The Center for Eating Disorders - NewYork-Presbyterian. The ...

The Center for Eating Disorders 

Ea#ng Disorders 

Research Unit 

NYSPI 

at Westchester 

Columbia 

Day Program 

@East 60th

Today’s Agenda 

9:00-‐9:30 A new model for anorexia nervosa 

B. Timothy Walsh, MD 

9:30-‐10:00 

10:00-‐10:30 

10:30-‐10:45 

10:45-‐11:15 

11:15-‐12:45 

The role of medicaDon in eaDng disorders treatment 

Evelyn AFa, MD 

What predicts weight loss success? 

Laurel Mayer, MD 

Coffee Break! 

NutriDonal and eaDng disorders 

Janet Schebendach, PhD 

Evidence-‐based treatments: A case-‐based discusssion 

A GoXlieb, P Raizman, J Steinglass, J Schebendach,

• Rita Golden 

• Mary Beth Kea7ng 

• Kathleen Propp 

• Mike Smith 

• Barbara Smolek 

Thank You!

The role for medicaDon in 

eaDng disorders treatment 

Evelyn AFa, MD 

May 18, 2012

NYS Psychiatric Unit 

Nichole Barbarich-‐Marsteller 

Allegra Bro? 

Michael Devlin 

Deborah Glasofer 

Juli Goldfein 

Diane Klein 

Rachel Marsh 

Laurel Mayer 

Pamela Raizman 

Janet Schebendach 

Robyn Sysko 

B Timothy Walsh 

New York-‐Presbyterian/ 

Westchester 

Zoe Bisbing 

Alessia GoOlieb 

Melissa Klein 

Dennis McNabb 

BeOy Morin 

Parinda Parikh 

Laura Price 

Diahann Smith-‐Roberts 

Columbia Eastside 

Chiara BaQstello 

Michelle Brill 

Heather Paley

Disclosure 

I receive support from Eli Lilly & Co

EaDng Disorders 

Anorexia Nervosa 

Bulimia Nervosa 

Binge EaDng Disorder


Key DiagnosDc Features 

• Recurrent episodes of binge eaDng 

• Recurrent inappropriate behaviors to avoid 

weight gain (e.g., vomiDng, laxaDve misuse) 

• Episodes occur > 2x/week for >3 months

Bulimia nervosa 

• Age of onset: late adolescence, young 

adulthood 

• Age of presentaDon > onset 

• Prevalence: 1-‐3 % 

• Females > males 

• Normal weight 

• Serious medical complicaDons uncommon 

• High rates of co-‐morbid depression


Dental Erosion

Bulimia Nervosa


• AnDdepressants: 

– High rates of co-‐morbid depression, 

anxiety 

– Evidence for noradrenergic, serotonergic 

disturbance 

• Mood stabilizers/anD-‐seizure 

• Opioid antagonists 

• Other novel agents

Controlled Trials of AnDdepressants 

in Bulimia Nervosa 

Author MedicaDon n Length 

Sabine et al Mianserin 36 8 

Pope et al Imipramine 19 8 

Mitchell & Groat Amitriptyline 32 8 

Hughes et al Desipramine 22 6 

Walsh et al Phenelzine 50 6 

Agras et al Imipramine 22 16 

Kennedy et al Isocarboxazid 18 6 

Barlow et al Desipramine 24 6 

Blouin et al Desipramine 10 6 

Horne et al Bupropion 49 8 

Pope et al Trazodone 42 6 

Mitchell et al Imipramine 74 10 

Enas et al FluoxeDne 382 8 

Walsh et al Desipramine 78 6 

Wheadon et al FluoxeDne 390 16 

Kennedy et al Brofaromine 36 8 

Alger et al Imipramine 22 8 

Freeman et al Fluvoxamine 8

AnDdepressant Treatment 

of Bulimia Nervosa 

med 

placebo 

60 mg/d 

20 mg/d

Bulimia Nervosa: 

Time Course of Response to FluoxeDne 

Fluoxetine, at 60 mg/d, was initiated on Day 1. 

Dose was well-tolerated!

