Hany Bissada, MD, FRCPCOttawa, ONPsychiatrist
Renuca Modi, MD, CCFPEdmonton, AB
Family Physician
Lionel Noronha, MD, CCFP, FCFPStirling, ON
Family Physician
Barry Simon, MD, FRCPToronto, ONPsychiatrist
Program Faculty
2
Speaker Disclosures
Relationships with commercial interests:
3
Program Objectives
After participating in this program, participants will be better able to:
– Describe the diagnostic criteria for binge eating disorder (BED)
– Identify patients who should be screened for BED
– Recognize the impact of BED on patient health and quality of life
– Apply appropriate therapeutic interventions to reduce the frequency of binge eating in patients with BED
What is BED?
5
BED is NOT:• Associated with the compensatory behaviour seen in BN and AN• Seen in the context of BN or AN• Associated with intense preoccupation with body weight or image
BED = binge eating disorder; DSM-5 = Diagnostic and Statistical Manual of Mental Disorders, Fifth EditionAmerican Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed.Arlington, VA: American Psychiatric Association; 2013.
BED is a Diagnostic Entity Distinct from Other Eating Disorders in the DSM-5
Anorexianervosa
(AN)
Underweight;food restrictions; distorted
body image (may binge and purge)
Bulimianervosa
(BN)
Binging and purging
BED
Binging only
6
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed.Arlington, VA: American Psychiatric Association; 2013.
DSM-5 Diagnostic Criteria
7
ARecurrent episodes of binge eating, including:– Eating more food than what most people would eat– Lack of control over the episode
Episodes are associated with ≥3 of the following:– Eating more rapidly than normal– Eating until feeling uncomfortably full– Eating large amounts of food when not feeling hungry– Eating alone due to embarrassment – Feeling disgusted with oneself, depressed or guilty afterward
B
Marked distress with regard to binge eatingC
Episodes occur, on average, at least once per week for 3 monthsD
No association with recurrent use of inappropriate compensatory behaviours as in bulimia nervosa; does not occur exclusively during the course of bulimia nervosa or anorexia nervosa
E
The DSM criteria do not specify a specific amount of food One study suggests that during binge-eating episodes,
individuals consume ~1500–2500 kcal This is equivalent to:
American Psychiatric Association. Diagnostic and Statistical Manual of MentalDisorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.Raymond NC et al. Int J Eat Disord 2007; 40(1):67-71.
How Much Food Constitutes a “Binge”?
1 L of ice cream
5–10 bowls of cereal
with milk
2 large bags of chips
8
1 large pizza
5–10 hamburgers
The minimum level of severity is based on the number of binge-eating episodes per week, and may be increased to reflect other symptoms and the degree of functional disability.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed.Arlington, VA: American Psychiatric Association; 2013.
Severity of BED (based on DSM-5)
MILD BED
Moderate BED5
10
15
20
1–3
4–7
BED severity categorization
Bin
ge-
eati
ng
ep
iso
des
/w
eek
Severe BED
8–13
Extreme BED
14 or more
9
Lifetime prevalence estimates based on survey of 9282 individuals; p 0.05 for sex differences for all three eating disorders.<Hudson JI et al. Biol Psychiatry 2007; 61(3):348-58; published correction appears in Biol Psychiatry 2012; 72(2):164.
BED is the Most Common Eating Disorder in Adults
BED: 2.8% of the general population
Anorexianervosa
Bulimia nervosa
Anorexianervosa
Bulimia nervosa
0.3%0.5%1.5%
0.9% 3.5%
2.0%
10
*p value not available; data (based on Version 3.0 of the World Health Organization Composite International Diagnostic Interview and DSM-IV criteria) from an eating disorder–assessed subsample (n = 2980) of the National Comorbidity Survey Replication, a nationally representative face-to-face household survey of English-speaking adults aged ≥18 years.Hudson JI et al. Biol Psychiatry 2007; 61(3):348-58; published correction appears in Biol Psychiatry 2012; 72(2):164.
