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Copyright © 2014 Neuroscience Education Institute. All rights reserved.
Diagnosis and Treatment Of
Eating Disorders
Handout for the Neuroscience Education Institute (NEI) online activity:
Copyright © 2014 Neuroscience Education Institute. All rights reserved.
Learning Objectives
• Describe changes to categories and criteria for
eating disorders in DSM-5
• Implement evidence-based treatment in the
management of patients with eating disorders
Copyright © 2014 Neuroscience Education Institute. All rights reserved.
Pretest Question 1
Which of the following is the most
prevalent eating disorder?
1. Anorexia nervosa
2. Binge eating disorder
3. Bulimia nervosa
Copyright © 2014 Neuroscience Education Institute. All rights reserved.
Pretest Question 2
Which of the following is the only
medication that has FDA approval for the
treatment of bulimia nervosa?
1. Citalopram
2. Fluoxetine
3. Lisdexamfetamine
4. Sertraline
Copyright © 2014 Neuroscience Education Institute. All rights reserved.
Eating Disorders
• Complex systemic diseases
• Comorbid with many psychiatric and somatic
disorders
• Tendency for chronicity
• Significant medical and psychiatric
consequences
• High socioeconomic impact
Copyright © 2014 Neuroscience Education Institute. All rights reserved.
Eating Disorders: Lifetime Prevalence
0
1
2
3
4
5
6
7
8
9
10
Anorexia nervosa Bulimia nervosa Binge eating disorder
Hudson JI et al. Biol Psychiatry 2007;61(3):348-58.
Pre
vale
nce (
%)
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Why Are Diagnostic Criteria Important?
They define
• What is normal and what is not
• What requires treatment
• Who pays for treatment
• Who may be eligible for disability benefits
• Who can be awarded damages in case of
litigation
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Changes From DSM-IV-TR to DSM-5
• Chapter called "Feeding and Eating Disorders"
• Major change: official recognition of binge
eating disorder
• "Feeding disorder of infancy and early
childhood" renamed "avoidant/restrictive food
disorder"
Copyright © 2014 Neuroscience Education Institute. All rights reserved.
DSM-IV-TR to DSM-5
Fairburn CG et al. Behav Res Ther 2007;45(8):1705-15;
Le Grange D et al. Eur Eating Disord Rev 2013;21(1):1-7.
Eating disorder NOS
Anorexia nervosa
Bulimia nervosa
Binge eating disorder
Goal of Revisions
Currently 60% of Dx in some centers
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DSM-IV-TR to DSM-5
• Criteria for anorexia nervosa broadened
• Reduced the frequency of diagnostic criteria
for bulimia nervosa
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DSM-5 Diagnostic Categories
• Anorexia nervosa (AN)
• Bulimia nervosa (BN)
• Binge eating disorder (BED)
• Avoidant/restrictive food intake disorder
• Other specified feeding or eating disorders
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Anorexia Nervosa
• Characterized by self-induced starvation and
excessive weight loss
• Third most common illness in adolescents
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Anorexia Nervosa
• Restriction of energy intake relative to
requirements
• Intense fear of gaining weight or becoming
overweight, even though underweight
• Disturbance in how one's body weight or shape
is experienced
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Anorexia Nervosa
• Core diagnostic criteria unchanged
• Exception: requirement for amenorrhea
eliminated
• Criterion A wording for low body weight
changed
• Criterion B expanded to include persistent
behavior that interferes with weight gain
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Anorexia Nervosa
• Removed: "refusal to maintain body weight at
or above a minimally normal weight for age
and height"
• Misperception: people with AN choose to keep
their weight in a certain range
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Anorexia Nervosa
• Remains: "intense fear of gaining weight or
becoming fat"
• Added: "persistent behaviors that prevent
weight gain, even though at a significantly low
weight"
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Anorexia Nervosa
• Division of anorexia into 2 subtypes, restricting
and binge eating/purging, remains
• Distinction between anorexia nervosa and
bulimia nervosa
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Bulimia Nervosa
• Reduction in minimum required average
frequency of both binge eating and
inappropriate compensatory behavior from
twice to once weekly
• Scheme distinguishing purging and non-
purging types eliminated
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Former EDNOS
• "Other specified feeding or eating disorders"
• Purging disorder
• Night eating syndrome
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Addition of Binge Eating Disorder
• Has been around for decades
• Formally recognized in 1994
• Part of eating disorder NOS in DSM-IV-TR
• Often underdiagnosed and undertreated
• Impact on quality of life
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BED
• Lifetime prevalence is 1.9–3%
• More prevalent than AN or BN
• Fewer than 40% of affected individuals receive
treatment
• If untreated, poses significant public health
challenge
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BED
• Recurrent binge eating episodes
• Occur during discrete periods of time
• Consumption of more food than is typical for
most people
• Associated with feelings of impaired control
over eating
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BED
• Episodes must occur at least once a week for a
minimum of 3 months
• Feeling of loss of control during eating
episodes
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BED
• Diagnostic crossover between BED, BN, and
AN occurs in a small percentage of individuals
• Distinguishing characteristic of patients with
BED: lack of recurrent inappropriate
compensatory behavior
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Comorbidities Associated With BED
• Hypertension, diabetes mellitus type 2,
dyslipidemia
• Disturbed sleep
• Obesity
• Obesity NOT a defining characteristic of
patients with BED
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BED and Psychiatric Comorbidities
0
10
20
30
40
50
60
70
80
90
100
Anxiety disorder Mood disorder Impulse-control disorder
Substance use
Hudson JI et al. Biol Psychiatry 2007;61(3):348-58.
