Review

Anorexia nervosa: aetiology, assessment, and treatment

Stephan Zipfel, Katrin E Giel, Cynthia M Bulik, Phillipa Hay, Ulrike Schmidt

Anorexia nervosa is an important cause of physical and psychosocial morbidity. Recent years have brought advances Lancet Psychiatry 2015
in understanding of the underlying psychobiology that contributes to illness onset and maintenance. Genetic factors Published Online
influence risk, psychosocial and interpersonal factors can trigger onset, and changes in neural networks can sustain October 27, 2015
http://dx.doi.org/10.1016/
the illness. Substantial advances in treatment, particularly for adolescent patients with anorexia nervosa, point to the
S2215-0366(15)00356-9
benefits of specialised family-based interventions. Adults with anorexia nervosa too have a realistic chance of achieving
Department of Psychosomatic
recovery or at least substantial improvement, but no specific approach has shown clear superiority, suggesting a Medicine, University of
combination of re-nourishment and anorexia nervosa-specific psychotherapy is most effective. To successfully fight Tübingen, Tübingen, Germany
this enigmatic illness, we have to enhance understanding of the underlying biological and psychosocial mechanisms, (Prof S Zipfel MD, K E Giel PhD);
Centre for Psychosocial
improve strategies for prevention and early intervention, and better target our treatments through improved
Medicine, Department for
understanding of specific disease mechanisms. General Internal Medicine and
Psychosomatics, Heidelberg
“The want of appetite is, I believe, due to a morbid based on conflicts with inclusion of male individuals, University Hospital,
mental state…I prefer---the more general term [anorexia] Heidelberg, Germany (K E Giel);
adolescents who have not yet reached menarche, and
University of North Carolina at
‘nervosa’, since the disease occurs in males as well as women who use exogenous hormones into the diagnostic Chapel Hill, Chapel Hill, NC,
females, and is probably rather central than peripheral.” criteria. This change is also based on a large body of USA (Prof C M Bulik PhD),
Sir William Gull, 1874 accumulated evidence13 showing no meaningful clinical Department of Medical
(Transactions of the Clinical Society of London 7: 22–28) Epidemiology and
differences between women with anorexia who
Biostatistics, Karolinska
menstruate and those who do not. DSM-5 also classifies Institutet, Stockholm, Sweden
Introduction an atypical anorexia nervosa, which includes restrictive (Prof C M Bulik PhD), School of
Anorexia nervosa is a highly distinctive serious mental behaviours without meeting the low weight criterion. Medicine and Centre for Health
Research Western Sydney
disorder. It can affect individuals of all ages, sexes, sexual In DSM-5, severity of anorexia nervosa is classified along
University, Penrith, NSW,
orientations, races, and ethnic origins; however, four levels by use of the individual’s BMI: extreme (BMI Australia (Prof P Hay MD); and
adolescent girls and young adult women are particularly <15 kg/m²), severe (BMI 15–15·99 kg/m²), moderate (BMI King’s College London, London,
at risk. This disorder is characterised by an intense fear of 16–16·99 kg/m²), and mild (BMI ≥17 kg/m²). A systematic UK (Prof U Schmidt MD)

weight gain and a disturbed body image, which motivate
severe dietary restriction or other weight loss behaviours
such as purging or excessive physical activity.1–3
Additionally, cognitive and emotional functioning are
markedly disturbed in people with this disorder. Serious
medical morbidity and psychiatric comorbidity are the
norm.4,5 Anorexia nervosa in adults and older adolescents
commonly has a relapsing or protracted course,6 and
levels of disability and mortality are high,7,8 especially
without treatment. Even partial syndromes (ie, sub-
syndromal anorexia nervosa) are associated with adverse
health outcomes.9 Quality of life is poor and the burden
placed on individuals, families, and society is high.10
This Review, like the Lancet Seminar published in
2010,4 which included all eating disorders, focuses on
factors associated with anorexia nervosa that are of
particular relevance to clinicians, such as recent
developments in diagnosis, epidemiology, pathogenesis,
treatment, and prognosis.
Classification and diagnosis
Low bodyweight or low body-mass index (BMI) is the
central feature of anorexia nervosa. Tables 1 and 2 give an
overview of diagnostic criteria for anorexia nervosa
according to DSM2 and ICD11. Restricting and binge-purge
subtypes and remission and severity specifiers exist.
Amenorrhoea is no longer required in the new DSM-5
diagnostic criteria and is also expected to be dropped in
ICD-11.12 Main reasons for eliminating this criterion are
review from 201514 reported evidence for distinct illness Correspondence to:
Prof Stephan Zipfel, Centre of
trajectories and neurocognitive features for eating
Excellence for Eating Disorders
disorders characterised by severe restriction (eg, Tuebingen (KOMET) University of
inflexibility) or by overeating (eg, impulsivity and risk of Tübingen, Department of
substance use disorders) and evidence for effective Psychosomatic Medicine and
Psychotherapy, Tübingen,
secondary prevention or early treatment. Preliminary
72076 Tübingen, Germany
evidence also exists for a specific shift in focus of treatment stephan.zipfel@med.uni-
to quality of life as primary outcome in patients with long- tuebingen.de
standing or intractable anorexia nervosa.15
Epidemiology
In high-income countries, the lifetime prevalence of
anorexia nervosa in the general population is reported to
be around 1% in women and less than 0·5% in men.9
Accurate point prevalence has been more difficult to
calculate, with studies often failing to identify any cases
of DSM-IV-defined anorexia nervosa. If the broader
DSM-5 criteria A and C (low weight in the presence of
overvaluation of weight or shape) are applied, the point
prevalence is about 0·3–0·5%.16 Some studies,17 but not
all clinical incidence studies, support an increase in
anorexia nervosa in adolescents in the past two to three
decades.9 Anorexia nervosa typically begins in early-to-
mid-adolescence, although it can emerge at any age.18
The sex ratio in adults is 1:8, with more female individuals
afflicted.19 In children, the sex distribution is less
skewed.20 Outcomes differ across age groups, with higher
rates of full recovery and lower mortality in adolescents
than in adults (mean mortality 2% vs 5%).21

www.thelancet.com/psychiatry Published online October 27, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00356-9 1