The Onset of BED Occurs at a Later Mean Age Compared with BN and AN*
Mean age of onset, years
BED
Bulimianervosa
Anorexianervosa
0 3010 20
25.4
19.718.9
11
• Negative attitudes toward eating, weight and shape during childhood and adolescence
• Lack of support
• Abuse/trauma• Life events• Daily stresses
• Social pressure about body image
• Childhood obesity• Low social support• Use of food as comfort and reward in childhood • Reward mechanisms
related to “wanting” food (mediated by mesolimbic dopamine activation) and/or “liking” food (via activation of opioid or cannabinoid receptors) may be defective in patients with BED
• Psychiatric comorbidities are also prevalent in patients with BED
Genetic factors are responsible for 40–60% of liability for binge eating
BED
Genetics
Femalegender
Neuro-chemistryStress
Family environment
Socio-cultural factors
Allen KL et al. Int J Eat Disord 2014; 47(7):802-12; Bulik CM et al. Int J Eat Disord 2003; 33(3):293-98; Cortese S et al. Nutr Rev 2007; 65(9):404-11; Fairburn C et al. Arch Gen Psychiatry 1998; 55(5):425-32; Hodges EL et al. Int J Eat Disord 1998; 23(2):145-5; Sullivan PF et al. Br J Psychiatry 1998; 173:75-9; Trace SE et al. Annu Rev Clin Psychol 2013; 9:589-620.
Several Risk Factors Contribute to BED
Environment Biology/physiology
12
BED is a psychiatric disordercharacterized by not only how an individual feels about their eating behaviours but also by the behaviours themselves
BingeEating Overeating≠
13
What does BED look like in practice?
14
• Childhood obesity
• Familial eating problems
• Family history of BED
• Parent with mood or substance use disorder
• History of family discord
• Female gender• Obesity• Weight gain• Metabolic syndrome components
Kornstein SG et al. Prim Care Companion CNS Disord 2016; 18(3):10.4088/PCC.15r01905.
Case-Finding Indicators for BED in Primary Care Practice
15
History/family
Physical
Psychological/Psychiatric
Case Presentation: Nicole
WeightConcerns
Case Presentation: Eric
MetabolicComorbidities
• Psychiatric disorders• Suicidal ideation• Role impairment• Sleep problems• Trauma/stressors
Case Presentation: Sara
History of Trauma
and
Psychiatric Comorbidities
Case Presentation: Rachel
PsychiatricComorbidity
– Concerned about weight gain– Wants to ask about “diet drugs”
and anti-obesity treatments
Reason for visit:
History:
– Has always been overweight, but gained 10% of body weight in the past year, going from a BMI of 28 kg/m2 to 31 kg/m2
– History of sporadic dieting– Comorbid PCOS
16
NICOLE
34-year-old high school
history teacher
BMI = body mass index; PCOS = polycystic ovary syndrome
Case Presentation
1
25
32
42
3
47
34
16
0
10
20
30
40
50
<18.5(underweight)
18.5–24.9 (normal)
25–29.9 (overweight)
30+(obese)
Per
cen
tag
e
BMI, kg/m2
p <0.05 for all weight categories, except for 25–29.9 (overweight)Kessler RC et al. Biol Psychiatry 2013; 73(9):904-14.
BED is Associated with a High BMI
But, be aware that BED occurs
in patients with normal
and overweight BMI as well…
Patients with BED (n = 722)
Individuals with no eating disorder (n = 22,949)
17
*Figures based on meta-analysis of 25 studies1. Borges MB et al. Obes Res 2002; 10(11):1127-34; 2. Dawes AJ et al. JAMA 2016; 315(2):150-63; 3. Spitzer RL et al. Int J Eat Disord 1992; 11(3):191-203.
BED is Very Common in the Weight-Loss Setting
of 1984 patients
attending hospital-affiliated
weight-loss programs had BED3
of 217 patients enrolled in a
Weight Watchers®
program had BED1
of 13,769 bariatric
surgery candidates met criteria for BED*2
30%17%16%
18
*After controlling for demographic/anthropometric variables; based on data collected from survey completed by 1827 individuals NS = non-significant Goldschmidt AB et al. J Adolesc Health 2012; 51(1):86-92.
History of Dieting Predicts Onset of BED
3.3
11.6
1.5
5.8
0
2
4
6
8
10
12
14
16
18
20
Males Females
Per
cen
tag
ew
ith
BE
D
p =NS*
p =0.005*
AT 5-YEAR FOLLOW UP
11.7
15.3
4.35.7
0
2
4
6
8
10
12
14
16
18
20
Males Females
Per
cen
tag
ew
ith
BE
D
p =0.008*
p =0.001*
AT 10-YEAR FOLLOW UP
Dieters at baseline
Non-dieters at baseline
Dieters at 5-year time point
Non-dieters at 5-year time point
19
3
8 810
6
11
16
26
6
0
5
10
15
20
25
30
Lost Lost Lost Lost Maintained Gained Gained Gained Gained
p values not availableBased on data from 68 consecutive obese patients with BED fromprimary care centresBarnes RD et al. Compr Psychiatry 2011; 52(3):312-8.