120 women 

CBT = Med 

CBT > SPT 

Tx/Meds > Tx/Pbo 

Walsh, Am J Psychiatry, 1997

FluoxeDne following unsaDsfactory response to 

psychotherapy for Bulimia Nervosa 

Walsh et al, 2001

Other medicaDons in BN 

• Mood stabilizers 

– Topiramate 

• AnD-‐emeDc 

– Odansetron 

• Other agents 

– Naltrexone 

– Baclofen

MedicaDon Treatment for BN 

• AnDdepressants useful for decreasing ED 

behaviors and improving mood 

• FluoxeDne HCl is the only medicaDon with 

specific FDA indicaDon for the treatment of BN 

• Higher doses may be needed than that generally 

prescribed for depression 

• When they work, they work fast 

• They are worth trying even in individuals who fail 

to respond to psychotherapy

Binge EaDng Disorder: 


• Recurrent binge eaDng (objecDvely large 

amount of food and loss of control) 

(same as bulimia) 

• No compensatory behavior 

(clearly different from bulimia) 

• Marked distress about the behavior

Binge EaDng Disorder 

Clinical Features 

Compared with paDents with anorexia nervosa 

and bulimia nervosa, those with Binge EaDng 

Disorders: 

are older (~middle aged) 

more frequently male (40-‐50%) 

Most are overweight or obese. 

Low levels of mood and anxiety disturbance are 

common.

Goals of Treatment for Obese PaDents 

With BED 

• NormalizaDon of eaDng paXerns and cessaDon 

of binge eaDng (BEHAVIORAL) 

• Management of obesity (SOMATIC) 

• ReducDon of overall distress: remediaDon of 

depressive symptoms and enhanced self-acceptance 

(PSYCHOLOGIC)

MedicaDons Examined 

for Treatment of BED 

• AnDdepressants 

– TCAs: desipramine, imipramine 

– SRIs: fluvoxamine, sertraline, fluoxeDne, citalopram 

• FDA approved anDobesity agents 

– sibutramine 

– orlistat 

• Other 

– Naltrexone 

– Topiramate 

– Zonisamide 

– AtomoxeDne 

– Baclofen

Controlled MedicaDon Trials in BED 

Author Medication(s) N 

Length 

(weeks) 

McCann (1990) Desipramine 23 12 

Alger (1991) 

Imipramine 

Naltrexone 

55 8 

Stunkard (1996) d-Fenfluramine* 28 8 

Hudson (1998) Fluvoxamine 85 9 

McElroy (2000) Sertraline 34 6 

Arnold (2002) Fluoxetine 60 6 

McElroy (2003) Citalopram 38 6 

McElroy (2003) Topiramate 58 14 

Appolinario(2003) 

Grilo (2005) 

Golay (2005) 

McElroy (2006) 

McElroy (2007) 

Wilfley (2008) 

Sibutramine 

Orlistat + CBT 

Orlistat 

Zonisamide 

Topiramate 

Sibutramine 

60 

50 

89 

60 

394 

304 

12 

12 

24 

16 

16 

24

Efficacy of Meds for Treatment of BED 

% Reduction in Binge Frequency 

placebo 

ac%ve 

medica%on 

McCann (1990) 

Desipramine 

Naltrexone 

Imipramine 

d-‐Fenfluramine 

Fluvoxamine 

FluoxeDne 

Citalopram 

Sibutramine 

Sertraline 

Topiramate 

Orlistat + CBT 

Orlistat 

Zonisamide 

AtomoxeDne 

Topiramate 

Sibutramine


Weight Loss (kg) 

acDve 

medicaDon 

McCann (1990) 

placebo 

Desipramine 


Fluvoxamine 

FluoxeDne 

Citalopram 

Topiramate 

Sibutramine 


Orlistat 

Zonisamide 

AtomoxeDne 

Topiramate 

Sibutramine


% Reduc%on in Binge Frequency 

placebo 


Desipramine 

Naltrexone 

Imipramine 


FluoxeDne 

Citalopram 

Sibutramine 

Fluvoxamine 

Sertraline 

Topiramate 


Orlistat 

Zonisamide 

Topiramate 

Sibutramine 

AtomoxeDne


Weight Loss (kg) 


placebo 

Desipramine 


Fluvoxamine 

Appolinario (2003) 

FluoxeDne 

Citalopram 

Topiramate 

Sibutramine 


Orlistat 

Zonisamide 

AtomoxeDne 

Topiramate 

Sibutramine

Example: 

Sibutramine for BED 

(Wilfley et al, 2008)

MedicaDon in BED: Summary 

• AnDdepressants are useful 

• Placebo effects are also high 

• Binge eaDng improvement > weight loss? 