 Review
DSM-IV
A A refusal to maintain bodyweight at or above A
a minimally normal weight for age and height
(eg, weight loss leading to a maintenance of
bodyweight less than 85% of that expected,
or failure to make expected weight gain
during period of growth, leading to
bodyweight less than 85% of that expected).
B Intense fear of gaining weight or becoming
fat, even though underweight.
C Disturbance in the way in which one’s
bodyweight or shape is experienced, undue
influence of bodyweight or shape on self-
evaluation, or denial of the seriousness of the
current low bodyweight.
D In postmenarcheal females, amenorrhoea—
ie, the absence of at least three or more
consecutive menstrual cycles. (A woman is
considered to have amenorrhoea if her
periods occur only following
hormone—eg, oestrogen administration).
DSM criteria were taken from the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental
disorders. DSM-IV-TR, Fourth Edition. Reprinted with permission from the Diagnostic and Statistical Manual of Mental
Disorders, Fifth Edition (Copyright ©2013). American Psychiatric Association. All Rights Reserved.
Table 1: Comparison of diagnostic criteria for anorexia nervosa according to DSM-IV versus DSM-5
ICD-1011
A Weight loss, or in children a lack of weight
gain, leading to a bodyweight of at least 15%
below the normal or expected weight for age
and height.
B The weight loss is self-induced by avoidance
of “fattening foods”.
C A self-perception of being too fat, with an
intrusive dread of fatness, which leads to a
self-imposed low weight threshold.
D A widespread endocrine disorder involving the D
hypothalamic-pituitary-gonadal axis,
manifest in the female as amenorrhoea, and
in the male as a loss of sexual interest and
potency (an apparent exception is the
persistence of vaginal bleeds in anorexic
women who are on replacement hormonal
therapy, most commonly taken as a
contraceptive pill).
E Does not meet criteria A and B of bulimia
nervosa (F50.2).
ICD criteria have been taken from the WHO International Statistical Classification of Diseases.11 *Proposed ICD-11
criteria have been taken from ICD-11 Beta Draft. BMI=body-mass index.
Table 2: Comparison of diagnostic criteria for anorexia nervosa according to ICD-10 versus ICD-11
(proposed criteria)
2 www.thelancet.com/psychiatry Published online October 27, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00356-9
DSM-52
Restriction of energy intake relative to
requirements, leading to a significantly low
bodyweight in the context of age, sex,
developmental trajectory, and physical health.
Significantly low weight is defined as a weight
that is less than minimally normal or, for
children and adolescents, less than that
minimally expected.
B Intense fear of gaining weight or of becoming
fat, or persistent behaviour that interferes
with weight gain, even though at a
significantly low weight.
C Disturbance in the way one’s bodyweight or
shape is experienced, undue influence of body
shape and weight on self-evaluation, or
persistent lack of recognition of the
seriousness of the current low bodyweight.
D ··
ICD-11 (proposed criteria)*
A Significantly low bodyweight for the
individual’s height, age, and developmental
stage (BMI less than 18·5 kg/m² in adults and
BMI-for-age under fifth percentile in children
and adolescents) that is not due to another
health condition or to the unavailability of
food.
B Low bodyweight is accompanied by a
persistent pattern of behaviours to prevent
restoration of normal weight, which may
include behaviours aimed at reducing energy
intake (restricted eating), purging behaviours
(eg, self-induced vomiting, misuse of
laxatives), and behaviours aimed at increasing
energy expenditure (eg, excessive exercise),
typically associated with a fear of weight gain.
C Low bodyweight or shape is central to the
person’s self-evaluation or is inaccurately
perceived to be normal or even excessive.
··
E ··
Psychiatric and physical comorbidity
Nearly three-quarters of patients with anorexia nervosa
report a lifetime mood disorder, most commonly major
depressive disorder.22 Between 25% and 75% of patients
with anorexia nervosa report a lifetime history of at
least one anxiety disorder,23 which typically precedes
anorexia nervosa and starts in childhood.24 Obsessive-
compulsive disorder occurs in 15–29% of individuals
with anorexia nervosa,25 with up to 79% experiencing
obsessions or compulsions at some point in their
lives.26 In population-based studies, the prevalence of
alcohol misuse or dependence in individuals with
anorexia nervosa is between 9% and 25% for anorexia
nervosa and typically lower in those with the restricting
subtype.27,28 Register-based studies29 confirmed
aggregation of autism spectrum disorder in probands
with anorexia nervosa and in their relatives; however,
the relation between anorexia nervosa and autism
spectrum disorder seems to be non-specific.29
Advances in studies of comorbidity are emerging from
the genetic literature with intriguing significant positive
genetic correlations emerging between anorexia nervosa
and schizophrenia (rg=0·19)30 and between anorexia
nervosa and obsessive-compulsive disorder (rg=0·55).31
These methods have taken us one step beyond reporting
the frequency with underlying mechanisms of co-
occurrence—in this case, by identifying shared genetic
factors.
Patients with anorexia nervosa display a broad variety
of somatic complications in several organ systems
(figure) across various stages of illness.32 In the acute
state, patients with anorexia nervosa present with many
common complaints such as dizziness, fatigue, or even a
syncope.33 In patients with a chronic course, almost every
organ system can be affected because of malnutrition or
the presence of binge-eating and purging behaviour.34
Although changes in multiple endocrine axes are mostly
adaptive (ie, to optimise energy expenditure),35 up to 21%
of patients with anorexia nervosa have osteoporosis and
more than 54% have osteopenia of the lumbar spine.36
Patients with anorexia nervosa have an increased life-
time prevalence of autoimmune disease, most
prominently type 1 diabetes.37 Type 1 diabetes often
precedes the onset of anorexia nervosa, is associated with
insulin purging, poor glycaemic control, diabetic
complications, and very high mortality.38 In children with
paediatric acute-onset neuropsychiatric syndrome (PANS)
or paediatric autoimmune neuropsychiatric disorder
associated with streptococcal infections (PANDAS), food
restriction also occurs and has been deemed to be a variant
of childhood onset anorexia nervosa.39
Prognosis
Regarding the core anorexia nervosa-psychopathology,
Steinhausen and colleagues21 analysed 119 studies covering
5590 patients with anorexia nervosa and reported that
59·6% of those patients showed a weight normalisation,
 Review