Most Individuals with BED Gained Weight in the Year Before Starting Treatment
Change in weight (in lbs) during year prior to initiating treatment
Per
cen
t o
f su
bje
cts
40+ 20–39 10–19 5–9 5–9 10–19 20–39 40+
Return to case menu 20
Reason for visit:– Return visit to discuss blood
pressure (BP), which is borderline high
History:– Currently not on any medications– No personal or family history of CVD– Has been overweight since he was
a teenager
21
ERIC
40-year-old accountant
Case Presentation
Physical exam:– BMI: 33 kg/m2
– BP: 142/92 mmHg– WC: 106 cm
Blood tests:– A1C: 6.2%– TC: 6.5 mmol/L – HDL-C: 0.9 mmol/L– LDL-C: 4.7 mmol/L– TG: 2.1 mmol/L
22
ERIC
40-year-old accountant
Case Presentation
*The metabolic comorbidities associated with BED are due to its association with increased BMI, rather than to BED itself, with the exception of fasting glucose, which is higher in patients with BED even after adjustment for BMI**Dyslipidemia, hypertension or type 2 diabetesHudson JI et al. Am J Clin Nutr 2010; 91(6):1568-73; Kessler RC et al. Biol Psychiatry 2013; 73(9):904-14.
BED is Associated with and Often Aggravates Several Physiological Comorbidities*
High rates of metabolic issues:(based on a survey of 9282 individuals, 1.2% of whom had BED in the last year)
23
Obesity/overweight (42%) Metabolic syndrome (any
component**) (40%) Hypertension (24%) Type 2 diabetes (10%)
Chronic pain ismore common:(based on community surveys of 24,124 individuals, 1.4% of whom had BED)
Patients with BED 1.5–1.8x more likely to experience chronic pain from non-BED controls
33.9
54.5
30.9
4.18.0
3.5
0
10
20
30
40
50
60
Total Men Women
Life
tim
e p
reva
len
ce o
f ty
pe
2 d
iab
etes
(%
)
p <0.001 for all comparisonsRaevuori A et al. Int J Eat Dis 2015; 48(6):555-62.
Increased Risk of Type 2 Diabetesin Patients with BED
Patients with BED (n = 171)
Controls (n = 656)
8.0
24Return to case menu
Reason for visit:– Requesting treatment for anxiety– She says the stress of exams and
moving away from home are making it difficult for her to sleep
History:– History of depression as a teenager– Only current medication is
oral contraception– Weight has increased from 140 lbs
to 157 lbs (and BMI from 26 kg/m2
to 29 kg/m2) since her last visit six months ago
25
RACHEL
22-year-old student
Case Presentation
DAILY STRESS INVENTORY MOOD RATINGS
17.6
62.5
8.8
19
0
10
20
30
40
50
60
70
Total number ofstressful events
How stressfulevents were*
LSM
*Measured on a scale of 1 to 7p <0.01 for all comparisons; data derived from self-monitoring of daily stress, mood and eating behaviour over three weeks; women in the binge group reported binging at least twice per week, reported three of five binge-eating behaviour criteria and had moderate to extreme distress related to their eatingLSM = least squares meanWolff GE et al. Addict Behav 2000; 25(2):205-16.
Binge-Eating Women Experience Higher Stress and Lower Mood than Non–binge-eating Peers
6.4 6.1 6.2 6.3
4.2 4.2
7.6
3.5
0
1
2
3
4
5
6
7
8
Depression Anger Positiveaffect
Guilt/self-blame
LSM
Results of study suggest stress and negative
mood are likely antecedents to
binge eating
Binge group (n = 20) Control group (n = 20)
26
32
65
12.5
19.8
85
1.84.4
0
10
20
30
40
50
60
70
Depression Anxiety Bipolar disorders ADHD
Per
cen
tag
e
ADHD = attention deficit hyperactivity disorderp values not available; prevalence of comorbidities in patients with BED based on a survey of 9282 individuals, 1.2% of whom had BED in the last year; ADHD prevalence in the general population derived from a probability subsample (n = 3199) of 18–44-year-old respondents in the United States National Comorbidity Survey Replication; prevalence of other comorbidities in the general population based on Canadian Mental Health Association statistics from the Canadian Mental Health Association. Fast Facts About Mental Illness. Available at: http://www.cmha.ca/media/fast-facts-about-mental-illness/#.VR6NWPnF-aI. Accessed: April 3, 2015; Hudson JI et al. Biol Psychiatry2007; 61(3):348-58; published correction appears in Biol Psychiatry 2012; 72(2):164; Kessler RC et al. Am J Psychiatry 2006; 163(4):716-23.
