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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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