accompanied by a normalisation of menstrual status in Neurocognition and social cognition For the ICD-11 Beta Draft see
57·0%, and a normalisation of eating behaviour in 46·8% Neurocognitive markers of anorexia nervosa include set http://apps.who.int/
classifications/icd11/browse/l-m/
of the whole group of patients with anorexia nervosa. In shifting difficulties (ie, difficulties switching between en
general, patients with an illness onset before their different tasks or task demands)47 and poor central
17th birthday achieve a better outcome than adult onset, coherence (ie, a preference for local [detail-focused] over
whereas prepubertal onset confers a worse course.40 Long- global [bigger picture] processing).48 These impairments
term follow-up studies8,21 have confirmed two broad have also been noted in unaffected sisters of people with
outcome groups with either a good outcome or chronic anorexia nervosa and to some extent persist after
course with a high risk of premature death. Regarding the recovery.49 Evidence suggests that both illness stage or
time course, several follow-up studies have shown that at duration and severity affect performance.50 People with
least in adult patients with full syndrome anorexia nervosa, anorexia nervosa also have difficulties in socio-emotional
time to complete remission is between 5 and 6 years.6 processing, showing attentional biases, impaired
In a meta-analysis41 of excess mortality in the 1990s, emotion recognition, regulation, and expressivity, and
anorexia nervosa was associated with the highest rate of poor theory of mind.51 These difficulties are present both
mortality among all mental disorders.41 Another meta- in the ill state and in muted form after recovery.
analysis7 showed a crude mortality rate (number of deaths Prospective longitudinal studies of children with a high
within the study population over a specified period) of familial risk of eating disorders suggest that some neuro-
5·1 deaths per 1000 person-years and the standardised cognitive and social cognitive vulnerabilities are present
mortality rate of 5·9 with a mean follow-up period of from an early age.52
14·2 years. Although most deaths due to anorexia nervosa
are a direct consequence of starvation-related medical Structural neuroimaging
complications, particularly cardiac complications and Patients with acute anorexia nervosa have been reported
severe infections, one in five deaths in patients with this to have global reductions in grey and white matter,
disorder results from suicide.9 Data for the course and increased cerebrospinal fluid and regional grey matter
outcome in male patients with anorexia nervosa are scarce; decreases in the left hypothalamus, and in reward-
however, an older age and lower BMI at admission, and a related regions of the basal ganglia and the
purging subtype of anorexia nervosa led to an increased somatosensory cortex.53 Studies in patients who
risk of death in male individuals with anorexia nervosa.42 recovered from anorexia nervosa and longitudinal
studies (before and after treatment) suggest that brain
Pathogenesis tissue abnormalities might recover with weight
Genetic factors regain.54,55 Many earlier structural studies have
Anorexia nervosa is strongly familial43 and heritability methodological limitations (eg, not correcting for age or
estimates range from 28% to 74%.44 Two genome-wide
association studies (GWAS),45,46 currently understood to be Organ systems or organ Pathological findings Leading systems
underpowered in view of the presumed genetic CNS Morphological and functional Cognitive deficits
architecture of anorexia nervosa, predictably did not detect cerebral changes; volume
reduction in cerebral grey
genome-wide significant loci. Boraska and colleagues45 and white matter
conducted sign tests to compare results from the discovery Dental system and Impaired dental status, Dental caries,
sample with those from the replication sample, and 76% parotis glands dental caries, increased enlargement of the
serum amylase parotid glands
of the results from the replication sample were in the
Endocrine system and Hypothalamus-pituritary- Amenorrhoea in women,
same direction as the discovery sample, a result highly reproductive function gonadal-axis, low T3 symptoms of
unlikely to be due to chance (p=4 × 10–⁶). This observation syndrome, hypercortisol on,
hypothyroidism , depression,
elevated stress levels
strongly suggests that true findings exist and that an
Cardiovascular system Hypotension, bradycardia, Syncope
increase of the sample size will yield significant results; arrhythmia
the field is currently accruing larger samples. A study30 Gastrointestinal tract Impaired gastric emptying, Constipation, ileus, upper
reported a significant negative genetic correlation between gastric dilation, gastro- gastrointestinal bleeding
anorexia nervosa and BMI and a significant positive duodenal ulcers

genetic correlation between anorexia nervosa and Haematological and Bone marrow hypoplasia, Anaemia, (bacterial)
immune system anaemia with reduced infections, compromised
schizophrenia, encouraging a deeper exploration of leucocytes and immune competence
metabolic factors in anorexia nervosa and a new genetic immunoglobulin
association between anorexia nervosa and schizophrenia. Renal tract Hypokalaemia, Nephrolithiasis, oedema,
hypophosphataemia, syncope
hypernatraemia
Neurobiological factors Bone Reduced bone density Bone fractures and
Most neurobiological studies have been done in currently (osteopenia) concomitant pain,
ill or recovered patients, thus abnormalities might result or osteoporosis spinal compression

from state-related consequences of malnourishment or

so-called scarring. Figure: Impaired organ function in anorexia nervosa

www.thelancet.com/psychiatry Published online October 27, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00356-9 3