BED is Associated with Higher Rates of Psychiatric Comorbidities vs. theGeneral Population
Patients with BED
General population
27Return to case menu
Reason for visit:– Follow-up visit to address her
depression and PTSD
History:– Had a difficult childhood, with parents
who suffered from addiction problems– Experienced sexual abuse as
a young adolescent– Has been overweight since she was
a teenager (current BMI of 29 kg/m2)
28
SARA
49-year-old store manager
Case Presentation
35.3
49.0
27.5
14.712.2
20.1
14.0
3.7
0
10
20
30
40
50
60
Sexual abuse Physical abuse Bullying bypeers
Discrimination
Per
cen
tag
e
The BED group consisted of black and white women recruited from the community with a mean age of 30 years who met the DSM-IV criteria for current BED; control group was recruited from the same communities and matched for ethnicity, age and level of education. Striegel-Moore RH et al. Am J Psychiatry 2002; 159(11):1902-7.
BED is Associated with Higher Rates of Abusive Experiences in Women
p =0.0001
p =0.0001
p =0.007
p =0.001
Women with BED(n = 102)
Healthy comparisonwomen (n = 164)
29
*Based on a study with 162 women who met DSM-IV criteria for BED, studied vs. psychiatric comparison group with with no history of clinically significant eating disorder symptoms who had a diagnosis of a DSM-IV Axis I psychiatric disorder.
Striegel-Moore RH et al. Psychol Med 2005; 35(6):907-17.
Family Relationships and Risk of BED
Childhoodobesity and familial eating problems are reliable specific risk factors for
BED
30Return to case menu
Patients with BEDreported higher exposure to:
Severe childhood obesity Family overeating Family discord High parental demands
– Obesity/overweight (42%)
– Metabolic syndrome (any component) (40%)
– Hypertension (24%)
– Type 2 diabetes (10%)
– Chronic pain
– Chronic headaches
Physiological
‒ Anxiety disorders (65.1%)
‒ Depressive disorders (32.3%)
‒ Post-traumatic stress disorder (PTSD) (26.3%)
‒ Substance abuse (23.3%)
‒ Attention-deficit/hyperactivity disorder (ADHD) (19.8%)
‒ Bipolar disorders (12.5%)
Psychiatric
BED is a Psychiatric Disorder Associated with Several Comorbid Conditions
1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.; 2. Kessler RC, et al. The prevalence and correlates of binge eating disorder in the World Health Organization World Mental Health Surveys. Biol Psychiatry. 2013;73(9):904-914.; 3. Brewerton TD, Rance SJ, Dansky BS, et al. A comparison of women with child-adolescent versus adult onset binge eating: results from the National Women's Study. Int J Eat Disord. 2014;47(7):836-843; 4.Fernandez-Aranda F, Aguera Z, Castro R, et al. ADHD symptomatology in eating disorders: a secondary psychopathological measure of severity? BMC Psychiatry. 2013;13:166; 5. Hudson JI, Lalonde JK, Coit CE, et al. Longitudinal study of the diagnosis of components of the metabolic syndrome in individuals with binge-eating disorder. Am J Clin Nutr. 2010;91(6):1568-1573.
79% of patients with BED meet criteria for other psychiatric disorders
Overweight/obese patients, particularly those with ≥1 other risk factor for BED, e.g.:
– Components of the metabolic syndrome or diabetes mellitus (especially if recalcitrant to treatment)
– Psychiatric disorders
– History of dieting
– Exposure to traumatic life events or stressors
Who Should be Screened for BED?
32
Why does BED matter?
33
MDD = major depressive disorder Citrome L. Int J Clin Pract 2016; 70(7):516-7; Citrome L. J Clin Psychiatry 2017; 78(Suppl 1):9-13.
Patients with BED Frequently Suffer from Comorbid Psychiatric Disorders
However, unlike many psychiatric disorders, patients with BED are generally relieved to be diagnosed
and respond well to treatment
Risk of suicide is elevated in BED patients, even when taking into
account comorbid MDD
of patients with BED meet the criteria for another
psychiatric disorder
80%
34
BED May be a Barrier to the Management of Chronic Disease
IDENTIFYINGBED
may shed light on the reasons certain patients are having difficulty managing comorbid conditions
TREATINGBED
may also help bring metabolic conditions under
control
35
In an online survey of 22,397 US adults, 344 met DSM-5 diagnostic criteria in the past 12 months (level of severity not specified).
*Data from a 2013 online survey of US adults aged ≥18 yearsCossrow N et al. Clin Psychiatry 2016;77(8):e968–74.
Reported Diagnosis of BED in US Adults
Of those, only 3.2% (11/344) reported ever receiving a diagnosis of BED by a healthcare provider*
36
Why is it Important to Identify and Treat BED?