Life
tim
e c
om
orb
idit
y (%
)
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Risk Factors Associated With BED
• Strong genetic component
• Childhood obesity
• Parent with a mood disorder or substance use
disorder
• Exposure to traumatic life events or life
stressors
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Obesity
Not included in DSM-5
as a mental disorder
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Neurotransmitters and Food Intake
• Dopamine (DA), serotonin (5HT), and
noradrenaline in hypothalamic and striatal
regions regulate food intake
– Affect hunger and satiety
– Mediate reward and motivation of feeding
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Dysregulation of Brain Reward Systems
• Alterations in dopamine, acetylcholine (ACh),
and opioid systems in reward-related areas
observed in patients with eating disorders
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Neurotransmitters and AN
• Reduced dopaminergic, serotonergic, and
noradrenergic neurotransmission in
hypothalamic and striatal regions
• Changes in dopamine D2 receptors and
5HT2C/2A receptors; compensatory changes
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AN and Animal Models
• Restricted access to food enhances the
reinforcing effects of DA when animal eats
• Alterations in mesolimbic DA and 5HT occur as
a result of restricted eating
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Neurotransmitters and BN and BED
• Monoaminergic neurotransmission is
downregulated in hypothalamic and striatal
regions
• Overactive alpha-2 adrenoreceptors may
contribute to an attenuated response to food
• More support for the treatment of BN and BED
with monoaminergic drugs
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Animal Models for BE
• Bingeing on palatable foods releases DA
• Purging attenuates the release of ACh that
might signal satiety
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Neurobiology of Binge Eating
• Alterations within endogenous opioid system
• Disparities in dopamine receptor and
dopamine receptor transportation gene
expression
• Alterations within dopaminergic reward
pathway
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Treatment of Eating Disorders
• Multidimensional
• Psychotherapy
• Nutritional rehabilitation
• Medication treatment
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AN Treatment
• Effect of all antidepressants has generally
been disappointing
• Meta-analysis of 8 studies of antipsychotics for
the treatment of anorexia nervosa failed to
demonstrate efficacy for body weight and
related outcomes in females
Kishi T et al. J Clin Psychiatry 2012;73(6):e757-66..
Copyright © 2014 Neuroscience Education Institute. All rights reserved.
Role of Oxytocin in AN
• Animal data suggest that oxytocin is a satiety
hormone
• Higher oxytocin levels were associated with
the severity of disordered eating
psychopathology in AN
• Treatment implications?
Copyright © 2014 Neuroscience Education Institute. All rights reserved.
BN Treatment
Walsh BT. J Clin Psychiatry 1991;52(suppl):34-8.
SSRI SNRI
Reduce the frequency of bingeing and purging
in both depressed and non-depressed persons with bulimia
MAOI
NRI
M1 NRI
SRI
H1
1 NA+
TCA
SRI
SRI
NOT RECOMMENDED
Copyright © 2014 Neuroscience Education Institute. All rights reserved. Copyright © 2014 Neuroscience Education Institute. All rights reserved.
Fluoxetine
in the Treatment of BN
• One and only treatment for any eating disorder
authorized by regulatory authorities
• 8-week, double-blind trial comparing 20 and 60
mg/day with placebo in 387 women
• Fluoxetine 60 mg/day superior to placebo
• Insomnia, nausea, asthenia, and tremor more
common with fluoxetine
Arch Gen Psychiatry 49(2):139-47.
Copyright © 2014 Neuroscience Education Institute. All rights reserved. Copyright © 2014 Neuroscience Education Institute. All rights reserved.
BN Treatment
Topiramate
• Multiple behavioral dimensions improved
• Binge and purge behavior reduced
• Improvement in self-esteem, eating attitude,
anxiety, and self-image
• Side effects limit usefulness
Copyright © 2014 Neuroscience Education Institute. All rights reserved. Copyright © 2014 Neuroscience Education Institute. All rights reserved.
BN Treatment
Topiramate
• First double-blind study: 2003
• 64 patients: 31 topiramate, 33 placebo
• Dose
• Primary efficacy measure: Eating Disorder
Inventory (EDI)
• Significantly greater improvement in topiramate
group
Hedges DW et al. J Clin Psychiatry 2003;64(12):1449-54.
Copyright © 2014 Neuroscience Education Institute. All rights reserved.