 Review
overall brain volume, not taking anorexia
nervosa-subtype or comorbidities into account; results
being confounded by effects of dehydration or
starvation). A series of studies by Frank and colleagues56,57
addressing these limitations reported increased grey
matter volume of the medial orbitofrontal cortex gyrus
in both adolescents and adults with anorexia nervosa,
which persisted into recovery. Similar changes were
found in bulimia nervosa, whereas obese adults showed
reduced orbitofrontal cortex gyrus rectus volume. The
orbitofrontal cortex assesses quality and value of reward
stimuli, such as food, and is implicated in regulating
sensory-specific satiety. Additionally, participants with
anorexia nervosa had increased right insula grey matter
compared with controls. The right anterior insula is
associated with self-recognition and interoceptive
awareness. Longitudinal studies in at-risk populations
are needed to fully assess whether these changes are
biomarkers of the illness.
Functional neuroimaging
Studies using visual food cue models have found
differences between anorexia nervosa and controls in
prefrontal areas and in limbic and paralimbic circuits,
associated with salience and reward processes with some
inconsistences between studies due to methodological
differences.58 Findings from studies56,57 using taste stimuli
to assess neural processing of food reward show that
people who recovered from anorexia nervosa have a
reduced functional brain response to predictably given,
but an increased response to unpredictably given, sugar
solutions with insula, striatum, or orbitofrontal cortex
response distinguishing anorexia nervosa from controls.
The same authors, contrasted people with anorexia
nervosa, bulimia nervosa, or obesity who underwent a
dopamine-related conditioning task (unexpected receipt
or omission of sweet taste) and found greater activation of
the ventral striatum, insula, and frontal cortex in patients
with anorexia nervosa than in healthy controls, but lower
activation in patients with bulimia nervosa and obesity,
suggesting that people with anorexia nervosa are highly
sensitive to uncertainty (unpredictable reward).
Neuroimaging studies of body-image disturbance in
anorexia nervosa suggest that this is a multidimensional
construct, with the posterior parietal network related to a
perceptive component and the prefrontal cortex-insula-
amygdala network related to an affective component of
body-image distortion in anorexia nervosa.59
In summary, these symptom provocation models have
largely suggested aberrant functioning of subcortical
regions promoting so-called bottom-up (stimulus-driven)
responses—ie, in parietal somatosensory regions, anxiety-
related mesolimbic circuits, and reward-related regions
(eg, striatum)—and in so-called top-down (evaluative)
prefrontal regions implicated in executive control.60 These
findings provide important pointers towards targets for
neurobiologically informed treatments.
4 www.thelancet.com/psychiatry Published online October 27, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00356-9
Neurobiological models of anorexia nervosa
Based on these neuroimaging findings, and integrating
additional evidence from studies on cerebrospinal fluid
(CSF) measures of metabolites, PET, and SPECT brain
imaging studies, Kaye and colleagues61,62 suggest that
some childhood temperamental and personality traits,
such as anxiety, obsessions, and perfectionism might
reflect neurobiological risk factors for the development
of anorexia nervosa. Restrictive eating thus might be a
means of reducing negative affect caused by imbalance
between serotoninergic (aversive or inhibitory) and
dopaminergic (reward) systems. Other neurobiologically
informed models of anorexia nervosa have highlighted
the role of stress, fear, and anxiety,63 the rewarding nature
of anorexia nervosa symptoms,64 and the subsequent
shift to compulsive or habitual behaviours65,66 as key
factors in the persistence of the illness.
Developmental factors
Several adverse experiences occurring around universal
stages and transitions of development are associated
with an increased prevalence of anorexia nervosa. These
developmental risk factors include adverse prenatal,
perinatal, and neonatal events, such as dysmaturity or
prematurity67,68 as well as feeding and sleeping difficulties
in infancy.68 Throughout childhood, emerging personality
traits associated with anxiety, depression, perfectionism,
and autism spectrum68 have been identified as risk
factors for anorexia nervosa. Puberty and adolescence are
characterised by profound changes, vulnerabilities, and
the transition to adulthood, and they represent the period
of first onset of anorexia nervosa. A possible explanation
for the crucial role of puberty for the onset of anorexia
nervosa might lie in hormonal changes and
dysregulations that interact with neurotransmitter
functioning, brain maturity, and genetic factors.69
Environmental factors
Female gender has consistently been shown to be a risk
factor for anorexia nervosa.68 The increase of anorexia
nervosa in low-income and middle-income countries
suggests that cultural transitions associated with
industrialisation, urbanisation, and globalisation might be
associated with environmental risk constellations for the
development of anorexia nervosa.9 These constellations
might include the adoption of the so-called western
lifestyle, including nutritional habits and thin ideal
internalisation. However, although body dissatisfaction
has been identified as a risk factor for the development of
any eating disorder,70 risk factors associated with thin ideal
internalisation and associated sociocultural pressures have
not been confirmed for anorexia nervosa. Appraising the
potential influence of environmental factors, it has to be
taken into account that the incidence of anorexia nervosa is
relatively low worldwide despite these pervasive
sociocultural pressures to be thin.71 It is possible that these
western influences could simply increase the number of