UNTREATEDBED
has a significant impact on patients’ physical and
mental well-being
PROPER MANAGEMENT OF
BEDmay simultaneously address physiological
and/or psychiatric comorbidities
37
The Primary Care Physician’s Perspective
The Physician’s Journey to the Diagnosis and Treatment of BED
38
The Psychiatrist’s Perspective
The Physician’s Journey to the Diagnosis and Treatment of BED
39
What can be done to manage BED?
40
Identify patients at risk Screen early Open a non-judgmental dialogue about eating behaviour
and the patient’s feelings about their eating patterns by: – Creating a safe and comfortable environment
– Ask open-ended questions at the beginning and then proceed with specific, non-judgmental questions to open a dialogue
Best Practices for Successful Screening
41
Useful Screening ToolsThe BED Screener-7 (BEDS-7)
42
White MA et al. J Consult Clin Psychol 2011; 79(1):75-83.
A Non-judgmental Dialogue with Simple Questions Can Help Identify Patients with BED
✔
Good opening question
If answer is
BED is unlikely
NO
If answer is
BED is likely
YES
Do you have any concernsabout your
eating?
Are there timeswhen you feel
disgusted aboutyour eatingbehaviour?
Do you ever eat
in secret becauseyou are ashamed
of how muchyou areeating?
Do you sometimes
eat when you arenot hungry?
43
Adapted from Amianto F et al. BMC Psychiatry 2015; 15:70.
Treatment Goals in BED Are Simple and Quantifiable
Primary goal:
‒ Abstinence from binge eating (full remission for 28 days) or
‒ Decreased binge eating (fewer binges/week, decreased frequency of binge days, decreased size of binges)
44
Secondary goal:
‒ Sustainable weight loss (once the binge eating is stable –premature or rapid shifting to weight loss may activate the restrict-binge cycle)
CBT = cognitive behavioural therapy; DBT = dialectical behaviour therapy; IPT = interpersonal therapyCarter WP et al. Int J Eat Disord 2003; 34(Suppl):S74-88; Hofmann SG et al. Psychiatr Clin North Am 2010; 33(3):701-10; Goracci A et al. J Addict Med 2015; 9(1):1-19; Ozier AD et al. J Am Diet Assoc 2011; 111(8):1236-41; Wonderlich SA et al. Int J Eat Disord 2003; 34(Suppl):S58-73; Sim LA et al. Mayo Clin Proc 2010; 85(8):746-51.
Treatment Involves Several ApproachesDietary‒ Nutritional counselling‒ Normalized food intake
and eating behaviour
Psychological‒ Individual/group therapy‒ CBT‒ IPT‒ DBT‒ Mindfulness-based
therapy
Pharmacological‒ Antidepressants‒ Anticonvulsants‒ Substance abuse
treatment agents‒ Centrally acting
sympathomimetics
Note: Lisdexamfetamine is the only drug approved for the treatment of BED in Canada
45
Goracci A et al. J Addict Med 2015; 9(1):1-19; Heatherton TF et al. Psychol Bull 1991; 110(1):86-108; Iacovino JM et al. Curr Psychiatry Rep 2012; 14(4):432-46; Ozier AD et al. J Am Diet Assoc 2011; 111(8):1236-41.
Treating BED from a Nutritional Perspective
Explain triggers
46
Evaluate food
habits
Provide nutritional counselling
Work as part of a multidisciplinary
team
BES = Binge Eating ScaleCompare A et al. Appetite 2013; 71:361-8.
Nutritional Counselling Should be Used in Conjunction with Other Treatment Modalities
33.6
32.3 32.3
32.3
30.3 30.5
28
29
30
31
32
33
34
Baseline End of therapy Six-month follow up
Mea
n
2
CHANGE IN BINGE EATING AND BMI IN 63 PATIENTS WITH BED TREATED WITH DIETARY COUNSELLING
FOR FIVE MONTHS
p =NS p =NS
p <0.001 p =0.035
BES (score)
BMI (kg/m2)
While dietary counselling helped
patients lose weight,no participants
achieved a BES score below
the threshold for BED
47
Adjunct therapies, such as exercise, virtual reality therapy and a mindfulness eating program (meditation), may bolster treatment responses.
Abstinence is defined as absence of binge-eating behaviour.Hilbert A et al. Br J Psychiatry 2012; 200(3):232-7; Iacovino JM et al. Curr Psychiatry Rep 2012; 14(4):432-46; Wonderlich SA et al. Int J Eat Disord 2003; 34(Suppl):S58-73.