• Weight loss medicaDons: limited tolerability 

• More opportunity to study this populaDon with 

DSM-‐5



• Relentless pursuit of thinness 

• Fear of becoming fat 

• Significantly underweight

DSM-‐IV: ANOREXIA NERVOSA 

A. Refusal to maintain body weight at or above a minimally 

normal weight for age and height (e.g., 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 body weight or 

shape is experienced, undue influence of body shape or 

weight on self-‐evaluaDon, or denial of the seriousness of 

current low body weight 

D. In postmenarchal females, amenorrhea 

Subtype: RestricDng vs. Binge/Purge

DSM-‐5: ANOREXIA NERVOSA 

A. RestricDon of energy intake relaDve to requirements 

leading to a significantly low body weight 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 becoming fat, or 

persistent behavior to avoid weight gain, even though at 

a significantlyslow weight 

C. Disturbance in the way in which one's body weight or 

shape is experienced, undue influence of body shape or 

weight on self-‐evaluaDon, or persistent lack of 

recogniDon of the seriousness of current low body weight 

Subtype: RestricDng vs. Binge/Purge

Anorexia nervosa 

Clinical characterisDcs 

• Females >> males 

• Adolescents and young adults 

• Pre-‐illness anxiety (disorder) in some

Behavioral 

Obsession with food 

Peculiar eaDng 

Binge eaDng 

LaxaDve/diureDc abuse 

Compulsive behavior 

Depression 

Anxiety 

Social isolaDon 

Increased physical acDvity 


Associated Features 

Physiological 

Hypothermia, bradycardia, 

hypotension 

Lanugo 

Edema 

Anemia, leukopenia 

Increased LFT’s 

Low estrogen, LH, FSH 

Low-‐normal T4 

High cholesterol 

Decreased brain mass 

Osteoporosis


Lanugo

QT ProlongaDon in an 

Underweight PaDent With AN 

Case #1. ECG at admission: the main feature is QT interval 

prolonga%on (QT=525 ms, QTc=594 ms). 

Journal of Electrocardiology Vol. 34 No. 3 July 2001

Long-‐Term Mortality in 


Sullivan, 1995

Anorexia Nervosa: Controlled Trials 

Class # Trials Medication Results 

Antidepressant 4 CMI, AMI (2), FLX - 

Antipsychotic 3 Sulpiride, Pimozide, Risperdal - 

4 Olanzapine + 

Serotonin Antagonist 3 Cyproheptadine +/- 

Lithium 1 - 

THC 1 - 

Cisapride 1 +/- 

Zinc 3 +/-

Olanzapine vs. Placebo in AN 

Bissada et al, Am J Psychiatry, 2008.

Olanzapine vs. placebo 

• Will outpaDents take olanzapine? 

• Does it help?

AFa, et al., Psychological Medicine, 2011 

Subject characterisDcs (N = 23) 

Age (years) 27.7+ 9.1 

BMI (kg/m 2 ) 17.2 + 1.3 

Gender Female = 22 

Male = 1 

AN Subtype Binge/Purge = 18 

Restricting = 5 

Duration of Illness (years) 8.0 + 8.9 

Site New York = 15 

Toronto = 8

Olanzapine vs Placebo: 

Weight change (N = 23)

Olanzapine vs. Placebo 

Weight change 

Olanzapine 

(n=11) 

Placebo 

(n=12) 

P 

Total weight gained 

during study 

participation (lbs) 

(n = 23) 

Wekly weight gained 

(lbs/wk) 

(n = 23) 

6.2 + 6.6 1.5 + 4.4 .059 

0.9 + 0.9 -0.2 + 1.1 .043 

BMI increase 1.2 0.2 .02

Psychological change 

20 

25 

15 

10 

5 

BAI 

20 

15 

10 

5 

YBC-‐EDS 

0 

30 

25 

20 

15 

10 

5 

0 

BDI 

0 

140 

130 

120 

110 

100 

BSQ 

Olanzapine 

Placebo

Olanzapine vs. placebo 

for outpaDents with AN 

• 5 sites 

– Columbia, Weill Cornell, Johns Hopkins, 

University of PiXsburgh, CAMH (Toronto) 

• 16 week trial, 8 weeks follow-‐up 

• “Real world” sample of 160 adults with AN 

• Sample straDfied for diagnosDc sub-‐type 

• Med-‐plus manual to encourage treatment 

adherence, assure medical monitoring 

• Primary outcomes: BMI, YBOCS 

• Began recruitment September 2010

Recruitment Update: CONSORT 

Informed of study=451 

Phone screened=196 

In-‐person screened=99 

Signed consent=74 

Excluded=255 

Other tx desired=37 

Not interested in med=43 

Ineligible=96 

None given=47 

Lost contact=32 

Excluded=92 

Screen pending=5 

Other tx desired=13 

Not interested in medicaDon=13 



Excluded=25 

Decided not to parDcipate=9 



Randomized=51 

Excluded=23 

Decided to pursue alternate tx, 

changed mind, or lost contact 

AcDve=12 

Completed=21 

Withdrawn by 

invesDgators=4 

Weight loss=1 

HospitalizaDon required=1 

Alcohol abuse=1 

High cholesterol=1 

Dropped out=14 

Pursued more intense tx=6 

Did not like medicaDon=1 


Other=3

Thank you!

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