Essential
Medical and psychiatric history Full examination
Physical assessment BMI, heart rate, blood pressure, temperature
Blood profile Full blood count, blood sedimentation rate
Biochemical profile Sodium, potassium, calcium, magnesium,
phosphate, creatinine, urea, liver enzyme profile,
blood glucose
Cardiovascular assessment ECG
SCID I and II=structured clinical interview for DSM axis I and II disorders. EDE=eating disorder examination interview. BMI=body-mass index. DEXA=dual-energy X-ray
absorptiometry. ECG=electrocardiograph.
Table 3: Investigations recommended at initial assessment, on admission, or at regular intervals over the course of refeeding
individuals who engage in behaviours such as strict dieting
or excessive exercise, which can then trigger eating
disorders in genetically susceptible individuals.
Treatment
Initial assessment and investigations
Initial assessment of the patient with anorexia nervosa
includes an in-depth interview, a physical examination,
and investigations to establish severity and nature of
eating disorder symptoms and diagnosis, comorbid
psychological and physical symptoms, diagnoses and risk,
past treatments, current motivation for treatment, and
available supports. An early task is to build good rapport
with the patient, as they are often highly ambivalent about
and fearful of treatment.72 Whenever possible, it is
important to involve significant others (family, partners)
in assessment and subsequent treatment. Table 3
summarises recommended physical investigations to be
done at assessment. We have also formulated indicators of
high risk, requiring rapid intensive specialist consultation
and intervention (panel 1).
Pathways (levels) of care
A Finnish epidemiological study74 reported that about
50% of people with anorexia nervosa in the community
do not access treatment. Those who do engage in
treatment typically show varying degrees of ambivalence
about change.75 However, with treatment, at least 40% of
people with anorexia nervosa (and more in younger
samples) will make a full recovery.21 Additionally, access
to care from a specialist service with expertise in anorexia
nervosa might be associated with better outcomes.76
Thus it is important that health-care practitioners at
all levels are competent to identify anorexia nervosa and
that there is early access to secondary and tertiary levels
of care. This early access is particularly important in
view of evidence that there is a critical window for
effective intervention in the early stages of illness (ie,
www.thelancet.com/psychiatry Published online October 27, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00356-9
Review
Optional
Structured diagnostic interview (eg, SCID I and II, EDE)
In case of severe oedema: albumin, total protein, protein
electrophoresis
In patients with a long-term course: bone density (DEXA) scan
In case of seizures or differential diagnosis: EEG and neuroimaging (CT,
MRI)
In case of unclear thoracic pain or abdominal symptoms: chest
radiograph, abdominal ultrasound, gastroscopy
In severe anaemia: reticulocytes, iron, ferritin, transferring, vitamin B12
In case of elevated creatinine: creatinine clearance
In case of low BMI (<12kg/m²) and in the early phase of nutritional
rehabilitation: monitoring of sodium, potassium, phosphate (at least
weekly)
In case of cardiovascular abnormalities: Holter ECG, echocardiography
Panel 1: Indicators of high medical risk and other reasons
for considering inpatient treatment
Weight
• BMI <14 kg/m² or rapid weight loss (adults) or <75% of
expected bodyweight or rapid weight loss (adolescents)
Medical status
• Heart rate <50 bpm
• Cardiac arrhythmia
• Postural tachycardia (increase >20 bpm)
• Blood pressure <80/50 mm Hg
• Postural hypotension >20 mm Hg
• QTc >450 ms
• Temperature <35·5°C
• Hypokalaemia <3·0 mmol/L
• Neutropenia
• Phosphate <0·5 mmol/L
Additional indicators
• Severe bingeing and purging (eg, several times daily)
• Failure to respond to outpatient or daypatient treatment
• Severe psychiatric comorbidity
• Suicidality
These indicators are only a guide and do not replace the need for individual
clinical judgement (adapted from Hay and colleagues, 2014,73 and Treasure
and colleagues, 20104). QTc=corrected QT.
duration of <3 years) beyond which full recovery
becomes much more difficult to achieve.77 Despite this
critical window, there should not be therapeutic nihilism
in those who develop severe and enduring anorexia
nervosa and have a very high risk of disability or death.
Findings from a randomised trial of outpatient
psychotherapy15 supported the efficacy of modifying
psychological approaches in longstanding illness such
that the focus shifts from weight regain and recovery to
improved quality of life.
5
 Review
Evidence
Adolescent anorexia nervosa84
Family-based treatment (FBT) Strong*
Maudsley family therapy (MFT) Strong*
Family system therapy (FST) Moderate*
Adolescent focused therapy (AFT) Moderate*
Cognitive behavioural treatment (broad; CBT-b) Weak/moderate
Cognitive behavioural treatment (enhanced; CBT-E) Moderate*
Adult anorexia nervosa4,73,83
Cognitive behavioural therapy (CBT) Weak
Cognitive behavioural therapy (enhanced; CBT-E) Moderate*
Behavioural therapies (BT) Weak
Interpersonal psychotherapy (IPT) Weak
Psychodynamic therapy (PT) Weak
Cognitive analytic therapy (CAT) Weak
Focal psychodynamic psychotherapy Moderate*
Maudsley model of anorexia nervosa treatment for adults (MANTRA) Moderate*
Specialist supportive clinical management (SSCM) Moderate*
Evidence grades are weak, moderate, or strong. Effect grades are: – for no beneficial effect; -/+ for mixed result or still
inconsistent result; + for slight beneficial effect; +(+) for moderate beneficial effect; ++ for moderate and lasting
beneficial effect (further improvement shown in follow-up); and +++ for strong beneficial effect (superiority
demonstrated in primary outcome of randomised trial). Evidence levels are: 1 for well established, 2 for probably
efficious, and 4 for experimental. *At least one multicentre randomised trial or more than one randomised trial.
Table 4: Behavioural treatments in adolescent and adult patients with anorexia nervosa
Practice guidelines (eg, from the American Psychiatric
Association,2 the German College for Psychosomatic
Medicine,78 the National Institute for Health and Care
Excellence,79 and the Royal Australian & New Zealand
College of Psychiatrist73) agree that most people with
anorexia nervosa can be treated as outpatients but that
day-patient and inpatient services are needed for those
with more severe illness and those who do not improve
with outpatient care. Brief inpatient care followed by
intensive outpatient care could achieve similar efficacy to
that of longer hospital stays in adolescents,80 but there is
a paucity of randomised trials to guide service use.
In a multicentre randomised trial, Herpertz-Dahlmann
and colleagues81 reported that a stepped care approach
(day-patient treatment after short inpatient care) was
equally effective and less costly than inpatient treatment
in patients with non-chronic adolescent anorexia nervosa
at the end of treatment and at 1 year follow-up.
Evidence-based psychological treatment in adolescent
and adult patients
Based on comprehensive systematic reviews4,82,83 and
complemented by well designed and sufficiently powered
treatment studies, we have reported on the first-line
behavioural treatments for adolescent and adult patients
with anorexia nervosa separately (table 4) and have
supplemented this by interventions for relapse
prevention and aftercare as well as specific interventions
for carers. Additionally, we have added information
(panel 2) on the setting, structure, and content of
6 www.thelancet.com/psychiatry Published online October 27, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00356-9
psychotherapeutic interventions applied in randomised
Effect
(evidence level) trials since 2010.
First, the overall evidence base for the treatment of
adolescent patients with anorexia nervosa is increasing.
+++ (1)
However, the number of empirically supported
+++ (1)
psychosocial treatments trials opposed to the number of
++ (2)
treatments for adolescent anorexia nervosa remains
++ (2)
scarce. In total, 12 randomised trials (n=1060 patients)
–/+ (4)
have compared different psychological treatments in
+ (4)
adolescent patients with the disorder (age <19 years).
Lock84 concluded in a systematic review on psychological
+ treatments in children and adolescents that there is clear
++ and growing evidence to support the efficacy of family
–/+ treatment in adolescent anorexia nervosa compared with
+ individually based approaches, and that there is evidence
+ that supports family-based treatment (FBT) with a focus
+ on eating disorder behaviour and weight gain as opposed
++ to more general family processes.
++ Second, over the past 30 years, 12 randomised trials
+ (+) (n=1157 patients) comparing different psychological
treatments in adult patients with anorexia nervosa (age
>18 years) have been done in outpatient settings. Since the
2010 review,4 several well designed and sufficiently
powered treatment studies for adult patients with anorexia
nervosa have been published, reporting substantial weight
gain and clear improvements of eating disorder and
general psychopathology at the end of treatment and at
follow-up.15,85–90 The largest of these trials (n=242) compared
three different first-line treatments: focal psychodynamic
psychotherapy (FPT), enhanced cognitive behaviour
therapy (CBT-E), and an optimised treatment as usual,
including psychotherapy as well as medical care by the
family doctor.87 Weight gain was similar in all three groups.
Considering a combined outcome (weight and eating
disorder psychopathology), FPT proved advantageous in
terms of recovery at 12-month follow-up, whereas CBT-E
was more effective with respect to speed of weight gain
and improvements in eating disorder psychopathology
than the other treatments. Results from one trial (n=56)91
showed that by the end of treatment, an intervention that
combined supportive therapy with sound clinical
management delivered by eating disorder specialists
(specialist supportive clinical management, SSCM) was
superior to two specific psychotherapies (cognitive
behavioural therapy [CBT] and interpersonal psychotherapy
[IPT]). However, a long-term follow-up of this trial did not
support the superiority of any treatment.92 Findings from
another randomised trial15 (n=63) showed that patients
with anorexia nervosa with severe and enduring course
can make meaningful improvements with both CBT or
SSCM.15 A novel anorexia nervosa-specific outpatient
therapy (Maudsley model of anorexia nervosa therapy for
adults, MANTRA) has been compared against SSCM in
two trials (n=214).85,86 Although overall outcome did not
differ between groups, patients preferred MANTRA to
SSCM, and patients with a more severe illness had a
greater weight gain in the MANTRA group than in the