Several Psychotherapies are Effective for the Treatment of BED
BED psychotherapies
Long-term abstinence rate (>1 year) is 76.7%
IPT
• Long-term abstinence rate (>1 year) is 52%
• Mindfulness CBT: abstinence rate post-treatment is 40%
CBT
Guided self-help abstinence rate is 50% at six months
Self-help
Abstinence rate is 56% at six months
DBT
48
Events, n/N
Study, Year (reference) RR (95%) CI) Treatment Placebo
Dingemans et al, 2007 (45)* 3.48 (1.38–8.81) 19/30 4/22
Peterson et al, 1998 (47)* 7.56 (1.13–50.45) 11/16 1/11
Peterson et al, 2009 (48)* 5.09 (2.42–10.71) 31/60 7/69
Tasca et al, 2006 (44)* 6.17 (2.37–16.06) 29/47 4/40
Overall* 4.95 (3.06–8.00) 90/153 16/142
*p <0.05CI = confidence interval; RR = relative riskBrownley KA et al. Ann Intern Med 2016; 165(6):409-20.
Effect of Therapist-led CBT on Abstinence from Binge Eating
Meta-analysis suggests CBT increases abstinence from binge eating by about 5x vs. placebo
0.01 0.1 1 10 100
Favours placebo Favours treatment
49
Based on an RCT of 139 patients with BED assigned to an internet-based CBT intervention or waitlist condition.RCT = randomized controlled trialWagner B et al. Behav Ther 2016; 47:500-14.
Online Interventions May be Effective and More Accessible than Traditional CBT
PERCENTAGE OF PATIENTS WITH BED IN REMISSION AND RECOVERY FOLLOWING AN ONLINE CBT PROGRAM OR BEING PLACED
ON A WAITLIST60
50
40
30
20
10
0
Per
cen
t o
f p
atie
nts
Post-treatment recovery Post-treatment remission
p <0.001
Treatment Group
Wait-List Group
50
p <0.001
Available Resources
NRI = norepinephrine reuptake inhibitor; SDRI = serotonin-dopamine reuptake inhibitor; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor Goracci A et al. J Addict Med 2015; 9(1):1-19.
Several Pharmacotherapies Have Been Investigated in Clinical Trials
Some of these treatments may be useful for managing associated comorbidities, such as mood disorders or
substance abuse. Refer to approved labeling.
All pharmacotherapies, except for lisdexamfetamine, are off-label.
52
Antidepressants
SSRIsSNRIsNRIs
SDRIs
Anticonvulsants
TopiramateCarbamazepine
PhenytoinValproate
Substance abuse treatment agents
NaltrexoneAcamprosateSamidorphan
Psychostimulants and centrally acting
sympathomimetics
AtomoxetineLisdexamfetamineMethylphenidate
Events, n/N
Study, Year (antidepressant) RR (95%) CI) Treatment Placebo
Arnold et al, 2002 (fluoxetine)* 2.60 (1.06–6.39) 13/30 5/30
Guerdjikova et al, 2008 (escitalopram) 1.83 (0.80–4.15) 10/21 6/23
Guerdjikova et al, 2008 (duloxetine) 1.67 (0.75–3.71) 10/20 6/20
Grilo et al, 2005 (fluoxetine) 0.86 (0.33–2.22) 6/27 7/27
Hudson et al, 1998 (fluvoxamine) 1.40 (0.73–2.68) 15/42 11/43
McElroy et al, 2000 (sertraline) 3.11 (0.75–12.87) 7/18 2/16
McElroy et al, 2003 (citalopram) 2.25 (0.84–6.06) 9/19 4/19
White and Grilo, 2013 (bupropion) 1.57 (0.76–3.24) 13/31 8/30
Overall* 1.67 (1.24–2.26) 83/208 49/208
*p <0.05Note: Second-generation antidepressants are not approved by Health Canada for treatment of BEDBrownley KA et al. Ann Intern Med 2016; 165(6):409-20.
Effect of Second-Generation Antidepressants on Abstinence from Binge Eating
Meta-analysis suggests antidepressants increase abstinence from binge eating by
1.7x vs. placebo
0.01 0.1 1 10 100
Favours placebo Favours treatment
53
Indications: – Anxiety (duloxetine)– Bulimia nervosa (fluoxetine)– Depression (all)– OCD (escitalopram, fluoxetine, fluvoxamine)– Pain (duloxetine)– Panic disorder (sertraline)– Smoking cessation (bupropion)
Second-generation antidepressants are not approved by Health Canada for treatment of BED
Dose and dosage adjustment:– Depends on individual drug
MAO = monoamine oxidase; OCD = obsessive-compulsive disorderHealth Canada. Drug Product Database. Available at: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/databasdon/index-eng.php. Accessed: November 16, 2016; Kennedy SH et al. Can J Psych 2016; 61(9):540-60.