BED Treatment
GOAL
• Reduce binge eating behavior
• Reduce risk of medical and psychiatric
comorbidities
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Treatment Reduced binge
eating behavior
Reduced associated
pathology
Weight loss
SSRIs, high dose ++ ++ Not clinically significant
TCAs +/- +/-
Duloxetine + + +
Orlistat +/- +
Topiramate ++ ++
Zonisamide + +
Naltrexone, high dose + +
Lisdexamfetamine +++ +++
Opioid antagonists +/-
CBT ++ ++
Interpersonal therapy ++ ++
Dialectical behavior
therapy ++ ++
Self-help ++ ++
Behavioral weight loss + + ++
Bariatric surgery ++ ++ ++
McElroy SL. Ther Clin Risk Manage 2012;8:219-41.
Copyright © 2014 Neuroscience Education Institute. All rights reserved. Copyright © 2014 Neuroscience Education Institute. All rights reserved.
Topiramate
• First study: McElroy et al. 1983
• Wide spectrum of actions
• Antibinge eating and antipurging actions
• Promotes weight loss
BED Treatment
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BED Treatment
Topiramate
• 16 weeks, multicenter, randomized controlled
trial with 407 patients
• Marked reduction in the frequency of binge
eating episodes with significant weight loss
• Final average dose: 300 mg/day
McElroy SL et al. Biol Psychiatry 2007;61(9):1039-48.
Copyright © 2014 Neuroscience Education Institute. All rights reserved. Copyright © 2014 Neuroscience Education Institute. All rights reserved.
BED Treatment
Zonisamide
• Significantly greater reduction in binge
eating episode frequency, body weight,
and scores on several rating scales
• Efficacious but not well tolerated
• Mean daily dose: 436 mg
McElroy SL et al. J Clin Psychiatry 2006;67(12):1897-906.
Copyright © 2014 Neuroscience Education Institute. All rights reserved. Copyright © 2014 Neuroscience Education Institute. All rights reserved.
BED Treatment
Atomoxetine
• Significantly greater reduction in binge
eating episode frequency, body weight,
and scores on rating scales than placebo
• Efficacious and fairly well tolerated
• Mean daily dose: 106 mg
McElroy SL et al. J Clin Psychiatry 2007;68(3):390-8.
Copyright © 2014 Neuroscience Education Institute. All rights reserved. Copyright © 2014 Neuroscience Education Institute. All rights reserved.
BED Treatment
Sibutramine
• Serotonin and norepinephrine reuptake
inhibitor
• 12-week study: reduces the frequency of
binge eating, promotes and maintains
weight loss
• Dose: 10 mg/day
• Withdrawn from market due to safety
issues Milano W et al. Adv Ther 2005;22(1):25-31.
Copyright © 2014 Neuroscience Education Institute. All rights reserved. Copyright © 2014 Neuroscience Education Institute. All rights reserved.
BED Treatment
Psychostimulants
• Methylphenidate produced greater
decrease in appetite in 1 case-controlled
study (Davis et al. 2007)
• Lisdexamfetamine dimesylate (LDX):
significantly greater reduction in binge
eating days per week (McElroy at al. 2012)
Davis C et al. Neuropsychopharmacol 2007;32(10):2199-206;
McElroy SL. Ther Clin Risk Manage 2012;8:219-41.
DAT
NET
VMAT
lysine DAT
NET
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BED Treatment
• LDX: phase 2, multi-center, randomized,
double-blind, placebo-controlled study
• 11-week
• Forced titration
• LDX 30-, 50-, and 70-mg/day groups and
placebo
• LDX 50- and 70-mg groups statistically
superior to placebo on primary endpoint
McElroy SL. Ther Clin Risk Manage 2012;8:219-41.
DAT
NET
VMAT
lysine DAT
NET
VMAT
lysine
Copyright © 2014 Neuroscience Education Institute. All rights reserved. Copyright © 2014 Neuroscience Education Institute. All rights reserved.
BED Treatment
Memantine
• Open-label trial
• Significantly reduced frequency of binge
eating days and episodes
Brennan BP et al. Int J Eating Disord 2008;41(6):520-6.
Copyright © 2014 Neuroscience Education Institute. All rights reserved.
Eating Disorders and Peptide Hormones:
New Treatment Targets
• Ghrelin agonists
• Neuropeptide Y1 and -5 antagonists
• Orexin receptor antagonists
• CRF receptor 2 antagonists
• Histamine 3 antagonists
Copyright © 2014 Neuroscience Education Institute. All rights reserved.
Summary
• Biggest news: addition of binge eating disorder
as independent category in DSM-5
• At the moment, there are no effective
treatments that address all the clinical features
of eating disorders
• Lack of dose standardization in RCT
Copyright © 2014 Neuroscience Education Institute. All rights reserved.
Summary
ONLY FLUOXETINE
is approved by regulatory authorities
for the treatment of BN
Copyright © 2014 Neuroscience Education Institute. All rights reserved.
Summary
• Significant progress made in recent decades
• More extensive RCT needed
• Focus on potential new targets
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