Panel 2: Novel and effective psychological treatments in anorexia nervosa
Family-based treatment (FBT)
Family-based treatment is a three-phase treatment for adolescent
patients with anorexia nervosa and their families over 16 1-h
sessions and a 9-month period (initially of 10 h during 6 months).
In the first phase, therapy is characterised by attempts to absolve
the parents from the responsibility of causing the disorder and by
complimenting them on the positive aspects of their parenting.
Families were encouraged to work out for themselves how best to
help restore the weight of their child with anorexia nervosa. In
phase 2, parents were helped to transition eating and weight
control back to the adolescent in an age-appropriate manner. The
third phase focused on establishing a healthy relationship between
the adolescent and the parents. 24 1-h sessions were provided over
the 1-year period (Lock and colleagues, 2010 and Agras and
colleagues 2014; appendix).
Specialist supportive clinical management (SSCM)
This treatment should be delivered by therapists specialised in the
treatment of eating disorders and should provide a standardised
form of usual outpatient treatment. Patients with anorexia
nervosa and a BMI of 15 kg/m² or lower receive up to
30 once-weekly individual therapy sessions and four monthly
follow-up sessions. In those patients with a BMI >15kg/m² the
number of sessions could be reduced to 20. It combines clinical
management (ie, giving information, advice, and encouragement)
with a supportive therapeutic style designed to build a positive
therapeutic relationship and to foster change. Therapy content
includes assessment, identification, and regular review of target
symptoms; psychoeducation; monitoring of physical status;
establishment of a goal weight range; and nutritional education
and advice. The aim is to help patients make a link between their
clinical symptoms and their abnormal eating behaviour and
weight, and to support patients in a gradual return to normal
eating behaviour and weight. Additional therapy content is
determined by the patient (McIntosh and colleagues 2006,
appendix).
Maudsley model of anorexia treatment for adults (MANTRA)
This treatment is an empirically based cognitive-interpersonal
treatment, which proposes that four broad factors, linked to
underlying obsessional and anxious (or avoidant) personality traits,
are central to the maintenance of anorexia nervosa. These are (1) a
thinking style characterised by inflexibility, excessive attention to
detail, and fear of making mistakes; (2) impairments in the
socio-emotional domain (eg, avoidance of emotional experience,
regulation, and expression); (3) positive beliefs about how
anorexia nervosa helps the person in their life; and (4) unhelpful
responses of close others (eg, overinvolvement, criticism,
accommodation to symptoms). These factors are targeted in
treatment with the aim of improving weight, eating disorder and
other symptoms, and psychosocial adjustment. The treatment
style is motivational. Treatment is centred around a patient-
manual. This manual has core (eg, formulation) and optional
modules (eg, module on building a so-called non-anorexic
identity). Treatment has a clear structure and hierarchy of
www.thelancet.com/psychiatry Published online October 27, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00356-9
Review
therapeutic procedures. Individual tailoring of treatment arises
from flexibility on how modules are combined and how much
emphasis they are given. Nutrition and other symptom
management or behaviour change, information or advice is given
if the patient is motivationally ready for this. Differences from
other treatments include that the model was developed specifically
for anorexia nervosa, it is based on biological and psychological
research, and is tailored to characteristic temperamental traits in
this disorder. It is unique in its use of a patient workbook,
developed in co-production with patients and therapists. It is also
unique in its involvement of carers in both the model or
formulation and the treatment. Separate carer materials based on
the model are available (Schmidt and colleagues, 2015, appendix).
Enhanced cognitive behaviour therapy (CBT-E)
According to Fairburn and colleagues CBT-E is the abbreviation for For more on CBT-E see http://
“enhanced cognitive therapy”, and it refers to a “transdiagnostic” www.credo-oxford.com
personalised psychological treatment for eating disorders. It was
developed as an outpatient treatment for adults but is an intensive
version for day patient and inpatient settings, and a version for
younger people. As an outpatient therapy treatment CBT-E has
four stages and is available in a short (20 sessions) and longer
version (40 sessions). In stage one, the focus is on gaining a mutual
understanding of the person’s eating problem and helping him or
her modify and stabilise their pattern of eating. In the brief second
stage progress is systematically reviewed and plans are made for
the main body of treatment. Stage three focused on the processes
that are maintaining the person’s eating problem (eg, addressing
concerns about shape and eating). In the last stage the emphasis
shifts onto the future. There is a focus on dealing with setbacks and
maintaining the changes that have been obtained (Fairburn, 2008;
appendix).
Focal psychodynamic psychotherapy (FPT)
The initial manualised treatment was designed as a 40 h
outpatient psychodynamic-oriented psychotherapy for
moderately ill patients with anorexia nervosa (BMI >15 kg/m²).
At the beginning of focal psychodynamic therapy, the therapist
identifies psychodynamic relevant foci using a standardised
operationalised, psychodynamic diagnostic interview (OPD-II).
The psychodynamic treatment manual can be divided roughly into
three treatment phases. The first phase focuses mainly on
therapeutic alliance, pro-anorectic behaviour and ego-syntonic
beliefs (attitudes and behaviour viewed as acceptable), and
self-esteem. In the second phase of treatment, main focus is placed
on relevant relationships and the association between
interpersonal relationships and eating (anorectic) behaviour. The
pertinent aspects of the final phase are the transfer to everyday life,
anticipation of treatment termination, and parting. Before every
treatment session the patient’s weight is assessed and
documented (Friederich and colleagues, 2014).