Second-Generation Antidepressants: Indication, Dosage and Use
54
Note: Second-generation antidepressants are not approved by Health Canada for treatment of BEDHealth Canada. Drug Product Database. Available at: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/databasdon/index-eng.php. Accessed: November 16, 2016; Kennedy SH et al. Can J Psych 2016; 61(9):540-60.
Second-Generation Antidepressants: Indication, Dosage and Use (cont’d)
Most common adverse effects in BED study:– Depends on individual drugs, but generally common side effects include: Dry mouth Insomnia Nausea Somnolence
Drug-drug interactions:– Depends on individual drugs, but co-administration of any second-
generation antidepressant with an MAO inhibitor can provoke serotonin syndrome and/or hypertensive crisis
Precautions:– Depends on individual drug
Return 55
AE = adverse effectNote: Anticonvulsants are not approved by Health Canada for treatment of BEDMcElroy SL et al. CNS Drugs 2009; 23(2):139-56.
Role of Anticonvulsants in the Treatment of BED
Topiramate Demonstrated efficacy in ≥3 RCTs However, dropout rates may be high due to AEs,
including cognitive impairment
Carbamazepine Not studied
Phenytoin Not studied
Valproate Reported to worsen binge eating in patients with BED and comorbid bipolar disorder
56
SE = standard errorNote: Topiramate is not approved by Health Canada for treatment of BEDMcElroy SL et al. Biol Psychiatry 2007; 61(9):1039-48.
Topiramate Significantly Reduced Mean Number of Binge Episodes/Week
0
2.5
5
7.5
0 2 4 6 8 10 12 14 16
Week
Ave
rag
e b
ing
e ep
iso
des
/w
eek
(SE
)
p <0.001
Topiramate
Placebo
195 193 189 175 166 160 153 145 141195 191 178 169199 197 184 178 162 156 153 145 140198 188 181 170
Topiramate n =Placebo n =
57
Indications: – Epilepsy– Migraine prophylaxis– Not approved by Health Canada for treatment of BED
Dose and dosage adjustment in BED study:– Started at 25 mg/day– Titrated weekly over eight weeks to 400 mg/day or maximum tolerated dose– Mean final dose was 300 mg/day
Most common adverse effects in BED study:– Nausea– Paresthesia– Somnolence– URTI
Note: mild cognitive impairment is another known side effect
Note: Topiramate is not approved by Health Canada for treatment of BEDMcElroy SL et al. Biol Psychiatry 2007; 61(9):1039-48;Topamax (topiramate tablets) Product Monograph. Janssen Inc.; 2015.
Topiramate: Indication, Dosage and Use
58
HCTZ = hydrochlorothiazideNote: Topiramate is not approved by Health Canada for treatment of BEDMcElroy SL et al. Biol Psychiatry 2007; 61(9):1039-48;Topamax (topiramate tablets) Product Monograph. Janssen Inc.; 2015.
Topiramate: Indication, Dosage and Use (cont’d)
Drug-drug interactions:– Concomitant use with valproic acid may result in hypothermia or hyperammonemia– Decreases in serum potassium seen when administered with HCTZ– Oral contraceptive efficacy may be decreased– Concomitant use with carbonic anhydrase inhibitors increases risk of kidney stones– Concomitant use with metformin may increase serum levels of both drugs– Topiramate may decrease serum levels of phenytoin– Carbamazepine, phenytoin and valproic acid may decrease serum levels of topiramate
Precautions:– Risk of fetal harm when administered to pregnant women– Patients should be monitored for suicidal ideation
59Return
Note: Anticonvulsants are not approved by Health Canada for treatment of BEDMcElroy SL et al. CNS Drugs 2009; 23(2):139-56.
Role of Substance Abuse Treatment Agents in the Treatment of BED
Opioid antagonists
Some suggestion from case reports of decreased binge eating However, the only RCT to include BED patients showed
no significant reduction in binge duration or frequency
AcamprosateIn trial of 40 patients with BED, no significant decrease in binge frequency, though some improvement in binge day frequency and measures of food craving
Samidorphan No significant difference from placebo in trial of 68 patients with BED
60Return
*p <0.05Brownley KA et al. Ann Intern Med 2016; 165(6):409-20.
