RM. Gender differences in patients with
binge eating disorder. Int J Eat Disord 2002; 31: 6370.
88 Wilfley DE, Welch RR, Stein RI, et al. A randomized comparison of
group cognitive-behavioral therapy and group interpersonal
psychotherapy for the treatment of overweight individuals with binge
eating disorder. Arch Gen Psychiatry 2002; 59: 71321.
89 Carter JC, Fairburn CG. Cognitive-behavioral self-help for binge
eating disorder: a controlled effectiveness study. J Consult Clin Psychol
1998; 66: 61623.
90 Loeb KL, Wilson GT, Gilbert JS, Labouvie E. Guided and unguided
self-help for binge eating. Behav Res Ther 2000; 38: 25972.
91 Pomeroy C, Mitchell JE, Roerig J, Crow S. Medical complications of
psychiatric illness. Washington: American Psychiatric Publishing,
2002:
92 Sharp CW, Freeman CPL. The medical complications of anorexia
nervosa. Br J Psychiatry 1993; 162: 45262.
93 Mitchell JE, Pyle RL, Eckert ED, Hatsukami D, Lentz R. Electrolyte
and other physiological abnormalities in patients with bulimia.
Psychol Med 1983; 13: 27378.
94 Mitchell JE, Hatsukami D, Pyle RL, Eckert ED, Boutacoff LI.
Metabolic acidosis as a marker for laxative abuse in patients with
bulimia. Int J Eat Disord 1987; 6: 55760.
95 Wolfe BE, Metzger ED, Levine JM, Jimerson DC. Laboratory
screening for electrolyte abnormalities and anemia in bulimia nervosa:
a controlled study. Int J Eat Disord 2001; 30: 28893.
96 Milosevic A. Eating disorders: a dentists perspective. Eur Eat Disord
Rev 1999; 7: 10310.
97 Grinspoon S, Thomas E, Pitts S, et al. Prevalence and predictive
factors for regional osteopenia in women with anorexia nervosa.
Ann Intern Med 2000; 133: 79094.
98 Vestergaard P, Emborg C, Stoving RK, et al. Fractures in patients with
anorexia nervosa, bulimia nervosa, and other eating disorders: a
nationwide register study. Int J Eat Disord 2002; 32: 30108.
99 Lennkh C, Zwaan M de, Bailer U, et al. Osteopenia in anorexia
nervosa: specific mechanisms of bone loss. J Psychiatr Res 1999; 33:
34956.
100 Wolfert A. Osteoporosis: prevention and treatment in anorexia nervosa.
Eat Weight Disord 2002; 7: 7281.
101 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:
898904.
102 Grinspoon S, Thomas L, Miller K, Herzog D, Klibanski A. Effects of
recombinant human IGF-I and oral contraceptive administration on
bone density in anorexia nervosa. J Clin Endocrinol Metab 2002; 87:
288391.
103 Franko DL, Blais MA, Becker AE, et al. Pregnancy complications and
neonatal outcomes in women with eating disorders.
Am J Psychiatry 2001; 158: 146166.
104 Franko DL, Spurrell EB. Detection and management of eating
disorders during pregnancy. Obstet Gynecol 2000; 95: 94246.
105 Patel P, Wheatcroft R, Park RJ, Stein A. The children of mothers with
eating disorders. Clin Child Fam Psychol Rev 2002; 5: 119.
106 Wilson GT, Fairburn CG. Treatments for eating disorders. In: Nathan
PE, Gorman JM, eds. A guide to treatments that work, 2nd edn. New
York: Oxford University Press, 2002: 55992.
107 Whittal ML, Agras WS, Gould RA. Bulimia nervosa: a meta-analysis of
psychosocial and pharmacological treatments. Behav Ther 1999; 30:
11735.
108 Nakash-Eisikovits O, Dierberger A, Westen D. A multidimensional
meta-analysis of pharmacotherapy for bulimia nervosa: summarizing
the range of outcomes in controlled clinical trials. Harv Rev Psychiatry
2002; 10: 193211.
109 Wilson GT. The clinical utility of randomized controlled trials.
Int J Eat Disord 1998; 24: 1329.
110 Wilson GT. Manual-based treatment and clinical practice.
Clin Psychol Sci Pract 1998; 5: 36375.
111 Fairburn C. A cognitive behavioural approach to the treatment of
bulimia. Psychol Med 1981; 11: 70711.
112 Fairburn CG, Marcus MD, Wilson GT. Cognitive-behavioral therapy
for binge eating and bulimia nervosa: a comprehensive treatment
manual. In: Fairburn CG, Wilson GT, eds. Binge eating: nature,
assessment and treatment. New York: Guilford Press, 1993: 361404.
113 Mitchell JE, Pyle RL, Eckert ED, et al. A comparison study of
antidepressants and structured intensive group psychotherapy in the
treatment of bulimia nervosa. Arch Gen Psychiatry 1990; 47: 14957.
114 Walsh BT, Wilson GT, Loeb KL, et al. Medication and psychotherapy
in the treatment of bulimia nervosa. Am J Psychiatry 1997; 154:
52331.
115 Weissman MM, Markowitz JC, Klerman GL. Comprehensive guide
to interpersonal psychotherapy. New York: Basic Books, 2000.