This panel describes effective psychological treatments applied in randomised trials (table 4,
including those treatment approaches shown the highest evidence and effectiveness for
adolescents and adults and published as randomised trials since the 2010 review by Treasure
and colleagues 20104). For references see appendix.
7
 Review
SSCM group. In summary, although the evidence base for
the treatment of adults with anorexia nervosa is advancing,
thus far no specific approach has shown clear superiority.
Across different individual psychotherapies for adults with
anorexia nervosa there are common elements. These
elements include a psychotherapeutic approach specific to
and focused on anorexia nervosa in combination with a
focus on weight regain and nutritional rehabilitation.73
Third, few studies have focused on relapse prevention
and aftercare in anorexia nervosa, and the little available
evidence suggests that patients who have a structured
intervention for relapse prevention—based on cognitive-
behavioural principles—after inpatient treatment have
fewer and later episodes of relapse in anorexia nervosa
during the first year after inpatient discharge than do
patients without a follow-up intervention.93–95
Finally, in view of the burden of anorexia nervosa on
families and partners, and evidence suggesting that carers’
distress and behaviours might inadvertently maintain the
illness, several randomised trials have also trialled
interventions targeting carers of adults with anorexia
nervosa. A new couple-based intervention for anorexia
nervosa (Uniting Couples in the Treatment of Anorexia
Nervosa)96 also focuses on leveraging the support of close
others in the treatment of anorexia nervosa. These studies
show that carer outcomes (distress and unhelpful
behaviours) can be improved and that this improvement in
turn might positively affect relationships with the patient
and patients’ clinical outcomes.97,98
Pharmacological treatments
Systematic reviews consistently conclude that
antidepressants neither improve weight gain99 nor reduce
eating disorder or other psychological symptoms in the
re-feeding phase.99 The utility of antidepressants for
relapse prevention in the post-weight restoration phase
remains uncertain.99 This mixed evidence is based on
two trials, one smaller positive trial and a second larger
trial that tested the efficacy of adding fluoxetine to CBT
on post-weight restoration and found no added benefit in
preventing relapse at 1 year (for references on single
See Online for appendix trials see appendix). A pooled meta-analysis of
four placebo-controlled randomised trials on
antidepressants (two on a tricyclic and two of fluoxetine)
and a relapse prevention trial also failed to find a
significant effect on weight gain.100 As a consequence,
treatment guidelines73 are cautious in recommending
use even for comorbid features such as depression until
it is established that these features are not due to the
starvation state and remit with weight restoration.
The review on eating disorders by Treasure and
colleagues4 reported emerging evidence for the use of
olanzapine, an atypical antipsychotic in reducing illness
preoccupations and anxiety during refeeding. The
inconsistent results and inability to achieve significance
in pooled meta-analyses of placebo controlled trials for
weight gain100–102 have led to a consensus in the medical
8 www.thelancet.com/psychiatry Published online October 27, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00356-9
literature that more, larger, and consistently positive
trials of antipsychotics are needed before their use can be
recommended.99,100
There has been little advance in evidence for any other
psychotropic medication in anorexia nervosa treatment
since the review by Treasure and colleagues.4 Other drugs
that are currently under investigation for a putative role
in anorexia nervosa treatment are tumour necrosis factor,
dronabinol (a cannabinoid receptor agonist), and ghrelin
agonists103 to promote appetite or antagonists to reduce
hyperactivity (for references on single trials see appendix).
These drugs do not have an evidence base for their use at
this stage.
Nutritional treatments
In moderately ill outpatients with anorexia nervosa,
nutritional counselling alone is not an adequate
treatment;94 however, dieticians are an important part of a
multidisciplinary treatment team. Patients who are
substantially underweight and malnourished should be
admitted to a specialist inpatient or day-patient eating
disorder unit for a combined programme of supervised
refeeding and anorexia nervosa-related psychotherapy.
First, it is important to accurately assess nutritional and
fluid intake and to document premorbid weight and the
course of weight loss. Depending on the duration of
weight loss and malnutrition, age of the patient, somatic
comorbidity, and the severity of purging behaviour,
recommended weight gain rates range from 500 g to
1400 g per week.73,79 Evidence exists that substantial
weight gain is best achieved in inpatient settings,104
particularly in patients with increased somatic risk.
Refeeding syndrome is a serious and potentially fatal
medical complication, particularly during the early stages
of refeeding in those patients at the highest risk, who
have been malnourished and emaciated for a long
time.27,79 Due to a switch from fasting gluconeogenesis to
carbohydrate-induced insulin release, there is a rapid
intracellular uptake of potassium, phosphate, and
magnesium with the consequence of a rapid onset of
hypophosphataemia, hypomagnesia, and hypo-
kalaemia.105 In accordance with the RANZP protocol
(2014),73 adult patients with anorexia nervosa should start
with a refeeding of 6000 kJ/day, increased by 2000 kJ/day
every 3 days, until an adequate intake to meet the
person’s needs for weight restoration is reached. As a
consequence, particularly in the early phase of refeeding,
electrolytes should be regularly monitored and this diet
should be supplemented by phosphate at 500 mg twice
daily and thiamine at least 100 mg daily for the first week,
and thereafter as clinically indicated for people at high
risk of refeeding syndrome (eg, those with BMI <13).
Nutritional therapy includes supervised meals and, if
necessary, additional high-protein oral liquid
supplements. In severely emaciated patients at high
medical risk, nasogastric feeding, including professional
and supportive supervision, could be indicated. On very