Effect of Lisdexamfetamine on Abstinence from Binge Eating
Meta-analysis suggests lisdexamfetamineincreases abstinence from binge eating by
2.6x vs. placebo
Events, n/N
Study, Year (reference) RR (95%) CI) Treatment Placebo
McElroy et al, 2015 (49)* 2.11 (1.28–3.48) 60/130 14/64
SPD489-343, 2015 (50, 52)* 2.84 (1.92–4.19) 77/192 27/191
SPD489-344, 2015 (51, 52)* 2.73 (1.83–4.09) 71/195 26/195
Overall* 2.61 (2.04–3.33) 208/517 67/450
0.01 0.1 1 10 100
Favours placebo Favours treatment
61
p <0.05 for 50 and 70 mg/day groups vs. placebo; p = NS for 30 mg/day vs. placeboLDX = lisdexamfetamine dimesylate; SD = standard deviationMcElroy SL et al. JAMA Psychiatry 2015; 72(3):235-46.
Effect of Lisdexamfetamine on Binge-Eating Behaviour
-3.1-3.5
-4.1 -4.1-4.5
-4
-3.5
-3
-2.5
-2
-1.5
-1
-0.5
0
Placebo(n = 62)
30mg/day(n = 66)
50mg/day(n = 66)
70mg/day(n = 66)
Ch
ang
e in
BE
day
s/w
eek
Change in Mean Number of Binge-Eating Days/Week from Baseline to
Week 11 or End of Treatment
LDX
1-week follow-up after last dose
8-week dose-maintenance period
3-week forced-dose titration
RandomizationPlacebo LDX 30 mg/day LDX 50 mg/day LDX 70 mg/day
Enrollment260 overweight/obese adults
Study Design
Primary endpoint: number of binge eating days
per week
62
418 adults with moderate to severe BED enrolled
Treated with LDX for 12 weeks
275 responders randomized to placebo or LDX for 26 weeks
Placebo (n = 138)
LDX (n = 137)
Hudson JL et al. JAMA Psychiatry 2017;74(9):903-10.
Maintenance of Efficacy: Lisdexamfetamine vs. Placebo
32.1
3.7
0
5
10
15
20
25
30
35
Placebo(n = 62)
LDX(n = 136)
Per
cen
t o
f p
atie
nts
rel
apsi
ng
Relapse Rate
P <0.001
Study Design
Primary outcome: time to relapse
(≥2 binge-eating days per week for two consecutive weeks and ≥2-point CGI-S score increases from
randomized withdrawal baseline)
63
Indication: moderate to severe BED in adults (18 to 55 years)
Recommended dose and dosage adjustment:– Start at 30 mg/day
– Titrate in 20 mg/day increments at approximately weekly intervals to recommended target dose of 50–70 mg/day
Vyvanse (lisdexamfetamine dimesylate capsules) Product Monograph. Shire Pharma Canada ULC; 2016.
Lisdexamfetamine Dimesylate: Indication and Dosage
64
Most common adverse effects:– Dry mouth– Headache– Insomnia
Drug-drug interactions:– Co-administration with MAOIs is contraindicated– Concomitant use with modafinil is not recommended
CV = cardiovascular; MAOI = monoamine oxidase inhibitorsVyvanse (lisdexamfetamine dimesylate capsules) Product Monograph. Shire Pharma Canada ULC; 2016.
Lisdexamfetamine Dimesylate: Adverse Effects, Precautions and Interactions
65
Vyvanse (lisdexamfetamine dimesylate capsules) Product Monograph. Shire Pharma Canada ULC; 2016.
Lisdexamfetamine Dimesylate: Adverse Effects, Precautions and Interactions (cont’d)
Precautions:– Amphetamines have a potential for abuse, misuse, dependence or
diversion for non-therapeutic uses that physicians should consider when prescribing this product
– Serious CV events have been reported in the ADHD population
Given the higher CV risk associated with obesity, the BED population may be at a higher risk
– Administration of stimulants may exacerbate symptoms of behaviour disturbance and thought disorder in patients with a pre-existing psychotic disorder
66Return
Patients are relieved to have condition
recognized and validated
Accessing multidisciplinary and online resources can
help support effective pharmacotherapy
Clear, quantifiable treatment goals make for simple follow up
Treatment of BED Can Be Simple, Effective and Rewarding
67
Untreated BED has a significant impact on patients’ physical and mental well-being
Overweight/obese individuals with ≥1 risk factor for BED should be screened for BED using specific and simple questions
Treatment goals in BED are simple, quantifiable and achievable through the use of dietary, psychological and pharmacological approaches
Proper management of BED may simultaneously help address physiological and/or psychiatric comorbidities
Key Messages
68
FAQs
69
Frequently Asked Questions
How much food constitutes a “binge”?
Are there any screening tools available?
In patients with BED and psychological comorbidities, which conditions should be prioritized?
How often after starting lisdexamfetamine should pulse and/or other cardiovascular measures be checked?
Can lisdexamfetamine be used in patients on NRIs or SNRIs?
Can lisdexamfetamine be used in patients with agitation?
How long should patients receive pharmacological treatment for BED?
70
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