116 Fairburn CG. Interpersonal psychotherapy for bulimia nervosa. In:
Garner DM, Garfinkel PE, eds. Handbook of treatment for eating
disorders. New York: Guilford Press, 1997: 27894.
117 Fairburn CG, Jones R, Peveler RC, Hope RA, OConnor ME.
Psychotherapy and bulimia nervosa: longer-term effects of
interpersonal psychotherapy, behavior therapy, and cognitive-
behavior therapy. Arch Gen Psychiatry 1993; 50: 41928.
118 Agras WS, Walsh BT, Fairburn CG, Wilson GT, Kraemer HC.
A multicenter comparison of cognitive-behavioral therapy and
interpersonal psychotherapy for bulimia nervosa. Arch Gen Psychiatry
2000; 57: 45966.
119 Davis R, Olmsted MP, Rockert W. Brief group psychoeducation for
bulimia nervosa: assessing the clinical significance of change.
J Consult Clin Psychol 1990; 58: 88285.
120 Treasure J, Schmidt U, Troop N, et al. Sequential treatment for
bulimia nervosa incorporating a self-care manual. Br J Psychiatry
1996; 168: 9498.
121 Mitchell JE, Fletcher L, Hanson K, et al. The relative efficacy
of fluoxetine and manual-based self-help in the treatment of
outpatients with bulimia nervosa. J Clin Psychopharmacol 2001; 21:
298304.
122 Palmer RL, Birchall H, McGrain L, Sullivan V. Self-help for bulimic
disorders: a randomised controlled trial comparing minimal guidance
with face-to-face or telephone guidance. Br J Psychiatry 2002; 181:
23035.
123 Carter JC, Olmsted MP, Kaplan AS, et al. Self-help for bulimia
nervosa: a randomised controlled trial. Am J Psychiatry (in press).
124 Mussell MP, Crosby RD, Crow SJ, et al. Utilization of empirically
supported psychotherapy treatments for individuals with eating
disorders: a survey of psychologists. Int J Eat Disord 2000; 27:
23037.
125 Crow S, Mussell MP, Peterson C, Knopke A, Mitchell J. Prior
treatment received by patients with bulimia nervosa.
Int J Eat Disord 1999; 25: 3944.
126 Mitchell JE, Halmi K, Wilson GT, et al. A randomized secondary
treatment study of women with bulimia nervosa who fail to respond
to CBT. Int J Eating Disord 2002; 32: 27181.
127 Gowers SG, Weetman J, Shore A, Hossain F, Elvins R. Impact of
hospitalisation on the outcome of adolescent anorexia nervosa.
Br J Psychiatry 2000; 176: 13841.
128 Meads C, Gold L, Burls A. How effective is outpatient care
compared to inpatient care for the treatment of anorexia nervosa?
A systematic review. Eur Eating Disord Rev 2001; 9: 22941.
129 Zipfel S, Reas DL, Thornton C, et al. Day hospitalization programs
for eating disorders: a systematic review of the literature.
Int J Eat Disord 2002; 31: 10517.
130 Wiseman CV, Sunday SR, Klapper F, Harris WA, Halmi KA.
Changing patterns of hospitalization in eating disorder patients.
Int J Eat Disord 2001; 30: 6974.
131 Lock J, le Grange D, Agras WS, Dare C. Treatment manual for
anorexia nervosa: a family-based approach. New York: Guilford
Press, 2001.
132 Russell GFM, Szmukler GI, Dare C, Eisler I. An evaluation of family
therapy in anorexia nervosa and bulimia nervosa. Arch Gen Psychiatry
1987; 44: 104756.
133 Dare C, Eisler I. Family therapy and eating disorders. In:
Fairburn CG, Brownell KD, eds. Eating disorders and obesity:
a comprehensive handbook, 2nd edn. New York: Guilford Press,
2002: 31419.
134 Goldner EM, Birmingham CL, Smye V. Addressing treatment
refusal in anorexia nervosa: clinical, ethical and legal considerations.
In: Garner DM, Garfinkel PE, eds. Handbook of treatment for
eating disorders, 2nd edn. New York: Guilford Press, 1997:
45061.
135 Russell GFM. Involuntary treatment in anorexia nervosa.
Psychiatr Clin North Am 2001; 24: 33749.
136 Mitchell JE. Psychopharmacology of eating disorders: current
knowledge and future directions. In: Striegel-Moore R,
Smolak L, eds. Eating disorders: innovative directions in research and
practice. Washington: American Psychological Association, 2001:
197214.
137 Treasure J, Schmidt U. Anorexia nervosa. In: Barton S, ed. Clinical
evidence: mental health. London: BMJ Publishing Group, 2002:
1322.
138 Kaye WH, Nagata T, Weltzin TE, et al. Double-blind placebo-
controlled administration of fluoxetine in restricting- and restricting-
purging-type anorexia nervosa. Biol Psychiatry 2001; 49: 64452.
139 Deng HW, Deng H, Liu YJ, et al. A genomewide linkage scan for
quantitative-trait loci for obesity phenotypes. Am J Hum Genet 2002;
70: 113851.
140 Bulik CM, Allison DB. The genetic epidemiology of thinness.
Obesity Rev 2001; 2: 10715.
SEMINAR
416 THE LANCET Vol 361 February 1, 2003 www.thelancet.com