rare occasions and after failure of the above nutritional
strategies, parenteral nutrition might be indicated. In
adolescent patients with a short duration of illness, a
more rapid refeeding protocol can be applied. In
principle, the least intrusive and most physiological
normal method of nutrition should be applied.73
Osteoporosis prevention and treatment
The most efficient strategy to improve bone density is to
restore weight and, in women, menstrual function.
Oestrogen-replacement therapy, primarily via transdermal
application, only partially increases bone density in
adolescents.35 Oral oestrogen-progesterone combinations
are ineffective in increasing bone mineral density in
adolescent and adult anorexia nervosa patients.106 Moreover,
neuroendocrine changes can have a direct effect on
neurocognition and mood as well as on core eating
disorder psychopathology.35
Experimental treatments
There is widespread agreement that new interventions
are needed to improve outcomes, especially in adults
with anorexia nervosa. Such interventions should target
specific disease mechanisms.107,108 We describe some of
the more promising experimental treatments.
Psychobiological treatments
Cognitive remediation therapy (CRT) for anorexia
nervosa targets neuropsychological inefficiencies in
executive functioning, chiefly poor set-shifting and weak
central coherence (extreme attention to detail at the
expense of the bigger picture). Two systematic reviews109,110
identified four small to medium sized
(n=32–82 participants) randomised trials of CRT (for
references on single trials see appendix). These studies
varied in populations, intensity of CRT (8–30 sessions),
comparison treatments (CBT, treatment as usual,
exposure treatment, non-specific neurocognitive
training), and primary outcomes (eating disorder
symptoms, test meal consumption, set-shifting,
treatment dropout). Therefore no meta-analysis was
possible. Two studies found differential short-term
improvements in neurocognition for CRT versus
comparison treatment. One trial of CRT plus treatment
as usual versus treatment as usual alone in inpatients
with either anorexia nervosa or bulimia nervosa found
greater improvement in quality of life at end of treatment
and greater improvement on eating disorders symptoms
at 6 months follow-up in the group containing CRT than
in the TAU alone group. These findings are promising
but well designed large-scale studies of CRT are as yet
not available.
Abnormalities in fear conditioning have been thought
to be causally implicated in anorexia nervosa. In line
with this thought, exposure therapy (to food or body
stimuli) might be another promising treatment for
anorexia nervosa. One systematic review111 identified one
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Review
placebo-controlled randomised trial (n=14) of food
exposure and D-cycloserine (DCS) in anorexia nervosa,
based on evidence that DCS enhances fear extinction
during exposure therapy in anxiety disorders (for
references on single trials see appendix). DCS compared
with placebo had no effect in any of the training or test
meals. One further randomised trial (n=32) compared
food exposure with CRT in weight-restored anorexia
nervosa and found greater test-meal consumption at end
of treatment in the exposure treatment group.
Other promising psychobiological treatments include
cognitive bias modification treatments,112 based on
converging evidence suggesting a range of cognitive
biases (attention, memory) in relation to illness-relevant
and emotional stimuli in anorexia nervosa. However,
randomised trials are so far not available.
Neurobiological treatments
Improved understanding of the neurocircuitry involved
in anorexia nervosa113 has given rise to the use of
neuromodulation treatments, such as deep brain
stimulation (DBS), repetitive transcranial current stimu-
lation (rTMS), and transcranial direct current stimulation
(tDCS), especially in severe and enduring anorexia
nervosa. We identified two systematic reviews114,115
summarising cases studies and three further case studies
describing use of these techniques (for references on
single trials see appendix). As yet, no randomised trials
of therapeutic use of neuromodulation treatments have
been published. Several cases studies or series of DBS
(nucleus accumbens, ventral capsule or ventral striatum,
or subcallosal cingulate cortex) targeting anorexia
nervosa symptomatology directly (n=12) or targeting
obsessive-compulsive disorder or depression with
parallel improvements in anorexia nervosa symptoms
(n=2) have been identified. These studies suggest that
DBS might have promise in highly selected severe and
enduring cases. Likewise, rTMS (DLPFC) or tDCS
(anodal, DLPFC) case studies (n=13) have shown promise
in enduring anorexia nervosa.
Evidence-based prevention programmes
Prevention efforts can be divided into universal, selective,
and indicated, depending on whether they address the
general population or populations with increased risk
(eg, children of eating disordered mothers; elite athletes)
or those exhibiting early signs of a disorder. Eating
disorder prevention has focused on either risk factors
(eg, body dissatisfaction) or eating disorder pathology or
caseness. A systematic review116 of eating disorders
prevention programmes for young people between the
ages of 12 and 25 years identified six reviews and
46 universal prevention trials, with psychoeducation the
most commonly tested intervention (26 trials).116 The
review also identified six reviews and 40 trials in at-risk
populations, where psychoeducation and cognitive
dissonance programmes were equally common (12 each).
9
 Review
Panel 3: Key unmet challenges in the management of anorexia nervosa
Adolescents with anorexia nervosa
• Which factors are essential to identify patients at risk and how could we address this
target group with adequate and effective prevention programmes?
• What are the predictors, moderators, and mediators of outcome in the treatment of
adolescent patients with anorexia nervosa?
• What to do when family-based treatment is unsuccessful or inappropriate
(eg, if there is substantial intrafamilial abuse)?
Adults with anorexia nervosa
• How can we improve treatment outcomes–ie, what works and for whom and in what
setting?
• What is the best first-line outpatient treatment?
• What treatments should be used as second-line treatments?
• How important is it to involve family members and partners in treatment?
• How can we prevent relapse after inpatient or day-patient treatment?
Across the age range
• What brain circuits are involved in the onset and maintenance of anorexia nervosa?
• Which structures are implicated for which subtypes of anorexia nervosa?
• Are there imaging markers to identify treatment responders and non-responders?
• In view of the typical age of onset of anorexia nervosa, does it make sense to have
separate adolescent and adult eating disorder services or should there be seamless
services across the ages?
• How should treatment and treatment goals be adjusted for different stages of illness?
• What is an adequate course of treatment for anorexia nervosa?
• How should treatment resistance and palliative care be defined?
• How can we help the subgroup of patients with severe hyperactivity?
Treatment of comorbidities (psychiatric or physical)
• How can we reduce mortality and suicide in individuals with anorexia nervosa?
• How can we help the subgroup of patients with severe psychiatric comorbidities?
• What is the treatment for patients suffering from comorbid post-traumatic stress
disorder, personality disorder, developmental disorders (eg, autism spectrum
disorder), and alcohol or substance misuse?
• How can we help the subgroup of patients with a severe somatic comorbid disorder?
• What is the treatment for patients with comorbidities such as diabetes mellitus or
inflammatory bowel disease?
• What is the optimum management of osteopenia and osteoporosis in anorexia
nervosa?
• What is the treatment for patients with a comorbidity such as food-related allergy?
Search strategy and selection criteria
We searched PubMed for articles published between Jan 1, 2010, and Dec 31, 2014,
covering the time period since the review by Treasure and colleagues,4 published in
The Lancet. We combined the search term “anorexia nervosa” each with “chronicity”,
“comorbidity”, ”epidemiology“, “prognosis”, or “mortality”, “risk factor” or “maintaining
factor”, “treatment” or “psychotherapy” or “pharmacological”, “prevention”. We narrowed
the search to titles and abstracts. We used no language restriction. From the identified
4612 publications, due to space considerations, we mainly cited selected landmark
studies, review articles, and meta-analyses. We additionally selected earlier landmark
studies we judged as relevant.
10 www.thelancet.com/psychiatry Published online October 27, 2015 http://dx.doi.org/10.1016/S2215-0366(15)00356-9
Meta-analyses of controlled trials from other reviews
were summarised as indicating that “prevention
programmes generally produce large effects on outcomes
related to eating disorder knowledge, and only small net
effects for other important prevention targets such as
reducing exhibited risk factors, changing attitudes, and
reducing eating pathology”.116 The review also found that
larger effect sizes are usually seen for studies of at-risk
populations and interactive programmes using multi-
session formats.
Other systematic reviews117 have specifically examined
school-based interventions,118 e-health interventions, and
the role of parental involvement119 in eating disorders and
body dissatisfaction prevention programmes for children
and adolescents, suggesting that these settings and ways of
delivery are fruitful avenues to explore in future studies.
Conclusions
The past 5 years have seen substantial advances in the
knowledge of anorexia nervosa. Recent treatment studies
suggest that patients with anorexia nervosa have a
realistic chance of recovery, especially if treated early, or
at least, to achieve substantial improvement. However,
there is widespread agreement that several challenges
remain in the management of anorexia nervosa (panel 3)
and new interventions are needed to improve outcomes,
especially in adults with the disorder. Such interventions
should target specific disease mechanisms. The neuro-
psychological constructs introduced within the research
domain criteria (RDoC) matrix offer a new systematic
basis for determining the neural substrates underlying
the biological predisposition to anorexia nervosa.120 A
clearer understanding of how anorexia nervosa behaviour
is encoded in neural circuits would provide a key for
developing more effective treatments. To conclude, we
still need to discover how to provide better, faster, and
lasting improvements in the management of this
enigmatic disorder.
Contributors
All authors contributed to the search and selection of the medical
literature and to the writing of the Review.
Declaration of interests
CB is a grant recipient from Shire Pharmaceuticals and an author for
Pearson and Walker. PH receives royalties or honoraria for works on
eating disorders from BMJ Publishing House, Hogrefe & Huber, and
McGraw Hill.
Acknowledgments
We thank the anonymous reviewers for their comments on early drafts
of this Review.
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